Organic Reactions, Vol. 71 [1st ed.] 9780470098998, 0470098996

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Published by John Wiley & Sons. Inc., Hoboken. New Jersey Copyright © 2008 by Organic Reactions. Inc. All rights reserved. Published simultaneously in Canada. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center. Inc.. 222 Rosewood Drive. Danvers. MA 01923. (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com. Requests for permission need to be made jointly to both the publisher, John Wiley & Sons, Inc., and the copyright holder. Organic Reactions. Inc. Requests to John Wiley & Sons. Inc., for permissions should be addressed to the Permissions Department. John Wiley & Sons. Inc.. 111 River Street, Hoboken. NJ 07030. (201) 748-6011, fax (201) 748-6008, or online at http://www.wiley.com/go/permission. Requests to Organic Reactions, Inc., for permissions should be addressed to Dr. Jeffery Press, 22 Bear Berry Lane. Brewster. NY 10509. E-Mail: [email protected]. Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specilically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Neither the publisher nor author shall be liable for any loss of prolit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762-2974. outside the United States at (317) 572-3993 or fax (317) 572-4002. Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at www.wiley.com. Library of Congress Catalog Card Number: 42-20265 ISBN 978-0-470-09899-8 Printed in the United States of America 10 9 8 7 6 5 4 3 2 1

CONTENTS

CHAPTER

1.

PAGE

IONIC AND ORGANOMETALLIC-CATALYZED ORGANOSILANE REDUCTIONS Gerald L. Larson and James L. Fry . . . . . . . . . . . . . . . . . . . . . .

1

CUMULATIVE CHAPTER TITLES BY VOLUME . . . . . . . . . . . . . . . . . . . . . . . 739 AUTHOR INDEX, VOLUMES 1–71 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 753 CHAPTER AND TOPIC INDEX, VOLUMES 1–71 . . . . . . . . . . . . . . . . . . . . . . 759

vii

CHAPTER 1

IONIC AND ORGANOMETALLIC-CATALYZED ORGANOSILANE REDUCTIONS GERALD L. LARSON Gelest, Inc., Morrisville, Pennsylvania 19067 JAMES L. FRY 6016 Trotwood Court, Fort Collins, Colorado 80524

CONTENTS ACKNOWLEDGMENTS . . . . . . INTRODUCTION . . . . . . . . . . . . . . MECHANISM General Considerations . . . . . Role of Trivalent Silicon Species . . . Role of Hypervalent Silicon Species . . Role of O/N-Silylated Cationic Intermediates Role of Metal Catalysts . . . . . SCOPE AND LIMITATIONS . . . . Reduction of Substituted Alkanes . . . Alcohols to Alkanes . . . . . Alkyl Halides and Triflates to Alkanes . Reduction of Unsaturated Hydrocarbons . Alkenes to Alkanes . . . . . Alkynes to Alkanes . . . . . Cyclopropanes to Alkanes . . . . Aromatic Substrates . . . . . Miscellaneous Unsaturated Substrates . Reduction of Ethers . . . . . Reduction of Allyl Acetates . . . . Reduction of Carboxylic Acids . . . Reduction of Acid Halides and Acid Anhydrides Reduction of Esters and Lactones . . . Reduction of Aldehydes . . . . Reduction to Alcohols . . . .

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[email protected] [email protected] Organic Reactions, Vol. 71, Edited by Scott E. Denmark et al.  2008 Organic Reactions, Inc. Published by John Wiley & Sons, Inc. 1

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PAGE 5 5 6 6 7 9 11 11 12 12 12 27 32 32 45 46 48 49 50 51 51 53 53 56 56

2

ORGANIC REACTIONS

Reductive Amidation of Aldehydes . . . . . . . . Reductive Esterification . . . . . . . . . . Reductive Etherification . . . . . . . . . . Reduction to Alkanes . . . . . . . . . . Reduction to Methylene Halides . . . . . . . . Reductive Amination . . . . . . . . . . . Reductive Thiolation . . . . . . . . . . . Reduction of Ketones . . . . . . . . . . . Reduction to Alcohols . . . . . . . . . . Reductive Amidation . . . . . . . . . . . Reductive Esterification . . . . . . . . . . Reductive Etherification . . . . . . . . . . Reductive Silylation . . . . . . . . . . . Reduction to Halocarbons . . . . . . . . . . Reduction to Alkanes . . . . . . . . . . Reductive Amination . . . . . . . . . . . Reductive Thiolation . . . . . . . . . . . Miscellaneous Ketone Reductions . . . . . . . . Reduction of Amides . . . . . . . . . . . Reduction of α,β-Unsaturated Aldehydes . . . . . . . Reduction of α,β-Unsaturated Ketones . . . . . . . . Reduction of α,β-Unsaturated Esters . . . . . . . . Reduction of α,β-Unsaturated Amides . . . . . . . . Reduction of α,β-Unsaturated Nitriles . . . . . . . . Reduction of Acetals, Ketals, Hemiacetals, Hemiketals, and Orthoesters . Reduction of Aminals and Hemiaminals . . . . . . . Reduction of Enamines . . . . . . . . . . . Reduction of Imines . . . . . . . . . . . Reduction of Oximes . . . . . . . . . . . Reduction of Nitroalkanes . . . . . . . . . . Reduction of Miscellaneous Nitrogen-Containing Compounds . . . Reduction of Miscellaneous Sulfur-Containing Compounds . . . . Reduction of Small-Ring Heterocycles . . . . . . . . Asymmetric Reduction of Ketones . . . . . . . . Asymmetric Reduction of α,β-Unsaturated Ketones . . . . . Asymmetric Reduction of α,β-Unsaturated Esters and Lactones . . . Asymmetric Reduction of α,β-Unsaturated Lactams . . . . . Asymmetric Reduction of Imines . . . . . . . . . . . . . . . . . . COMPARISON WITH OTHER METHODS Asymmetric Hydrogenation of Olefins . . . . . . . . Asymmetric Hydrogenation of Ketones . . . . . . . . Asymmetric Hydrogenation of Enol Acetates . . . . . . . Asymmetric Hydrogenation of α,β-Unsaturated Acids . . . . . Asymmetric Hydrogenation of Acetamidoacrylates . . . . . Asymmetric Hydrogenation of Enamides . . . . . . . Asymmetric Hydrogenation of Imines . . . . . . . . EXPERIMENTAL CONDITIONS . . . . . . . . . . EXPERIMENTAL PROCEDURES . . . . . . . . . . 2-Decyl-5-methoxy-1-naphthol [Reduction of a Secondary Benzylic Alcohol to a Methylene Group with Concomitant Loss of a MOM Protecting Group] . Cyclohexane [Aluminum Chloride Catalyzed Reduction of a Dichloroalkane to a Hydrocarbon] . . . . . . . . . . . .

63 63 64 69 72 73 74 74 74 79 80 80 82 84 84 85 86 86 87 88 88 93 96 96 97 99 100 101 102 102 103 104 105 105 108 109 110 110 111 111 112 116 116 117 118 119 120 121

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121

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121

ORGANOSILICON HYDRIDE REDUCTIONS 1-Dodecanol [Fluoride-Promoted Reduction of an Ester to an Alcohol] . . Dibenzyl Ether [Brønsted Acid Promoted Reduction of an Aldehyde to a Symmetrical Ether] . . . . . . . . . . . . . . Ethyl Benzyl Ether [Brønsted Acid Promoted Reduction of an Aldehyde to an Unsymmetrical Ether] . . . . . . . . . . . 1-Heptyl 3-Phenylpropyl Ether [Electrogenerated Acid-Promoted Reduction of an Aldehyde to an Unsymmetrical Ether] . . . . . . . . Dicyclohexyl Ether [Brønsted Acid Promoted Reduction of a Ketone to a Symmetrical Ether] . . . . . . . . . . . . . . Benzyl 3-Phenylpropyl Ether [Trityl Perchlorate Catalyzed Reduction of an Aldehyde to an Unsymmetrical Ether] . . . . . . . . . . Di-n-pentyl Ether [TMSI-Catalyzed Reduction of an Aldehyde to a Symmetrical Ether]. . . . . . . . . . . . . . . Cyclohexyl Ethyl Ether [TMSI-Catalyzed Reduction of a Ketone to an Unsymmetrical Ether] . . . . . . . . . . . . . . 4-Methylbenzyl Chloride [Reductive Halogenation of an Aldehyde to a Benzyl Chloride] . . . . . . . . . . . . . . (1R,2S)-2-[(Ethoxycarbonyl)amino]-1-phenyl-1-propanol [Brønsted Acid Promoted Reduction of an α-Amino Ketone to an Erythro α-Hydroxy Amine] . . . Phenylcyclopentane [Brønsted Acid Catalyzed Reduction of an Alkene to an Alkane] . . . . . . . . . . . . . . n-Hexadecane [Tris(pentafluorophenyl)boron-Catalyzed Reduction of an Acid Chloride to an Alkane] . . . . . . . . . . . . . n-Dodecane [Tris(pentafluorophenyl)boron-Catalyzed Reduction of a Carboxylic Acid to an Alkane] . . . . . . . . . . . . . 4-Iodobenzyloxytriethylsilane [Tris(pentafluorophenyl)boron-Catalyzed Reduction of a Carboxylic Acid to a Benzyl Triethylsilyl Ether] . . . . . . N -(Phenylmethylsilyl)-1,2,3,4-tetrahydropyridine [Reduction of a Pyridine] . Camphor [Reduction of an α-Bromo Ketone to a Ketone] . . . . . 2-Phenyl-5-decylpyrimidine [Reduction of an Aryl Triflate to an Arene] . . n-Hexadecane and 1-(Triethylsiloxy)hexadecane [Reduction of a Symmetrical Ether] 3-Phenyl-1-propanol [Reduction of a Carboxylic Acid to an Alcohol] . . Cys(SBu-t)Gly [Reductive Deprotection of Boc and tert-Butyl Ester Groups in the Presence of a tert-Butyl Sulfide] . . . . . . . . . N -Boc-cyclododecylamine [Reductive Boc-protection of an Oxime] . . . (3R)-N -Acetyl-3-(tert-butyldimethylsiloxy)pyrrolidine [Reduction of an Aminal to an Amine] . . . . . . . . . . . . . . 3,5-Dimethyl-l-cyclohexen-l-yl Dimethylphenylsilyl Ether [Reductive 1,4-Hydrosilylation of an Enone] . . . . . . . . . 6,8-Dioxabicyclo[3.2.1]octan-4-one [1,2-Reduction of an Enone in the Presence of an Acetal] . . . . . . . . . . . . . . N -(exo-2-Norbornyl)acetamide [Reductive Amidation of a Ketone] . . . Dihydro-β-Ionone [1,4-Reduction of an α,β-Unsaturated Ketone] . . . β-Ionol [1,2-Reduction of an α,β-Unsaturated Ketone] . . . . . Undec-10-enal [Reduction of an Amide to an Aldehyde] . . . . . 4-Phenylpent-1-ene [Reductive Allylation of an Aryl Ketone] . . . . 6-Phenylhex-1-ene [Reduction of an Aliphatic Ketone Function to a Methylene Function] . . . . . . . . . . . . . . 10-Undecen-1-ol [Reduction of an Ester to an Alcohol] . . . . . Tricarbonyl(1-endo-allyltetralin)chromium [Stereoselective Reduction of an Alcohol to a Hydrocarbon] . . . . . . . . . . . . . 5-Methoxytetralin [Partial Reduction of a Substituted Naphthalene to a Tetralin]

3 121 122 122 122 123 123 123 124 124 125 125 125 126 126 126 127 127 127 128 128 128 129 129 129 130 130 130 131 131 131 132 132 132

4

ORGANIC REACTIONS

1,2,3-Trideoxy-D-ribo-hex-1-enopyranose Diacetate [Reduction of an Allyl Ester] 6-(2-Butyl)-4-hydroxy-3-ethyl-2-pyrone (Germicidin) [Reduction of a Ketone Carbonyl to a Methylene Group in a Multifunctional Compound] . . . . . 1-(1-Chloroethyl)-4-nitrobenzene [Deoxygenative Chlorination of a Ketone] . Methyl 2-(Phenylcarbamoyl)butanoate [Hydrocarbamoylation of an α,β-Unsaturated Ester] . . . . . . . . . . . . . . Benzyl Bromide [Reductive Bromination of an Acetal] . . . . . 2-(Benzyloxy)-3-bromo-5-[(2-ethoxycarbonyl)ethyl]phenyl Ethyl Carbamate [Reduction of an Enamide to an Amide] . . . . . . . . . . 3-Nitrobenzylamine [Reduction of an Imine to an Amine] . . . . . Cyclohexyl Iodide [Iodoreduction of an Oxirane to an Iodoalkane] . . . (R)-3,3-Dimethyl-5-(2-phenylethyl)cyclohexanone [Asymmetric 1,4-Reduction of an Enone] . . . . . . . . . . . . . . TABULAR SURVEY . . . . . . . . . . . . . Chart 1. Catalysts and Ligands Used in Tables . . . . . . . Chart 2. Organosilane Compound Designations Used in Tables . . . . Table 1. Organosilane Reduction of Alkenes . . . . . . . . Table 2. Organosilane Reduction of Alkynes . . . . . . . . Table 3. Organosilane Reduction of Aromatic Hydrocarbons . . . . . Table 4. Organosilane Reduction of Halocarbons . . . . . . . Table 5. Organosilane Reduction of Alcohols . . . . . . . Table 6. Organosilane Reduction of Ethers . . . . . . . . Table 7. Organosilane Reduction of Allyl Esters . . . . . . . Table 8. Organosilane Reduction of Acids . . . . . . . . Table 9. Organosilane Reduction of Acid Halides . . . . . . . Table 10. Organosilane Reduction of Esters and Lactones . . . . . Table 11. Organosilane Reduction of Aldehydes . . . . . . . Table 12. Organosilane Reduction of Ketones . . . . . . . Table 13. Organosilane Reduction of Amides . . . . . . . Table 14. Organosilane Reductive Amination of Aldehydes and Ketones . . Table 15. Organosilane Reduction of α,β-Unsaturated Aldehydes . . . . Table 16. Organosilane Reduction of α,β-Unsaturated Ketones . . . . Table 17. Organosilane Reduction of α,β-Unsaturated Esters . . . . . Table 18. Organosilane Reduction of α,β-Unsaturated Amides . . . . Table 19. Organosilane Reduction of α,β-Unsaturated Nitriles . . . . Table 20. Organosilane Reduction of Acetals, Ketals, and Hemiketals . . . Table 21. Organosilane Reduction of Aminals and Hemiaminals . . . . Table 22. Organosilane Reduction of Enamines . . . . . . . Table 23. Organosilane Reduction of Imines . . . . . . . . Table 24. Organosilane Reduction of Hydroxylimines . . . . . . Table 25. Organosilane Reduction of Nitroalkanes . . . . . . . Table 26. Organosilane Reduction of Miscellaneous Nitrogen Compounds . . Table 27. Organosilane Reduction of Miscellaneous Sulfur Compounds . . . Table 28. Organosilane Reduction of Small-Ring Compounds . . . . Table 29. Miscellaneous Organosilane Reductions . . . . . . . Table 30. Asymmetric Organosilane Reduction of Ketones . . . . . Table 31. Asymmetric Organosilane Reduction of α,β-Unsaturated Ketones . . Table 32. Asymmetric Organosilane Reduction of α,β-Unsaturated Esters . . Table 33. Asymmetric Organosilane Reduction of α,β-Unsaturated Lactams . . Table 34. Asymmetric Organosilane Reduction of Imines . . . . . . . . . . . . . . . . . . . REFERENCES

133 133 134 134 134 135 135 136 136 136 141 151 152 175 182 192 209 242 252 258 262 265 302 345 446 455 466 468 509 531 533 534 571 576 582 593 599 602 610 611 616 618 687 694 704 705 719

ORGANOSILICON HYDRIDE REDUCTIONS

5

ACKNOWLEDGMENTS

The authors thank Mr. Thomas C. Johns of E. I. du Pont de Nemours and Company, Mr. Christopher W. Fry, Ms. Diane Micham, and the Department of Chemistry, University of Pennsylvania, for valuable assistance in the literature survey. INTRODUCTION

The purpose of this chapter is to present a critical review of synthetically useful variations of ionic methods for hydrogenation of organic compounds. In practice, ionic hydrogenation involves the formal introduction of hydride from a donor source to an electron-deficient carbon center. The electrophilic centers can be formed by the departure of a leaving group (nucleofuge) from a saturated center or by the addition of an electrophile to a multiple bond. In the former mechanism, substitution of hydrogen for the leaving group is the net chemical consequence. In the latter, addition across the multiple bond is the result. In this chapter, we cover the use of organosilicon hydrides as the source of ionic hydride with the goal of completing and updating earlier review works on the subject.1 – 4 Similar chemistry is observed when molecular hydrogen5,6 or various hydrocarbons7 – 9 are used as hydride sources; these methods have been reviewed previously and are not covered herein. The use of organosilicon hydride-metal catalyst mixtures10 – 12 for effecting reductions is included in this review, but use of trichlorosilane-tertiary amine combinations13 is not. Organosilicon compounds with at least one Si-H bond (called hydrosilanes, organosilicon hydrides, or simply silanes) have the ability to serve as mild air- and water-stable sources of hydride and thus have reducing properties. For example, triethylsilane is reported to reduce a variety of inorganic metal salts directly to the free metals.14,15 Even the hexachloroantimonate anion can be reduced to Sb(0) upon contact with this silane.16 Organotellurium chlorides are reduced to tellurium metal by a number of organosilicon hydrides.17 Reaction of organosilicon hydrides with strong Brønsted acids leads to decomposition of the silane and the production of hydrogen gas.14 In general, organosilicon hydrides do not undergo spontaneous reactions with organic compounds unless the organic substrate is a reasonably strong electrophile or the silane has been first activated by the interaction of a nucleophilic species with the silicon center. The organosilicon hydrides are covalent compounds that have little or no nucleophilic properties of their own. Aside from the parent silane, SiH4 , which is pyrophoric, the organosilicon hydrides are fairly innocuous compounds whose physical properties bear resemblance to their hydrocarbon analogs. Thus, their physical and chemical reducing properties differ from those of many familiar metal hydride reducing agents.18,19 The use of organosilicon hydrides often provides a means of effecting reductions of organic substrates under very mild conditions and with excellent functional group selectivity. Consideration of the nature of the Si–H bond provides insight into the chemical behavior of organosilicon hydrides. Comparison of the bond strengths as

6

ORGANIC REACTIONS

represented by bond dissociation energy (BDE) of hydrosilanes with those of hydrocarbon analogs shows that, in general, the Si–H bond is not much weaker than the C–H bond. Thus, the BDE values for the respective Si–H bonds in TMS–H and (C2 H5 )3 Si–H are 90.320 and 90.1 kcal/mol21 compared with a value of approximately 92 kcal/mol20 for the tertiary C–H bond in (CH3 )3 C–H. On the other hand, there is a significant difference between the polarization characteristics of the Si–H and C–H bonds.22 Compared to the Pauling electronegativity of hydrogen (2.20), the electronegativity of carbon (2.50) is greater and that of silicon (1.90) is less.23 Carbon-hydrogen bonds are thus polarized in the direction Cδ− –Hδ+ , whereas Si–H bonds are Siδ+ –Hδ− . As will be seen, this enhanced hydridic nature manifests itself in the chemical behavior of essentially all hydrosilanes. Limited studies of the germanium and tin hydride analogs of the silicon hydrides show that they share this ability to function as hydride sources in ionic hydrogenations; however, their relatively greater reactivity toward acids appears to restrict their practical applications in organic synthesis.24,25 MECHANISM

General Considerations The mechanistic discussion of silane reductions will be limited to those of cationic reductions, thus excluding the many silane reductions that involve metal catalysis. Since tetravalent organosilicon hydrides intrinsically lack nucleophilicity, they react only with atomic centers that are substantially electron deficient, for example, carbocations. Because of this, organosilicon hydride reductions are potentially very selective. The “ionic” reductions of organic compounds by organosilicon hydrides are understood on the basis of two mechanisms. In the first, substitution by hydrogen of a leaving group bonded to a saturated carbon occurs. This path may be called a σ -route as it involves the stepwise cleavage of a σ -bond to a saturated center and the intervention of a carbocation intermediate that is captured by donation of hydride from the organosilicon hydride (Eq. 1). Alternatively, addition of an electrophile/hydride pair takes place across a multiple bond. This path may be termed a π-route (Eq. 2). Complexation of an electrophile to one end of a π-bond is followed by capture of the intermediate cation or complex by organosilicon hydride. The electrophile may be as simple as a proton or be one of a variety of Lewis acids or alkylating agents. The group Y can be C, O, N, or S. Sometimes the product of Eq. 2 can continue reacting by way of Eq. 1, with the moiety Y–E acting as a leaving group. When this occurs, the net effect is to replace the C=Y functionality with CH2 . The normal caveats regarding carbocation behavior such as the possible occurrences of eliminations, skeletal isomerizations, and bimolecular reactions prior to capture by hydride must be expected in all of these scenarios. –X– X

+

R3SiH

H

(Eq. 1)

ORGANOSILICON HYDRIDE REDUCTIONS + Y

Y

+

R3SiH

Y

H

(Eq. 2)

Y

E

E

7

E

It is necessary for the intermediate cation or complex to bear considerable carbocationic character at the carbon center in order for effective hydride transfer to be possible. By carbocationic character it is meant that there must be a substantial deficiency of electron density at carbon or reduction will not occur. For example, the sesquixanthydryl cation 1,26 dioxolenium ion 2,27 boron-complexed imines 3, and O-alkylated amide 4,28 are apparently all too stable to receive hydride from organosilicon hydrides and are reportedly not reduced (although the behavior of 1 is in dispute29 ). This lack of reactivity by very stable cations toward organosilicon hydrides can enhance selectivity in ionic reductions.

O

O + + O O

O 1

R

H

EtO

Ph

Et

N+ BF3–

Et

N+ Et

2

3

4

Role of Trivalent Silicon Species The overall stoichiometry of hydride transfer from a silicon center to an electron-deficient carbon center is quite straightforward. Almost without exception, it appears that there is simple interchange of hydride to the carbocation while the silicon center receives the elements of the carbocation’s counterion (Eq. 3). R 3C + X –

+

R'3SiH

R3CH

+

R'3SiX

(Eq. 3)

When the counterion is complex, for example metal-halogen anions such as BF4 − , the most electronegative portion of the counterion becomes attached to the silicon center. Because of this attachment, it is natural to consider the intermediacy of a silicenium cation (silylium or silylenium ion) intermediate in such reactions (Eq. 4). Bond energies derived from electron impact studies indicate that Eq. 4 is exothermic in the gas phase by about 8 kcal/mol.26,29 There seems little doubt that trivalent silicon-centered cationic species do exist in the gas phase30,31 or that processes similar to that shown in Eq. 4 do occur there.32,33 Me3C+

+ (CH3)3SiH

(CH3)3CH

+ (CH3)3Si+

(Eq. 4)

The existence of trivalent silicenium cations as reactive species in solution is more controversial. Many early attempts to demonstrate the solution-phase existence of stable silicenium ions by using techniques analogous to those successfully applied to carbocation formation failed.34 – 36 Other reports of attempts

8

ORGANIC REACTIONS

to generate silicenium ions in solution under stable ion conditions37 – 46 and in solvolyses47 are more convincing, but not without controversy.48 – 51 The singlecrystal X-ray determination of a non-planar triethylsilylium moiety paired in the crystalline state with the tetrakis(pentafluorophenyl)borate gegenion and toluene solvate stirred much debate about its interpretation and extension to reaction systems.52,53 Recent crystallographic evidence supports the notion of a threecoordinate structure of a trimesitylsilylium cation paired with a carborane anion in the solid phase.54,55 The balance of experimental evidence seems to indicate that, whereas trivalent silicenium cations may have fleeting existence as reaction intermediates, it is unlikely that they exist as stable, long-lived species in solution.56 The failure to observe such trivalent species in solution is related to the very strong ability of electron-deficient silicon centers to coordinate with the media in which they are formed.53,57,58 This is true even in solvents that exhibit little or no nucleophilicity toward carbocations and is further enhanced by the relatively long bond lengths to silicon centers that allow a close approach by coordinating species.53 The available experimental information is suggestive, but not unambiguously conclusive, of the intervention of electron-deficient silicon-centered species that may resemble silicenium cations in simple hydride exchanges occurring in solvents with low coordinating abilities. For example, substituted triarylmethane derivatives such as chlorotriphenylmethane (trityl chloride) undergo reduction through halogen-hydride exchange with organosilicon hydrides. The reactions proceed more rapidly in solvents with high ionizing power, but are kinetically first order with respect to both organosilicon hydride and triarylmethane derivative in benzene solvent.59 In benzene, the exchange of halogen with hydride occurs with retention of configuration at the silicon center.60 These results have led to the suggestion that the exchanges proceed by way of a four-center transition state 5, in which there is simultaneous attack by the halide of the carbocation-halide ion pair on the silicon center as hydride undergoes transfer to the carbocation center.60 H

Ph3Si +

Cl–

CPh3

5

Simple variation of the solvent has a very significant effect on the stereochemistry at the silicon center for these exchange reactions. The stereochemistry changes from essentially complete retention to inversion and even to racemization. For example, in dichloromethane the halogen is delivered to the silicon center with complete racemization.61 This implies that the degree of “tightness” of the carbocation-counterion pair must change depending on the solvent. Organosilicon hydride reductions of preformed stable carbocations such as triphenylmethyl (trityl) tetrafluoroborate and hexafluoroantimonate salts are rapid

ORGANOSILICON HYDRIDE REDUCTIONS

9

and essentially quantitative.62,63 Reductions of these and similar stable ions in dichloromethane/trifluoroacetic acid (TFA) show primary deuterium kinetic isotope effects in the range kH /kD = 1.2764 to 1.8965 at room temperature, whereas effects equal to kH /kD = 1.50–2.33 are seen for the reduction of diarylcarbenium ions with deuteriosilanes at −70◦ .66 The kinetic rate dependence for similar reactions in acetic acid is first order in both the cation and the silane. The rates of a series of substituted arylsilanes correlate with σ constants, but not with σ + constants, to produce Hammett plots with ρ = −1.84 for triarylsilanes and ρ = −1.0165 to −2.4666 for aryldimethylsilanes. These results are interpreted to mean that the reactions occur through a four-center transition state in which the silicon center assumes a trigonal-bipyramidal shape with hydride exiting from an equatorial position while the carbocation’s counterion approaches axially.65 Trityl and tropylium (cycloheptatrienyl) cation salts having complex metalhalide anions such as SbX6 − , AsF6 − , PF6 − , FeCl4 − , and BF4 − undergo reduction with trialkylsilanes and aryldialkylsilanes at rates that are independent of the nature of the anion or of ring strain in the organosilicon hydride, are kinetically first order with respect to both cation and organosilicon hydride, and that display primary deuterium kinetic isotope effects of kH /kD = 1.41–1.49 in dichloromethane.67,68 It is argued that these reactions proceed by way of a threestep mechanism involving a rate-determining single-electron transfer step69 to create a charge-transfer complex between the carbocation and the organosilicon hydride followed by a faster transfer of hydride to the carbon center and the creation of a silicenium ion intermediate that is then rapidly captured by the counterion present (Eq. 5).68 Others regard this argument as doubtful compared to the polar mechanism in which Si–H bond cleavage is rate determining.66 + R'3SiH + R3C

R'3SiH

+ CR3

+

+

R'3Si

slow

H CR3

R'3Si

(Eq. 5) + R3CH

Uncertainties in understanding the exact mechanistic details of these reactions are sure to stimulate continued work to define the nature of trivalent silicon cations in ionic reductions by organosilicon hydrides. Role of Hypervalent Silicon Species It is well known that strong electrophiles such as carbocations are reduced by organosilicon hydrides (Eq. 1).3,70,71 On the other hand, simple mixtures of organosilicon hydrides and compounds with weakly electrophilic carbon centers such as ketones and aldehydes are normally unreactive unless the electrophilicity of the carbon center is enhanced by complexation of the carbonyl oxygen with Brønsted acids3,70 – 73 or certain Lewis acids (Eq. 2).1,70,71,74,75 Using these acids, hydride transfer from the silicon center to carbon may then occur to give either alcohol-related or hydrocarbon products.

10

ORGANIC REACTIONS

Alternatively, unreactive mixtures of organosilicon hydrides and carbonyl compounds react by hydride transfer from the silicon center to the carbon center when certain nucleophilic species with a high affinity for silicon are added to the mixture.76 – 94 This outcome likely results from the formation of valence-expanded, pentacoordinate hydrosilanide anion reaction intermediates that have stronger hydride-donating capabilities than their tetravalent precursors (Eq. 6).22,95 – 101 R3SiH + Nu–

1. R'2C=O

R3SiHNu–

2. H2O

R3SiNu

+ R'2CHOH

(Eq. 6)

The bicyclic silatrane molecule 6, which has a strong degree of coordination between the silicon center and the nitrogen bridgehead, has been shown to have unusually strong reducing properties compared to normal tetravalent organosilicon hydrides.102 The hypothesis that valence-expanded pentacoordinate silicon species are the actual reducing species76,77,83 is plausible, for such species are well known.96,99,101,103 – 107 Other examples are known of the enhanced reducing powers of organosilicon hydrides that undergo intramolecular coordination and expansion to pentavalent82 and even hexavalent states.84,101,108 – 111

:

N

OO

Si O H 6

A variety of nucleophilic species cause valence expansion of organosilanes and the enhancement of reducing reactivity. These include formate, thiocyanate, tartrate, and phthalate salts,78 as well as alkoxides91,92,96,99,107 and catecholates.93 The strong propensity of fluoride ion to cause silicon centers to undergo valence expansion95,112 makes it especially effective in activating organosilicon hydrides as reducing agents. Aldehydes, ketones, and esters may all be reduced by such a technique, frequently with excellent functional group and stereochemical selectivity.76 – 89 The valence-expanded silicon intermediate retains some measure of stereochemical integrity up to the point of hydride transfer as evidenced by the small degrees of asymmetric induction that are observed in the reduction of prochiral ketones coupled with similar degrees of chirality found at the silicon center.85 The transfer of hydride from the silicon center to the carbonyl carbon takes place in the rate-determining step as judged by the primary deuterium kinetic isotope effect of 1.50 observed in the fluoride-induced reduction of acetophenone with dimethylphenylsilane-d1 .88 There is also evidence that the pentacoordinate silicon hydride can serve as a single-electron-transfer donor since radical-coupling products are sometimes obtained, although the general importance of this process is open to question.89,99

ORGANOSILICON HYDRIDE REDUCTIONS

11

A diaryldihydrosilane with a hexacoordinated silicon center, produced through intramolecular coordination, is reported not to react with benzaldehyde, although the silane is capable of reducing silver ion to silver metal.113 There is also a report of a heptacoordinate silicon hydride species with the ability to transfer hydride to trityl cation while remaining inactive toward methanol.108,114 Role of O/N-Silylated Cationic Intermediates An interesting variation of the reaction mechanisms discussed above has been offered following studies of the hydrosilation reductions of aldehydes, ketones, and esters to their corresponding silyl ethers and acetals, respectively, when catalyzed by tris(pentafluorophenyl)borane, (C6 F5 )3 B,115,116 and related boranes.117 This mechanism proposes a pathway in which the first step is the reversible formation of a linear silane-borane adduct that undergoes subsequent nucleophilic attack by the carbonyl compound of the substrate to yield an O-silylated cationic intermediate along with a boron hydride anion.118 The boron hydride ion then transfers a hydride to the carbon center of the O-silylated cation to yield the reduction product and regenerated free borane. A simplified view of the suggested mechanism is shown below (Scheme 1). Similar reaction paths have been proposed for the hydrosilation of enones and silyl ethers119 as well as imines.120

δ+ δ − R3Si—H

R3Si-H + (C6F5)3B + Y

+ SiR3

Y B(C6F5)3 H

Y SiR3

H(C6F5)3B–

Y SiR3

+ (C6F5)3B

Scheme 1

Role of Metal Catalysts A wide variety of metals can effectively catalyze the reduction of multiple bonds by organosilicon hydrides (Eq. 2). No doubt, the function of some of these metals is to serve as Lewis acids by adding to the most electron-rich end of a bond and promoting transfer of hydride to the other center. On the other hand, it is clear that many transition metal complexes function through significantly different and more complex catalytic pathways to promote silane reductions. A common reaction stage suggested for many of the catalytic cycles is the creation of a reactive intermediate having a metal-hydrogen bond that is formed by hydrogen transfer from the silane to the catalytic metal center.116 This reducing center, often with appropriate coordinating ligands, subsequently delivers hydrogen to the substrate and the metal center is freed for additional catalytic cycles. When the catalytic metal ligands are chiral, this process can lead to very high degrees of enantiomeric selectivity in the reduction of prochiral substrates.121 – 125

12

ORGANIC REACTIONS SCOPE AND LIMITATIONS

Reduction of Substituted Alkanes Alcohols to Alkanes. Many alcohols are converted directly into hydrocarbons when treated with acid in the presence of organosilicon hydrides (Eq. 7). The mechanism normally follows the pathway shown in Eq. 1. ROH

"acid"

RH

R'3SiH

(Eq. 7)

The reaction generally proceeds cleanly and in high yields (70–100%) when the starting alcohol permits the formation of reasonably stable carbocation intermediates. Alcohols capable of producing carbenium ions spanning a range of stabilities of more than 24 pKR+ units undergo this reduction.26 Depending on the reaction conditions, secondary126 and tertiary127 aliphatic alcohols, secondary and tertiary benzylic alcohols,26,126 some ring-substituted primary benzylic alcohols,26,128,129 and cyclopropylcarbinols130 are reduced to the corresponding alkanes. However, olefinic and rearrangement products can occur from side reactions under these acid conditions.126,131,132 Phenols are not reduced under the same conditions. Almost any organosilicon hydride causes reduction of the cations produced, although the order of reactivity of simple alkyl and aryl-substituted silanes is observed to be triethyl > trioctyl ∼ diethyl > diphenyl ∼ triphenyl.26 A detailed quantitative study of the reactions of organosilicon hydrides with diarylcarbenium ions in dichloromethane at −70◦ indicates a relative reactivity order of R3 SiH > R2 SiH2 > RSiH3 , with alkyl substituent groups generally producing greater reactivity than aryl substituents.61 Use of a deuterated silane yields the corresponding deuterated hydrocarbon (Eq. 8).127,133,66 ROH

"acid" R'3SiD

RD

(Eq. 8)

Normally, only a small stoichiometric excess (2–30 mol%) of silane is necessary to obtain good preparative yields of hydrocarbon products. However, because the capture of carbocation intermediates by silanes is a bimolecular occurrence, in cases where the intermediate may rearrange or undergo other unwanted side reactions such as cationic polymerization, it is sometimes necessary to use a large excess of silane in order to force the reduction to be competitive with alternative reaction pathways. An extreme case that illustrates this is the need for eight equivalents of triethylsilane in the reduction of benzyl alcohol to produce only a 40% yield of toluene; the mass of the remainder of the starting alcohol is found to be consumed in the formation of oligomers by bimolecular Friedel-Crafts-type side reactions that compete with the capture of the carbocations by the silane.129 Both Brønsted and Lewis acids are effective in coordinating with the hydroxyl oxygen to induce heterolysis of the C–O bond and cause formation of the necessary carbocation intermediate. The reactions are frequently conducted

ORGANOSILICON HYDRIDE REDUCTIONS

13

under homogeneous conditions in inert solvents such as dichloromethane or chloroform. Conditions used include the treatment of alcohols with organosilicon hydrides in neat acetic acid,26,29 neat trifluoroacetic acid134 or trifluoroacetic acid/ammonium fluoride135 as well as mixtures of trifluoroacetic acid,26 methanesulfonic acid,126 or triflic (trifluoromethanesulfonic) acid with triflic anhydride126 in dichloromethane or chloroform, mixtures of acetic acid and sulfuric or p-toluenesulfonic acid,134 acetic acid and hydrogen chloride/aluminum chloride,136 and boron trifluoride126 or boron trifluoride etherate in dichloromethane137,133 or chloroform.138 The use of very strong Brønsted acids such as methanesulfonic and triflic acids may cause decomposition of the organosilane through hydrogen production14 and/or cleavage of Si–C bonds139 which compete with the desired reduction of the alcohol.126 These undesirable side reactions may be avoided or reduced by running the reaction at −78◦ .140 Sulfuric acid may cause undesirable oxidations to occur.134 On balance, the most commonly chosen set of conditions for the reduction of alcohols is triethylsilane and trifluoroacetic acid (Et3 SiH/TFA) in dichloromethane solution. The experimental evidence is convincing, at least with benzyl alcohols, that a “free” carbenium ion intermediate devoid of influence from its progenitor is the species that is captured by the non-nucleophilic organosilicon hydride. When optically active 2-phenyl-2-butanol is treated with Et3 SiH/TFA in chloroform, the 2-phenylbutane product is formed with complete racemization.26 When a dichloromethane solution of the same alcohol is treated with trifluoroacetic acid in the presence of enantiomerically enriched 1-naphthylphenylmethylsilane, the 2-phenylbutane product obtained shows a small, but reproducible enantiomeric excess of 2–3%.141 The predominant enantiomer formed in the product is dependent only on the predominant enantiomer of silane used as the reducing agent and is independent of whether one of the pure enantiomers or the racemic alcohol is used as substrate.142 The same stereochemical results are obtained in the hydrocarbon product when the alkene 2-phenyl-1-butene is the precursor to the carbenium ion intermediate (π-route, Eq. 2) instead of the tetrahedral alcohol (σ -route, Eq. 1).142 A similar conclusion is reached from a study of the reduction of optically active 1-phenylethanol to phenylethane-d1 with boron trifluoride etherate and triethylsilane-d1 .133 These experiments illustrate the lack of nucleophilicity or SN 2-like behavior of the organosilicon hydrides in these reactions and presage the stereochemistry expected from such transformations. Primary Alkyl Alcohols. Primary alkyl alcohols do not undergo reduction when treated with Brønsted acids and organosilicon hydrides under usual laboratory conditions.143 This reflects the relative instability of primary alkyl carbenium ions in the condensed phase and the weak intrinsic nucleophilicity of organosilicon hydrides. On the other hand, the combination of excess Et3 SiH and catalytic amounts (5–10 mol%) of (C6 F5 )3 B reduces primary aliphatic alcohols to the alkanes in high yields (Eq. 9), but the reaction stops at the non-reductive silylation of the alcohol with only a single equivalent of the silane.144,145 This type of reaction is thought to proceed via a direct nucleophilic displacement rather than by way of a carbenium ion mechanism.145

14

ORGANIC REACTIONS

Ph

OH

Et3SiH, B(C6F5)3

Ph

CH2Cl2, rt, 20 h

(>95%)

(Eq. 9)

Secondary Alkyl Alcohols. Treatment of secondary alkyl alcohols with trifluoroacetic acid and organosilicon hydrides results only in the formation of the trifluoroacetate esters; no reduction is reported to occur.1,2 Reduction of secondary alkyl alcohols does take place when very strong Lewis acids such as boron trifluoride126,129 or aluminum chloride136,146 are used. For example, treatment of a dichloromethane solution of 2-adamantanol and triethylsilane (1.3 equivalents) with boron trifluoride gas at room temperature for 15 minutes gives upon workup a 98% yield of the hydrocarbon adamantane along with fluorotriethylsilane (Eq. 10).129 OH

Et3SiH

(98%) + Et3SiF

CH2Cl2, BF3

(Eq. 10)

In contrast, when boron trifluoride etherate is substituted for the free boron trifluoride, only a trace of the hydrocarbon is formed, even after weeks of reaction.143 The unique effectiveness of boron trifluoride gas in promoting these reductions is believed to be due to several factors, including the ability of the coordinatively unsaturated boron center to rapidly and tightly coordinate with oxygen centers and to the thermodynamically favorable creation of a Si–F bond.1 A slight pressure of boron trifluoride gas must be maintained over the surface of the solution throughout the reaction because boron trifluoride has only limited solubility in the weakly coordinating dichloromethane solvent. The formation of alkenes and alkene-related polymerization products can seriously reduce the yields of desired alkane products from secondary alcohols, which can undergo elimination reactions. For example, reduction of 2-octanol at 0◦ with boron trifluoride gas in dichloromethane containing 1.2 equivalents of triethylsilane gives only a 58% yield of n-octane after 75 minutes (Eq. 11).129 The remainder of the hydrocarbon mass comprises nonvolatile polymeric material.126 OH n-C6H13

Et3SiH CH2Cl2, BF3

n-C8H18

(58%)

+ polymer

(Eq. 11)

Aluminum chloride, used either as a stoichiometric reagent or as a catalyst with gaseous hydrogen chloride, may be used to promote silane reductions of secondary alkyl alcohols that otherwise resist reduction by the action of weaker acids.136 For example, cyclohexanol is not reduced by organosilicon hydrides in the presence of trifluoroacetic acid in dichloromethane, presumably because of the relative instability and difficult formation of the secondary cyclohexyl carbocation. By contrast, treatment of cyclohexanol with an excess of hydrogen chloride gas in the presence of a three-to-four-fold excess of triethylsilane and 1.5 equivalents of aluminum chloride in anhydrous dichloromethane produces 70% of cyclohexane and 7% of methylcyclopentane after a reaction time of 3.5 hours at

ORGANOSILICON HYDRIDE REDUCTIONS

15

room temperature (Eq. 12).136 The cyclohexane is presumably formed by capture of the secondary cyclohexyl cation, whereas the methylcyclopentane must arise from hydride capture of the more stable tertiary methylcyclopentyl cation formed by rearrangement of the cyclohexyl cation.147,148 Diminishing the amount of aluminum chloride to only 0.5 equivalents results in no reaction after one-half hour and the formation of only 8% of cyclohexane after four hours reaction time. The reaction proceeds slowly in the absence of hydrogen chloride, producing 53% of cyclohexane and 6% of methylcyclopentane after 16.5 hours using two equivalents of aluminum chloride. Et3SiH

(70%)

+

OH HCl, AlCl3

(Eq. 12)

–H2O +

Et3SiH

(7%)

Tertiary Alkyl Alcohols. Tertiary alkyl alcohols generally undergo facile reduction when treated with acids in the presence of organosilicon hydrides.127,136 This comparative ease of reduction reflects the enhanced stability and ease of formation of tertiary alkyl carbenium ions compared with primary and secondary carbenium ions. Thus, treatment of 1-methylcyclohexanol with mixtures of triethylsilane and aluminum chloride in dichloromethane produces near quantitative yields of methylcyclohexane with or without added hydrogen chloride in as little as 30 minutes at room temperature, in contrast to the more vigorous conditions needed for the reduction of the secondary alcohol cyclohexanol.136 Similarly, and in contrast to the behavior of its secondary isomer, 2-adamantanol, 1-adamantanol undergoes smooth, quantitative reduction to adamantane in less than an hour at room temperature in dichloromethane solution containing triethylsilane under the catalysis of either free boron trifluoride129 or boron trifluoride etherate (Eq. 13).143 Et3SiH, CH2Cl2 OH

BF3 or Et2O•BF3

(100%)

(Eq. 13)

Although the synthetic yields of hydrocarbon products obtained from the reduction of tertiary alkyl alcohols are frequently quite high, studies show that the reaction pathways taken by the reactants are not always as direct or straightforward as might be suggested by the structural relationships between reactants and products. For example, preparative-scale treatment of a dichloromethane solution of 3-ethylpentan-3-ol and triphenylsilane (1.2 equivalents) with excess trifluoroacetic acid (1.5 M) at room temperature for 24 hours gives 3-ethylpentane in 78% yield (Eq. 14).127 Under these reaction conditions, the alcohol rapidly

16

ORGANIC REACTIONS

undergoes elimination to 3-ethyl-2-pentene, which is the actual species undergoing reduction. Et

OH

TFA

Et

Et

Et

CH2Cl2

Et

Et

Ph3SiH Et

Et

(Eq. 14)

(78%)

The tertiary alcohol cis,cis,trans-perhydro-9b-phenalenol (7) is converted stereospecifically and in high yield (92%) to trans,trans,trans-perhydrophenalene (10) when treated with either triethylsilane or triphenylsilane and trifluoroacetic acid in dichloromethane (Eq. 15). Studies indicate that the reaction path follows the cation rearrangement 8 → 9 and that the trans trifluoroacetate ester related to cation 9 is an intermediate, which accumulates during the reaction.127 H

OH

H

H

H+

+

H

1,2-H~

H

H

H

R3SiH

H

H

H

(Eq. 15) H 7

+ 9

H 8

H 10 (92%)

The conversion of alcohols directly into the structurally related hydrocarbons by ionic hydrogenation can provide a means of synthesis for compounds that would be extremely difficult or impossible to obtain by other methods. A good example is the synthesis of 2-tert-butyladamantane (12, R = Me). This interesting, highly strained compound may be synthesized in moderate overall yield by a conventional multiple-step route.149 Alternatively, it is obtained in 90% isolated yield upon treatment of a dichloromethane solution of the readily available 2-tert-butyl-2-adamantanol (11, R = Me)150 and one equivalent of either tri-nhexylsilane151,152 or triethylsilane153 with trifluoroacetic acid at room temperature (Eq. 16). OH R

R

R'3SiH

R = Me (90%) R = Ph (96%)

CH2Cl2, TFA 11

(Eq. 16)

12

In a similar fashion, 2-cumyladamantane (12, R = Ph) is formed in nearly quantitative yield upon treatment of the easily synthesized 2-cumyl-2-adamantanol (11, R = Ph)154 with triethylsilane and methanesulfonic acid in dichloromethane at −78◦ .155 The high yield of a single very strained hydrocarbon product in each reaction is quite surprising in view of the very complex interconversions of carbocations known to take place from the alcohol precursors.140,151,152,156 The remarkable chemoselectivity of this reductive technique is demonstrated by the conversion of the functionally rich compound 13 into 14 in 86% yield upon treatment with Et3 SiH/TFA at room temperature for two hours (Eq. 17).157

ORGANOSILICON HYDRIDE REDUCTIONS

HO

O

EtO2C

N H

N

N O

Et3SiH

N

TFA

17

O

(Eq. 17)

(86%) O

EtO2C

N H

13

N

14

Several sterically congested aryldiadamantylmethanols are reduced to atropisomeric diastereomeric mixtures of the corresponding aryldiadamantylmethanes with Et3 SiH/TFA (Eq. 18).158 – 161 Et

Et

Et

Et Et3SiH, TFA, CH2Cl2

Ad Ad HO

O

–10°, rt, 16 h

Et

Et

H + Ad Ad O Ad Ad H

(Eq. 18)

O

(—) 1:1

This reagent combination reduces a tertiary alcohol in the presence of a quinone moiety (Eq. 19).162 Tertiary alcohols are also reduced with the reagent combinations Et3 SiH/MeSO3 H140 and Et3 SiH/AlCl3 /HCl.136 OMe O HO

OMe O Et3SiH, TFA, CH2Cl2 –78° to 0°

CO2Et

CO2Et

O

(Eq. 19)

O (95%)

Cyclopropylcarbinols. Treatment of cyclopropylcarbinols 15 (R = Ph, c-C3 H5 ) with trifluoroacetic acid in dichloromethane leads to the rapid formation of ring-opened 4-substituted 3-butenyl-1-trifluoroacetate esters 16 (Eq. 20).130 Cyclopropylcarbinyl trifluoroacetates are not formed. Ring opening is facilitated by phenyl substituents. Addition of organosilicon hydrides to the reaction mixture favors the formation of cyclopropylmethanes 17 and suppresses the formation of the ring-opened esters.130 R OH R 15 R = c-C3H5 R = Ph

R'3SiH CH2Cl2, TFA

R

O2CCF3 R

R 16

R' = Et R' = Et

R + 17

(Eq. 20)

16 + 17 (—), 16:17 = 1:99 16 + 17 (—), 16:17 = 19:81

Triethylsilane and diethylsilane are somewhat more effective than triphenylsilane at increasing the amount of reduced product 17.130 Yields of 17 in excess of 90% may be obtained. The remainder of the product is butenyl ester 16. Hydrogenolysis of the cyclopropyl rings does not occur under these conditions. A better yield of 17 is obtained when the reaction is carried out at −15◦ than at room

18

ORGANIC REACTIONS

temperature. Under the same set of reaction conditions (dichloromethane, 0.5 M trifluoroacetic acid, 0.5 hour, room temperature), the amount of hydrocarbon product 17 (R = Ph) obtained from diphenylcyclopropylcarbinol changes from 16% with triphenylsilane as the hydride-donating reagent to 45% with triphenylgermane, 85% with triphenylstannane, and 78% with tri-n-butylstannane.24 Benzyl Alcohols. Benzyl alcohols of nearly all kinds undergo reduction when treated with acid in the presence of organosilicon hydrides. The most obvious exception to this is the behavior of benzyl alcohol itself. It resists reduction by the action of trifluoroacetic acid and triethylsilane, even after extended reaction times.26 Reducing systems consisting of triethylsilane and sulfuric acid/acetic acid or p-toluenesulfonic acid/acetic acid mixtures also fail to reduce benzyl alcohol to toluene.134 As previously mentioned, substitution of boron trifluoride for trifluoroacetic acid results in the formation of modest yields of toluene, but only when a very large excess of the silane is used in order to capture the benzyl cation intermediate and suppress Friedel-Crafts oligomerization processes.129,143 Ring-substituted benzyl alcohols sometimes undergo such reduction more effectively than unsubstituted alcohols. For example, treatment of a dichloromethane solution of 2,4,6-trimethylbenzyl alcohol with trifluoroacetic acid and triphenylsilane produces a 41% isolated (89% by GLC) yield of isodurene.26 Treatment of 2-methyl-4,6-di-tert-butylbenzyl alcohol with a three-fold excess of triethylsilane and trifluoroacetic acid in dichloromethane at room temperature gives an 85% yield of 2-methyl-4,6-di-tert-butyltoluene together with 15% of 3,5-di-tert-butyltoluene. The latter is presumably formed by loss of protonated formaldehyde from the C1 ring-protonated substrate.128 Similar treatment of 2,4,6-tri-tert-butylbenzyl alcohol produces a 90% yield of 2,4,6-tri-tertbutyltoluene within one hour (Eq. 21).128 OH Bu-t

t-Bu

R3SiH

Bu-t

t-Bu

(90%)

CH2Cl2, TFA

(Eq. 21)

t-Bu

t-Bu

The reduction of 2-(hydroxymethyl)-1,4,6,8-tetramethylazulene to 1,2,4,6,8pentamethylazulene occurs quantitatively upon treatment with triethylsilane and trifluoroacetic acid at 60◦ for 19 hours (Eq. 22).163

HO

Et3SiH TFA, 60°

(100%)

(Eq. 22)

Treatment of either the cis or trans isomer of 4-tert-butyl-1-phenylcyclohexanol with trifluoroacetic acid and one of a variety of organosilicon hydrides in dichloromethane yields a mixture of cis- and trans-4-tert-butyl-1-phenylcyclohexane and the elimination product, 4-tert-butyl-1-phenylcyclohexene

ORGANOSILICON HYDRIDE REDUCTIONS

19

(22–72%) (Eq. 23).26 More elimination product is obtained from the cis than from the trans alcohol. The trans/cis ratio of reduced products is independent of the isomer of starting alcohol used and depends only on the nature of the silane used. This ratio is ca. 1.8 for triorganosilanes (e.g., triethyl, tri-n-octyl, triphenyl) and ca. 4.0 for diorganosilanes (e.g., diethyl, diphenyl) and phenylsilane. The most important factor for the stereoselectivity of product formation seems to be the degree of steric bulk provided by the organic groups bonded to silicon, rather than the electronic nature of the substituents. The smaller the effective steric bulk of the reducing agent, the greater is the trans/cis product ratio.26 Replacement of the silanes with germanes or stannanes as the hydride donors causes a decrease in the amount of elimination product formed so that it becomes a minor product (10–38%).24 The trans/cis ratio of reduced products is ∼2 when triphenylgermane is used, ∼1.4 with triphenylstannane, and ∼0.85 with tri-n-butylstannane.24 Ph OH

t-Bu

Ph

R3SiH CH2Cl2, TFA

t-Bu

R = Et R = Et

cis trans

Ph H + t-Bu

(Eq. 23) (41%) (22%)

(59%) (78%)

Reduction of either the exo or endo isomer of 2-phenyl-2-norbornanol with trifluoroacetic acid and triethylsilane, triphenylsilane, or phenylsilane in dichloromethane gives endo-2-phenylnorbornane quantitatively (Eq. 24).164 The stereospecific formation of only the endo-hydrocarbon can be understood on the basis that only exo approach by organosilicon hydride toward the 2-phenylnorbornyl cation intermediate is kinetically competitive for product formation.164

R3SiH OH Ph

(100%)

CH2Cl2, TFA

(Eq. 24)

Ph

The bornyl system is less subject than the norbornyl system to exclusive exo approach by organosilicon hydrides and related reducing agents because of the steric restraints imposed by the additional methyl groups. Thus, treatment of a dichloromethane solution of p-anisylisoborneol (18) with trifluoroacetic acid and triphenylsilane quantitatively provides the isomeric reduced products p-bornylanisole (19) and p-isobornylanisole (20) in a ratio of 68 : 32 (Eq. 25).24 Replacement of the triphenylsilane with triphenylstannane produces 98% of 19 and 2% of 20. Use of the sterically less demanding phenylsilane gives 19 as the exclusive product. By comparison, trapping of the cation derived from 18 with borohydride gives 87% of 19 and 13% of 20.165

20

ORGANIC REACTIONS

R3SiH OH

+

CH2Cl2, TFA

PMP 18 PMP = 4-MeOC6H4

PMP

PMP R = Ph

(Eq. 25)

19 20 19 + 20 (100%), 19:20 = 68:32

Reductions of tertiary or benzylic alcohols do not always take place as quickly and simply as might be expected. A study of the reduction of 2-methyl-1phenylpropan-1-ol (21, R = OH) and its isomer, 2-methyl-1-phenylpropan-2-ol (22, R = OH), illustrates this observation.166 Both of these alcohols are reduced in high yield (98%) by the action of acid and triphenylsilane to the same hydrocarbon, 2-methyl-1-phenylpropane (21 or 22, R = H). The immediate products formed from either alcohol in a 55% solution of trifluoroacetic acid in nitrobenzene are the trifluoroacetate esters (R = CF3 CO2 ). Surprisingly, at 25◦ in the absence of organosilicon hydride, ester 21 (R = CF3 CO2 ) undergoes complete isomerization to ester 22 (R = CF3 CO2 ) within two hours. Use of triphenylsilaned1 as the reducing agent indicates that alcohol 21 (R = OH) actually produces a mixture of the two isotope-position isomers of the reduction product (21 and 22, R = D), with isomer 22 favored by a factor of 2 to 3 over isomer 21. Similar results are found when the starting alcohol is 22. The conclusion is reached that the species actually captured by the organosilicon hydride consists of a dynamic mixture of the two cations derived from 21 and 22.166 Ph

Ph R

R

21

22

In some instances, treatment of polyfunctional benzylic alcohols with acid in the presence of organosilicon hydrides causes multiple functional group transformations to occur simultaneously. This phenomenon is illustrated by the reduction of the secondary benzylic alcohol function and concomitant loss of the methoxymethyl protecting group of 2-(1-hydroxydecyl)-5-methoxy-1-(methoxymethyleneoxy)naphthalene upon treatment with Et3 SiH/TFA in dichloromethane (Eq. 26).167 O

MeO

OMe CHC9H19-n OH

OH C10H21-n

Et3SiH, TFA

(68%)

CH2Cl2, rt

(Eq. 26)

MeO

An example of an exclusive chemoselective reduction of a benzylic hydroxy function in a polyfunctional compound is seen in the conversion of 23 into 24

ORGANOSILICON HYDRIDE REDUCTIONS

21

in 76% yield using Et3 SiH/TFA (Eq. 27).168 The benzylic hydroxy group in a complex polypeptide derived from lysobactin is selectively reduced with the same reagents (Eq. 28).169 O OBn PMP

OEt CH2Cl2, rt

OH OBn 23

OEt

O OBn

Et3SiH, TFA PMP

(76%)

(Eq. 27)

OBn 24

O OH

H2 N O

NH NH

HO

NH O

CO2H H N

H 2N O

O

Ph N H

OH H N

HN

O

O HO

N H

OH O

O

H HN N

O

O

(Eq. 28) NH HN

NH2

H N

Et3SiH, TFA 0°, 1 h

H2 N O

O

Ph N H

H N O HO

O N H

(—)

Studies reveal an advantage to using boron trifluoride in dichloromethane at reduced temperatures instead of Brønsted acids in the organosilicon hydride reductions of a number of dialkylbenzyl alcohols.126,129 The use of Brønsted acids may be unsatisfactory under conditions in which the starting alcohol suffers rapid skeletal rearrangement and elimination upon contact with the acid, and also in which the alcohol does not yield a sufficient concentration of the intermediate carbocation when treated with protic acids.126 An example of an alcohol that can undergo rapid skeletal rearrangement is 3,3-dimethyl-2-phenyl-2-butanol (Eq. 29). Attempts to reduce this alcohol in dichloromethane solution with 1-naphthyl(phenyl)methylsilane yield only a mixture of the rearranged elimination products 3,3-dimethyl-2-phenyl-1-butene and 2,3-dimethyl-3-phenyl-1-butene when trifluoroacetic acid or methanesulfonic acid is used. Use of a 1 : 1 triflic acid/triflic anhydride mixture with a 50 mol% excess of the silane gives good yields of the unrearranged reduction product 3,3-dimethyl-2-phenylbutane, but also causes extensive decomposition of the silane.126 In contrast, introduction of boron trifluoride gas into a dichloromethane solution of the alcohol and a 10 mol% excess of the silane

22

ORGANIC REACTIONS

at −60◦ produces 86.5% of the desired, structurally intact hydrocarbon, 3,3dimethyl-2-phenylbutane, along with 13.5% of the methyl-shifted product, 2,3dimethyl-2-phenylbutane, within only six minutes. Clean formation of the fluorosilane related to the organosilicon hydride accompanies the reduction. The workup consists of quenching with solid potassium carbonate followed by addition of water, drying of the dichloromethane solution, and normal product isolation.126 OH Ph

Ph(1-Np)MeSiH

Bu-t

Ph

CH2Cl2, BF3, –65°

Bu-t

+

Ph

(Eq. 29)

(100%) 86.5:13.5

A variety of para-substituted 2-phenyl-2-butanols undergo quick and efficient reductions to the corresponding 2-phenylbutanes when they are dissolved in dichloromethane and a 2–10% excess of phenylmethylneopentylsilane and boron trifluoride is introduced at 0◦ (Eq. 30).126 Several reactions deserve mention. For example, when R = CF3 , use of trifluoroacetic acid produces no hydrocarbon product, even after two hours of reaction time. In contrast, addition of boron trifluoride catalyst provides an 80% yield of product after only two minutes. When R = MeO, both trifluoroacetic acid and boron trifluoride produce a quantitative yield of the hydrocarbon within two minutes. However, when R = NO2 , attempts to promote the reduction with either trifluoroacetic acid or even methanesulfonic acid fail; even after reaction periods of up to eight hours, only recovered starting alcohol is obtained. Use of boron trifluoride provides a quantitative conversion into 2-(p-nitrophenyl)butane after only ten minutes. It is significant that the normally easily reducible nitro group survives these conditions entirely intact.126,129 Triethylsilane may be used as the silane.143 OH Et3SiH CH2Cl2, BF3 R

(100%)

(Eq. 30)

R

Treatment with triethylsilane and boron trifluoride etherate allows a variety of methyl β-hydroxy-β-arylpropionates to be reduced to methyl β-arylpropionates in yields of 85–100% as part of a synthetic sequence leading to the preparation of indanones (Eq. 31).170 Small amounts of dehydration products formed simultaneously are reduced to the methyl β-arylpropionates by mild catalytic hydrogenation.170 OH Ph

CO2Me

Et3SiH BF3•OEt2

Ph

CO2Me

(100%)

(Eq. 31)

Diaryl and triaryl benzylic alcohols generally undergo smooth reduction to the corresponding hydrocarbons. Thus, both diphenyl- and triphenylcarbinol quickly give good to excellent yields of the corresponding substituted methanes when

ORGANOSILICON HYDRIDE REDUCTIONS

23

treated with triphenylsilane or Et3 SiH/trifluoroacetic acid in dichloromethane26 or with triethylsilane and mixtures of either sulfuric or p-toluenesulfonic acids in acetic acid.136 The reductions do not occur with the parent, unsubstituted carbinols using only acetic acid; however, tri-p-anisylcarbinol, 2,2′ ,2′′ ,6,6′ ,6′′ hexamethoxytriphenylcarbinol, 9-phenyl-9H -xanthen-9-ol, 9-p-anisyl-9H xanthen-9-ol,26 and 9-(2,6-dimethoxyphenyl)-1,8-dimethoxy-9H -xanthen-9-ol29 all undergo smooth conversion to the respective hydrocarbons when treated with acetic acid containing triethylsilane. In fact, the use of acetic acid as both solvent and catalyst may be the method of choice in effecting the reductions of very electron-rich benzylic alcohols and those that form acid-labile reduction products. When 2,2′ ,2′′ ,6,6′ ,6′′ -hexamethoxytriphenylcarbinol is treated with Et3 SiH/trifluoroacetic acid in dichloromethane, the reduction goes beyond the triarylmethane stage to produce one equivalent of 2,2′ ,6,6′ -tetramethoxydiphenylmethane and one equivalent of mdimethoxybenzene.26 These additional products are thought to arise from protonation of one of the electron-rich rings of the initially formed 2,2′ ,2′′ ,6,6′ ,6′′ hexamethoxytriphenylmethane at C1 by the trifluoroacetic acid. Expulsion of a molecule of m-dimethoxybenzene followed by hydride capture of the 2,6,2′ ,6′ -tetramethoxydiphenylmethyl “daughter” cation formed accounts for the final mixture of products.26 Sesquixanthydrol 25 undergoes reduction to the hydrocarbon only reluctantly, presumably because of the great stability of the sesquixanthydryl cation (1). An early report indicates that the alcohol is able to resist reduction upon treatment with trifluoroacetic acid and excess triethylsilane in dichloromethane for 24 hours and to remain unreduced when dissolved in acetic acid containing triethylsilane.26 A later report indicates formation of the hydrocarbon in 89% yield (Eq. 32).29 O OH O

O H

Et3SiH, HOAc O

reflux, 40 h

O

O

(89%)

(Eq. 32)

25

Intramolecular Friedel-Crafts reactions can sometimes compete with organosilicon hydride reductions of benzylic-type alcohols to cause formation of undesired products. An example is the attempted reduction of alcohol 26 to the corresponding hydrocarbon. When 26 is treated with triethylsilane in trifluoroacetic acid at room temperature for 15 hours, a mixture of the two fluorene isomers 27 and 28 is obtained in a combined yield of 45%. None of the hydrocarbon structurally related to the substrate alcohol 26 is obtained.171 Whether this problem could be circumvented by running the reduction at a lower temperature or with a different acid remains subject to experimentation. Both benzylic and secondary aliphatic alcohols are reduced with the combination of Ph2 ClSiH and a catalytic amount of indium trichloride. This combination

24

ORGANIC REACTIONS F

F

F

OH

OH OH

OH CO2Me

CO2Me

CO2Me

27

26

28

chemoselectively reduces benzyl alcohols in the presence of both ester and halide functions (Eq. 33).172 Ph

Ph2SiHCl, InCl3

CO2R

Ph

CO2R

OH R Et CH2Cl

(Eq. 33)

Conditions ClCH2CH2Cl, 50°, 0.5 h CH2Cl2, rt, 3 h

(68%) (95%)

The combination of excess Et3 SiH and catalytic amounts (5–10 mol%) of (C6 F5 )3 B reduces benzylic alcohols to the hydrocarbons (Eq. 34), although the reaction stops at the non-reductive simple silylation of the alcohol with only a single equivalent of the silane.144,145 OH Ph

Et3SiH, (C6F5)3B CH2Cl2, rt, 20 h

Ph

Ph

Ph

(Eq. 34)

(98%)

Allyl Alcohols. Secondary cyclic allylic alcohols are reduced with the combination of Et3 SiH and ethereal LiClO4 , even in the presence of a tertiary alcohol (Eq. 35) or ketal function.173 Primary allylic alcohols do not undergo deoxygenation under similar conditions.173 OH

HO

Et3SiH, LiClO4 Et2O, rt, 16 h

OH

(Eq. 35)

(52%)

Treatment of 1-[2-(2-methoxy-5-isopropylphenyl)-1-hydroxyethyl]-2,6,6-trimethylcyclohexene with triethylsilane and boron trifluoride etherate in dichloromethane at −10◦ leads to its reduction to 2-(2,6,6-trimethyl-1-cyclohexenyl)-1(2-methoxy-5-isopropylphenyl)ethane in 69% yield (Eq. 36).174 OMe

OMe Et3SiH, CH2Cl2

OH

Et2O•BF3, –10°

(69%)

(Eq. 36)

Metal-Complexed Alcohols. It is well known that carbocations are frequently stabilized when organotransition metal centers are present in adjacent portions of

ORGANOSILICON HYDRIDE REDUCTIONS

25

the molecule.175 – 177 It is thus not surprising that alcohols possessing such centers are prone to undergo facile reduction upon treatment with acids and organosilicon hydrides. Perhaps it is more surprising that the coordinated metal centers survive the reduction conditions so well. Methylferrocenylcarbinols bearing several functional groups (R = H, Cl, CO2 Me, CN) on the distal C5 ring undergo reduction to the corresponding ethylferrocenes when treated with an excess of Et3 SiH/TFA in acetic acid solution at 20◦ (Eq. 37).178 The yields of reduced product are no less than 85% within three hours, except when R = CN. Then the conversion into the ethylferrocene is only 55% complete after 20 hours of reaction time, reflecting the destabilizing effect of the cyano group on the intermediate carbocation. In a similar fashion, symmetrically disubstituted ferrocenylcarbinols undergo facile double deoxidative reduction in yields of more than 80% within three hours at 20◦ when dissolved in trifluoroacetic acid and treated with two equivalents of triethylsilane (Eq. 38).179 The “half-sandwich” cyclopentadienylmanganese tricarbonyl (cymantrene) carbinol undergoes reduction in a similar way to that of its ferrocenylcarbinol analogs (Eq. 39).180

OH

Fe R

Et3SiH, TFA HOAc, 20°

(55-95%)

Fe R

(Eq. 37)

R = H, Cl, CO2Me, CN R Fe

R OH

R Et3SiH, TFA Fe

R

(83-90%)

(Eq. 38)

OH R = H, Me, CH2CN Et Mn(CO)3

Et3SiH, TFA OH

Et Mn(CO)3

(92%)

(Eq. 39)

Highly diasteroselective and chemoselective reductions may be performed on the hydroxy functions of (η6 -arene)-tricarbonylchromium complexes. Treatment of the chromium-complexed benzylic alcohol 29 with triethylsilane and boron trifluoride etherate in dichloromethane at −78◦ to 0◦ gives only diastereomer 30 in 75% yield (Eq. 40).181 In a similar fashion, treatment of the complexed exoallyl-endo-benzylic alcohol 31 with an excess of Et3 SiH/TFA in dichloromethane at room temperature under nitrogen produces only the endo-allyl product 32 in 92% yield after 1.5 hours (Eq. 41). It is noteworthy that no reduction of the isolated double bond occurs.182

26

ORGANIC REACTIONS OH OBn

OBn Et3SiH, CH2Cl2 BF3•OEt2, –78° to 0°

OMe

(CO)3Cr

(CO)3Cr

29

(75%)

(Eq. 40)

(92%)

(Eq. 41)

OMe 30

(CO)3Cr

Et3SiH, CH2Cl2 OH

(CO)3Cr

TFA

31

32

Treatment of α-hydroxyalkylidynetricobalt nonacarbonyl complexes of type 33 with strong acids produces the related highly stabilized carbocations 34.183 As expected, heating a tetrahydrofuran solution of the methyl compound (33, R = Me) with trifluoroacetic acid and triethylsilane at reflux for four hours produces the related hydrocarbon complex (35, R = Me) in 72% yield. Somewhat surprising, however, is the report that the hexafluorophosphate salt of the phenylsubstituted carbocation (34, R = Ph, X− = PF6 − ), preformed by treatment of the corresponding alcohol with hexafluorophosphoric acid, produces only 7% of the related hydrocarbon complex when exposed to triethylsilane in tetrahydrofuran for 1.5 hours at room temperature. This lower yield of hydrocarbon complex from the phenyl system compared with the methyl analog is probably a reflection of the greater stability and lower reactivity of the intermediate cation. OH (CO)9Co3CC H R 33

H + – (CO)9Co3CHC X R 34

(CO)9Co3CCH2R 35

33–35 R = Me, Ph

Polyfunctional Hydroxy Compounds. Different classes of alcohols can serve as the precursors to carbocations that have different stabilities and different degrees of ease of formation. It is thus no surprise that selective acid-catalyzed organosilicon hydride reductions of alcohols of one type may be effected in the presence of others if the proper reaction conditions are employed. For example, either tertiary or secondary benzylic hydroxy groups may be replaced by hydrogen without affecting primary aliphatic-type hydroxy groups in the same molecule when boron trifluoride etherate and triethylsilane are used.137 This Et3 SiH/BF3 • OEt2 reagent combination is also selective for a benzylic alcohol over an aliphatic alcohol function.137 Treatment of 1,1-diphenylpropane-1,3-diol with two equivalents each of boron trifluoride etherate and triethylsilane in dichloromethane at 0◦ gives a 90% yield of 3,3-diphenylpropan-1-ol after 30 minutes (Eq. 42). Replacement of the terminal CH2 OH group by a CO2 Et group and similar treatment produces a product mixture containing 50% of the reduced product and 18% of the corresponding

ORGANOSILICON HYDRIDE REDUCTIONS

27

alkene elimination product. The carboethoxy group is unaffected by these reduction conditions.137 Ph

OH

Ph

Ph

Et3SiH, CH2Cl2

(Eq. 42)

(90%)

BF3•OEt2, 0°, 0.5 h

OH

OH Ph

The secondary benzylic alcohol 1-phenylethan-1,2-diol requires 20 hours of treatment at room temperature to produce a 64% yield of 2-phenylethanol (Eq. 43).137 Under the same conditions, methyl mandelate fails to undergo reduction, presumably because of the greater carbocation-destabilizing effect of a neighboring carboalkoxy compared to a hydroxymethyl group (Eq. 43).137 OH Ph

Et3SiH, BF3•OEt2 Ph

rt, 20 h

R

(64%)

R

(Eq. 43)

R CH2OH CO2Me

(64%) (0%)

Triethylsilane/boron trifluoride etherate in chloroform at room temperature reduces only the benzylic 12-hydroxy group of the polyfunctional compound 36 to form (±)-homochelidonine 37 in 92% yield (Eq. 44).138 OH HO H

HO H

O O N

MeO

Et3SiH, CHCl3

H Me

O O

BF3•OEt2

H N Me

MeO

(92%)

OMe

OMe 36

37

(Eq. 44)

It is possible to effect reduction of tertiary benzylic hydroxy functions in the presence of primary halogens. Treatment of 1,1-diphenyl-1-hydroxy-2haloethanes in chloroform with a slight excess of triethylsilane and a 9- to 10-fold excess of trifluoroacetic acid yields the corresponding 2,2-diphenyl-1-haloethanes (Eq. 45). The yield of the chloride is 77% after one hour at −15◦ , whereas that of the bromide is 66% following one hour at 0◦ .184 X OH Ph

Ph

Et3SiH, CHCl3 TFA

X Ph

Ph

X Cl Br

(77%) (66%)

(Eq. 45)

Alkyl Halides and Triflates to Alkanes. The normal requirements for conversion of alkyl halides (and triflates) to alkanes using organosilicon hydrides are essentially the same as those needed for the reduction of the corresponding alcohols, namely, the substrates must generally be able to serve as precursors to

28

ORGANIC REACTIONS

carbocations that may be captured by the hydride. The reduction of alkyl halides has been accomplished with triethylsilane/aluminum chloride. Substrates that undergo reduction under these conditions include primary alkyl halides,146,185,186 secondary alkyl halides,146,187,188 gem-dihalides,189 vicinal dihalides,189 and tertiary alkyl halides.187,188 As expected, haloarenes generally do not undergo such reductions, even under vigorous conditions.146,190 An exception to the need for carbocation formation is found when the silyl hydride functional group is part of a valence-expanded hydrosiliconate species. For example, potassium tetraethoxyhydridosilicate104 is capable of reducing primary alkyl and benzylic bromides and chlorides directly to the corresponding hydrocarbons without the need for additional catalysis (Eq. 46).95 The reaction is not a simple nucleophilic displacement of hydride for halide, however, since dimers can be formed as part of the reaction product mixture. In addition, when 6bromo-1-hexene is used as the substrate, 4.4% of methylcyclopentane is obtained along with 63% of 1-hexene product.95 The presence of the ring-closed product is suggestive of the operation of single-electron transfer (SET) processes.191 [(EtO)4SiH]– K+ + RX

THF, 48 h RH + RR + Si(OEt)4

(Eq. 46)

R = primary alkyl, benzyl

Alkyl Halides. Commonly, reductions with liquid silanes and liquid alkyl halides do not require the use of a solvent.186 When the alkyl halide is a solid, either pentane186 or dichloromethane may be used as solvent.192 No significant difference in reactivities is observed between alkyl chloride and bromide substrates,186 but allyl halides are more reactive than 2-halopropanes, which, in turn, are more reactive than 1-halopropanes.190,146 With halides having a strong propensity to undergo ionization, such as trityl halides, reductions may occur in the absence of added Lewis acids.29,54 Otherwise, the presence of Lewis acids is required. Catalytic amounts of aluminum bromide and aluminum chloride seem to be equally effective unless there are other Lewis base centers such as oxygen in the molecule to compete with the halogen for complexation with the Lewis acid.192 Then it is necessary to add more than one equivalent of the Lewis acid to effect reduction of the carbon-halogen function.136,146 Skeletal rearrangements may occur during these reductions, as in the reduction of bromocycloheptane (Eq. 47).146,185 Br Et3SiH, AlCl3

+

HCl (39%)

(Eq. 47) (26%)

In contrast to the behavior of primary alcohols, which resist reduction by organosilicon hydrides even in the presence of very strong acids, primary halo alkanes, including methyl iodide and ethyl bromide,186 undergo reduction when treated with aluminum chloride and organosilicon hydrides.146,185,186 Slow addition of a catalytic amount of aluminum chloride to a nearly equimolar

ORGANOSILICON HYDRIDE REDUCTIONS

29

mixture of 1-chlorohexane and triethylsilane produces a vigorous reaction that, after 28 hours and simple distillation, gives a 57% yield of n-hexane and an 88% yield of chlorotriethylsilane (Eq. 48).185 Similar treatment of 2,2-dimethyl1-chloropropane gives 2-methylbutane in 37% yield (Eq. 49), whereas treatment of 3,3-dimethyl-1-chlorobutane gives a 50% yield of 2-methylbutane (Eq. 50).185 Polymeric hydrocarbon by-products accompany the products of the latter two reactions. The structures of the products are clear evidence of the occurrence of 1,2-alkyl shifts leading to more stable carbocationic intermediates. Cl

Et3SiH

(57%)

AlCl3 Et3SiH

Cl

AlCl3 Et3SiH

Cl

AlCl3

(Eq. 48)

(37%)

(Eq. 49)

(50%)

(Eq. 50)

The use of a deuterium-labeled organosilicon hydride and location of the deuterium isotope in the reduced product shows that 1,2-hydride shifts also occur. Thus, reduction of 1-bromohexane with triethylsilane-d1 yields hexane with all of the deuterium at C2 (Eq. 51); similar treatment of cyclohexylmethyl bromide produces methylcyclohexane-1-d1 (Eq. 52).186 Et3SiD Br

AlCl3

Br

D

(—)

(Eq. 51)

D Et3SiD

(Eq. 52)

(—)

AlCl3

Trialkylsilanes are generally more effective than dialkyl- or monoalkylsilanes in minimizing isomerizations. The reduction of 2-bromododecane to dodecane proceeds under aluminum chloride catalysis in 82% yield using n-butylsilane and in 87% yield with tri-n-butylsilane.186 However, similar treatment of bromocycloheptane with triethylsilane yields a mixture of 39% cycloheptane and 26% methylcyclohexane. The same substrate yields 65% methylcyclohexane and less than 1% cycloheptane when n-butylsilane is the reducing agent.186 Total reduction of unbranched open-chain and cyclic derivatives of dichloro and dibromo alkanes occurs at room temperature within 30 minutes in dichloromethane solutions containing ca. 2.5 equivalents of triethylsilane and ca. 0.25 equivalents of aluminum chloride.189 The reaction occurs equally well with geminal, vicinal, and ω-dihalo alkanes. For example, 1,5-dibromopentane gives n-pentane in 85% yield when treated in this way (Eq. 53).189 Br

Br

Et3SiH CH2Cl2, AlCl3

(85%)

(Eq. 53)

30

ORGANIC REACTIONS

Chlorocyclohexane is converted into cyclohexane in dichloromethane using ethyldichlorosilane as reducing agent.192 The product yield is 40% with 25 mol% aluminum chloride and 45% with aluminum bromide. 1-Chloro-1-methylcyclohexane gives a 94% yield of methylcyclohexane using aluminum chloride and a 92% yield with aluminum bromide. Ethyldichlorosilane is superior as a hydride donor to either cumene or dicumylmethane.192 2-Bromoadamantane and 1-bromoadamantane are reduced to adamantane in yields of 84% and 79%, respectively, when treated with triethylsilane and catalytic amounts of aluminum chloride.186 Similar treatment of benzhydryl chloride and exo-2-bromonorbornane gives the related hydrocarbons in yields of 100% and 96%, respectively.186 In contrast, 2-bromo-1-phenylpropane gives only a 43% yield of 1-phenylpropane; the remainder consists of Friedel-Crafts alkylation products.186 Some alkyl halides resist reduction by this method, even when forcing conditions are employed. These include p-nitrobenzyl bromide, 3-bromopropanenitrile, and 5-bromopentanenitrile.186 The reduction of 4-chloro-4-methyltetrahydropyran with triethylsilane requires more than a catalytic amount of aluminum chloride. No 4-methyltetrahydropyran is obtained after 20 hours at room temperature even when 0.75 equivalents of the catalyst is used, but a 92% yield is obtained after only 30 minutes when two equivalents of catalyst and three equivalents of triethylsilane are used.136,146 This is presumably a result of the ability of the Lewis acid to coordinate at the ring oxygen as well as at the chlorine. The introduction of alkyl groups at C2 appears to introduce enough steric hindrance near the ring oxygen to enable less than one equivalent of aluminum chloride to effect reduction, but also makes the products unstable to the reaction conditions so that the synthetic yields decline compared with the unsubstituted substrate.136 Dichloromethane solutions of some sterically congested benzyl chlorides and triethylsilane need only the addition of excess trifluoroacetic acid to promote rapid conversion of the chlorides to the related hydrocarbons.128 Thus 2,4,6trimethylbenzyl chloride produces a 79% yield of isodurene at room temperature after 2.5 hours, 2-methyl-4,6-di-tert-butylbenzyl chloride gives 50% 1, 2-dimethyl-4,6-di-tert-butylbenzene after 40 minutes at reflux, and 2,4,6-tert-butylbenzyl chloride gives a 100% yield of 2,4,6-tri-tert-butyltoluene within 17 minutes at reflux (Eq. 54). The unsubstituted parent benzyl chloride remains unreacted under these conditions even after 30 days.128

R1

R1 Cl

R2

Et3SiH, CH2Cl2 TFA

R2

R2 R1

R2

Me Me t-Bu

Me t-Bu t-Bu

(79%) (50%) (100%)

R2

(Eq. 54)

ORGANOSILICON HYDRIDE REDUCTIONS

31

It is clear that the ionizing power of the solvent used is important in many of these reductions. When 2,4,6-trimethylbenzyl chloride is heated with diphenylsilane in nitrobenzene at temperatures as high as 130◦ , no isodurene is formed.193 Not unexpectedly, the same lack of reactivity is reported for a series of benzyl fluorides, chlorides, and bromides substituted in the para position with nitro or methyl groups or hydrogen when they are heated in nitrobenzene solutions with triethylsilane, triethoxysilane, or diphenylsilane.193 The combination of boron trifluoride etherate and triethylsilane can cause the reduction of tertiary fluoride centers even in polyfunctional compounds (Eq. 55).194 O Ph

O O

Ph

Et3SiH, BF3•OEt2

O

(100%)

CH2Cl2, –20°, 8 h

F

(Eq. 55)

Alkyl iodides, benzyl chlorides, benzyl bromides, and adamantyl bromides and iodides undergo reduction with triethylsilane/palladium chloride.195 The reduction of a β-chloro ether occurs in excellent yield with this system (Eq. 56).195 MeO

Cl

O

Et3SiH, PdCl2

MeO

rt, 10 min

(>95%)

O

(Eq. 56)

Allyl Halides. Reduction of a polyfunctional allyl chloride occurs without rearrangement and without reduction of the tosylate using Ph2 SiH2 /ZnCl2 / Pd(PPh3 )4 (Eq. 57).196 Ph2SiH2, ZnCl2, Pd(PPh3)4 SO2Tol Cl

SO2Tol

THF, rt, 12 h, 50°, 6 h

(Eq. 57)

(58%)

α-Halocarbonyl Compounds. The reduction of α-chloro and α-bromo ketones and esters has been accomplished with combinations of PhSiH3 / Mo(CO)6 ,197 Ph2 SiH2 /ZnCl2 /Pd(PPh3 )4 ,197 Ph2 SiH2 /Pd(OAc)2 ,197 and Et3 SiH/ PdCl2 ,195 with the first reagent combination giving the best results.197 One example of an α-chloro amide reduction is reported.198 2-Bromopropiophenone is reduced to propionic acid with polymethylhydrosiloxane (PMHS, 38), an inexpensive industrial commodity, and Pd(PPh3 )4 in 35% yield.199 This reagent combination also reduces α-halo ketones in high yields (Eq. 58).199 O

O Br

PMHS, Pd(PPh3)4, Bn3N MeCN/Me2SO (1:1), 110°, 3 h

Me3Si O

H Si O SiMe3 Me n

38

(80%)

(Eq. 58)

32

ORGANIC REACTIONS

Vinyl and Aryl Halides and Triflates. The organosilane reduction of aryl halides is possible in high yields with triethylsilane and palladium chloride.195 The reaction is equally successful with aryl chlorides, bromides, and iodides. Aryl bromides and iodides, but not chlorides, are reduced with PMHS/Pd(PPh3 )4 in moderate to excellent yields.199 This system also reduces vinyl bromides.199 p-Chlorobenzophenone is reduced to benzophenone with sym-tetramethyldisiloxane and Ni/C in excellent yield (Eq. 59).200 There is a report of the organosilane reduction of aryl and vinyl triflates in very high yields with the combination of Et3 SiH/Pd(OAc)2 /dppp (1,3-bis(diphenylphosphino)propane) (Eq. 60).201 O

O HMe2SiOSiMe2H, 10% Ni/C

(96%)

(Eq. 59)

PPh3, dioxane, reflux, 15 h Cl N

CF3

n-C10H21

OTf N

CF3

Et3SiH, Pd(OAc)2 dppp, DMF, 60°, 3 d

N

CF3

N

CF3 (95%)

n-C10H21

(Eq. 60) Reduction of Unsaturated Hydrocarbons Alkenes to Alkanes. The “ionic hydrogenation” of many compounds containing carbon-carbon double bonds is effected with the aid of strong acids and organosilicon hydrides following the π-route outlined in Eq. 2. A number of factors are important to the successful application of this method. These include the degree and type of substituents located around the double bond as well as the nature and concentrations of the acid and the organosilicon hydride and the reaction conditions that are employed. The most common reaction conditions for alkene reductions use excess trifluoroacetic acid and triethylsilane either neat202 – 204 or in an inert solvent such as nitrobenzene,134 2-nitropropane,205 carbon tetrachloride,206 chloroform,207 or dichloromethane.127,164 Reaction temperatures from −78◦ to well over 100◦ are reported. Ambient or ice-bath temperatures are most commonly used, but variations of these conditions abound. Among other silicon hydrides reported are n-butylsilane, diethylsilane, triisopentylsilane, tricyclopentylsilane, triphenylsilane, tri-sec-butylsilane, di-tertbutylsilane, di-tert-butylmethylsilane, tri-tert-butylsilane,204 phenylsilane, diethylmethylsilane,202 diphenylsilane,134,208,209 dichloroethylsilane,192 PMHS,77 and polyethylhydrosiloxane.207 Acids that are used in addition to trifluoroacetic acid include trifluoroacetic acid with added sulfuric acid203 or boron trifluoride etherate,210,211 perfluorobutyric acid,212 hydrogen chloride/aluminum chloride,136,146,213 perchloric acid in chloroform,214 p-toluenesulfonic acid alone134 or with aluminum bromide or aluminum chloride,192 concentrated sulfuric acid in two-phase systems with dichloromethane, alcohol, or ether solvents,209,215 trifluoromethanesulfonic acid,216 chlorodifluoroacetic acid,134 and the monohydrate of boron trifluoride

ORGANOSILICON HYDRIDE REDUCTIONS

33

(BF3 •OH2 ).217 The use of a sulfonated phenol-formaldehyde polymer in conjunction with formic acid is also reported.208 Acids that are ineffective include phosphoric,208 trichloroacetic, dichloroacetic, and acetic acids.134 It is reported that addition of lithium perchlorate to the reaction mixture improves product yields.193,205 Other organosilane/acid reagent combinations that are used in the reduction of olefins to alkanes include Et3 SiH/NH4 F/TFA,135 Et3 SiH/HClO4 ,214 Et3 SiH/ TiCl4 ,218 PMHS/Pd-nanocomposite,219 Et3 SiH/TFA/HClO4 ,205 Et3 SiH/PdCl2 ,220 polyethylhydrogensiloxane (PEHS)/TFA,207 Et3 SiH/TMSOTf,216 and Et3 SiH/ HCO2 H.208 The triethylsilane/trifluoroacetic acid reagent system reduces alkenes to alkanes in poor to excellent yields depending largely on the ability of the alkene to form carbocations upon protonation. Under these conditions the more substituted olefins are reduced in better yields and styrene double bonds are reduced in high yields.127,202,207,221 – 228 The reduction of 1,2-dimethylcyclohexene with this reagent gives a mixture of cis- and trans-1,2-dimethylcyclohexane.229 The formation of the trifluoroacetate esters is a side reaction.205,230 Potential problems associated with double bond reduction by this method may be understood in terms of Eq. 61. Protonation of the double bond leads to the formation of the more stable carbocation. This carbocation may rearrange by a first-order process or react competitively with either indigenous nucleophiles or added silicon hydride by second-order processes. If strong nucleophiles such as those associated with weak Brønsted acids are present, then the limited degree of reversibility of carbocation regeneration following nucleophilic capture may lead to diversion of the desired reduction products to unwanted nucleophilic substitution products.209 Another problem exists if bimolecular polymerization reactions compete with carbocation capture by organosilicon hydrides because of the proximity of carbocations and unprotonated alkene substrate. When this occurs, yields of reduced product suffer. The yields of hydrocarbons from alkenes are, in fact, frequently lower than those of the same products derived from the corresponding alcohols because of this problem.134,142

H X

(Eq. 61) + X–

HX H

R3SiH H H

When trifluoroacetic acid is used as the source of protons, it is known that rapid formation of trifluoroacetate esters precedes reduction to hydrocarbons.134,204,206 Use of acetic acid in place of trifluoroacetic acid, for example, would be expected to fail to produce good conversion to reduced product because of the combination of decreased acidity and increased nucleophilicity of acetic acid relative to

34

ORGANIC REACTIONS

trifluoroacetic acid as well as its weaker ionizing power as a solvent. This is consistent with experimental observations.134,209 The relative stability of the carbenium ion resulting from double bond protonation is a controlling factor in the limitation of this method of hydrogenation. On a practical level, only alkenes that can produce carbenium ions at least as stable as tertiary aliphatic ones undergo reduction to alkanes in useful yields. This distinction serves as a basis for selectivity of reduction. Under essentially every set of conditions reported, 1-methylcyclohexene, which forms a tertiary aliphatic carbenium ion upon protonation, undergoes reduction to methylcyclohexane in good to excellent yields, whereas cyclohexene, which can only form a secondary aliphatic carbenium ion intermediate upon protonation, does not normally undergo reduction. Indeed, treatment of an equimolar mixture of cyclohexene and 1-methylcyclohexene with two equivalents of triethylsilane and four equivalents of trifluoroacetic acid at 50◦ gives, after 10 hours, a 70% yield of methylcyclohexane together with completely recovered, unreacted cyclohexene.231 An exception is reported when the reactions are conducted using a twofold excess of dichloroethylsilane with equal equivalents of either aluminum chloride or aluminum bromide and p-toluenesulfonic acid at 40◦ for two hours in dichloromethane. Under these conditions, 1-methylcyclohexene affords methylcyclohexane in 65–75% yield, whereas cyclohexene gives cyclohexane in 17–23% yield.192 The use of deuterated organosilicon hydrides in conjunction with proton acids permits the synthesis of site-specific deuterium-labeled compounds.59,126,221 Under such conditions, the deuterium atom in the final product is located at the charge center of the ultimate carbocation intermediate (Eq. 62). With the proper choice of a deuterated acid and organosilicon hydride, it may be possible to use ionic hydrogenation in a versatile manner to give products with a single deuterium at either carbon of the original double bond, or with deuterium atoms at both carbon centers.127 +

+ X–

HX H

R3SiD

(Eq. 62) H D

Monosubstituted Alkenes. Simple unbranched terminal alkenes that have only alkyl substituents, such as 1-hexene,203 1-octene,209 or allylcyclohexane230 do not undergo reduction in the presence of organosilicon hydrides and strong acids, even under extreme conditions.1,2 For example, when 1-hexene is heated in a sealed ampoule at 140◦ for 10 hours with triethylsilane and excess trifluoroacetic acid, only a trace of hexane is detected.203 A somewhat surprising exception to this pattern is the formation of ethylcyclohexane in 20% yield upon treatment of vinylcyclohexane with trifluoroacetic acid and triethylsilane.230 Protonation of the terminal carbon is thought to initiate a 1,2-hydride shift that leads to the formation of the tertiary 1-ethyl-1-cyclohexyl cation.230 On the other hand, if the single substituent can stabilize an adjacent carbocation center following protonation of the alkene, then reduction may occur.

ORGANOSILICON HYDRIDE REDUCTIONS

35

Styrene is reported to undergo reduction upon treatment with trifluoroacetic acid and triethylsilane,203 although competing polymerization reactions limit the yield of ethylbenzene to only 30% (Eq. 63).70 Vinylcyclopropane is reduced to ethylcyclopropane within 30 minutes under similar conditions (Eq. 64).232 It is important to note that the cyclopropane ring of ethylcyclopropane can be opened under these reaction conditions, albeit with longer reaction times, to give some trans2-pentene in the final reaction mixture.233 Et3SiH

(30%)

(Eq. 63)

(100%)

(Eq. 64)

TFA Et3SiH TFA, rt

Examples of the behavior of other substituted vinyl substrates upon exposure to the action of trifluoroacetic acid and triethylsilane are known. For example, n-butyl vinyl ether, when reacted at 50◦ for 10 hours, gives n-butyl ethyl ether in 80% yield (Eq. 65).234 In contrast, n-butyl vinyl thioether gives only a 5% yield of n-butyl ethyl sulfide product after 2 hours and 15% after 20 hours of reaction.234 It is suggested that this low reactvity is the result of the formation of a very stable sulfur-bridged carbocation intermediate that resists attack by the organosilicon hydride (Eq. 66). Et3SiH

O

S

H+

+S

Et3SiH

(Eq. 65)

(80%)

O

TFA

S

(15%)

(Eq. 66)

20 h

Attempted reduction of vinyl acetate yields a mixture containing 8% ethyl acetate and 3% ethyl trifluoroacetate after 10 hours. The amounts of the two esters change to 13% and 12%, respectively, at reaction times beyond 60 hours.234 Vinyl trifluoroacetate does not undergo reduction under these conditions, even after 75 hours.234 Treatment of N -vinyl-3-methyl-6-pyridazone with excess trifluoroacetic acid and triethylsilane at 65◦ for 25 hours yields 67% of the reduced product N -ethyl3-methyl-6-pyridazone (Eq. 67).235 It is noteworthy that only the vinyl group in this compound undergoes reduction under these conditions, and not the ring or carbonyl sites. Examination of a solution of the starting N -vinyl-3-methyl6-pyridazone in neat trifluoroacetic acid by 1 H NMR spectroscopy shows the existence of the trifluoroacetate ester expected from the carbocation formed by protonation of the vinyl group at the terminal carbon. It is of interest that a similar compound, N -allyl-3-methyl-6-pyridazone, is inert under these conditions (Eq. 68). This reflects the differences of the relative stabilities of the carbocations formed upon protonation of the C=C groups in each reaction.

36

ORGANIC REACTIONS

N N

N N

Et3SiH TFA

O

(67%)

(Eq. 67)

O

N N

Et3SiH

(Eq. 68)

no reaction

TFA

O

Disubstituted Alkenes. Simple 1,2-disubstituted alkenes such as 2-octene or cyclohexene, which produce only secondary aliphatic carbocation reaction intermediates, do not undergo reduction upon treatment with a Brønsted acid and an organosilicon hydride. Even when extreme conditions are employed, only traces of reduction products are detected.192,203,207 – 210,214 An exception is the report that 4-methyl-2-pentene forms 2-methylpentane in 70% yield when heated to 50◦ for 20 hours with a mixture of Et3 SiH/TFA containing a catalytic amount of sulfuric acid. It is believed that 4-methyl-2-pentene is isomerized to 2-methyl-2-pentene prior to reduction.203 Unlike cyclohexene, its oxa analog, 3,4-dihydro-2H -pyran, undergoes facile reduction to tetrahydropyran in yields ranging from 70 to 92% when treated with a slight excess of triethylsilane and an excess of either trifluoroacetic acid or a combination of hydrogen chloride and aluminum chloride (Eq. 69).146 This difference in behavior can be understood in terms of the accessibility of the resonance-stabilized oxonium ion intermediate formed upon protonation. Et3SiH

HX

(70-92%) O

O X– +

O

(Eq. 69)

The behavior of the isomeric dihydronaphthalenes emphasizes the importance of the relative stabilities of carbocation intermediates in ionic hydrogenations. Treatment of 1,2-dihydronaphthalene with Et3 SiH/TFA at 50–60◦ gives a 90% yield of tetralin after one hour. Under the same conditions, the 1,4dihydronaphthalene isomer gives less than 5% of tetralin after 70 hours.224 This difference in reactivity is clearly related to the relatively accessible benzylic cation formed upon protonation of the 1,2-isomer compared to the less stable secondary cation formed from the 1,4-isomer.224 The behavior of members of the bicyclo[2.2.1]heptene family is also different from that of other common 1,2-disubstituted alkenes.230 The parent bicyclo[2.2.1]heptene gives bicyclo[2.2.1]heptane in only 3.5% yield when it is treated with Et3 SiH/TFA. The major product is reported to be a 2-bicyclo[2.2.1]heptyl trifluoroacetate of unspecified configuration (Eq. 70).230 The carbocation intermediate is presumably the 2-norbornyl cation. Addition of small amounts of boron trifluoride etherate to the reaction mixture causes the yield of hydrocarbon product to rise to 22% after a reaction time of 24 hours at room temperature. Further

ORGANOSILICON HYDRIDE REDUCTIONS

37

exposure of the reaction mixture to the reaction conditions does not result in additional hydrocarbon formation from the ester. Et3SiH

+

O2CCF3

TFA

(Eq. 70)

(3.5-22%)

A mixture of exo- and endo-isomers of 5-methylbicylo[2.2.1]hept-2-ene is hydrogenated with the aid of five equivalents of triethylsilane and 13.1 equivalents of trifluoroacetic acid to produce a 45% yield of endo-2-methylbicylo[2.2.1] heptane (Eq. 71). The same product is formed in 37% yield after only five minutes. The remainder of the reaction products is a mixture of three isomeric secondary exo-methylbicylo[2.2.1]heptyl trifluoroacetates that remains inert to the reaction conditions. Use of triethylsilane-1-d1 gives the endo-2-methylbicylo[2.2.1]heptane product with an exo-deuterium at the tertiary carbon position shared with the methyl group. This result reflects the nature of the internal carbocation rearrangements that precede capture by the silane.230 Et3SiH

H(D)

+

TFA, rt, 24 h (45%)

(Eq. 71) (55%)

O2CCF3

Alkenes with a 1,1-disubstitution pattern form tertiary carbocations upon treatment with a Brønsted acid. Consequently, such compounds are often easily reduced (Eq. 72). An example of this is the formation of 2-methylpentane in 93% yield after only 5 minutes when a dichloromethane solution of 2-methyl1-pentene and 1.4 equivalents of triethylsilane is treated with 1.4 equivalents of trifluoromethanesulfonic acid at −75◦ .216 Similar treatment of 2,3-dimethyl-1butene gives a 96% yield of 2,3-dimethylbutane.216 CF3SO3H R R = alkyl

Et3SiH, –75°

R R = n-Pr (93%) R = i-Pr (96%)

(Eq. 72)

Use of deuterated silane and/or acid with this method leads to site-specific deuterium incorporation in the reduced products. Thus, treatment of 2-methyl-1pentene with one equivalent of deuterated triethylsilane and two equivalents of trifluoroacetic acid at 50◦ for 24 hours gives 2-methylpentane-2-d1 in 90% yield (Eq. 73).221 In the same way, isopropenylcyclopropane gives an 80% yield of deuterated isopropylcyclopropane after 30 minutes at −10◦ (Eq. 74).221 Et3SiD TFA, 50° Et3SiD TFA, –10°

(90%)

(Eq. 73)

(80%)

(Eq. 74)

D D

38

ORGANIC REACTIONS

Preferential protonation of oxygen in comparison to carbon prevents 4-methylenetetrahydropyran from undergoing reduction to 4-methyltetrahydropyran even when held at 70◦ for 10 hours in the presence of triethylsilane and a 20-fold excess of trifluoroacetic acid.146 However, when the reaction conditions are changed so that a dichloromethane solution of the same substrate is treated with a mixture of four equivalents of triethylsilane and three equivalents of aluminum chloride in the presence of excess hydrogen chloride, a 40% yield of 4-methyltetrahydropyran product is obtained at room temperature after one hour (Eq. 75).136

Et3SiH O

(40%)

HCl, AlCl3

(Eq. 75)

O

The cis-to-trans ratios of the isomeric 4-tert-butyl-1-methylcyclohexanes derived from treatment of 4-tert-butyl-1-methylenecyclohexane with trifluoroacetic acid vary with the steric features of the organosilicon hydrides that are used (Eq. 76).204 The ratio is 0.04 with n-butylsilane, 0.09 with diethylsilane, 0.11 with triethylsilane, 0.10 with triisopentylsilane, and 0.19 with either tri-sec-butylsilane or di-tert-butylsilane. R3SiH

(—) cis:trans = 0.04-0.19

TFA, rt

(Eq. 76)

Trisubstituted Alkenes. With very few exceptions, trisubstituted alkenes that are exposed to Brønsted acids and organosilicon hydrides rapidly undergo ionic hydrogenations to give reduced products in high yields. This is best illustrated by the broad variety of reaction conditions under which the benchmark compound 1methylcyclohexene is reduced to methylcyclohexane.134,146,192,202,203,207 – 210,214,234 When 1-methylcyclohexene is reduced with one equivalent of deuterated triethylsilane and two equivalents of trifluoroacetic acid at 50◦ , methylcyclohexane1-d1 is obtained in 80% yield after 24 hours (Eq. 77).221 Under similar conditions, 2-methyl-2-butene gives 2-methylbutane-2-d1 (90%) and 1-methylcyclopentene gives methylcyclopentane-1-d1 (60%).221 D Et3SiD

(80%)

(Eq. 77)

TFA, 50°

Surprisingly, α-cyanoacrylic acid is reported to react spontaneously with triethylsilane in the absence of any additional acid to give a quantitative yield of the triethylsilyl ester of α-cyanopropionic acid.236 Ethyl α-cyanoacrylate requires the presence of trifluoroacetic acid to undergo reduction to ethyl 2-cyanopropionate.236 Many of these reductions are highly stereoselective. For example, treatment of

ORGANOSILICON HYDRIDE REDUCTIONS

39

2-phenylnorbornene with a solution of trifluoroacetic acid and triethylsilane in dichloromethane is reported to yield only endo-2-phenylnorbornane (Eq. 78).164 Et3SiH Ph

(Eq. 78)

(100%)

TFA, CH2Cl2

Ph

A mixture of Et3 SiH/TFA in dichloromethane reduces 3-methyl-5-α-cholest2-ene to give the pure equatorial methyl isomeric product, 3β-methyl-5αcholestane, in 66% yield (Eq. 79).126 On the other hand, attempts to reduce cholest-5-ene using the same technique yield neither 5α-cholestane nor 5βcholestane, but instead an isomeric mixture of rearranged olefins. This result is presumably because of the inability of hydride attack to compete with carbocation skeletal isomerization and elimination.126

Et3SiH

(Eq. 79)

TFA, CH2Cl2 (66%)

Treatment with trifluoroacetic acid and triethylsilane causes octahydro-6,7,8, 12,13,14,16,17-15H -cyclopenta[a]phenanthrene to form decahydro-6,7,8,9,11,12, 13,14,16,17-15H -cyclopenta[a]phenanthrene by reduction of the conjugated double bond.237 Similar treatment of the 3-methyl ether of 9(11)-dehydro-D-homoestrol gives the 3-methyl ether of estradiol in better than 50% yield.226 A similar transformation occurs as a critical step in the total synthesis of (+)estrone by a Diels-Alder cycloaddition-cycloreversion pathway (Eq. 80).227 It is worth noting that in this reaction the conjugated double bond is stereoselectively reduced while both an isolated double bond and a ketone carbonyl are preserved. O

O H

H Et3SiH

H

H

TFA, CH2Cl2

H H MeO

H

(Eq. 80) H H

MeO (87%)

Treatment of progesterone with trifluoroacetic acid and triethylsilane in dichloromethane followed by saponification of the mixture of the trifluoroacetate ester intermediates of 5-β-pregnane-3α,20β-diol and 5-β-pregnane-3α,20α-diol and Jones oxidation yields 5-β-pregnanedione in 65% yield (Eq. 81).238 O

H O

O

1. TFA, Et3SiH, CH2Cl2 2. H2O, OH–

(Eq. 81)

3. CrO3, Me2CO

H O

(65%)

40

ORGANIC REACTIONS

Hydrogenation of the carbon-carbon double bond occurs without alteration of the ester function when citronellyl acetate is treated with 2.5 equivalents of trifluoroacetic acid and two equivalents of triethylsilane in 2-nitropropane.205 The reduced product is obtained in 90% yield after 22 hours at room temperature in the presence of one equivalent of added lithium perchlorate (Eq. 82). The yields are lower in the absence of this added salt. Similar reduction of an unsaturated phenolic chroman derivative occurs to give an 85% yield of product with only the carbon-carbon double bond reduced (Eq. 83).205 TFA, Et3SiH, LiClO4 OAc

OAc

(CH3)2CHNO2

(Eq. 82)

(90%) HO

TFA, Et3SiH, LiClO4

HO

(Eq. 83)

(CH3)2CHNO2

O

O (85%)

A dichloromethane solution of 4-methyl-5,6-dihydro-2H -pyran gives 4-methyltetrahydropyran in 35% yield when treated with a mixture of five equivalents of triethylsilane and 2.5 equivalents of aluminum chloride in the presence of excess hydrogen chloride at room temperature for one hour (Eq. 84).136 This behavior is essentially the same as that exhibited by the disubstituted 4methylenetetrahydropyran isomer under similar conditions.136 Et3SiH TFA

O

(35%)

(Eq. 84)

O

Exceptions to the generally facile ionic hydrogenation of trisubstituted alkenes include the resistance of both 2-methyl-1-nitropropene (R = NO2 ) and 3,3-dimethylacrylic acid (R = CO2 H) to the action of a mixture of triethylsilane and excess trifluoroacetic acid at 50◦ (Eq. 85).234 The failure to undergo reduction is clearly related to the unfavorable effects caused by the electron-withdrawing substituents on the energies of the required carbocation intermediates. R

Et3SiH TFA

No Reaction

(Eq. 85)

R = NO2, CO2H

Tetrasubstituted Alkenes. Tetrasubstituted alkenes lacking electron-withdrawing substituents undergo facile ionic hydrogenation to alkanes in very good yields. Simple examples include 2,3-dimethyl-2-butene,208,214 1,2-dimethylcyclopentene, 1,2-dimethylcyclohexene,229 and 9(10) -octalin.126,204,212 Interesting variations are observed in the stereoselectivities of these ionic hydrogenations. Reduction of 1,2-dimethylcyclopentene with Et3 SiH/TFA near

ORGANOSILICON HYDRIDE REDUCTIONS

41

room temperature gives 1,2-dimethylcyclopentane with a cis to trans ratio of 0.083, compared to a ratio of 0.63 for 1,2-dimethylcyclohexene.229 The reduction of 9(10) -octalin to cis- and trans-decalins occurs with cis to trans stereoselectivities that vary with the nature of the organosilicon hydride employed. The ratios are 0.28–0.59 with n-butylsilane, 0.67 with diethylsilane,204 0.34212 or 0.72204 with triethylsilane, 0.67 with diphenylsilane, 0.77 with diphenylmethylsilane,212 1.38204 –1.80127,212 with triphenylsilane, 0.54 with triisopentylsilane, 1.17 with tricyclopentylsilane, 2.57 with tri-sec-butylsilane, 3.35 with di-tert-butylsilane, 4.88 with di-tert-butylmethylsilane, and 13.3 with tri-tertbutylsilane.204 Opinions differ about the mechanistic significance of these changes in isomer ratios.204,212 Treatment of 8(9) -dehydroestradiol with trifluoroacetic acid and triethylsilane gives estradiol in 96% yield (Eq. 86).239 The 3-methyl ether is similarly reduced to the 3-methyl ether of estradiol in >50% yield.239 The structurally related 18-ethyl and 18-propyl 17-keto compounds experience reduction of the 8(9) function in excess of 70% yield without concomitant reduction of the 17-keto group.239 OH

OH Et3SiH

H

H

TFA

HO

H

(Eq. 86)

(96%) H

HO

Treatment of 8(9) -dehydro-D-homoestradiol (39, R = H) (or its 3-methyl ether, R = Me) with Et3 SiH/TFA followed by saponification of the trifluoroacetate ester intermediate leads to D-homoestradiol (40) (or its 3-methyl ether) containing 2–15% D-homoequilenol (41) (or its 3-methyl ether).240 By contrast, reduction and saponification of 3,17-diacetyl- 8(9) -dehydro-D-homoestradiol (39, R = AcO) gives a 60% yield of D-homoestradiol without the presence of any D-homoequilenol (Eq. 87).240 OR

OH 1. TFA, Et3SiH

H RO

H

2. NaBH4

H

H

HO 39

40 R = Ac (60%)

OH

(Eq. 87)

+ H HO 41 R = Ac (0%)

Polyenes. The behavior of substrates with multiple carbon-carbon double bonds toward the conditions employed for ionic hydrogenations with organosilicon hydrides depends heavily on the number and kinds of substituents and

42

ORGANIC REACTIONS

whether or not the multiple double bonds are conjugated. In the absence of conjugation, the individual double bonds react independently. The full reduction of 1,3-dienes with Et3 SiH/TFA occurs in certain systems although the yields are only modest.231 For example, 1,3-cyclohexadiene gives a 65% yield of cyclohexyl trifluoroacetate, presumably by way of cyclohexene (Eq. 88).211 On the contrary, 1,4-cyclohexadiene fails to undergo reaction with 10 equivalents of triethylsilane and 20 equivalents of trifluoroacetic acid even after 24 hours at room temperature (Eq. 89). O2CCF3

Et3SiH

TFA

(65%)

TFA Et3SiH

(Eq. 89)

No Reaction

TFA

(Eq. 88)

Additional evidence of this pattern of behavior is shown upon treatment of the conjugated diene 1-propenylcyclohexene with two equivalents of triethylsilane and three equivalents of trifluoroacetic acid at 50◦ . This diene gives a 70% yield of completely reduced propylcyclohexane after 10 hours (Eq. 90).231 No partially reduced intermediates are found. Et3SiH

(70%)

TFA

(Eq. 90)

Similar treatment of the isomeric, nonconjugated 1-(3-propenyl)cyclohexene gives a mixture of products containing 55% of the partially reduced 3-propenylcyclohexane and 15% of the completely reduced propylcyclohexane (Eq. 91).231 The yield of the latter product increases to 25% when the amounts of Et3 SiH/TFA used are raised to 6.5 and 12.1 equivalents, respectively, and the reaction time is increased to 24 hours.230 The nonconjugated 1-(3-butenyl)cyclohexene gives a 65% yield of partially hydrogenated 3-butenylcyclohexane under identical conditions.231 Et3SiH

+

(Eq. 91)

TFA (55%)

(15%)

Reduction of dienes incorporated into steroid structures may lead to different configurations in the products. For example, treatment of 8(9),14(15)bisdehydroestrone 42 (R = H) for four hours at room temperature with twenty equivalents of trifluoroacetic acid and two equivalents of triethylsilane leads to an ionic hydrogenation product mixture containing the natural 8β,9α,14α-estrone 43 as a minor component (11%) and the 8α,9β,14β-isomer 44 as the major component (83%) (Eq. 92).241 The related methyl ether (42, R = Me) behaves in a similar fashion.241 The yield of natural isomer 46 formed from the methyl ether of 8(9),14(15) -bisdehydroestradiol analog 45 increases from 22 to 34%, and that of

ORGANOSILICON HYDRIDE REDUCTIONS

43

isomer 47 decreases from 78 to 66%, when the solvent is changed from benzene to dichloromethane (Eq. 93).242 O

O Et3SiH

H

TFA RO

+ H

H RO

42

O

43 R = H (11%) R = Me (27%)

(Eq. 92)

H H

H

RO 44 R = H (83%) R = Me (66%) OH

OH Et3SiH

H

TFA MeO

H

H MeO

OH

46 (22-34%)

45

(Eq. 93)

H

+ H

H

MeO 47 (78-66%)

Treatment of linalyl p-tolyl sulfone (R = SO2 C6 H4 Me-p) with 2.5 equivalents of trifluoroacetic acid and two equivalents of triethylsilane in 2-nitropropane containing one equivalent of lithium perchlorate gives, after 20 hours at room temperature, an 87% yield of the product in which only the double bond distal to the sulfone function is reduced (Eq. 94).205 TFA, Et3SiH, LiClO4 (CH3)2CHNO2

R

(Eq. 94)

R R = Ts (87%)

Surprisingly, linalyl acetate (R = OAc) fails to undergo reduction under these conditions; instead, it rapidly decomposes through cyclization and polymerization pathways.205 The same reaction conditions transform geranyl p-tolyl sulfone (R = SO2 C6 H4 Me-p) into a mixture of 7% reduced and 93% cyclized products within 20 hours, whereas geranyl acetate (R = OAc) gives only a 20% yield of cyclized and no reduced product (Eq. 95).205 TFA, Et3SiH, LiClO4 R

R

(CH3)2CHNO2 R = Ts (7%) R = OAc (0%)

R

+ (93%) (20%)

(Eq. 95)

44

ORGANIC REACTIONS

Homoconjugation results in enhanced reactivity of substrates toward ionic hydrogenation. Bicyclo[2.2.1]hepta-2,5-diene forms a mixture of the trifluoroacetate esters of bicyclo[2.2.1]hepten-2-ol, tricyclo[2.2.1.02,6 ]heptan-3-ol, and bicyclo[2.2.1]heptan-2-ol in a 62 : 20 : 17 ratio on treatment with 10 equivalents of triethylsilane and 20 equivalents of trifluoroacetic acid for 24 hours at room temperature (Eq. 96).230 Et3SiH O2CCF3 +

TFA

O2CCF3 +

O2CCF3

(Eq. 96)

(—) 62:20:17

Treatment of 5-methylenebicyclo[2.2.1]hept-2-ene with 10 equivalents of triethylsilane and 20 equivalents of trifluoroacetic acid either for 24 hours at room temperature or 3 hours at 50◦ gives an 85% yield of completely hydrogenated endo-2-methylbicyclo[2.2.1]heptane (Eq. 97). The combination of Et3 SiH/TFA/ BF3 •OEt2 gives this product in 80% yield.230 The reaction presumably proceeds by way of 2-methyltricyclo[2.2.1.02,6 ]heptane as a reaction intermediate, since this compound is expected to rapidly give the same final product when it is subjected to these reaction conditions.230 The analogous stereospecific behavior is exhibited by 5-ethylidenebicyclo[2.2.1]hept-2-ene.230 Et3SiH

Et3SiH

TFA

TFA

(85%)

(Eq. 97)

Transannular interactions lead to ring closures and reductions to adamantane compounds when dienes of the bicyclo[3.3.1]nonane family are treated with Brønsted acids and triethylsilane. Compounds 48–51 form reaction mixtures containing various amounts of products 52–54 (R = OH, O2 CCF3 , Cl) under such conditions.243 The best yields of hydrocarbon 52 occur when the dienes are treated with a 25% excess of sulfuric acid and a 50% excess of triethylsilane in dichloromethane at 20◦ .243 The stereospecific nature of these transannular reductions is demonstrated by the observation that the enantiomeric purity of the chiral diene 55 is retained in the chiral hydrocarbon product 56 (Eq. 98).243 Dienes of

48

49

50

51

R 52

53 R = OH, OTFA, Cl

54

ORGANOSILICON HYDRIDE REDUCTIONS

45

the type shown can be reduced to the chlorides (Eq. 99).243 When HCl is replaced with TFA, methyladamantane and methyladamantanol are formed (Eq. 100). Ph

Et3SiH, CH2Cl2

Ph

(73%)

H2SO4 55

(Eq. 98)

56 Et3SiH, HCl

(Eq. 99)

(96%)

CH2Cl2, rt, 6 h

Cl

Et3SiH, TFA

+

CH2Cl2, rt, 6 h

(Eq. 100)

OH (29%)

(45%)

Alkynes to Alkanes. In contrast to the facile ionic hydrogenations that many alkenes undergo, alkynes as a group are very resistant to reduction with the organosilicon hydride/acid combinations. Only those alkynes having an electronrich aryl group in conjugation with the carbon-carbon triple bond give even modest amounts of reduced products as seen in the example of p-tolylacetylene (Eq. 101).244 Alkenes are not observed as products.244 Et3SiH, TFA rt, 120 h

(Eq. 101)

(21%)

The use of stronger acid conditions provides somewhat better synthetic yields of alkanes from alkynes. A useful method consists of treatment of the substrate with a combination of triethylsilane, aluminum chloride, and excess hydrogen chloride in dichloromethane.146 Thus, treatment of phenylacetylene with 5 equivalents of triethylsilane and 0.2 equivalents of aluminum chloride in this way at room temperature yields 50% of ethylbenzene after 1.5 hours. Diphenylacetylene gives a 50% yield of bibenzyl when treated with 97 equivalents of triethylsilane and 2.7 equivalents of aluminum chloride after 2.8 hours. Even 1-hexyne gives a mixture of 44% n-hexane and 7% methylpentane of undisclosed structure when treated with 10 equivalents of triethylsilane and 0.5 equivalent of aluminum chloride for 0.5 hour.146 The reductive cyclization of enynes has been used to prepare exo-methylenecycloalkanes. Two systems have proven successful in this transformation, namely PMHS/Pd2 (dba)3 •CHCl3 245 (Eq. 102) and Et3 SiH/Pd(dppe)Cl2 /HCO2 H (Eq. 103).246 PMHS, Pd2(bpa)3•CHCl3, (o-Tol)3P TBSO

OTMS

HOAc, ClCH2CH2Cl, rt

TBSO

(90%) OTMS

(Eq. 102)

46

ORGANIC REACTIONS

O

Et3SiH, Pd(dppe)Cl2, HCO2H

Ph

O

O

+

Ph

1,4-dioxane, 70°, 10 h

(Eq. 103)

Ph (73%)

(8%)

The triethylsilane/Pd2 (dba)3 combination is also used for these reductive cyclizations, although lower yields are reported.247 1,6-Diynes are reductively cyclized to 1,2-dialkylidenecyclopentanes in good yields with Et3 SiH/Pd2 (dba)3 •CHCl3 (Eq. 104).248 OMe

OMe Et3SiH, Pd2(dba)3•CHCl3

TBSO

TBSO

(o-Tol)3P, HOAc, rt, 15 min

H

(86%)

(Eq. 104)

o-Bromobenzyl alkynylalkyl ethers can be reductively cyclized in modest yields with Et3 SiH/Pd(PPh3 )4 /Cs2 CO3 as shown in Eq. 105.249 In a like manner, enynes with a vinyl bromide as the olefin function undergo reductive cyclization (Eq. 106).249 O

Cs2CO3, DMF, 80°, 3 h

Br EtO2C EtO2C

O

Et3SiH, Pd(PPh3)4

Br

Et3SiH, Pd(PPh3)4

EtO2C

Cs2CO3, DMF, 80°, 4 h

EtO2C

(48%)

(Eq. 105)

(72%)

(Eq. 106)

Cyclopropanes to Alkanes. Cyclopropanes that can form ring-opened tertiary aliphatic or benzylic carbenium ion intermediates undergo ionic hydrogenation with reasonable ease when treated with Brønsted acids and organosilicon hydrides. Ring opening occurs preferentially between the most and least highly substituted ring carbons. For example, treatment of 1,1,2trimethylcyclopropane with one equivalent of triethylsilane and two equivalents of trifluoroacetic acid gives a mixture of 2,3-dimethylbutane (75%) and 2methylpentane (25%) (Eq. 107).233 The conversion into the hydrocarbon mixture is 15% after 15 minutes, 65% after 12 hours, and complete after 16 hours at room temperature.222,232 Essentially the same results are obtained when 2,3dimethyl-2-butene is used as the substrate.222 The disubstituted isomer 1-methyl2-ethylcyclopropane gives an alkane reaction mixture consisting primarily of 3-methylpentane along with 2-methylpentane (Eq. 108).222 Et3SiH

+

(Eq. 107)

TFA (75%)

(25%)

ORGANOSILICON HYDRIDE REDUCTIONS Et3SiH

+

TFA

47

(Eq. 108)

(major)

(minor)

Unlike its disubstituted isomer, the monosubstituted isopropylcyclopropane undergoes reduction to 2-methylpentane to the extent of only 50% after 24 hours (Eq. 109),232 a result similar to that observed when 2-methyl-1-pentene is the substrate.222 It is interesting that deuterated triethylsilane produces 2-methylpentane that contains the deuterium label only at the C2 position.250 This label position suggests that in this reaction ring protonation and opening are followed by a 1,2-hydride shift that precedes capture by the silyl hydride of any initially formed carbocation intermediates.250 Ethylcyclopropane, with an unbranched side chain, shows no sign of reduction under these conditions even after 200 hours.232 Phenylcyclopropane is reduced to 1-phenylpropane.222 Et3SiD

(Eq. 109)

(50%)

TFA, rt

D

Bicyclic hydrocarbons that contain a three-membered ring slowly undergo ionic hydrogenation when treated with at least one equivalent of triethylsilane and an excess of trifluoroacetic acid at room temperature.229 Thus, bicyclo[3.1.0]hexane gives a product mixture containing methylcyclopentane (28%) and cyclohexane (3%) when reacted with one equivalent of triethylsilane and four equivalents of trifluoroacetic acid for 140 hours (Eq. 110). The main products are the trifluoroacetates of cyclohexanol and cis-and trans-2-methylcyclopentanol in a ratio of 10 : 35.229 Under the same conditions, bicyclo[4.1.0]heptane yields a mixture containing mainly methylcyclohexane (79%) with some cycloheptane (5%) and the corresponding trifluoroacetates (16%) (Eq. 111).229 Et3SiH TFA Et3SiH TFA

(28%)

(79%)

+

+

(3%)

(Eq. 110)

(15%)

(Eq. 111)

After ten days at room temperature in the presence of one equivalent of triethylsilane and two equivalents of trifluoroacetic acid, both 1-methylbicyclo[3.1.0]hexane and 1-methylbicyclo[4.1.0]heptane form mixtures of the two isomers of their respective 1,2-dimethylcycloalkanes (Eqs. 112 and 113).229 Et3SiH TFA Et3SiH TFA

(89%) trans:cis = 10.0

(Eq. 112)

(74%) trans:cis = 1.5

(Eq. 113)

48

ORGANIC REACTIONS

Based on the few reported examples, the pattern of ring cleavage that accompanies the ionic hydrogenation of alkylidenencyclopropanes seems to be related to the pattern and degree of substitution on both the ring and the double bond.233 Thus, treatment of 1,1-dimethyl-2-methylenecyclopropane with two equivalents of triethylsilane and four equivalents of trifluoroacetic acid for 90 hours at room temperature yields 65% of 2,3-dimethylbutane (Eq. 114).229 Exposure of 1,1dimethyl-2-isopropylidenecyclopropane to the same ratio of reactants at 50◦ for 16 hours produces a complex mixture containing 63% of 2,5-dimethylhexane, 18.5% of 2,5-dimethyl-3-hexene, 1.6% of 2,5-dimethyl-2-hexene, and 7% of 2,5-dimethyl-2-hexyl trifluoroacetate (Eq. 115).229 Et3SiH

Et3SiH

(63%)

TFA

(Eq. 114)

(65%)

TFA

+

+

(1.6%)

(18.5%)

+

O2CCF3 (7%)

(Eq. 115) Aromatic Substrates. Aromatic hydrocarbons can be reduced with organosilanes to dienes, alkenes, or alkanes. The combination of Et3 SiH/TFA/BF3 •OEt2 reduces furans to tetrahydrofurans in good yields (Eq. 116).211 In general, poor yields are obtained with the Et3 SiH/TFA reduction of benzofurans,251 but the C3substituted benzofuran shown undergoes reduction of the furan ring in excellent yield with this reagent (Eq. 117).252 Similarly, benzothiophenes are reduced in 60 to 90% yields under the same conditions.253 The Et3 SiH/TFA system reduces thiophenes to tetrahydrothiophenes in good yields.254 – 257 In α-hydroxy thiophenes, both double bonds of the thiophene unit and the hydroxy group are reduced (Eq. 118).258 Et3SiH, TFA, BF3•OEt2 O

20°, 4 min Et3SiH, TFA, 20°, 1.5 h

(95%)

O

S

C15H31-n OH

(Eq. 116)

(70%)

O

(Eq. 117)

O Et3SiH, TFA, 50°, 48 h S

C16H33-n

(—)

(Eq. 118)

Similar reactivity is realized with 2-acetylthiophene using triethylsilane with aluminum chloride.259 Treatment of the ethylene glycol acetal of 2-thiophenecarbaldehyde with Et3 SiH/TFA results in reduction of the ring and oxidation of

ORGANOSILICON HYDRIDE REDUCTIONS

49

the side chain to the silylated carboxylic acid (Eq. 119),260 whereas similar treatment of 2-thiophenecarbaldehyde gives 2-methyltetrahydrothiophene and 2acetylthiophene gives 2-ethylthiophene.257 Some thiophenes are reduced to a mixture of tetrahydrothiophenes and 2,5-dihydrothiophenes.210,259,261 Et3SiH, TFA, 55°, 15 h

O S

O S

O

(45%)

(Eq. 119)

OSiEt3

Partial reduction of polyarenes has been reported. Use of boron trifluoride hydrate (BF3 •OH2 ) as the acid in conjunction with triethylsilane causes the reduction of certain activated aromatic systems.217,262 Thus, treatment of anthracene with a 4–6 molar excess of BF3 •OH2 and a 30% molar excess of triethylsilane gives 9,10-dihydroanthracene in 89% yield after 1 hour at room temperature (Eq. 120). Naphthacene gives the analogously reduced product in 88% yield under the same conditions. These conditions also result in the formation of tetralin from 1-hydroxynaphthalene (52%, 4 hours), 2-hydroxynaphthalene (37%, 7 hours), 1-methoxynaphthalene (37%, 10 hours), 2-methoxynaphthalene (26%, 10 hours), and 1-naphthalenethiol (13%, 6 hours). Naphthalene, phenanthrene, 1-methylnaphthalene, 2-naphthalenethiol, phenol, anisole, toluene, and benzene all resist reduction under these conditions.217 Use of deuterated triethylsilane to reduce 1-methoxynaphthalene gives tetralin-1,1,3-d3 as product, thus yielding information on the mechanism of these reductions.262 2-Mercaptonaphthalenes are reduced to 2,3,4,5-tetrahydronaphthalenes in poor to modest yields.217,263 Et3SiH, BF3•OH2

(89%)

CH2Cl2, rt, 1 h

(Eq. 120)

The combination of PhMeSiH2 (or Ph2 SiH2 ) and Cp2 TiMe2 (10 mol%) reduces pyridines to N-silylated-di- or tetrahydropyridines or the N-silylated piperidines.264,265 With quinoline, only the pyridine ring is reduced preferentially to the benzene ring (Eq. 121). PhMeSiH2, Cp2TiMe2

+ N SiPhMeH (56%)

80°, 8 h

N

N SiPhMeH (18%)

(Eq. 121)

Miscellaneous Unsaturated Substrates. Exposure of 1,1′ -bis(trans-2cyanovinyl)ferrocene to a mixture of two equivalents of triethylsilane and 320 equivalents of trifluoroacetic acid at 50◦ for three hours gives a product with the carbon-carbon double bonds reduced in 83% yield, but leaving the nitrile groups intact (Eq. 122).179 CN Fe

CN

CN

Et3SiH TFA

Fe

(Eq. 122) CN

50

ORGANIC REACTIONS

Treatment of a chloroform or dichloromethane solution of 1-bromo-2,2-diphenylethene or 1-bromo-2,2-bis(4′ -methoxyphenyl)ethene with a slight excess of triethylsilane and a 9- to 10-fold excess of TFA gives the corresponding ethanes in 62% and 88% yields, respectively, after one hour at 0◦ (Eq. 123).184 Ar Ar

Ar

Et3SiH Br

TFA Ar Ph 4-MeOC6H4

Br Ar

(Eq. 123) (62%) (88%)

The carbonyl groups of 1,3-indanediones are generally resistant to the action of combinations of acid and silanes at room temperature.266 Accordingly, treatment of a variety of 2-benzylidene-1,3-indanediones with Et3 SiH/TFA (ratio of 1 : 5 : 10) in CCl4 at 55◦ for 7–20 hours gives the corresponding substituted 2benzyl-1,3-indanediones in 54-78% yields (Eq. 124).266 Use of a 27-fold excess of trifluoroacetic acid in the absence of a cosolvent reportedly leads to reduction of the carbonyl groups to give a mixture of products.267 O

O Et3SiH

CHAr O

(Eq. 124)

CH2Ar

TFA O

An interesting hydroiodination reaction occurs when a mixture of cyclohexene and triethylsilane in dichloromethane is treated with a mixture of bis(pyridine) iodonium tetrafluoroborate and tetrafluoroboric acid in diethyl ether (Eq. 125). A 50% yield of iodocyclohexane is produced after one hour at 20◦ .268 I

Et3SiH

(Eq. 125)

I(py)2BF4, HBF4

Reduction of Ethers Because of the high stability of the triphenylmethyl carbocation, the reductive ether cleavage of trityl ethers with Et3 SiH/trimethylsilyl triflate (TMSOTf) is highly successful. This reaction even occurs in the presence of highly reactive sugar ketals, leaving the ketals intact (Eq. 126).269 OTr BzO BzO

OH O

BzO O

OTr O OH

Et3SiH, Et3SiOTf CH2Cl2, rt, 5 min OTr

OH

BzO BzO

O BzO O

OH O OH

+ Ph3CH OH

OH (87%)

(Eq. 126) The combination of PMHS and Pd(PPh3 )4 reduces allyl ethers to propene and alcohols.270 The best combination for the reductive cleavage of ethers appears

ORGANOSILICON HYDRIDE REDUCTIONS

51

to be Et3 SiH/(C6 F5 )3 B, which gives excellent yields of the alcohol (via the silyl ether) and alkane (Eq. 127).145 n-C16H33

O

Et3SiH, (C6F5)3B C16H33-n

n-C16H34 (98%) + n-C16H33OSiEt3 (98%)

CH2Cl2, rt, 20 h

(Eq. 127) Dialkyl ethers are reduced with the combination of Et3 SiH/TFA, although the yields vary.144,271 tert-Butyl triphenylcyclopropenyl ether is reduced to the corresponding cyclopropene (Eq. 128),272 and a dibenzyl-like ferrocene-derived ether is reduced to the corresponding alkane (Eq. 129).179 Ph

Ph

Et3SiH, TFA

Ph

Fe

O

OBu-t

(Eq. 128)

(45%)

Ph Ph

Ph

Et3SiH, TFA, rt, 3 h

Ph

Fe

Ph

(80%)

(Eq. 129)

Reduction of Allyl Acetates Allyl acetates are reduced to the corresponding olefins with PMHS/Pd(PPh3 )4 or Ph2 SiH2 /Pd(PPh3 )4 .196,273 Unfortunately, double bond migration occurs in many of these reactions (Eqs. 130 and 131).196,273 The combinations of Ph2 SiH2 / Pd(P(Tol-p)3 )4 /ZnCl2 274 and Et3 SiH/TFA275 are also employed in this transformation. PMHS, Pd(PPh3)4 +

PPh3, THF, 5 d

OAc

(48%)

(52%)

(Eq. 130) OAc

Ph2SiH2, Pd(PPh3)4

CN

THF, rt, 30 h

CN

(Eq. 131)

(100%)

The Et3 SiH/TFA reduction of a 3-acetoxy enol ether is reported. The diastereoselectivity is high for the Z isomer, but much lower for the E isomer (Eq. 132).276 BnO Ph

PhMe2SiH, TFA OAc

rt, 16 h

BnO Ph

BnO OAc

+ Ph

OAc

(Eq. 132)

(73%) syn:anti = 99:1

Reduction of Carboxylic Acids Aromatic and aliphatic carboxylic acids are reduced to the trifluoroacetates of the alcohol with Et3 SiH/TFA.277 Use of an excess of the triethylsilane can give

52

ORGANIC REACTIONS

further reduction to the methyl group. The combination of PMHS/TBAF (tetran-butylammonium fluoride) reduces benzoic acids to the benzyl alcohols in good yields.278 Comparable yields of this useful transformation can be realized through the use of PMHS/Ti(OPr-i)4 (or PMHS/Ti(OEt)4 ).279 Both aromatic and aliphatic carboxylic acids can be reduced with EtMe2 SiH and the ruthenium-based catalyst 57 (Eq. 133).280 The latter reagent/catalyst combination also reduces esters to alcohols in high yield. O OH

EtMe2SiH, 57

OH

1,4-dioxane, 20°, 0.5 h

(72%)

(Eq. 133) (CO)2Ru

Ru(CO)2 Ru (CO)2 O 57

The highly reactive reagent combination of Et3 SiH/(C6 F5 )3 B reduces carboxylic acids to methyl groups (Eq. 134).281,282 Isolation of the intermediate silyl ether is also possible.282 CO2H

Et3SiH, (C6F5)3B

(94%)

CH2Cl2, rt, 20 h

(Eq. 134)

Benzoic acids with electron-donating groups on the ring are reduced to toluene derivatives with the reagent combination Et3 SiH/TFA/TFAA.283 p-Anisic acid gives 4-methylanisole in 97% yield under these conditions (Eq. 135). Formation of the corresponding benzyl trifluoroacetates occurs for substrates without activating groups. p-Nitrobenzoic acid is unreactive under these conditions, as are dibasic acids such as phthalic or succinic acid.283 The same conditions reduce alkyl carboxylic acids to trifluoroacetates.277 Use of the silane 58 or 59 provides cinnamaldehyde in fair yield from cinnamic acid (Eq. 136).284 CO2H

Et3SiH, TFA, (CF3CO2)2O 60°, 5 h

MeO O Ph

Ph Ph SiH2

Ph Si H H

NMe2 58

(Eq. 135)

O

58 or 59, >180° OH

(97%) MeO

NMe2 59

H

58 (65%) 59 (50%)

(Eq. 136)

ORGANOSILICON HYDRIDE REDUCTIONS

53

Reduction of Acid Halides and Acid Anhydrides The organosilane reduction of acid chlorides to aldehydes has been accomplished in high yields with the use of the pentacoordinated organosilane 60 (Eq. 137).107 This transformation has been reported to occur with tribenzylsilane and triethylsilane, but yields were not reported.285,286 O Cl

O

60, rt

Cl

H

H

O

(85%)

O Ph SiHMe NMe2

(Eq. 137)

60

The combination Et3 SiH/(C6 F5 )3 B reduces acid chlorides to methyl groups (Eq. 138).281,282 If a smaller amount of triethylsilane is used, the same combination reduces aryl acid chlorides to the trimethylsilyl ethers of the benzyl alcohols.281,282 O n-C13H27

Et3SiH, (C6F5)3B CH2Cl2, rt, 20 h

Cl

n-C14H30

(Eq. 138)

(97%)

One study of the Et3 SiH/TFA reduction of acid anhydrides reports the formation of one equivalent each of the alcohol and the trifluoroacetate ester of the acid (Eq. 139).287 O

O O

n-C3F7

Et3SiH, TFA 50°, 3 h

C3F7-n

n-C3F7CH2OH +

n-C3F7CH2O2CCF3

(Eq. 139)

(60%)

Reduction of Esters and Lactones The combination of (EtO)3 SiH/CsF (or KF) provides a convenient reagent for the reduction of esters to alcohols.76,80,83 The yields are in the 70% range. Potassium tetraethoxyhydridosilicate also reduces esters in moderate yields.288 The combination of PMHS/Cp2 TiCl2 /n-BuLi reduces esters in high yields even in the presence of an epoxide and a trisubstituted olefin (Eq. 140).289 The reagent combination can reduce a methyl ester in the presence of a tert-butyl ester (Eq. 141).290 PMHS, Cp2TiCl2, n-BuLi

H O

O MeO

OEt

H

THF, rt, 1 h O

O

O

THF, –78°, 1 h

(Eq. 140)

O

PMHS, Cp2TiCl2, n-BuLi OBu-t

(91%) OH

(87%) HO

OBu-t

(Eq. 141)

54

ORGANIC REACTIONS

Ester reductions with (EtO)3 SiH/(EBTHI)TiCl2 /n-BuLi (EBTHI = ethylenebis(η5 -tetrahydroindenyl)titanium) result in good yields of the corresponding alcohols.290 Excellent yields of alcohols result from the reduction of esters with the PMHS/Ti(OPr-i)4 system.279,291,292 The reaction catalyzed by (EBTHI)TiCl2 / n-BuLi occurs in lower yields.289 Methyl cinnamate is reduced with PMHS/TBAF in good yield.278 The ruthenium complex 57 (Eq. 135) catalyzes the EtMe2 SiH reduction of esters to alcohols, although a mixture of the alcohol and the ether are often obtained (Eq. 142).280 O

EtMe2SiH, 57 OEt

OH

1,4-dioxane, 20°, 0.5 h

OEt

+

(55%)

(11%)

(Eq. 142) High yields in the reduction of esters with Ph2 SiH2 /[RhCl(cod)]2 are reported.293 The combination of (MeO)3 SiH/LiOMe is reported to reduce esters to the alcohols, although the advantages of this system over others does not seem to warrant working with the highly hazardous trimethoxysilane.294 The reduction of the carbonyl group of an ester or lactone is possible. This results in the formation of the corresponding ether. This reaction can be carried out employing PhSiH3 /(PPh3 )(CO)4 MnC(O)Me,295 PhSiH3 /Mn(CO)5 Br,295 Cl3 SiH/γ -irradiation,296 or Et3 SiH/TiCl4 /TMSOTf.297 The reduction of lactones to cyclic ethers is nicely accomplished with the EtMe2 SiH/ruthenium catalyst system 57 (Eq. 143).280 The same transformation can be carried out with Et3 SiH/TiCl4 297 or PhSiH3 /Mn(CO)5 Br.295 The reductive etherification of esters occurs by treating an ester with Et3 SiH/ZnCl2 (Eq. 144).298 EtMe2SiH, 57 n-C7H15

O

O

1,4-dioxane, 20°, 0.5 h Et3SiH, ZnCl2

O OEt

heat, 3-4 h

n-C7H15

(79%)

O

O

(76%)

(Eq. 143) (Eq. 144)

The reduction of esters to aldehydes is a useful transformation and can be accomplished in good yields with Et3 SiH/[RuCl2 (CO)3 ]2 299 or with Ph3 SiH/ (C6 F5 )3 B.116 Thio esters are reduced to aldehydes in good yields with Et3 SiH/Pd/C.300 Lactones can be reduced to hemiacetals with PMHS/Cp2 TiF2 or PMHS/Cp2 Ti(OC6 H4 Cl-4)2 (Eq. 145).301,302 BnO

BnO O O

O O

O

PMHS, Cp2Ti(OC6H4Cl-4)2 TBAF/alumina, MeC6H5, rt

OH (91%)

O

O

(Eq. 145)

ORGANOSILICON HYDRIDE REDUCTIONS

55

The reduction of an ester to the silylated acetal occurs with Et3 SiH/ Et2 NH/[RuCl2 (CO)3 ]2 (and other Ru catalysts) (Eq. 146),299 Et3 SiH/ (C6 F5 )3 B,281,282 or Ph3 SiH/(C6 F5 )3 B,115 and with Ph2 MeSiH/Mn(CO)5 C(O)Me.295 The latter system reduces methyl benzoate to toluene. An intramolecular version of the ester to silylated acetal transformation is effected with TBAF (Eq. 147).303,304 O OMe

OMe

MeC6H5, 100°, 16 h

SiMes2H CO2Et

O Et

OSiEt3

Et3SiH, EtI, Et2NH, [RuCl2(CO)3]2

(92%)

(Eq. 146)

Mes2Si O TBAF, 0°

OEt

O

O Et

Et

(91%) dr = 98:2

(Eq. 147)

O Et

The reaction of lactones of benzyl alcohols with Et3 SiH/TFA results in complete reduction of the alcohol part of the lactone to the methylene group while preserving the carboxylate function (Eq. 148).305 O

CO2H

O Et3SiH, TiCl4

MeO

MeO (87%)

CH2Cl2, 0°

(Eq. 148)

OMe

OMe

The β-hydroxy ester resulting from the reaction of the tert-butyldimethylsilyl ketene acetal of ethyl acetate with a lactone under acid conditions can be reduced to the β-alkoxy ester.306 The overall yields are excellent (Eq. 149). OTBS O

O

1. OEt , SbCl5, TMSCl, SnI2, CH2Cl2, –78°, 30 min 2. Et3SiH, –23°, 2.5 h

OEt

O

(Eq. 149) O

(91%) cis:trans >99:1

The reaction of tert-butyl esters with Et3 SiH/TFA results in the reductive deprotection of the ester and formation of isobutane. The yields of the isobutane are not recorded, but the acids are obtained nearly quantitatively (Eq. 150).307 In a similar manner, the lactone shown in Eq. 151 is converted into the acid in good yield.308 In like manner, the reductive deprotection of allyl esters provides the carboxylic acids in high yields.270

56

ORGANIC REACTIONS

O t-BuO

N H

O

SBu-t H N

CO2Bu-t

Et3SiH, TFA CH2Cl2, rt, 15 min

O

O

CO2H + Me3CH

O (100%)

Et3SiH, TiCl4 CH2Cl2, –78°, 20 min

Ph

H2N

SBu-t H N

O

O Ph

O

(91%)

(Eq. 150)

(Eq. 151)

OH

The reduction of trifluoroacetates to alkanes occurs with the trifluoroacetates of benzylic and tertiary alcohols. This transformation is reported to occur with reagent combinations such as Ph3 SiH/nitrobenzene193 and EtCl2 SiH/AlBr3 .192 Secondary trifluoroacetates give more modest yields.192 Reduction of Aldehydes Reduction to Alcohols. Aldehydes do not normally react spontaneously with organosilicon hydrides to form alcohols. Exceptional behavior is displayed with organocobalt cluster complex carbonyl compounds, which form the corresponding alcohols (R = H, Me, Ph, etc.) after treatment with one equivalent of triethylsilane in refluxing benzene under a carbon monoxide atmosphere and acid workup (Eq. 152).309,310 Aside from these specific examples of anomalous behavior, the generally observed lack of reactivity is due to the combination of the relatively weak electrophilicity of the aldehyde carbonyl carbon center and the extremely feeble nucleophilicity of most tetravalent silyl hydrides. The reduction of aldehyde carbonyl groups by organosilicon hydrides can be promoted by several means. One way is by the introduction of acidic or electrophilic substances that coordinate with the carbonyl oxygen and thereby enhance the electrophilicity of the carbonyl carbon toward receiving a weakly nucleophilic silyl hydride. As mentioned previously, a second way is through the introduction into the reaction medium of substances possessing high nucleophilicity toward silicon centers. Such substances are thought to activate the silyl hydride by forming valenceexpanded silicon species with enhanced hydride-donating properties capable of attacking even weakly electrophilic centers such as the carbonyl groups of common aldehydes. Both means of promotion can be synthetically useful.

(CO)9Co3CCOR

1. Et3SiH, C6H6, CO 2. H2SO4 3. H2O

(CO)9Co3CCH(OH)R R = H (46%) R = Me (88%) R = Ph (68%)

(Eq. 152)

Promotion by Acid. In principle, the reduction of aldehydes to alcohols and alcohol derivatives by organosilicon hydrides should occur upon exposure to either Lewis or Brønsted acids, as represented in Eq. 2. In practice, although

ORGANOSILICON HYDRIDE REDUCTIONS

57

organosilicon hydride reductions of either aliphatic or aromatic aldehydes do occur rapidly under acid conditions, they are frequently complicated by the formation of other products. The reductions rarely give clean yields of alcohols when conducted under anhydrous conditions. The reaction of a mixture of 1-butanal and triethylsilane that occurs upon addition of excess trifluoroacetic acid is a typical example. Analysis of the reaction mixture immediately following the addition of acid shows the formation of 37% of di-n-butyl ether along with n-butyl alcohol and n-butyl trifluoroacetate in a combined yield of 58% (Eq. 153).311 No unreacted aldehyde remains. The same process transforms benzaldehyde into dibenzyl ether in 80% yield (Eq. 154).311,312 In both reactions, the silicon-containing products are triethylsilyl trifluoroacetate and hexaethyldisiloxane. The Et3 SiH/TFA combination can also lead to the trifluoroacetate and toluene derivatives when used with some aryl aldehydes.69 Et3SiH

n-C3H7CHO

(n-C4H9)2O + n-C4H9OH + n-C4H9O2CCF3 (37%) (58%)

TFA

CHO

Et3SiH

O

(80%)

TFA

(Eq. 153) (Eq. 154)

The reduction of aldehydes with the combination Et3 SiH/BF3 •OEt2 gives both the alcohol and the symmetrical ether,70 as do the Et3 SiH/TFA (and other acids) combinations.313 Addition of boron trifluoride etherate to a mixture of 1-octanal and triethylsilane leads to the formation of di-n-octyl ether in 66% yield and n-octyl alcohol in 34% yield (Eq. 155).74 n-C7H15CHO

Et3SiH BF3•OEt2

(n-C8H17)2O (34%) + n-C8H17OH (66%)

(Eq. 155)

The addition of water and a non-hydrogen-bonding solvent to the reduction medium causes the reactions to shift toward the formation of alcohol products.313 For example, triethylsilane in a mixture of concentrated hydrochloric acid and acetonitrile (5 : 4) reduces 1-heptanal to 1-heptanol in quantitative yield after 3 hours at room temperature. In a mixture of triethylsilane in sulfuric acid, water, and acetonitrile (2 : 2 : 5), n-heptanal gives a 97% yield of the same alcohol after 1.25 hours (Eq. 156).313 n-C6H13CHO

Et3SiH, H2O, MeCN H2SO4 or HCl

n-C7H15OH (97%)

(Eq. 156)

Triethylsilane reduces benzaldehyde to benzyl alcohol in 98% yield after 32 hours in a reaction medium containing sulfuric acid, water, and sulfolane (1 : 2 : 5) (Eq. 157). Neither benzene nor dimethylformamide is effective as an interfacing solvent for producing alcohol products under these conditions.313 CHO

Et3SiH, H2O H2SO4, sulfolane

OH

(98%)

(Eq. 157)

58

ORGANIC REACTIONS

In contrast to the propensity of Brønsted and some Lewis acids such as boron trifluoride etherate to promote the organosilicon hydride reduction of aldehydes to ethers under anhydrous conditions, uncomplexed boron trifluoride used with triethylsilane in dichloromethane solvent leads to the formation of primary alcohols in good yields from aliphatic aldehydes and from aromatic aldehydes containing electron-withdrawing groups.1 The success of this method depends on the absence of significant quantities of Brønsted acids in the reaction medium and requires that the boron trifluoride gas be scrubbed of hydrogen fluoride prior to introduction. Using this method, 1-undecanal gives a 92% isolated yield of 1-undecanol after only 10 minutes at 0◦ (Eq. 158). n-C10H21CHO

Et3SiH BF3, CH2Cl2

n-C11H23OH

(92%)

(Eq. 158)

The same technique causes the transformation of p-anisaldehyde (R = MeO) and p-cyanobenzaldehyde (R = CN) into the corresponding substituted benzyl alcohols in quantitative yields within 10 minutes at 0◦ (Eq. 159).1 The reduction of aryl aldehydes to benzyl alcohols without over-reduction to the arylmethanes also occurs with the reagent combinations PMHS/TBAF,278 PMHS/Triton B,278 and Ph3 SiH/(C6 F5 )3 B.116 The Ph3 SiH/(C6 F5 )3 B combination can be used to isolate the benzyl silyl ethers.282 Treatment of p-nitrobenzaldehyde (R = NO2 ) with a catalytic amount of the Lewis acid trimethylsilyl iodide (TMSI, generated in situ from trimethylsilyl chloride and sodium iodide) and tetramethyldisiloxane gives the benzyl alcohol in 91% isolated yield.314 CHO R

CH2OH

Et3SiH BF3, CH2Cl2 R MeO CN

R

(Eq. 159) (100%) (100%)

The reagent combinations PMHS/ZnCl2 ,315 PMHS/[Bu2 (AcO)Sn]2 O,316 and PMHS/HCuPPh3 317 all promote reduction of aldehydes to the corresponding alcohols in good yields. Trichlorosilane in dimethylformamide reduces aldehydes to alcohols in high yields.318 Promotion by Valence Expansion. Addition of nucleophilic substances to mixtures of aldehydes and organosilicon hydrides promotes the reduction of the carbonyl group as depicted previously in Eq. 6. The reductions can occur under homogeneous83 or heterogeneous79,80,319 conditions, both with83,320 and without solvent.83,319 When the reactions occur under anhydrous conditions with catalytic amounts of nucleophile, the first-formed product is frequently a silyl ether. This ether can be regarded as an intermediate that normally undergoes facile acidor base-catalyzed hydrolysis to give a final alcohol product (Eq. 160).80 The silicon-containing products are usually silanols and/or disiloxanes produced by

ORGANOSILICON HYDRIDE REDUCTIONS

59

hydrolysis of the intermediate silyl ethers. These reductions are normally quite chemoselective and tolerate many other functional groups. R3SiH + R'CHO

Nu–

R3SiOCH2R

H2O

(R3Si)2O + R3SiOH + R'CH2OH

R = H, alkyl, aryl R' = alkyl, alkenyl, aryl

(Eq. 160)

Fluoride ion is effective in promoting the reduction of aldehydes by organosilicon hydrides (Eq. 161). The source of fluoride ion is important to the efficiency of reduction. Triethylsilane reduces benzaldehyde to triethylbenzyloxysilane in 36% yield within 10–12 hours in anhydrous acetonitrile solvent at room temperature when tetraethylammonium fluoride (TEAF) is used as the fluoride ion source and in 96% yield when cesium fluoride is used.83 The carbonyl functions of both p-anisaldehyde and cinnamaldehyde are reduced under similar conditions. Potassium bromide or chloride, or tetramethylammonium bromide or chloride are not effective at promoting similar behavior under these reaction conditions.83 Moderate yields of alcohols are obtained by the KF-catalyzed PMHS, (EtO)3 SiH, or Me(EtO)2 SiH reduction of aldehydes.80,83,79 ArCHO + Et3SiH

F– MeCN

ArCH2OSiEt3

Ar = Ph (36-96%)

(Eq. 161)

Diphenylsilane reacts with two equivalents of neat n-heptanal in the presence of anhydrous cesium fluoride within three minutes at room temperature to form di-n-heptoxydiphenylsilane quantitatively (Eq. 162).319 Potassium fluoride and potassium phthalate are considerably less effective promoters, even at temperatures up to 140◦ .319 2 n-C6H13CHO + Ph2SiH2

CsF

(n-C7H15O)2SiPh2 (100%)

(Eq. 162)

Alkoxy-substituted organosilicon hydrides are more reactive toward carbonyl functions in the presence of nucleophiles than are organosilicon hydrides that have only alkyl or aryl substituents at the silicon center. The order of reactivity of the silanes used is (EtO)3 SiH > (EtO)2 SiMeH, and that of the fluoride salts is CsF > KF.83 The use of these silane/fluoride salt pairs can lead to some very chemoselective transformations.79,80,319 For example, after hydrolytic workup, an equimolar mixture of benzaldehyde, diethoxymethylsilane, and cesium fluoride gives an 80% yield of benzyl alcohol after only 10 minutes at room temperature under heterogeneous conditions.80 The use of triethoxysilane and potassium fluoride gives a 90% yield of benzyl alcohol after six hours at room temperature. The same combination of reagents converts 1-heptanal into 1-heptanol in 70% yield within four hours without affecting benzophenone or 1,3-diphenylpropan-2-one when either is added to the same reaction mixture (Eq. 163).83 n-C6H13CHO + (EtO)3SiH

1. KF 2. H2O

n-C7H15OH

(70%)

(Eq. 163)

60

ORGANIC REACTIONS

These reaction conditions also permit the chemoselective quantitative reduction of benzaldehyde to benzyl alcohol without any concomitant reduction of either acetophenone or 3,3-dimethylbutan-2-one present in the same reaction mixture.83 Additionally, this useful method permits the reduction of aldehyde functions in polyfunctional compounds without affecting amide, anhydride, ethylenic, bromo, chloro, or nitro groups.79,80,319 An improved variation of this reduction method involves the use of potassium fluoride (either anhydrous or as the dihydrate) or potassium formate in a polar aprotic solvent such as dimethylformamide or dimethyl sulfoxide in conjunction with either diethoxymethylsilane or PMHS. The intermediate silyl ethers are worked up by acidic hydrolysis when diethoxymethylsilane is used and by methanolysis when PMHS is the reducing agent.82 A high chemoselectivity among carbonyl group reductions may be accomplished using this method by adjusting the reaction conditions. Aldehydes are especially easy to reduce this way. The combination of diethoxymethylsilane and KF in dimethylformamide produces a 90% yield of benzyl alcohol from benzaldehyde in 0.25 hour at 20◦ following workup.82 In a similar way, 1-heptanal forms 1-heptanol in 85% yield within 1.75 hours at 10◦ . Other combinations of the salts, solvents, and organosilicon hydrides give useful, if somewhat lower, yields of products. Potassium fluoride dihydrate, although a more active catalyst than the anhydrous salt, requires use of an excess of organosilicon hydride because the water that is present destroys some of the silane. Use of potassium formate and PMHS in dimethylformamide permits facile selective reduction of both alkyl and aryl aldehydes in the presence of ketones and esters.82 The system of Me(EtO)2 SiH and KO2 CH is very selective toward the reduction of aldehydes in the presence of ketones.82 In a similar approach aldehydes are reduced with [HSi(OEt)4 ]K.288 Fluoride ion catalyzes the hydrosilylation of both alkyl and aryl aldehydes to silyl ethers that can be easily hydrolyzed to the free alcohols by treatment with 1 M hydrogen chloride in methanol.320 The most effective sources of fluoride are TBAF and tris(diethylamino)sulfonium difluorotrimethylsilicate (TASF). Somewhat less effective are CsF and KF. Solvent effects are marked. The reactions are facilitated in polar, aprotic solvents such as hexamethylphosphortriamide (HMPA) or 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H )-pyrimidinone (DMPU), go moderately well in dimethylformamide, but do not proceed well in either tetrahydrofuran or dichloromethane. The solvent effects are dramatically illustrated in the reaction of undecanal and dimethylphenylsilane to produce undecyloxyphenyldimethylsilane. After one hour at room temperature with TBAF as the source of fluoride and a 10 mol% excess of silane, yields of 91% in HMPA, 89% in DMPU, 56% in dimethylformamide, 9% in tetrahydrofuran, and only 1% in dichloromethane are obtained (Eq. 164).320 TBAF n-C10H21CHO + PhMe2SiH

rt

n-C11H23OSiMe2Ph

(1-91%)

(Eq. 164)

The reduction of aldehydes to alcohols takes place under mild conditions upon treatment with a mixture of trimethoxysilane and lithium methoxide (20 mol%

ORGANOSILICON HYDRIDE REDUCTIONS

61

excess of each) in diethyl ether at room temperature (Eq. 165). The reaction occurs with both alkyl and aryl aldehydes and can be used to reduce aldehydes in the presence of ketones, esters, and nitriles. Workup is by treatment with 1 M aqueous hydrochloric acid.91 For example, benzaldehyde forms benzyl alcohol in 85% isolated yield within 20 hours under these conditions, whereas onitrobenzaldehyde and p-anisaldehyde give the corresponding alcohols in yields of 55 and 86%, respectively. 1-Octanal yields 1-octanol in 80% yield after just six hours.91 Triethoxysilane and diethoxymethylsilane are not as effective as reducing agents as trimethoxysilane. Sodium methoxide, alkali metal ethoxides, and, especially, potassium methoxide also are effective nucleophilic promoters. Lithium and sodium pinacolates are strong promoters that cause the reduction of both aldehydes and ketones.91 RCHO + (MeO)3SiH

MeOLi RCH2OH

Et2O, rt

R = n-C7H15 (80%) R = Ph (85%) R = 2-O2NC6H4 (55%) R = 4-MeOC6H4 (86%)

(Eq. 165)

There seems little doubt that the active reducing agents in these kinds of reductions are pentavalent hydridosilicates. In fact, it is possible to produce the stable potassium salts of these species in high yield by reacting equivalent amounts of the appropriate trialkoxysilanes and potassium alkoxides in large amounts of tetrahydrofuran or 1,2-dimethoxyethane (DME) at room temperature (Eq. 166).107 A variety of alkoxy groups may be used (R = Et, i-Pr, Ph), but neither lithium nor sodium alkoxides are effective in this reaction.107 Potassium tetraethoxyhydrosilicate shows high reducing properties toward both aldehydes and ketones without the need for added catalysts (Eq. 167).288 It reduces benzaldehyde to benzyl alcohol in 90% yield and 1-pentanal to 1-pentanol in 80% yield following aqueous acid workup.288 (RO)3SiH + ROK R = Et, i-Pr, Ph

THF or DME

[(EtO)4SiH]– K+ + RCHO

[(RO)4SiH]– K+

1. THF, 0° or rt 2. H3O+

(80-90%)

RCH2OH R = n-Bu (80%) R = Ph (90%)

(Eq. 166)

(Eq. 167)

A similar reducing system is created by combining dilithium catecholate and trichlorosilane at −78◦ in tetrahydrofuran. It is speculated that the relatively unstable pentacoordinate bis(1,2-benzenediolato)hydridosilicate (61) is formed in situ and that it is this species that can reduce aldehydes and ketones, but not esters, to alcohols when they are added to the reaction mixture at 0◦ (Eq. 168).93 In a like manner, the dilithium salt of 2,2′ -dihydroxybiphenyl, which forms a pentacoordinate intermediate that is stable enough to react at room temperature, can also be used to promote the reduction reaction. The alkoxides of aliphatic diols

62

ORGANIC REACTIONS

such as 1,2-ethanediol and pinacol are not very effective as ligand promoters in this system and those of simple alcohols are without effect. Use of the dilithium catecholate/trichlorosilane combination gives benzyl alcohol from benzaldehyde in 96% yield within two hours. Substitution of 2,2′ -dihydroxybiphenyl for catechol provides a 92% yield of 2,2-dimethylpropanol from 2,2-dimethylpropanal within five hours at room temperature.93 OLi + HSiCl3

2 OLi

THF –78°

OHO Si O O 61

1. RCHO, 0° 2. H2O

RCH2OH

–

(Eq. 168) R = t-Bu (92%) R = Ph (96%) R = 4-MeC6H4 (96%)

Chemoselectivity between aldehydes and ketones is demonstrated by this method in the competitive reduction of a mixture of pentanal and cyclohexanone. The ratios of primary and secondary alcohols are 75 : 25 when catechol is used at 0◦ and 79 : 21 when 2,2′ -dihydroxybiphenyl is used at room temperature. These regents are not as chemoselective as other reducing agents such as LiAlH(OBu-t)3 (87 : 13) and LiAlH(OCEt3 )3 (94 : 6) at 0◦ .93 Several types of organosilicon hydrides are effective reducing agents toward carbonyl functions because of valence expansion produced by intramolecular effects. Aryl silyl hydrides with amine functions are especially prone to having the proper configuration to permit such intramolecular valence expansion.321,322 The valence expanded silicon hydrides compounds 58–60 react spontaneously with both p-nitrobenzaldehyde and p-anisaldehyde to give, within 0.5 to 3 days, the respective benzyl alcohols in quantitative yields following aqueous acidic workup.321 Under the same conditions, a mixture of α-naphthylphenylsilane and N ,N -dimethylbenzylamine fails to react even after 17 days.321 It is of interest to note that the silyl hydrides 58, 59, and 60 (Eqs. 136 and 137) all have trigonal bipyramidal structures in which the active hydrogens occupy equatorial positions. Compound 58 is such an effective carbonyl reducing agent that it reduces carbon dioxide to formaldehyde via a stable silylformate intermediate.323 The 10-Si-5-hydridosiliconate ion 62 is known in association with lithium,323 tetrabutylammonium,101 and bis(phosphoranyl)iminium93 cations. It is synthesized by hydride addition to the 8-Si-4-silane 63, which is derived from hexafluoroacetone.101 Benzaldehyde and related aryl aldehydes are reduced by solutions of 62 in dichloromethane at room temperature101 or in tetrahydrofuran at 0◦ 96 within two hours. The alkyl aldehyde, 1-nonanal, is also reduced by 62 in tetrahydrofuran at 0◦ .96 Good to excellent yields of the respective alcohols are obtained following hydrolytic workup. The reactions are not accelerated by addition of excess lithium chloride,96 but neutral 63 catalyzes the reaction, apparently through complexation of its silicon center with the carbonyl oxygen prior to delivery of hydride from 62.101

ORGANOSILICON HYDRIDE REDUCTIONS

CF3 CF3

– CF3 CF3

O Si H

O Si

O CF3 62

63

O CF3 63

CF3

CF3

The solid bases CaO and hydroxyapatite catalyze the hydrosilylation of benzaldehyde by triethoxysilane at 90◦ in yields of 59% and 72% within one and two hours, respectively.323,324 These reductions also very likely involve activation by valence expansion of the silicon hydride reagent. Reductive Amidation of Aldehydes. The reductive amidation of aldehydes using an organosilane as the reducing agent has been realized. Benzaldehyde reacts over a 74-hour period with triethylsilane and acetonitrile in 75% aqueous sulfuric acid at room temperature to produce an 80% isolated yield of N benzylacetamide (Eq. 169).313 Octanal fails to react under the same conditions.313 Reductive amidation of aldehydes also occurs with the reagent combination Et3 SiH/TFA/primary amide (Eq. 170).326 CHO + MeCN

CHO HO2C

aq. H2SO4

NHCOMe

Et3SiH

(80%)

(Eq. 169)

Ph

(Eq. 170)

O Et3SiH, TFA, PhCONH2

N H

MeC6H5, 120°, 18 h

(96%)

HO2C

Reductive Esterification. Aldehydes can give ester products when treated with combinations of organosilicon hydrides and carboxylic acids that have appreciable basicity. Benzaldehyde gives a product mixture consisting of 12% dibenzyl ether and 88% of benzyl formate when it is treated for 8 hours at room temperature with a slight excess of triethylsilane in formic acid.313 p-Nitrobenzaldehyde produces 33% bis(p-nitrobenzyl) ether and 66% of p-nitrobenzyl trifluoroacetate when it reacts with Et3 SiH/TFA for 5 hours at room temperature. Other aldehydes give small, variable amounts of esters under similar reaction conditions. Although this general approach to the synthesis of esters from aldehydes is an attractive one, it appears not yet to be optimized for maximum synthetic utility because of the frequent formation of considerable amounts of ether products (Eq. 171).313 RCHO + R'CO2H R = alkyl, aryl R' = H, CF3, Cl2CH

Et3SiH

(RCH2)2O + RCH2O2CR' (variable)

(Eq. 171)

64

ORGANIC REACTIONS

Reductive Etherification. As indicated earlier, aldehydes as well as ketones often give very good yields of ethers when they are treated with Brønsted acids or other electrophilic species in the presence of organosilicon hydrides (Eq. 172). In the absence of added alcohols, symmetrical ethers are obtained. RCHO

R'3SiH

(Eq. 172)

(RCH2)2O

HX

When alcohols are added to the reaction mixture, unsymmetrical ether products may be obtained. Starting with a mixture of aldehydes can also give rise to the formation of unsymmetrical ethers. These ether products are formed under conditions different from those used in the formation of ethers directly from alcohols. Thus, it is postulated that the reaction sequence that leads from the carbonyl substrate to the ether involves the intermediate formation of hemiacetals, acetals, or their protonated forms and alkoxycarbenium ions, which are intercepted and reduced to the final ether products by the organosilicon hydrides present in the reaction mix. The probable mechanistic scheme that is followed when Brønsted acids are present is outlined in Scheme 2.311,327,328 RCH=O + H+ R = alkyl, aryl RCH=OH+ + RCH2OH +

RCH=OH+ H H R C OCH2R + OH R'3SiH

RCHOCH2R

R'3SiH

RCH2OH +

RCHOCH2R + H2O

RCH2OCH2R

R = alkyl, aryl

Scheme 2

Reduction of aldehydes to symmetrical ethers can be accomplished in good to excellent yields with Et3 SiH/Ph3 C+ ClO4 − ,329 Et3 SiH/ZnCl2 ,330 Me2 ClSiH/ In(OH)3 ,331 Et3 SiH/BiCl3 ,332 (HMe2 Si)2 O/TMSOTf (or TMSCl/NaI),314 Et3 SiH (or PhMe2 SiH)/Bu4 NClO4 ,333 Et3 SiH/TMSOTf,334 Et3 SiH/H2 SO4 ,328 and Et3 SiH/ TFA.313 The reaction of 1.4 equivalents of triethylsilane with two equivalents of trifluoroacetic acid rapidly reduces benzaldehyde to dibenzyl ether in 80% yield at temperatures below 40◦ .311 Similar treatment of n-butanal with two equivalents of triethylsilane and three equivalents of trifluoroacetic acid produces di-n-butyl ether in a more modest 37% yield.311 Variations of these simple reaction conditions permit greater yields of desired ether products to be obtained. For example, 1heptanal reacts with a 10 mol% excess of triethylsilane to give a 90% yield of di-n-heptyl ether within 45 minutes at room temperature when the reaction is run in a twenty-fold excess of trifluoroacetic acid acting as solvent.313 With the exception of p-nitrobenzaldehyde, which gives only a 33% yield of the symmetrical ether (the remainder is converted into p-nitrobenzyl trifluoroacetate), other representative aryl aldehydes normally give yields of symmetrical ethers on the order of 80% or greater.313

ORGANOSILICON HYDRIDE REDUCTIONS

65

Unsymmetrical ethers may be produced from the acid-promoted reactions of aldehydes and organosilicon hydrides when alcohols are introduced into the reaction medium (Eq. 173).327,328 An orthoester can be used in place of the alcohol in this transformation.327,335 A cyclic version of this conversion is reported.336 Treatment of a mixture of benzaldehyde and a 10 mol% excess of triethylsilane with methanol and sulfuric, trifluoroacetic, or trichloroacetic acid produces benzyl methyl ether in 85–87% yields.328 Changing the alcohol to ethanol, 1-propanol, 2-propanol, or 1-heptanol gives the corresponding unsymmetrical benzyl alkyl ethers in 45–87% yield with little or no side products.328 A notable exception is the tertiary alcohol 2-methyl-2-propanol, which requires 24 hours.328 1-Heptanal gives an 87% yield of n-heptyl methyl ether with added methanol and a 49% yield of benzyl n-heptyl ether with added benzyl alcohol under similar conditions.328 RCHO + R"OH R = alkyl, aryl R'' = alkyl

R'3SiH

RCH2OR"

HX

(45-87%)

(Eq. 173)

R' = aryl

The yield of ethyl n-pentyl ether formed from the reduction of 1-pentanal by Et3 SiH/TFA in ethanol is 57% after 6–8 hours at 50–60◦ .327 The yield of product increases to 72% when one equivalent of ethyl orthoformate and some anhydrous hydrogen chloride are added to the reaction medium.327 Presumably, this reduces the amount of free water in the reaction medium. An interesting and effective variation of this general synthetic approach uses electrogenerated acid (EG acid) to assist in the formation of ethers from aldehydes.333 This method permits the synthesis of both symmetrical and unsymmetrical ethers. The experiments are conducted using platinum electrodes in a simple undivided cell. A mixture of aldehyde and a 20 mol% excess of either triethylsilane or dimethylphenylsilane in dichloromethane solvent containing lithium perchlorate and tetra-n-butylammonium perchlorate is electrolyzed by the passage of small amounts of current (0.04–0.45 Faradays/mol) to give symmetrical ethers (Eq. 174). In this way, both dibenzyl and dialkyl ethers may be produced in excellent yields (86–96%).333 Unsymmetrical ethers are produced in 50–99% yields when alkoxytrimethylsilanes are added to the reaction mixture (Eq. 175).333 The alkoxy groups can include allyl, propargyl, and 3-phenylpropyl moieties. Phenol trimethylsilyl ether is ineffective in producing phenyl ethers.333 RCHO R = alkyl, Ph PhCHO + TMSO

R'3SiH EG acid

RCH2OCH2R

(86-96%)

(Eq. 174)

R' = Me, Et, Ph Et3SiH, EG acid, CH2Cl2, rt

Ph

O

(95%)

(Eq. 175)

Various chemical species with Lewis acid properties are also effective in promoting the direct conversion of aldehydes into ethers by organosilicon hydrides.

66

ORGANIC REACTIONS

They offer the advantage that reductions can be effected under conditions that permit the conversion of substrates that may be adversely sensitive to the presence of strong Brønsted acids. For example, in the presence of a 10% excess of triethylsilane, addition of one-half equivalent of boron trifluoride etherate to octanal results, within one hour, in the formation of a 66% yield of dioctyl ether after a basic hydrolytic workup. Benzaldehyde provides a 75% yield of dibenzyl ether under the same reaction conditions. The remainder of the mass is found as the respective alcohol.70 Zinc chloride is also capable of catalyzing this reaction. With its use, simple alkyl aldehydes are converted into the symmetrical ethers in about 50% yields.330 Superior yields of ethers from aldehydes are obtained by the use of several other electrophilic species. The addition of 5 mol% of trityl perchlorate to a mixture of triethylsilane and 3-phenylpropanal in dichloromethane at 0◦ produces an 83% yield of bis-(3-phenylpropyl) ether within 10 minutes (Eq. 176).329 Reductive polycondensation of isophthalaldehyde occurs with two equivalents of triethylsilane in the presence of 10 mol% of trityl perchlorate to give 40–72% yields of polyether with average molecular weights ranging from 6,500 to 11,400 daltons (Eq. 177).337 Addition of one equivalent of an alkoxytrimethylsilane to the reaction mixture produces unsymmetrical ethers in good to excellent yields. Thus, a mixture of (E)-cinnamaldehyde, 3-phenylpropoxytrimethylsilane, and triethylsilane in dichloromethane reacts under the influence of a catalytic amount of trityl perchlorate to give the unsymmetrical ether in 88% yield (Eq. 178).329 Ph3C+ClO4–

O Bn

H

OHC

CHO

O

Bn

Et3SiH, CH2Cl2, 0°

Ph3C+ClO4–

Bn

—OCH2

(Eq. 176)

(83%)

CH2—

Et3SiH, CH2Cl2

(Eq. 177)

n

(40-72%) +

Ph

CHO + Ph

OTMS

Ph3C ClO4

–

Et3SiH, CH2Cl2, 0°

Ph

O

Ph

(88%)

(Eq. 178) The use of trimethylsilyl-based electrophilic catalysts with organosilicon hydrides also promotes the conversion of aldehydes into ethers and avoids the need to employ the potentially hazardous trityl perchlorate salt.314,334,338 One reagent pair that is particularly effective in the reductive conversion of aldehydes into symmetrical ethers is a catalytic amount of trimethylsilyl triflate combined with either trimethylsilane, triethylsilane, PMHS,334 or 1,1,3,3tetramethyldisiloxane (TMDO, 64) as the reducing agent (Eq. 179).314 Either Me Me H Si O Si H Me Me 64

ORGANOSILICON HYDRIDE REDUCTIONS

67

dichloromethane or benzene can be used as the solvent. The reactions occur at temperatures ranging from 0◦ to 80◦ . These conditions produce symmetrical ethers from both aromatic and aliphatic aldehydes in yields frequently exceeding 90%. Aromatic aldehydes tend to give minor amounts of benzyl alcohols as byproducts.334 The synthesis of cyclic ethers from dialdehydes or keto aldehydes is also possible (Eqs. 180 and 181).339 (HMe2Si)2O

RCHO

TMSOTf or TMSI

(RCH2)2O

(Eq. 179)

R = alkyl, aryl

O O

Et3SiH, TMSOTf

Ph Et3SiH, TMSOTf

O

O

CH2Cl2, rt, 45 min

CH2Cl2, rt, 45 min

(92%)

(Eq. 180)

(71%)

(Eq. 181)

Ph O

O

The formation of unsymmetrical ethers from the reduction of aldehydes in the presence of tetrahydropyran (THP) ethers is reported (Eq. 182).340 O O

OTHP

+ PhCHO

Et3SiH, TMSOTf MeCN, 0°, 1 h

O O

OBn (90%)

(Eq. 182) Trimethylsilyl iodide can be substituted for the trimethylsilyl triflate catalyst in the reactions of aliphatic aldehydes. TMSI can be generated conveniently in situ either from trimethylsilyl chloride and sodium iodide in acetonitrile314 or from hexamethyldisilane and iodine in dichloromethane334 or pentane.338 It is noted that neither triisopropylsilane nor PMHS is an effective reducing agent for this purpose when used with TMSI under these conditions.314,334 Equivalent amounts of aldehydes and alkoxytrimethylsilanes react to form unsymmetrical ethers in near quantitative yields in the presence of either trimethylsilane or triethylsilane and catalytic amounts (ca. 10 mol%) of TMSI in dichloromethane.329,333,334,341 The procedure is particularly convenient experimentally when trimethylsilane is used with TMSI because the catalyst provides its own color indicator for the reduction step (color change from deep violet to vivid red-gold) and the only silicon-containing product following aqueous workup is the volatile hexamethyldisiloxane (bp 99–100◦ ). It is possible to introduce trimethylsilane (bp 7◦ ) either as a previously prepared solution in dichloromethane or by bubbling it directly into the reaction mixture. Cyclohexyloxytrimethylsilane and n-butanal react by this method to give a 93% isolated yield of n-butyl cyclohexyl ether (Eq. 183).334

68

ORGANIC REACTIONS OC4H9-n

OTMS 1. TMSH, TMSI, CH2Cl2

n-C3H7CHO +

(93%)

2. H2O

(Eq. 183)

Trimethylsilane in pentane is a particularly good system for the TMSIcatalyzed reductive coupling of tertiary alkoxytrimethylsilanes with aldehydes to form sterically crowded tertiary-primary ethers.337 In this way, 1-(tertbutoxymethyl)-3-methylbenzene is formed in 87% yield (Eq. 184).338 Reaction of terephthaldehyde with two equivalents of the trimethylsilyl ether of 1adamantanol under these conditions leads to a good yield of the diadamantyl ether of 1,4-benzenedimethanol (Eq. 185).338 CHO

CH2OBu-t

TMSH

+ t-BuOTMS

(87%)

(Eq. 184)

TMSI, n-C5H12 OHC

TMSH, TMSI, n-C5H12

+ 2

OTMS

CHO

–78° to rt, 5-6 h

(Eq. 185)

O (78%)

O

Cyclic ethers can also be formed in a fashion similar to that of the reactions described previously (Eq. 186),306,342 and also result from the reductive etherification of bis(trimethylsilylated) diols and dialdehydes (Eq. 187).343 O OTMS

H Ph H + O

2. Et3SiH, –23°, 2.5 h

OTMS

O

H

1. SbCl5, TMSCl, SnI2, CH2Cl2, –78°, 30 min

TMSO

Ph

O

O

(76%)

(Eq. 186)

O

Et3SiH, BiBr3, CH2Cl2

(7%)

MeCN, –30° to 0° O

O

(Eq. 187) The reductive silylation of aldehydes provides a one-step route to silyl ethers. This is accomplished with the reagent combinations PhMe2 SiH/CuH(PPh3 ),317 Et3 SiH/ZnCl2 (or SnCl2 or NiCl2 ),343 Ph2 SiH2 /CsF (or KF, BnMe3 NF, KO2 CH),75,319 Et3 SiH/(C6 F5 )3 B,115,281 PhMe2 SiH/CsF,320,345 – 347 and Et3 SiH/ TBAF.76 Montmorillonite clay that has been subjected to ion exchange with ferric ion catalyzes the hydrosilylation of benzaldehyde with triethylsilane to give benzyl triethylsilyl ether in 79% yield.324,325

ORGANOSILICON HYDRIDE REDUCTIONS

69

Various non-conjugated diene aldehydes react with Et3 SiH/Ni(cod)2 /PPh3 to give O-triethylsilylated cycloalkanols in low to high yields. Acyclic dienes can lead to the silylated cycloalkanols in moderate yields with the proper catalyst (Eq. 188).348 Bicyclic systems are also generated by this methodology (Eq. 189).349 MeO2C

CHO

PhMe2SiH, Ni(cod)2

OSiEt3

MeO2C

MeO2C

+

MeO2C P Ph, THF, rt, 5 h

OSiEt3

MeO2C

(Eq. 188)

MeO2C (61%) 7.3:1

H

Et3SiH, Ni(cod)2, PPh3

OSiEt3 (81%)

THF, 30°, 4 h

CHO

(Eq. 189)

H

Et3 SiH/Ni(cod)2 brings about the reaction of an aldehyde and an alkyne to provide the silylated allyl alcohol (Eq. 190).350 The reaction also occurs in an intramolecular mode. CHO

Et3SiH, Ni(cod)2 +

Ph

Et3SiO Ph

:

Mes N

H Ph

(84%)

(Eq. 190)

N Mes

Reduction to Alkanes. Carbonyl groups can be reductively deoxygenated to methylene functions if both of the two steps represented by Eqs. 1 and 2 proceed to completion. With aldehydes, this process leads to the transformation of the CHO group into a CH3 group. The relative instability of primary alkyl carbenium ions in the condensed phase and the weak intrinsic nucleophilicity of organosilicon hydrides are the reasons that primary alkyl alcohols are not reduced to hydrocarbons. For these same reasons, aliphatic aldehydes do not undergo complete deoxygenation to methylterminated hydrocarbons when treated with acids and organosilicon hydrides under usual laboratory conditions. In contrast, many aryl aldehydes can be transformed into methylarenes by this method. Since the organosilane reduction of benzyl alcohols to the corresponding toluene derivatives is known, it is not surprising that the reduction of an aryl aldehyde to a toluene is possible. This transformation has been carried out with Et3 SiH/TFA,69,351,352 (EtO)3 SiH, and Et3 SiH with various catalysts,353 Et3 SiH/(C6 F5 )3 B,281 PMHS/Pd/C,316 and PMHS/ (C6 F5 )3 B.354 The last combination also reduces alkyl aldehydes to the corresponding alkanes (Eq. 191).281,282,354 CHO

PMHS, (C6F5)3B CH2Cl2, rt, 5-20 min

(90%)

(Eq. 191)

70

ORGANIC REACTIONS

Trifluoroacetic acid solutions of benzaldehydes having electron-donating ring substituents form the corresponding methyl arenes when at least two equivalents of an organosilicon hydride are added to the solution at room temperature. The reaction conditions permit preservation of the integrity of functions such as halogen, alkoxy, carboxylate, cyano, and nitro. There is little difference in the reducing abilities of triethylsilane, tri-n-propylsilane, and tri-n-hexylsilane in these reactions. Thus, the silane reducing agent can be chosen that best suits purification of the desired product. Basic aqueous workup converts the silicon reaction products derived from the organosilicon hydride into the corresponding silanols and disiloxanes, which may be removed from the desired reduction products by simple distillation.69 Benzaldehyde itself forms no toluene; only dibenzyl ether and benzyl trifluoroacetate are formed. Triethylsilane (2.2 equivalents) causes the transformation of p-anisaldehyde into p-methylanisole in 76% yield after only 30 minutes. Use of a three-fold excess of dimethylphenylsilane in place of the triethylsilane results in a slight improvement in yield to 83% after 45 minutes.69 Similar treatment of a trifluoroacetic acid solution of p-tolualdehyde with triethylsilane gives only a 20% yield of p-xylene after 11 hours reaction time followed by basic workup. Use of 2.5 equivalents of dimethylphenylsilane enhances the yield to 52% after only 15 minutes. This reaction proceeds stepwise through the formation of a mixture of the trifluoroacetate and the symmetrical ether. These intermediates slowly form the desired p-xylene product along with Friedel-Crafts side products under the reaction conditions (Eq. 192).73 Addition of co-solvents such as carbon tetrachloride or nitromethane helps reduce the amount of the Friedel-Crafts side products.73 CHO

R3SiH

O

O2CCF3

+

TFA

(Eq. 192) R3SiH

+

TFA

Friedel-Crafts products

Treatment of a polyfunctional chromium-tricarbonyl-complexed hydroxy aldehyde with an excess of Et3 SiH/TFA for 4.5 hours gives an 82% yield of fully reduced product with both the formyl and hydroxy groups completely and selectively reduced (Eq. 193).352 OHC MeO HO Cr(CO)3

Et3SiH, CH2Cl2 TFA, 0° to 60°

(82%)

(Eq. 193)

MeO Cr(CO)3

The sequence of reagent and substrate addition can be quite important in these reactions. For example, a trifluoroacetic acid solution of 2,4,6-trimethylbenzaldehyde forms isodurene in 98% yield within 15 minutes when 2.2 equivalents of triethylsilane are added to the reaction mixture at room temperature.69 In

ORGANOSILICON HYDRIDE REDUCTIONS

71

contrast, when trifluoroacetic acid is added to a stirred solution of triethylsilane and 2,4,6-trimethylbenzaldehyde, isodurene is formed in only 70% yield after basic aqueous workup. Minor side products under these reaction conditions are mesitylene (formed via acid-catalyzed decarbonylation of the aldehyde) and the Friedel-Crafts product 2,4,6,2′ ,3′ ,4′ ,6′ -heptamethyldiphenylmethane (Eq. 194).311 CHO Et3SiH

+

TFA (70%)

+

(5%)

CH2

(Eq. 194)

(8%)

The Et3 SiH/BF3 •OEt2 combination fails to cause complete deoxidative reduction of aldehydes, forming instead mixtures of primary alcohols and symmetrical ethers.74 By contrast, aryl aldehydes lacking electron-withdrawing ring substituents, when reacted in dichloromethane with at least two equivalents of triethylsilane and gaseous boron trifluoride at 0◦ , form the corresponding methylarenes within a few minutes (Eq. 195).1 Even benzaldehyde produces a 52% yield of toluene by this method when 18 equivalents of triethylsilane are added to suppress formation of Friedel-Crafts oligomers. The method offers the advantage that fluorotriethylsilane is formed, which is volatile and is easily separated from the desired organic products.1 ArCHO

Et3SiH, CH2Cl2 BF3, 0°

ArMe + Et3SiF Ar = Ph (52%) Ar = 4-MeC6H4 (45%) Ar = 4-ClC6H4 (68%) Ar = 4-MeOC6H4 (100%)

(Eq. 195)

If Friedel-Crafts products are desired, a clever method exists for the direct conversion of aryl aldehydes into diarylmethanes. Reaction of a mixture of an aromatic aldehyde and a catalytic amount of trimethylsilyl trifluoromethanesulfonate and excess polymethylhydrosiloxane in either benzene or toluene at reflux results in the formation of the respective arylphenyl or tolylmethanes in reasonably good yields within 1–3 hours (Eq. 196).314 Thus, benzaldehyde reacts in refluxing benzene containing a few drops of TMSOTf and excess PMHS to give diphenylmethane in 92% yield within two hours and in refluxing toluene within one hour to give a 95% yield of a mixture of phenyl-p-tolylmethane and phenyl-o-tolylmethane in a 70 : 30 ratio. p-Tolualdehyde gives a 60% yield of phenyl-p-tolylmethane when heated at reflux in benzene for 2.5 hours and an 80% yield of di-p-tolylmethane and p-tolyl-o-tolylmethane in a 90 : 10 ratio when heated at reflux in toluene for 30 minutes. o-Chlorobenzaldehyde gives a mixture of 25% phenyl-o-chlorophenylmethane and 55% of bis(o-chlorophenyl)ether, and p-chlorobenzaldehyde gives a 65% yield of a mixture of phenyl-p-chlorophenylmethane and bis(p-chlorophenyl)ether in a 75 : 25 ratio when heated at reflux in benzene for 3 hours.314

72

ORGANIC REACTIONS PMHS ArCHO + Ar'H

ArCH2Ar'

TMSOTf

(25-95%)

(Eq. 196)

Ar = Ph, 4-MeC6H4, 4-ClC6H4, 2-ClC6H4 Ar' = Ph, 4-MeC6H4

The TFA-catalyzed triethylsilane reductive condensation of an aldehyde with indoles provides a convenient route to 3-substituted indoles in modest to good yields (Eq. 197).355 Cl H

CO2Et

+

O

N Ph

CO2Et

Cl

Et3SiH, TFA

(79%) N

Ph

Ph

Ph

(Eq. 197) Reduction to Methylene Halides. Treatment of aryl aldehydes with selected organosilicon hydrides and an appropriate trimethylsilyl halide produces benzyl chlorides, bromides, and iodides directly in good to excellent yields by reductive halogenation (Eq. 198). This protocol offers the advantage of being simple and leading only to the monohalo derivatives. The method is specific for the carbonyl group of both aryl ketones and aldehydes and preserves the integrity of many other groups (e.g. ring halogen, alkyl, alkoxy, cyano, nitro, hydroxy, ester) that may be found in polyfunctional compounds. Alkyl aldehydes form symmetrical ethers instead of halides under these reaction conditions.314,356,357 Several variations of this general method exist. In the most straightforward approach for synthesizing iodides, the addition of an external trimethylsilyl reagent is not required. Aromatic aldehydes normally react within minutes at room temperature with iodine and TMDO in dichloromethane solution to produce benzyl iodides in high yields (66–87%) (Eq. 199). A reactive silyl iodide is believed to be formed in situ from tetramethyldisiloxane and iodine under these conditions. The reaction is not limited to aryl rings with only electron-donating groups; chloro-, hydroxy-, alkyl-, alkoxy-, cyano-, and carboalkoxy-substituted rings all undergo the transformation.357 The same transformation can be carried out with diiodosilane.358 TMDO ArCHO

TMSX

ArCH2X

(40-97%)

(Eq. 198)

Ar = various substituted aryl CH2I

CHO TMDO

(87%)

I2, CH2Cl2, rt OH

OH

(Eq. 199)

ORGANOSILICON HYDRIDE REDUCTIONS

73

Another variation of this method involves the treatment of an acetonitrile solution of the aryl aldehyde, trimethylsilyl chloride, and either sodium iodide, if iodide products are desired, or lithium bromide, if bromide products are desired, with TMDO. After an appropriate reaction time (5–195 minutes) at a temperature in the range of −70◦ to 80◦ , the upper siloxane layer is removed and the benzyl iodide or bromide product is isolated from the remaining lower portion after precipitation of the inorganic salts by addition of dichloromethane. For example, p-anisaldehyde reacts to form p-methoxybenzyl bromide in 84% isolated yield under these conditions (Eq. 200).314,356 CHO

TMDO, MeCN

MeO

CH2Br

TMSCl, NaBr

(Eq. 200)

(84%) MeO

In the preparation of iodides, but not bromides, PMHS may be substituted for the TMDO. Chlorides can be obtained if thionyl chloride and zinc iodide are added to suppress the formation of symmetrical ethers.314 An example of this type of reductive chlorination is shown by the TMDO-mediated conversion of ptolualdehyde into p-methylbenzyl chloride (Eq. 201).313 To obtain chlorides from aldehydes having electron-withdrawing groups such as nitro or carbomethoxy, the initial reaction is first carried out at −70◦ and the mixture is then heated to reflux in order to reduce the formation of symmetrical ether by-products. Zinc chloride is substituted for zinc iodide for the synthesis of chlorides of substrates with electron-donating groups such as methoxy and hydroxy.314 CHO

TMDO, TMSCl

Cl

SOCl2, ZnI2 (cat.)

(Eq. 201)

(87%)

Reductive Amination. Reaction of an aminohydrodimethylsilane with aldehydes in the presence of a Lewis acid catalyst gives the corresponding amine in good to high yields (Eq. 202).359 The use of an Et3 SiH/TFA/amine reagent combination also leads to the reductive amination of aldehydes (Eq. 203).360 Comparable reductive aminations of aldehydes are possible in moderate yields with PhSiH3 /Bu2 SnCl2 /amine,361,362 and in good yields with PMHS/TiCl4 /amine363 or with amine/Cl3 SiH.364 CHO

Et2NSiHMe2, TiCl4

NEt2

CH2Cl2, 0° to rt, 36 h

CHO NH N

CN

Et3SiH, TFA, CH2Cl2 N H

Ph

SO2Pr-n

CN

SO2Pr-n

+

(Eq. 202)

(91%)

Ph

N

rt, 2-4 h NH N (90%)

(Eq. 203)

74

ORGANIC REACTIONS

Reductive Thiolation. Treatment of aldehydes with triethylsilane, thiols, and boron trifluoride monohydrate6,217 yields sulfides in a one-flask process. For example, this method gives a 97% yield of benzyl isopropyl sulfide from benzaldehyde and 2-propanethiol (Eq. 204).365 PhCHO

1. i-PrSH, BF3•OH2, CH2Cl2, 0°, 1 min 2. Et3SiH, 0° to rt, 3 h

Ph

(97%)

SPr-i

(Eq. 204)

Reduction of Ketones The selective organosilane reduction of ketone functions can be effected in the presence of a number of other functional groups including epoxides,320,366 ketals,86,367 thioketals,368 other ketones,369,370 β-lactams,371 alkynes,372 esters,79,80,83,84,87,320,373,374 α-bromides,76,80,83 amides80,83,84,86,276,320,375 84,276 83,376 83,86 ureas, trifluoroacetamides, sulfonamides, and nitro groups.80 Reduction to Alcohols. The organosilane-mediated reduction of ketones to secondary alcohols has been shown to occur under a wide variety of conditions. Only those reactions that are of high yield and of a more practical nature are mentioned here. As with aldehydes, ketones do not normally react spontaneously with organosilicon hydrides to form alcohols. The exceptional behavior of some organocobalt cluster complex carbonyl compounds was noted previously. Introduction of acids or other electrophilic species that are capable of coordination with the carbonyl oxygen enables reduction to occur by transfer of silyl hydride to the polarized carbonyl carbon (Eq. 2). This permits facile, chemoselective reduction of many ketones to alcohols. Certain catalysts promote the reduction of ketones with organosilanes. The reduction of acetophenone with Et3 SiH is catalyzed by the diphosphine 65 and gives only a small amount of overreduction to ethylbenzene.377 Aryl alkyl enones and ynones are reduced to the corresponding alcohols with triethoxysilane and the titanium-based catalyst 66.378 Trichlorosilane reduces acetophenone in 90% yield with N -formylpyrrolidine catalysis.379 O

O

O

N

N PPh2

Ph2P 65

O Ti

O

O

66

Ph

Ph (dimer)

Promotion by Acid. The same range of Lewis and Brønsted acids that promote the silane reduction of aldehydes can be used for the reduction of ketones. These acid-catalyzed reductions appear to proceed by direct hydride transfer rather than by a single-electron transfer mechanism.380 Similar to the case of aldehydes, the silane reductions of ketones promoted by Brønsted acids rarely give clean yields of alcohols when conducted under anhydrous conditions. Instead, mixtures of alcohols, esters, and silyl ethers often result.313,381 The reagent combination of Et3 SiH/HCl (or H2 SO4 ) gives good yields of the alcohol, although

ORGANOSILICON HYDRIDE REDUCTIONS

75

by-products of the sym-ether among others can complicate the reduction.313 Use of zinc chloride to promote organosilicon hydride reduction of ketones to siloxanes that can be hydrolyzed to alcohols is well known. It is one of the first Lewis acid catalysts reported to be useful for this purpose,382,383 although others are known.384 The combination of Et3 SiH/TFA/NH4 F provides a good yield of the alcohol with some ether formation.135 High yields of the alcohol from both aryl and alkyl ketones are realized by the HMDS/(AcOBu2 Sn)2 O316 and HMDS/Sn(OTf)2 385 reagent combinations. The Et3 SiH/(C6 F5 )3 B combination cleanly reduces aryl ketones to the substituted benzyl alcohols.116 Under certain conditions, the trifluoroacetic acid catalyzed reduction of ketones can result in reductive esterification to form the trifluoroacetate of the alcohol. These reactions are usually accompanied by the formation of side products, which can include the alcohol, alkenes resulting from dehydration, ethers, and methylene compounds from over-reduction.68,70,207,208,313,386 These mixtures may be converted into alcohol products if hydrolysis is employed as part of the reaction workup. An example is the reduction of cyclohexanone to cyclohexanol in 74% yield when treated with a two-fold excess of both trifluoroacetic acid and triethylsilane for 24 hours at 55o and followed by hydrolytic workup (Eq. 205).203 OH

O 1. Et3SiH, TFA

(Eq. 205)

(74%)

2. aq. K2CO3

Promotion by Valence Expansion. As in reactions of aldehydes, addition of nucleophilic substances to mixtures of ketones and organosilicon hydrides promotes reduction of the carbonyl group as depicted in Eq. 6. Ketones are conveniently reduced in high yields with reagent combinations of (EtO)3 SiH or Me(EtO)2 SiH and KF (or CsF).80 The pentacoordinate silane 67 itself reduces ketones in high yields (Eq. 206).84 In a somewhat similar approach, the lithium salt of silicate 68 is a good reducing agent for ketones (Eq. 207).96 Other hydridosilicates are known to similarly reduce ketones.93 O

SiPhH2 NMe2

+

OH rt, 12 h

(100%)

(Eq. 206)

(88%)

(Eq. 207)

67 CF3

CF3

O O

OH +

Li+ H

–

THF, 0°, 2 h

Si O

CF3

CF3 68

76

ORGANIC REACTIONS

The PMHS/TBAF system provides both an excellent and practical approach to the reduction of aryl ketones to the benzyl alcohols.278 Similarly, the PMHS/ TritonB combination gives high yields of the benzyl alcohols.278 Diastereoselective Reductions. The diastereoselectivity of organosilane reductions of ketones has been the topic of a number of studies. Extensive studies of the Brønsted acid promoted reductions of alkyl-substituted cyclohexanones by mono-, di-, and trialkylsilanes show that chain branching and other steric features of both the silane and the carbonyl substrate can be important factors in determining the isomeric compositions of reduction product mixtures.68,381,384,386 In general, the reduction of various substituted cyclohexanones does not show effective diastereoselectivity even when very sterically hindered silanes such as Ph3 SiH387,388 or (t-Bu)3 SiH386 are employed. A quite good system is a silane under TritonB or TBAF catalysis.278 The best system for the trans-selective reduction of 4-tert-butylcyclohexanone is the sterically encumbered (TMSO)3 SiH/TBAF (Eq. 208).278 This system is not successful in the stereoselective reduction of 2-methylcyclohexanone, giving a cis:trans selectivity of 18 : 82, although 3-methylcyclohexanone gives a cis:trans ratio of 7 : 93 and a high (>90%) yield of 3-methylcyclohexanol. The combination of PMHD/dibutylacetoxytin oxide (DBATO) reduces 4-tertbutylcyclohexanone exclusively to trans-4-tert-butylcyclohexanol.316 The active reducing agent in this system is likely a tin hydride species. A system of Ph2 MeSiH (or Ph3 SiH)/TBAF/HMPA reduces 2-methylcyclohexanone in a cis:trans ratio of 95 : 5.320 Only cis-2-methylcyclohexanol is isolated from the reduction of 2-methylcyclohexanone with Ph3 SiH/(C6 F5 )3 B.116 Other systems give only moderate selectivities in the reduction of substituted cyclohexanones.70,79,93,116,278,313,367,381,382,384,386,389 – 392 t-Bu

t-Bu (TMSO)3SiH, TBAF

t-Bu (99%)

+

(1%)

OH

O

(Eq. 208)

OH

Naphthoquinone is reduced to 1,2,3,4-tetrahydronaphthalene with Et3 SiH/TFA in 60% yield.393 Quinones can be reduced to hydroquinones in good yields with hydridosiloxanes such as TMDO with iodide present (Eq. 209).314,316,357 The reductive dehydration of a 1,3-diketone leads to an enone (Eq. 210).374 O

OH Et3SiH, TFA

(Eq. 209)

(60%)

60-65°, 10 h O

OH

O

O Ph2SiH2, (Ph3P)4RhH CH2Cl2, rt, 12 h O

O

(46.6%)

+

(2.5%)

(Eq. 210)

ORGANOSILICON HYDRIDE REDUCTIONS

77

Reduction of the ketone carbonyl of cis-1,2,3,4,4a,9b-hexahydro-8-hydroxydibenzofuran-3-one with trifluoroacetic acid and triethylsilane at 0◦ produces a mixture of the α- and β-isomers of the C3 alcohol with an α : β ratio of 1 : 4 (Eq. 211).394 This result can be compared with the isomer ratio of 100 : 1 that results when sodium borohydride is used as the reducing agent.394 The same cis pair of alcohol isomers is formed in 77% combined yield, but in a reversed ratio of α : β = 4 : 1, when the less saturated tetrahydrodibenzofuran analog is used as the substrate (Eq. 212).394 HO

HO

H O O H

HO

H

Et3SiH

H

TFA

OH

O H

H OH

+ O H

H

1:4

(Eq. 211) HO

HO Et3SiH O

TFA

HO

H H OH

O H

O

H OH

+ O H

(Eq. 212)

H

(77%) 4:1

Treatment of a pentacyclic 1α,11-(2-oxethano) thioketal steroid with excess Et3 SiH/TFA causes reduction of the carbon-carbon double bonds as well as the 17-carbonyl group to give a single reaction product (Eq. 213).368 Other work utilizes trifluoroacetic acid, triethylsilane, and anisole in the presence of a catalytic amount of boron trifluoride etherate to reduce the acetyl carbonyl of a 3-acetyl2-azetidinone derivative with a dr of 8 : 1 (Eq. 214).395 O O

O

OH

H

1. xs Et3SiH, TFA, CH2Cl2

(73%)

2. H2O, OH–

S

H

S S

S

H

(Eq. 213) O

HO

H H OBn N

O

Et3SiH, BF3•OEt2

OBn

TFA, PhOMe, –10°

DAM DAM = (4-MeOC6H4)2CH

HO

H H

OBn

N O

H H

+ N

DAM

O

(Eq. 214)

DAM

(71%) 8:1

In a similar way, a mixture consisting of 2% boron trifluoride etherate in trifluoroacetic acid and triethylsilane brings about the regioselective reduction of the acyclic carbonyl group of the diketovinyl chloride shown in Eq. 215 in high yield (>94%), but with formation of approximately equal amounts of the two possible diastereomers formed from the creation of a new chiral center.396

78

ORGANIC REACTIONS Cl

Cl

O

OH

Et3SiH

OH

+

TFA, 2% BF3 • OEt2

O CO2Me

Cl

O CO2Me

O CO2Me

(79%) 1:1

(Eq. 215) The stereoselective reduction of the carbonyl group of β-hydroxy ketones can be accomplished by a silylation-intramolecular reduction sequence. The best results are obtained when diisopropylchlorosilane is employed.397 The clever use of an intramolecular hydride transfer from a pre-anchored silyl hydride site allows β-hydroxy ketones to be reduced to 1,3-diols with a very high degree of diastereoselectivity.397 – 399 A specific example is the reaction of the hydroxy ketone shown in Eq. 216, first with chlorodiisopropylsilane to form the acyclic siloxane and then with a Lewis acid catalyst to cause intramolecular hydride transfer with formation of a pair of cyclic trans- and cis-disiloxanes. The respective anti- and syn-diols are obtained after fluoride ion catalyzed hydrolysis. The trans:cis ratio of the disiloxane intermediates varies with the Lewis acid employed: TiCl4 (30 : 1), MgBr2 •OEt2 (60 : 1), SnCl4 (120 : 1), and BF3 •OEt2 (320 : 1).397 – 399 A similar reduction with chlorodimethylsilane also gives good results (Eq. 217).400 OH O

Pr-i

i-Pr Si O

Si +

O

SiH(Pr-i)2 O

SnCl4, CH2Cl2

Pr-i

i-Pr

O

O

(i-Pr)2SiHCl

O

OH OH

aq. HF

OH OH +

MeCN

(67%), anti:syn = 120:1

(Eq. 216) O Ph

OSiMe2H Ph

OH OH

1. TBAF, THF, –78°, 3.5 h 2. aq. HCl

Ph

Ph

(76%)

(Eq. 217)

The diastereoselectivity of the reduction of α-substituted ketones has been the subject of much investigation. The reagent combination of trifluoroacetic acid and dimethylphenylsilane is an effective method for the synthesis of erythro isomers of 2-amino alcohols, 1,2-diols, and 3-hydroxyalkanoic acid derivatives.86,87,276,375 Quite often the selectivity for formation of the erythro isomer over the threo isomer of a given pair is >99 : 1. Examples where high erythro preference is found in the products are shown below (Eqs. 218–220).276 Similar but complementary results are obtained with R3 SiH/TBAF, where the threo isomer product

ORGANOSILICON HYDRIDE REDUCTIONS

79

predominates (Eqs. 221 and 222).86,87,320 The threo isomer also predominates with the PMHS/TBAF system (Eq. 223).401 O NHCO2Et

Ph O

CO2Me

Ph O

O2CPh

Ph

OH

PhMe2SiH, TFA

NHCO2Et

Ph

0°, 2.5 h

(Eq. 218)

OH

PhMe2SiH, TFA

(Eq. 219)

O2CPh

(Eq. 220)

OH

OH

PhMe2SiH, TFA

(87%)

CO2Me

Ph

0°, 3 h

0°, 6 h

(87%)

O2CPh

Ph

+

Ph

(72%) 93:7 O Ph

HMPA, rt, 12 h

OH

OH

PhMe2SiH, TBAF

NMe2

NMe2

Ph

+

NMe2

Ph

(Eq. 221)

(83%) 95%)

2. P(OEt)3 HO

O

OTr

O

(Eq. 286)

OTr

Reduction of α,β-Unsaturated Esters The reduction of the C=C bond of α,β-unsaturated esters has been carried out with various silane/catalyst combinations. The combination of Et3 SiH/ RhCl(PPh3 )3 gives the silyl ketene acetal along with the silylated hemiacetal, the result of the 1,2-reduction of the carbonyl group (Eq. 287).466 The use of other silanes in this transformation gives similar results. Acrylates give hydrosilylation of the C=C bond, leading to β-silyl esters and their silyl ketene acetals as the major products (Eq. 288).466,467 O

Et3SiH, ClRh(PPh3)3 OEt

C6H6, 80°, 2 h

OSiEt3 OEt (74%)

OSiEt3 +

OEt (6%)

(Eq. 287)

94

ORGANIC REACTIONS Et3SiH, ClRh(PPh3)3

O OEt

OSiEt3

O +

C6H6, 70°, 3 h

Et3Si

Et3Si

OEt (52%)

OEt

(Eq. 288)

(28%)

Triethoxysilane and RhH(PPh3 )4 produce the silyl ketene acetal in high yield.374 Methyl acrylate is reduced to methyl propionate with Cl3 SiH/CoCl2 448 or PMHS/Pd-nanocomposite catalyst,219 and to a mixture of methyl propionate, the methyl β-silylpropionate, and the methyl α-silylpropionate with R3 SiH/H2 PtCl6 or R3 SiH/RhCl(PPh3 )3 where R = Me, Et, or n-Pr.467 The reduction of ethyl acrylate shows similar behavior.451,466 The combination of Et3 SiH/Mo(CO)6 works well for the conjugate reduction of α,β-unsaturated esters.450 This method appears to be free of some of the side reactions mentioned above. The use of metallic nickel, triphenylphosphine, and phenylsilane reduces α,β-unsaturated esters to the saturated esters in moderate yields.438 Dimethylphenylsilane carries out the same transformation in the presence of CuCl.444,445 Triethylsilane and trifluoroacetic acid can reduce α,β-unsaturated esters in good yields468 as can Et3 SiH/TMSOTf.469 Excellent yields of the silane reduction of α,β-unsaturated esters are obtained by the reaction of PMHS and sodium tert-butoxide in the presence of catalyst 73 (Eq. 289).454 O Ph

O

PMHS, 73, NaOBu-t OEt

CN

Ph

OEt CN (93%) dr = 1.5:1

MeC6H5, t-BuOH, rt, 4 h Pr-i N

i-Pr

(Eq. 289)

N

Pr-i CuCl Pr-i 73

The Ph2 SiH2 /AlCl3 reduction of β-sulfonyl-α,β-unsaturated esters results in the formation of the β-sulfonyl ester. Good yields are obtained and AlCl3 is the best Lewis acid catalyst for this reaction (Eq. 290).373 Ts

CH2Cl2, 20°, 15 h

S CO2Me

Ts

Ph2SiH2, AlCl3

(86%)

S

(Eq. 290)

CO2Me

In the reductive aldol condensation of an α,β-unsaturated ester and an aldehyde shown in Eq. 291, the initial step is believed to be the addition of an in situ formed rhodium hydride to the α,β-unsaturated ester, followed by reaction of the resulting rhodium enolate with the aldehyde.470 The reaction has been carried out both inter-470 and intramolecularly471,472 as well as in an asymmetric fashion (Eq. 291).

ORGANOSILICON HYDRIDE REDUCTIONS O

OSiEt3

Et3SiH, RhH(PPh3)4 H

95

OSiEt3

CO2Pr-i +

MeC6H5, 50°, 16 h CO2Pr-i

CO2Pr-i

(20%)

(40%)

(Eq. 291) Similarly, methyl methacrylate reacts with ketones and TMSH/RuCl3 •3H2 O to give β-trimethylsiloxy-2,2-dimethyl methyl esters in good yields. A lactone example is shown in Eq. 292.473 Methyl acrylate, trans methyl (E)-cinnamate, and 3,4-dehydro-δ-lactone react in an analogous manner, albeit in lower yields.473 O O

+

TMSH, RhCl3•3 H2O, rt

O

TMSO

O

O

(Eq. 292)

(34%)

Allyl acrylates have been reacted with the combination of ClMe2 SiH/ [(cod)RhCl]2 /Me-DuPHOS (1,2-bis(2,5-dimethylphospholano)benzene) to bring about reduction of the α,β-unsaturated ester followed by a Claisen rearrangement to the γ ,δ-unsaturated carboxylic acid (Eq. 293).474 Other silanes did not perform as well in this sequence. O

O MeCl2SiH, [(cod)RhCl]2

O

O

MeDuPhos, C6H6, rt, 15 h

O

O

(Eq. 293)

HO2C (50%) dr = 23:1

In yet another example of an in situ reductive generation of an enolate, βamido esters are formed via the reaction of an α,β-unsaturated ester with a silane in the presence of an isocyanate (Eq. 294).475 The yields obtained using methyl acrylate and methyl crotonate as substrates are generally excellent.

CO2Me

Et2MeSiH, [Rh(cod){P(OPh) 3}2]OTf PhNCO, CH2Cl2, 45°, 13 h

Ph

H N

(Eq. 294)

CO2Me (88%) O

The organosilane reduction of pentafluorophenyl acrylate in the presence of an imine was shown to lead to β-lactams in good yields (Eq. 295).476 The conversion of an ethyl ynoate into an E-ethyl enoate in high yield is shown in Eq. 296.477 Et2MeSiH, [Ir(cod)Cl]2, P(OPh)3, CH2Cl2, 18 h

O OC6F5

N

PhN

O

Ph H

(Eq. 295) (80%) trans:cis >20:1

96

ORGANIC REACTIONS OH

OH CO2Et TBSO

(EtO)3SiH, CH2Cl2 Cp*Ru(NCMe)3PF6

NMe2

CO2Et NMe2

TBSO

(Eq. 296)

O (92%)

O

Reduction of α,β-Unsaturated Amides The conjugate hydrosilylation of α,β-unsaturated amides can be carried out in high yields with PhSiH3 /Mo(CO)6 (Eq. 297)450 or Ph2 SiH2 /ZnCl2 /Pd(PPh3 )4 .436 Primary, secondary, and tertiary amides are equally reactive.450 The reduction of a β-tributylstannyl-α,β-unsaturated tosylamide is also reported.469 O

PhSiH3, Mo(CO)6 NH2

O NH2

THF, reflux, 1.7 h

(Eq. 297)

(100%)

Reduction of α,β-Unsaturated Nitriles The reaction of α,β-unsaturated nitriles with organosilanes in the presence of Wilkinson’s catalyst gives the α-silyl nitriles in good yields (Eq. 298).466 The PhSiH3 /Mo(CO)6 combination reduces α,β-unsaturated nitriles to the nitriles in good yields, although the β,β-disubstituted 3-methylcrotonitrile does not react.450 Cinnamonitrile is reduced to the saturated nitrile in good yield with PMHS/Pdnanocomposite219 and in only modest yield with Ph2 SiH2 /ZnCl2 /Pd(PPh3 )4 .436 The ferrocenyl unsaturated nitrile shown in Eq. 299 is reduced with Et3 SiH/TFA in good yield.179 The PhSiH3 /Co(dpm) reductive aldolizations of an α,βunsaturated nitrile and an aldehyde also occur in good yields (Eq. 300).478

CN

PhMe2SiH, ClRh(PPh3)3

CN

60°, 4 h

SiPhMe2

(87%)

CN

CN Et3SiH, TFA, rt, 3 h

Fe

Fe

(83%)

CN CHO +

(Eq. 298)

(Eq. 299)

CN

CN

OH

PhSiH3, Co(dpm)2 ClCH2CH2Cl, 20°, 12 h

OH

+ CN

Ph (70%)

(5%)

(Eq. 300)

ORGANOSILICON HYDRIDE REDUCTIONS

97

Reduction of Acetals, Ketals, Hemiacetals, Hemiketals, and Orthoesters The ketals of both aryl and alkyl ketones can be reduced to the methylene derivatives in good yields (Eqs. 301 and 302).479

O Ph

1. Et3SiH, SnBr2–AcBr, CH2Cl2, rt, 24 h

O

MeO

OMe

1. Et3SiH, SnBr2–AcBr, CH2Cl2, rt, 24 h

(Eq. 301)

(Eq. 302)

(67%)

2. (n-Bu)3SnH, AIBN, C6H6, reflux, 0.5 h

Ph

(77%)

Ph

2. (n-Bu)3SnH, AIBN, C6H6, reflux, 0.5 h

Ph

Simple dimethylacetals and ketals are reduced with the Et3 SiH/acid combination where the acid catalyst can be TMSOTf,339,480 – 482 BF3 •OEt2 ,483 – 485 TFA,327,486 Nafion-H,335 tin-montmorillonite,353 FSO3 H/BSA,487 TiCl4 ,488 – 492 AlCl3 /HCl,146 and FSO3 H/BSU.487 Of these, Nafion-H, BF3 •OEt2 , BSA, and TMSOTf all give excellent isolated yields of the corresponding ether. The 1, 3-propanediol acetals of acetophenone and benzaldehyde are reduced to monoortho-benzyldiols with PhSiH3 /RhCl(PPh3 )3 (Eq. 303),493 Et3 SiH/TFA,494 Et3 SiH/BF3 •OEt2 ,495 or PMHS/AlCl3 (Eq. 304).496 Ph O

PhSiH3, RhCl(PPh3)3

O

THF, rt, 48 h

Ph

Ph

PMHS, AlCl3

O O

N3

Et2O, CH2Cl2, rt, 12 h

O

OH

(89%)

(Eq. 303)

N3 (69%)

(Eq. 304)

BnO HO 7

7

This reduction technique also applies to the benzaldehyde acetals of sugars with reduction of the benzaldehyde acetals taking place in preference to reduction of the anomeric acetal (Eq. 305).497 Ph

O O BnO

OBn O BnO OMe

Et3SiH, BF3•OEt2 CH2Cl2, rt, 4 h

HO BnO

O

(83%)

(Eq. 305)

BnO OMe

A highly useful and important regioselective reduction of substrate 84 leads to a mixture of 3-hydroxy ethers 85 and 86 in a 32 : 1 ratio (Eq. 306). Compound 85 is further converted to the anti-influenza drug oseltamivir phosphate, better known as Tamiflu.498

98

ORGANIC REACTIONS

Et

O

Et

O

Et

CO2Et Et3SiH, TiCl4 CH2Cl2, –34°, 2-6 h

Et

OMs 84

CO2Et

O

HO

+

HO

Et

OMs 85

CO2Et

Et

(56%) 32:1

O OMs 86

(Eq. 306) The triethylsilane reduction of the peroxy ethyl ether shown in Eq. 307 takes place at the C–O bond of the methyl ether without reduction of either the iodide or the peroxide functionalities (Eq. 307).499 In contrast, a bridged peroxy ether undergoes reduction of both C–O bonds of the peroxide linkage rather than at the ether bridge (Eq. 308).499 MeO

H

O O

Et3SiH, HOTf

O O I

I

(Eq. 307)

H

H O

(56%)

Et3SiH, HOTf

O

O

O

(51%)

(Eq. 308)

single unidentified diastereomer

The Et3 SiH/tetracyanoethylene combination reduces acetals and ketals to the corresponding ethers but the yields are mixed.500 The full reduction of benzaldehyde acetals to the toluene derivatives is realized by the initial reduction with Et3 SiH/SnBr2 –AcBr followed by Bu3 SnH/AIBN (azobis(isobutyronitrile)) or LiAlH4 .479 The overall yields are excellent. Diphenylmethylsilyl-protected hemiacetals are reduced upon treatment with Ph2 SiH2 /Mn(CO)3 Ac.295 Et3 SiH/TiCl4 reduces tert-butyldimethylsilyl ketals.306 The combination of TBSH/Sn(OTf)2 and a silyl ether converts ethylene glycol acetals and ketals into ethers (Eq. 309).501 Ph O

O

TBSH, n-C6H13OTMS Sn(OTf)2, MeCN, –20°, 3-6 h

Ph

OC6H11-n

(86%)

(Eq. 309)

α-Trimethylsilyloxythianes are reduced to the respective thianes with Et3 SiH/ TMSCl/InCl3 (Eq. 310).426,502 Trimethylsilane with TMSI or TMSOTf effects this conversion as well.392 OTMS Ph

SEt

Et3SiH, TMSCl, InCl3 CH2Cl2, rt, 5 h

Ph

SEt

(68%)

(Eq. 310)

A number of conditions are available for the reduction of the anomeric acetals to the reduced sugars. Among these are the combinations Et3 SiH/BF3 •OEt2 / TFA483 and Et3 SiH/TMSOTf,503,504 although some isomerization is found to

ORGANOSILICON HYDRIDE REDUCTIONS

99

occur with this latter system. The polysaccharide shown in Eq. 311 is converted into the the deoxysugar in good yield.483 MeO O O

MeO

MeO

MeO AcO MeO

1. Et3SiH, BF3•OEt2, TFA, 0° 2. Ac2O, rt, 24 h

O

O

(81%)

MeO

(Eq. 311)

6

Diiodosilane reduces acetals to alkyl iodides in a reductive iodination reaction (Eq. 312).358,505 Alkyl bromides are formed from the reductive bromination of benzaldehyde acetals with the combination Et3 SiH/SnBr2 .506 O

I2SiH2, CH2Cl2, rt, 4 h

O

I

CHO

CHO

(Eq. 312)

(94%)

There is a report of a reductive amination of an acetal. Thus, (Et2 N)Me2 SiH/ TiCl4 reacts with the dimethylacetal of benzaldehyde to form benzyldiethylamine in good yield (Eq. 313).359 OMe

Et2NSiHMe2, TiCl4

OMe

NEt2

CH2Cl2, 0° to rt, 36 h

(79%)

(Eq. 313)

Hemiacetals and hemiketals also undergo reduction to ethers with organosilanes under acid catalysis. These reductions generally occur in good yield. They are carried out with Et3 SiH/BF3 •OEt2 ,497,507 – 512 Et3 SiH/TFA,162,513 – 516 PhMe2 SiH/TMSOTf,517 and Et3 SiH/TMSOTf,518,519 which prove especially useful for sugar systems. The combination of Ph3 SiH/TiCl4 reduces hemiketals in the presence of a dithioketal (Eq. 314).520 S S Ph

O OH

S

Ph3SiH, TiCl4

S

CH2Cl2, –78°, 5 min

Ph

(72%)

(Eq. 314)

O

The PhSiH3 /RhCl(PPh3 )3 combination reduces trimethyl orthobenzoate to the dimethyl acetal of benzaldehyde with small amounts of methyl benzyl ether product (Eq. 315).493 Ph

OMe OMe OMe

PhSiH3, RhCl(PPh3)3 PPh3, 60°, 48 h

OMe Ph OMe (80%)

+

OMe

(Eq. 315)

Ph (7%)

Reduction of Aminals and Hemiaminals As demonstrated with acetals and ketals, aminals are also readily reduced with silanes under acid catalysis. The Et3 SiH/BF3 •OEt2 combination reduces

100

ORGANIC REACTIONS

aminals to the amines in excellent yields (Eq. 316).521 – 523 A similar reduction with Et3 SiH/TFA occurs in equally high yield (Eq. 317).524 Hemiaminals are reduced with Et3 SiH/TFA (Eq. 318).525 TBSO

TBSO Et3SiH, BF3•OEt2 N Ac

OMe

N Ac

CO2Me

CO2Me Et3SiH, TFA

N

N H Me HO

rt, 4 h

O

N

N H Me H

CHCl3, rt, 20 h

N

(79%)

(Eq. 317)

O

Et3SiH, TFA

MeO2C

(Eq. 316)

(97%)

CH2Cl2, –40°, 1-2 h

(63%)

MeO2C

(Eq. 318)

N Me

OH

Amidoaminals and amidohemiaminals are reduced to the amides with organosilanes and an acid catalyst. Best among the reported reagent combinations are Et3 SiH/TiCl4 ,524 and Et3 SiH/BF3 •OEt2 .521 Et3 SiH/TFA526 (Eq. 319) and Et3 SiH/ BF3 •OEt2 527 are effective in reducing amidoaminals in high yields. O

O N H

OH

Et3SiH, TFA

NHMe

CHCl3, rt, 1-4 h

MeO

(91%)

(Eq. 319)

MeO

N -Trimethylsilyloxymethylimines can be reduced to the corresponding N alkylimines with Et3 SiH/BF3 •OEt2 (Eq. 320).522 OTMS CF3

Ph

Et3SiH, BF3•OEt2

Ph

N

CH2Cl2, 50°, 24 h

Ph

CF3

(61%)

N

(Eq. 320)

Ph

O-Aminomethyl lactones are reduced to amino acids with the Et3 SiH/TFA combination (Eq. 321).528 Fmoc N

O O

Et3SiH, TFA CHCl3, rt, 22 h

Fmoc N O Me OH

(98%)

(Eq. 321)

Reduction of Enamines Enamines are reduced to amines in good yields with Et3 SiH/TFA.529 – 533 This reagent combination causes a variety of indoles to undergo stereoselective cis

ORGANOSILICON HYDRIDE REDUCTIONS

101

reduction of the indole ring while other potentially reducible functional groups in the molecule are unaffected (Eq. 322).534 The organosilane reduction of enamides proceeds in excellent yields with the Et3 SiH/TFA reagent system (Eq. 323).524,535 H N

O

H N

O NPh

NPh Et3SiH, TFA

N

N

50°, 64 h MeO

(58%)

(Eq. 322)

MeO N H

MeO

H N

Br

OEt O

MeO

N H

MeO

H N

Br

Et3SiH, TFA

OEt (99%)

–10°, 0.5 h

(Eq. 323)

O

MeO

The enamide double bond is reduced in preference over that of the enone moiety in each of the two examples shown below (Eqs. 324 and 325).536,537 Other enamides are reduced under similar conditions.235,537,538 O

O Et3SiH, TFA, CH2Cl2

Cl

N CO2Me

N

O

(56%)

Cl

(Eq. 324)

N CO2Me

N O

O

0°, 6 h; then rt, 6 h

Et3SiH, TFA, CHCl3

O O

20°, 24 h

(75%)

(Eq. 325)

O

Reduction of Imines The reduction of imines with organosilanes is reported to take place with the reagent combinations PMHS/ZnCl2 ,539 Et3 SiH/TFA,540,541 Cl3 SiH,318,542 PMHS/ butyltin trioctanoate,543 PhSiH3 ,544 Et3 SiH/HCO2 H,208 PhMe2 SiH/TFA,276 Cl3 SiH/BF3 •OEt2 ,545 Et3 SiH (and related silanes)/RhCl(PPh3 )3 ,546 and Cl2 SiH2 .545 Imines are reduced in high yields with various silanes in the presence of Wilkinson’s catalyst or PdCl2 .120 Triethylsilane and diethylsilane are the most effective reducing agents. Diimine 87 undergoes reduction of the imine functions with diethylsilane without reduction of the amide functionality, even though the amide carbonyl is in the more reactive α-heteroaryl position (Eq. 326).547

102

ORGANIC REACTIONS O Cl

O

N

Cl

N

Et2SiH2, RhCl(PPh3)3

N N Ph

87

CH2Cl2, rt, 16 h N Ph

O Cl

O

N

Cl

N N

HN Ph

(81%)

NH Ph

(Eq. 326)

Reduction of Oximes Oximes can be reductively converted into the Boc-protected primary amines in good yields with the combination of PMHS/(Boc)2 O/Pd/C (Eq. 327).548 OBenzyloxyimines549 are reported to be reduced in good to excellent yields by this method. O HO

O

O

PMHS, (t-BuCO)2O 10% Pd/C, 40-50°, 6 h

N

Boc

OMe

O

O

(85%)

H N

(Eq. 327)

OMe

O

O-Benzoyloximes are nicely reduced to O-benzoylhydroxylamines with Et3 SiH/TFA (Eq. 328).550,551 O-Acetyloximes are reduced with Et3 SiH/TMSOTf in moderate to high yields.552 The diethylphosphatoimine 88 is reduced to the hydroxylamine derivative.553 BzO

BzO

N

NH

Et3SiH, TFA, 40°, 12 h

O P OEt EtO 88

O P OEt EtO

(79%)

(Eq. 328)

Reduction of Nitroalkanes The combination PMHS/Pd/C reduces nitrobenzenes to anilines in high yields (Eq. 329),316 as does Et3 SiH/RhCl(PPh3 )3 (Eq. 330).554 This latter combination can also reduce both nitro and enone functionalities.554 NO2

PMHS, Pd/C

NH2

EtOH, 80° O O

O2N

O O

Et3SiH, RhCl(PPh3)3 O

(Eq. 329)

(89%)

MeC6H5, reflux, 4 h

O H2N

(Eq. 330)

ORGANOSILICON HYDRIDE REDUCTIONS

103

Tertiary nitro alkanes or activated nitro groups are reduced to the alkane with loss of the nitro group by a combination of PhSiH3 and catalytic amounts of (n-Bu)3 SnH and 1,1′ -azobis(cyclohexanecarbonitrile) (ACHN), even in the presence of other potentially reducible functional groups.555 The examples shown in Eqs. 331 and 332 illustrate this behavior.555 PhSiH3, (n-Bu)3SnH, ACHN

NO2 CN O

NO2

CN O

PhSiH3, (n-Bu)3SnH, ACHN OEt

(Eq. 331)

(67%)

MeC6H5, 110°, 5 h

O OEt

MeC6H5, 110°, 5 h

(76%)

(Eq. 332)

O

Reduction of Miscellaneous Nitrogen-Containing Compounds The combination of PhSiH3 with a catalytic amount of bis(tri-n-butyltin) oxide reduces azides to primary amines in excellent yields (Eq. 333).556 The reducing agent is (n-Bu)3 SnH formed in situ by the silane. Azides are converted into Boc-protected primary amines with the PMHS/Pd/C reagent (Eq. 334).557,558 N3

NH2

PhSiH3, [(n-Bu)3Sn]2O, n-PrOH, C6H6

(99%)

AIBN, reflux, 90-120 min OH N3

(Eq. 333)

OH

PMHS, 10% Pd/C

(90%)

(Boc)2O, EtOH, rt, 5 h

(Eq. 334)

NHBoc

The combination of Et3 SiH/Co2 (CO)8 reduces nitriles to the N ,N -bis(trimethylsilyl)amine (Eq. 335).559 These derivatives can be readily hydrolyzed to the primary amines. CN

TMS N TMS

TMSH, Co2(CO)8 CO, –20°

(64%)

(Eq. 335)

The organosilane reduction of hydrazones to hydrazines is readily accomplished in good yields with Et3 SiH/TFA (Eq. 336).560,561 N -Tosylimines294 are reduced to their N -Boc tosylamino counterparts,294 and are also reduced with (MeO)3 SiH/LiOMe in good yields.294 Benzyl-protected hydroxylamines are reduced with PhMe2 SiH/TFA.551 O Ph

N H

N

O

Et3SiH, TFA 0°, 4 h

Ph

N H

H N

(86%)

(Eq. 336)

104

ORGANIC REACTIONS

In an analogous fashion to the reductive deprotection of allyl alcohols and allyl esters, the deallylation of allylamines is also possible (Eq. 337).270 H N

NH2

PMHS, Pd(PPh3)4

(Eq. 337)

+

(90%)

THF, rt, 3-5 h

The tetrachloroferrate or tetrafluoroborate salts of alkylated alkyl- or arylnitriles (nitrilium ions) are reduced to imines with triethylsilane. Subsequent hydrolysis of the intermediate imines leads to aldehydes in good yields, thus providing an excellent overall route to aldehydes from nitriles (Eq. 338).28,562 +

NEt BF4−

CHO

1. Et3SiH, CH2Cl2, rt, 0.5-6 h

(90%)

2. H2O

(Eq. 338)

Aryldiazonium salts are reduced to the benzene derivatives in good yields (Eq. 339).563 N2

+

BF4−

Et3SiH, MeCN

(Eq. 339)

(72%)

rt, 16 h

O2 N

O 2N

Reduction of Miscellaneous Sulfur-Containing Compounds Et3 SiH/TFA reduces disulfides to the corresponding mercaptans in modest yields (Eq. 340).564 Naphthyl thio ethers are reduced in rather poor yields to tetrahydronaphthalene with the combination Et3 SiH/BF3 •OH2 (Eq. 341).263 There is one report of the reduction of a diaryl sulfide to the hydrocarbon but the yield is low (Eq. 342).217 S

SH

Et3SiH, TFA S

SMe

Et3SiH, BF3•OH2

(Eq. 341)

(20%)

CH2Cl2, 0°, 24 h

SH

Et3SiH, BF3•OH2

S

(Eq. 340)

(45%)

60°, 25 h

(Eq. 342)

+

CH2Cl2, 0°, 22 h (25%)

(25%)

The reduction of 2,2′ -dithiobis(1,3-dithiolanium) bis(tetrafluoroborate) to the thiocarbonate compound by triethylsilane takes place quantitatively (Eq. 343).565 S + S

S

(BF4)2 2

Et3SiH, MeCN, 90% ee.579 The complex 96 is highly successful in the diphenylsilane reduction of aryl alkyl ketones with high yields and >90% ee values.580,581 Dialkyl ketones are reduced with more mixed results, with 2-octanone showing 63% ee and ethyl 4-oxopentanoate 95% ee. The same system can be used to reduce 2-phenylcyclohexanone with no cis/trans selectivity, but excellent enantioselectivity (Eq. 347).390 + Ph2P (NBD)Rh

O

O —

OTf

S t-Bu

Ph

O

N Rh Cl3

Ph2P 95

Ph2SiH2, RhCl3, 96

O

N N

PPh2

94 O

O N

N

96 OH

OH Ph

AgBF4, THF, 0°, 1 d

+

Ph

(Eq. 347) (46%) 1S,2R 99% ee

(46%) 1S,2S 96% ee

A chiral oxazolinoferrocene ligand with iridium(I) is used for the diphenylsilane reduction of aryl alkyl ketones in nearly quantitative yields and >83% ee

ORGANOSILICON HYDRIDE REDUCTIONS

107

values.582 The dialkyl ketone, 2-octanone, is reduced with a poor 19% ee under these conditions. A catalyst prepared by the alkylation of [1,2-bis(tetrahydroindenyl)ethane]titanium(IV) 1,1′ -binaphth-2,2′ -diolate with methyllithium or n-butyllithium can be employed in the methyldiethoxysilane reduction of acetophenone with 99% ee.583,584 Other ketones do not show nearly the same ee values. Methylsilane is the actual proposed reducing agent in this system. The phosphinophenyloxazoline 97 is an effective ligand for the asymmetric rhodium(I) diphenylsilane reduction of aryl alkyl ketones, even with propiophenone, which has proven difficult with other systems, showing 91% ee and 91% yield (Eq. 348).585 A more general system involving mesitylphenylsilane and catalyst 98 permits the reduction of aryl alkyl ketones in very high chemical yields and >96% ee.586 The reduction of dialkyl ketones ranges from 72% ee for 2-octanone to 96% ee for the more stereo-differentiated adamantly methyl ketone.

Ph2P

O H Ph2P

N

N H 97

O

Fe

98

OH

Ph2SiH2, [Rh(cod)Cl]2

(Eq. 348)

97, MeC6H5, rt

Alkylated (R,R)-tetrahydroindenyltitanium difluoride and phenylsilane serve to asymmetrically reduce a variety of ketones, especially aryl alkyl ketones, in excellent chemical yields and >96% ee.587 The use of the easier to handle and less expensive PMHS is also highly effective in these transformations. In a related study using the (R,R)-tetrahydroindenyltitanium 1,1′ -binaphth-2,2′ -diolate precursor to the active catalyst, similarly impressive results are obtained.588 The in situ generation of CuH from organosilanes in the presence of either a BIPHEP (99) or a SEGPHOS (100) type ligand represents a general method for the asymmetric hydrosilylation of aryl alkyl ketones at low temperatures.

t-Bu OMe MeO MeO

P P

2

MeO MeO

Bu-t Bu-t

P P

2

OMe t-Bu

2

99

100

2

108

ORGANIC REACTIONS

These excellent catalyst systems show high reactivity, substrate-to-ligand ratios of >100,000 : 1, high chemical yields, the ability to employ the inexpensive PMHS as the hydride donor, and typical ee values in the >90% range.589,590 The most promising ligand found to date is DTBM-SEGPHOS (5,5′ -bis[di(3,5-di-tertbutyl-4-methoxyphenyl)phosphino]-4,4′ -bi-1,3-benzodioxole) 100 (Eq. 349). The BIPHEP ligand with copper(I) is also capable of asymmetrically reducing aryl alkyl ketones under similar conditions and with comparable results.589,591

OH

O Ph2MeSiH, CuCl, t-BuONa

(90%) 95% ee

100, MeC6H5, –78°

(Eq. 349)

Asymmetric Reduction of α,β-Unsaturated Ketones The enantioselective hydrosilylation of 2-pentylcyclopentenone is effected with PMHS and an active catalyst derived from (R,R)-ethylenebis(tetrahydroindenyl)titanium difluoride and phenylsilane (EBTHI)Ti (Eq. 350).587 The use of diphenylsilane, a rhodium catalyst, and (R,R)-(S,S)-BuTRAP as the chiral ligand gives similar results.576 Other related approaches give greatly inferior enantioselectivies.592 – 594 1. PhSiH3, (EBTHI)Ti, MeOH, 60°, pyrrolidine, MeOH, THF

O

OH

(Eq. 350)

2. PMHS, ketone, MeOH, 15°, 4 h (90%) 84% ee

The PMHS, copper-catalyzed reduction of β-substituted α,β-unsaturated ketones to saturated ketones is accomplished in good yield with ee values in the 90 to 95% range when (S)-p-Tol-BINAP is employed as the chiral ligand.595,596 Higher ee values are achievable with the use of a copper catalyst and (R)-100 as the chiral ligand (Eq. 351).597

O

O PMHS, CuH(PPh3), (R)-100 MeC6H5, –35°, 16 h Ph

(95%) 99.5% ee

(Eq. 351)

Ph

The sequence of chiral 1,4-reduction of a β-substituted cyclopentenone followed by electrophilic trapping of the intermediate enolate provides an efficient route to chiral 2,3-disubstituted cyclopentanones that generates two chiral centers in the process (Eq. 352).459

ORGANOSILICON HYDRIDE REDUCTIONS O

109

OSiPh2H

Ph2SiH2, CuCl, NaOBu-t (S)-p-TolBINAP, MeC6H5, 0°, 2-3 h

Ph

Ph 95% ee

(Eq. 352)

O BnBr, TBAT

Bn

CH2Cl2, MeC6H5, rt

(69%) dr = 94:6 Ph

Asymmetric Reduction of α,β-Unsaturated Esters and Lactones The chiral hydrosilylation of β-substituted α,β-unsaturated esters to their saturated counterparts is the subject of reports by two groups. The combination of triphenylphosphinecopper hydride and (R)-DTBM-SEGPHOS is reported to give excellent yields of the β-substituted esters (Eq. 353).598 Comparable yields, but with lower ee values, are reported for this transformation.599,600 O

O OEt

PMHS, CuH(PPh)3, (R)-100 H

t-BuOH, MeC6H5, 0°

OEt

(92%) 98% ee

(Eq. 353)

Ph

Ph

The copper-catalyzed chiral reduction of β-substituted α,β-unsaturated lactones with PMHS and (S)-p-Tol-BINAP in the presence of a hindered alcohol can be carried out in moderate to good yields with moderate ee values.599 The reaction is useful for both butenolides and pentenolides. Inferior results are realized with diphenylsilane as the reducing agent. Excellent results employing PMHS and the DTBM-SEGPHOS ligand are possible (Eq. 354).598 O

O PMHS, CuH(PPh3), 100

O Ph

O

t-BuOH, MeC6H5, 0°

(96%) 99% ee

(Eq. 354)

Ph

The asymmetric reductive rhodium- and iridium-catalyzed aldol reaction of α,β-unsaturated esters with aldehydes470,601,602 is proposed to involve a rhodium(I) or iridium(I) hydride as the active catalyst, which adds to the α,βunsaturated ester, followed by reaction of the intermediate rhodium or iridium enolate with an aldehyde.470 These transformations provide an excellent entry into α-alkyl-β-hydroxy esters in both high yields and high enantiomeric ratios. The reactions were first carried out with moderate success using the BINAP (2,2′ bis(diphenylphosphino)-1,1′ -binaphthyl) ligand to introduce the asymmetry.470,603 The use of various pybox ligands improves the yields of these transformations.604 The best results are obtained from the ligand indane-pybox (101) and an iridium catalyst,604 which was applied to an enantioselective synthesis of the macrocycle borrelidin (Eq. 355).601,602

110

ORGANIC REACTIONS O

Et2MeSiH, [(cod)IrCl]2

O + OMe

BnO

101, rt, 24 h

H

OH O BnO

OMe

(59%) syn:anti = 9.5:1 er syn = 98:2 O

N N

(Eq. 355)

O N

101

Asymmetric Reduction of α,β-Unsaturated Lactams The chiral reduction of β-substituted α,β-unsaturated lactams with PMHS in the presence of (S)-p-Tol-BINAP as the chiral ligand with a copper catalyst results in β-substituted lactams in excellent yield and with greater than 90% ee.599 This method has been applied in an efficient enantioselective synthesis of the antidepressant (−)-paroxetine (Eq. 356). O

O

PMPN

PMHS, CuCl2, NaOBu-t, t-AmOH

PMPN

(S)-p-Tol-BINAP, C6H5F, air, rt, 3 h F

(Eq. 356) (90%) 90% ee

F

(–)-paroxetine

Asymmetric Reduction of Imines Various chiral ligands with metal catalysts can be employed in the organosilane reduction of imines to amines. Many of these provide modest success. These include (oxazolino)diphenylphosphinoferrocene ligands with ruthenium,605 (−)DIOP/Rh(I),606,607 3,3′ -BINOL (1,1′ -bi-2-naphthol) and LiHMDS,608 and (S)phenyl N -formylprolinamide with trichlorosilane.609 Some excellent findings in the asymmetric organosilane reduction of both aryl alkyl and dialkyl imines have resulted in the development of practical, scaleable methodologies for this key transformation. The reduction of imines with the ethylenebis(η5 -tetrahydroindenyl)titanium (EBTHI)–TiF2 -derived catalyst 102 with either phenylsilane or PMHS as the reducing agent gives high chemical yields of the corresponding amine and ee values well in excess of 90% with most at 99% (Eq. 357).610 – 613 Straight-chain dialkyl imines are not as successful; for example, 2-(N -benzylimino)octane gives a 96% yield of (S)-(2benzylamino)octane with 69% ee.612 The CuH approach employed so successfully for the asymmetric organosilane reduction of ketones can be applied with equal success to the reduction of phosphoryl imines, thus providing a route to the asymmetric reduction of imines to primary amines via the hydrolysis of the resulting aminophosphorane.598,614

ORGANOSILICON HYDRIDE REDUCTIONS N

Cl

HN

PhSiH3, 102 OMe

111

OMe

i-BuNH2, 65°, 2.5 h Cl

E:Z = 15:1

Ti F

(92%) 99% ee

(Eq. 357)

F

102

COMPARISON WITH OTHER METHODS

Many different methods are known and used for the reduction of organic functional groups. These have been reviewed many times over the years and are too numerous to repeat here. The sequence of hydrosilylation of a multiple bond followed by removal of the silyl group is tantamount to the addition of hydrogen. Coupled with the keen current interest in asymmetric reductions, the use of hydrogen in asymmetric reductions and related reactions is highlighted here. The numerous asymmetric hydrogenations and asymmetric reductions with metal hydrides, including lithium aluminum hydride, sodium borohydride, and borane, coordinated or reacted with chiral diols, amino alcohols, diamines, and variations of these have been extensively reviewed.615 – 631 In view of the very large number of methods for the reduction of organic functional groups and the high interest in asymmetric reductions, the choice of competitive examples is limited to those that are representative of asymmetric hydrogenations. Asymmetric Hydrogenation of Olefins EBTHI–Ti, when treated with n-BuLi, catalyzes the hydrogenation of trisubstituted olefins in good yields and excellent enantioselectivity though undetermined configuration (ee = 83% to >99%) (Eq. 358)632 A zirconium version of this approach is also successful in the asymmetric hydrogenation of terminal olefins, although the enantioselectivities are not high.633 On the other hand, this system gives excellent ee values when applied to the hydrogenation of disubstituted cyclic olefins (Eq. 359)634 Ph

EBTHI–Ti, n-BuLi H2 (2000 psi)

Ph

Ph

Ph

(91%) 99% ee

(Eq. 358)

EBTHI–Zr, H2 (1000 psi) Ph

PhMe2NH(C6F5)4B

Ph

(Eq. 359)

(89%) 99% ee cis:trans = 98:2

Chiral phosphinodihydrooxazole iridium ligands are used to hydrogenate trisubstituted olefins in moderate yields and high enantioselectivity albeit of

112

ORGANIC REACTIONS

undetermined configuration.635 In a similar fashion and with equally impressive results, phosphine-oxazoline complexes of iridium 104, derived from [Ir(cod)Cl]2 and 103, are able to catalyze the hydrogenation of stilbenes (Eq. 360) and βmethyl cinnamic esters with both excellent conversion and enantioselectivity of undetermined configuration.636 The complex 105 also gives excellent results (Eq. 361).637

O R1

2P

N

R2 103 R1, R2 = alkyl, aryl + +

H O R12P

N

O

BARF–

Ir

R

BARF–

105 R = i-Pr, t-Bu, i-Bu, Ph, Bn

104 R1 = c-C6H11, Ph R2 = t-Bu, adamantyl, 3,5-(t-Bu)2C6H3, CHPh2 Ph

N

P t-Bu

R2

Ir

104 H2 (10-100 bar), rt-50°, CH2Cl2

Ph

Ph

Ph

(Eq. 360)

31% to >99% conversion 83-98% ee O Ph

105, H2 (50-100 bar) OMe

CH2Cl2

O Ph OMe >99% conversion 98-99% ee

(Eq. 361)

The asymmetric hydrogenation of trisubstituted olefins with iridium complexes of chiral phosphinite-oxazoline ligands of the general structure 106 also provides excellent results with ee values in the 85–99% range.638 The asymmetric hydrogenation of imines with these systems gives only moderate results. A similar fused phosphinite-oxazoline iridium catalyst, 107, gives good results with 1,1disubstituted and trisubstituted olefins with ee values of >97%, although ethyl β-methylcinnamate gives poor results.639 Asymmetric Hydrogenation of Ketones A number of asymmetric hydrogenations of prochiral ketones to highly enantiomerically enriched alcohols are available. A select few are highlighted here.

ORGANOSILICON HYDRIDE REDUCTIONS

113

R R N Ar1

O P(Ar2)2

Ir

O

106 R Bn Bn Me Bn Bn

1

+

Ar2 P Ir(cod) N Ph O

BARF–

107

Ar Ph Ph Ph 3,5-Me2C6H3 3,5-(t-Bu)2C6H3

Ar2

Ar = Ph, 2-MeC6H4

Ph 2-MeC6H4 Ph Ph Ph

The PennPhos ligands, for example 108, complexed with rhodium, provide an excellent system for the hydrogenation of aryl alkyl ketones with ee values in the range of 94–96% (Eq. 362). Phenyl isopropyl ketone shows only a 72% ee under similar conditions. Dialkyl ketones exhibit ee values in the range of 73–94% with this system (Eq. 363).640

P

P 108

O

[Rh(cod)Cl]2, 108, H2

OH

(Eq. 362)

2,6-lutidine, MeOH, 24 h, 20° (93%) 95% ee O

[Rh(cod)Cl]2, 108, H2

OH

(Eq. 363)

2,6-lutidine, MeOH, 24 h, rt (96%) 75% ee

Enantioselectivities in the range of 97.7–99.9%, with the majority in the range of 98.4–99.1%, are obtained in the asymmetric hydrogenation of aryl alkyl ketones with ruthenium catalyst 109.641 The same systems can hydrogenate β-keto esters (95.2–98.6% ee) and α,β-unsaturated acids (96.2% in a single example).642 Asymmetric transfer hydrogenation can be employed in the asymmetric hydrogenation of prochiral ketones with a ruthenium complex of bis(oxazolinylmethyl) amine ligand 110. Enantioselectivities are greater than 95%.643 The BINAP system of general structure 111 can be used in asymmetric hydrogenations; the compound in which Ar = 3,5-Me2 C6 H3 , R1 = R2 = 4-MeOC6 H4 ,

114

ORGANIC REACTIONS OMe N

Ar2 Cl H2 N P Ru N P Ar2 Cl H2

MeO MeO N

Ph Ph

OMe 109 Ar = Ph, 4-MeC6H5, 3,5-Me2C6H3

H N O

N N

O

Ph Ph 110

Ar2 Cl H2 N P Ru N P Ar2 Cl H2

R1 R3 R2

111 Ar 3,5-Me2C6H3 3,5-Me2C6H3 3,5-Me2C6H3

R2 R1 4-MeOC6H4 i-Pr —(CH2)4 — Ph Ph

PPh2

Fe

PR2

112 R3 4-MeOC6H H H

R c-C6H11 t-Bu 3,5-Me2-4-MeOC6H2 Ph 3,5-(CF3)2C6H3

and R3 = i-Pr effects the asymmetric hydrogenation of cyclopropyl methyl ketone (95% ee), cyclopropyl phenyl ketone (96% ee), and other aryl alkyl ketones (94 to 100% ee), and is also useful for the 1,2-reduction of enones (>90% ee).644 2,4-Pentanedione is hydrogenated to the 2-(R)-4-(R)-2,4-pentanediol in 97% ee with ligand 112 and [RuI2 (p-cymene)]2 . This system gives a wider range of enantioselectivity with prochiral ketones (22–97% ee) and α,β-unsaturated acids and esters (8–95% ee).645 o-BINAPO ligands of the type 113 complexed with ruthenium give good enantioselectivity in the hydrogenation of β-keto esters with the more hindered ortho-substituted aryl substituents giving the best results.646 The selectivities range from 87–99% ee. These same systems hydrogenate the double bond of β-amido acrylates in >90% ee. The TunaPhos ligands of general structure 114, when complexed with [RuPhCl2 ]2 , bring about the asymmetric hydrogenation of β-keto esters with

ORGANOSILICON HYDRIDE REDUCTIONS R

R H Me Ph 3,5-Me2C6H3 Ph

OPAr2 OPAr2 R

115

Ar Ph Ph Ph Ph 3,5-Me2C6H3

113

O (CH2)n O

PPh2 PPh2

114 n = 1-6

high ee values. The results compare very favorably with those obtained with (R)-BINAP and (R)-BIPHEP. The best results are found where n = 4, which gives a dihedral angle of the phosphines of 88 degrees.647 (R)-BINAP-RuBr2 can be successfully applied to the enantioselective hydrogenation of β-keto esters in the synthesis of (+)-(2R,3R)-corynomycolic acid 115. (S)-MeO-BIPHEP-RuBr2 was used in a similar manner in the synthesis of (R)-fluoxetine (116, Prozac) and (S)-duloxetine (117).648 CF3 OH O n-C15H31

OH C14H29-n

O

O NHMe•HCl

115

116

O

NHMe 117

The highly enantioselective reductive amination of α-keto acids as a route to amino acids is possible with ligand 118 [(3R,4R)-1-(N-benzyl)-3,4bis(diphenylphosphanyl)pyrrolidine, DEGUPHOS] and [Rh(cod)2 ]BF4 .649 (R,R)NORPHOS (2-exo-3-endo-bis(diphenylphosphino)bicyclo[2.2.1]heptene) and (2S,3S)-CHIRAPHOS (bis(diphenylphosphino)butane) are also good ligands for this transformation. Arylpyruvic acids give the best results (>95% ee). PPh2 BnN PPh2 118

The industrially important cis-(+)-methyl jasmonate 119 is conveniently prepared by the hydrogenation of enone 120 with Me-DuPHOS and [Ru(1,2 : 5,6-ηcod)(η3 -methallyl)2 .650

116

ORGANIC REACTIONS CO2Me

O

CO2Me

O 119

120

(S)-C3 -TunePhos (1,13-bis(diphenylphosphino)-7,8-dihydro-6H -dibenzo[f,h] [1,5]dioxonin) ruthenium catalyzes the hydrogenation of α-phthalimido ketones with enantioselectivities of >94%,651 leading to a highly enantioselective route to β-aminoethanols. Asymmetric Hydrogenation of Enol Acetates The diphosphine ligand 108 is useful in the asymmetric hydrogenation of enol acetates to chiral acetates, with 80.9% to >99% ee values being realized.652 The ruthenium TunaPhos complexes from ligand 114 catalyze the asymmetric hydrogenation of enol acetates with high enantiomeric excesses (Eq. 364).653 High yields and high ee values are obtained via hydrogenation of enol acetates with an achiral ruthenium catalyst and a lipase.654 This same system is used to convert prochiral ketones into chiral acetates with high enantiomeric excess. OAc OAc

Ru-(S)-C2-TunaPhos

(>99%) 95.9% ee

EtOH, H2 (3 atm), rt, 12 h

(Eq. 364)

Asymmetric Hydrogenation of α,β-Unsaturated Acids A study of various diphosphine ligands with rhodium catalyst systems for the hydrogenation of 2-methylenesuccinamic acid favors the DuPHOS (substituted 1,2-bis(phospholano)benzene) Rh(I) and Et-ferroTANE (1,1′ -bis-2,4diethylphosphotano)ferrocene) Rh(I) systems, with the former being slightly better than the latter (Eq. 365).655 The conversions are high for both systems. BINAP-ruthenium complexes are successful in the asymmetric hydrogenation of α,β-unsaturated acids, with catalyst 121 showing the best results of those complexes studied.656 The chiral diaminoferrocenediphosphine ligand 122 catalyzes the reduction of trisubstituted acrylic acids with ee values of >92% (Eq. 366).657 O HO2C

O

[(R,R)-Me-DuPHOS Rh(cod)]BF4 NH2

H2, MeOH, rt

HO2C

NH2

(Eq. 365)

(98%) 94% ee

Itaconic acids are reduced in very high enantiomeric excesses (>97%) with Rh-TangPhos catalysts.658 Itaconic acid is reduced in 99.5% ee with the sugar-derived ferrocenyl phosphine 123.659

ORGANOSILICON HYDRIDE REDUCTIONS CO2H

CO2H

122 (NR2 = piperidyl)

Ph

Ph

H2, THF, MeOH

Ph2 P O O Ru P O O Ph2

117

Ph2P

(100%) 98.4% ee

N Me Fe

121

NR2

(Eq. 366)

PPh2 122 O

P O

O

Fe P

O 123

Asymmetric Hydrogenation of Acetamidoacrylates The understandably strong interest in the synthesis of highly enantiomerically enriched α- and β-amino acids has made the asymmetric hydrogenation of α- and β-acetamidoacrylates an active area of investigation. The catalyst Rh-TangPhos catalyze the reduction of β-aryl-α-acetamidoacrylates with high enantioselectivity (>99% and >97%, respectively).660 Chiral norbornadienyl diphosphoryl rhodium(I) complexes of the type 124 catalyze the asymmetric hydrogenation of α-acetamidoacrylates with high ee values (Eq. 367).661 Rhodium(I) trap complexes catalyze the hydrogenation of the α-acetamidoacrylates with ee values in the 80-88% range.662 Ph

CO2H

H2, 124, MeOH

Ph

NHCOMe

CO2H NHCOMe

(—) 98.4% ee

(Eq. 367) t-Bu

Rh +

BF4– Bu-t

124

The rhodium(I) complexes with hydroxyphospholane ligand 125663 or 126660 catalyze the asymmetric hydrogenation of α-acetamidoacrylates with ee values in excess of 98%. System 125 is also very effective in the asymmetric hydrogenation of β-acetamidoacrylates (up to 99.6% ee).664 The planar-chiral heterocyclic ligand 127 complexed with rhodium(I) catalyzes the hydrogenation of α-acetamidoacrylates in excellent yields and ee values from 79–96% under mild conditions.665 Other systems that prove successful in the highly enantioselective hydrogenation of α-acetamidoacrylates include the spirophosphinites 128 (94.2–97.2% ee)666 and the Josiphos ligands 129 with rhodium(I) (84–96% ee). Excellent

118

ORGANIC REACTIONS

Ph2P P

P

HO

P

P P

OH

Fe

t-Bu Bu-t OH

HO 125

126

127

results are also obtained with dimethyl itaconate and styrenes.667 The bis (phospholanes) of type 130, again with rhodium(I), catalyze the hydrogenation of α-acetamidoacrylates in 92.6–99.1% ee.668 The ligands 131,659 132,669 133,670 and 134670 all show good results in the asymmetric hydrogenation of αacetamidoacrylates, with 131 being especially effective, often rendering ee values of 0>99.9%.

Ph2PO

Cy2P

OPPh2

PPh2

RO

OR

P

P

Fe 128

P

RO

OR 130 R = Bn, t-Bu

129 O Fe

O

O Ph2P

O 131

O

O N P Me O

P N Me O 133

PPh2 132

O P NMe2 O 134

The various TunaPhos ligands with ruthenium(0) all catalyze the asymmetric hydrogenation of 2-acetylaminocyclopent-1-enecarboxylic acid ethyl ester in >99% ee.671 The larger ring sizes give lower ee values. Good results are obtained in the asymmetric hydrogenation of β-acetamidoacrylates with the Et-ferroTANE rhodium(I) complex.672 The Rh-TangPhos catalyst system brings about the hydrogenation of α-aryl-β-substituted enamides with high enantioselectivity.660 Asymmetric Hydrogenation of Enamides Enamides, in addition to the acrylates shown above, are also asymmetrically hydrogenated with many of the same systems that prove useful for the acetamidoacrylate reductions. The Rh(I)/BICP (2(R)-2′ (i)-bis(dipenylphosphino)1(R),1′ (R)-dicyclopentane) 132 and Rh(I)/DuPHOS systems work well (>90% ee) for the asymmetric hydrogenation of β-acetamidovinyl methoxymethyl ethers

ORGANOSILICON HYDRIDE REDUCTIONS

119

in an approach to enantiomerically enriched β-aminoethanols.673 The Rhbinaphane system 138 catalyzes the reduction of aryl alkyl enamides in up to 99.6% ee.674 Cyclic enamides are reduced in 37–99% enantiomeric excess with the Rh(I)/135 system (Eq. 368).675 NHAc

[Rh((S)-135)(NBD)]SbF6, H2

NHAc 98% ee

OMe MeO

Ph

MeO MeO

PPh2 PPh2

MeO

(Eq. 368)

Ph OMe 135

The Rh(I)/136 or Rh(I)/137 combination can be used in the asymmetric hydrogenation of 1-arylenamides in 90–99% ee, with Rh(I)/137 being the better of the two.676 Me-DuPHOS and related ligands with rhodium(I) reduce 1-aryl2-alkylenamides in >90% ee677 whereas the Rh(I)/DIOP combination carries this out in 97.3–99% ee selectivity.678 Finally, the Rh(I)/138 system reduces βsubstituted-α-arylenamides in 95–99% ee, and α-substituted acetamidoethylenes in 75.7–90% ee.674

NHPPh2 NHPPh2

136

NHPPh2 NHPPh2

137

P

P

138

Asymmetric Hydrogenation of Imines As an extension of the asymmetric hydrogenation of prochiral ketones to enantiomerically enriched alcohols, the reduction of imines has been a topic of interest in obtaining chiral amines of high enantiomeric purity. Several entries to enantiomerically enriched amines based on the approaches outlined above are available. These asymmetric hydrogenations have proved to be more difficult than those for prochiral ketones, but nevertheless show good promise. Iridium(III) hydride forms complexes with DIOP, BDPP (2,4-bis(diphenylphosphino)pentane), NORPHOS, and BINAP ligands to produce amines in 11– 80% ee.679 Similar modest results are obtained in the reduction of N arylketimines with an iridium(III) complex with (2S,3S)-CHIRAPHOS as the chiral ligand.680 The indium complexes with chiral phosphinodihydrooxazoles catalyze the enantioselective hydrogenation of imines in supercritical carbon dioxide with up to 80% ee, but generally lower ee values are observed in

120

ORGANIC REACTIONS

dichoromethane. The Rh(I)/chiral phosphine-catalyzed hydrogenation of imines is reported to give the chiral amines in up to 60% ee.681 This work presents a crystal structure of an intermediate rhodium(diphos)imine complex. The iridium(III) complex with the diphosphine ligand 138 gives amines in up to 99% ee and in excellent yields (Eq. 369).682 Cyclic imines undergo asymmetrical reduction via transfer hydrogenation using the catalyst EBTHI-Ti 102 (Eq. 370).683 NH2 N

138, H2 (1000 psi)

(77%) 99% ee

CH2Cl2, rt

MeO MeO

102, HCO2H N

(Eq. 369)

MeO MeO

NH

(95%) 95% ee

(Eq. 370)

The asymmetric hydrogenation of acyclic imines with the ansa-titanocene catalyst 102 gives the chiral amines in up to 92% ee.684,685 This same system applied to cyclic imines produces the chiral amines with >97% ee values.684,685 The mechanism of these reductions has been studied.686 EXPERIMENTAL CONDITIONS

Normal precautions to protect laboratory workers from exposure to chemical reagents should be followed. Strong acids such as trifluoroacetic acid and trifluoromethanesulfonic acid are often used in the preparations and should be handled with extreme care. The physical properties of organosilicon hydrides are similar to those of the analogous hydrocarbons, after taking account of the differences in molecular weights. They are generally lipophilic in nature. As previously mentioned, the chemical properties of organosilicon hydrides are considerably more benign than those of many metal-based reducing agents. However, organosilicon hydrides do react with strong bases and acids to produce hydrolysis products and hydrogen gas. This reaction occurs more rapidly with bases than with acids. Also, some of the lower molecular weight organosilicon hydrides, especially the parent compound SiH4 , are pyrophoric. A few of the organosilicon hydrides, such as trimethoxysilane and triethoxysilane, are toxic and have the ability to cause corneal damage. Many of the synthetically useful reactions of organosilicon hydrides are conducted in solution using solvents such as CH2 Cl2 , CHCl3 , CCl4 , MeCN, or THF. In general, it is important that anhydrous reaction conditions be used and that normal purification procedures be followed to ensure that the solvents used are pure and anhydrous. Finally, it must be mentioned that there are advantages in synthetic methods using polymeric organosilicon hydride reagents, such as PMHS, which are both relatively inexpensive and give high molecular weight products that are reasonably easy to separate from the desired organic products.

ORGANOSILICON HYDRIDE REDUCTIONS

121

EXPERIMENTAL PROCEDURES MOMO

OH

OH

C9H19-n

C10H21-n

Et3SiH

(68%)

TFA OMe

OMe

2-Decyl-5-methoxy-1-naphthol [Reduction of a Secondary Benzylic Alcohol to a Methylene Group with Concomitant Loss of a MOM Protecting Group].167 To a solution of 2-(1-hydroxydecyl)-5-methoxy-1-methoxymethyleneoxynaphthalene (0.525 g, 1.4 mmol) and Et3 SiH (1.628 g, 14 mmol) in CH2 Cl2 (8 mL) was added TFA (2.16 mL, 28 mmol) in CH2 Cl2 (3 mL) at room temperature and under an atmosphere of argon. The reaction mixture was stirred for 2 hours at room temperature, and then was poured into a saturated aqueous NaHCO3 solution (20 mL) and extracted with CH2 Cl2 (3 × 15 mL). The extract was washed with saturated aqueous NaHCO3 solution (15 mL), brine (15 mL), dried with MgSO4 , and evaporated. The crude product was purified by chromatography (SiO2 , benzene as eluent) to afford 2-decyl-5-methoxy-1-naphthol as needles: 0.319 g (68%); mp 61–62◦ (hexane); IR (CCl4 ) 3600, 1600, 1505, 1254, 1055, 880 cm−1 ; 1 H NMR (100 MHz, CDCl3 ) δ 7.60 (d, J = 9 Hz, 1H), 7.45 (dd, J = 2, 8 Hz, 1H), 7.15 (t, J = 8 Hz, 1H), 7.02 (d, J = 9 Hz, 1H), 6.56 (dd, J = 2, 8 Hz, 1H), 4.90 (br s, 1H), 3.94 (s, 3H), 2.68 (t, J = 7 Hz, 2H), 1.68 (m, 2H), 1.26 (m, 14H), 0.90 (t, J = 8 Hz, 3H). Cl Cl

Et3SiH, CH2Cl2 AlCl3, 0°

(74%)

Cyclohexane [Aluminum Chloride Catalyzed Reduction of a Dichloroalkane to a Hydrocarbon].189 After a solution of cis-1,2-dichlorocyclohexane (0.1582 g, 1.033 mmol) in CH2 Cl2 (3 mL) was cooled to 0◦ , Et3 SiH (0.299 g, 2.57 mmol) and AlCl3 (0.0345 g, 0.173 mmol) were added. The mixture was stirred for 30 minutes and then quenched with water (10 mL). Heptane (23.1 mg, 0.231 mmol) was added as an internal standard and the aqueous layer was separated and extracted with CH2 Cl2 . The combined organic layer was dried (MgSO4 ) and analyzed by GLC: 0.064 g (74%). 1. (EtO)3SiH, CsF, N2 30 min, 60° n-C11H23CO2Et

2. aq. HCl, 30 min

n-C12H25OH

(90%)

1-Dodecanol [Fluoride-Promoted Reduction of an Ester to an Alcohol].83 A mixture of ethyl dodecanoate (2.18 g, 10.0 mmol) and triethoxysilane (3.77 g, 23.0 mmol) was added to CsF (1.52 g, 10.0 mmol) under nitrogen. The reaction was followed by IR spectroscopy. After 30 minutes at 60◦ , 12 N HCl (1 mL) in acetone (5 mL) was added. After 30 minutes, the mixture was extracted

122

ORGANIC REACTIONS

with ether (2 × 150 mL). The combined extracts were dried with MgSO4 and the solvents were removed. The residue was distilled under vacuum to give 1dodecanol: 1.8 g (90%); bp 145◦ /15 Torr. The GLC retention time was identical with that of an authentic sample. CHO

Et3SiH, TFA

O

(80%)

Dibenzyl Ether [Brønsted Acid Promoted Reduction of an Aldehyde to a Symmetrical Ether].311 To a stirred solution of benzaldehyde (5.4 g, 0.05 mol) and TFA (11.4 g, 0.1 mol) under argon was added dropwise, with cooling, Et3 SiH (8.1 g, 0.07 mol) at a rate such that the temperature of the reaction mixture did not exceed 40◦ . The solution turned a crimson color that gradually disappeared. Analysis by GLC showed the complete absence of the aldehyde immediately after addition of all of the silane. The products were separated by vacuum distillation at 20 Torr, collecting the fractions up to 125◦ . Dibenzyl ether was obtained from the residue by freezing out: 4 g (0.02 mol, 80%); mp 3–6◦ ; nD 25 1.5608. CHO +

EtOH

CH2OEt

1. Cl3 CCO2H, Et3SiH, 50-60°, 4 h

(90%)

2. H2O, NaHCO3

Ethyl Benzyl Ether [Brønsted Acid Promoted Reduction of an Aldehyde to an Unsymmetrical Ether].327 To a cooled mixture of benzaldehyde (4.3 g, 41 mmol) and absolute ethanol (3.7 g, 80 mmol) was added trichloroacetic acid (18.2 g, 111 mmol). Et3 SiH (6.96 g, 60 mmol) was then added dropwise with stirring while the mixture was maintained at 50–60◦ . After 4 hours, the reaction mixture was diluted with water, neutralized with aqueous NaHCO3 solution, and extracted with Et2 O. The dried ether extract was distilled and the 170–190◦ fraction was collected. Distillation from sodium gave ethyl benzyl ether: 4.8 g (90%); bp 187–189◦ .

n-C6H13CHO +

PhMe2SiH Ph

OTMS

EG acid

n-C7H15

O

Ph

(82%)

1-Heptyl 3-Phenylpropyl Ether [Electrogenerated Acid-Promoted Reduction of an Aldehyde to an Unsymmetrical Ether].333 A mixture of 1-heptanal (1.0 mmol), 3-phenylpropoxytrimethylsilane (1.2 mmol), tetra-nbutylammonium perchlorate (0.1 mmol), and lithium perchlorate (0.1 mmol) was dissolved in CH2 Cl2 (3 mL) in an undivided cell. The mixture was electrolyzed under constant current (1.67 mA cm−2 ) with platinum electrodes at ambient temperature. After 5 minutes, dimethylphenylsilane (1.2 mmol) was added dropwise and the electrolysis was continued (0.06 Faraday/mol). After completion of the reaction, one drop of Et3 N was added and the solution was concentrated. The residue was chromatographed on SiO2 to give 1-heptyl 3-phenylpropyl

ORGANOSILICON HYDRIDE REDUCTIONS

123

ether: 0.82 mmol (82%); bp 80–83◦ /1.0–2.0 Torr; IR (neat) 2955, 2925, 1605, 1110 cm−1 ; 1 H NMR (CDCl3 ) δ 7.22 (s, 5H), 3.37 (t, J = 6 Hz, 2H), 2.86–2.47 (m, 2H), 1.50–2.10 (m, 2H), 1.31 (br m, 10H), 0.87 (m, 3H). O

(n-Bu)3SiH, TFA, –35°

O (80%)

Dicyclohexyl Ether [Brønsted Acid Promoted Reduction of a Ketone to a Symmetrical Ether].313 Cyclohexanone (3.92 g, 40 mmol) and tri(n-butyl) silane (1.78 g, 20 mmol) were placed in a round-bottomed flask. TFA (75 mmol) was added slowly over a one-hour period to the reaction mixture, which was held at −35◦ . After complete addition, the reaction flask was placed in a freezer at −15◦ for 70 hours. Direct distillation gave dicyclohexyl ether: 2.91 g (16 mmol, 80%); bp 119–121◦ /18 Torr. CHO +

1. TrClO4, 0°, 5 min Ph

OTMS

2. Et3SiH, 5 min

BnO

Ph

(83%)

Benzyl 3-Phenylpropyl Ether [Trityl Perchlorate Catalyzed Reduction of an Aldehyde to an Unsymmetrical Ether].329 Under an argon atmosphere, a CH2 Cl2 (2 mL) solution of benzaldehyde (53 mg, 0.5 mmol) and 3phenylpropoxytrimethylsilane (0.5 mmol) was added to trityl perchlorate (9 mg, 0.026 mmol), and the solution was stirred for 5 minutes at 0◦ . A CH2 Cl2 (1 mL) solution of Et3 SiH (59 mg, 0.5 mmol) was added and stirring was continued for another 5 minutes. Then phosphate buffer was added, and the organic materials were extracted with Et2 O and dried over MgSO4 . After removal of the solvents under reduced pressure, isolation by TLC on SiO2 provided 94 mg (83%) of benzyl 3-phenylpropyl ether: IR (NaCl) 1100 cm−1 ; 1 H NMR (CDCl3 ) δ 7.10 (s, 5H), 7.00 (s, 5H), 4.30 (s, 2H), 3.30 (t, J = 6 Hz, 2H), 2.8-2.4 (m, 2H), 2.1-1.5 (m, 2H). 1. NaI, TMSCl, MeCN, rt CHO

2. TMDO

O

(84%)

Di-n-pentyl Ether [TMSI-Catalyzed Reduction of an Aldehyde to a Symmetrical Ether].314 A mixture of sodium iodide (0.15 g, 1 mmol), 1pentanal (1.06 mL, 10 mmol), and trimethylsilyl chloride (2.0 mL, 15.4 mmol) was stirred in MeCN (5.0 mL) at room temperature for 10 minutes, after which 1,1,3,3-tetramethyldisiloxane (TMDO, 1.79 mL, 10 mmol) was added. When the exothermic reaction had ended (30 minutes), a solution of 2.5 N HF in MeOH (30 mL) was added to the reaction mixture, which was then refluxed for 5 minutes. Work-up was carried out by diluting the solution with CH2 Cl2 (40 mL), washing with water (30 mL) and saturated aqueous NaHCO3 solution (20 mL), drying, and evaporating the solvents. Crude di-n-pentyl ether was purified by distillation: 0.65 g (84%); bp 185–189◦ /760 Torr.

124

ORGANIC REACTIONS O + EtOTMS

OEt

1. HMDS, I2, 0°, 10 min

(91%)

2. TMSH, 0° to 15°

Cyclohexyl Ethyl Ether [TMSI-Catalyzed Reduction of a Ketone to an Unsymmetrical Ether].334 In a 100-mL, three-necked flask equipped with a rubber septum, thermometer, magnetic stirring bar, and nitrogen inlet were placed finely powdered iodine (0.13 g, 0.50 mmol) and hexamethyldisilane (0.079 g, 0.54 mmol) in CH2 Cl2 (14 mL). The violet solution was stirred 10 minutes at room temperature, cooled to 0◦ , and a solution of cyclohexanone (1.04 g, 10 mmol) and ethoxytrimethylsilane (1.10 g, 10 mmol) in 10 mL of CH2 Cl2 was introduced via syringe. The reaction mixture was stirred for 10 minutes at 0◦ , after which TMSH was added directly from a gas cylinder by means of Tygon tubing attached to a hypodermic needle inserted through the rubber septum. The gas was allowed to slowly bubble through the solution until the color changed from violet to red-gold. During this time the internal temperature rose from 0◦ to 15◦ . The cold bath was removed and stirring was continued at room temperature for 2 hours. The mixture was washed with 10% aqueous Na2 S2 O3 solution (4 × 30 mL) and water (4 × 30 mL), and dried over MgSO4 . The volatiles were removed under reduced pressure on a steam bath to obtain pure cyclohexyl ethyl ether: 1.37 g (91%); bp 141–144◦ , 13 C NMR (CDCl3 ) δ 76.8, 63.0, 32.6, 26.4, 24.2, 15.9.

CHO

1. TMSCl, TMDO, SOCl2, 0° 2. ZnI2, reflux, 45 min

Cl

3. aq. HF, reflux, 10 min

(87%)

4-Methylbenzyl Chloride [Reductive Halogenation of an Aldehyde to a Benzyl Chloride].314 A mixture of 4-methylbenzaldehyde (1.18 g, 10 mmol), chlorotrimethylsilane (2.0 mL, 15.7 mmol), 1,1,3,3-tetramethyldisiloxane (TMDO, 1.79 mL, 10 mmol), and thionyl chloride (1.0 mL, 13.7 mmol) was cooled at 0◦ . Then ZnI2 (0.02 g) was added and a very exothermic reaction took place. When the spontaneous heating had ended, the mixture was heated at reflux with stirring for 45 minutes, and a 2.5 M solution of HF in MeOH (10 mL) was added. After being heated at reflux for 10 minutes, the solution was cooled to 0◦ , filtered, and taken up in CH2 Cl2 (30 mL)/water (40 mL). The aqueous layer was extracted with CH2 Cl2 (2 × 10 mL). The combined organic phases were dried (Na2 SO4 ) and the solvents were evaporated to afford crude 4-methylbenzyl chloride, which was purified by distillation: 1.22 g, 87%; bp 190–195◦ /760 Torr. O Ph

NHCO2Et

OH

PhSiMe2SiH, TFA 0°, 2.5 h

Ph

NHCO2Et (87%)

(1R,2S )-2-[(Ethoxycarbonyl)amino]-1-phenyl-1-propanol [Brønsted Acid Promoted Reduction of an α-Amino Ketone to an Erythro α-Hydroxy

ORGANOSILICON HYDRIDE REDUCTIONS

125

Amine].276 Dimethylphenylsilane (0.184 mL, 1.20 mmol) was added slowly to a TFA (1 mL) solution of (S)-2-[(ethoxycarbonyl)amino]-1-phenyl-1-propanone (221 mg, 1.00 mmol) at 0◦ , and the solution was stirred for 2.5 hours at 0◦ . Saturated aqueous NaHCO3 solution (20 mL) was added, and the resulting mixture was extracted with CH2 Cl2 (10 mL). The extract was dried over MgSO4 , filtered, and concentrated under reduced pressure to give the crude product, whose 1 H NMR spectrum showed exclusive formation (>99% selectivity) of (1R, 2S)2-[(ethoxycarbonyl)amino]-1-phenyl-1-propanol. Purification by preparative TLC (SiO2 , AcOEt/hexane, 1/1) afforded (1R, 2S)-2-[(ethoxycarbonyl)amino]-1phenyl-1-propanol (194 mg, 87%) as colorless crystals: mp 71◦ ; [α]20 D − 40◦ (c 0.245, CH2 Cl2 ); IR (KBr) 3350, 1694, 1552, 1273, 1043, 1028, 708 cm−1 ; 1 H NMR (CDCl3 ) δ 7.34 (s, 5H), 4.9 (br s, 1H), 4.84 (d, J = 3 Hz, 1H), 4.10 (q, J = 7.2 Hz, 2H), 4.2-3.8 (m, 1H), 2.83 (br s, 1H), 1.24 (t, J = 7 Hz, 3H), 0.99 (d, J = 7 Hz, 3H); MS (70 eV) m/z (relative intensity): M+ 223 (trace), 117 (18), 116 (66), 107 (11), 88 (21), 79 (15), 77 (14), 72 (11), 51 (5), 44 (100), 29 (23), 27 (7), 18 (5). Anal. Calcd for C12 H17 NO3 : C 64.55, H 7.67, N 6.27. Found: C 64.35, H 7.53, N 6.25. Ph

1. Et3SiH, NH4F, CH2Cl2, 0°, 0.5 h 2. rt, 3 h

Ph

(85%)

Phenylcyclopentane [Brønsted Acid Catalyzed Reduction of an Alkene to an Alkane].135 To a stirred solution of 1-phenylcyclopentene (1.44 g, 10 mmol), NH4 F (0.48 g, 13 mmol), and Et3 SiH (1.5 g, 13 mmol) was added TFA (5.1 g, 50 mmol) at 0◦ over a 10-minute period. The reaction mixture was then stirred for 20 minutes at 0◦ and at room temperature for 3 hours. The reaction mixture was quenched with ice water and extracted with CH2 Cl2 . The organic extract was washed with 10% aqueous saturated NaHCO3 solution, dried (CaCl2 ), and concentrated. Distillation provided phenylcyclopentane: 1.22 g (85%); bp 108–111◦ /20 Torr.

n-C15H31COCl

1. Et3SiH, (C6F5)3B, CH2Cl2, rt, 20 h 2. aq. HF, reflux, 7 h

n-C16H34 (96%)

n-Hexadecane [Tris(pentafluorophenyl)boron-Catalyzed Reduction of an Acid Chloride to an Alkane].282 Et3 SiH (20 mmol) was added to a stirred solution of hexadecanoyl chloride (5 mmol) and tris(pentafluorophenyl)boron (5 mol%) in CH2 Cl2 . The reaction mixture was stirred for 20 hours at room temperature, quenched with Et3 N (0.25 g), filtered through Celite, and concentrated. The residue was mixed with 40% HF (5 mL) in EtOH (30 mL) and heated at reflux for 7 hours. Water (60 mL) was added, and the crude product was extracted with pentane (3 × 30 mL). The combined pentane solutions were washed with water and dried over MgSO4 . After the solvent and triethylfluorosilane were removed under vacuum, the product was purified by flash chromatography to give a 96% yield of n-hexadecane.

126

ORGANIC REACTIONS 1. Et3SiH, (C6F5)3B, CH2Cl2, rt, 20 h

n-C11H23CO2H

2. aq. HF, reflux, 7 h

n-C12H26 (91%)

n-Dodecane [Tris(pentafluorophenyl)boron-Catalyzed Reduction of a Carboxylic Acid to an Alkane].282 Dodecanoic acid (5 mmol) in CH2 Cl2 was added to a CH2 Cl2 solution of tris(pentafluorophenyl)boron (5 mol%) and Et3 SiH (30 mmol). The reaction mixture was stirred for 20 hours at room temperature, quenched with Et3 N (0.25 g), filtered through Celite, and concentrated. The residue was mixed with 40% HF (5 mL) in EtOH (30 mL) and heated at reflux for 7 hours. Water (60 mL) was added and the crude product was extracted with pentane (3 × 30 mL). The combined pentane solutions were washed with water and dried over MgSO4 . After the solvent and triethylfluorosilane were removed under vacuum, the product was purified by flash chromatography to give a 91% yield of n-dodecane. CO2H

Et3SiH, (C6F5)3B, CH2Cl2 rt, 20 h

I

OSiEt3

(94%)

I

4-Iodobenzyloxytriethylsilane [Tris(pentafluorophenyl)boron-Catalyzed Reduction of a Carboxylic Acid to a Benzyl Triethylsilyl Ether].282 Et3 SiH (16.5 mmol) was added to a stirred solution of 4-iodobenzoic acid (5 mmol) and tris(pentafluorophenyl)boron (5 mol%) in CH2 Cl2 . The reaction mixture was stirred for 20 hours at room temperature, quenched with Et3 N (0.25 g), filtered through Celite, and concentrated. The solvent was removed under vacuum and the product was purified by flash chromatography to give a 94% yield of 4iodobenzyloxytriethylsilane. 1 H NMR (CDCl3 , 500 MHz) δ 7.48 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 8.4 Hz, 2H), 4.71 (s, 2H), 1.02, 0.68 (q, J = 8.0 Hz, 6H); 13 C NMR (CDCl3 , 126 MHz) δ 140.8, 131.7, 128.3, 121.07, 64.4, 7.2, 4.9; GC–MS m/z (% relative intensity, ion): 300 (1, M+ ), 271 (77, M–Et), 169 (100). PhMeSiH2, Cp2TiMe2 N

80°, 12 h

(50%) N SiHMePh

N -(Phenylmethylsilyl)-1,2,3,4-tetrahydropyridine [Reduction of a Pyridine].264 Phenylmethylsilane (3.5 mL, 25.6 mmol) and pyridine (1.0 mL, 12.5 mmol) were added to Cp2 TiMe2 (0.13 g, 0.7 mmol, 6 mol%). The solution color changed to dark blue, then purple, accompanied by gas evolution. The mixture was stirred for 12 hours at 80◦ . The 1 H-NMR spectrum showed that >95% of the pyridine had reacted to give a yield of ca. 80% of the crude product, which was distilled under vacuum to give 1.29 g (50%) of the title compound as a colorless liquid: bp 57◦ /0.12 Torr; 1 H NMR (300 MHz, C6 D6 ) δ 7.5 and 7.2 (2m, 5H), 5.01 (q, J = 3.3 Hz, 1H), 4.62 (m, 1H), 2.99 (m, 2H), 2.00 (m, 2H), 1.57 (m, 2H), 0.28 (d, J = 3.3 Hz, 3H); 29 Si NMR (59.9 MHz, C6 D6 ) δ −10.5;

ORGANOSILICON HYDRIDE REDUCTIONS

127

EIMS m/z (% relative intensity, ion): 203 (100, M+ ), 188 (18.5, M+ –CH3 ), 121 (76.6, M+ –C5 H8 N). PhSiH3, Mo(CO)6, NaHCO3 (81%)

THF, reflux, 1.5 h

Br O

O

Camphor [Reduction of an α-Bromo Ketone to a Ketone].197 A mixture of α-bromocamphor (2.24 g, 9.69 mmol), Mo(CO)6 (0.11 g, 0.53 mmol), phenylsilane (1.30 g, 12 mmol), and NaHCO3 (0.88 g, 10.5 mmol) in THF (6 mL) was heated at reflux for 1.5 hours. The mixture was cooled to room temperature, water (0.15 mL) was added, and the solvent was removed under reduced pressure. Distillation afforded camphor in 81% yield.

N n-C10H21

OTf N

Et3SiH, Pd(OAc)2, dppp DMF, 60°, 4 h

N n-C10H21 N (99%)

2-Phenyl-5-decylpyrimidine [Reduction of an Aryl Triflate to an Arene].201 To a mixture of 2-(4-trifluoromethanesulfonyloxyphenyl)-5-decylpyrimidine (1 mmol), Pd(OAc)2 (4.5 mg, 0.02 mmol), and dppp (8 mg, 0.02 mmol) in DMF (5 mL) at 60◦ was added Et3 SiH (0.4 mL, 2.5 mmol). At this time the solution changed color from light brown to deep brown. Stirring was continued for 4 hours, and the reaction mixture was cooled and diluted with Et2 O. The ether phase was washed with water, and with aqueous saturated solutions of NaHCO3 and NaCl. The ether layer was dried (Na2 SO4 ) and concentrated. The crude product was purified (99% yield) by chromatography: IR (KBr) 1549, 1435, 745, 691, 654 cm−1 ; 1 H NMR: δ 8.62 (s, 2H), 8.41 (m, 2H), 7.46 (m, 3H), 2.62 (t, J = 7.7 Hz, 2H), 1.8-1.4 (m, 2H), 1.27 (br s, 14H), 0.88 (t, J = 6.2 Hz, 3H).

(n-C16H33)2O

Et3SiH, (C6F5)3B CH2Cl2, rt, 20 h

n-C16H34 + n-C16H33OSiEt3 (98%)

(98%)

n-Hexadecane and 1-(Triethylsiloxy)hexadecane [Reduction of a Symmetrical Ether].145 Et3 SiH (1.1 mmol) was added to tris(pentafluorophenyl)boron (5 mol%) and bis-(n-hexadecyl) ether (1 mmol) in 1 mL of CH2 Cl2 . The reaction mixture was stirred for 20 hours at room temperature and then quenched with Et3 N (0.05 mL), filtered through Celite, and concentrated. GLC analysis with an internal standard showed the presence of n-hexadecane (98%) and 1(triethylsiloxy)hexadecane (98%).

128

ORGANIC REACTIONS CO2H

1. EtMe2SiH, 57, 1,4-dioxane, 20°, 0.5 h

OH

2. Add acid, stir 0.5 h

(CO)2Ru

(72%)

Ru(CO)2 Ru (CO)2 O 57

3-Phenyl-1-propanol [Reduction of a Carboxylic Acid to an Alcohol].280 To a solution of ruthenium catalyst 57 (616.5 mg, 25.2 µmol) in dioxane (0.45 mL) was added dimethylethylsilane (0.84 mL, 6.3 mmol). After the mixture had been stirred for 30 minutes at room temperature, hydrocinnamic acid (380 mg, 2.55 mmol) was added, and the stirring was continued for 30 minutes. Vigorous gas evolution occurred. The reaction was quenched with aqueous HCl, and the mixture was extracted with Et2 O. The organic phase was washed with aqueous saturated NaHCO3 and aqueous saturated NaCl solutions, and then dried with MgSO4 . The solvent was removed under vacuum and the product was purified by chromatography (EtOAc/hexane 1/9) to give 3-phenylpropyl alcohol: 248 mg, 72%.

t-BuO2C

N H

SBu-t H N

CO2Bu-t

Et3SiH, TFA, CH2Cl2 rt, 1.5 h

O

H2N

SBu-t H N

CO2H + Me3CH

O (100%)

Cys(SBu-t)Gly [Reductive Deprotection of Boc and tert-Butyl Ester Groups in the Presence of a tert-Butyl Sulfide].307 Boc•Cys(SBu-t)Gly•OBu-t (1 mmol) was stirred with TFA (13 mmol), CH2 Cl2 (32 mmol), and Et3 SiH (2.5 mmol) at room temperature for 1.5 hours. After solvent removal, the residue was triturated with Et2 O and the precipitated product was removed by filtration, washed with Et2 O, and dried: 100%. N

OH

PMHS, (t-BuCO)2O, 10% Pd/C 40-50°, 7 h

H N

Boc (80%)

N -Boc-cyclododecylamine [Reductive Boc-protection of an Oxime].549 To a stirred solution of cyclododecanone oxime (1 mmol) in EtOH (10 mL) were added PMHS (180 mg, 3.0 mmol), di-tert-butyl dicarbonate (240 mg, 1.1 mmol), and 10% Pd/C (10 mg). The reaction mixture was stirred at 40–50◦ for 7 hours, after which time it was filtered and the filtrate concentrated under vacuum. The crude product was purified by column chromatography to give N -Boccyclododecylamine: 80%.

ORGANOSILICON HYDRIDE REDUCTIONS TBSO

129

TBSO Et3SiH, BF3•OEt2 N Ac

OMe

(97%)

CH2Cl2, –40°, 1-2 h

N Ac

(3R)-N -Acetyl-3-(tert-butyldimethylsiloxy)pyrrolidine [Reduction of an Aminal to an Amine].521 A solution of N -acetyl-2-methoxy-4-tert-butyldimethylsiloxy)pyrrolidine (2 mmol) and Et3 SiH (4 mmol) in dry CH2 Cl2 (3 mL) was treated with BF3 •OEt2 (4 mmol) at −40◦ . The reaction was monitored by TLC (1–2 hours). The mixture was diluted with CHCl3 and washed with aqueous saturated NaHCO3 and aqueous saturated NaCl solution. The organic layer was dried (MgSO4 ) and evaporated under reduced pressure. Purification of the residue by chromatography on SiO2 (hexane/EtOAc 10 : 1) gave the title compound as a colorless syrup: 97%; [α]24.5 D −23.4◦ (c 1.22, CHCl3 ); IR (film) 3350, 1650 cm−1 ; 1 H NMR (CDCl3 ) δ 4.58 − 4.25 (m, 1H), 3.80-3.10 (m, 4H), 2.10–1.60 (m, 2H), 1.98, 1.95 (2s, 3H), 0.80 (s, 9H), 0.01 (s, 6H); MS m/z: 228 (M+ –CH3 ); Anal. Calcd for C12 H25 NO2 Si: C 59.21; H 10.35; N 5.75; Si 11.54. Found: C 58.85; H 10.38; N 5.80; Si 11.18. O

PhMe2SiH, RhH(PPh3)4

OSiMe2Ph (87%) cis:trans = 92:8

CH2Cl2, 50°, 48 h

3,5-Dimethyl-l-cyclohexen-l-yl Dimethylphenylsilyl Ether [Reductive 1,4-Hydrosilylation of an Enone].374 3,5-Dimethyl-2-cyclohexen-1-one (0.124 g, 1.0 mmol) and RhH(PPh3 )4 (6 mg, 0.0052 mmol) were treated with PhMe2 SiH (0.177 g, 1.3 mmol) at 50◦ for 48 hours. After hexane (1 mL) was added, the reaction mixture was filtered and concentrated under vacuum. The crude product was purified by Kugelrohr distillation (90◦ / 1 Torr) to give a colorless liquid: 225 mg, 87%: IR 2952, 2918, 2913, 2902, 2870, 1666, 1428, 1369, 1253, 1197, 1182, 1121, 1079, 826, 787, 699 cm−1 ; 1 H NMR (200 MHz, CDCl3 ) δ 7.58 (m, 2H), 7.37 (m, 3H), 4.66 (s, 1H), (s, 1H), 2.21 (br s, 1H), 1.93 (m, 1H), 1.63 (m, 4H), 0.90 (d, J = 7.9 Hz, 3H), 0.86 (d, J = 7.0 Hz, 3H), 0.43 (s, 6H); 13 C NMR δ 149.7, 138.0, 133.4, 129.5, 127.7, 111.3, 40.8, 38.4, 30.9, 29.6, 22.6, 22.0, −0.9, −1.0; EIMS m/z: M+ calcd for C16 H24 OSi, 260.1596; found 260.1584. Anal. Calcd for C16 H24 OSi: C 73.80; H 9.30; found: C 73.78; H 9.25. O

O Ph2SiH2, ZnCl2, CHCl3

O

Pd(PPh3)4, rt, 1 h O

(95%)

O O

6,8-Dioxabicyclo[3.2.1]octan-4-one [1,2-Reduction of an Enone in the Presence of an Acetal].436 6,8-Dioxabicyclo[3.2.1]oct-2-ene-4-one (19 mg, 0.15 mmol) was dissolved in 3 mL of CHCl3 along with Ph2 SiH2 (55 mg,

130

ORGANIC REACTIONS

0.30 mmol) and ZnCl2 (20 mg, 0.15 mmol). Pd(PPh3 )4 (17 mg, 0.015 mmol) was added and the mixture was stirred at room temperature until the reaction was complete as determined by GLC. The reaction mixture was filtered through a short SiO2 column and purified by Kugelrohr distillation to give 18 mg (95%) of 6,8-dioxabicyclo[3.2.1]octan-4-one, having physical properties identical with literature values.

O

Et3SiH, H2SO4, H2O MeCN, 28°, 65 h

H N

Ac

(78%)

N -(exo-2-Norbornyl)acetamide [Reductive Amidation of a Ketone].313 To an acetonitrile (15 mL) solution of norcamphor (6.6 g, 60 mmol) and triethylsilane (7.7 g, 66 mmol) was added water (3.0 mL) followed by 9.0 mL of concentrated H2 SO4 (9.0 mL) at ice-bath temperature. The heterogeneous reaction mixture was stirred rapidly at room temperature for 65 hours. The mixture was then quenched by addition of 50% aqueous NaOH solution (30 mL) and the aqueous solution was extracted with CH2 Cl2 (3 × 50 mL). The combined extracts were passed through anhydrous MgSO4 and the CH2 Cl2 was removed under reduced pressure. The residue was washed three times with pentane to remove hexamethyldisiloxane and other soluble reaction products. The crude product was crystallized from Et2 O to give N -(exo-2-norbornyl)acetamide (6.5 g, 78%) whose 1 H-NMR spectrum and melting point were in accord with literature values.

O

Et3SiH, RhCl(PPh)3 50°, 2 h

O (88%)

Dihydro-β-Ionone [1,4-Reduction of an α,β-Unsaturated Ketone].435 A mixture of β-ionone (1.91 g, 10 mmol), Et3 SiH (1.27 g, 11 mmol), and RhCl(PPh3 )3 (9 mg, 0.01 mmol) was stirred at 50◦ for 2 hours under nitrogen. The NMR spectrum of the reaction mixture showed the exclusive formation of the 1,4-addition (silyl enol ether) product: 1 H NMR (CCl4 ) δ 5.23 (m, 1H), 4.28 (t, J = 7 Hz, 1H), 2.25-1.75 (m, 4H), 1.72 (br s, 3H), 1.63 (br s, 3H), 1.751.20 (m, 3H), 0.4–1.20 (m, 21H). The silyl enol ether was readily desilylated by treatment with K2 CO3 (10 mg)/MeOH (10 mL) with stirring for 1 hour at room temperature. After solvent removal, the crude product was distilled under reduced pressure to give dihydro-β-ionone: 1.70 g, 88.1% bp 88◦ /2.5 Torr. O

Ph2SiH2, RhCl(PPh3)3 rt, 30 min

OH

(89%)

β-Ionol [1,2-Reduction of an α,β-Unsaturated Ketone].435 A mixture of β-ionone (1.93 g, 10 mmol), Ph2 SiH2 (2.02 g, 11 mmol), and RhCl(PPh3 )3 (9 mg, 0.01 mmol) was stirred at room temperature under nitrogen. An

ORGANOSILICON HYDRIDE REDUCTIONS

131

exothermic reaction took place and the reaction was complete in 30 minutes. The NMR spectrum of the reaction mixture indicated the 1,2-reduction (silyl ether) product was formed exclusively: 1 H NMR (CCl4 ) δ 7.80-7.10 (m, 10H), 5.55-5.18 (m, 3H), 5.40 (s, 1H), 4.39 (m, 1H), 2.30-1.00 (m, 5H), 1.53 (m, 3H), 1.27 (d, J = 6 Hz, 3H), 1.0 (m, 5H), 0.86 (s, 3H), 0.77 (s, 3H). To the reaction mixture was added n-hexane (50 mL), and the precipitated catalyst was removed by filtration. Then MeOH (10 mL) and K2 CO3 (10 mg) were added to the filtrate. Methanolysis was complete within 1 hour at room temperature. The ratio of dihydro-β-ionone/β-ionol was 0 : 100 based on GLC and NMR analyses. After solvent evaporation, the residue was distilled to give β-ionol: 1.74 g, 89%; bp 99◦ /2 Torr. O 8

O

Ph2SiH2 NEt2

Ti(OPr-i)4, 20°

8

H

(90%)

Undec-10-enal [Reduction of an Amide to an Aldehyde].433 To a dry flask containing neat N ,N -diethylundec-10-enamide (0.155 mL, 0.65 mmol) under argon was added Ph2 SiH2 (0.135 mL, 0.72 mmol) and Ti(OPr-i)4 (0.196 mL, 0.65 mmol). Initial effervescence was observed [CAUTION!] and the reaction mixture was stirred at room temperature until TLC analysis showed complete consumption of the starting material (ca. 5 hours). The mixture was diluted with THF (20 mL), treated with 1 M HCl (10 mL), stirred for 1 hour, and poured onto Et2 O (80 mL). The organic layer was washed with 1 M HCl (3 × 10 mL), saturated aqueous NaHCO3 solution (2 × 10 mL), and saturated aqueous NaCl solution (10 mL), and then dried (MgSO4 ) and concentrated under vacuum. Flash column chromatography on SiO2 (hexane:Et2 O 15 : 85) afforded undecenal (99 mg, 90%). O

Me2ClSiH, TMSCH2CH=CH2 InCl3, CH2Cl2, rt, 2 h

Ph

Ph

(86%)

4-Phenylpent-1-ene [Reductive Allylation of an Aryl Ketone].427 Acetophenone (2.0 mmol) was added to a mixture of InCl3 (0.1 mmol), ClMe2 SiH (2.2 mmol), and allyltrimethylsilane (2.2 mmol) in CH2 Cl2 (10 mL) at room temperature. The reaction mixture was stirred for 2 hours, quenched with water (20 mL), and extracted with Et2 O (3 × 20 mL). After the organic layer was dried (MgSO4 ) and concentrated under vacuum, the residue was purified by chromatography (hexane) on SiO2 to give 4-phenylpent-1-ene (86%). O

PMHS, (C6F5)3B CH2Cl2, rt, 5-20 min

(88%)

6-Phenylhex-1-ene [Reduction of an Aliphatic Ketone Function to a Methylene Function].354 To a solution of 6-phenylhex-1-ene-4-one (1 mmol) in

132

ORGANIC REACTIONS

dry CH2 Cl2 (5 mL) and tris(pentafluorophenyl)boron (5 mol%) was slowly added PMHS (3 mmol) at room temperature. After 20 minutes, a vigorous effervescence was observed. The solvent was evaporated and the reaction mixture was dissolved in hexane and then filtered through a SiO2 pad using hexane. Evaporation of the volatiles afforded the 6-phenylhex-1-ene (88%) in pure form.

6

CO2Me

(EtO)3SiH, Ti(OPr-i)4

OH 6

50°, 16 h

(87%)

10-Undecen-1-ol [Reduction of an Ester to an Alcohol].291 Triethoxysilane (1.7 mL, 9 mmol) and methyl 10-undecenoate (594 mg, 3 mmol) were added to a test tube. Ti(OPr-i)4 (45 µL, 0.15 mmol) was added, and the test tube was fitted with a drying tube packed with Drierite to exclude excess moisture. The contents of the vessel were then stirred while being heated in an oil bath at 50◦ for 16 hours. The reaction mixture was washed into a 100-mL round-bottomed flask with THF (10 mL). Then 1 N NaOH (20 mL) was added slowly with stirring. NOTE: CAUTION: vigorous bubbling was observed. After 4 hours, the mixture was added to Et2 O (50 mL) and water (50 mL). After shaking, the layers were separated, and the aqueous layer was extracted with an additional 50 mL of Et2 O. The combined organic extracts were washed with 1 M HCl (2 × 50 mL), dried (MgSO4 ), filtered, and concentrated under vacuum to afford 10-undecen-1-ol as a clear oil: 443 mg, 87%. The product was >95% pure as determined by GLC and 1 H NMR analyses. Et3SiH, TFA

(CO)3Cr

(CO)3Cr

(92%)

CH2Cl2, rt, 1.5 h

HO

Tricarbonyl(1-endo-allyltetralin)chromium [Stereoselective Reduction of an Alcohol to a Hydrocarbon].182 A solution of tricarbonyl(1-exo-allyl-1endo-tetralol)chromium (150 mg, 0.46 mmol), Et3 SiH (0.22 mL, 1.4 mmol), and CH2 Cl2 (1 mL) was stirred at room temperature for 1.5 hours under nitrogen. The mixture was poured into water (10 mL) and extracted with Et2 O (2 × 10 mL). Evaporation of the organic layer under reduced pressure and purification by silica gel chromatography on SiO2 (1 : 8 Et2 O/petroleum ether) afforded tricarbonyl(1endo-allyltetralin)chromium as yellow crystals: 131 mg, 92%; mp 88–89◦ ; IR (CHCl3 )1960, 1880, 1635 cm−1 ; 1 H NMR (CDCl3 ) δ 6.15-4.80 (m, 7H), 2.952.10 (m, 5H), 2.05-1.35 (m, 4H). OMe Et3SiH, BF3•OH2 CH2Cl2, rt, 6 h

OMe (100%)

OMe

5-Methoxytetralin [Partial Reduction of a Substituted Naphthalene to a Tetralin].262 1,5-Dimethoxynaphthalene (300 mg, 1.0 mmol) dissolved in

ORGANOSILICON HYDRIDE REDUCTIONS

133

CH2 Cl2 (3–4 mL) was added dropwise to a flask containing BF3 •OH2 (1.1 g, 13 mmol) at 0◦ . After the addition was completed, the mixture was stirred for 10–15 minutes and allowed to warm to room temperature, and Et3 SiH (742 mg, 6.4 mmol) was added dropwise. The reaction mixture was stirred at room temperature for an additional 5–6 hours, neutralized with cold saturated aqueous Na2 CO3 solution, and extracted with CH2 Cl2 (3 × 15 mL). The combined organic extracts were washed with water (2 × 10 mL), dried (MgSO4 ), and evaporated to leave ca. 270 mg of brownish oil, which according to NMR and GC analyses contained ca. 90% of 5-methoxytetralin. Purification of the crude product was accomplished by column chromatography on SiO2 (CH2 Cl2 /Et2 O). OAc O OAc

OAc Ph2SiH2, ZnCl2, Pd(PPh3)4

O

THF, rt, 13 h, 50°, 2 h

AcO

(90%)

AcO

1,2,3-Trideoxy-D-ribo-hex-1-enopyranose Diacetate [Reduction of an Allyl Ester].196 To a THF (10 mL) solution containing tri-O-acetylglucal (349 mg, 1.28 mmol), diphenylsilane (489 mg, 403 mmol), and ZnCl2 (541 mg, 4.0 mmol) was added Pd(PPh3 )4 (70 mg, 0.06 mmol, 12 mol%). The solution was stirred at room temperature for 13 hours, then at 50◦ for 2 hours, and then mixed with Et2 O and washed several times with water. The ether layer was dried over Na2 SO4 and the solvent was evaporated. The yield of 1,2,3-trideoxy-D-ribo-hex1-enopyranose diacetate was 90% as determined by NMR using bibenzyl as an internal standard. The product was partially decomposed upon chromatographic purification over SiO2 , yielding 120 mg (53%). OH O

OH Et3SiH, TFA, LiClO4 (0.01 eq)

(86%)

rt, 4 h s-Bu

O

O

s-Bu

O

O

6-(2-Butyl)-4-hydroxy-3-ethyl-2-pyrone (Germicidin) [Reduction of a Ketone Carbonyl to a Methylene Group in a Multifunctional Compound].423 A TFA (15 mL) solution containing 3-acetyl-6-(2-butyl)-4-hydroxy-2-pyrone (2 mmol), Et3 SiH (1.29 mL, 8.0 mmol), and LiClO4 (2 mg, 0.02 mmol) was stirred at room temperature for about four hours while being monitored by TLC. The solvent was evaporated under vacuum and the residue was purified by column chromatography on silica gel (CHCl3 eluent) to yield racemic 6-(2butyl)-4-hydroxy-3-ethyl-2-pyrone: 337 mg, 86%; mp 95–97◦ (Et2 O/hexane); IR (KBr) 1160, 1285, 1430, 1595, 1680, 2885, 2945, 2980 cm−1 ; 1 H NMR (CDCl3 ) δ 6.22 (s, 1H), 2.48 (q, J = 7.4 Hz, 2H) and (m, 1H), 1.75-1.24 (m, 2H), 1.20 (d, J = 6.7 Hz, 3H), 1.11 (t, J = 7.5 Hz, 3H), 0.89 (t, J = 7.5 Hz, 3H); 13 C NMR (CDCl3 ) δ 69.6, 168.8, 168.0, 105.0, 100.9, 39.8, 27.5, 17.7, 16.4, 12.4, 11.6.

134

ORGANIC REACTIONS O

Cl HSiMe2Cl, In(OH)3

(99%)

CHCl3, rt, 2 h O2 N

O2N

1-(1-Chloroethyl)-4-nitrobenzene [Deoxygenative Chlorination of a Ketone].331 To a mixture of In(OH)3 (0.1 mmol) and p-nitroacetophenone (2.0 mmol) in CHCl3 (4.0 mL) was added ClSiMe2 H (2.4 mmol) under nitrogen. The reaction mixture was stirred for 2 hours at room temperature, and then was poured into EtOAc (50 mL) and washed with saturated aqueous NaHCO3 solution (50 mL). The organic layer was dried over MgSO4 and concentrated under vacuum to yield 99% of 1-(1-chloroethyl)-4-nitrobenzene. The physical and spectral data of the product were in excellent accord with known values. Et2MeSiH, PhNCO [Rh(cod){P(OPh)3}2]OTf

O

CH2Cl2, 45°, 13 h

OMe

O Ph

N H

O OMe (88%)

Methyl 2-(Phenylcarbamoyl)butanoate [Hydrocarbamoylation of an α,βUnsaturated Ester].475 To a solution of [Rh(cod){P(OPh)3 }2 ]OTf (9.9 mg, 0.01 mmol) in CH2 Cl2 (4 mL) was added a mixture of phenyl isocyanate (121 mg, 1.0 mmol), methyl crotonate (210 mg, 2.1 mmol), and Et2 MeSiH (205 mg, 2.0 mmol) in CH2 Cl2 (2 mL). The resulting mixture was heated at reflux for 13 hours under a nitrogen atmosphere. The solvent was removed under reduced pressure and the residue was purified by flash column chromatography on SiO2 (4 : 1 hexane/EtOAc) to afford methyl 2-(phenylcarbamoyl)butanoate: 194 mg, 88%; mp 76.0–77.0◦ (hexane/EtOAc); IR (CCl4 ) 3371, 1722, 1689 cm−1 ; 1 H NMR (CDCl3 ) δ 8.74 (br s, 1H), 7.54 (d, J = 8.4 Hz, 2H), 7.30 (dd, J = 8.4 and 7.5 Hz, 2H), 7.10 (t, J = 7.5 Hz, 1H), 3.76 (s, 3H), 3.32 (t, J = 7.3 Hz, 1H), 2.03 (dq, J = 7.4 and 7.3 Hz, 2H), 0.99 (t, J = 7.4 Hz, 3H); 13 C NMR (CDCl3 ) δ 172.7, 166.3, 137.4, 128.8, 124.3, 119.9, 54.9, 52.5, 24.9, 11.8. Anal. Calcd for C12 H15 NO3 : C 65.14; H 6.83; N 6.33. Found: C 65.30; H 6.57; N 6.28. OMe Et3SiH, SnBr2, MeCOBr OMe

CH2Cl2, rt, 3 h

Br

(89%)

Benzyl Bromide [Reductive Bromination of an Acetal].506 To a suspension of tin(II) bromide (5.1 mg, 0.02 mmol) and benzaldehyde dimethyl acetal (54.8 mg, 0.36 mmol) in CH2 Cl2 (2.5 mL) were added successively Et3 SiH (65.0 mg, 0.56 mmol) and acetyl bromide (96.8 mg, 0.79 mmol) in CH2 Cl2 (1 mL) at room temperature under an argon atmosphere. The mixture was stirred for 3 hours at room temperature and quenched with a phosphate buffer (pH 7).

ORGANOSILICON HYDRIDE REDUCTIONS

135

The organic materials were extracted with CH2 Cl2 and the extract was dried over Na2 SO4 . Benzyl bromide (54.7 mg, 89%) was isolated by TLC on SiO2 . H N

Br

OEt O

BnO

Et3SiH, TFA –10°, 0.5 h

OCO2Et

H N

Br

OEt O

BnO

(94%)

OCO2Et

2-(Benzyloxy)-3-bromo-5-[(2-ethoxycarbonyl)ethyl]phenyl Ethyl Carbamate [Reduction of an Enamide to an Amide].535 A mixture of Et3 SiH (170 µL, 1.07 mmol) and (E)-2-(benzyloxy)-3-bromo-5-(2-ethoxycarbonyl) vinyl)phenyl ethyl carbamate (32 mg, 0.69 mmol) was cooled to −10◦ in an ice-salt bath under nitrogen, and treated with pre-cooled TFA (1.0 mL) in one portion. The two-phase mixture was rapidly stirred at −10◦ for 0.5 hour, poured into ice-cold saturated aqueous NaHCO3 solution, and worked up by extraction with CH2 Cl2 . The extracts were dried (Na2 SO4 ) and concentrated to give essentially pure title product: 30 mg, 94%; 1 H NMR (CDCl3 ) δ 7.5-7.3 (m, 5H), 7.29 (d, J = 2.0 Hz, 1H), 6.96 (d, J = 2.0 Hz, 1H), 4.99 (s, 2H), 4.74 (br t, J = 5.6 Hz, 1H), 4.21 (q, J = 7.2 Hz, 2H), 4.10 (q, J = 7.2 Hz, 2H), 3.38 (dt, J = 5.6 and 6.8 Hz, 2H), 2.74 (t, J = 6.8 Hz, 2H), 1.29 (t, J = 7.2 Hz, 3H), 1.22 (t, J = 7.2 Hz, 3H); 13 C NMR (CDCl3 ) δ 156.5, 152.9, 146.8, 145.1, 136.6, 136.4, 131.1, 128.4, 128.3, 128.2, 122.6, 118.1, 75.5, 65.2, 60.8, 41.7, 35.2, 14.6, 14.1; HRMS (CI) m/z: [M + H]+ calcd for C21 H25 BrNO6 , 466.0865; found, 466.0864.

N

NO2

PMHS, ZnCl2, Et2O rt, 12 h

N H

NO2 (75%)

3-Nitrobenzylamine [Reduction of an Imine to an Amine].539 To PMHS (300 mg) in a 25-mL flask fitted with a septum inlet and magnetic stirring bar was added freshly fused ZnCl2 (270 mg, 5 mmol) in dry Et2 O (5 mL) under a nitrogen atmosphere. After 10 minutes, N -phenyl-3-nitrophenylmethanimine (225 mg, 1 mmol) was added, and the reaction mixture was stirred at room temperature for 12 hours and extracted with 1 M HCl (2 × 15 mL). The aqueous layer was washed with CH2 Cl2 (15 mL) to remove non-amine impurities. The purified aqueous layer was made basic (pH ∼ 10) with 1 N NaOH and extracted with EtOAc (3 × 15 mL). The combined organic layers were washed with water (15 mL) and brine (15 mL), and dried (Na2 SO4 ). The volatiles were removed and the residue was purified by column chromatography to yield 170 mg (75%) of the title product: 1 H NMR (CDCl3 ) δ 7.20 (d, J = 7.5 Hz, 2H), 7.70-6.50 (m, 7H), 3.50 (s, 2H); MS m/z: M+ 228, 136, 106, 91, 77.

136

ORGANIC REACTIONS I

1. TMSCl, NaI, MeCN, 5-10° O

(75%)

2. TMDO, reflux, 0.5 h

Cyclohexyl Iodide [Iodoreduction of an Oxirane to an Iodoalkane].357 A mixture of cyclohexene oxide (1.01 mL, 10 mmol), NaI (2.00 g, 13.3 mmol), and TMSCl (1.92 mL, 15 mmol) in anhydrous MeCN (10 mL) was stirred at 5–10◦ for 2–3 minutes. Then TMDO (1.79 mL, 10 mmol) was added and the mixture was heated at reflux for 0.5 hour. The remaining siloxane products were destroyed by adding 45% aqueous HF (2.0 mL) and heating at reflux for 5 minutes. The reaction mixture was taken up in CH2 Cl2 (30 mL), and the organic layer was washed with water (20 mL), 1 N NaHSO3 (10 mL), and water (20 mL) again. Drying (Na2 SO4 ) and evaporation of the solvents afforded crude cyclohexyl iodide, which was purified by Kugelrohr distillation to give pure product, 1.58 g (75%); bp 180–183◦ ; 1 H NMR (CCl4 ) δ 4.14 (m, 1H), 1.92 (m, 4H), 1.41 (m, 6H). O

O (PPh3)CuH, (R)-DTBM-SEGPHOS PMHS, MeC6H5, –35°, 6 h Ph

(95%) 99.5% ee Ph

(R)-3,3-Dimethyl-5-(2-phenylethyl)cyclohexanone [Asymmetric 1,4-Reduction of an Enone].597 To a 5-mL round-bottomed flask, flame-dried and purged with argon, was added CuHPPh3 (2.3 mg, 7.0 µmol) and (R)-DTBMSEGPHOS (1.9 mg, 1.6 µmol). Toluene (0.60 mL) was added and the solution was cooled to −35◦ . After PMHS (215 µL, 3.3 mmol) was introduced by syringe, 3-(2-phenylethyl)-5,5-dimethylcyclohexenone (192 mg, 0.84 mmol) was added. The mixture was stirred at −35◦ for 12 hours until the reaction was complete as determined by TLC (20% Et2 O/ligroin) and was then quenched by pouring into 3 N NaOH. Ether and water were added, and the mixture was stirred for 2 hours at room temperature. The aqueous layer was extracted with Et2 O (2 x), and the combined organic layers were washed with brine, dried over MgSO4 , filtered, and concentrated. The residue was purified by flash chromatography (10% Et2 O/ligroin) to afford the title ketone as a clear oil: 185 mg (95%), chiral GC (ketal from (R,R)-2,3-butanediol, Chiraldex B-DM 140) showed 99.5% ee. 1 H NMR (CDCl3 , 400 MHz) δ 7.31-7.17 (m, 5H), 2.64 (t, J = 8.2 Hz, 2H), 2.44 (ddd, J = 9.2, 2.0, 2.0 Hz, 1H), 2.21 (d, J = 13.2 Hz, 1H), 2.10 (ddd, J = 13.2, 2.2, 2.2 Hz, 1H), 1.35 (t, J = 12.4 Hz, 1H), 1.09 (s, 3H), 0.88 (s, 3H), 1.99-1.91 (m, 2H), 1.73-1.62 (m, 3H); 13 C NMR (CDCl3 , 125 MHz) δ 25.3, 32.3, 33.2, 34.6, 35.4, 39.3, 45.3, 47.6, 54.7, 126.0, 128.4, 128.6, 142.2, 212.0; HRMS calcd for C16 H22 O 230.1671; found 230.1663. TABULAR SURVEY

A thorough coverage of the literature through 2004 has been carried out based on the search of certain silanes. A small number of additional pertinent articles,

ORGANOSILICON HYDRIDE REDUCTIONS

137

particularly regarding the asymmetric silane reductions that were published later, are included. Tables are organized by the functional group classes undergoing change in the substrates. Table entries are ordered by increasing carbon count of the starting substrate. Protecting groups are included in the carbon count. Unspecified yields are denoted by (—). The following abbreviations are used in the tables: 10-C-6 18-C-6 Ac acac ACHN Ad AIBN An BARF BDE BINAP BINOL BIPHEMP BIPHEP bipy Bipymox Bmpp Bn Boc BOM BOX BPPFA BSA BTAF Bz Cbz cod coe cot Cp Cp* CSA DAST dba DBATO dbpp DBU

10-crown-6 18-crown-6 acetyl acetylacetone 1,1′ -azobis(cyclohexylnitrile) adamantyl azobis(isobutyronitrile) anthracenyl tetrakis[3,5-bis(trifluoromethyl)phenyl]borate bond dissociation energy 2,2′ -bis(diphenylphosphino)-1,1′ -binaphthyl 1,1′ -bi-2-naphthol 2,2′ -bis(diphenylphosphino)-6,6′ -dimethyl-1,1′ -biphenyl 2,2′ -bis(diphenylphosphino)-1,1′ -biphenyl bipyridyl 6,6′ -bis(oxazolinyl)-2,2′ -bipyridine benzylmethylphenylphosphine benzyl tert-butyloxycarbonyl benzyloxymethyl bis(oxazolino) 1′ ,2-bis[diphenylphosphinoferrocenyl]ethyldimethylamine bis(trimethylsilyl)acetamide benzyltrimethylammonium fluoride benzoyl carbobenzyloxy 1,5-cyclooctadiene cyclooctene cyclooctatetraene cyclopentadienyl pentamethylcyclopentadienyl camphorsulfonic acid (diethylamino)sulfur trifluoride dibenzylidene acetone dibutylacetoxytin oxide di-(tert-butylphenyl)phosphite 1,8-diazabicyclo[5.4.0]undece-7-ene

138

DCE de dea dee DIBALH DIPOF DIOP diphos DME DMF DMI DMPU DMSO DMTS dpm dppb dppbz dppe dppf dppfc dppm dppp dr ds dma ebpe EBTHI ee EE EG EH er Fc Fmoc HAp HMDS H-MOP HMPA/HMPT KU-1 LAH Me-DuPHOS MEM

ORGANIC REACTIONS

1,2-dichloroethane diastereomeric excess diethanolamine diethoxyethane diisobutylaluminum hydride [2-(4,5-diphenyl-4,5-dihydro-1,3-oxazolin-2-yl)ferrocenyl]diphenylphosphine (2S,3S)-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane 1,2-bis(diphenylphosphino)ethane (see dppe) 1,2-dimethoxyethane N ,N -dimethylformamide 1,3-dimethyl-2-imidazolidinone 1,3-dimethyl-3,4,5,6-tetrahydro-2-(1H )-pyrimidinone dimethyl sulfoxide dimethylthexylsilyl 2,2,6,6-tetramethylheptane-3,5-dionate (“dipivaloylmethanato”) 1,4-bis(diphenylphosphino)butane 1,2-bis(diphenylphosphino)benzene 1,2-bis(diphenylphosphino)ethane bis(diphenyllphosphino)ferrocene diphenylphosphinoferrocene bis(diphenylphosphino)methane 1,3-bis(diphenylphosphino)propane diastereomeric ratio diastereoselectivity dimethylacetamide N ,N ′ -ethylenebis(1-phenylethylamine) ethylenebis(η5 -tetrahydroindenyl)titanium enantiomeric excess ethoxyethyl electrogenerated 2-ethylhexanoate enantiomeric ratio ferrocene fluorenylmethoxycarbonyl hydroxyapatite hexamethyldisilazane 2-diphenylphosphino-1,1′ -binaphthyl hexamethylphosphoric triamide phenol-formaldehyde sulfocationite lithium aluminum hydride 1,2-bis-(2,5-dimethylphospholano)benzene methoxyethoxymethyl

ORGANOSILICON HYDRIDE REDUCTIONS

MOM Ms mont MPM NBD Nf nmdpp NMP NORPHOS Np NR Ns o-dppb OTFA PE Piv PEHS PMB PMHS PNB PPA PPFA ppf PPHF PPTS PTC P(tm-tp)3 P(tp)3 p-Tol-BINAP PTSA pybox pymox rt SEGPHOS TADDOL TASF TBAF TBAT TBDPS TBS TEA TEAF TES

methoxymethyl methanesulfonyl montmorillonite methoxyphenylmethyl norbornadiene nonaflate (S)-neomenthyldiphenylphosphine N -methylpyrrolidone (−)-(R,R)-2-exo-3-endo-bis(diphenylphosphino)bicyclo[2.2.1]hept-5-ene naphthyl no reaction 4-nitrobenzenesulfonate 1,2-bis(diphenylphosphino)benzene trifluoroacetate phosphatidylethanolamine pivaloyl polyethylhydrogensiloxane p-methoxybenzyl polymethylhydrogensiloxane p-nitrobenzoate polyphosphoric acid [N ,N -dimethyl-1[2-(diphenylphosphino)ferrocenyl]ethylamine 2-[diphenylphosphinoferrocenyl]ethyldimethylamine pyridinium poly(hydrogen fluoride) pyridinium p-toluenesulfonate phase-transfer catalysis tris(2,2′′ ,6,6′′ -tetramethyl-m-terphenyl-5′ -yl)phosphane tris(m-terphenyl-5′ -yl)phosphane 2,2′ -bis(p-tolylphosphino)-1,1′ -binaphthyl p-toluenesulfonic acid pyridinebis(oxazoline) pyridinemono(oxazoline) room temperature (4,4′ -bi-1,3-benzodioxole)-5,5′ -diylbis(diarylphosphine) α,α,α ′ ,α ′ -tetraaryl-1,2-dioxolane-4,5-dimethanol tris(diethylamino)sulfonium difluorotrimethylsilicate tetra-n-butylammonium fluoride tetrabutylammonium triphenyldifluorosilicate tert-butyldiphenylsilyl tert-butyldimethylsilyl triethylamine tetraethylammonium fluoride triethylsilyl

139

140

Tf TFA TFAA TFPB THEATi(OPr-i) THF THP TIPS TMDO TMEDA TMS TMSBr TMSCl TMSI Tol Tr TRAP TRISPHOS Trityl Ts Vi

ORGANIC REACTIONS

trifluoromethanesulfonyl trifluoroacetic acid trifluoroacetic anhydride tetrakis-3,5-bis(trifluoromethylphenyl)borate [tris(hydroxyethyl)amino]titanium(IV)isopropoxide tetrahydrofuran tetrahydropyran triisopropylsilyl 1,1,3,3-tetramethyldisiloxane N ,N ,N ′ ,N ′ -tetramethylethylenediamine trimethylsilyl trimethylsilyl bromide trimethylsilyl chloride trimethylsilyl iodide tolyl triphenylmethyl 2,2′ -bis[(dialkylphosphino)methyl]-1,1′ -biferrocene 2,2′ ,2′′ -tris(2,4,8,10)-tetra-tert-butyldibenzo[d,f ][1,3,2]dioxaphosphepin-6-yl-6-oxy)tri-2-propylamine triphenylmethyl p-toluenesulfonyl vinyl

141

R2P

H

Fe

H

Fe

PPh2

Ph2P

Fe

H

Y Y

NMe2

H

Ar

6

Fe

PR2

SePh

Ar

PPh2

Fe

H NMe 2

19: C6F5

Y

30: Te

29: Se

28: S

18: 4-CF3C6H4

17: 3-CF3C6H4

16: Ph

H

2: n-Pr

1: Et

R

3

SPh

NMe2

PPh2

Ph2P

20

PPh2

NMe2

SPh

H

7

H

Fe

Fe

Fe

H

Fe

31

Fe

Fe

H

Ph2P

Fe

SeR

SPh

n-Pr

9:

OAc

Fe

H

Se

NMe2

Fe

14: 2,4,6-(i-Pr)3C6H2

13: Ph

12: c-C6H11

11: CH2Bu-t

10: n-Bu

allyl

8:

R

PPh2

PPh2

PPh2

21

H

NMe2

4

Fe

H

CHART 1. LIGAND AND CATALYST STRUCTURES USED IN TABLES

32

Se

PR2

H

Fe

Fe

SePh

TePh

R

NMe2

27: Ph

26: i-Pr

25: n-Bu

24: n-Pr

23: Et

22: Me

NMe2

PPh2

H

15

H

5

H PR 2

Fe

Fe

H

142

Fe

H

Se

Fe

NMe2

N

Ph

PPh2

N Ar

O

N

O

Ph

Ar

PR2

Fe

Ar = 3,5-(CF3)2C6H3 46

i-Pr

i-Pr

38

O

33

Se

H

Bn

1-naphthyl

39

44:

O

O

c-C6H11

R

Ph

Ph

Ph2P

43:

NMe2

N

O

47

PPh2

34

N

PPh2

i-Pr

Fe Cp*

N

O

R

45

P

Ph2P

N

O

Fe

N

48

H

N

O

PPh2

PPh2

O

CHART 1. LIGAND AND CATALYST STRUCTURES USED IN TABLES (Continued)

H

42:

41:

40:

R

Ph

t-Bu

i-Pr

Me

R

t-Bu

37:

i-Pr

R 36:

35:

143

N

MeS

67

N Pr-n

O

R

O

N

O

N PPh2

O

N

49

63

N

PPh2

N

Bn

58:

N R

O

Ph

R 57:

O

Ph2P

N

R

O

i-PrS

72: t-Bu

71: i-Bu

70: s-Bu

69: n-Bu

O

N

R

PPh2

Ph

68: i-Pr

R

50

N

O

64

N

N

N

O

N

i-Pr

N

R

O Ph

R

O

N

O

R

N

65

74: c-C6H11

73: Ph

R

N

CH2OTIPS

CH2OTBS

61:

Ph

60:

Et

O

N

53: SePh

52: SPh

59:

R

R 51: SMe

75

N

R

N

Bn

O

O

N

Y

62

N

N

N

Y

N

N

66

O

R

N

O

76

Et

O

56:

55:

54: S

S

O

Y

SMe

Bn

i-Pr

i-Pr

R

144

N

77

R

O

N

Ph

N

O

O

N

N

N

N

N R

78

N

O

Ph

Ph

93:

N

Et

92:

O

Me

R

Ph

91:

bornyl

N

bornyl

O

O

96

84

N

N

N

O

Ph

Ph

79

N

Ph

Ph

N

N

N

N

O

O

O

97

94

N

85

N

N N

N

N

80

O

Ph

O

O

N

Ph

Ph

N

O Ph

R

O

O

N

O

Pr-i

N

N

N

N

N

CHART 1. LIGAND AND CATALYST STRUCTURES USED IN TABLES (Continued)

98

N

95

N

N

N

R

O

R

O

N

N

O

90:

89:

88:

87:

86:

O

Pr-i

Ph

Ph

s-Bu

t-Bu

i-Pr

Me

R

CH2OH CH2OMe

83:

Me

R 82:

81:

145

O

R

PAr2

MeO

Ar

O

O

P

P R

P

OMe

125

Ph

N P

OMe

Ph

122: 3,5-Me2-4-MeOC6H2

Np-2

N

R

R

O 104:

103:

O OR

O

O

R

Ph

Et

R

Ph2P

126

t-Bu

S

O

119: Et

118: Me

(NBD)Rh

OR

112: 2-naphthyl

111: 2,4,6-Me3C6H2

110: 4-MeC6H4

109: Ph

O

Rh Cl3

N

Np-2 Np-2 O

Ph

O

O

Ph

N

O 2-Np

Ph

Ph

Ph

R

O

121: 3,5-Me2C6H3

117: Et

116: Me

108: i-Pr

OR

OR

R

102: Me

107: Ph

R

101: i-Bu

100: s-Bu

99: i-Pr

PAr2

O

O

O

N

O

MeO

Ph

O

P O Ph

Ph

R

N

P O

Rh Cl3

N

Ph Ph

Ph

O

Ph

O

Ph

N

O

Ph

R

O

R

PAr2

PAr2

+

Ph

Ar

Ph

120

Ph

O

Ph

Np-2

2-Np

O

Rh

–

OTf

R

Ar

106: i-Pr

105: Ph

115: 2-naphthyl

114: 4-MeC6H4

113: Ph

Cl

O

124: 3,5-Me2-4-MeOC6H2

Ph

P

Ph

P Ar O

O

Np-2

R

N

P O

O

O

Ph

O

O

Ph

123: 3,5-Me2C6H3

Ph

Ph

Ph

2-Np

O

O

146

Ph

MeO HN

N H

Ph

Ph

153

OMe

HN

NH

147

NH

Ph

R

R

NHPh

148

BnNH

137: Ph

136: n-Bu

135: H

R

R

PhS 127

Ph2PO

Ph2PO

NHBn

NHR

NHR

R

HN

Ar

t-BuS

Ph2PO

NHBn

Ar

R

Ar

Ar 138: 2-MeOC6H4 139: Ph

159

N

N

150: 2,5-(MeO)2C6H3

149: 2-MeOC6H4

Ph

130

158: CH2naphthyl-1

157: c-C6H11

156: neo-C6H13

155: i-Bu

154: H

BnNH

Ar

Ph

NH

Ar

129: PMPS

128: PhS

R

Ph

NH

NHR

Ph

160

N

N

HN

R

151

NH

RNH

Ph

HN

CHART 1. LIGAND AND CATALYST STRUCTURES USED IN TABLES (Continued) R

Ph

Ph

146: Bn

152

NH HN

145: 2,4,6-Me3C6H2

144: 4-MeOC6H4

143: 3-MeOC6H4

142: CH2naphthyl-1

141: (CH2)2OMe

140: H

R

134: 1-naphthyl

133: c-C6H11

132: 4-ClC6H4

131: Ph

Ph

147

H 2N

170

Bn

PhN

O

O 177

P

NH2

OLi

161

O

NHPh

OH

OH

N H 171

OLi

O

Ph

Ar Ar

N N

OLi

Ph

172

O

178

H2N

LiO

H

MeN

NHAr

Ar

Ar

N

Ph

173

HO

N

186: O

O

185: 2,4,6-(MeO)3C6H2

184: 2,4,6-Me3C6H2

183: 2-naphthyl

182: 1-naphthyl

OLi

167: 3,5-Cl2C6H4

166: 3,5-(CF3)2C6H4

165: 3,5-Me2C6H4

164: 3,5-(MeO)2C6H4

163: 4-MeOC6H4

162: Ph

179

N

N Ph

N H

N

174

O

O

187

N

Ar

Ph

Ph

168

OH

H

n-BuN

Ph

N

NHMe

Me

N

Me

N

Ar

OH 175

Ph

H

MeN

O

Ar 181: 1-naphthyl

180: Ph

Ph

169

O

NMePh

NMe2

176

OH

148

i-Pr

i-Pr

O

O

191

O O

200

Ti

196

N

HN

SPh SPh

t-BuO

Ti

NH

HN

192

Cl

Cl

O

O

188

NH

i-Pr

Pr-i

SePh SePh

LiN

X

OBu-t

197

Ti

X

193

LiN

Ti

Ph

O

O

N

Cl

201

Cl

Ti

i-Pr Pr-i

X2 = 1,1'-binaphth-2,2'-diolate

N

NH

O O

N

Ph

(dimer)

Ph

189

N

Ph

Ti

F

Ph

N

202

H

198

Ti

Ti

Ph

F

H

NLi

194

Ti

HN

OPr-i

OPr-i

N

Cl

Me

P Ph2

+

Ti

PPh3

NO

195

NLi

Re

Si

199

Cl

Ti

203

Rh

N

Me

N

Ph

Ph2P

190

(dimer)

N

Ph

CHART 1. LIGAND AND CATALYST STRUCTURES USED IN TABLES (Continued)

PF6–

menthyl

Cl

Cl

R N

N

149 + R N X–

P tol2 c-C6H11 207

Cl

Ru

NO

BF4 Cl BF4

216: 2-Ad

X

N

N

PF6–

215: t-Bu

R

PPh3

Re

+

+ – W(CO)2Cp B(C6F5)4

208

Ph

O

O

217

P

O

+

NO

O

O

209

N

N

PPh3

Re

205 (SReSC)

Ph2P

Rh

Ph2P

O

O

+ Cu –Cl

PF6–

i-Pr

i-Pr

PPh3

P

O

218

O

O

O

O

3

213: X = Cl

X–

212: X = BF4

N

N

PF6–

211: X = Cl

Pr-i

X–

Pr-i

NO

+

210: X = BF4

N

N

Ph

Re

206 (SReSC)

Ph2P

Rh

Ph2P

+

214: Me

204

tol2 P Cl N

Ph2P

Rh

Ph2P

+

150

Si

P

O

O

O

3

Si

(CO)2Ru

219

O

O

Me

225

Si 228

Me

O

Ru(CO)2

B

220

4

–

F

F

F

F

B

OH

OH

C6F5

C6F5

2

4

Ru(CO)2

221

Ru (CO)2 226

(CO)2 Ru

Na+

(CO)2Ru

CF3

CF3

Ph

Ph

230

Ph

Yb(hmpa)4

Si

Si

222

SiPh3

OH

OH

SiPh3

Me

Si

Si Me

O

Si

227

223

229

Me

O

F

F

F

F

Ru(CO)2 Ru (CO)2 O

Me

(CO)2Ru

CHART 1. LIGAND AND CATALYST STRUCTURES USED IN TABLES (Continued)

F

F

B C6F5

C6F5

F

F

4

(CO)2Ru

B C 6F 5

C 6F 5

224

3

Ru (CO)2

4

O

Ru(CO)2

151 I

E

O

NMe2

SiH2

Ph

O

O O – Si

H

A

NMe2

K+

O J

O

H O O – Si

CF3

CF3

F

– Si O

H

Li+

O

B

SiH2

SiH2

CF3

CF3

NMe2

Ph

Ph

CF3 CF3

Bu4N+

O

K

Si

O

CF3

CF3

G

CF3

CF3

CF3

O

– H Si

O

CF3

C

O O – Si H O O

O L

O

H O O – Si

Li+

K+

Li+

CF3

O

– H Si

O

CF3

CHART 2. ORGANOSILANE COMPOUND DESIGNATIONS USED IN TABLES

H

CF3

CF3

D

O

Li+

M

O

Li+

+ Ph3P=N=PPh3

H O O – Si

O O – Si H O O

152

C5

C4-6

2 2 2

OAc

O2CCF3

SC4H9-n 20 h

75 h

75 h

10 h

Time

(39) (31)

20° 20°

15 h

2.5

(35)

20°

2.5

4h

2.5

1.5 h

1h

4

(40)

0.5 h

4

(41)

I

20°

0.1 h 20°

I (—)

D

(15)

(0)

(13)

(80)

R

0°

Time Temp

2.5

x

Et3SiH, TFA (x eq)

rt, 30 min

Et3SiH (1 eq), TFA (2 eq),

50°, 24 h

Et3SiD (1 eq), TFA (2 eq),

50°, 10 h

Et3SiH (1 eq), TFA (2 eq),

PhSiH3, 202

1

OBu-n

or

x

Et3SiH (x eq), TFA, 50°

Conditions

+

(10)

(6)

(2.8)

(10.8)

(6.3)

(—)

II

(—)

(90)

(—)

(—)

II

Product(s) and Yield(s) (%)

TABLE 1. ORGANOSILANE REDUCTION OF ALKENES

R

R

Alkene

233

232

221

203

687

234

Refs.

153

C6

C5-16

RN

1

O

(CH2)5CO2Et (CH2)5CO2Et (CH2)5CO2Et (CH2)5CO2Et Me

Ac

Ac

Ac

Ac

H Me

(CH2)5CO2Et

Ac

R2

H

R2

NR

1

R1

O

60 h 60 h 20 h 20 h

Ph3SiH Ph2SiD2 Ph3GeD Et3SiH

50°, 10 h

Et3SiH (1 eq), TFA (2 eq),

CD2Cl2, –75°, 5 min

Et3SiH, TMSOTf,

KU-1, 55°, 5 h

Et3SiH (1.1-1.2 eq), HCO2H,

HOAc, KU-1, 55°, 5 h

Et3SiH (1.1-1.2 eq), HCO2H,

CH2Cl2, 20°, 30 min

Et3SiH (1.2 eq), 65% HClO4,

20 h

60 h

Et3SiH or Et3SiD

Et3SiH

20 h

1

rt

I

I (92)

I (42)

(83)

(—)

(98)a

(78) 92

50

96 98

rt (65)

95

(30)

50°

50

(70) 94

%I

I + II (70)

1

RN (D)H

(27)

R2

NR + H(D)

1

rt

I

O

(92)

(23)

rt

rt

50°

O

RN (D)H

Time Temp

Et3SiH or Et3SiD

R3SiH

50°, 20 h

R3SiH (1 eq), TFA,

HCl, CH2Cl2, rt

Et3SiH (2 eq), AlCl3 (1.0 eq),

II

O

R2

NR1 H(D)

203

216

208

208

214

688

136

154

C6

Alkene

400 h 3h 6h 24 h 24 h

20° 50° 50° 50° 80°

(52) (40)

–10° 20° 20°

0.5 h 3h 50 h

3 2 2

–10°, 0.5 h

D

(59)

–10°

0.5 h

Et3SiD (1 eq), TFA (2 eq),

I (78)

Temp

Time

I

(20)

2

D

I (93)a

(80)

(87)

(67)

(48)

(75)

I

x

Et3SiH, TFA (x eq)

rt, 72 h

Et3SiH (1 eq), TFA (2 eq),

CD2Cl2, –75°, 5 min

Et3SiH, TMSOTf,

50°, 24 h

Et3SiD (1 eq), TFA (2 eq),

CD2Cl2, –75°, 5 min

Et3SiH, TMSOTf,

Time

Temp

Et3SiH (1 eq), TFA (2 eq)

Conditions

+

+

II

(80)

(—)

(2)

(0.5)

(0)

II

I

(96)a

(90)

I + II (80)

+ II

Product(s) and Yield(s) (%)

TABLE 1. ORGANOSILANE REDUCTION OF ALKENES (Continued)

221

233

232

216

221

216

222

Refs.

155

O

O

I

(41)

1h 3h

4 5

HCl, CH2Cl2, rt, 3 h

Et3SiH (5 eq), AlCl3 (2.5 eq),

HCl, 20°, 1 h I (35)

I (40)

(40)

3.5 h

Et3SiH (3 eq), AlCl3 (2 eq),

O (23)

Time

3

I (—)

I (100)

I (17)

x

HCl, CH2Cl2, rt

Et3SiH (x eq), AlCl3 (3 eq),

20°, 24 h

Et3SiH (10.2 eq), TFA (13.2 eq),

PhSiH3, 202

PMHS, Pd/C, EtOH, 80°

PTSA (1 eq), 40°, 2 h

EtCl2SiH (2 eq), AlCl3 (1 eq),

PTSA (1 eq), 40°, 2 h

EtCl2SiH (2 eq), AlBr3 (1 eq),

50°, 50 h

Et3SiD (1 eq), TFA (2 eq),

50°, 10 h

Et3SiH (1 eq), TFA (2 eq),

20°, 90 h

Et3SiH (2 eq), TFA (4 eq),

I

O

D

O

CF3

(23)

(60)

(—)

(65)

(65)

136

146

136

230

687

316

192

192

221

203

233

156

C7

Alkene

50° 50° 20° 50° 20°

2 2 2.5 10 120 h

10 h

120 h

10 h

10 h

Time

AlCl3 (0.2 eq), CH2Cl2, rt

Et3SiH (1.4 eq), HCl (xs),

CH2Cl2, 20°, 30 min

Et3SiH (1.2 eq), 65% HClO4,

TFA (8 eq), O2NC6H5, 50°, 3 h

Et3SiO(EtHSiO)nSiEt3 (0.1 eq),

O2NC6H5, 50°, 3 h

Et3SiH (1 eq), TFA (8 eq),

Temp

x 1.5

Et3SiH (1 eq), TFA (x eq)

50°, 24 h

Et3SiD (1 eq), TFA (2 eq),

50°, 10 h

Et3SiH (1 eq), TFA (2 eq),

Et3SiH (0.87 eq), TFA, rt, 120 h

KU-1, 55°, 5 h

Et3SiH (1.1-1.2 eq), HCO2H,

Conditions

I

(78)

(72)

(73)

(67)

(40)

I (100)

I (97)

I (94)

I (92)

I

I (—)

D

(80)

(78)

(100)

Product(s) and Yield(s) (%)

TABLE 1. ORGANOSILANE REDUCTION OF ALKENES (Continued)

213

214

207

207

203

221

203

202

208

Refs.

157

(72) (65) (73) (—) (—) (—) (68) (93)

rt rt 60° 60° rt rt 60° 60°

2h 2h 2h 3.5 h 2.5 h 2.5 h 2h 2h

n-BuOH n-C8H17OH n-C12H25OH n-C12H25OH (n-Bu)2O (n-C8H17)2O (n-C8H17)2O n-C4H9OC12H25-n

(37) (5) (0)

MeOH CH2Cl2 I

(77)

HOAc

(50) (25) (5) (0) (0) (35)

CF3CO2H ClF2CCO2H Cl3CCO2H Cl2HCCO2H CH3CO2H 4-MeC6H4SO3H

Acid

acid, 130°, 10 h

Ph2SiH2 (1 eq), O2NC6H5,

(96)

HCO2H HCO2H, HOAc

Solvent

KU-1, 55°, 5 h

I

(100)

60°

1.5 h

Et3SiH (1.1-1.2 eq), HCO2H,

96% H2SO4

Temp

Time

EtOH

I

Solvent

Ph2SiH2 (1.2 eq), H2SO4 (30 eq)

(89)

(70)

(69)

(61)

(65)

(—)

(63)

(62)

(—)

90% H2SO4

134

208

209

158

C8

C7

or

Alkene

CHCl3 4-O2NC6H5

3 5 5h

5h

Time

PMHS, Pd/C, EtOH, 80°

20°, 24 h

Et3SiH (10.2 eq), TFA (20.3 eq),

PhSiH3, 202

BF3•OEt2 (0.4 eq), 20°, 24 h

Et3SiH (5 eq), TFA (10 eq),

20°, 24 h

Et3SiH (5 eq), TFA (10 eq),

PhSiH3, 202

PTSA (1 eq), 40°, 2 h

EtCl2SiH (2 eq), AlCl3 (1 eq),

Solvent

x

TFA (x eq), solvent, 20°

(0.1 mol%),

Et3SiO(EtHSiO)nSiEt3

(0.25 mol%), TFA, 50°, 20 h

Et3SiO(EtHSiO)nSiEt3

Ph2SiH2, O2NC6H5, 130°

Conditions

I

(89)

(52)

I

I (—)

I (22)

I (—)

I (65)

I

I (100)

CF3CO2

+

+

O2CCF3

(88)

II III I + II + III (—), I:II:III = 62:20:17

+

O2CCF3

(3.5)

(98)

Product(s) and Yield(s) (%)

TABLE 1. ORGANOSILANE REDUCTION OF ALKENES (Continued)

O2CCF3

(—)

316

230

687

230

230

687

192

207

207

193

Refs.

159

C8-9

O

R

Cl

I (95)

(47)

Me

R

II

(85)

H R

D

Cl

(—)

(45)

BF3•OEt2 (1 eq), 20°, 24 h

O

O

I

+

(20) +

Et3SiH (6.5 eq), TFA (12.1 eq),

CF3CO2D (2.5 eq), 60°, 7 h

Et3SiH (1.5 eq),

TFA (x eq), 3 h

Et3SiH (1.5 eq),

C6H6, rt, 6 h

PMHS-Pd nanocomposite,

C6H6, rt, 4 h

I (—)

PhSiH3, 202

I

PMHS-Pd nanocomposite,

50°, 10 h

Et3SiH (1 eq), TFA (2 eq),

20°, 24 h

Et3SiH (5.1 eq), TFA (13.1 eq),

Et3SiH (1 eq), TFA (2 eq), 20°

20°, 24 h

Et3SiH (5.1 eq), TFA (13.1 eq),

x

(66)

60° 5

(80)

(85)

(48)

(54) 60°

70°

Temp

1.5

(74)

3.5

2.5

1.5

(72)

1.3

(58)

24 h 240 h

1.5

(13)

2h 144 h

I:II

I + II

Time

O2CCF3

230

251

251

219

219

687

203

230

229

230

160

C9

C8-18

1d 1.5 d 1d 1.5 d 1d

n-C10H21

n-C12H25

n-C14H29

n-C16H33

60°, 10 h

Et3SiH (1 eq), TFA (8 eq),

C6H6, rt, 3 h

PMHS-Pd nanocomposite,

BF3•OEt2 (1 eq), 20°, 24 h

Et3SiH (6.5 eq), TFA (12.1 eq),

Et3SiH (2 eq), TFA (3 eq)

I

(55)

MeO

(73)

I (25) + II (—)

I

I (75)

BF3•OEt2 (1 eq), 20°, 24 h

Et3SiH (6.5 eq), TFA (12.1 eq),

(96)

(97)

(73)

(97)

(90)

(100)

I (70)

R

Et3SiH (2 eq), TFA (3 eq)

Et3SiH, TFA

PMHS, Pd/C, EtOH, 80°

1d

Time

n-C8H17

EtOH

Et3SiH (2 eq), PdCl2 (10 mol%),

Conditions

+

(95)

II

(—)

(25)

(15)

Product(s) and Yield(s) (%)

TABLE 1. ORGANOSILANE REDUCTION OF ALKENES (Continued)

n-C6H13

R

MeO

R

Alkene

689

219

230

231

230

231

233

316

220

Refs.

161

C10

O

O

37 40 42 35 54 58 72 77 83 93

0.60 1.1 1.1 1.1 1.1 1.1 0.55 1.1 1.1

Et3Si (i-C5H11)3Si (c-C5H9)3Si Ph3Si (s-Bu)3Si (t-Bu)2HSi (t-Bu)2MeSi (t-Bu)3Si

R3Si 0.36

I

n-BuH2Si

D

Et2HSi

D

rel % I

H

H

O

O

O

O

x

rt, 95)

Product(s) and Yield(s) (%)

TABLE 4. ORGANOSILANE REDUCTION OF HALOCARBONS

197

195

186

146

185

195

59

195

199

Refs.

193

C6

C5-11

C5

R

Br

O

Br

Cl

Br

Cl

Cl

Br

Br

Cl

Br

Cl

Cl

Cl

Cl

Cl

Br

I (~55%)

I

Et3SiH (5 eq), AlCl3 (0.1 eq)

I

I (57)

R

I (85)

I (72)

I (72)

I (70)

I

I (100)

Et3SiH (0.89 eq), AlCl3, rt, 15 h

20°, 30 min

Et3SiH (2.5 eq), AlCl3 (0.25 eq),

20°, 30 min

Et3SiH (2.5 eq), AlCl3 (0.25 eq),

20°, 30 min

Et3SiH (2.5 eq), AlCl3 (0.25 eq),

20°, 30 min

Et3SiH (2.5 eq), AlCl3 (0.25 eq),

20°, 30 min

Et3SiH (2.5 eq), AlCl3 (0.25 eq),

20°, 30 min

Et3SiH (2.5 eq), AlCl3 (0.25 eq),

20°, 30 min

Et3SiH (2.5 eq), AlCl3 (0.25 eq),

diglyme, 75°, 1.2 h

PPh3 (16 mol%), NaHCO3 (80 mol%),

PhSiH3 (160 mol%), Mo(CO)6 (4 mol%),

+

+ R

(72)

II

(67)

I

II

(7) (58)

(—)

(68)

n-C4H9 n-C8H17

(5) (7)

(64) (72) n-Pr

Et

R

(8)

146

185

189

189

189

189

189

189

189

197

194

C6

Br

Br

Cl

Cl

Br

Cl

Cl

Br

Halocarbon

20°, 30 min

Et3SiH (2.5 eq), AlCl3 (0.25 eq),

20°, 30 min

Et3SiH (2.5 eq), AlCl3 (0.25 eq),

C5H12, 40°, 95)

I

O

O

O

O

I (88)

I (74)

(0)

20 h

0.75

3

(>95)

(80)

OEt

(37)

1.5 h

1.5

3

(75)

(75)

(75)

0.5 h

(>95)

(92)

0.5 h

2

2

Time

2

y

3

x

195

195

197

197

197

195

136

189

189

196

C7

C6-12

R

X

Br

Br

Cl

Br

Cl

Br

Cl

Halocarbon

R3 = Et3, EtMe2, Ph2Et, (C6H11)2Et

AlCl3 (25 mol%),

R3SiH (1.3 eq), CH2Cl2,

20°, 30 min

Et3SiH (6 eq), AlCl3 (0.55 eq),

20°, 30 min

Et3SiH (6 eq), AlCl3 (0.55 eq),

20°, 30 min

Et3SiH (2.5 eq), AlCl3 (0.25 eq),

C5H12, 40°, 95)

Time

2-I 4-I 10 min 25 min

2-Br 2 min

X

Product(s) and Yield(s) (%)

TABLE 4. ORGANOSILANE REDUCTION OF HALOCARBONS (Continued)

Ar

ArOTf

RX

X

Halocarbon

188

201

288

195

Refs.

201

O

O

Cl

Br

Cl

DMSO, Bn3N (1.4 eq), 110 °, 3 h

PMHS, (Ph3P)4Pd (5 mol%), MeCN,

NaHCO3 (110 mol%), C6H6, 80°, 3.25 h

Mo(CO)6 (6 mol%), PPh3 (27 mol%),

PhSiH3 (120 mol%),

PPh3 (0.16 eq), THF, rt, 24 h

Ph2SiH2 (1.4 eq), Pd(OAc)2 (8 mol%),

THF, rt, 0.1 h

PhSiH3 (1.5 eq), (Ph3P)4Pd (8 mol%),

THF, rt, 20 h

Et3SiH (1.5 eq), (Ph3P)4Pd (8 mol%),

THF, rt, 0.5 h

Ph2SiH2 (1.5 eq), (Ph3P)4Pd (8 mol%),

(Ph3P)4Pd (7 mol%), CHCl3, rt, 1 h

Ph2SiH2 (1.3 eq), ZnCl2 (2.8 eq),

THF, 65°, 4.5 h

PPh3 (18 mol%), NaHCO3 (70 mol%),

PhSiH3 (140 mol%), Mo(CO)6 (4 mol%),

Ph2HSi, Ph3Si, (C6H11)2EtSi

R3Si = Et3Si, Et2MeSi, n-BuH2Si,

AlCl3 (25 mol%)

R3SiH (1.2-1.5 eq), CH2Cl2,

I (80)

I (95)

I (70)

I (60)

I (5)

I (73)

I (70)

I

O (90)

(80-95)

199

197

197

197

197

197

197

197

188

202

C8

Ph

Ph

Br

Br

Br

CO2H

O

I

Br

Halocarbon

DMSO, Bn3N (1.4 eq), 60°, 3 h

PMHS, (Ph3P)4Pd (5 mol %), MeCN,

DMSO, Bn3N (1.4 eq), 110°, 18 h

PMHS, (Ph3P)4Pd (5 mol %), MeCN,

rt, 10 min

Et3SiH (1.4 eq), PdCl2 (5-10 mol%),

MeC6H5, 95°, 1.0 h

PPh3 (19 mol%), NaHCO3 (140 mol%),

PhSiH3 (200 mol%), Mo(CO)6 (5 mol%),

C6H6, 80°, 2.0 h

PPh3 (33 mol%), NaHCO3 (130 mol%),

PhSiH3 (150 mol%), Mo(CO)6 (8 mol%),

THF, 65°, 4.5 h

PPh3 (20 mol%), NaHCO3 (150 mol%),

PhSiH3 (210 mol%), Mo(CO)6 (5 mol%),

Conditions

Ph

Ph

I (>95)

I (>95)

Br

CO2H

I

O

(37)

(55)

(>95)

(100)

Product(s) and Yield(s) (%)

TABLE 4. ORGANOSILANE REDUCTION OF HALOCARBONS (Continued)

199

199

195

197

197

197

Refs.

203

C10

C9

Cl

O

O

Br

Br

OTf

Br

80°, 4 h

Et3SiH (1.4 eq), PdCl2 (5-10 mol%),

CH2Cl2, 18-20°, 15 min

H(Ph2Si)4H (0.6 eq), AlCl3 (0.25 eq),

CH2Cl2, 18-20°, 15 min

Et3SiH (1.3 eq), AlCl3 (0.25 eq),

K2CO3 (1.8 eq), THF, rt, 12 h

Ph2SiH2 (3 eq), (Ph3P)4Pd (10 mol%),

MeC6H5, 75°, 12.0 h

PPh3 (24 mol%), NaHCO3 (130 mol%),

PhSiH3 (280 mol%), Mo(CO)6 (65 mol%),

THF, 65°, 2.5 h

PhSiH3 (160 mol%), Mo(CO)6 (11 mol%),

Et3N (2 eq), DMF, rt, 40 min

Et3SiH(2.5 eq), Pd(OAc)2, dppp,

Et3SiH (5 eq), AlCl3 (0.1 eq), HCl

C5H12, 40°, 99)

(>95)

(>95)

(—)

(91)

(0)

(—)

I

R-H I + ROSiEt3 II

I (53) + II (6)

I (70)

Product(s) and Yield(s) (%)

TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS

R

R-OH

C6-C10

C6

Alcohol

II (7)

144

136

136

Refs.

210

C8

C7

OH

OH

OH

OH

Alcohol

CH2Cl2, 0°, 0.5 h

Et3SiH (x eq), Et3SiD (x eq),

CH2Cl2, rt, 1 h

Ph2ClSiH (2 eq), InCl3 (0.05 eq),

I

I (88)

I

Et3SiH (x mol%), TFA (y mol%), 50°, 15 h

I

I

I (94)

Et3SiH (1 eq), acid, rt, 96 h

C6H14 or CH2Cl2, rt, 20 h

Et3SiH (3.0 eq), (C6F5)3B (5 mol %),

CH2Cl2, rt

Et3SiH (3 eq), AlCl3 (1.5 eq),

HCl, CH2Cl2, rt, 45 min

Et3SiH (2 eq), AlCl3 (1.1 eq),

CH2Cl2, rt, 24 h

Ph3SiH (1.2 eq), TFA (6.5 eq),

Conditions

+

I

x

Solvent

D

4-O2NC6H5

kH/kD 1.05 0.99 1.01 0.98

1.0 0.71 0.5

(56)

(94)

x

12

9

y

1.67

0.2

0.5

(80)

CHCl3

(24)

H2SO4/HOAc TFA

Acid

(>95)

(91)

(78)

Product(s) and Yield(s) (%)

TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)

133

172

134

134

145

136

136

127

Refs.

211

C9

R

H

OH

OH

OH

OH

3h 3h

ClCH2CH2Cl 80° ClCH2CH2Cl 80°

Br NO2

Et3SiH, TFA, CH2Cl2

Ph3SiH, TFA, CH2Cl2

BF3, CH2Cl2, rt, 10 min

Ph(t-BuCH2)MeSiH (2-10 mol%),

CH2Cl2, rt, 20 h

Et3SiH (2 eq), BF3•OEt2 (2 eq),

2h

rt

CH2Cl2

OH

Time

Temp

Solvent

Cl

Ph2ClSiH (2 eq), InCl3 (0.05 eq) R

OH

Et3SiD, CH2Cl2, 0°, 0.5 h

I

(95)

(83)

(70)

D

+

(64)

+

H

II

(50)

D

H

+

+

( —)

H

III

H H IV V I + II + III + IV + V (100), I:II:III:IV:V = 95:5:0:0:0

+

OH

(—)

I + II + III + IV + V (100), I:II:III:IV:V = 83:7:0:6:4

R

H

131

131

126

133

172

133

212

C9

HO

H

OH

SMe

CO2Me

OH

OH

S

OH

Alcohol

ClCH2CH2Cl, 80°, 6 h

Ph2ClSiH (2 eq), InCl3 (5 mol%),

CH2Cl2, rt, 1 h

Ph2ClSiH (2 eq), InCl3 (5 mol%),

ClCH2CH2Cl, 80°, 5 h

Ph2ClSiH (2 eq), InCl3 (5 mol%),

C6H14 or CH2Cl2, rt , 20 h

Et3SiH (3.0 eq), (C6F5)3B (5 mol%),

0°, 1 h; 20°, 3 h

Et3SiH, BF3•OEt2, CH2Cl2,

Et3SiH, TFA, CH2Cl2

Ph3SiH, TFA, CH2Cl2

Conditions

H IV

H

II

+

+

H V

H

I (54)

I (90)

I (0)

S

SMe

CO2Me

I

III

I + II + III + IV + V (100), I:II:III:IV:V = 90:6:3:0:1

+

+

(>95)

(36) + S

SMe

CO2Me (—)

I + II + III + IV + V (100), I:II:III:IV:V = 62:13:7:3:15

I

Product(s) and Yield(s) (%)

TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)

172

172

172

145

708

131

131

Refs.

213

C10

O OMe

OH

OH

OH

Cl

OH

70° 80° 63° 80°

DCE C6H14 C6H6 THF MeCN

InCl3 InCl3 InCl3 InCl3 InCl3

Me2ClSi Ph2ClSi Ph2ClSi Ph2ClSi Ph2ClSi

ClCH2CH2Cl, 80°, 4 h

Ph2ClSiH (2 eq), InCl3 (0.05 eq),

ClCH2CH2Cl, 80°, 4 h

Ph2ClSiH (2 eq), InCl3 (0.05 eq),

rt

DCE

InCl3

Et3Si

I (74)

I (76)

80°

80°

DCE

(0)

(0)

(20)

(33)

(0)

(0)

(19)

(tr)

80°

BF3•OEt2 DCE

80°

DCE

AlCl3

Ph2ClSi InCl3

80°

DCE

none

Ph2ClSi

Ph2HSi

(5) (23)

80°

DCE

InCl3

Ph2ClSi

(76)

Temp

Solvent

Catalyst

Ph2ClSi

I

OMe

O

R3Si

R3SiH (2 eq), catalyst (5 mol%), 4 h

CH2Cl2, 0°, 30 min

Et3SiH (2 eq), BF3•OEt2 (2 eq),

ClCH2CH2Cl, 80°, 0.5 h

Ph2ClSiH (2 eq), InCl3 (0.05 eq), Cl

(0)

(95)

172

172

172

133

172

214

C10

HO

HO

H

H

OH

OH

OH

OH

OH

Alcohol

Et3SiH, BF3, CH2Cl2, rt, 30 min

Et3SiH, BF3, CH2Cl2, rt, 30 min

CH2Cl2, rt, 30 min

Et3SiH (3.3 eq), BF3,

CH2Cl2, 80°, 3 h

Ph2ClSiH (2 eq), InCl3 (0.05 eq),

TFA (5 eq), 0°, 0.5 h; rt, 3 h

Et3SiH (1.3 eq), NH4F (1.3 eq),

Et3SiH (3 eq), LiClO4, Et2O, rt, 16 h

Et3SiH (3 eq), LiClO4, Et2O, rt, 16 h

Conditions

I (86)

I (99)

(68)

(52)

(100)

(100)

I (97)

OH

Product(s) and Yield(s) (%)

TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)

132

132

126

126, 172

135

173

173

Refs.

215

HO

HO

HO

OH

OH

OH

OH

OH

III (10) +

II (40-45) + IV (40) +

Et3SiH, BF3, CH2Cl2, 5-10 min

II

II (35-40) + IV (35-40) + VI (20-25)

I (15) + II (95:5

(—) + Ph

(16) +

1.5 (38)

(49)

(13)

3.8

1.5 (51)

1.8

(29)

4.3

(22)

(50)

(28) (20)

3.8

(84)

(13)

(3) (40)

4.5

(47)

(42)

(11)

(36)

1.8

(34)

(54)

(12)

(24)

1.4

(72)

(18)

1.8

IV:III

+

(10)

Ph

(64)

Ph

V (41)

IV

H

(21)

(39)

IV

+ t-Bu

(15)

(20)

III

Ph

Product(s) and Yield(s) (%)

TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)

t-Bu

Ph

V

137

133

24

26

Refs.

227

C17

C16

OH

OH

PMP

OH

N

HO

N

N

Ar

Pr-i CH2CN

SMe

OMe CH2CN

CH2CN

Cl

Ar =

SMe

N

HO

(CO)3Cr

N

Fe

MeO

MeO HO

(22)

8.2 4.3 2.0

8 8.1 7.8

Ph3SiH, TFA, CH2Cl2, rt, 0.5 h

CH2Cl2, rt, 1.5 h

Et3SiH (3 eq), TFA (3 eq),

(18)

8.2

4

N

OMe

N

O

SMe

N

(92)

IV

Cl

OAr

N SMe II

N

Ar

(83)

(92)

(—) only isomer

+

+

CH2CN

N

CH2CN

Pr-i

CH2CN

Ar

PMP

(CO)3Cr

(33)

(34)

(15)

y I

I 8.3

SMe

N

2

N

Fe

MeO

x

Et3SiH (x eq), TFA (y eq)

Et3SiH (2 eq), TFA, rt, 3 h

Et3SiH (2.7 eq), TFA (7.8 eq), 80°, 2 h

MeO

N

+

SMe III

N N

II + III + IV (—)

N

OAr

24

182

721

179

720

228

C18

Ph

OEt

OMe

OH

Bu-t

OH

Bu-t

N

OH

O

O

Bu-t

OH

OH

Bu-t

Bu-t

Bu-t

H

Ph

Ph OH

Ph

C17 Ph OH

Alcohol

Et3SiH, TFA, CH2Cl2, rt, 16 h

Et3SiH, TFA, CH2Cl2, rt, 16 h

Et3SiH, TFA, CH2Cl2, rt, 16 h

Et3SiH, TFA, 0-5°, 24 h

CH2Cl2, 0°, 30 min

Et3SiH (2 eq), BF3•OEt2 (2 eq),

CH2Cl2, 0°, 30 min

Et3SiH (2 eq), BF3•OEt2 (2 eq),

Conditions

Ph

Ph

Bu-t

Bu-t

OEt

OMe

O

Bu-

t

Bu-t

N

I

O

O

Ph

Bu-t

H

Ph

Ph

(78)

(80)

(31)

(trace)

+

+

Ph II

t-Bu

Ph

(89)

O OEt

Bu-t (38)

I + II (68), I:II = 73:27

Product(s) and Yield(s) (%)

TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)

153

153

153

722

137

137

Refs.

229

C19

O

R1

Ph

S

(CO)3Cr

MeO

C18-21

N H Cl

OH

Bu-t

OH

OH

Bu-t

OH

R2

O O

N

N

MeO HO

O

OMe OH

EtO2C

HO

N

CH2Cl2, –78°, 12 h; 0°, 10 h

Et3SiH (10 eq), MeSO3H (1 eq),

Et3SiH, TFA, CH2Cl2, rt, 16 h

Et3SiH, TFA, 50°, 48 h

Et3SiH (xs), TFA

Et3SiH (1.1 eq), TFA, rt, 18 h

Et3SiH (xs), TFA, rt, 2 h

OMe

OMe

N H

R1 S

(CO)3Cr

EtO2C

Ph

Bu-t

O

MeO

N

(75)

(86)

Me

H

H

R1

(65)

(—)

(81)

(95)

N

R2

Cl

O O

N

R2

n-C12H25

n-C16H33

n-C15H31

140

153

258

723

486

157

230

O

Ph

MeO (CO)3Cr

OHC

Ph

C19 Ph

O

COH

HO

OH

3

OH

O

O

OH

Alcohol

Et3SiH (4 eq), HOAc, reflux, 40 h

Ph3SiH (3 eq), TFA, rt, 48 h

O

I (80)

I (74)

Ph3SiH (3 eq), TFA, rt, 48 h

Et3SiH (3 eq), HOAc, rt, 48 h

I

3

CH

O

O

O

(89)

I (95)

(59)

Ph

(80)

4-MeC6H4CO2H/HOAc TFA

(82)

(88)

I (98)

(—)

Product(s) and Yield(s) (%)

H2SO4/HOAc

Acid

Ph

(CO)3Cr

MeO

Ph

Et3SiH (1 eq), acid, rt, 30 min

C6H14 or CH2Cl2, rt, 20 h

Et3SiH (3.0 eq), (C6F5)3B (5 mol%),

60°, 4.5 h

Et3SiH (6 eq), TFA (9 eq),

CH2Cl2, rt, 20 h

Et3SiH (1 eq), TFA (17 eq),

Conditions

TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)

29

26

26

26

134

145

352, 725

724

Refs.

231

HO

C20

S

Ts

Bu-t

R

1:1

Ph

Bu-t

OH

OH

Bu-t

OH

Bu-t

Ph

OH

Bu-t

OH R = Me, Et, n-Pr, n-Bu, n-C5H11

O

t-Bu

n-C13H27

C19-23

Ph

t-Bu

OH

Et3SiH, TFA, CH2Cl2, rt, 16 h

Et3SiH, TFA, CH2Cl2, rt, 16 h

Et3SiH, TFA, CH2Cl2, rt, 16 h

Et3SiH, TFA, 50°, 48 h

Et3SiH, TFA, rt

CD2Cl2, rt, 1 h

Et3SiH (3.2 eq), TFA (5.9 eq),

O

Ph

Bu-t

O

I

(90)

(81)

+

(78)

R

(95)

Bu-t

S (—)

Ts

Bu-t

t-Bu

n-C13H27

Ph

t-Bu

+

Ph

Bu-t

n-C13H27

II

R

I + II (73), I:II = 3:2

S (—)

153

153

153

258

726

128

232

C20

HO

O

O

O

Cl

OH

O

OMe O HO

MeO

O

OH

Alcohol

CO2Et

N

CH2Cl2, –78° to 0°

Et3SiH (3 eq), TFA (3 eq),

Et3SiD, TFA, CH2Cl2, rt, 15 min

Et3SiH, TFA, CH2Cl2, rt, 15 min

Ph3SiH (3 eq), TFA, rt, 48 h

Et3SiH (3 eq), TFA, rt, 48 h

Et3SiH (1.1 eq), TFA, rt, 18 h

Conditions

O

O

O

OMe O

D

I (94)

O

Ph

Ph

OMe

Cl

(75)

(88)

(95)

I (68)

(37)

CO2Et

N

Product(s) and Yield(s) (%)

TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)

162

64

64

26

26

486

Refs.

233

C22

C21

O

N

Ar

Et3SiH (3 eq), TFA, rt, 24 h O

N N H

CO2Me

OMe

Bz

N

N H H Me

N

I

Bn

N

Bz

N

N Et3SiH, TFA, rt, 4 h

I (60)

(CO)3Cr

(CO)3Cr

(CO)3Cr

i-Pr

Et3SiH, BF3•OEt2, CH2Cl2, –10°, 1 h

Et3SiH, TFA, CH2Cl2, rt, 1 h

Et3SiH, HPF6, CH2Cl2, –30°, 1 h

Et3SiH, HPF6, CH2Cl2, –30°, 0.25 h

Et3SiH, HPF6, CH2Cl2, –30°, 1 h

CO2Me

OH

OH

OH

i-Pr

OMe

Bz

N

Bn

N

Bz H

N

N H Ar = 3,5-(MeO)2C6H3

Ar

N

OH

H HO Me OH

(CO)3Cr

(CO)3Cr

(CO)3Cr

H

(55.5)

(79)

(69)

(65)

(89)

(52)

729

728

174

727

727

727

727

234

C24

C23

C22

O

OH

O OH O

HO CO2Me

H

N

3

N

F

(CO)3Cr

OH

HO

OH

OMe

CO2Me

OBn

OBn

COH

MeO Ar OH OMe Ar = 2,6-(MeO)2C6H3

O

HO

Me

MeO

Alcohol

Et3SiH, TFA, rt, 15 h

Et3SiH, BF3•OEt2, CH2Cl2, –78° to 0°

Et3SiH (4 eq), HOAc, reflux, 24 h

–20°, 24 h

2. Et3SiH (1.5 eq), BF3•OEt2 (1.1 eq),

1. i-Bu2AlH, hexanes, MeC6H5, –78°

Et3SiH, TFA, CH2Cl2, rt

Ph3SiH (3 eq), TFA, rt, 48 h

Conditions

H

N

F

(CO)3Cr

MeO

O

Me

MeO

Ar

O

N

I

HO

(83)

CO2Me

(65)

(87)

+

OBn

OBn

OMe

OMe

OH

O OH O

CO2Me

3

CH

F

(75)

(—)

Product(s) and Yield(s) (%)

TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)

HO

II

171

I + II (45)

CO2Me

181

29

510

730

26

Refs.

235

C26

C25

Ad

Ad

Ad

Ad

3

N

O

OH

O

OH

OMe

OMe

OH

Se

OH

S

OH

t-BocN

Ph

Ad

Me N

Ad

Ad

Ad

O

Ph

OMe

COH

Et3SiH, TFA (15 eq), CH2Cl2

Et3SiH, TFA, CH2Cl2, –10° to rt, 16 h

2. Et3SiH (3 eq), rt, 1 min

1. HOAc, rt, 24 h

Et3SiH, HOAc

Et3SiH (2.4 eq), TFA, CH2Cl2, rt, 4 h

Et3SiH (2.4 eq), TFA, CH2Cl2, rt, 4 h

Et3SiH (2.3 eq), TFA, CH2Cl2, rt, 3 h

HN

O

H

OMe

OMe

Ad

N

Ad

Me

Ph

Se

I

H

S

I

H

H Ad I

Ad

Ad

I (95)

Ad

Ad

Ad

O

N

O

3

Ad

Ad

II

H

II

H

Ph

OMe

+ Ad

(86)

I (100)

H Ad II

Se

Ad

S

Ad

O Ad

(18)

CH

+

+

+

O Ad

(78)

I + II = (53), I:II = 1:1.8

I + II = (81), I:II = 1:1

I + II = (86), I:II = 2:1

732

731

26

65

160

160

160

236

O

Ad

Ad

Ad

S

Ad

Ad

Ad

Ad

S

Ad

OH

OH

S

OH

OH

Et3SiH (2.4 eq), TFA, CH2Cl2, rt, 4 h

Et3SiH (2.5 eq), TFA, CH2Cl2, rt, 2 h

Et3SiH (2.5 eq), TFA, CH2Cl2, rt, 16 h

I (93)

Ad Ad

S

I

I

H

S

H

H

I

H

Ad I (56)

Ad

Ad

Ad

O

Et3SiH (2.4 eq), TFA, CH2Cl2, rt, 2 h

O

Ad

O

Ad

OH

Et3SiH (3.0 eq), TFA, CH2Cl2, rt, 20 h

Conditions

+

+

+

+

Ad

Ad

Ad

Ad II

H

Ad

H

O

H

S

(27)

O

II

Ad II

Ad

Ad

O

I + II (82), I:II = 1:1

I + II (58), I:II = 1:2

I + II (30), I:II = 3 to 1:1

Product(s) and Yield(s) (%)

TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)

Ad

Ad

C26

Alcohol

160

160

160

160

160

Refs.

237

C28

Ad Ad

CF3

Ad Ad

OMe

Ad Ad

EtO

C27-29

C27

OH

OH

OH

Ph n

OMOM

OH

S

0.52 0.49 0.60 0.41 0.39 5.4

Ph3Si (i-Pr)3Si Et3Si Me2PhSi (TMS)3Si

I:II

I (—) +

0.52

H

Ph2HSi

Ad

Ad

n-C6H13H2Si

R3Si

R3SiH, TFA, CH2Cl2, 3 h

CF3

Ad

Ad

H

H Ad

CF3

Ad

S

159

733

(—)b 161

II (—)

159

159

Ad H Ad II

n = 13 (30)

HO

I + II (—), I:II = 0.53

Ad

+

159

+

H Ad

S

n = 11 (—)

EtO

I + II (—), I:II = 0.72

Ph

+

I + II (—), I:II = 0.32

I

H

n

OMOM

H

S

Ph3SiH, TFA, CH2Cl2, 3 h

Ad Ad

OMe

Ad Ad

EtO

i-Pr3SiH, TFA, CH2Cl2, 3 h

Ph2SiH2, TFA, CH2Cl2, 3 h

Et3SiH, TFA, rt

TFA, CH2Cl2

Et3SiH or PhMe2SiH,

238

Ad

Ad

Ad

Ad

C28-32

C28

I

(74) (79) (57) (94) (83) (66) (77) (71) (85)

5-Me 5-t-Bu 4-Cl 5-Cl 4-F 5-F 4-MeO 3,4,5-Me3

I (—)

H

4-Me

Et3SiH, TFA, CH2Cl2, 3 h

Ad

(34)

(27)

Me2PhSi

Ad

(41)

(8)

Et3Si

+

(28)

(0)

(i-Pr)3Si

(9)

(37)

(0)

(21) R

(58)

(45)

(9)

Ph2HSi Ph3Si

(Me3Si)3Si

(49)

(47)

(12)

Ad Ad

(54)

(31)

(40)

(38)

(36)

(91)

(—)

(—)

n-C6H13H2Si

Ad III

Ad

None

H I

R3Si

Ad II

Ad

OMe + MeO

H

R

Ad

II

(17)

(9)

(11)

(14)

(15)

(8)

(5)

(9)

IV

H II

+

+

Product(s) and Yield(s) (%)

I

R3SiH, TFA, CH2Cl2, –10° to rt, 16 h

Conditions

TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)

H

OH R

R

OH

OMe

Alcohol

I:II = —

Ad

Ad

O

Ad

III

O

159

CF3 158

IV

OH

O

Refs.

239

MeO

Ad

X

OH

OBn

OBn OEt

Ad R, X = H, H; Me, i-Pr

R H HO

C29-33

C29

Et3SiH (large xs), TFA

Et3SiH, TFA, CH2Cl2, 0°, 2 h

R H

MeO

H

Ad Ad

X (—)

OBn

OBn OEt (76)

734

168

240

C32

C31

Ad

Ad

Ad

t-Bu

OH

Ad

Bu-t

OH

Alcohol

23

(TMS)3Si

I:II 2.9 5.8 1.6 NR 6.2 2.5 1.2

R3Si n-C6H13H2Si Ph2HSi Ph3Si (i-Pr)3Si Et3Si Me2PhSi (TMS)3Si

R3SiH, TFA, CH2Cl2, 24 h

4.1

Me2PhSi

I

21 3.4

Et3Si

H

2.5

(i-Pr)3Si

Ad

1.3

Ph3Si

+

0.74

Ph2HSi

Bu-t

H Ad

Ad

t-Bu

Ad

n-C6H13H2Si

Ad I

+

I:II

Ad

Ad

t-Bu

Ad

II

H

II

H

t-Bu (—)

Product(s) and Yield(s) (%)

R3Si

R3SiH, TFA, CH2Cl2, 3 h

Conditions

TABLE 5. ORGANOSILANE REDUCTION OF ALCOHOLS (Continued)

(—)

159

159

Refs.

241

C57

O

O N H

H N

O N H

product ratios were observed for this reaction.

O

O

NH

Et3SiH, TFA

O HO

OH

CO2H

NH

OH

The yield was determined by gas chromatography.

b Various

a

H2 N

H N

Ph

HO

O

H2N

O

H N

O

HN

HN

HN

NH

NH2

NH

O

O

OH

H2N O

H N

O N H

Ph H N O HO

HO

O

(—)

N H

NH CO2H

O

H2N

O

O

O

NH

OH

H N

O

HN

HN

HN

NH

NH2

NH

O

OH O

169

242

C8

C7

C6

C5

O

O

O

Ph

Et

O

O

O

O

OMe

OSiEt3

O

Ether

CH2Cl2, rt, 20 h

Et3SiH (1.1 eq), (C6F5)3B (5 mol%),

CH2Cl2, rt, 20 h

Et3SiH (3.0 eq), (C6F5)3B (5 mol%),

C6H14, rt, 20 h

Et3SiD (1.5 eq), (C6F5)3B (5 mol%),

CH2Cl2, rt, 20 h; then TBAF

Et3SiH (3.0 eq), (C6F5)3B (5 mol%),

CH2Cl2, rt, 20 h

Et3SiH (1.1 eq), (C6F5)3B (5 mol%),

CH2Cl2, rt, 20 h; then TBAF

Et3SiH (3.0 eq), (C6F5)3B (10 mol%),

reflux, 24 h

Et3SiH (2 eq), TFA (10 eq),

CH2Cl2, rt, 20 h

Et3SiH (1.1 eq), (C6F5)3B (5 mol%),

CH2Cl2, rt, 20 h

Et3SiH (1.1 eq), (C6F5)3B (10 mol%),

CH2Cl2, rt, 20 h

Et3SiH (3.0 eq), (C6F5)3B (5 mol%),

Conditions

D Ph

OH

OSiEt3

OH

OH

(88)

(>99) + CH4

(91)

(>99)

(78)

(—) 41% ee

(79)

(60)

(>95) + C3H8

OH

(97)

Product(s) and Yield(s) (%)

OSiEt3

OH

OSiEt3

TABLE 6. ORGANOSILANE REDUCTION OF ETHERS

145

145

145

145

145

144

271

144, 145

144, 145

144, 145

Refs.

243

C11

C10

C9-16

C9

EtO2C

RO

OMe

3

O

OMe

OEt

THF, rt, 3-5 h

PMHS (2 eq), (Ph3P)4Pd (0.01 eq),

CH2Cl2, rt, 20 h

Et3SiH (1.1 eq), (C6F5)3B (5 mol%),

THF, rt, 3-5 h

PMHS (2 eq), (Ph3P)4Pd (0.01 eq),

CH2Cl2, rt, 20 h

Et3SiH (1.1 eq), (C6F5)3B (5 mol%),

reflux, 24 h

Et3SiH (2 eq), TFA (10 eq),

(92) (85) (89) (85) (90)

THPO(CH2)4 AcO(CH2)4 MOMO(CH2)4 TBSO(CH2)4

EtO2C

(87)

TsO(CH2)4

OH

(86)

(96) + CH4

(90)

PMBO(CH2)4

OSiEt3

(92)

BnO(CH2)4

(92) (88)

(90)

4-FC6H4

PrenylO(CH2)4

(89)

2-C10H7 (90)

(85)

2-i-Pr-4-Me-c-C6H9

4-NO2C6H4

(87)

Ph2CH

4-MeOC6H4

(94)

Ph(CH2)3

(>99) + CH4

(7)

PhMeCH

R

ROH +

OSiEt3

OH

270

145

270

145

271

244

C12

C11

OMe OMe

OMe

OMe

OMe

OMe

OMe

Ether

CH2Cl2, rt, 6 h

Et3SiH (6.4 eq), BF3•OH2 (12.8 eq),

CH2Cl2, rt, 24 h

Et3SiD (6.4 eq), BF3•OH2 (12.8 eq),

CH2Cl2, rt, 6 h

Et3SiH (6.4 eq), BF3•OH2 (12.8 eq),

CH2Cl2, rt, 24 h

Et3SiD (6.4 eq), BF3•OH2 (12.8 eq),

CH2Cl2, rt, 10 h

Et3SiH (1.3 eq), BF3•OH2 (4-6 eq),

CH2Cl2, rt, 24 h

Et3SiD (6.4 eq), BF3•OH2 (12.8 eq),

CH2Cl2, rt, 10 h

Et3SiH (1.3 eq), BF3•OH2 (4-6 eq),

Conditions

OMe

OMe

D

OMe

I (26)

D

I

D

D

D

D

D

(37)

(100)

(100)

(100)

(100)

(100)

Product(s) and Yield(s) (%)

TABLE 6. ORGANOSILANE REDUCTION OF ETHERS (Continued)

262

262

262

262

217

262

217

Refs.

245

SMe

SMe

MeO

MeO

MeO

OMe

OMe

OMe

OMe

OMe

OMe

OMe

CH2Cl2, 0°, 24 h

Et3SiH (3-5 eq), BF3•OH2 (12.8 eq),

CH2Cl2, rt, 24 h

Et3SiH (6.4 eq), BF3•OH2 (12.8 eq),

CH2Cl2, rt, 144 h

Et3SiD (6.4 eq), BF3•OH2 (12.8 eq),

CH2Cl2, rt, 48 h

Et3SiH (6.4 eq), BF3•OH2 (12.8 eq),

CH2Cl2, rt, 6 h

Et3SiH (6.4 eq), BF3•OH2 (12.8 eq),

CH2Cl2, rt, 37 h

Et3SiD (6.4 eq), BF3•OH2 (12.8 eq),

CH2Cl2, rt, 24 h

Et3SiH (6.4 eq), BF3•OH2 (12.8 eq),

CH2Cl2, rt, 24 h

Et3SiH (6.4 eq), BF3•OH2 (12.8 eq),

I (100)

SMe

I (50)

MeO

I (95)

MeO

I

D

D

I

D

D

(24)

(80)

(100)

D

D

D

(65)

(60)

263

262

262

262

262

262

262

262

246

C14

C13

C12

TBSO

NMe2

Fe

Ac

N

O

O

SMe OMe

OMe

OMe

Ether

reflux, 24 h

Et3SiH (2 eq), TFA (10 eq),

CH2Cl2, rt, 20 h

Et3SiH (3.0 eq), (C6F5)3B (5 mol%),

CH2Cl2, rt, 20 h

Et3SiH (1.1 eq), (C6F5)3B (5 mol%),

CH2Cl2, –40°, 1-2 h

Et3SiH (2 eq), BF3•OEt2 (2 eq),

CH2Cl2, rt, 24 h

Et3SiH (6.4 eq), BF3•OEt2,

Et3SiH (2 eq), TFA, rt, 20 min

CH2Cl2, 0°, 24 h

Et3SiH (3-5 eq), BF3•OEt2,

Conditions

I (86)

I

TBSO

NMe2

Fe

SMe

Ac

N

OH

(77) +

(3)

(97)

(100)

(88)

(70)

OSiEt3

Product(s) and Yield(s) (%)

TABLE 6. ORGANOSILANE REDUCTION OF ETHERS (Continued)

(93)

271

145

145

521

262

179

263

Refs.

247

C20

C16

C15

n-C10H21

O

O

O

O

O

N H

O

O

CO2H

OBu-t

O N H CO2H

C10H21-n

OPr-i

O

O

OBu-t

rt, 35 min

Et3SiH (2.5 eq), TFA, CH2Cl2,

CH2Cl2, rt, 20 h

Et3SiH (3.0 eq), (C6F5)3B (10 mol%),

CH2Cl2, rt, 20 h

Et3SiH (1.1 eq), (C6F5)3B (10 mol%),

reflux, 24 h

Et3SiH (2 eq), TFA (10 eq),

THF, rt, 3-5 h

PMHS (2 eq), (Ph3P)4Pd (0.01 eq),

CH2Cl2, rt, 45 min

Et3SiH (2.5 eq), TFA,

OH

HO

N H

O

O

(60)

CO2H

OH

(85)

(96) + Me3CH

I (>99)

I

O

O N H

CO2H

(100) + Me3CH

OH

n-C10H22 (93) + n-C10H21OSiEt3 (95)

O

O

O

O

307

144

144

271

270

307

248

C21

C20

O

O

Fe

O

O

HO

H

O

O

O

O

O

Ph

OH

OH

Ether

O

O

O

O

Et3SiH (4 eq), TFA, rt, 3 h

2. Et3SiH (23 eq), rt, 16 h

0°, 30 min

1. BF3•OEt2 (2.25 eq), CH2Cl2,

2. Et3SiH (13.9 eq), rt, 16 h

0°, 1 h

1. BF3•OEt2 (2.25 eq), CH2Cl2,

Conditions

O

O

O

Fe

O

HO

HO

O

O

O

Ph

O

(80)

O

(44)

HO

HO

OH

O

O

OH OH

OH

O

O

+

(36)

Product(s) and Yield(s) (%)

TABLE 6. ORGANOSILANE REDUCTION OF ETHERS (Continued)

OH

O

(44)

179

735

735

Refs.

249

C25

C23

C22

Ph

Ph

MeO

MeO

Ph

OBu-t

O

H

O

O

O

CO2H

OBu-t

OH

OMe

OMe

Et3SiH, TFA

Et3SiH (3 eq), HOAc, rt, 48 h

CH2Cl2, rt, 15 min

Et3SiH (2.5 eq), TFA,

0°, 1 h; rt, 16 h

BF3•OEt2 (1.5 eq), CH2Cl2,

Et3SiH (4.5 eq), MeO

MeO

I (45)

Ph

Ph

MeO

I

H

MeO

Ph

OMe H

OH

O

(80)

O

OMe

OH

OH

O

OH

OH

+

OMe (3)

OMe

484, 736

272

26

CO2H (99) + Me3CH 307

OH

(66)

250

C32

C30-44

(93) (89) (93)

1 min, 16 sec 4 min 24 min

0.01 0.01 0.01

MPM TBDPS MOM

AcO AcO

TrO

AcHN

O OMe

CH2Cl2, rt, 32 min

Et3SiH (3.6 eq), TMSOTf (0.01 eq),

CH2Cl2, rt, 20 h

Et3SiH (3.0 eq), (C6F5)3B (5 mol%),

CH2Cl2, rt, 20 h

OH + Ph3CH

Product(s) and Yield(s) (%)

AcO AcO

HO

I (95)

I

AcHN

O OMe

(86) + Ph3CH

n-C16H34 (98) + n-C16H33OSiEt3 (98)

(93)

1 min, 20 sec

0.01

Bn

Et3SiH (1.1 eq), (C6F5)3B (5 mol%),

(95)

3 min, 30 sec

0.01

Bz

C16H33-n

(99)

2 min

0.02

Piv

O

(96)

Time

8

4 min, 30 sec

RO

0.005

Et3SiH (1.2 eq), Et3SiOTf (x eq),

Ac

OTr

R

8

Conditions

TABLE 6. ORGANOSILANE REDUCTION OF ETHERS (Continued)

CH2Cl2, rt x

n-C16H33

RO

Ether

269

145

145

269

Refs.

251

C92

C90

C47

C42

TrO

BnO BnO

TrO

BzO BzO

TrO

BnO BnO

BnO

TrO BnO

BzO BzO

TrO

OMe

O

BnO

O

BzO

O

O

BnO

O

OTr

OMe

OMe

BnO

BnO

O

AcHN

O

O

OBz

O OTr OBn OBn OTr

OBz

CH2Cl2, rt, 40 min

Et3SiH (2.5 eq), Et3SiOTf (0.01 eq),

CH2Cl2, rt, 5 min

Et3SiH (1.2 eq), Et3SiOTf (0.01 eq),

CH2Cl2, rt, 11 min

Et3SiH (1.2 eq), TMSOTf (0.01 eq),

CH2Cl2, rt, 5 min

Et3SiH (1.2 eq), TMSOTf (0.01 eq),

CH2Cl2, rt, 65 min

Et3SiH (1.2 eq), Et3SiOTf (0.01 eq),

CH2Cl2, rt, 32 min

Et3SiH (1.2 eq), TMSOTf (0.01 eq),

HO

BnO BnO

HO

BzO BzO

HO

BnO BnO

BnO

HO BnO

O OMe

O

BnO

O

BzO

O

BnO

BnO

O

(96)

O

BnO

(86)

O

OBz

O

OH + Ph3CH

+ Ph3CH

OBn OBn OH

OBz

(88) + Ph3CH

(89) + Ph3CH

(99) + Ph3CH

OH

OMe

OMe

Ph3CH

O

I

AcHN

I (92) +

BzO BzO

HO

269

269

269

269

269

269

252

C11

C10

AcO

AcO

AcO

AcO

O

H2N

Ph

OAc

CO2H

S

O

O

[(p-tol)3P]4Pd, 5 h

Ph2SiH2 (2 eq), ZnCl2 (1.9 eq),

I

O

O

O

[(p-tol)3P]4Pd, 4 h

Ph2SiH2 (2 eq), ZnCl2 (2.4 eq),

I OAc

CN

CN

CN

CN

OEt I OAc

OAc

O

OAc

OEt

[(p-tol)3P]4Pd, 3 h

Ph2SiH2 (2.1 eq), ZnCl2 (1.8 eq),

I

+

(87)

+

(—)

+

+

+

+ OMe

II

O

II OAc

O

CN

CN

OEt II OAc

O

II CO2Me

O

OAc

I + II (63), I:II = 75:25

I + II (68), I:II = 50:50

I + II (92), I:II = 44:56

I + II (75), I:II = 33:67

II

(—)

Product(s) and Yield(s) (%)

I + II (98), I:II = 1:1

CO2H

S

OMe

OAc

N

OH

O

[(p-tol)3P]4Pd, 2 h

Ph2SiH2 (2.5 eq), ZnCl2 (2.1 eq),

THF, rt, 4 d

PMHS (2.0 eq), (Ph3P)4Pd (4.0 mol%),

Et3SiH, TFA, CH2Cl2, BF3•OEt2

H2 N

Ph

O

OMe

OAc

THF, rt, 3-5 h

O

CO2Me

O

OAc

N

O

PMHS (2 eq), (Ph3P)4Pd (0.01 eq),

Conditions

TABLE 7. ORGANOSILANE REDUCTION OF ALLYL ESTERS

I CO2Me

O

Allyl Ester

273

273

273

273

196, 273

275

270

Refs.

253

C12

AcO

AcO

Ph

Ph I

AcO

Ph

THF, rt, 13 h; 50°, 2 h

(Ph3P)4Pd (12.0 mol%),

Ph2SiH2 (3.5 eq), ZnCl2 (3-4 eq),

[(p-tol)3P]4Pd, 24 h

Ph2SiH2 (4 eq), ZnCl2 (2.2 eq),

I (90)

I

O

OAc

O

OEt OAc

I

OAc

OEt

O

[(p-tol)3P]4Pd, 3 h

+

CN

(93)

(58)

+

I + II (100), I:II = 6:4

Ph

I + II (99), I:II = 1:1

O Ph2SiH2 (1.7 eq), ZnCl2 (2 eq),

I I + II (99), I:II = 1:1

OAc

THF, 20 min

PMHS (2.2 eq), (Ph3P)4Pd (4.6 mol%),

THF, 0°, 24 h

Ph2SiH2 (2.0 eq), (Ph3P)4Pd (10 mol%),

THF, rt, 24 h

PMHS (2.1 eq), (Ph3P)4Pd (4.0 mol%),

(Ph3P)4Pd (7.2 mol%), THF, rt, 30 h

Ph2SiH2 (2.0 eq), ZnCl2 (3-4 eq),

THF, rt, 5 d

PMHS (1.7 eq), (Ph3P)4Pd (5.0 mol%),

PPh3 (20 mol%), THF, 5 d

PMHS (1.75 eq), (Ph3P)4Pd (6 mol%),

OAc

CN

OAc

OAc

OAc

II

O

+

II

OEt

OAc

Ph

(52)

I + II (55), I:II = 25:75

I + II (79), I:II = 6:1

II

(48)

196

273

273

273

196

196

196

196

273

254

C13

C12

OAc

AcO

O

O

O

OAc

OAc

OAc

O

OAc

CN

OAc

CN

THF, 48 h

PMHS (2.5 eq), (Ph3P)4Pd (3.5 mol%),

THF, 1.5 h

PMHS (1.8 eq), (Ph3P)4Pd (3 mol%),

THF, rt, 3-5 h

PMHS (2 eq), (Ph3P)4Pd (0.01 eq),

[(p-tol)3P]4Pd, 80 h

Ph2SiD2 (2.7 eq), ZnCl2 (8.4 eq),

[(p-tol)3P]4Pd, 120 h

Ph2SiH2 (2 eq), ZnCl2 (4 eq),

[(p-tol)3P]4Pd, 24 h

Ph2SiD2 (4 eq), ZnCl2 (8 eq),

D N Boc

AcO

AcO

AcO

D

O

OH

O

OAc

O

OAc

O

OAc

O

D

O [(p-tol)3P]4Pd, 24 h

OAc Ph2SiD2 (2.6 eq), ZnCl2 (5.4 eq),

Conditions

I

CN

+

(100)

+

(—)

I + II (75), I:II = 10:1

CN

(85)

(10)

(26)

(42)

(59)

Product(s) and Yield(s) (%)

TABLE 7. ORGANOSILANE REDUCTION OF ALLYL ESTERS (Continued) OAc

OAc

N Boc

AcO

AcO

AcO

Allyl Ester

II

CN

273

273

270

273

273

273

273

Refs.

255

C15

C14

Ph

AcO

Ph

OAc

OAc

OAc

O

O

n-C8H17

AcO

O

O

O O

[(p-tol)3P]4Pd, 10 h

Ph2SiH2 (3.3 eq), ZnCl2 (5 eq),

Et3SiH (3 eq), LiClO4, Et2O, rt, 16 h

Et3SiH (3 eq), LiClO4, Et2O, rt, 16 h

THF, rt, 1.5 h

PMHS (3.7 eq), (Ph3P)4Pd (8.0 mol%),

[(p-tol)3P]4Pd, 4 h

Ph

Ph

O

O

n-C8H17

I

O Ph2SiH2 (2 eq), ZnCl2 (1.9 eq),

I

CN

O

I (100)

OAc

(Ph3P)4Pd (12.0 mol%), THF, rt, 4 h

Ph2SiH2 (3.5 eq), ZnCl2 (3-4 eq),

THF, rt, 30 h

Ph2SiH2 (2.2 eq), (Ph3P)4Pd (7.2 mol%),

THF, rt, 48 h

PMHS (2.5 eq), (Ph3P)4Pd (3.5 mol%),

OAc

CN

OAc

CN

OAc

O

I

O

O

(92)

O

+

(63)

(48) +

(74)

+

CN

II

O

II OAc

CN

(75)

H

O O

(12)

I + II (65), I:II = 50:50 O

I + II (73), I:II = 1:1

273

173

173

196, 273

273

196

196

196

256

C17

C16

C15

Ph

Ph

AcO

AcO

Ph

O

O

Bz

Bz

O

OAc

OAc

OAc

CO2Et

O

O

Allyl Ester

Br

THF, rt, 1 h

Ph2SiH2 (1.9 eq), (Ph3P)4Pd (5.7 mol%),

THF, 1.5 h

PMHS (1.8 eq), (Ph3P)4Pd (3 mol%),

Et3SiH (3 eq), LiClO4, Et2O, rt, 16 h

[(p-tol)3P]4Pd, 4 h

Ph2SiH2 (2.9 eq), ZnCl2 (2.4 eq),

[(p-tol)3P]4Pd, 4 h

Ph2SiH2 (2.9 eq), ZnCl2 (2.4 eq),

[(p-tol)3P]4Pd, 10 h

Ph2SiD2 (3.7 eq), ZnCl2 (16.9 eq),

Conditions

I

I

I

O

Bz

Bz

CO2Et

O

O

O

D

+

(89)

+

I + II (90), I:II = 1:1

Ph

Ph

Ph

O

Ph

O

+

Ph

CO2Et

Bz

Bz

(5)

II

Br

I + II (79), I:II = 50:50

I + II (79), I:II = 50:50

I + II (89), I:II = 1:1

Br

+

O

II

II

(55)

Product(s) and Yield(s) (%)

TABLE 7. ORGANOSILANE REDUCTION OF ALLYL ESTERS (Continued)

196

196, 273

173

273

273

273

Refs.

257

C40

C26

C20

C18

MeO2C

Bz

O

O

Bz

O

O

NBn2

O

O

NHCbz

O

OAc

MeO2C AcO

TBSO

Ph

AcO

AcO

O O OAc

OAc Et3SiH, TMSOTf, CH2Cl2, 0-20°, 23 h

THF, rt, 3-5 h

PMHS (2 eq), (Ph3P)4Pd (0.01 eq),

THF, rt, 3-5 h

PMHS (2 eq), (Ph3P)4Pd (0.01 eq),

[(p-tol)3P]4Pd, 6 h

Ph2SiH2 (1.6 eq), ZnCl2 (2.4 eq),

Ph

MeO2C O

O

O

NBn2

O

II

O OAc

(87)

+

O

OAc

II

(85)

O

OH

OH

NHCbz

Bz +

Bz

MeO2C AcO

TBSO

I

O

OAc

I

O

+

O

[(p-tol)3P]4Pd, 4 h

O Ph2SiH2 (1.4 eq), ZnCl2 (2.4 eq),

OAc

OAc

OAc

+

Bz

Bz

(16)

(—)

(—)

I + II (91), I:II = 50:50

I + II (94), I:II = 50:50

737

270

270

273

273

258

C7-10

C7

C5

Ar

F

t-Bu

O

O

OH

O

O

OH

OH

OH

Carboxylic Acid

THF, rt

PMHS (3 eq), TBAF (2 mol%),

A, 150-170°

B, >180°

Et3SiH (xs), TFA, TFAA, 60°, 5 h

2. Add acid, 18 h

1,4-dioxane, 20°, 0.5 h

1. EtMe2SiH (4 eq), 201 (1 mol%),

TFAA, 60°, 5 h

Ph2SiH2 (2 eq), TFA (10 eq),

TFAA 60°, 5 h

Et3SiH (2 eq), TFA (10 eq),

Conditions

Ar

I (60)

F

I (80)

t-Bu

O H

(72)

(30)

(70)

(74) (67) (69) (75) (78) (70) (72) (79)

4-ClC6H4 2,4-Cl2C6H3 3,5-Cl2C6H3 3-MeC6H4 4-MeC6H4 2,4-Me2C6H3 3,4,5-(MeO)3C6H2

(82) 4-BrC6H4

Ph

Ar

(46)

O2CCF3

OH

O2CCF3

OH

I

I

Product(s) and Yield(s) (%)

TABLE 8. ORGANOSILANE REDUCTION OF ACIDS

278

284

284

277

280

277

277

Refs.

259

C7-18

C7-11

R

R

Ar

O

O

O

OH

OH

OH

THF, 16 h

PMHS (10 eq), Ti(OEt)4 (100 mol%),

CH2Cl2, rt, 20 h

Et3SiH (6 eq), (C6F5)3B (5 mol%),

CH2Cl2, rt, 20 h

Et3SiH (3.3 eq), (C6F5)3B (5 mol%),

R

RMe

Ar

OH

OSiEt3 (93) (94) (91) (96)

4-BrC6H4 4-IC6H4 4-MeC6H4 2-C10H7

(86) (88) (94) (91)

Bn(CH2)3 Bn(CH2)4 n-C11H23 n-C17H35

(78) (81) (81) (86)

4-O2NC6H4 4-HOC6H4 Bn n-C17H35

Ph

(92)

(37)

Bn(CH2)2

R

(91)

BnCH2

Ph (85)

(93)

4-FC6H4

R

(95)

Ph

Ar

279

281

281, 282

260

C10

C9

C8

C7-18

O

O

O

O

OH

OH

n-C9H19

Ph

Ph

Ar

R

O

OH

OH

OH

Carboxylic Acid

2. Add acid, 6 h

1,4-dioxane, 20°, 0.5 h

1. EtMe2SiH (4 eq), 223 (1 mol%),

A, 150-170°

B, >180°

2. Add acid, 0.5 h

1,4-dioxane, 20°, 0.5 h

1. EtMe2SiH (4 eq), 223 (1 mol%),

CH2Cl2, rt, 20 h

Et3SiH (6.0 eq), (C6F5)3B (5 mol%),

Et3SiH (xs), TFA, TFAA, 60°, 5 h

Ti(OPr-i)4 (14 mol%), THF

PMHS (10 eq),

Conditions

16 h

Ph (86) (69) (76) (70) (88)

30 h 48 h 30 h 16 h

4-MeC6H4 4-MeOC6H4 2-MeOC6H4 n-C17H35

O

4-MeC6H4

OH

H

OH

(63)

16 h

4-O2NC6H4

Time

R

(80)

(50)

(72)

(94)

(45)

4-MeOC6H4 (97)

Ar

I

OH

n-C9H19

I (65)

Ph

Ph

Ph

ArMe

R

Product(s) and Yield(s) (%)

TABLE 8. ORGANOSILANE REDUCTION OF ACIDS (Continued)

280

284

284

280

282

283

279

Refs.

261

C17

C12

C11

n-C16H33

Ph

n-C10H21

Ph

Ph

O

O

OH

OH

O O

O OH

OH

OH

CH2Cl2, rt, 20 h

Et3SiH (6.0 eq), (C6F5)3B (5 mol%),

CH2Cl2, rt, 20 h

Et3SiH (6.0 eq), (C6F5)3B (5 mol%),

CH2Cl2, rt, 20 h

Et3SiH (6.0 eq), (C6F5)3B (5 mol%),

CH2Cl2, rt, 20 h

Et3SiH (6.0 eq), (C6F5)3B (5 mol%),

CH2Cl2, rt, 20 h

Et3SiH (6.0 eq), (C6F5)3B (5 mol%), I

n-C17H36

Ph

n-C11H24

Ph

Ph

(94)

(91)

+

(93)

(93)

II

I + II (—), I:II = 37:63

282

282

282

282

282

262

C7

C3

C2-12

Ph

Ph

EtS

R

O

O

Br

Cl

Cl

Cl

O

O

Acyl Halide

(86) (90) (91) (87) (86) (90) (82) (80)

PhCH=CH 4-O2NC6H4 4-MeOC6H4 2-C4H3O 2-C4H3S Br(CH2)3 Cl(CH2)3 EtO2C(CH2)8

286 109

286

711

281

286

286

I (45)a

(91)

(—)

109

I (—)

Cl

(87)

BnCH2

109

Refs.

A, rt

I (—)

Ph

SiCl3

(90)

Ph

(>95)a

(—)

(—)

t-Bu

Me

R

Product(s) and Yield(s) (%)

Et3SiH, Et2O, reflux

Bn3SiH, Et2O, reflux

MeCN, rt, 1 h; 85°, 0.5 h

Cl3SiH (3 eq), (n-Pr)3N (1 eq),

CH2Cl2, rt, 20 h

PhMe (84)

H

H

I (—)

I

O

O

H

Et3SiH (6 eq), (C6F5)3B (5 mol%),

Ph

EtS

R

O

Et3SiH, AlCl3, Et2O, reflux

Bn3SiH, Et2O, reflux

A, rt

C, rt

Conditions

TABLE 9. ORGANOSILANE REDUCTION OF ACYL HALIDES

263

C9

C8

C7

EtO

Cl

Cl

Cl

O

Cl

Cl

X = Cl, Br

X Bn3SiH, Et2O, reflux

C, rt

C, rt

A, rt

C, rt

EtO

H

H

I (89)

H

O

O

O

O

Cl

C, rt

O N

Cl

Cl

O

Et3SiH, AlCl3, Et2O, reflux

O

O

O

Cl

O

O

Cl

O

H

H

H

I

I

N

O

O

Cl

O

O

O

O

I

O

H

H

H

(15)a

H

(—)

(—)

(>95)a

(85)

(89)

286

109

109

109

109

109

286

264

C22

C16

C14

C11

C10

a

O

Cl

O

O

Cl

Cl

Cl

O

8

O

Cl OMe Et3SiH, TFA, CCl4, 15 min

CH2Cl2, rt, 20 h

Et3SiH (4 eq), (C6F5)3B (5 mol%),

CH2Cl2, rt, 20 h

Et3SiH (4.0 eq), (C6F5)3B (5 mol%),

CH2Cl2, rt, 20 h

Et3SiH (2.2 eq), (C6F5)3B (5 mol%),

C, rt

Conditions O 8

n-C16H34

n-C14H30

H

O

O

(95)

(97)

OSiEt3

H

H

OMe

(95)

(85)

(—)

Product(s) and Yield(s) (%)

TABLE 9. ORGANOSILANE REDUCTION OF ACYL HALIDES (Continued)

The yield was determined by NMR analysis.

n-C15H31

n-C13H27

Cl

O

Acyl Halide

285

281

282

281, 282

109

Refs.

265

C4

O

O

O

OEt

Ester

(1.5-3.0 mol%), C6D6, rt, 25 min

PhSiH3 (1.2 eq), Mn(CO)5Br

Et3SiH (2.2 eq), 201 (0.2 mol%), rt, 26 h

(3.0 mol%), C6D6, hν, 20°, 35 min

Ph2SiH2 (1.2 eq), Mn(CO)5SiMe2Ph

(1.5-3.0 mol%), C6D6, rt, 4 h

Ph2SiH2 (1.2 eq), Mn(CO)5Ac

(1.5-3.0 mol%), C6D6, rt, 4 h

Ph2SiH2 (1.2 eq), Mn(CO)4PPh3Ac

(1.5-3.0 mol%), C6D6, rt, 4 h

PhSiH3 (1.2 eq), Mn(CO)5Br

(1.5-3.0 mol%), C6D6, rt, 1.5 h

PhSiH3 (1.2 eq), Mn(CO)5Ac

(1.5-3.0 mol%), C6D6, rt, 15 min

PhSiH3 (1.2 eq), Mn(CO)4PPh3Ac

(3.0 mol%), C6D6, rt, 1.75 h

Ph2MeSiH (1.2 eq), Mn(CO)5Ac

Conditions (84)

+

O (35)

EtOEt ( 99:1

O

O

I (83) cis:trans = 10:90

O

I (90)

O

(79) cis:trans > 99:1

(84) cis:trans = 12:88

(87)

Product(s) and Yield(s) (%)

TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)

306

306

306

306

306

306

Refs.

271

C7

HO

O

O

O

O

O

O

O

O

OH

O

O

OMe

OMe

OEt , SbCl5, TMSCl, SnI2, CH2Cl2, –78°, 30 min

OEt , TrSbCl6(5-30 mol%), CH2Cl2, –78°, 30 min

OEt , SbCl3,

OEt , SbCl5, TMSCl, SnI2, CH2Cl2, –78°, 30 min

OEt , TrSbCl6(5-30 mol%), CH2Cl2, –78°, 30 min

THF, 65°, 0.5 h

(MeO)3SiH (3.5 eq), LiOMe (6 mol%),

THF, 65°, 9.5 h

(MeO)3SiH (3.5 eq), LiOMe (6 mol%),

(EtO)3SiH (2.2 eq), CsF (1 eq), rt, 1 min

2. Et3SiH (1.5 eq), –23°, 2.5 h

1.

OTBS

2. Et3SiH (1.5 eq), –23°, 2.5 h

1.

OTBS

TMSCl, SnI2, CH2Cl2

Et3SiH,

OTBS

2. Et3SiH (1.5 eq), –23°, 2.5 h

1.

OTBS

2. Et3SiH (1.5 eq), –23°, 2.5 h

1.

OTBS

I

OEt

I

O OEt

OEt

HO

HO

OH

OH

I (89) cis:trans > 99:1

O

O

O

I (82) cis:trans = 4:96

O

O

(50)

OH

(63)

(100)

OH

(82) cis:trans > 99:1

(84)

(87) cis:trans = 7:93

294

294

81

306

306

306

306

306

272

C7

S

S

O

O

O

CO2Et

O

O

O

OEt

Ester

OEt , SbCl5, TMSCl, SnI2,

OTBS

OEt , TrSbCl6 (5-30 mol%), CH2Cl2, –78°, 30 min

OEt , SbCl5, TMSCl, SnI2,

OEt , TrSbCl6 (5-30 mol%), CH2Cl2, –78°, 30 min

MeC6H5, rt

Ph3SiH, (C6F5)3B (1 mol%),

2. Et3SiH (1.5 eq), –23°, 2.5 h

1.

OTBS

2. Et3SiH (1.5 eq), –23°, 2.5 h

CH2Cl2, –78°, 30 min

1.

OTBS

2. Et3SiH (1.5 eq), –23°, 2.5 h

1.

OTBS

2. Et3SiH (1.5 eq), –23°, 2.5 h

CH2Cl2, –78°, 30 min

1.

rt, 0.5-2 h

2. (EtO)3SiH (2 eq), ester addition,

THF, –15°, 15 min

1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),

Conditions

I

O

OH

OEt

I

O

OEt

S

CHO

S

(45)

I (81) cis:trans > 99:1

O

(85) cis:trans > 99:1

(91) cis:trans > 99:1

(75)

I (86) cis:trans > 99:1

O

O

Product(s) and Yield(s) (%)

TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)

116

306

306

306

306

290

Refs.

273

C7-28

C7-9

R1

R1

O

O

OR2

R2

R3Si Ph2HSi (EtO)2MeSi (EtO)3Si Ph2HSi (EtO)3Si Ph2HSi (EtO)2MeSi (EtO)3Si (EtO)2MeSi (EtO)3Si Ph2HSi (EtO)2MeSi (EtO)3Si (EtO)3Si Ph2HSi (EtO)2MeSi (EtO)3Si (EtO)3Si (EtO)3Si (EtO)3Si

R2 Et Et Et Et Et Me Me Me Et Et Me Me Me Me Me Me Me menthyl menthyl menthyl

R1 n-C4H9 n-C4H9 n-C4H9 Ph Ph MeO2C(CH2)7 MeO2C(CH2)7 MeO2C(CH2)7 n-C11H23 n-C11H23 H2C=CH(CH2)8 H2C=CH(CH2)8 H2C=CH(CH2)8 H2C=CH(CH2)8 n-C8H17CH=CH(CH2)7 n-C8H17CH=CH(CH2)7 n-C8H17CH=CH(CH2)7 H2C=CH(CH2)8 H2C=CH(CH2)8 n-C8H17CH=CH(CH2)7

R3SiH (x eq), CsF (1 eq)

(EtO)3SiH (1.5 eq), HAp, rt

x

2.2

2.2

2.2

2.2

2.2

1.1

2.2

2.2

2.2

1.1

2.2

2.2

2.2

2.2

1.1

2.2

1.1

2.2

2.2

1.1

rt

60°

rt

rt

120°

140°

60°

rt

80°

140°

60°

100°

rt

120°

140°

100°

140°

rt

120°

140°

Temp

R2

R2

R1

Time

+

Ph OH

72 h

9h

72 h

4h

3h

4h

0.5 h

20 h

48 h

10 h

0.5 h

20 h

12 h

2h

4h

3h

4h

1 min

3h

4h

(80)

(75)

(75)

(90)

(85)

(70)

(70)

(65)

(65)

(70)

(90)

(90)

(65)

(65)

(65)

(65)

(65)

(90)

(90)

(90)

EtO

20 h

n-C5H11 MeO 24 h

R1

I

O

Time

R1

R1

R2

(97)

(44)

R1 II

R2

81

353

274

C8

Br

O

O

O

O

O

O

O

O

O

OEt

CF3

OMe

O

O

O

O

OEt

OMe

Ester

ester addition, –20° to rt, 8 h

2. (EtO)3SiH (2 eq),

THF, –15°, 15 min

1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),

ester addition, rt, 0.5-2 h

2. (EtO)3SiH (3.3 eq),

THF, –15°, 15 min

1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),

TBAF/alumina (1 mol%), MeC6H5, rt

PMHS (5 eq), Cp2TiF2 (2 mol%),

TBAF/alumina (1 mol%), MeC6H5, rt

Cp2Ti(OC6H4Cl-4)2 (2 mol%),

PMHS (5 eq),

TBAF/alumina (1 mol%), MeC6H5, rt

Cp2Ti(OC6H4Cl-4)2 (2 mol%),

PMHS (5 eq),

TBAF/alumina (1 mol%), MeC6H5, rt

PMHS (5 eq), Cp2TiF2 (2 mol%),

EtCl2SiH (2 eq), AlBr3 (1 eq), 20°, 2 h

MeC6H5, 100°, 16 h

Et3SiH, EtI, Et2NH, [RuCl2(CO)3]2,

Conditions

Br

O

OH

I

O

OH

O

OH

I (76)

HO

I

(69)

OH

(89)

(75)

OMe

OSiEt3

(78)

OH

+

OH

(92)

(78)

(88)

OH

OH (14)

Product(s) and Yield(s) (%)

TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)

290

290

301

301, 302

302

301

192

299

Refs.

275 O

O

OMe

OMe

EtI, Et2NH, MeC6H5, 100°, 16 h

Et3SiH (1.5 eq), [RuCl2(CO)3]2,

40-55°, 16 h

(EtO)3SiH (2.5 eq), Ti(OPr-i)4 (5 mol%),

ester addition, rt, 0.5-2 h

2. (EtO)3SiH (2 eq),

THF, –15°, 15 min

1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),

n-BuLi (2 eq, 5 mol%), THF, rt, 1 h

PMHS (2.5 eq), Cp2TiCl2,

2. Add ester, 2 h

1,4-dioxane, 20°, 0.5 h

1. EtMe2SiH (4 eq), 223 (1 mol%),

Ph3SiH, (C6F5)3B (1 mol%), MeC6H5, rt

(5 mol%), 40-55°, 6 h

(EtO)3SiH (2.5 eq), Ti(OPr-i)4,

EtMgBr (2 eq), THF, rt, 3 h

PMHS (5 eq), Cp2TiCl2 (15 mol%),

I (71)

I (47)

Br

I (75)

I (53)

Br

OH

OH

CHO

I

+

+

(90)

(88)

(65)

O

H (70)

OH

OEt

(6)

(40)

299

291

290

289

280

116

291

289

276

C8

S

O

O

OEt

OEt

OMe

O

O

Ester

2. Add ester, 24 h

1,4-dioxane, 20°, 0.5 h

1. EtMe2SiH (4 eq), 223 (1 mol%),

EtMgBr (2 eq), THF, rt, 1.5 h

PMHS (2.5 eq), Cp2TiCl2 (2 mol%),

Ti(OPr-i)4 (5 mol%), 40-55°, 16 h

(EtO)3SiH (2.5 eq), PhSiH3 (1.4 eq),

ester addition, rt, 0.5-2 h

2. (EtO)3SiH (2 eq),

THF, –15°, 15 min

1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),

EtMgBr (2 eq), THF, rt, 17.5 h

PMHS (2.5 eq), Cp2TiCl2 (5 mol%),

ester addition, rt, 0.5-2 h

2. (EtO)3SiH (2 eq),

THF, –15°, 15 min

1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),

65°, 24 h

PMHS (2.5 eq), Ti(OPr-i)4 (25 mol%),

(5 mol%), 40-55°, 22 h

(EtO)3SiH (2.5 eq), Ti(OPr-i)4,

EtMgBr (2 eq), THF, rt, 17.5 h

PMHS (2.5 eq), Cp2TiCl2 (5 mol%),

Conditions

I (52)

I (94)

I (75)

I (92)

I (88)

I (8)

S

O

I

+

I

OH

S

OH

OH

(93)

(93)

(75)

OH

S (20)

Product(s) and Yield(s) (%)

TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)

280

289

291

290

289

290

292

291

289

Refs.

277

N

CO2Et

EtO

O

O

O

OEt

OEt

MeMgCl (1 eq)

Zn(EH)2

Me2N(CH2)2OH (1 eq) H2N(CH2)2NH2 (1 eq) Me2N(CH2)2NMe2 (1 eq)

ZnEt2 ZnEt2 ZnEt2

Cp2TiMe2 (10 mol%), 80°, 39 h

PhMeSiH2 (1.5 eq),

(1.5-3.0 mol%), C6D6, rt, 20 min

PhSiH3 (1.2 eq), Mn(CO)5Br

(1.5-3.0 mol%), C6D6, rt, 30 min

OEt

OEt

N II

I

+

OSi(OEt)PhMe

(84)

(84)

(13)

(13)

(78)

(66)

(62)

(8)

(100)

(2)

(96)

(100)

N

EtO

LiAlH4

ZnCl2

PhSiH3 (1.2 eq), Mn(CO)5Br

AlH(Bu-t)2 (1 eq) LiH

Znl2

I

Zn(EH)2

AlEt3 (2 eq)

NaBH4 (1 eq)

Zn(OAc)2

BH3 (1 eq)

NaBH4 (1 eq)

Zn(O2CC6H5)2

Zn(EH)2

NaBH4 (1eq)

Zn(EH)2

Zn(EH)2

Additive

Zinc catalyst

additive, (i-Pr)2O, 70°, 4 h

PMHS (xs), zinc catalyst (0.2 eq),

I + II (90), I:II = 4:1

(68)

(81)

264

295

295

738

278

C8-14

C8-11

R1

Ar

O

(83) (90) (93) (93)

3-MeC6H4

4-MeC6H4

2,4-Me2C6H3

Temp 23 23 65 65 65 65 70 40 70 40

x 100 100 100 100 25 25 25 100 25 100

R2 Et Et Me Et Me Et Me Me Me Me

Br(CH2)5

I(CH2)5

2-FC6H4

2-BrC6H4

4-MeOC6H4

n-C9H19

CH2=CH(CH2)8

CH C(CH2)8

1-adamantyl

t-BuO2C(CH2)7

OR2

5.5 h

24 h

22 h

24 h

24 h

24 h

1.25 h

2h

24 h

24 h

Time

(94)

3,5-Cl2C6H3

(56)

(>99)

(63)

(78)

(93)

(89)

(87)

(80)

(79)

(87)

OH

(81)

(97)

2,4-Cl2C6H3

3,4,5-(MeO)3C6H2

(96)

4-ClC6H4

OH

(95)

R1

Ar

4-BrC6H4

PMHS (2.5 eq), Ti(OPr-i)4 (x mol%)

THF, rt

PMHS (3 eq), TBAF (2 mol%),

Ph

Ar

OMe

Conditions

Product(s) and Yield(s) (%)

TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)

R1

O

Ester

292

278

Refs.

279

C9

C8-19

Br

R

O

1 1

10 10 10 10 10 10 10 5 2 10

BnCH2 (E)-PhCH=CH 4-O2NC6H4 4-HOC6H4 4-MeOC6H4 n-C11H23 n-C17H35 n-C17H35 n-C17H35 n-C17H35

O

O

O

O

O

O

1

10

Bn

O2CCF3

1

80 h

16 h

16 h

16 h

16 h

16 h

16 h

16 h

5h

16 h

8h

5h

Time

TBAF/alumina (1 mol%), MeC6H5, rt

PMHS (5 eq), Cp2TiF2 (5 mol%),

TBAF/alumina (1 mol%), MeC6H5, rt

Cp2Ti(OC6H4Cl-4)2 (2 mol%),

PMHS (5 eq),

CH2Cl2, rt, 20 h

Et3SiH (6.0 eq), (C6F5)3B (5 mol%),

AlCl3 (0.5 eq), 40°, 2 h

EtCl2SiH (2 eq),

AlBr3 (0.25 eq), 40°, 2 h

EtCl2SiH (2 eq),

0.5

1

0.5

1

1

1

1

1

y

x 10

Ph

THF

PMHS (x eq), Ti(OPr-i)4 (y eq),

OMe R

(87)

(92)

(93)

(98)

(89)

(88)

(81)

(84)

(82)

(65)

(76)

Br

O

OH

O

(69)

+

(>99)

(87)

(88)

OH

OSiEt3

OH

(86)

I I (84)

R

OH

(2)

301, 302

301, 302

282

192

192

279

280

C9

O2N

Br

R

Bn

O

OEt

O

OEt

OEt

OEt

O

O

O

OEt

OMe

O

Ester

Ti(OPr-i)4 (5 mol%), 40-55°, 20 h

(EtO)3SiH (1.3 eq), PhSiH3 (1.4 eq),

EtMgBr (2 eq), THF, rt, 3 h

PMHS (2.5 eq), Cp2TiCl2 (15 mol%),

ester addition, rt, 0.5-2 h

2. (EtO)3SiH (3.3 eq),

THF, –15°, 15 min

1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),

CsF (1 eq), 60°, 30 min

(88)

+

R

O2 N

Br

R

OH

OH

(75)

(40)

NH2

OH

(88) (81)

OH

(9)

291

289

290

83

82, 83

I (90)

OH

(81)

278

(EtO)3SiH (2.3 eq),

OH

(76)

289

288

I

OH

(88)

Refs.

I (86)

Bn

OH

Product(s) and Yield(s) (%)

[HSi(OEt)4]K, THF, rt, 8-15 h

DMSO, 80°, 6.5 h

PMHS (1.2 eq), KF•2H2O (1.3 eq),

PMHS (3 eq), TBAF (2 mol%), THF, rt

EtMgBr (2 eq), THF, rt, 5 h

PMHS (2.5 eq), Cp2TiCl2 (5 mol%),

Conditions

TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)

281

N

AcO

Ar

Ph

Ph

Ph

Ph

N

O

+

CO2Et

OEt

O

OMe

OMe

OMe

OMe

OMe

CO2Et

O

OH

O

OH

O

O

OH

Ph

O OMe

C6D6, rt, 12 h

Mn(CO)4PPh3Ac (3.0 mol%),

PhSiH3 (1.2 eq),

TMSOTf (3.1 eq), CH2Cl2, rt, 20 h

Et3SiH (5.0 eq), TiCl4 (1.5 eq),

C6D6, rt, 30 min

Mn(CO)4PPh3Ac (3.0 mol%),

PhSiH3 (1.2 eq),

Cp2TiMe2 (10 mol%), 6 d

PhMeSiH2 (1.5 eq),

Cp2TiMe2 (10 mol%), rt, 24 h

PhMeSiH2 (1.5 eq),

(1.5-3.0 mol%), C6D6, rt, 25 min

PhSiH3 (1.2 eq), Mn(CO)5Br

THF, 65°, 9.5 h

(MeO)3SiH (3.5 eq), LiOMe (6 mol%),

THF, 65°, 9.5 h

(MeO)3SiH (3.5 eq), LiOMe (6 mol%),

THF, rt

PMHS (3 eq), TBAF (2 mol%),

EtO

Ar

Ph

N I

N

I

OH

I (78)

Ph

Ph

OH

+

Ph

(70)

OH

(94)

OMe

OMe

(40) (72)

(12)

N

(20)

I + II (100), I:II = 3:2

4-O2NC6H4

N II

(80)

+

+

4-BrC6H4

Ph

Ar

(83)

OSi(OEt)PhMe

(80)

(—)

(90) >95% ee

OSi(OEt)PhMe

OEt

OH

OH

295

297

295

264

264

295

294

294

278

282

C9-15

C9-10

C9

R

1

X

OEt

2

SEt

SEt

O

OMe

OEt

OR

O

O

O

O

PhS

Ph

Ph

Ph

O

O

O

OEt

Ester

PPh3 (5 eq), THF, rt

Ph2SiH2 (3 eq), catalyst (1.25 mol%),

Ph3SiH (1 eq), (C6F5)3B (2 mol%)

acetone, rt, 30-60 min

Et3SiH (2-3 eq), Pd/C (2-5 mol%),

acetone, rt, 30-60 min

Et3SiH (2-3 eq), Pd/C (2-5 mol%),

MeC6H5, rt

Ph3SiH, (C6F5)3B (2 mol%),

EtI, Et2NH, MeC6H5, 100°, 16 h

Et3SiH (1.5 eq), [RuCl2(CO)3]2,

MeC6H5, rt

Ph3SiH, (C6F5)3B (2 mol%),

Conditions

R1

X

PhS

Ph

Ph

Ph

H

H

H

OH

O

O

O

CHO

O

OEt

OSiPh3

(75)

(91)

X = Me, Cl, NO2 (—)

X = H (80)

(78)b

(80)c

(65)

OEt

OSiPh3

Product(s) and Yield(s) (%)

TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)

293

115

300

300

116

299

116

Refs.

283

C10

(95)

6h 72 h 6h 72 h

[RhCl(cod)]2 RhCl(PPh3)3 [RhCl(cod)]2 RhCl(PPh3)3 [RhCl(cod)]2

i-Bu i-Bu i-Pr i-Pr O O

n-C9H19

n-C9H19

n-C11H23

n-C11H23

O

O

O2CCF3

CH2CN

N

OAc

O

OBu-t

ester addition, –20° to rt, 8 h

2. (EtO)3SiH (2 eq),

THF, –15°, 15 min

1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),

TFA (13 eq), rt, 1 h

Et3SiH (1.2 eq),

MeC6H5, rt

TBAF/alumina (1 mol%),

PMHS (5 eq), Cp2TiF2 (2 mol%),

TBAF/alumina (1 mol%), MeC6H5, rt

Cp2Ti(OC6H4Cl-4)2 (2 mol%),

PMHS (5 eq),

HO

O

OAc

I

CH2CN

N

(63)

(80)

I (97)

F

(92)

72 h

[RhCl(cod)]2

Et

n-C9H19

MeO

O

F

(98)

72 h

[RhCl(cod)]2

n-C10H21

Me

O

(94)

72 h

[RhCl(cod)]2

Et

Bn

Ph3SiH, O2NC6H5, 80°, 13 h

(92)

72 h

RhCl(PPh3)3

Et

Br(CH2)6

O2CCF3

(92)

24 h

[RhCl(cod)]2

Et

Br(CH2)6

n-C7H15

(92)

72 h

RhCl(PPh3)3

Et

Ph

(66)

(56)

24 h

[RhCl(cod)]2

Et

Ph

(70)

Time 144 h

Catalyst

R2

R1

O

O

(90)

OBu-t

(81)

OH

(87)

(96)

290

739

301

301, 302

193

284

C11

C10-11

C10

O

O

OMe

OMe

O2CCF3

O OAc

OMe

CO2Me

O

OMe

O

OEt

O

O

CH2CO2Me

N

OMe

N Boc

Bn

O

Ar

Ph

Ph

Ph

Ph

Ester

TBAF/alumina (1 mol%), MeC6H5, rt

PMHS (5 eq), Cp2TiF2 (2 mol%),

TBAF/alumina (1 mol%), MeC6H5, rt

Cp2Ti(OC6H4Cl-4)2 (2 mol%),

PMHS (5 eq),

Et3SiH (1.2 eq), TFA (13 eq), rt, 1 h

EtMgBr (2 eq), THF, rt, 23 h

PMHS (2.5 eq), Cp2TiCl2 (5 mol%),

TMSOTf (3.1 eq), CH2Cl2, rt, 20 h

Et3SiH (5.0 eq), TiCl4 (1.5 eq),

THF, rt

PMHS (3 eq), TBAF (2 mol%),

THF, 65°, 9.5 h

(MeO)3SiH (3.5 eq), LiOMe (6 mol%),

2. Add ester, 0.5 h

1,4-dioxane, 20°, 0.5 h

1. EtMe2SiH (2.4 eq), 223 (1 mol%),

40-55°, 10 h

Ti(OPr-i)4, (5 mol%),

(EtO)3SiH (2.5-3.0 eq),

Conditions

I (87)

Bn

O

OAc

OH

OMe

OH

OH

OH

OH

O I

OH

CH2CO2Me

N

OMe

N Boc

Ar

Ph

Ph

Ph

Ph

(93)

(80)

(70)

4-MeOC6H4

Ph

Ar

(84)

(76)

(97)

(89)

(89)

(75)

Product(s) and Yield(s) (%)

TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)

301

301, 302

739

289

297

278

294

280

291

Refs.

285

Ph

O

CO2Me

O

OEt

O OMe

2. Add ester, 1 h

1,4-dioxane, 20°, 0.5 h

1. EtMe2SiH (2.4 eq), 2 (1 mol%),

EtMgBr (2 eq), THF, rt, 23 h

PMHS (2.5 eq), Cp2TiCl2 (5 mol%),

ester addition, –20° to rt, 8 h

2. (EtO)3SiH (1.2 eq),

THF, –15˚, 15 min

1. Cp2TiCl2 (5 mol%), n-BuLi (10 mol%),

Ti(OPr-i)4 (100 mol%), 65°, 8 h

PMHS (2.5 eq),

EtMgBr (2 eq), THF, –78° to rt, 1.5 h

PMHS (2.5 eq), Cp2TiCl2 (5 mol%),

I (55)

I (94)

Ph I

O

+

OH

Ph

OH

OH

(44)

II

+

OEt

(82)

(58)

HO

(11)

OH

(28)

280

289

290

292

289

286

C11

Ph

O OEt

Ester

2h 5h 21 h 21 h 21 h 24 h 1h 2h 2h 8h 22 h 1h

20° 20° 20° 20° 20° 20° 20° 20° 20° 20° 20° 10°

1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane C6H6 Et2O tetrahydropyran oxepane C5H5N 1,4-dioxane

HMe2Si(CH2)2(Me)2Si Et2MeSi PhMe2Si Ph2MeSi Et3Si (i-Pr)3Si EtMe2Si EtMe2Si EtMe2Si EtMe2Si EtMe2Si EtMe2Si

2. Add ester

I (56)

1h

20°

1. EtMe2SiH (2.4 eq), 224 (1 mol%)

Time

Temp

Ph

1,4-dioxane

+

OEt

Solvent

I

EtMe2Si

Ph

R3Si

2. Add ester

1. R3SiH (2.4 eq), 223 (1 mol%), solvent

Conditions

III

(100)

(0)

(69)

(94)

(100)

(100)

(0)

(7)

(74)

(95)

(100)

(100)

(100)

H

28:0:72

0:0:0

61:0:39

53:0:47

45:16:39

42:0:58

0:0:0

0:100:0

16:0:84

17:0:83

76:0:24

16:0:84

20:0:80

I:II:III

II OSiR3

Ph

% Conversion

+

O

Product(s) and Yield(s) (%)

TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)

280

280

Refs.

287

Ph

Ph

OH

O

O OMe

OEt

1.5 TMSOTf TMSOTf

— 1.5 AgOTf 1.5 AgOTf, TMSCl 3.0, 3.0

5.0 5.0 5.0

z

3.0

3.0

3.0

—

5.0

Co-catalyst

y 3.0 None

x 5.0

co-catalyst (z eq), CH2Cl2, rt, 20 h

Et3SiH (x eq), TiCl4 (y eq),

THF, 65°, 0.5 h

(MeO)3SiH (3.0 eq), LiOMe (6 mol%),

2. Add ester, 1 h

THP, 20°, 0.5 h

1. Et2MeSiH (2.4 eq), 223 (1 mol%),

2. Add ester

1. EtMe2SiH (2.4 eq), 226 (1 mol%)

2. Add ester

1. EtMe2SiH (2.4 eq), 225 (1 mol%)

+

Ph

Ph

(76)

(63)

(—)

(81)

(27)

OH

I (87)

I (40) +

I (34)

(92)

OMe

OH

II (0.8)

II (0.3)

297

294

280

280

280

288

C12

C11-16

C11

Ph

O

O

O

CO2R

O2CCF3

O

O

n-C6H13

Ph

O

n-C7H15

Ester

Ph2SiH2, O2NC6H5, 80°, 7 h

TMSOTf (3.1 eq), CH2Cl2, rt, 20 h

Et3SiH (5.0 eq), TiCl4 (1.5 eq),

TMSOTf (3.1 eq), CH2Cl2, rt, 20 h

Et3SiH (5.0 eq), TiCl4 (1.5 eq),

2. Add ester, 2 h

1,4-dioxane, 20°, 0.5 h

1. EtMe2SiH (4 eq), 223 (1 mol%),

2. Add ester, 3 h

1,4-dioxane, 20°, 0.5 h

1. EtMe2SiH (4 eq), 223 (1 mol%),

Conditions

Ph

O

n-C6H13

n-C7H15

Ph

O

O

(90)

OR

(67)

(39) (79)

i-Pr n-Bu Ph

(67)

c-C6H11 (34)

(78)

(81) Et

Me

R

(73)

(79)

Product(s) and Yield(s) (%)

TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)

193

297

297

280

280

Refs.

289

O

n-C9H19

8

O

O

OMe

OEt

2.5 1.0 2.5 2.5 2.5 1.0 1.0

4 4 4 3 2 3 3 3 24 h

6h

6h

72 h

72 h

72 h

72 h

72 h

Time

23 65 65 23 65 65 23

25 25 100 25 100 100

Ti(OPr-i)4 Ti(OPr-i)4 Ti(OPr-i)4 Ti(OPr-i)4 Ti(OBu-n)4 Ti(OBu-n)4 THEATi(OPr-i)

PMHS PMHS Ph2SiH2 Cl3SiH PMHS PMHS Ph2SiH2

ester addition, –20° to rt, 8 h

2. (EtO)3SiH (2 eq),

n-BuLi (10 mol%), THF, –15°, 15 min

1. (EBTHI)2TiCl2 (5 mol%),

65°, 2.5 h

I (67)

O

65

25 100

Ti(OPr-i)4

PMHS

PMHS (2.5 eq), Ti(OPr-i)4 (100 mol%),

Temp

x

Catalyst

I

n-C9H19

Silane

Silane (2.5 eq), catalyst (x mol%)

y 5.0

x

PPh3 (2y eq), THF, rt

Ph2SiH2 (x eq), [Rh(cod)]2 (y mol%),

I

OH

8

OH

96 h

2h

24 h

24 h

25 h

2h

25 h

24 h

Time

(56)

(51)

(96)

(72)

(98)

(40)

(92)

(96)

I

(81)

(0)

(90)

(75)

(0)

(100)

(100)

(100)

(100)

290

292

292

293

290

C12

BnO

O

O

6

6

6

O

O

OEt

6

OMe

OMe

OEt

O

O

O

OMe

OEt

Ester

PMHS (10 eq), Ti(OPr-i)4 (1 eq), THF

EtMgBr (2 eq), THF, rt, 1 h

PMHS (2.5 eq), Cp2TiCl2 (5 mol%),

ester addition, –20° to rt, 8 h

2. (EtO)3SiH (2 eq),

THF, –15°, 15 min

n-BuLi (10 mol%),

1. (EBTHI)2TiCl2 (5 mol%),

Ti(OPr-i)4 (5 mol%), 40-55°, 22 h

(EtO)3SiH (2.5 eq), PhSiH3 (1.4 eq),

Ti(OPr-i)4 (5 mol%), 40-55°, 18 h

(EtO)3SiH (2.5-3.0 eq),

Ti(OPr-i)4 (5 mol%), 40-55°, 21 h

(EtO)3SiH (2.5-3.0 eq),

THF, rt

PMHS (3 eq), TBAF (2 mol%),

Ti(OPr-i)4 (5 mol%), 40-55°, 16 h

(EtO)3SiH (2.5-3.0 eq),

MeC6H5, rt

Ph3SiH, (C6F5)3B (1 mol%),

Ti(OPr-i)4 (5 mol%), 40-55°, 10 h

(EtO)3SiH (2.5-3.0 eq),

Conditions

BnO

I (91)

I (83)

O

I (95)

I (69)

6

6

6

OH

I

I

I

6

(95)

(89)

OH

OH

OH

OH

OH

(80)

(70)

(83)

(87)

Product(s) and Yield(s) (%)

TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)

279

289

290

291

291

291

278

291

116

291

Refs.

291

HO

Ph

PhO

Ph

8

9

O

O

O

OAc

O

O

9

O

O

OEt

OMe

SEt

O

OMe

OMe

SEt

Ti(OPr-i)4 (5 mol%), 40-55°, 10 h

(EtO)3SiH (2.5-3.0 eq),

[HSi(OEt)4]K, THF, rt, 8-15 h

PMHS, KF•2H2O, DMSO, 80°, 6 h

(EtO)3SiH, CsF, 60°, 0.5 h

acetone, rt, 30-60 min

Et3SiH (2-3 eq), Pd/C (2-5 mol%),

acetone, rt, 30-60 min

Et3SiH (2-3 eq), Pd/C (2-5 mol%),

TMSOTf (3.1 eq), CH2Cl2, rt, 20 h

Et3SiH (5.0 eq), TiCl4 (1.5 eq),

CH2Cl2, rt, 20 h

Et3SiH (3.3 eq), (C6F5)3B (5 mol%),

9

HO

8

O

O

OAc

O

I (70)

Ph

PhO

Ph

9

I

OH

H

H

O

(84)

(65)

(88)

(94)

(92)

(70)

H

OH

(40)

CH2OSiEt3

291

288

83

83

300

300

297

282

292

R1

6

OEt

SEt

OMe

OBu-t

O

OR2

CO2Me

O

O

O

i-Pr i-Pr Si H O O

H

BocHN

n-C11H23

Ph

C13-16

C13

Ester

TBAF (0.5 eq), CH2Cl2, rt, 15 min

MeOH, rt

2. Camphorsulfonic acid (0.1 eq),

acetone, rt, 30-60 min

1. Et3SiH (2-3 eq), Pd/C (2-5 mol%),

2. Add ester, 3 h

1,4-dioxane, 20°, 0.5 h

1. EtMe2SiH (4 eq), 223 (1 mol%),

2. Add ester, 12 h

1,4-dioxane, 20°, 0.5 h

1. EtMe2SiH (4 eq), 223 (1 mol%),

ester addition, –20° to rt, 8 h

2. (EtO)3SiH (2 eq),

THF, –15°, 15 min

n-BuLi (10 mol%),

1. (EBTHI)2TiCl2 (5 mol%),

DMSO, 80°, 6 h

PMHS (2.3 eq), KF•2H2O (1 eq),

CsF (1 eq), 60°, 30 min

(EtO)3SiH (2.3 eq),

Conditions

R1

O

i-Pr

H

Si

BocHN

n-C11H23

Ph

I (62)

I (70)

OH

OH

O OR2

CO2Me

(70)

(95)

OMe

Me Me Et Me Me

n-Pr n-Pr n-Bu Ph

(97) (95) (98) (98) (96)

1:1 2:1 1:1 1:1 2:1

R2 cis:trans n-Pr

R1

Ph

+ n-C11H23

(80) +

(69)

OH

OMe

OMe

Pr-i

I

6

Product(s) and Yield(s) (%)

TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)

(17)

OBu-t (7)

303

300

280

280

290

83

83

Refs.

293

C15

C14-15

C14

PhO

PhO

Ph

O

O

O

N H

N H

CO2H

CO2Bu-t

OMe

NH2 CO2Bu-t

O

CO2H

CO2Bu-t

CO2R

OEt

CO2Bu-t

N H

CO2Me

HN

n-C11H23

O

O

HO

t-BuO

n-Bu

i-Pr i-Pr Si H O O

CH2Cl2, rt, 35 min

Et3SiH (2.5 eq), TFA,

CH2Cl2, rt, 45 min

Et3SiH (2.5 eq), TFA,

TMSOTf (3.1 eq), CH2Cl2, rt, 20 h

Et3SiH (5.0 eq), TiCl4 (1.5 eq),

2. Add ester, 22 h

THP, 20°, 0.5 h

1. Et2MeSiH (4 eq), 223 (1 mol%),

Et3SiH (xs), TFA, 18°, 18 h; 45°, 3 h

CH2Cl2, rt, 65 min

Et3SiH (2.5 eq), TFA,

TBAF (0.5 eq), AcOEt, rt, 15 min

H2N

PhO

Ph

O

+

(65)

(72)

(100) + Me3CH (—)

t-Bu

i-Pr

R

OEt

Me3CH (—)

(98) + Me3CH (—)

OR

CO2H

NH2 CO2H

O

N H

(96)

(81)

(17) + n-C11H23

CO2H

OH

(87)

OMe CO2H

O

P r-i

CO2H

Si

CO2Me

n-C11H23

O

HN

H2N

n-Bu

O

i-Pr

(75)

307

307

297

280

714

307

303

294

C17

C16

C15

PhO

EtS

BnO

N H

t-BuO

O

N H

O

SMe

OBn

O

O

O

EtS

CO2Bu-t

OMe

O

O

O

O

O

O

Ester

O

MeC6H5, rt

TBAF/alumina (1 mol%),

Cp2Ti(OC6H4Cl-4)2 (3 mol%),

PMHS (5 eq),

Et3SiH, TFA, CH2Cl2

acetone, rt, 30-60 min

Et3SiH (2-3 eq), Pd/C (2-5 mol%),

CH2Cl2, rt, 25 min

Et3SiH (2.5 eq), TFA,

Et3SiH, Pd/C

MeC6H5, rt

(2 mol%), TBAF/alumina (1 mol%),

PMHS (5 eq), Cp2Ti(OC6H4Cl-4)2

Conditions

H2N

H

O

BnO

O

O

CO2H

N H

OBn

OH

O

OH

O

SMe

OMe

HO

O

O

O

(94)

H

(97)

(100) + Me3CH (—)

O

(95) + Me3CH (—)

(—)

(91)

Product(s) and Yield(s) (%)

TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)

302

741

300

307

740

302

Refs.

295

C17-18

MeO

R1

AcO

Ph

N

O

R3

O

O

SEt

R4

CO2Bu-t

R4

CO2H

H (88)

(88)

R2

(100)

MeO H

MeO

MeO

24 h

H H

R3

24 h

18 h

MeO H

R2

H

O

H

O

Me3CH (—)

+

R4 MeO MeO MeO

H MeO MeO

—OCH2O—

R3

Me3CH (—)

Me3CH (—)

24 h

N

Cbz

O

CO2H

+

+

R1

MeO

R1

AcO

Ph

TBSO

(90)

(100)

CO2H

Time

Et3SiH (3 eq), TFA (5 eq)

acetone, rt, 30-60 min

Et3SiH (2-3 eq), Pd/C (2-5 mol%),

acetone, rt, 30-60 min

Et3SiH (2-3 eq), Pd/C (2-5 mol%),

CH2Cl2, rt, 15 min

H2N

H N

Et3SiH (2.5 eq), TFA,

CO2H

OBz

SBu-t

H2N

N

O

H N

CH2Cl2, rt, 45 min

Et3SiH (2.5 eq), TFA,

CH2Cl2, rt, 25 min

Et3SiH (2.5 eq), TFA,

PhO

SBu-t

CO2Bu-t

OBz

CO2Bu-t

SEt

O

H

R2

Cbz

O

TBSO

O

N H

N H

O

N

O

t-BuO

PhO

PhO

(85)

(54)

(80)

(63)

305

300

300

307

307

307

296

C18

C17-19

n-C16H33

O

O

N H

R4

N H

R3

O

t-BuO

PhO

R2

R1

MeO

H

MeO MeO MeO MeO MeO

MeO MeO MeO MeO MeO

O

(73)

(78)

(81)

(73)

(82)

(80)

(83)

(87)

R5

O CO2Bu-t

H2N

CH2Cl2, rt, 20 h

Et3SiH (4.0 eq), (C6F5)3B (5 mol%),

CH2Cl2, rt, 90 min

n-C17H36

O (96)

H N

Et3SiH (2.5 eq), TFA,

SBu-t

H N

CO2Bu-t SBu-t

CH2Cl2, rt, 45 min

SMe H2N

5h

5h

4h

6h

3h

2h

3h

3h

Time

R4

R3 R6

CO2H

(100)

(100)

+

+

Me3CH (—)

Me3CH (—)

Product(s) and Yield(s) (%)

CO2H

CO2H

H N

MeO

MeO

H

MeO

H

H

MeO

H

H

R6 H

H —OCH2O—

R5 MeO

R4

Et3SiH (2.5 eq), TFA,

MeO

H

MeO

MeO

H MeO

MeO

MeO

MeO

MeO

MeO

H

H

H

MeO

MeO

H

R3

H

MeO

MeO

—OCH2O—

R2

R1

R2

R1

SMe

R6

Et3SiH (3 eq), TiCl4, CH2Cl2, 0°

Conditions

TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)

H N

R5

OMe

O

O

O

Ester

282

307

307

305

Refs.

297

C19

O

O

7

H

CO2Me

7

O

OMe

CO2Me

O

O

OMe 1-Np

n-C17H35

O

CO2Me

N SO2Ph

OMe

O

SEt

CO2Me

n-BuLi (2 eq), THF, rt, 1.5 h

PMHS (2.5 eq), Cp2TiCl2 (2 mol%),

65°, 24 h

PMHS (2.5 eq), Ti(OPr-i)4 (100 mol%),

PMHS (10 eq), Ti(OPr-i)4 (1 eq), THF

Et3SiH (xs), TFA

2. Add ester, 6 h

1,4-dioxane, 20°, 0.5 h

1. EtMe2SiH (4 eq), 223 (1 mol%),

CH2Cl2, rt, 20 h

Et3SiH (6 eq), (C6F5)3B (5 mol%),

acetone, rt, 30-60 min

Et3SiH (2-3 eq), Pd/C (2-5 mol%),

TMSOTf (3.1 eq), CH2Cl2, rt, 20 h

Et3SiH (5.0 eq), TiCl4 (1.5 eq),

I (82)

7

H

OMe

n-C17H33

OH

OH

7

Np-1

(78)

(32)

O

OH

(98)

OH

CO2H

I

O

n-C18H38

O

CO2Me

N SO2Ph

H

n-C17H33

(92)

(89)

(90)

+

(43)

OMe

OMe

(22)

289

292

279

304

280

281

300

297

298

C21

C20

C19

BnO

O

7

O

N H

O

n-C17H33

7

7

O CO2Bu-t

BnC(O)NH

7

CH2Cl2, rt, 40 min

O

7

7

O

7

OH

H N

Et3SiH (2.5 eq), TFA,

CH2Cl2, rt, 20 min

Et3SiH (2.5 eq), TFA,

I

O

n-C17H33

I (64)

7

7

SBu-t

N H

CO2Bu-t

ester addition, –20° to rt, 8 h

2. (EtO)3SiH (2 eq),

THF, –15°, 15 min

n-BuLi (10 mol%),

1. (EBTHI)2TiCl2 (5 mol%),

2. Add ester, 6 h

1,4-dioxane, 20°, 0.5 h

1. EtMe2SiH (4 eq), 223 (1 mol%),

THF, rt, 1 h

(EBTHI)TiCl2 (5 mol%), n-BuLi (2 eq),

PMHS (2.5 eq),

65°, 5 h

PMHS (2.5 eq), Ti(OPr-i)4 (100 mol%),

Ti(OPr-i)4 (5 mol%), 40 to 55°, 10 h

(EtO)3SiH (2.5-3.0 eq),

H N

O

OEt

OMe

OMe

Conditions

N H

OMe

(85) + Me3CH (—)

n-C17H33

(78) + Me3CH (—)

CO2H

CO2H

O

OH

(90)

(85)

(92)

(32) +

OH

OH

Product(s) and Yield(s) (%)

TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)

SBu-t

O

7

O

OMe

7

O

7

O

Ester

(22)

307

307

290

280

289

292

291

Refs.

299

C26

C25

C22

C21

O

O

MeO

BnO

N H

N H

Boc

N

DMTSO

O

BnO

O

8

O

H

HN

O

H N

CO2Bu-t

Ph

NH2

CO2Bu-t

OBz

Ph

O

O

O

SEt

SEt

OBn

2

O

Et3SiH (2.5 eq), TFA, CH2Cl2, rt, 35 min

3. TBAF, AcOH, MeOH

2. Camphorsulfonic acid (0.1 eq), MeOH

CH2Cl2, rt, 40 min

1. Et3SiH (5 eq), Pd/C (15 mol%),

MeC6H5, rt

TBAF/alumina (1 mol%),

Cp2Ti(OC6H4Cl-4)2 (5 mol%),

PMHS (5 eq),

CH2Cl2, rt, 30 min

Et3SiH (2.5 eq), TFA,

CsF (1 eq), 60°, 9 h

(EtO)3SiH (1.1 eq),

BnO

O

MeO

DMTSO

HO

BnO

O

N H

O

N

Boc

N H

8

N

HN

O MeO

N

CO2H

Ph

Ph

(98)

O

+

OBn

H

H

(92)

(75)

CO2H

OBz

OH

(83) + Me3CH (—)

(65)

Me3CH (—)

307

300

302

307

79

300

C28

C27

H

O

H N

O

OAc

NH

7

N H SBu-t

O

OBn

O

CO2Bu-t

CO2Bu-t

CH2Cl2, rt, 95 min

Et3SiH (2.5 eq), TFA,

–20°, 24 h

Et3SiH (1.5 eq), BF3•OEt2 (1.1 eq),

(EtO)3SiH, CsF, rt, 72 h

BnMe2SiH, TFA, rt, 20 h

CH2Cl2, rt, 75 min

Et3SiH (2.5 eq), TFA,

Conditions

H2N

O H

n-C8H17

n-C8H17

H2N

H N

O

I

NH

H N

N H SBu-t

O

N H

OBn

CO2H

(100)

(65)

(80)

n-C8H17

OH

SBu-t

O

7

+

Me3CH

(CH2)7CO2Me

+

II

SPh

(—)

Me3CH (—)

I + II (62)

CO2Bu-t (100) +

Product(s) and Yield(s) (%)

(CH2)7CO2Me

OAc

OAc

SPh

O

Ph

TABLE 10. ORGANOSILANE REDUCTION OF ESTERS AND LACTONES (Continued)

(CH2)7CO2Me

SPh

OAc

O

H N

n-C8H17

OAc

N H SBu-t

O

(CH2)7CO2Me

OAc

SPh

t-BuO2NH

O

AcO

n-C8H17

+

n-C8H17

BOCNH

Ph

Ester

307

510

83

742

307

Refs.

301

C39

C36

C35

C33

C29

BnO

The yield was determined by NMR spectroscopy.

No reduction occurred in this reaction.

The product was isolated as the phenylhydrazone.

c

TBAF (10 mol%), 0°

TBAF (10 mol%), 0°

b

CO2Et

SiMes2H

CO2Et

SiMes2H

TBAF (10 mol%), 0°

TBAF (10 mol%), 0°

TBAF (10 mol%), 0°

a

Ph

BnO

BnO

CO2Et

SiMes2H

CO2Et

SiMes2H

O

Et

TBSO

Et

O

CO2Et

SiMes2H

BnO

Mes Si O

Mes Si O

O

O

Mes Si O

Mes

Mes

BnO

Mes

Mes2Si

BnO Ph

O Et

TBSO

Et

O

Mes2Si

OEt

OEt

OEt

OEt

OEt

(79) dr = 93:7

(82) dr = 85:15

(—) dr = 96:4

(—) dr = 96:4

(91) dr = 98:2

743

743

743

743

743

302

C4-7

C3

C2-7

C2-7

C2

R

Et

R

R

H

H

H

O

H

H R = n-Pr, Ph

O

4-ClC6H4, 4-MeC6H4, 4-NCC6H4

R = Me, Et, i-Pr, t-Bu, Ph,

O

O

O

Aldehyde

ClRh(PPh3)3 (5x10-4 M)

Ph(Np-1)2SiH2,

CH2Cl2, 0°, 2 h

Et3SiH, TMSOTf, c-C6H11OTMS3,

CH2Cl2, rt, 2 h

Et3SiH (2 eq), TMSOTf (0.1 eq),

Et3SiH, HClO4, MeCN, rt

PhCONH2, solvent, 18 h

Et3SiH (3 eq), TFA (2.9 eq),

–78° to rt, 5-6 h

1-AdOTMS (1.25 eq), n-C5H12,

Me3SiH (1.25 eq), TMSI (0.3 eq),

Conditions

R

Et

Et

R

Ph N H

C6H11-c

Et

(—)

R

H

OSiHPhNp-1

O

O

OH

O

OEt

(—)

(100)a

(100)a

120°

MeC6H5

c-C6H11

22° 120°

MeC6H5

MeCN

Me t-Bu

Temp

Solvent

R

(69)

Product(s) and Yield(s) (%)

TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES

(92)

(90)

(95)

744

334

334

380

326

338

Refs.

303

C5

C4-7

C4-9

C4

R

R1

2h 2h

0° 0°

TMSH, TMSI, c-C6H11OTMS, CH2Cl2 Et3SiH, TMSI, n-C8H17OTMS, CH2Cl2

Bn Bn

n-C7H15

4-MeO2CC6H4

S O

2-octyl

Ph

H

Ph

Ph

H

Bn

Ph

50°, 30 h

Et3SiH (4 eq), TFA (8 eq),

TFA (y eq), 50-60°

Et3SiH (1 eq), EtOH (x eq),

1h

98:2 >98:2

HMPA, rt, 2.5 h

Ph2SiH2 (1.1 eq), TBAF (5 eq),

18-C-6 (0.05 eq), CH2Cl2, rt, 11 h

PhMe2SiH (1.1 eq), CsF (0.1 eq),

0°, 4-6 h

S

99:1 85:15

(65)

>98:2

OH

88:12

(64)

75:25

n-C5H11

R

68:32

(64)

74:26

(87) (72) (80)

(E)-PhCH=CH PhC C H2C=CH(CH2)8

OSiMe2Ph

(62)

(64)

(98) BnCH2

OSiMe2Ph

(98) (100)

(95)

4-ClC6H4 4-MeOC6H4

(98)

Ph 4-O2NC6H4

(99)

(81)

Ar

OH

2-C4H3S

2-C4H3O

R

I:II 91:9

R

OH

(73)

I

+ I + II

Ar

OH

Z:E

R

OH

>98:2

Cl3SiH (1.5 eq), CH2Cl2/DMF (4:1),

Ph

O

R

R THF, –78°, 3.5 h

2-C4H3O

H

OSiMe2H , TBAF (6 mol%),

Ar

n-C5H11

R

Ar

O II

320

347

318

400

306

C7

C6

18-C-6 (0.5 mol%), CH2Cl2, rt

PhMe2SiH (1.1 eq), CsF (10 mol%),

18-C-6 (5 mol%), CH2Cl2, rt, 0.5 h

PhMe2SiH (1.1 eq), CsF (10 mol%),

H

2. H3O+

KO2CH (1 eq), DMF, 45°, 19 h

1. Cyclohexanone, Me(EtO)2SiH (1.2 eq),

KF (1 eq), DMF, 10°, 1.75 h

Me(EtO)2SiH (1.5 eq),

(85)

II (72) +

I

II (97)

Et3SiH (1.25 eq), H2SO4, H2O (11 eq), 28°, 1.25 h

II (100)

n-C6H13

I (50)

n-C6H13

Et3SiH (1.1 eq), HCl, 28°, 3 h

(EtO)3SiH (1.1 eq), KF (1 eq), rt, 4 h

Ph2SiH2 (0.5 eq), CsF, rt, 3 min

Ph2SiH2 (0.5 eq), KF, 100°, 6 h

100°, 24 h

Ph2SiH2 (0.5 eq), 1,2-C6H4(CO2K)2,

(60)

(54)

4h

4-pyridinyl O

(67)

9h 20 h

2

OH

SiPh2

(70)

(100)

(60)

c-C6H10O (recovered)

O

OSiPh2H

II

I

(58)

Product(s) and Yield(s) (%)

OSiMe2Ph

OSiMe2Ph

3-pyridinyl

Ar

O

2-pyridinyl

Time

O

H

Conditions

TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)

Ar

H

n-C6H13

Ar

O

O

Aldehyde

82

83

313

313

79, 83

83, 319

319

319

345

346, 347

Refs.

307

+

Bn

O Bn

III (92) III (48) III (96) III (90)

PhMe2SiH, EG acid, CH2Cl2, rt, Et3SiH, ZnCl2 (HMe2Si)2O, TMSCl, C6H6, rt, 30 min (HMe2Si)2O, TMSCl, NaI,

t-BuOTMS (1.25 eq)

n-C5H12, –78° to rt, 5-6 h,

TMSH (1.25 eq), TMSI (0.3 eq),

(EtO)3SiH (2.3 eq), KF (1 eq), rt, 20 h

EtOTMS ( 1 eq), CH2Cl2, 0-15°; rt, 2 h

TMSH (1.1 eq), TMSI (5 mol%),

PhMe2SiH, EG acid

Et3SiH, TFA, BnOH, rt, 1 h

O

OEt

n-C6H13

OBu-t

O

n-C6H13

n-C6H13

OBn

III

n-C6H13

III (90)

TMSH, TMSI, TMSOEt, CH2Cl2, 0°, 2 h

III (87)

Et3SiH, H2SO4, MeOH, rt, 1 h

C6H6, rt, 30 min

III (90)

n-C6H13

Et3SiH, TFA, rt, 45 min

TMSOTf (cat.), C6H6, 80°, 30 min

HMe2SiOSiMe2H (1.0 eq),

(63)

OH (100)

(90)

Ph

(49)

C6H13-n

+ Ph

(82)

(96)

O Ph

(0)

338

83

334

333

328

334

328

314

330

330

333

313

314

308

C7

H

O

c-C6H11

H

O

O

O

CO2Et

H

H

OTMS

Aldehyde

OBn , Et3SiH (1 eq),

OBn , Et3SiH (1 eq),

Et3SiH (3 eq), TFA

5-Chloro-N-benzhydrylindole,

MeC6H5

R3SiH (x eq), (Ph3P)CuH (3 mol%),

OTMS TMSOTf (0.1 eq), CH2Cl2, –30°

MeO

O

OTMS TMSOTf (0.1 eq), CH2Cl2, –30°

BnO

n-C5H12, –78° to rt, 5-6 h

TMSH (1.25 eq), TMSI (0.3 eq),

t-BuOTMS (1.25 eq),

i-PrOH, DCE, O2, rt

PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),

2. Et3SiH (1.5 eq), –23°, 2.5 h

CH2Cl2, –78°, 30 min

1. TrSbCl6 (5-30 mol%),

2. Et3SiH (1.5 eq), –23°, 2.5 h

CH2Cl2, –78°, 30 min

1. SbCl5, TMSCl, SnI2,

Conditions

Cl

MeO

BnO

O

O

Ph

O

c-C6H11

c-C6H11

I (91)

O I

OBn

(84)

Ph

(36)

(84)

x

CO2Et

—

2h

Time

(79)

Ph2MeSi 2.5

PhMe2Si 1.3

R3Si

C6H11-c

OSiR3

N

OBn

(92)

C6H11-c

OBu-t

OH

(89)

Product(s) and Yield(s) (%)

TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)

(98)

(95)

355

317

341

341

338

367

306

306

Refs.

309

Ph

O H

II (90)

Me(EtO)2SiH (2.3 eq), KF (1 eq),

Bn

Ph

II (90)

KF KF•2H2O KF•2H2O KO2CH KO2CH

Me(EtO)2SiH PMHS PMHS PMHS Me(EtO)2SiH

Temp 20° 35° rt 80° 80°

Solvent DMF DMF DMSO DMF DMF

II Salt

Silane, salt, solvent Silane

II (90)

Me(EtO)2SiH, KF, 20°, 0.25 h

DMF, 20°, 0.25 h

OH

OSiEt3

O I

11 h

4h

1h

1h

0.25 h

Time

III

Ph

PhMe (84)

(EtO)3SiH (2.3 eq), KF (1 eq), rt, 6 h

MeC6H5, reflux, 1 h

PMHS, TMSOTf (cat.),

PMHS, TMSOTf (cat.), C6H6, reflux, 2 h

PMHS, Pd/C, EtOH, 80°

EtOH, reflux

[Bu2(AcO)Sn]2O (2 mol%),

PMHS (10% xs), II

Ph

Et3SiH (1 eq),

Ph

I (59)

(EtO)3SiH (1.1 eq), CaO, rt, 0.3 h

(Ph3P)3RhCl (0.1 mol%), rt, 5 min

I (72)

Ph

(EtO)3SiH (1.1 eq), HAp, rt, 0.3 h

Et3SiH (1.1 eq), Fe-mont, rt, 0.3 h

(75)

(64)

(67)

(76)

(90)

Bn

(92)

+

(80)

(95)

(100)

Ph

IV

III + IV (95)

82

83

83

83

314

314

316

316

411

353

353

353

310

C7

Ph

O H

Aldehyde

367

II (68)

PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),

I (92)

Et3SiO(EtHSiO)nSiEt3 (0.5 mol%),

CH2Cl2, rt, 2 h

Et3SiH (2 eq), TMSOTf (0.1 eq),

I (major)

I (80)

Et3SiH, TFA, 30-40°

TFA (8 eq), CHCl3, 50°, 1 h

I (75)

Et3SiH (1.1 eq), BF3•OEt2 (2.0 eq), rt

II (minor)

II (69)

M, LiCl (4 eq),

+

II (61)

L, THF, 0°, 2 h

THF, 0°, 2 h

96

II (95)

J, THF, 0°, 2 h

334

207

311

74

96

96

101

II (95)

K, CH2Cl2, rt, 2 h

i-PrOH, DCE, O2, rt

93

II (96)

G, 0°, 2 h

77

315

77

II (25)

(72)

II (96)

+

OH

Et3SiH, CsF, MeCN, 12 h

II

Refs.

II (36)

Ph

Product(s) and Yield(s) (%)

Et3SiH, TBAF, MeCN, 12 h

Et2O, rt, 24 h

PMHS (1 eq), ZnCl2 (1 eq),

Conditions

TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)

311

I (93) I (89) I (96) I (93) I (75) I (91) I (96) I (84)

Et3SiH, TFA, CHCl3, rt, 15 min Et3SiH, TFA, CCl4, rt, 15 min Et3SiH, TFA, MeCN, rt, 15 min Et3SiH, Cl2CHCO2H, rt, 30 min Et3SiH, BF3•OEt2, rt, 1 h Et3SiH, EG acid, CH2Cl2, rt PhMe2SiH, EG acid, CH2Cl2, rt Et3SiH, TrClO4,

MeCN, 57-58°, 1 h

Cl3SiH (3 eq), (n-Pr)3N (1 eq),

C6H6, 80°, 20 min

(HMe2Si)2O, TMSOTf,

BnOTMS, CH2Cl2, 0°, 10 min

Et3SiH, TrClO4,

Ph

I (97)

I (72)

I (87)

Et3SiH, TFA, rt, 30 min

CH2Cl2, 0°, 10 min

I (80)

(HMe2Si)2O, TFA, EtOH, 30-40°

SiCl3

(5)

+ Ph

Cl

SiCl3 (42)

711

314

329

329

74

333

333

313

313

313

313

313

313

312

C7

Ph

O H

Aldehyde

V

VI

47 h 21 h

rt rt rt rt

Cu-mont Na-mont silica Ca-Y-zeolite

Et3Si Et3Si Et3Si Et3Si

(87) (85) (87) (68) (69) (81) (26) (45)

CF3CO2H CCl3CO2H H2SO4 H2SO4 H2SO4 CF3CO2H CF3CO2H H2SO4

Me Me Et n-Pr i-Pr n-C7H15 t-Bu t-Bu

(87)

H2SO4

(0)

(0)

(0)

(77)

(—)

(94)

OR

Me

Et3SiH (1.1 eq), ROH, acid, 28° Acid R

3h

40°

Fe-mont

(EtO)3Si

7h

3h

rt

Fe-mont

Ph

1h

rt

Fe-mont

Et3Si PhMe2Si

3h

Ph H Time

Temp

Catalyst

OSiR3

(86)

OSiMe2Ph

OSiEt3

VI (57)

Ph

V (96)

Ph

R3Si

R3SiH (1.5 eq), catalyst, MeC6H5

18-C-6 (0.05 eq), CH2Cl2, rt, 11 h

PhMe2SiH (1.1 eq), CsF (0.1 eq),

HMPA, rt, 1.5 h

PhMe2SiH (1.2 eq), TBAF (2 eq),

MeCN, rt, 10 h

Et3SiH (1.5 eq), CsF (1.5 eq),

MeCN, rt, 12 h

Et3SiH (1.4 eq), TBAF (1.4 eq),

Conditions

(91)

(36)

Product(s) and Yield(s) (%)

TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)

328

324

347

320

76

76

Refs.

313

OTHP, Et3SiH (2.2 eq),

, Et3SiH (2.2 eq),

O

CH2Cl2, 0°, 2 h

TMSH, TMSI, c-C6H11OTMS,

OTMS , Et3SiH (1 eq), TMSOTf (2.0 eq), CH2Cl2, –78° to –30°

AcO BnO

O

OTMS , Et3SiH (1 eq), O TMSOTf (0.1 eq), CH2Cl2, 0° to rt

TMSI (0.3 eq), n-C5H12, –78° to rt, 5-6 h

1-AdOTMS (1.25 eq), TMSH (1.25 eq),

TMSOTf (10 mol%), MeCN, 0°, 1 h

Ph

OTHP

Ar OTHP, Et3SiH (2.2 eq), TMSOTf (10 mol%), MeCN, 0°, 1 h

OTHP , Et3SiH (2.2 eq), AcO TMSOTf (10 mol%), MeCN, 0°, 1 h

OTHP , Et3SiH (2.2 eq), BnO TMSOTf (10 mol%), MeCN, 0°, 1 h

TMSOTf (10 mol%), MeCN, 0°, 1 h

Ph

Ph

AcO

O

Ph

Ar

AcO

BnO

Ph

O

BnO

O

C6H11-c

OBn

O

(98)

(98)

Ar = 4-MeOC6H4

(96)

(89)

(75)

(98)

(95)

(95)

(97)

OBn

OBn

OBn

OBn

OBn

OBn

OBn

334

341

341

338

340

340

340

340

340

314

C7

Ph

O H

Aldehyde

Ph

Ph

Ph

Ph

VII

CH2Cl2, rt,

Et3SiH, EG acid, TMSOCH2C CH,

Ph

Ph

Et3SiH, H2SO4, EtOH, rt, 1 h

O

OEt

VII (85)

Et3SiH, Cl3CCO2H, MeOH, rt, 1 h

(98) OMe

(88)

TMSOTf Ph

(20)

TMSI

Et3SiH, TFA, MeOH, rt, 1 h

(96)

O

O

(87)

(87)

Ph

Ph

Ph

(95)

Ph (63)

(83)

(99)

(—)

(81)

Product(s) and Yield(s) (%)

C6H13-n

C7H15-n

BF3•OEt2

Ph

O

O

O

O

O

Sn(OTf)2

Catalyst

OTHP, Et3SiH (2.2 eq), Ph catalyst (10 mol%), MeCN, 0°, 1 h

PhMe2SiH, EG acid, TMSO(CH2)2OTMS, Ph CH2Cl2, rt,

CH2Cl2, 0°, 10 min

Et3SiH, Ph3CClO4, Ph(CH2)3OTMS,

CH2Cl2, rt,

PhMe2SiH, EG acid, Ph(CH2)3OTMS,

CH2Cl2, 0°, 10 min

n-C6H13CH(Me)OTMS,

Et3SiH, Ph3CClO4,

Et3SiH, TFA, n-C7H15 OH, rt, 1 h

Conditions

TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)

333

328

328

328

340

333

329

333

329

328

Refs.

315 + Ph

O

Ph

Et3SiH, H2SO4, t-BuOH, rt, 1 h

, TBAF (6 mol%),

OSiMe2H

2. H3O+

THF, –78°, 3.5 h

1. Ph

PDMS (2.3 eq), K2CO3 (1 eq), 60°, 2.5 h

(EtO)3SiH (2.3 eq), KF (1 eq), rt, 36 h

ROTMS (0.83 eq), CH2Cl2

Et3SiH (1 eq), TMSOTf (0.1 eq),

TFA (4 eq), 50 to 60°

Et3SiH (1 eq), MeOH (2 eq),

2. Et3SiH, Nafion®-H, CH2Cl2, reflux, 3 h

O

O

O

O

O

Ph

OH

R

Temp

+

Ph IX

(0)

Ph

(16) 0° to rt

Ph

OH

(99) 0° to rt

c-C6H11 t-Bu

(92) 0° to rt –78° to –30°

(81) 0° to rt

(99)

(96)

i-Pr

–30° to 0°

–78° to –30°

i-Bu

OH

H2C=CHCH2

Bn

R

(45)

(69)

(68)

(71)

VIII + IX (91), VIII:IX = 97:3

Ph

Bu-t

Pr-i

Pr-n

VIII

OH

II (100)

II (100)

Ph

VII (83)

VII (94.6)

Ph

Et3SiH, H2SO4, i-PrOH, rt, 1 h

1. HC(OMe)3, CH2Cl2, rt, 2 h

Ph

Ph

Et3SiH, H2SO4, n-PrOH, rt, 1 h

CH2Cl2, rt,

Et3SiH, EG acid, TMSOCH2CH=CH2,

400

83

83

341

327

335

328

328

328

333

316

C7

Ph

O H

Aldehyde

120° 120° 22° 22° 22° 22° 22°

MeC6H5 MeC6H5 MeC6H5

MeCN MeCN MeC6H5 MeC6H5

Ph 4-FC6H4 4-MeOC6H4 MeC6H5 MeCN

Bn

PhO BnO t-BuO PhNH BnNH

18 h

18 h

18 h

18 h

18 h

18 h

18 h

18 h

36 h

CHCl3, rt, 5.5 h

Me2ClSiH (1.2 eq), InCl3 (5 mol%),

CHCl3, rt, 5.5 h

Me2ClSiH (1.2 eq), In(OH)3 (5 mol%),

120°

120°

Solvent

R

Temp Time

RCONH2, PhCHO (x eq), solvent

Et3SiH (3 eq), TFA (2-3 eq),

, TBAF (6 mol%), –78°, 15 h

OSiMe2H

Conditions

XII

Ph

OSiMe2H

+

+

OH

OH

XI

XIII

Ph

OSiMe2H

Ph

OSiMe2H

Product(s) and Yield(s) (%)

XIV

R

Cl

(89)

(92)

(92)

(95)

(90)

(95)

(92)

(91)

(92)

(90)

x = 0.33

N H

O

(88)

(97)

(81)

(92)

(85)

(91)

(93)

(94)

(68)

x=3

X + XI + XII + XIII (75), X:XI:XII:XIII = 27:6:53:14

OH

Ph

OSiMe2H

XIV (60)

Ph

Ph

+

X

OH

TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)

331

331

326

400

Refs.

317

Br

Cl

Ar

Ph

R1

Cl

O

O

O

Cl

O

H

D

H

H

O

O

H

H

i-Pr

n-C6H13

(34)

4-ClC6H4

2-ClC6H4

Ar I

II (55)

I:II = 75:25

I + II (65)

(25)

314

(EtO)3SiH (1.1 eq), KF (1 eq), 100°, 1 h

MeCN, 51-64°, 1 h

Cl3SiH (3 eq), (n-Pr)3N (1 eq),

Br

Cl

I (34)

Me2ClSiH (1.2 eq), In(OH)3 (5 mol%), CHCl3, rt, 2 h

Cl

Cl

I

OH

SiCl3

Cl

II Ar = 4-ClC6H5 (90)

In(OH)3 (5 mol %), CHCl3, rt, 2 h

Et3SiH (1.2 eq), TMSCl (1.2 eq),

C6H6, 80°, 20 min

(HMe2Si)2O, TMSOTf,

(90)

(61)

79, 80

711

331

331

314

333

Ar

586

II Ar = 4-ClC6H5 (86)

II

O

(86)

(92)

(94)

365

PhMe2SiH, EG acid, CH2Cl2, rt,

Ar

s-Bu

Ph

(74) 95% ee

t-Bu

Ph

(97)

(91)

313

+

D

i-Pr

Ph

R2

Ph

Ph

R1

II Ar = 4-ClC6H5 (80)

I

SR2

OH

ArBn

Ph

R1

Et3SiH, TFA, 0°, 10 h

C6H6, reflux, 3 h

PMHS, TMSOTf (cat.),

(–)-4, THF, rt

MesPhSiH2, [Rh(cod)Cl]2 (2.5 mol%),

2. Et3SiH, 0° to rt, 3 h

1. R SH, BF3•OH2, CH2Cl2, 0°, 1 min

2

318

C7

O2N

O H

Aldehyde

ROTMS (0.83 eq), CH2Cl2, 0° to rt

Et3SiH (1.0 eq), TMSOTf (0.1 eq),

(Ph3P)CuH (3 mol%), MeC6H5, 2 h

PhMe2SiH (1.3 eq),

B (1 eq), rt, 12 h

i-PrOH, DCE, O2, rt

PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),

Et2O, rt, 24 h

PMHS (1 eq), ZnCl2 (1 eq),

KF (1 eq), 100°, 2 h

(EtO)3SiH (2.3 eq),

C (1 eq), rt, 12 h

CH2Cl2, 30°, 2 h

(HMe2Si)2O, TMSOTf,

Et3SiH, TFA, rt, 5 h

Conditions

O2N

O2N

I (100)

I (80)

I (65)

O2N

I (100)

I (55)

O2N

O

R

(89)

NO2

(73) (63) t-Bu

(88)

(33)

i-Pr

n-C6H13

R

(80)

OSiMe2Ph

I

OH

I

O

Product(s) and Yield(s) (%)

TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)

341

317

84

367

315

83, 80, 79

84

314

313

Refs.

319

C7-8

Ar

Ph

R

30° 80° 80° rt –78° 30° 80° rt

C6H6 C6H6 TFA CH2Cl2 CH2Cl2 C6H6 TFA

2-ClC6H4

4-ClC6H4

4-ClC6H4

4-O2NC6H4

4-O2NC6H4

4-HO2CC6H4

4-HO2CC6H4

TMSOTf (cat.), solvent

HMe2SiOSiMe2H (1.0 eq),

MeC6H5, rt

Temp

R

240 min

120 min

120 min

70 min

30 min

20 min

20 min

20 min

Time

Ph3SiH (1 eq), (C6F5)3B (2 mol%),

C6H6

Ph

O

Solvent

+

Et2O, rt

(MeO)3SiH (1.3 eq), LiOMe (1.2 eq),

18-C-6 (0.5 mol%), CH2Cl2, rt, 1 h

PhMe2SiH (1.1 eq), CsF (10 mol%),

Ph

H

H

H

H

O

Ar

O

O

O

N

, Et3SiH (1 eq), OTMS TMSOTf (2.0 eq), CH2Cl2, –78° to –30°

AcO BnO

O

Ar

Ph

R

OH

N

BnO

I

(46)

(97)

(55)

(9)

(94)

(90)

(94)

(97)

O

H

OH

AcO

Arr

(52)

II

R

OEt

>99:1

6:1

I:II

R

Ph

(80)

6h

Me

(86)

15 h

4-MeOC6H4 n-C7H15

OH

(55)

(85)

15 h

20 h

Time

(58)

NO2

2-O2NC6H4

Ph

R

OSiMe2Ph

+

O

O

314

116

91

345

341

320

C7-8

X

Ar

R1

H

PhMe2Si

n-C6H13

O

PhMe2Si

4-ClC6H4

H

PhMe2Si

4-MeC6H4

O

PhMe2Si

Ph

OTHP, Et3SiH (2.2 eq),

Ph3SiH (1 eq), (C6F5)3B (2 mol%)

TMSOTf (10 mol%), MeCN, 0°, 1 h

Ph

n-C5H12, –78° to rt, 5-6 h

t-BuOTMS (1.25 eq),

Me3SiH (1.25 eq), TMSI (0.3 eq),

Et3Si

Ph

LiClO4 (0.1 eq), CH2Cl2, electrolysis

R23SiH (1.2 eq), n-Bu4NClO4 (0.1 eq), R23Si

H

Conditions

X

Ar

Ar

R1

R1

O

OBu-t

(91.8)

(86.3)

(94.5)

(95.7)

(91.0)

O

OSiPh3

Ph

(21) (64)

2-MeOC6H4 Ar

(98)

(82) (81) (96)

Me Cl NO2

H

(81)

(90) 4-MeC6H4 X

(90) 4-O2NC6H4

(95)

(98)

4-MeOC6H4

4-ClC6H4

Ph

(87)

2-MeC6H4

(71)

4-MeC6H4 3-MeC6H4

(77)

(67)

4-FC6H4

Ph

Ar

Product(s) and Yield(s) (%)

TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)

R1

O

Aldehyde

115

340

338

333

Refs.

321

C7-9

R1

Ar

R

R1

O

O

O

O

10 min 10 min 5 min

4-MeOC6H4 4-NCC6H4 4-O2NC6H4

(n-Bu)4NClO4 (0.1 eq),

PhMe2Si Et3Si Et3Si PhMe2Si Et3Si

Bn(CH2)2 Bn(CH2)2 H2C=CHCH2 HC CCH2 (CH2)2OTMS H2C=CHCH2 HC CCH2

Ph Ph Ph Ph (E)-PhCH=CH (E)-PhCH=CH

Et3Si

R33Si PhMe2Si

R2

n-C6H13

LiClO4 (0.1 eq), CH2Cl2, electrolysis

R1

H

R33SiH (1.2 eq), R2OTMS,

MeC6H5, rt

Ph3SiH, (C6F5)3B (2 mol%),

Time 11 min

Ph

2. BF3•OEt2, rt

1. Et3SiH, BF3, CH2Cl2

CH2Cl2, rt, 5 h

InCl3 (20 mol%), R2STMS (1.2 eq),

R

H

H

H

Et3SiH (1.2 eq), TMSCl (50 mol%),

R1

Ar

R

R1

O

R2

OH

(100)

(100)

(0)

(—)

I

OH

(49.8)

(51.1)

(63.2)b

(95.0)

(71.2)

(98.8)

(81.9)

I

SR2

(0)

(0)

(100)

(52)

II

+

i-Pr Ph Et

Ph Ph BnCH2

(82) (81) (96)

4-ClC6H4 4-O2NC6H4

(87)

(78)

(81)

(82)

(83)

(87)

4-MeC6H4

Ph

Ar

RMe II

Et

Et

Ph

n-C8H17

R2

R1

333

116

1

426

322

C7-9

R

1

R2 BnCH2CH2 BnCH2CHMe HO2C(CH2)11 Et n-C9H19 Bn BnCH2CH2 BnCH2CHMe BnCH2CH2 BnCH2CH2 BnCH2CHMe BnCH2CH2 BnCH2CHMe

c-C6H11

Ph

Ph

Ph

Ph

Ph

Ph

Bn

BnCH2

BnCH2

n-C7H15

n-C7H15

R OH, CH2Cl2, rt

2

Et3SiH (1.3 eq), BiCl3 (0.11 eq),

c-C6H11

H

Conditions

R1

(64)

(63)

(69)

(73)

(61)

(82)

(93)

(80)

(95)

(74)

(38)

(70)

(77)

O

R2

Product(s) and Yield(s) (%)

TABLE 11. ORGANOSILANE REDUCTION OF ALDEHYDES (Continued)

R1

O

Aldehyde

332

Refs.

323

C7-8

Ar

H H H Me Me H H H

(E)-PhCH=CH

BnCH2

Ph

(E)-PhCH=CH

Ph

(E)-PhCH=CH

(E)-PhCH=CH

X, PhSiH3 (2 eq),

H

H

Me

Me

H

H

H

H

H

R3

OMe

OMe

NMe2

NMe2

NMe2

NMe2

NMe2

NMe2

NMe2

X

(10)

50:50

(80)

20 h

20°

Time 20 min 60 min 45 min 180 min 195 min 15 min 150 min 180 min

2-ClC6H4

4-ClC6H4

4-O2NC6H4

3-HOC6H4

4-MeC6H4

4-MeOC6H4

4-MeO2CC6H4

ZnI2 (cat.)

–70°

–70°

70°

–70°

–70°

70°

70°

70°

Temp

Ar

Cl

II (—) (45) (—) (20) (—) (—) (40) (40)

I (55) (85) (80) (40) (87) (60) (60)

O

(91)

+ Ar

Ar II

(14)

—

(70)

4h

20°

I

(31)

—

(50)

5h

20°

(14)

(12)

72:28

(68)

4h

20°

50:50

(10)

70:30

(72)

3h

50°

(62)

(trace)

70:30

(90)

6h

20°

20 h

(3) (trace)

72:28

(96)

4h

20°

20°

III

I:II 80:20

R1

(95)

+

I + II

I

X

OH

2h

R2

R3

O

20°

OH

Temp Time

TMSCl (1.57 eq), SO2Cl2 (1.37 eq),

HMe2SiOSiMe2H (1.0 eq),

Ph

H

Ar

O

H

R2

Ph

2. H3O+

R1

BnCH2

O R1 R3 Co(dpm)2 (0.05 mol%), DCE, temp

1. R2

R2

X II

R3

O + R1 OH III

314

478

324

C7-9

R

Ar

Ar

O

O

O

(70) (66) (75) (75) (83)

10 min 10 min 15 min 45 min 8 min

4-MeC6H4

4-MeOC6H4

4-NCC6H4

4-MeO2CC6H4

2,4-Me2C6H3

H

(87)

5 min

3-HOC6H4

O

(72)

10 min

2-ClC6H4

Et3SiH (1.2 eq), BiBr3, (10-30 mol%), rt

(80)

10 min

Ph

Ar

I2 (0.6 eq), CH2Cl2, –5° Time

R

15 min

4-MeOC6H4 R

80 min

4-MeO2CC6H4

HMe2SiOSiMe2H (1.0 eq),

20 min

4-MeC6H4

H

45 min

3-HOC6H4

I

20 min

R

(84)

(80)

(97)

(77)

(90)

(64)

15 min

2-ClC6H4

4-ClC6H4

I

+

(94)

Ar

Br

30 min

I

Ph

Ar

Ar

TMSCl (1.5 eq), LiBr (1.7 eq),

HMe2SiOSiMe2H (1.0 eq),

Conditions

(85) (0) (88)

20 h 2h 4-Me2NC6H4 n-C7H15

(83) 98)

(>98)

(>98)

(50)

(77)

(84)

OH

R2 Me Ph

Ph Ph

—(CH2)5—

R1

4h Ph

(30)

(40)

(70)

(73)

15 h (53) Me

Time

0.5 (50) Ph R

1.0

0.5

x (80)

(36)

Me

Me

R

78

288

750

378

388

C8-17

C8-13

Ar

R1

Ar

O

O

O

R

R2

R

Me Et ClCH2CH2 Me

p-ClC6H4 Ph Ph PhCH2CH2

p-NO2C6H4

Ph Ph

Ph

p-EtO2CC6H4 Me

R

Ar

Ketone

Et3SiH (x eq), TFA (y eq), solvent, rt

Et3SiH (1.1 eq), H2SO4, H2O, MeCN, 28°

1 h; 60°, 2 h

2h

1 h; 60°, 3 h

2h

1 h; 60°, 3 h

2h

2h

InCl3 (5 mol%), CH2Cl2, rt

Me2ClSiH, TMSCH2CH=CH2,

Conditions

Ar

R1

Ar

R

R2

NHAc

(75)

(99)

(44)

mixture

(70)

(67)

(84)

R

R2 Me Ph

Ph Ph

—(CH2)5—

R1

(85) (63)

48 h

(30) 72 h

72 h

Time

Product(s) and Yield(s) (%)

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

73

313

427

Refs.

389

C8-18

R1

O

5.4 9.5 10.0 6.5 9.9 5.0

2.5 2.2 2.5 2.6 2.2 2.2 2.2 5.0 2.4 2.2 2.4 3.0 2.2

Et n-Pr i-Pr c-C3H5 n-Bu HO2C(CH2)3 c-C4H7 c-C4H7 HO2C(CH2)4 Ph Ph Ph n-C10H21

Ph Ph Ph Ph Ph Ph Ph Ph Ph Ph 4-O2NC6H4 4-HO2CC6H4 Ph

R2 H H H H Me Ph TMS H

1

Et t-Bu c-C6H11 Ph Ph Ph Ph 2-MeC6H4

R

10.0

4.4

BrCH2

Ph

R2

5.4

2.2

Me

4-ClC6H4

y

Me

Ph

TFA

CCl4-TFA

TFA

TFA

TFA

CCl4-TFA

H2O-TFA

TFA

TFA

H2O-TFA

TFA

TFA

TFA

TFA

TFA

TFA

Solvent

MeC6H5, 0°, 1 h

Et3SiH, (C6F5)3B (2 mol%),

10.0

6.7

7.7

15.0

7.0

7.0

6.7

10.0

x 2.2

R

Ar

Time

15 min

120 h

47 h

15 min

5.5 h

7.5 h

6h

48 h

15 min

7h

15 min

15 min

15 min

44 h

200 h

15 min

R1

OH

(100)

(100)

(100)

(100)

(100)

(26)

(25)

(100)

(100)

(48)

(100)

(100)

(100)

(93)

(100)

(100)

I

I:II 4.4:1 >30:1 5.0:1 7.0:1 5.0:1 3.0:1 7.7:1 15:1

(100) (100) (93) (90) (100) (100) (100) (94)

R1

I + II

R2

+

OH

II

R2

372

390

C9

O

O

Ketone

H2SO4 H2SO4

Et3Si (n-Bu)3Si

(t-Bu)2SiH2 (1 eq), TFA (6.6 eq), rt, 20 h

Et3SiH (1.1 eq), acid, rt

H2SO4 H2SO4

TFA (6.8 eq)

Et3Si n-BuH2Si

BF3•OEt2

Et3Si

Et2HSi

BF3•OEt2 BF3•OEt2

n-BuH2Si

Acid Catalyst

Et2HSi

R3Si

2. Aq. OH–

0° to rt, 24 h

1. R3SiH (1.1 eq), acid catalyst (1 eq),

DMSO, 60°, 7 h

PMHS (1.5 eq), KF•2H2O (1 eq),

DMF, 60°, 5.5 h

Me(EtO)2SiH (1.5 eq), KF (1 eq),

(EtO)3SiH (1 eq), CsF, rt, 1 h

Conditions

I:II

I

OH

I

O2CCF3

I + II (100)

11:89

10:90

15:85

26:74

16:84

5:95

9:91

13:87

I (85)

I (75)

I

OH

(11)

+

90:10

TFA H2SO4

+

84:16

BF3•OEt2

II

(89)

I + II (—)

O2CCF3

I:II 95:5

Acid

II

OH

(95)

Product(s) and Yield(s) (%)

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

386

74

381, 384

82

82

80

Refs.

391

O

O

O

O

O

O Pr-n

MeC6H5, –20°

Ph2SiH2 (1.0 eq), Cp2Ti(PPh3)2,

MeC6H5, –20°

Ph2SiH2 (1.0 eq), Cp2Ti(PPh3)2,

i-PrOH, DCE, O2, rt

PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),

(Ph3P)4RhH (0.4 mol%), CH2Cl2, rt, 7 h

Ph2SiH2 (1.3 eq),

i-PrOH, DCE, O2, rt

PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),

TFA (6.6 eq), rt, 20 h

(t-Bu)2MeSiH (1 eq),

HO

I

HO

I

OH +

OH

(85), exo:endo = 36:64

II I + II + III (85)

OH

+

II

HO

Pr-n +

(53), endo:exo = 1:7

+

O

(40)

III

III

OH

OH

II

+

OH

Pr-n

III

OH

I + II (56), (I + II):III = 16:1, I:II = 13:1

+

HO

I + II (64), (I + II):III = 23:1, I:II = 22:1

Pr-n

I

O

OH

I (99:1

NMe2

I + II (94), I:II = 2:98

NEt2

OH

OH

O

Ph O I + II (97), I:II = 6:94 I + II (19), I:II = 68:32

Ph

(81)

TMSOTf

OH

6:1:2 20:1:1.3

(67)

(MeO)3SiH (1.2 eq), LiOMe (0.04 eq),

I:II:III

I + II + III

OH

+

BF3•OEt2

I

O

Pr-i

+

II

OH

(90) + Ph2SiHCl (—)

Product(s) and Yield(s) (%)

OEt

NMe2

NEt2

O

I + II (97), I:II = 98:2

n-Bu

I

OH

NC

OH

Catalyst

CH2Cl2, –78°, 6 h; 0°, 12 h

Ph3SiH (4 eq), catalyst (2.2 eq),

TBAF (5-10 mol%), HMPA, rt, 12 h

Ph2SiH2 (1.1-1.2 eq),

TBAF (5-10 mol%), HMPA, rt, 10 h

PhMe2SiH (1.1-1.2 eq),

PhMe2SiH (1.2 eq), TFA, 0°, 3 h

CH2Cl2, 20°, 19 h

Ph2SiH2 (1.2 eq), AlCl3 (1 eq),

Conditions

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

366

366

407

320

320

87, 276

373

Refs.

393

O Ph

+ n-C11H23

O OEt

Ph

I

Ph

OH

(0)

354

83

MeC6H5, 22 h

317

n-C11H23

II (78)

+

749

749

749

PMHS (2.5 eq), (Ph3P)CuH (3 mol%),

(86)

(100)

(100)

749

749

80

Ph

Ph

Ph

(95)

366

II (70)

II

HO

I (96)

I (99)

I

t-BuMe2SiO

I (98)

Et3SiO

I + II (96), I:II = 4:96

(EtO)3SiH (1 eq), CsF, rt, 1 h

CH2Cl2, rt, 5-20 min

PMHS (3 eq), (C6F5)3B (5 mol%),

(EtO)2MeSiH (2.3 eq), CsF (1 eq), rt, 5 h

neat, 150°, microwave, 15 min

NaOMe (3 mol%), o-dppb (0.05 mol%),

t-BuMe2SiH (1.2 eq), CuCl (0.5 mol%),

MeC6H5, rt, 90)

Catalyst

R3Si

R3SiH, Triton-B or TBAF

390

316

278

400

C10

t-Bu

O

Ketone

20 h 3h 1.5 h 64 h 24 h 12 h 20 h 18 h 0.25 h 0.25 h

80° 110° rt 80° 80° 80° 80° rt rt

Et3Si Et3Si Ph3Si Ph3Si PhMe2Si (EtO)3Si Cl3Si Et2HSi Ph2HSi

57:43

46:54

37:63

29:71

29:71

12:88

19:81

12:88

11:89

23:77

12:88 41:59

20 h 24 h 10 h 12 h 12 h

Et3Si Ph3Si PhMe2Si Et2HSi Ph2HSi

I:II

8h

Et3Si

49:51

7:93

5:95

8:92

Time

R3Si

2. TsOH, aq. MeOH, rt, 1 h

C6H6, 80°

1. R3SiH (1.5 eq), (Ph3P)3RuCl2 (2 mol%), I + II (60-90)

144 h

rt 45°

33:67

II I:II

t-Bu

+

I

(—)

OH (—)

Product(s) and Yield(s) (%)

t-Bu

OH

Time

Et3Si

Temp

Et3Si

R3Si

2. TsOH, aq. MeOH, rt, 1 h

(Ph3P)3RhCl (2 mol%), C6H6

1. R3SiH (1.5 eq),

Conditions

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

391

391

Refs.

401 I + II + III (70) +

Et3SiH (1.1 eq), H2SO4, H2O, MeCN, 28°, 65 h

t-Bu III

O CH2Cl2, rt, 2 h

Et3SiH (2 eq), TMSOTf (0.1 eq),

4h

5°

72

(74) 39:61

(92) 33:67

1d

0°

87

I:II

(87) 35:65

4h

rt

I + II

Time

Temp

I + II

I + II (98), I:II = 1:14

95

Ligand

ligand (2 mol%), AgBF4 (2 mol%), THF

Ph2SiH2 (1.5 eq), (Ph3P)3RhCl (1 mol%),

i-PrOH, DCE, O2, rt

PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),

CH2Cl2, rt, 5 h

Ph2SiH2 (1.3 eq), (Ph3P)4RhH (0.3 mol%), I + II (81), I:II = 16:84

t-Bu

(4) +

Bu-t

t-Bu

NHAc

(100)a

(21)

313

334

572

367

374

402

C10

t-Bu

O

Ketone

0.83

(s-Bu)3Si

(t-Bu)2SiH2 (1 eq), TFA (6.6 eq), rt, 2 h

7.0

7.0

1.1

(i-Bu)3Si

1.22

1.08

+

IX

t-Bu

(6)

(14)

(11)

(17)

(34)

(50)

(74)

VIII

O

VI

O

Bu-t

Bu-t

3

18

13

25

30

53

67

VI (%)

24

43

35

48

55

40

29

73

39

52

27

15

7

4

Refs.

72, 74

386

VII (%) VIII (%)

trans, trans cis, trans cis, cis

(3)

t-Bu

Bu-t

t-Bu

+

VI + VII + VIII

VII

IV (66) + V (31) +

(94)

(86)

0.79

0.49

7.0

(89)

(83)

7.5

0.25

0.031

1.0

Et3Si

(50)

(26)

(c-C5H9)3Si 0.75

0.8

PMHS

2.1

IV:V

0.23

1.05

n-PrH2Si

2.5

IV + V

+ t-Bu

V

IV O

t-Bu

(66)

1.0

n-BuH2Si

y

+

O2CCF3

Product(s) and Yield(s) (%)

t-Bu

O2CCF3

6.8

x

R3Si

R3SiH (x eq), TFA (y eq)

Conditions

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

403 (t-Bu)2MeSiH (1.17 eq), TFA (3 eq), rt

(t-Bu)3SiH (1.2 eq), TFA (3 eq), rt

94 97 +

264 h 720 h +

+

85

93 h

I

IV

(—)

(—)

(—)

(10)

(9)

+

IV IX (5.5)

+

IX

(10)

(9.3)

(9)

X (3)

(1.8) (27)

0.6 h (0.7) (70) (27) (6) (41) (18) (8) (28) (10) (8) (27)

21 h 46 h 96 h

(39)

(38)

I + IV IX XIV XV

Time

(20)

(16)

(7)

(0.5)

II + V

(18)

(50) (6.5) (38)

O2CCF3 386

(3)

(1.2)

(0.8)

(0.6)

(0.5)

(10)

(20)

(51)

(57)

(64)

386

XI XII + XIII

t-Bu XI

(22) (4.2)

OSiMe(Bu-t)2

(8)

+

(9.3) (7.4) (3.7)

(8)

V

t-Bu XIII

t-Bu XV

V

(21)

(13)

(13)

(12)

(10)

+

X t-Bu OSi(Bu-t)3

O2CCF3

t-Bu XIV

+

OSiMe(Bu-t)2

53

27 h

II

50

I

% Conv.

21 h

t-Bu XII Time

+

OSi(Bu-t)3

I + IV + V + IX +

404

C10

t-Bu

O

Ketone

In(OH)3 (5 mol%), CHCl3, 60°, 2 h

Me2ClSiH (1.2 eq),

Et3SiH (1.1 eq), HCO2H (2.0 eq), rt

TBSOTf (0.01 eq), rt, 2 h

TBSH (3 eq),

t-Bu

Cl

t-Bu

Refs.

(76) cis:trans = 12:88

331

74

XVII + XVIII (81), XVII:XVIII 66:34 392

(100) cis:trans = 38:62

XVIII

XVII OCHO

t-Bu

t-Bu

+

74

III (55) + XVI (55) cis:trans = 60:40

Et3SiH (1.1 eq), AlCl3 (0.1 eq), rt OTBS

74

III (50) + XVI (50) cis:trans = 42:58

Et3SiH (1.1 eq), SnCl2 (0.1 eq), rt

OTBS

74

XVI (100) cis:trans = 61:39

74

74

Et3SiH (1.1 eq), BF3•OEt2 (3.0 eq), rt

XVI

(100) cis:trans = 32:68

Product(s) and Yield(s) (%)

XVI (100) cis:trans = 67:33

t-Bu

OSiEt3

Et3SiH (1.1 eq), ZnCl2 (0.1 eq), rt

Et3SiH (1.1 eq), ZnCl2 (1.0 eq), rt

Conditions

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

405

O

O

O

O

CH2Cl2, rt, 2 h

Et3SiH (2 eq), TMSOTf (0.1 eq),

CH2Cl2, rt, 1 h

Et3SiH (1.3 eq), BF3•OEt2 (4-6 eq),

CH2Cl2, 0° to rt, 2 h

Et3SiH (1.5 eq), CF3SO3H (4 eq),

2. EtMe2SiH (2.2 eq), 0°, 60 min

1. BF3, CH2Cl2, 0°

i-PrOH, DCE, O2, rt

PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),

n-C6H14, rt, 6 h

Et3SiH (1.5 eq), H2SO4/carbon,

PMe3 (60 mol%), MeC6H5, –20°

PhMeSiH2 Cp2Ti(PMe3)2 (10 mol%),

i-PrOH, DCE, O2, rt

PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),

H I

I

+ H II

OH

(22)

+

III

OH

(100)

(99)

(95)

II (78)

III

O

I (79)b + II (20)b

OH

OH

(100)a

I + II:III = 6:1, I:II = 70:1, I + III (72)

OH

OH

II

HO

334

217

420

1

367

243

428, 429

367

406

C10

O

O

Ketone

CH2Cl2, 0° to rt

n-C6H13OTMS (0.83 eq),

Et3SiH (1 eq), TMSOTf (1 eq),

i-PrOH, DCE, O2, rt

PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),

(EtO)3SiH (1 eq), CsF, rt, 1 min

c-C6H11OTMS, CH2Cl2, 0°, 2 h

Et3SiH, TMSOTf, TMSI,

reflux, 3 h

2. Et3SiH, Nafion®-H, CH2Cl2,

1. HC(OMe)3, CH2Cl2, rt, 2 h

CH2Cl2, rt, 2 h

Ph3CH (0.1 eq), 220 (0.09 eq),

TMSH (xs), TMSCl (cat.),

CH2Cl2, rt, 2 h,

TMSH (xs), 220 (0.09 eq), Ph3CCl (0.1 eq),

Conditions

II

I (trace)

I

+

I + II + III (98), I:II:III = 8:15:75

+

(93)

OC6H13-n

OH

(100)a

(88)

(95)

OC6H11-c

OMe

I + II + III (75), I:II:III = 26:40:29

I

OH

Product(s) and Yield(s) (%)

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

III

O

341

367

80

334

335

424

424

Refs.

407 O

Br

O

none none none hexane

0.1 0.1 0.1 1.0 0.1

Et2HSi PhMeHSi Ph2HSi Et3Si PhMe2Si

i-PrOH, DCE, O2, rt

PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),

(EtO)3SiH (1.1 eq), CsF (1 eq), 70°, 3 h

none

none

0.1

Ph3Si

Solvent

mmol Cat.

R3Si

R3SiH, (Ph3P)3RhCl, solvent, 0-80°

OH

Br

OH

OSiR3

H

I II (9)

(0)

(trace)

(60)

(0)

(30) (70)

(73) (27)

(75) (25)

(91)

(90) (10)

I

+ H II

OSiR3

367

79, 80

388

408

C10

O

O

O

Ketone

0.1

PhMe2Si none

hexane

none

none

none

none

II

(0) (0)

(64) (36)

(85) (15)

(86) (14)

(83) (17)

(90) (10)

I

+

18:82 39:61 64:36

HOAc HOAc BF3•OEt2

n-BuH2Si Et3Si

I:II

I + II (—)

Et3Si

I

+

II

Acid Catalyst

OH

I + II (92), I:II 45:55

I

OH

OMe

(88)

II

HO

OH

Product(s) and Yield(s) (%)

R3Si

0° to rt, 24 h

R3SiH (1.1 eq), acid catalyst (1 eq),

P(tm-tp)3 (2 mol%), C6H6, rt, 20 h

[Rh(C2H4)2]2 (0.5 mol%),

PhMe2SiH (1.2 eq),

1.0

Et3Si

0.1

PhMeHSi 0.1

0.1

Et2HSi Ph2HSi

0.1

mol% Cat. Solvent

Ph3Si

R3Si

R3SiH, (Ph3P)3RhCl, solvent, 0-80°

reflux, 3 h

2. Et3SiH, Nafion®-H, CH2Cl2

1. HC(OMe)3, CH2Cl2, rt, 2 h

Conditions

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

384

389

387, 388

335

Refs.

409

O

O

O NEt2

NHPh

O

OH

O

O

O Pr-i

OH

O

DMPU, 0°, 22 h

PhMe2SiH (1.2 eq), TASF (10 mol%),

PhMe2SiH (1.2 eq), TFA, 0°, 6 h

(EtO)3SiH (2.3 eq), CsF (1 eq), rt, 10 min

2. SnCl4, CH2Cl2, –80°

1. (i-Pr)2SiClH, Et3N, DMAP, hexane

2. SnCl4, CH2Cl2, –80°

1. (i-Pr)2SiClH, Et3N, DMAP, hexane

I

I

O

NEt2

+

(90)

O

Pr-i

III

Si

II

Si

H

O

Pr-i

OH

Pr-i

OH

II

O NEt2

I + III (75), I:III = 300:1

O

I + II (91), I:II = 2:98

O

NHPh

O

i-Pr

II

O

i-Pr

H

I + II (82), I:II 250:1

O

I + II (93), I:II 23:77

OH

OH

+

O

I

—

Pr-i

(47) i-Pr

>99:1

(81)

+

+

BF3•OEt2

OH

Pr-i

TMSOTf Si

H I:II

I

O I + II

H

Catalyst

CH2Cl2, –78°, 6 h; 0°, 12 h

Ph3SiH (4 eq), catalyst (2.2 eq),

87, 276

87, 276

80, 83

397

397

407

410

C10

Ph

Ph

O

O

O

O

O

CO2Et

OMe

Ketone

O

CH2Cl2, 20°, 20 h

OMe

Ph

(90)

95:5 73:27

(EtO)3SiH OH

95:5

(MeO)3SiH

Ph2SiH2 (1.2 eq), AlCl3 (1 eq),

95:5

(TMSO)3SiH

I + II (>90)

+

II

II

OH

HO

I:II = 90:1

I (78), I + II:III = 99:1

+ Ph2HSiCl (—)

(39) 93% ee

(67)

CO2Et III

OH

+ EtO2C

PMHS

I

OH

OH

+

I

OH

I:II

Ph

Ph

EtO2C

Product(s) and Yield(s) (%)

Silane

Silane, Triton-B

Li-(R)-BINOL (10 mol%), 0°, 24 h

(MeO)3SiH (1 eq), Et2O:TMEDA (30:1),

CH2Cl2, rt, 6 h

Et3SiH (1.3 eq), BF3•OEt2 (4-6 eq),

MeC6H5, 21°

Ph2SiH2 (1.0 eq), Cp2Ti(PPh3)2,

Conditions

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

373

278

592

217

428

Refs.

411

Ph

Ph

Ph

Ph

O

O

MeO

Ph

O

O

CF3

O

O

CO2H

NHCOCF3

MeO

O

LiI, CHCl3, rt, 11 h

Me2ClSiH (1.2 eq), In(OH)3 (5 mol%),

CHCl3, 60°, 3 h

Me2ClSiH (1.2 eq), In(OH)3 (5 mol%),

CHCl3, 0°, 0.3 h

Me2ClSiH (1.2 eq), In(OH)3 (5 mol%),

Et3SiH (2.2 eq), TFA, rt

reflux, 2 h; rt, 16 h

Et3SiH (4 eq), BF3•OEt2 (20 eq),

reflux, 2 h; rt, 16 h

Et3SiH (3.42 eq), TFA,

MeC6H5, rt, 4 h

CuCl (0.5 mol%), NaOBu-t (3 mol%),

TBSH (1.2 eq), 123 (0.1 mol%),

CH2Cl2, 20°, 22 h

Ph2SiH2 (1.2 eq), AlCl3 (1 eq),

Ph

Ph

Ph

O

Ph

Ph

O

O

OH

CF3

I

Cl

Cl

Ph

(74)

(92)

(78)

+ Ph

(78)

(50)

CO2H

+ Ph2SiHCl (—)

(90)b 80% ee

(30)

(86)

NHCOCF3

NHCOCF3

MeO

OH

MeO

Ph

OH

(14)

331

331

331

73

376

376

749

373

412

C11

R

C10-23

1

O

O

O

O

R2

BnNH BzO

Ph Ph

O O

OH

OEt

Pr-i

Bn2N

N-piperidinyl

Ph

Bn2N

Et2N

Ph

Ph

AcO

Ph

Me

BnO

Me

BnMeN

MeO

Ph

Ph

R2

R1

Ketone

DMF, 30°, 5 h

PMHS (1.2 eq), KF•2H2O (1.3 eq),

CH2Cl2, –78° to 20°, 12 h

Ph3SiH (4 eq), BF3•OEt2 (2.2 eq),

CH2Cl2, 0°, 2 h

Ph2MeSiH (2 eq), TMSOTf (1 eq),

THF, 0-5°, 2 h

PMHS, (2-2.5 eq), TBAF (1 eq),

Conditions

R

1

O

I

O

O

H

(59)

OH

Pr-i

II

R2

OH

(81) cis:trans > 20:1

(50) trans:cis = 1:1

95:5 100:0

(95)

97:3

(71) (90)

26:74

(88) 100:0

100:0

(80)

(87)

97:3 100:0

(76)

73:27

(79) (76)

87:13

(77)

R1

I:II

+

I + II

O

R2

OH

Product(s) and Yield(s) (%)

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

82

407

336

401

Refs.

413

i-PrO

Ph

O

H

Me2Si

O

O

O

O

H

O

O

O

O CF3

O O

O

OMe

OPr-i

+

(53)

H O

OH CF3

(EtO)3SiH (1 eq), CsF, rt, 0.5 h

Me(EtO)2SiH (2.3 eq), CsF, rt, 2.5 h

Me(EtO)2SiH (1 eq), CsF, rt, 2.5 h

TFA (0.2 eq), –80°, 30 min

rt, 15 min

ZnCl2 (0.25 eq), –80°, 30 min;

i-PrO

Ph

Ph

O

O

OH

OH

O

O

O

OMe

I + II (—), I:II = 2:1

I + II (—), I:II = 1:4

OPr-i

(85)

(85)

(70)

I + II (—), I:II = 1:6

79, 80

83

80, 83

399

399

399

399

ZnBr2 (0.12 eq), –80°, 8 h; rt, 16 h

399

399

410

I + II (—), I:II = 23:1

(—)

409

I + II (—), I:II = 14:1

+ O O O Si Si Me2 Me2 I + II (37), I:II = — II I

(58)

CF3

MgBr2•OEt2 (0.1 eq), rt, 24 h

O

H O

O CF3

O O

BF3•OEt2 (0.5 eq), –80°, 2 h

SnCl4 (0.1 eq), –80°, 2 h

PMHS, TFA, rt, 2 d

20°, 20 min

Et3SiH (4 eq), TFA (36 eq),

414

C11

Ph

Ph

Ph

O

O

OMe

NEt2

NEt2

OAc

NMe2

O

O

O

O

O

O

Ketone

TBAF (5-10 mol%), HMPA, 0°, 20 h

PhMe2SiH (1.1-1.2 eq),

TBAF (5-10 mol%), HMPA, rt, 12 h

PhMe2SiH (1.1-1.2 eq),

TASF (10 mol%), DMPU, rt, 12 h

PhMe2SiH (1.2 eq),

PhMe2SiH (1.2 eq), TFA, 0°, 3 h

PhMe2SiH (1.2 eq), TFA, 0°, 16 h

DMPU, 0°, 24 h; rt, 72 h

PhMe2SiH (1.2 eq), TASF (10 mol%),

PhMe2SiH (1.2 eq), TFA, 0°, 20 h

Conditions

Ph

Ph

Ph

Ph

I

I

I

I

OH

Ph

OMe

Ph

+

Ph

I + II (—)

+

OH

OH

OH

I + II (87), I:II 99:1

(95)

S

98:2

(95)

4-ClC6H4 Cl

(46)

Ar

I:II

+

(84)

(64)

94:6

NHCO2Me

CO2H

O

OEt

(97)

I

O

OH

O

OMe

I + II

Ar

s-Bu

Ph

Cl

MeO2C

Cl

CO2H CO2Me II

N

Product(s) and Yield(s) (%)

Ph

2. PhMe2SiH, TiCl4, CH2Cl2, –78° to rt

1. TMSCl, Et3N

rt, 4 h

Et3SiH, TFA, LiClO4 (0.01 eq),

In(OH)3 (5 mol %), CHCl3, rt, 2 h

Me2ClSiH (1.2 eq),

In(OH)3 (5 mol%), CHCl3, rt, 3.5 h

Me2ClSiH (1.2 eq),

Conditions

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

Ar

NHCO2Me

O

OEt OH

O

O

Ketone

421

423

331

331

Refs.

417

C11-16

Ph

O R1

(4-MeOC6H4)Me2Si 0° rt

(4-MeC6H4)Me2Si PhMe2Si Ph2MeSi (i-PrO)Ph2Si (i-PrO)3Si PhMe2Si PhMe2Si

OAc OAc OAc OAc OAc OAc OBz OEE 0°

0°

–50°

rt

rt

0°

0°

18 h

6h

12 h

3h

14 h

14 h

4h

4h

4h

4h

(4-CF3C6H4)Me2Si

0°

PhMe2Si

OAc

20 h

OAc

Time

0°

PhMe2Si

OAc

Temp

R3Si

R1

TBAF (5-10 mol%), HMPA

R3SiH (1.1-1.2 eq), Ph I

OH

(55)

(82)

(71)

(91)

(89)

(99)

(88)

(83)

(72)

(93)

90:10

96:4

78:22

86:14

92:8

93:7

93:7

93.1:6.9

93.1:6.9

93.3:6.7

I:II 95:5

(95)

+

I + II

R1 Ph II

OH R1 320

418

C11-16

TFA TFA TFA TFA

NHCO2Me OBn NHSO2Ph OBz

2,5-(MeO)2C6H3

n-Bu

Ph

Ph

AlCl3 (1 eq)

Ph TMSOTf (1 eq)

0°

TFA

NHCO2Et NHCO2Et

Ph NHCO2Et

0°

TFA

NHCO2Me

Ph

Ph

rt

Ph

0°

0°

0°

0°

0°

0°

rt

AlCl3 (1 eq) TFA

CO2Me NMe2

Ph

rt

TMSOTf (1 eq)

Temp

Acid

CO2Me

PhMe2SiH (1.1-1.2 eq), acid

R2

R2

Ph

O

Conditions

R1

OH

(72)

(66)

(82)

(84)

(65)

(64)

(87)

(87)

(0)

(66)

(83)

I + II

I

R2

I:II

R1

93:7

98:2

47:53

>99:1

71:29

70:30

>99:1

>99:1

—

78:22

79:21

+

OH

II

R2

Product(s) and Yield(s) (%)

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

R1

R1

Ketone

276

Refs.

419

C12

O

Ph

Ph

HO

O

OBz

O

O

O

Ph

TBAF (5-10 mol%), HMPA, 0°, 4 h

PhMe2SiH (1.1-1.2 eq),

CH2Cl2:DMF (4:1), 0°, 12 h

Cl3SiH (1.5 eq),

MeC6H5, 0°, 1 h

Et3SiH, B(C6F5)3 (2 mol%),

CH2Cl2, 0°, 2 h

Ph2MeSiH (2 eq), TMSOTf (1 eq),

i-PrOH, DCE, O2, rt

PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),

Ph3CH (0.1 eq), CH2Cl2, rt, 2 h

TMSH (xs), 220-TFPB (0.09 eq),

I

+

(79)

Ph

OBz

OH

+ II

OH

(85)

I + II (98), I:II = 1:1.5

Ph

(13)

I + II (76), I:II = 33:67

I

OH

Ph

Ph

OH

O

OH

OBz

II

OH

(91) cis:trans = 40:60

320

318

372

336

367

424

420

C12

t-Bu

Ph

O

HO

HO

O

O

N

O

O

H

O N

NHCO2Et

Ph

H

Ketone

O

O

TASF (10 mol %), DMPU, 0°, 16 h

PhMe2SiH (1.2 eq),

PhMe2SiH (1.2 eq), TFA, 0°, 2.5 h

PMe3 (60 mol%), MeC6H5, –20°

Ph2SiH2, Cp2Ti(PMe3)2 (10 mol%),

Et3SiH (3.2 eq), TFA, rt, 24 h

Et3SiH (3.2 eq), TFA, 0°, 1 h

Conditions

I

H

t-Bu

Ph

HO

OH

OH

Ph I

N

H

OH +

HO

Ph II

N

II

OH

H

III

N

Ph

O

I

O N

+ t-Bu

OH

II

O N

(87) threo:erythro > 99:1

I + II (90), I:II = 91:9

NHCO2Et

I + II + III (75), (I + II):III = 99:1, I:II = 1:1

+

+

HO

I + II (56), I:II = 1:4

O

I + II (77), I:II = 4:1

HO

Product(s) and Yield(s) (%)

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

H

OH

320

86

428, 249

394

394

Refs.

421

C12-13

Cl

MeO

MeO

EtO2C

Ph

MeO

Ph

O

O

O

O

O

O

O OEt

NHCOCF3

O

O

n

CO2H

NHCO2Me

NHCOCF3

2. Et3SiH, TiCl4, CH2Cl2, 0°, rt

1. TMSCl, Et3N

TFA, reflux, 2 h, rt, 16 h

Et3SiH (3.42 eq),

CH2Cl2, rt, 10 h

Et3SiH (2.6 eq), BF3•OH2 (4-6 eq),

CH2Cl2, rt, 5-20 min

PMHS (3 eq), (C6F5)3B (5 mol%),

CH2Cl2, rt, 5-20 min

PMHS (3 eq), (C6F5)3B (5 mol%),

CH2Cl2, 20°, 18 h; 40°, 4 h

Ph2SiH2 (1.2 eq), AlCl3 (1 eq),

reflux, 2 h; rt, 16 h

Et3SiH (3.42 eq), TFA,

Cl

MeO

MeO

EtO2C

Ph

MeO

Ph

OH

O

OH

(70)

OEt

n

(82)

CO2H

+ Ph2HSiCl (—)

n = 2 (85)

n = 1 (89)

(74)

(78)

(88)

NHCOCF3

O

(72)

NHCO2Me

NHCOCF3

421, 752

376

217

354

354

373

376

422

C12-15

C12-14

Cl

Fe

Solvent none none none none CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2

TFA TFA BF3•OEt2 BF3•OEt2 TiCl4 TiCl4 TiCl4 AlCl3 SnCl4

Me

H

Me

H

Me

TMS

TMS

TMS

Et3SiH, acid, solvent

Acid

CO2R

NHCO2Me

H

O

rt

rt

rt

rt

rt

rt

70°

reflux

reflux

Temp

Et3SiH (2.5 eq), TFA (5 eq), 20°

Conditions

Cl

Cl

+

Fe

(85)

I

(—)

(45)

(88)

(25)

(67)

(12)

(—)

(25)

(—)

(—)

(—)

(38)

(—)

(—)

(—)

(—)

(—)

II

IV

O

II: X = Cl

Cl

(—)

(23)

(—)

(—)

(—)

(28)

(—)

(—)

(—)

III

O

(—)

(—)

(—)

(—)

(—)

(—)

(65)

(49)

(54)

IV

Cl

+

NHCO2Me

CO2R

+

(65)

CO2Me CN NHCO2Me

(45)

(40)

Cl

H

I: X = H

X

(—)

X

X

(—)

(—)

(—)

(—)

(—)

(—)

(6)

(10)

(7)

V

Product(s) and Yield(s) (%)

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

R

X

O

Ketone

V

O

III

O

NHCO2Me

CO2R

NHCO2Me 421

180

Refs.

423

C12-18

R

O

(87) (81) (80) (80) (75) (82) (78) (67)

2 3.0 2 2.67 3.0 2.5 3.0 2.07

2.33 2.67 2.33 2.67 2.5 2.5 2.6 2.4

n-Pr

i-Pr

n-Bu

n-C6H13

c-C6H11

Ph

4-MeC6H4

4-BrC6H4

(84) (90) (73) (75) (80) (81) (81) (52) (87) (70) (84)

1.1 1.06 1.07 1.07 1.0 1.02 1.02 1.02 1.37 1.02 1.02

Me

Et

n-Pr

i-Pr

n-Bu

n-C6H13

c-C6H11

Ph

4-MeC6H4

4-BrC6H4

CCo3(CO)9

Me

x

R

OH

(92)

2

2.33

Et

Et3SiH (x eq), CO, C6H6, reflux, 8 h

(90)

2.07

x

CCo3(CO)9

2.4

R

R

Me

y

THF, reflux, 6 h

Et3SiH (x eq), TFA (y eq),

R

CCo3(CO)9

310

310, 425

424

O

R2 Me i-Pr i-Pr i-Pr i-Pr i-Pr n-Bu

Me

i-Pr

i-Pr

i-Pr

i-Pr

n-Bu

O

i-Pr

O

R2

C6H13-n

R1

H

O

CO2Et

R1

(i-Pr)2Si

EtO2C

n-C6H13

C13-17

C13

Ketone

0.1 0.1

SnCl4 SnCl4 SnCl4 0.1 0.5 0.5

TiCl4 BF3•OEt2 SnCl4

MgBr2•OEt2 0.1

x 0.1

Catalyst

Catalyst (x eq), CH2Cl2

SnCl4 (0.1 eq), –80°, 2 h

24 h

2h

2h

2h

Time

–80°

–80°

2h

2h

–80° 30 min

rt

–80°

–80°

–80°

Temp

PMe3 (60 mol%), MeC6H5, –20°

Ph2SiH2, Cp2Ti(PMe3)2 (10 mol%),

MeC6H5, –20°

Ph2SiH2 (1.0 eq), Cp2Ti(PPh3)2,

i-PrOH, DCE, O2, rt

PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),

Conditions

CO2Et I

EtO2C CO2Et II

HO

(43)

O

I + II

R1

I

(44)

(—)

(—)

(—)

(67)

(68)

(61)

I + II

O Si (Pr-i)2

R2

+ EtO2C III

CO2Et

HO

+ O

40:1

320:1

30:1

60:1

120:1

40:1

50:1

I:II

R1

II

O Si (Pr-i)2

R2

(69) 40:1 i-Pr

(67) 50:1

I + II I:II Me

R2 i-Pr Me

R1

I + II (68), I + II:III = 99:1, I:II = 10:1

+

C6H13-n

I (65), I + II:III = 9:1, I:II 99:1

EtO2C

HO

n-C6H13

OH

Product(s) and Yield(s) (%)

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

398

399

429

428

367

Refs.

425

O

O

OH

O

Ph

O

O

HO

Ph

Ph

Ph

O

2.2:1 3:1 3.5:1 5:1 6:1

(59) (50) (63) (55)

–5° 0° 21° 50°

II (II + III):I

HO

II

+

(88)

(63)

I

Ph

Ph

–20°

OH

I (85)

I (83)

I (90)

I (85)

O I

OTBS

Temp

Cp2Ti(PPh3)2, MeC6H5

Ph2SiH2 (1.0 eq),

CH2Cl2, 0°, 2 h

Ph2MeSiH (2 eq), TMSOTf (1 eq),

CH2Cl2, 0°, 2 h

Ph2MeSiH (2 eq), TMSOTf (1 eq),

CH2Cl2, 0°, 15 min

Et3SiH (10 eq), TMSOTf (1 eq),

CH2Cl2, 0°, 2 h

Ph2MeSiH (2 eq), TMSOTf (1 eq),

CH2Cl2, 0°, 15 min

Et3SiH (10 eq), TMSOTf (1 eq),

Et2O, rt, 99:1

N

C8H17-n

O

+

OH

I + II (86), I:II = 99:1

NEt2

I + II (99), I:II < 1:99

Ar

OH

Ph

OH

I + II (98), I:II > 99:1

N

I + II (99), I:II < 1:99

Ph

OH

+

I + II (98), I:II > 99:1

NEt2

I + II (98), I:II < 1:99

Ph

OH

II

O

II

O

II

O

II

O

I + II (45), (I + II):III = 8.5:1, I:II:III = 4:1.6:1

N

Ar = 4-ClC6H4

Ar = 4-ClC6H4

NEt2

N

NEt2

423

320

87, 276

87

87, 276

87, 320

87, 276

87, 320

428

432

C14

MeO

MeO

MeO

MeO

Ph

Ph

Ph

Ph

O

MeO

(75)

(78)

(85)

NHCOCF3

(22)

(100)

Cl

(83)

NHCOCF3

CO2Et

Ph

OSiEt3

Ph

(90)

OH

MeO

MeO

MeO

O

O

CO2Me Et3SiH (3.0 eq), TFA, 0° to rt, 16 h

reflux, 2 h; rt, 16 h

Et3SiH (4 eq), BF3•OEt2 (20 eq),

Ph

Ph

Et3SiO

O

Ph

Product(s) and Yield(s) (%)

OH

NHCOCF3

rt, 48 h

Et3SiH (3.66 eq), BF3•OEt2 (20 eq),

C6H14, 70°, 4 h

Et3SiH (2.5 eq), (Ph3P)3RhCl (0.5 mol%),

Et3SiH (2.2 eq), TFA, rt

CH2Cl2, rt, 5-20 min

PMHS (3 eq), (C6F5)3B (5 mol%),

2. Et3SiH (1.5 eq), –23°, 2.5 h

CH2Cl2, –78°, 30 min

1. SbCl5, TMSCl, SnI2,

Conditions

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

CO2Me

O

Cl

OTMS

NHCOCF3

CO2Et

O

O

O

O

O

HO2C

Ph

O

Ketone

416

753

753

411

73

354

306

Refs.

433

C15

i-Pr

Fe

Fe

H

Ph

O

O

O

O

O

OEt

H

(i-Pr)2Si

O

N

O

O

Pr-i

I

Fe

Fe

Fe

O

O

H

I

O Si (i-Pr)2

OEt

H

(86)

(80)

+

OEt

H

II

N

i-Pr

H OH

Ph

I + II (—), I:II = 35:1 I + II (—), I:II = 2:1 I + II (—), I:II = 5:1

TFA (0.2 eq), –80°, 30 min TBAF (0.2 eq), –80°, 30 min (Ph3P)3RhCl (0.08 eq), C6H6, reflux, 12 h

I + II (—), I:II = 2:1 I + II (—), I:II = 1:2.5

ZnCl2 (0.25 eq), –80°, 30 min; rt, 15 min

BF3•OEt2 (0.5 eq), –80°, 2 h ZnBr2 (0.12 eq), –80°, 8 h; rt, 16 h

I + II (—), I:II = 30:1 I + II (—), I:II = 320:1

TiCl4 (0.5 eq), –80°, 30 min

O Si (i-Pr)2 II

Pr-i

I+II = (—), I:II = 38:62

O I + II (—), I:II = 60:1

Pr-i

O

(55)

+

I + II (—), I:II = 60:1

i-Pr

O

N

MgBr2•OEt2 (0.1 eq), rt, 24 h

SnCl4 (0.1 eq), –80°, 2 h

Et3SiH (4 eq), TFA, rt, 4 h

Et3SiH (20 eq), TFA, rt, 20 h

Et3SiH (2 eq), TFA, rt, 120 h

Et3SiH, TFA

OH

Ph

399

179

179

179

754

434

C15

O

O

MeO

Ph

Ph

O

O

Ph

O

OSiMe2H

Ph

OSiMe2H

OMe

OTMS

OTMS

Ketone

DCE, reflux, 10 h

Et3SiH (5 eq), CF3SO3H (1 eq),

DCE, reflux, 20 h

Et3SiH (5 eq), Sn-mont,

Et3SiH (2.5 eq), TFA (5 eq), 20°

2. Et3SiH (1.5 eq), –23°, 2.5 h

CH2Cl2, –78°, 30 min

1. TrSbCl6 (5-30 mol%),

2. Et3SiH (1.5 eq), –23°, 2.5 h

CH2Cl2, –78°, 30 min

1. SbCl5, TMSCl, SnI2,

2. Et3SiH (1.5 eq), –23°, 2.5 h

CH2Cl2, –78°, 30 min

1. TrSbCl6 (5-30 mol%),

2. Et3SiH (1.5 eq), –23°, 2.5 h

CH2Cl2, –78°, 30 min

1. SbCl5, TMSCl, SnI2,

DMF, 100°, 24 h

DMF, 100°, 24 h

Conditions

I (54)

I (75)

MeO

I (96)

Ph

I (77)

I

O

I

OH

OH

I

O

Ph

OH

OH

Ph

Ph

I

+

II

(92)

OH

OMe

OH

(68)

(67)

Ph

(10)

I + II (26), I:II = 1:4

Product(s) and Yield(s) (%)

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

353

353

180

306

306

306

306

400

400

Refs.

435

C15

C15-16

Ph

Ph

Ph

Ph

O

O

O

MeO

MeO

Ph

MeO2C

O

Ph

O

O

O

Ph

TMS

TMS

CF3

N

OR

O

Ph

O

MeC6H5, 0°, 1 h

Et3SiH, (C6F5)3B (2 mol%),

MeC6H5, 0°, 1 h

Et3SiH, (C6F5)3B (2 mol%),

TASF (5-10 mol%), HMPA

PhMe2SiH (1.1-1.2 eq),

TBAF (5-10 mol%), HMPA, 0°

PhMe2SiH (1.2 eq),

reflux, 2 h, rt, 16 h

Et3SiH (4 eq), BF3•OEt2 (20 eq),

CH2Cl2, rt, 5-20 min

PMHS (3 eq), (C6F5)3B (5 mol%),

TFA, 0°, 10 min, rt, 3 h

Et3SiH (2.6 eq), PPHF,

Et3SiH , TFA, CH2Cl2

Ph

Ph

Ph

Ph

I

OH

OH

I

OH

MeO

MeO

Ph

MeO2C

+

OR

CF3

N

Ph

(88)

I

+

II

OH

THP

Ph

Ph

Ph

OH

I + II (100), I:II = 6.5:1

TMS

+

II

OH

16 h (77)

12 h (95)

Time

I + II (100), I:II = 1:1

TMS

(88)

(96)

t-Bu

R

(98)

I + II (90), I:II = 93:7

Ph

OH

O

Ph

Ph

II

TMS

87:13

95:5

TMS

threo:erythro

372

372

320

86

376

354

135

415

436

C16

C15

O

Ph

O

O

O

H

H

O

PMP

PMP

Ph

Ph

O

O

O

O

N

HO O

NEt2

H

N

O

O

OPh

NHSO2Ph

H

H

Ketone

O

PMP

N

N

87, 320

320

CH2Cl2, 0°, 10 min

Ph2MeSiH (10 eq), TMSOTf (1 eq),

CH2Cl2, 0°, 10 min

Et3SiH (10 eq), TMSOTf (1 eq), H

H

H I I (88) trans:cis 4:1

O

O

O

H

H

O (75) trans:cis = 3:1

I + II (93), I:II < 1:99

336

336

375

II

O

II

O

87

II (90) H

Ph

OH

II

NEt2

Et3SiH (1.1 eq), TFA, 0°, 4 h

+

I + II (92), I:II = 99:1

N

+

OH

O

373

87, 276

N

PMP

OH

+ Ph2SiHCl (—)

I + II (92), I:II > 99:1

NEt2

+

(77)

86

I + II (90), I:II = 99:1

O

O

O

OPh

(66) threo:erythro = 2:98

PhMe2SiH (1.2 eq), TASF, 0°

I

I

O

NHSO2Ph

Refs.

Ph

OH

PMP

OH

I

OH

OH

PMP

Ph

Ph

OH

Product(s) and Yield(s) (%)

PhMe2SiH (1.2 eq), TFA, 0°, 5 h

DMPU, 0°, 16 h

PhMe2SiH (1.2 eq), TASF (10 mol%),

DMPU, 0°, 16 h

PhMe2SiH (1.2 eq), TASF (10 mol%),

CH2Cl2, 20°, 24 h

Ph2SiH2 (1.2 eq), AlCl3 (1 eq),

PhMe2SiH (1.1-1.2 eq), TFA, 0°, 20 h

Conditions

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

437

C17

Bn

O

Ph

O O

O

O

O

Ph

OBz

Mn(CO)3

Fe

O

CN

CN

OTMS

CF3

CH2Cl2, rt, 45 min

Et3SiH (8 eq), TMSOTf (1 eq),

PhMe2SiH (1.2 eq), TFA, 0°, 6 h

HMPA, 0°, 12 h

PhMe2SiH (1.2 eq), TBAF (5-10 mol%),

2. Et3SiH (1.5 eq), –23°, 2.5 h

CH2Cl2, –78°, 30 min

1. TrSbCl6 (5-30 mol%),

2. Et3SiH (1.5 eq), –23°, 2.5 h

CH2Cl2, –78°, 30 min

1. SbCl5, TMSCl, SnI2,

Et3SiH, TFA, CHCl3, 50-60°, 15 h

Et3SiH (6 eq), TFA, rt, 5 h

Ph

O

OH

I

O

OH

I (95)

Bn

Ph

OH

Ph

OH

OBz

Mn(CO)3

Fe CN

CN

(98)

(72) threo:erythro = 7:93

(82) threo:erythro = 96:4

(80)

CF3

(95)

(41)

339

86

86

306

306

351

179

438

C18

C17

Ph

Ph

H

O

O

O

O

O

OMe

OMe

H

O

Ph

OSiMe2H

Ph

HO

Bu-n

OSiMe2H

OMe

CO2H O

O

H

H

(i-Pr)2Si

n-Bu

Ketone

O

THF, –78°, 3.5 h

BnOSiMe2H, TBAF (6 mol%),

TBAF (6 mol%), THF, –78°, 3.5 h

I

Ph

+

OH

I (0)

BnOSiMe2H, TBAF (6 mol%),

OH Ph

THF, –78°, 3.5 h

H

H

O

O

I

OH

Ph

OH

I

Bu-n +

n-Bu O

O

II

OH

Ph

Ph

OMe

OMe

H

H

OH Ph

(88)

(76)

(80)

O

I + II (46), I:II = 13:87

(81) trans:cis = 3:1

II

O Si (i-Pr)2

Bu-n

Product(s) and Yield(s) (%)

I + II (60), I:II = 40:1

O Si (i-Pr)2

OMe

I

CO2H

O

n-Bu

TBAF (6 mol%), THF, –78°, 3.5 h

Et3SiH, TFA

CH2Cl2, 0°, 2 h

Ph2MeSiH (2 eq), TMSOTf (1 eq),

SnCl4 (0.1 eq), –80°, 2 h

Conditions

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

400

400

400

400

417

336

399

Refs.

439

C19

C19-23

C18-23

C18-22

C18-19

Ar

S

(67)

O

Ar = 3-CF3C6H4

O

Et3SiH (5.1 eq), TFA, rt, 48 h

Et3SiH (2.5 eq), TFA, CH2Cl2, rt, 40 h

Ar

O

O

MeO

(58)

n-C5H11

Et3SiH (3 eq), TFA (5 eq), 6 h

(74)

n-Bu

R = Me, n-Pr, n-C5H11

(78)

i-Pr

(76)

(81) (78)

I

n-Pr

CH2Cl2, 0°, 30 min

I (70-90)

Et

Et3SiH (8 eq), TFA (10 eq),

Et3SiH (3 eq), TFA (5 eq), 50°, 6 h

Me

R

Et3SiH (8 eq), TFA (10 eq), 50°

H

R

HO2C

MeO

O

R = H, Et, n-Bu

O

O

O

O

O

O

(22)

I

(87)

H

OH

+

MeO

S

R

R

(11)

H

H

2h

(70-90)

OMe

6h

H

OH

(57)

(62)

(78)

6h

Br

(57)

24 h

Cl

Time

F

R

S

402

696

755

756

755

418

440

C20

C19-26

MeO

MeO

MeO

HO

TBSO

Bn

H

H O

H

H

O

H

H

H

H O

H

H

O

O OH

H

H

CH2Cl2, 0°, 2 h

Ph2MeSiH (2 eq), TMSOTf (1 eq),

i-PrOH, DCE, O2, rt

PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),

MeO

MeO

MeO

O H

(93)

BzOCH2

HO

(97)

Ph

i-PrOH, DCE, O2, rt

(96)

Br(CH2)6

O

H

H

H

(91)

(97)

EtO2CCH2

BnOCH2

(95)

H2C=CHCH2

H

H

H

H

O

OH

>99:1 OH

>99:1

>99:1

>99:1

>99:1

>99:1

>99:1

>99:1

I:II

Bn

(82)

H

+

HOCH2

I + II

R

>99:1

I

O

(95)

PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),

Bn

(90)

O

MeCN, rt

Et3SiH (1.2 eq), BiBr3 (5 mol%),

H

H

II

O

O

(61)

(47)

R

(75) trans:cis = 3:1

Product(s) and Yield(s) (%)

i-Pr

R

Conditions

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

Me

R

O

Ketone

336

367

367

342

Refs.

441

C21

C20-23

Ph

O

Ph

Fe

O

N

O

O

O

O

O

O

O Ph

O

N

Me

O

Ph

C9H19-n

N

O R O

(CO)9Co3C

Ph

O

2. HCl, acetone

18-C-6 (5 mol%), CH2Cl2, rt

1. PhMe2SiH (4 eq), CsF (5 mol%),

Et3SiH (20 eq), TFA, rt, 240 h

Et3SiH (6 eq), TFA (20 eq), 20°

Et3SiH, TFA

PhMe2SiH (1.2 eq), TFA, 0°, 4 h

I

Ph

HO

Ph

Fe

O

N

O

N

+

Ph

OH

Me

Ph

II (25) (20) (30) (20)

I (41) (47) (43) (43)

Me Et n-Pr n-Bu

(40)

(73)

O

II

R

+

(88)

I + II (98), I:II < 1:99

OH HO I

O

O Ph

O

C9H19-n

N

O R O

(CO)9Co3C

Ph

OH

O

O R

N

II

O Ph

O

369

179

757

183

87, 276

442

C21

O

O

O

O

H

H

N

H H

H

H

O

H

H

H

CO2Me

CO2Me

PMP

Ph

O

Ketone

O

Ph2SiH2, Rh-(–)-diop, C6H6, 22°

Ph2SiH2, Rh-(+)-diop, C6H6, 22°

Ph2SiH2, Rh-(–)-diop, C6H6, 22°

Ph2SiH2, Rh-(+)-diop, C6H6, 22°

2. Et3SiH, CH2Cl2

1. TFA, 2 h

H

H

H

H I

I

H

H

H +

OH

+

HO

+

OH

(17)

N

H

II

H

H

H

II

I + II (—), I:II = 67:33

H

I CO2Me

I + II (—), I:II = 64:36

HO

I:II = 7:3

I (25)

H

CO2Me

I + II (90), I:II = 1:1

Et3SiH, TFA, CH2Cl2, rt, 16 h

+

OH H H

PMP O I + II (50), I:II = 1:4

PhMe2SiH, TFA, THF, 0°, 22 h

I

N

Ph

I + II (90), I:II = 1:8

O

OH H H

H

(18)

OH

I:II 7:3

OH

H

CO2Me

H

II

H

H

Ph

CO2Me

PMP

Product(s) and Yield(s) (%)

PhMe2SiH, TASF, THF, HMPA, rt, 23 h

PhMe2SiH, TASF, THF, rt, 70 h

Conditions

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

573

573

573

573

758

758

371

371

371

Refs.

443

C24-26

C24

C23

Bn

S H

O

O

O

O

OTBS

S

O

Ph

Ph

O

O

O

Ph

O

R

R

Ph

CCl4, 50-55°, 8 h

Et3SiH (5 eq), TFA (10 eq),

Et3SiH (6 eq), TFA (20 eq), 50°, 6 h

MeCN, rt

Et3SiH (1.2 eq), HBr (15 mol%),

MeCN, rt

+ Bn

OH

O

O

O

O

Ph

Ph

I + II (99), I:II > 99:1

R

I + II (97) I:II > 99:1 I + II (99), I:II > 99:1

O I

H

Et3SiH (1.2 eq), TMSBr (15 mol%),

S

MeCN, rt

S

Bn

Et3SiH (1.2 eq), BiBr3 (5 mol%),

2. KOH, MeOH, THF, rt

CH2Cl2, 50°, 20 h

1. Et3SiH (10 eq), TFA (50 eq),

O

R

Ph

(49) (30) Et

(33) Me

H

R

R = H, Me, Et (—)

O II

(73)

266

757

342

342

342

368

444

C31

C28

C27

O

O

HO

n-C10H21

O

O

H

C8H17-n

OPMP

CH(PMP)2

OBn

O TBSO

N

H

H

Ketone

2. TBSOTf, 2,6-lutidine, 0°

1. t-BuMe2SiH, BiBr3, MeCN, 0°

MeOC6H5, –25°, 1.5 h

BF3•OEt2 (0.23 eq),

Et3SiH (3 eq), TFA (4 eq),

i-PrOH, DCE, O2, rt

PhSiH3 (0.4 eq), Mn(dpm)3 (3 mol%),

CH2Cl2, rt, 5-20 min

PMHS (3 eq), (C6F5)3B (5 mol%),

Conditions

I

n-C10H21

TBSO

O

OH

HO

O

OH

III

N

CH(PMP)2

OBn

H

H

O

OBn +

+

OH

(92)

II

O OPMP

(93)

OBn

O IV

N H

CH(PMP)2 OH

N

I + II (71), I:II = 8:1, III + IV (10)

N

H

H

C8H17-n

(—)

Product(s) and Yield(s) (%)

TABLE 12. ORGANOSILANE REDUCTION OF KETONES (Continued)

OBn

404

395

367

354

Refs.

445

C38

C37

H

O

O

H

O

HO H H

H

HO H

O

O

O

c This

CH2Cl2, 0°, 2 h

TMSOTf (1 eq),

Ph2MeSiH (2 eq),

CH2Cl2, 0°, 2 h

TMSOTf (1 eq),

Ph2MeSiH (2 eq),

column gives the amount of acid used in a one mmol reaction.

The yield was determined by gas chromatography.

H

O

H

H

The yield was determined by NMR spectroscopy.

O

H

O

b

H

H

H

O

H

a

BnO

BnO

BnO

BnO

BnO

BnO

BnO

BnO

H

H

H

O

O

H

H

O H

O H

O

H

H

O

O

(62) trans:cis = 6:1)

H

H

(55) trans:cis = 3:1

H

H

H

H

H

O

O

336

336

446

C5

C5-13

H H Me Ph

n-C7H15

Me

Ph

H

NH2

H

Ph

t-BuO

H

H

4-MeC6H4

O

H

—(CH2)6—

Ph

Me

Bn

H

Me

Me

—(CH2)5—

—(CH2)2O(CH2)2—

Me

—(CH2)4—

Me

Me

—(CH2)2O(CH2)2—

R3

—(CH2)3—

H

—(CH2)5—

R2

H

R2

—(CH2)4—

R3

N

H

R1

R1

O

Amide

EtI EtI EtI none none EtI none none EtI EtI none EtI none none

(Ph3P)2RuCl2(CO)2 (Ph3P)2RuCl2(CO)2 (Ph3P)2RuCl2(CO)2 Ru3(CO)12 Ru3(CO)12 (Ph3P)2RuCl2(CO)2 Ru3(CO)12 Ru3(CO)12 [RuCl2(CO)3]2 [RuCl2(CO)3]2 Os3(CO)12 [RuCl2(CO)3]2 Os3(CO)12 Ru3(CO)12

(50.3) (97.1) (56.0) (99.5) (99.5) (93.2)

Et2NH Et2NH Et2NH Et2NH none

(92) (81)

3

t-BuO

(95.9)

Et2NH

O

(99.2)

none

(92.3)

(86.6)

(87.7)

(87.0)

(86.1)

NHBn

R2

(92.9)

R3

N

none

none

none

none

none

none

none

Cat-3

R1

0.33

x

PhCHO (x eq), MeCN, 22°, 18 h

Et3SiH (3 eq), TFA (2-3 eq),

Cat-2

Cat-1

MeC6H5, 100°

cat-2 (5 mol%), cat-3 (5 mol%),

Et3SiH (3-3.5 eq), cat-1 (1 mol%),

Conditions

Product(s) and Yield(s) (%)

TABLE 13. ORGANOSILANE REDUCTION OF AMIDES

326

432

Refs.

447

C7

O

N

16 h 40 h 16 h 16 h 16 h

none Et2NH Et2NH Et2NH pyridine

(Ph3P)2RuCl2(CO)2 I2 EtI EtI none none none none none none none

(Ph3P)3RuH2(CO) Ru(acac)3 Os3(CO)12 Os3(CO)12 (Ph3P)4RhH IrCl3 K2IrCl6 Pd(OH)2/C PtCl2

(EtO)3Si

[RuCl2(CO)3]2

EtI

Et2NH

none

Me(EtO)2Si (Ph3P)2RuCl2(CO)2 EtI

16 h

16 h

16 h

16 h

Et2NH none

Os3(CO)12

ClMe2Si

none

40 h

Et2NH EtI

Me2(EtO)Si (Ph3P)2RuCl2(CO)2 EtI

16 h none

(Ph3P)2RuCl2(CO)2 EtI [RuCl2(CO)3]2

t-BuMe2Si

16 h

Time

(78.5)

(77.7)

(92.6)

(94.4)

(99.5)

(99.3)

(99.8)

(88.0)

(94.4)

(94.1)

i-Pr3Si

none

Cat-2

(Ph3P)2RuCl2(CO)2 EtI

PhMe2Si

MeC6H5, 100° Cat-1 R3Si

cat-2 (5 mol%), cat-3 (5 mol%), Cat-3

16 h

Et2NH I

40 h

Et2NH

R3SiH (3-3.5 eq), cat-1 (1 mol%),

16 h

16 h

Et2NH

none

16 h

(96.1)

16 h

none

(Ph3P)2RuCl2(CO)2 MeI

Et2NH

(88.2)

16 h

none

(Ph3P)2RuCl2(CO)2 EtI (98.1)

(95.6)

none

Ru3(CO)12

16 h

Et2NH

none

Re2(CO)10 none

(89.3)

Et2NH

none 16 h

16 h

Cat-3

Cat-2

I

Mn2(CO)10

Time

N

Cat-1

MeC6H5, 100°

cat-2 (5 mol%), cat-3 (5 mol%),

Et3SiH (3-3.5 eq), cat-1 (1 mol%),

I

(86.1)

(90.8)

(93.1)

(80.1)

(50.6)

(70.4)

(90.2)

432

432

448

C8

C7

C7-8

O

MeC6H5 MeC6H5 MeCN

Bn

4-MeOC6H4

BnO

O NH2

N Bu-n

O

18 h

22°

MeC6H5

PhNH

18 h

18 h

22° 22°

18 h

120°

THF, rt, 3.5 h

(Ph3P)3RhH(CO) (1 mol%),

Ph2SiH2 (4.3 eq),

THF, rt, 0.5 h

(Ph3P)3RhH(CO) (0.1 mol%),

Ph2SiH2 (2.1 eq),

MeCN, 22°, 18 h

EtCH(OEt)2 (0.33 eq),

Et3SiH (3 eq), TFA (2.9 eq),

MeC6H5

18 h

22°

MeCN

PhO

BnNH

18 h

120°

MeC6H5

4-FC6H4

36 h

18 h

120°

MeC6H5

120°

Temp Time

Solvent

Ph

PhCHO (x eq)

Et3SiH (3 eq), TFA (2-3 eq),

Conditions

N H

Ph

N Bu-n

N Bu-n

O N H

(89)

(95)

(95)

(92)

(92)

(90)

(92)

(91)

(70)

(88)

(92)

(91)

(68)

(97)

(85)

(93)

(94)

x = 0.33 x = 3

Ph

R

O

(66)

(65)

Product(s) and Yield(s) (%)

TABLE 13. ORGANOSILANE REDUCTION OF AMIDES (Continued)

R

NH2

O N Bu-n

Ph

R

O

Amide

431

431

326

326

Refs.

449

C9-14

(88) (93) (90) (91) (96) (94) (77)

Cp2TiMe2 Cp2TiF2 Cp2TiMe2 Cp2TiF2 Cp2TiMe2 Cp2TiF2 Cp2TiF2 Cp2TiMe2 Cp2TiF2

H H H 4-Cl 4-Cl 4-Me 4-CF3 4-MeO H

Me Et Et Et Et Et Et Et Ph

Me

Et

Et

Et

Et

Et

Et

Et

Me

(92)

(80)

Cp2TiF2 (84)

Catalyst

H

Me

Me

R3

R1R2N

R3

MeC6H5, 80°, 1 h

PhMeSiH2 (2 eq), catalyst (1 mol%),

R2

R2

N

R1

R1

R3

O

50:50

56:44

53:47

62:38

53:47

53:47

53:47

52:48

52:48

52:48

meso:rac

I

NR1R2

R3

430

450

C10

C9-14

Et Et Et Et Et Ph

Et

Et

Et

Et

Et

Me

N

Me

R1

NEt2

R2

Me

O

N R2

R1

R3

O

+

MeC6H5, 20°, 30 min

2. PhMeSiH2 (2 mmol), amide (1 mmol),

MeC6H5, 70°, 10 min

Cp2TiF2 (0.1 mol),

1. PhMeSiH2 (3 mmol),

MeC6H5, 80°, 1 h

(0)

II

N

O

O

(25)

R3 III

NEt2

(41.1)

(23.5)

I (43.5) meso:rac = 56:44 + II (34.1) +

I N N (27) meso:rac = 57:43

N

(44.2)

55:45

(14.7)

H

PhMeSiH2 (2 eq), Cp2TiF2 (1 mol%),

(20.6)

53:47

(55.9)

4-CF3

NEt2

(0)

50:50

(100)

Et2N

(0)

53:47

(100)

(0)

(2.3) (25.3)

4-Me

III (16.7)

II

+

(2.0)

R1

(0)

4-MeO

II

R2

N

(29.9)

(44.8)

4-Cl

54:46

meso:rac

R3

R3

53:47

(97.7)

H

+

NR1R2

Product(s) and Yield(s) (%)

60:40

I

I

(81.3)

R3

R1R2N

H

MeC6H5, 20°, 30 min

2. PhMeSiH2 (2 mmol), amide (1 mmol),

MeC6H5, 70°, 10 min

Cp2TiF2 (0.1 mol),

1. PhMeSiH2 (3 mmol),

Conditions

TABLE 13. ORGANOSILANE REDUCTION OF AMIDES (Continued)

R3

Amide

430

H (22.4) 430

H

430

Refs.

451

C11

C10-19

Ph

Ph

R

1

O

O

48 h

NBu2 NBu2 NEt2 NMe(C6H11-c) N(C6H11-c)2

i-Pr t-Bu 4-MeO2CC6H4 Ph Ph

NEt2

NMe2

24 h

NEt2

4-BrC6H4

O

20 h

NEt2

Ph

85:15:0 43:9:48 92:8:0 59:1:49

80° 20° 80°

[—(Me)(H)SiO—]4 80° 80°

n-C6H13SiH3 [—(Me)(H)SiO—]4 20° 20°

n-C6H13SiH3

PMHS PMHS

(—)

51:30:19

100:0:0

92:8:0

20°

PhSiH3

I:II:III

PhSiH3

I

Ph

+

NMe2

NEt2

NEt2

(83)

(91)

(70)

(86)

(90)

(85)

(85)

(98)

NR2

Temp

Ph

Et2N

Ph

Ph

R1

Silane

MeC6H5, 1 h

Silane (1 eq), Cp2TiF2 (0.1 mol),

2. Acid, 0.5 h

1,4-dioxane, 20°, 0.5 h

1. EtMe2SiH (2.5 eq), 2 (1 mol%),

2. Add acid, 0.5 h

1,4-dioxane, 20°, 0.5 h

1. EtMe2SiH (2.5 eq), 2 (1 mol%),

48 h

4h

4.5 h

2h

3h

N(CH2)5

Time

NR2

MeO2CCH2CH2

(Ph3P)3RhH(CO) (0.1 mol%), THF, rt

Ph2SiH2 (2.1 eq),

R1

NR2

II

NEt2

(—)

56:44

55:45

52:48

56:44

55:45

57:43

54:46

I meso:rac

Ph

(56)

(75)

Ph

(0)

(37)

(81)

(40)

(90)

(66)

(83)

(86)

+

III

O H

430

280

280

431

452

C14

C12

C11

Br

Ph

O

S

8

O

8

O

8

O

O

NHBu-t

NEt2

O

O

NMe2

NMe2

O

N Bn

NEt2

NEt2

Amide

Ti(OPr-i)4 (1.0 eq), 20°

Ph2SiH2 (1.1 eq),

Ti(OPr-i)4 (1.0 eq), 20°

Ph2SiH2 (1.1 eq),

Ti(OPr-i)4 (1.0 eq), 20°

Ph2SiH2 (1.1 eq),

Ti(OPr-i)4 (1.0 eq), 20°

Ph2SiH2 (1.1 eq),

Ti(OPr-i)4 (1.0 eq), 20°

Ph2SiH2 (1.1 eq),

THF, rt, 3 h

(Ph3P)3RhH(CO) (0.1 mol%),

Ph2SiH2 (2.1 eq),

2. Add acid, 2 h

1,4-dioxane, 20°, 0.5 h

1. EtMe2SiH (2.5 eq), 225 (1 mol%),

Conditions

S

8

I

H

H

O

O

8

O

I (90)

Br

Ph

N Bn

H

H

(90)

O

O

(74)

NMe2

(45)

(65)

(80)

(65)

Product(s) and Yield(s) (%)

TABLE 13. ORGANOSILANE REDUCTION OF AMIDES (Continued)

433

433

433

433

433

431

280

Refs.

453

C16

C15

O

O

2-Np

O 8

8

O

NHBu-t

NHBu-t

NEt2

NBn2

O

Catalyst (Ph3P)3RhH(CO) (Ph3P)4RhH [Rh(cod)2]BF4 (Ph3P)3RhCl RhCl3•3H2O (Ph3P)3RhH(CO)

R3Si Ph2HSi Ph2HSi Ph2HSi Ph2HSi Ph2HSi Ph3Si

THF, rt

—

48 h

48 h

42 h

0.5 h

1h

Time

R3SiH (2.1 eq), catalyst (0.1 mol%),

Ti(OPr-i)4 (1.0 eq), 20°

Ph2SiH2 (1.1 eq),

Ti(OPr-i)4 (1.0 eq), 20°

Ph2SiH2 (1.1 eq),

MeC6H5, 20°, 30 min

2. PhMeSiH2 (2 mmol), amide (1 mmol),

70°, 10 min

Cp2TiF2 (0.1 mol), MeC6H5,

1. PhMeSiH2 (3 mmol),

Cp2TiF2 (1 mol%), MeC6H5, 80°, 1 h

PhMeSiH2 (2 eq), Np-2

NEt2 + 2-Np

O

O

(0)

(95)

(93)

(86)

(93)

(94)

NBn2

8

8

O

H

H

(50)

(90)

O

(9)

2-Np

II

NEt2

I (51.2) meso:rac = 48:52 + II (39.6) +

I (83) meso:rac= 54:46

2-Np

Et2N

H

(9.2)

431

433

433

430

430

454

C20

C18

C17

C16

N

BnO

7

8

O

TBSO

8

O

NHBu-t

O 10

9

O

5

O

8

O NMe2

N(Pr-i)2

N(Pr-i)2

NHBu-t

NMePh

5

O

N(Pr-i)2

Amide

Ti(OPr-i)4 (1.0 eq), 20°

Ph2SiH2 (1.1 eq),

Ti(OPr-i)4 (1.0 eq), 20°

Ph2SiH2 (1.1 eq),

Ti(OPr-i)4 (1.0 eq), 20°

Ph2SiH2 (1.1 eq),

Ti(OPr-i)4 (1.0 eq), 20°

Ph2SiH2 (1.1 eq),

Ti(OPr-i)4 (1.0 eq), 20°

Ph2SiH2 (1.1 eq),

Ti(OPr-i)4 (1.0 eq), 20°

Ph2SiH2 (1.1 eq),

Ti(OPr-i)4 (1.0 eq), 20°

Ph2SiH2 (1.1 eq),

Conditions

N

BnO

7

8

O

TBSO

8

O

O

O 10

9

O

5

O

H

5

H

H

H

H

O 8

H

H

(80)

(80)

(81)

(83)

(87)

(78)

(83)

Product(s) and Yield(s) (%)

TABLE 13. ORGANOSILANE REDUCTION OF AMIDES (Continued)

433

433

433

433

433

433

433

Refs.

455

C5

C4-12

C4

R

N

O

O

N H

H

H

O

CHO

Aldehyde/Ketone

4h 4h

3-C5H4N Ph

2-C4H3S (CH2)3NMe2

Ph Ph

N

N

N

Ar = 4-TBSOC6H4

Me2SiH(NEt2) (1.2 eq)

Ar

4h

4-FC6H4

Ph

CN

NH2

4h

Ph

2-C4H3S

CN

CH2Cl2, 0° to rt, 36 h

TiCl4 (0.20 eq),

TBAF, 20° or reflux, 24-300 h

(n-Bu)2SnCl2 (0.02 eq), THF,

PhSiH3 (1.1 eq),

THF, 20° or reflux, 24-300 h

(n-Bu)2SnCl2 (0.02 eq),

PhSiH3 (1.1 eq),

4h

Ph

4-MeOC6H4

CN

NH2

2h

Ph

n-Pr

CN

N

Time

R3

R

N H

Et3SiH (2 eq), TFA, CH2Cl2, rt

2

R3

SO2R2

Conditions

R1

R1

Amine

N

N

O

HO

R1

H N R

NEt2

(90)

(93)

(95)

(93)

(94)

(90)

HN

N

N

N

(56)

n-C11H23

(57)

(10) n-C11H23

(17) Bn

(41)

(25) Ph

i-Pr

n-Pr

R

(50)

Bn

R

(72)

Ph

H N

(70)

(63) i-Pr

n-Pr

R

(65)

N

R3

SO2R

2

Product(s) and Yield(s) (%)

TABLE 14. ORGANOSILANE REDUCTIVE AMINATION OF ALDEHYDES AND KETONES

359

362

362

360

Refs.

456

C7

C6

O

Ph

O

c-C6H11

t-Bu

H

O

O H

O

Aldehyde/Ketone

PhNH2

BnNH2

Me2SiH(NEt2) (1.2 eq)

N H

PhNH2

BnNH2

MeCN

MeCN

Amine

2. PMHS (2 eq), THF, 5 h

THF, rt, 1 h

1. Ti(OPr-i )4 (1.25 eq),

2. PMHS (2 eq), THF, 5 h

THF, rt, 1 h

1. Ti(OPr-i )4 (1.25 eq),

0° to rt, 36 h

ZnI2 (0.10 eq), CH2Cl2,

2. PMHS (2 eq), THF, 5 h

THF, rt, 1 h

1. Ti(OPr-i )4 (1.25 eq),

2. PMHS (2 eq), THF, 4.5 h

THF, rt, 1 h

1. Ti(OPr-i )4 (1.25 eq),

2. PMHS (2 eq), THF, 4.5 h

THF, rt, 1 h

1. Ti(OPr-i )4, (1.25 eq),

H2O, 28°, 65 h

Et3SiH (1.1 eq), H2SO4,

H2O, 28°, 65 h

Et3SiH (1.1 eq), H2SO4,

Conditions

Ph

Ph

c-C6H11

N

HN

NHPh

NHBn

Ph

O

(92)

(90)

(81)

(85)

(87)

(88)

(78)

(67)

Product(s) and Yield(s) (%)

NEt2

H N

NHBn

N H

O

TABLE 14. ORGANOSILANE REDUCTIVE AMINATION OF ALDEHYDES AND KETONES (Continued)

363

363

359

363

363

363

313

313

Refs.

457

C7-9

R

I

O

O2N

H

O H

O H

N

PMP

N NH2

NH2

N

N Ar1 Ar1 = 4-TBSOC6 H4

BnNH2

PhNH2

PhNH2

BnNH2

PhNH2

Ar1

PMP

N H

N

N

H N

PMP

NH

Ph

0°, 4 h

(86)

(85)

(85)

(37)

(74) BnCH2

(93)

(E)-PhCH=CH (81)

c-C6H11

NHPh

NHPh

NHBn

(80)

R NHBn

NHPh

(78)

Ph

(85)

Ar2 N Ar2 = 4-HOC6H4

N

N

2. Cl3SiH, CH2Cl2/DMF (4:1),

R

I

O2N

O2N

Ph

Ar2

PMP

Ph

1. MgSO4, CH2Cl2, rt, 1 h

THF, rt, 2-24 h

(n-Bu)2SnCl2 (0.02 eq),

PhSiH3 (1.1 eq),

THF, rt, 2-24 h

(n-Bu)2SnCl2 (0.02 eq),

PhSiH3 (1.1 eq),

2. PMHS (2 eq), THF, 4 h

THF, rt, 1 h

1. Ti(OPr-i )4 (1.25 eq),

THF, rt, 2-24 h

(n-Bu)2SnCl2 (0.02 eq),

PhSiH3 (1.1 eq),

THF, TBAF, 20°, 24 h

(n-Bu)2SnCl2 (0.02 eq),

PhSiH3 (1.1 eq),

THF, 20°, 24 h

(n-Bu)2SnCl2 (0.02 eq),

PhSiH3 (1.1 eq),

2. PMHS (2 eq), THF, 5.5 h

THF, rt, 1 h

1. Ti(OPr-i )4 (1.25 eq),

318

361

361

363

361

362

362

363

458

C7-10

R

1

R2 H H H H H Me H Me H H H H H Me H H Me

Ph

Ph

4-MeC6H4

4-MeC6H4

4-O2NC6H4

Ph

BnCH2

BnCH2

Ph

BnCH2

Ph

BnCH2

Ph

Ph

BnCH2

BnCH2

BnCH2

R

2

R1

O

Aldehyde/Ketone

R4

Me

Me

Me

Me

Me

Me

Me

Me

H

H

H

H

H

CO2Me

CO2Me

CO2Me

CO2Me

CO2Me

—(CH2)2O(CH2)2—

—(CH2)2O(CH2)2—

—(CH2)4—

—(CH2)4—

Me

Me

Me

Me

Me

Me

Me

Me

R3

R3R4NSiHMe2 (1.2 eq)

Amine

Ph3CClO4

Ph3CClO4

Ph3CClO4

Ph3CClO4

Ph3CClO4

ZnI2

TiCl4

ZnI2

TiCl4

TiCl4

ZnI2

TiCl4

TiCl4

TiCl4

TiCl4

TiCl4

TiCl4

Catalyst

36 h

0.1

1h

(86)

(88)

0.05

(40)

1h

0.05

(53)

(94)

(66)

(83)

(71)

(77)

(67)

(72)

(87)

(94)

(85)

(67)

(73)

(64)

R2

3h

1h

R1

NR3R4

0.05

0.05

2h

36 h

0.2 0.05

36 h

36 h

48 h

36 h

36 h

48 h

36 h

36 h

36 h

36 h

Time

0.1

0.3

0.2

0.1

0.4

0.2

0.4

0.2

0.4

0.2

x

Catalyst (x eq), CH2Cl2, 0° to rt

Conditions

Product(s) and Yield(s) (%)

TABLE 14. ORGANOSILANE REDUCTIVE AMINATION OF ALDEHYDES AND KETONES (Continued)

359

Refs.

459

C7-13

R1

Pd-C Ti(OPr-i)4 AlCl3 Pd-C Ti(OPr-i)4

Bn Ph Ph Ph

Me Me Me Me

Ph

Ph

Ph

Ph

Pd-C

Ph

Bn

AlCl3

Ph

Me

Ti(OPr-i)4

Bn

Ph

H

(E)-PhCH=CH

Pd-C

Bn

AlCl3

H

(E)-PhCH=CH

AlCl3

Bn

Bn

H

(E)-PhCH=CH

Ti(OPr-i)4

Ph

Me

H

(E)-PhCH=CH

Pd-C

Ph

Ph

H

Ph

AlCl3

Ph

Ti(OPr-i)4

H

Ph

Ti(OPr-i)4

Bn

Ph

H

Ph

Pd-C

Bn

H

H

Ph

AlCl3

(E)-PhCH=CH

H

Ph

Activator

R3 Bn

THF

EtOH

MeC6H5

THF

EtOH

MeC6H5

THF

EtOH

MeC6H5

THF

EtOH

MeC6H5

THF

EtOH

MeC6H5

THF

EtOH

MeC6H5

6h

10 h

13 h

6h

10 h

13 h

4.5 h

9h

12 h

4h

8h

10 h

5h

10 h

12 h

5h

10 h

12 h

Solvent Time (2)

2. PMHS (2 eq), THF

solvent, rt, 1 h

1. Activator (1.25 eq),

H

H

R NH2

3

(E)-PhCH=CH

R2

Ph

R2

R1

O R1

(90)

(58)

(50)

(90)

(55)

(45)

(88)

(56)

(45)

(85)

(55)

(48)

(92)

(62)

(52)

(90)

(60)

(40)

R2

NHR3 363

460

C7-13

R1

Ar

(46) (86)

Ph H

Ph

4-PhC6H4

H Me H Ph

Ph

n-C7H15

Ph

—(CH2)5—

Ph

R1 R2

(84)

H

4-MeO2CC6H4

48 h

72 h

72 h

74 h

72 h

Time

(63)

(0)

(85)

(80)

(30)

N H

(39)

Et

Ph

R2

(84)

H

4-NCC6H4

H2O, 28°

(92)

H

4-MeOC6H4

R2

(91)

H

4-MeC6H4

R1

(65)

Me

Ph

Et3SiH (1.1 eq), H2SO4,

(85)

H

4-O2NC6H4

MeCN

(78)

H

O

(90)

H

R

4-ClC6H4

Ar

NEt2

R

CH2Cl2, 0° to rt, 36 h

TiCl4 (0.20 eq),

Conditions

Ph

R

Me2SiH(NEt2) (1.2 eq)

Amine

O

Product(s) and Yield(s) (%)

TABLE 14. ORGANOSILANE REDUCTIVE AMINATION OF ALDEHYDES AND KETONES (Continued)

Ar

O

Aldehyde/Ketone

313

359

Refs.

461

C8

C7-23

PMP

Ar

O

1.1 1.1 1.1 1.1 1.1 0.5 0.33 0.20 2.0 1.1

Et3Si Ph3Si Ph2HSi Ph2HSi PhH2Si PhH2Si PhH2Si PhH2Si PhH2Si PMHS PhH2Si

THF, rt, 2-24 h

(n-Bu)2SnCl2 (0.02 eq),

PhSiH3 (1.1 eq),

x 1.1

R3Si

PhNH2 (1.0 eq), THF, rt, 21 h

PMP

(91)

NHMePh

(46)

4-TBDPSOC6H4

N H

(0) N Me

(82)

(—)

(83)

(83)

(83)

(82)

(—)

(88)

(0)

(0)

(90)

4-TBSOC6H4

(n-Bu)2SnCl2 (0.02 eq),

(75)

4-BnOC6H4

H

(96)

4-AcOC6H4

O

(91)

Ph

Ph

NHCOPh

4-HO2CC6H4

PMP

Ar

(96)

R3SiH (x eq),

MeC6H5, 120°, 18 h

Et3SiH (3 eq), TFA (2.9 eq),

4-MeO2CC6H4

PhNH2

PhCONH2 (3 eq)

4-FC6H4

Ar

H

(83)

361

361

326

462

C8

O

O

PMP

5

O

O

O H

Aldehyde/Ketone

PhNH2

PhNH2

Et2NH

N H

N H Ph N

O

THF, rt, 2-24 h

(n-Bu)2SnCl2 (0.1 eq),

PhSiH3 (1.1 eq),

THF, rt, 2-24 h

(n-Bu)2SnCl2 (0.02 eq),

PhSiH3 (1.1 eq),

THF, rt, 16 h

(n-Bu)2SnCl2 (0.02 eq),

PhSiH3 (1.1 eq),

THF, rt, 16 h

(n-Bu)2SnCl2 (0.02 eq),

PhSiH3 (1.1 eq),

THF, rt, 16 h

(n-Bu)2SnCl2 (0.02 eq),

PhSiH3 (1.1 eq),

PhSiH3 (1.1 eq), THF, rt, 16 h

THF, rt, 16 h

(n-Bu)2SnCl2 (0.02 eq),

O

O

NHPh

PMP

PMP

PMP

I (13)

I

(70)

(49)

(67)

(78)

NHPh

NPh

O

(91)

NEt2

N

N

N

(85)

N H

(85)

PhSiH3 (1.1 eq),

(85)

Product(s) and Yield(s) (%) Ar

4-t-BuC6H4

N H (82)

PMP

PMP

4-O2NC6H4

THF, rt, 2-24 h

(n-Bu)2SnCl2 (0.02 eq),

PhSiH3 (1.1 eq),

Conditions

4-MeOC6H4

Ar

ArNH2

Amine

TABLE 14. ORGANOSILANE REDUCTIVE AMINATION OF ALDEHYDES AND KETONES (Continued)

361

361

361

361

361

361

361

361

Refs.

463

C9

Ph

Ph

Ph

O

O

O

H

H

N H

BnNH2

PhNH2

Me2SiH(NEt2) (1.2 eq)

N H

BnNH2

PhNH2

PhNH2

2. PMHS (2 eq), THF, 4.5 h

THF, rt, 1 h

1. Ti(OPr-i)4 (1.25 eq),

2. PMHS (2 eq), THF, 4 h

THF, rt, 1 h

1. Ti(OPr-i )4 (1.25 eq),

2. PMHS (2 eq), THF, 4.5 h

THF, rt, 1 h

1. Ti(OPr-i)4 (1.25 eq),

THF, rt, 2-24 h

(n-Bu)2SnCl2 (0.02 eq),

PhSiH3 (1.1 eq),

0° to rt, 36 h

ZnI2 (0.10 eq), CH2Cl2,

2. PMHS (2 eq), THF, 6 h

THF, rt, 1 h

1. Ti(OPr-i )4 (1.25 eq),

2. PMHS (2 eq), THF, 6 h

THF, rt, 1 h

1. Ti(OPr-i )4 (1.25 eq),

2. PMHS (2 eq), THF, 6 h

THF, rt, 1 h

1. Ti(OPr-i )4 (1.25 eq),

THF, rt, 2-24 h

(n-Bu)2SnCl2 (0.1 eq),

PhSiH3 (1.1 eq),

I

N

Ph

Ph

I (88)

Ph

Ph

Ph

Ph

NHPh

I

NHBn

I (90)

Ph

N

NHBn

NHPh

NEt2

(88)

(90)

(70)

(85)

(85)

(70)

(72)

363

363

363

361

359

363

363

363

361

464

C13

C10

Ph

Ph

O

t-Bu

Ph

O

CO2Bu-t O

N

O

O

Aldehyde/Ketone

ArNH2

N H

Ph

(85)

Ph

NHAr

N

(88)

(80)

NEt2

NHBn

t-Bu

(83)

Ph

Ph

Ph

+

t-Bu

+

(46)

II

O

t-Bu

OH

I

+

Bu-t

t-Bu

(21)

I + II (70)

NHEt

Product(s) and Yield(s) (%)

(86)

(4)

CO2Bu-t

N

NHPh

Bn

2. PMHS (2 eq), THF, 4.5 h

THF, rt, 1 h

1. Ti(OPr-i )4 (1.25 eq),

2. PMHS (2 eq), THF, 4.5 h

THF, rt, 1 h

1. Ti(OPr-i )4 (1.25 eq),

0° to rt, 36 h

ZnI2 (0.10 eq), CH2Cl2,

2. PMHS (2 eq), THF, 4.5 h

THF, rt, 1 h

1. Ti(OPr-i )4 (1.25 eq),

H2O, 28°, 65 h

Et3SiH (1.1 eq), H2SO4,

THF, rt, 2-24 h

(n-Bu)2SnCl2 (0.02 eq),

PhSiH3 (1.1 eq),

Conditions

Ph

Ar

Me2SiH(NEt2) (1.2 eq)

BnNH2

MeCN

PhNH2

Amine

TABLE 14. ORGANOSILANE REDUCTIVE AMINATION OF ALDEHYDES AND KETONES (Continued)

363

363

359

363

313

361

Refs.

465

C14

H OBn

O PhNH2 THF, rt, 2-24 h

(n-Bu)2SnCl2 (0.02 eq),

PhSiH3 (1.1 eq), OBn

NHPh (82) 361

466

C9

C5

C4

C3

Ph

O

O

O

H

O

H

H

H

Unsaturated Aldehyde

Ph

(EtO)3SiH (1.1 eq), KF (1 eq),

(85) (65) (65) (100)

C6H4(CO2K)2-1,2 CsF

I

Ph2SiH2 (0.5 eq), salt Salt KF

I (95)

Me(EtO)2SiH (1.1 eq), CsF (1 eq), rt, 2 h

HCO2K

I (80)

(EtO)3SiH (1.1 eq), CsF (1 eq), rt, 1 h

rt, 24 h

I (98.6)

I (—)

I (—)

Ph

I

I

O

O

O

H

H

(9)

O

OH n-Pr

PhSiH3 (1.01 eq), Ni, PPh3 (0.02 eq)

0° to rt, 2 h

Ph2SiH2 (1.1 eq), (Ph3P)3RhCl,

C6H6, 45°, 1 h

Et3SiH (1.1 eq), (Ph3P)3RhCl,

rt, 3 min

Ph2SiH2 (2.3 eq), CsF (1 eq),

PhSiH3 (1.01 eq), Ni, PPh3 (0.02 eq)

PhSiH3 (1.01 eq), Ni, PPh3 (0.02 eq)

CHCl3, 40°, 6 h

Et3SiH (3 eq), TFA (6 eq),

Conditions

OH

H

Pr-n

(100)

(100)

(100)

+

(10) +

(95)

(—)

O2CCF3 (—)

+ CF3CO2Pr-n

OH (12) +

Product(s) and Yield(s) (%)

TABLE 15. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ALDEHYDES

319

79, 83

79

79, 83

438

435

435

83

438

438

434

Refs.

467

C10

O

H

O

O

H

H

H

I

O +

0:100

Ph2SiH2

(Ph3P)4Pd (0.012 eq), CHCl3, rt, 1.5 h

Ph2SiH2 (2.0 eq), ZnCl2 (0.12 eq),

O

3:97

Et2HSi

H

H

49:51

Et3SiD (1.1 eq), (Ph3P)3RhCl

100:0

I:II

H

(i-Pr)2HSi

D O

(80)

(—)

I + II

(97)

(95)

(94)

(97)

(92)

(96)

(100)

(100)

Et3Si

O

OSiEt3

OSiMe2Ph

100:0

Ph

Ph

EtMe2Si

R3Si

R3SiH (1.1 eq), (Ph3P)3RhCl

MeC6H5, 5 h

PhSiH3 (1.5 eq), [(Ph3P)CuH]6 (5 mol%),

Et3SiH (0.72 eq), H2PtCl6

HMPA, rt, 0.5 h

PhMe2SiH (1.2 eq), TBAF (2 eq),

II

OH

436

435

435

447

76

320

76

Ph

Et3SiH (1.5 eq), CsF (1.5 eq), (—)

83

I (100)

(EtO)3SiH, CsF, rt, 5 min OSiEt3

83

I (95)

(EtO)3SiH (2.3 eq), KF (1 eq), rt, 24 h

MeCN, rt, 10 h

83

315

I (95)

I (69)

Me(EtO)2SiH (2.3 eq), CsF (1 eq), rt, 2 h

Et2O, rt, 24 h

PMHS (1 eq), ZnCl2 (1 eq),

468

C4

O

Unsaturated Ketone

H , Et2MeSiH,

1h 15 h 3h 3h 7h 9h

20° 20° 0° –15° 20° –15° –15° –15°

none hexane hexane hexane C6H6 toluene CH2Cl2 THF

5h

1h

Time

Temp

Solvent

Rh4(CO)12 (0.5 mol %), solvent

Ph

CH2Cl2, rt, 20 h O

(Ph3P)4RhH (0.3 mol%),

(EtO)3SiH (1.1 eq),

CH2Cl2, rt,1.56 h

(Ph3P)4RhH (0.2 mol%),

ClCH2Me2SiH (1.1 eq),

CH2Cl2, 50°, 24 h

(Ph3P)4RhH (0.5 mol%),

PhMe2SiH (1.1 eq),

C6H6, rt, 5 h

PMHS-Pd nanocomposite,

PMHS, Pd/C, EtOH, 80°

CCl4, 50°, 6 h

Et3SiH (3 eq), TFA (10 eq),

Conditions

(100)

(94)

Ph I

Et2MeSiO

O

OSi(OEt)3

(85), E:Z = 1:2

(73), E:Z = 33:67

(53)

(93)

(98)

(64)

(85)

(95)

(97)

(42)

I + II

+

I:II

78:22

85:15

87:13

81:19

88:12

86:14

77:23

50:50

Ph II

Et2MeSiO

(75), E:Z = 56:44

OSiMe2CH2Cl

OSiMe2Ph

I I (95)

O

OH

O

Product(s) and Yield(s) (%)

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES

464

374

374

374

219

316

434, 439

Refs.

469

C5

C4-10

R3

O

O

H H Me Me H H

Me

Me

Me

Me

Ph

Me

O

R2

R1

R1

R2

Ph

H

Me

Me

H

H

R3

(98) (96)

15 min 30 min 15 min 30 min

50° 50° 60° 60°

none MePh2P MePh2P

n-C5H9 n-C5H9 Ph 0°

15°

0°

Temp

20 h

6h

6.5 h

Time

CH2Cl2, rt, 12 h

(Ph3P)4RhH (0.3 mol%),

PhMe2SiH (1.1 eq),

(Ph3P)4Pd (0.005 eq), CHCl3, rt, 0.5 h

Ph2SiH2 (1.2 eq), ZnCl2 (0.16 eq),

DMI (0.5 eq), 80°, 10 h

PhMe2SiH (2 eq), CoCl2 (0.175 eq),

or CD3CN, DMI (0.5 eq), rt, 5 h

Cl3SiH (2 eq), CoCl2 (0.175 eq), neat;

Ligand

R

ligand, RCHO, hexane I

O

R1

(83)

(92)

OSiMe2Ph

I (99)

I (65)

I

O

R

Et2MeSiO

(90)

(94)

(97)

30 min

60°

(95)

Time 15 min

60°

R3

OSiR3 R2

Temp

Et2MeSiH, Rh4(CO)12 (0.5 mol%),

Et3Si

Et3Si

PhMe2Si

Et3Si

Ph3Si

Et3Si

R3Si

R3SiH (1 eq), (Ph3P)3RhCl (0.5 mol%)

I:II 73:27 74:26 84:16

(21) (45) (100)

R

Et2MeSiO

I + II

+ II

O

374

436

451

451

464

411

470

C6 O

1:99 13:87 57:43

(95) (93) (90) (98) (99) (95)

Et3Si (i-Pr)2HSi Et2HSi PhMeHSi Ph2HSi PhH2Si

reflux, 23 h

Mo(CO)6 (3-5 mol%), THF,

PhSiH3 (1.3-1.5 eq),

reflux, 24 h

Mo(CO)6 (3-5 mol%), THF, II (95)

II (5)

1:99

(98)

99:1

93:7

61:39

0:100

(99)

EtMe2Si

Ph2SiH2 (1.3-1.5 eq),

(75)

(90)

Product(s) and Yield(s) (%)

II (10)

PhMe2Si

+

O

I:II

I + II

I (71)

II (99)

II

I

OH

I + II

R3Si

R3SiH (1.1 eq), (Ph3P)3RhCl

HCl, CH2Cl2, rt, 4 h

Et3SiH (3 eq), AlCl3 (1.2 eq),

(Ph3P)4Pd (0.007 eq), CHCl3, rt, 1 h

Ph2SiH2 (2.0 eq), ZnCl2 (0.35 eq),

CH2Cl2, –5°, 1 h

Et3SiH (1.2 eq), TiCl4 (2.4 eq),

CHCl3, 60°, 4 h

Et3SiH (3 eq), TFA (6 eq),

Conditions

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

450

450

435

136

436

449

434

Refs.

471

O

O

O

140°, 1.5 h

Ph2SiH2 (0.5 eq), o-C6H4(CO2K)2,

(0.4 mol%), CH2Cl2, rt, 4 h

Ph2SiH2 (1.3 eq), (Ph3P)4RhH

2. BnOCH2CHO, TiCl4, CH2Cl2, –78°

MeC6H5, rt, 1 h

1/6 [(Ph3P)CuH]6 (5 mol%),

1. HMe2SiOSiMe2H (1.5 eq),

(0.3 mol%), CH2Cl2, rt, 10 h

ClCH2Me2SiH (1.1 eq), (Ph3P)4RhH

(0.2 mol%), CH2Cl2, rt, 6 h

PhMe2SiH (1.1 eq), (Ph3P)4RhH

C6H6, 20°, 7 h

Rh4(CO)12 (0.5 mol%),

PhCHO, Et2MeSiH,

MePh2P, C6H6, 20°, 7 h

Rh4(CO)12 (0.5 mol%),

PhCHO, Et2MeSiH,

I

HO

O

Ph

O

(83)

OBn

II

+

(79)

OH

(83), E:Z = 4:1

(82), E:Z = 77:23

II III I + II + III (70), I:II:III = 65:0:35

+

+

Et2MeSiO

I + II (86), I:II = 80:20

OSiMe2CH2Cl

OH

I

I

O

OSiMe2Ph

I + II (0)

Ph

Et2MeSiO

O

319

374

455

374

374

464

464

472

C6

O +

OH

(Ph3P)4Pd (0.005 eq), rt, 0.5 h

Ph2SiH2 (1.2 eq), ZnCl2 (0.16 eq),

DMA, 0° to rt, 17 h

PPh3 (50 mol%), TBAF (20 mol%),

PhMe2SiH (1.2 eq), CuCl (50 mol%),

DMA, 0° to rt, 2 h

(Ph3P)3CuF•2 EtOH (1.0 eq),

PhMe2SiH (2 eq),

DMA, 0° to rt, 17 h

PPh3 (50 mol%), TBAF (25 mol%),

PhMe2SiH (1.2 eq), CuCl (50 mol%),

2. Add enone, 0° to rt, 2 h

DMA, 0°, 0.5 h

1. PhMe2SiH (2 eq), (Ph3P)3CuF•2 EtOH,

(Ph3P)3CuF•2 EtOH (1 eq)

PhMe2SiH (2 eq), DMA,

II (100)

II (67)a

II (92)

III (67)

III (92)

III (91)

436

444

444

444

444

446

445

III (100)

PhMe2SiH (4 eq), CuCl (2 eq), DMI, rt, 22 h

93

I + II (91), I:II = 97:3

H, 0°, 5 h

319

93

II III I + II + III (65), I:II:III = 60:10:30

+

O

Refs.

I (85)

I

OH

Product(s) and Yield(s) (%)

G, 0°, 2 h

Ph2SiH2 (0.5 eq), CsF, 140°, 1.5 h

Conditions

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

473 CH2Cl2, rt, 12 h

(Ph3P)4RhH (0.3 mol%),

PhMe2SiH (1.1 eq),

CH2Cl2, rt, 0.5 h

(Ph3P)4RhH (0.1 mol%),

ClCH2Me2SiH (1.1 eq),

–78° to –30°

BnOTMS (0.83 eq), CH2Cl2,

Et3SiH (1 eq), TMSOTf (0.1 eq),

L-D, CH2Cl2, rt, 2 h

or CD3CN, DMPU (0.25 eq), rt, 5 h

Cl3SiH (2 eq), CoCl2 (0.05 eq), neat,

CD3CN, DMI (0.5 eq), rt, 5 h

Cl3SiH (2 eq), CoCl2 (0.175 eq),

THF, reflux, 4 h

Mo(CO)6 (3-5 mol%),

PhSiH3 (1.3-1.5 eq),

PPh3 (0.02 eq)

PhSiH3 (1.01 eq), Ni,

MeC6H5, 8 min

[(Ph3P)CuH]6 (5 mol%),

PhSiH3 (1.5 eq),

D

(50)

OSiMe2Ph

OSiMe2CH2Cl

OBn

O

II (88)

II (88)

II (25)

II (93.1)

II (100)

(84)

(83)

374

374

341

101

451

451

450

438

447

474

C6

O

O

O

O

O

O

I

OH

OH

Ph

+

(Ph3P)4Pd (0.10 eq), CHCl3, rt, 1 h

Ph2SiH2 (2.0 eq), ZnCl2 (1.0 eq),

3. TsOH (cat.), C6H6, reflux, 1.5 h

BF3•OEt2, CH2Cl2

2. 2-Br-5-benzyloxybenzaldehyde,

1/6 [CuH(PPh3)]6 (5 mol%), MeC6H5, rt

1. PhMe2SiH (1.5 eq),

MePh2P, MeC6H5, 0°, 5 h

O

O

O

O

(95)

OBn

Br

O

(77)

NO2

II

(73)

OH Ph I + II (57), I:II = 75:25

Product(s) and Yield(s) (%)

Et2MeSiH, PhCHO, Rh 4(CO)12 (0.5 mol%), I + II (75), I:II = 73:27

MeC6H5, 15°, 15 h

Rh4(CO)12 (0.5 mol%),

Et2MeSiH, PhCHO,

2. 4-O2NC6H4CHO, BF3•OEt2, CH2Cl2, –78°

MeC6H5, rt, 1 h

1/6 [CuH(PPh3)]6 (5 mol%),

1. PhMe2SiH, (1.5 eq),

Conditions

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

436

455

464

464

455

Refs.

475

C6-12

O

O

(65) (42)

MeI n-BuI

BnCH2

BnCH2

Temp rt rt rt 50 rt rt rt

Solvent CH2Cl2 THF CH2Cl2:MeC6H5 (1:1) CH2Cl2 CH2Cl2:MeC6H5 (1:1) CH2Cl2:MeC6H5 (1:1) CH2Cl2:MeC6H5 (1:1)

R

Me

Me

Me

BnCH2

BnCH2

BnCH2

BnCH2

2. BnBr, TBAT (1.2 eq), solvent

MeC6H5, 0°, 2-3 h

NaOBu-t (5%), (S)-p-Tol-BINAP,

(69)

(67)

(64)

(60)

(62)

(53)

(62)

R

(64)

Allyl bromide

BnCH2

R

(67)

BnBr

BnCH2

O

85:15

(52)

1-Bromo-3-methyl-2-butene

Me

1. Ph2SiH2 (0.53 eq), CuCl (5%),

73:27

(52)

BrCH2CO2Et

Me

Bn

76:24

94:6

80:20

94:6

dr 92:8

(62)

BnBr

Me

R1

R2

R2X

CH2Cl2/MeC6H5 (1:1), rt, 24 h

O

R1

R1

2. R2X, TBAT (1.2 eq),

MeC6H5, 0°, 2-3 h

NaOBu-t (5%), (S)-p-Tol-BINAP,

1. Ph2SiH2 (0.53 eq), CuCl (5%),

459

459

476

C6-9

C6

R1

O

O

R2 H H H H Me

H

Cl

Me

MeO

Me

R3

R2

R1

O

O

(85) (96) (90) (98) (90)

H H Me

OH

OH

H

R1

I (81)

OH

OH

H

R3

CH2Cl2, reflux, 30 min

NaI (10 mol%), TMSCl (10 mol%),

HMe2SiOSiMe2H (1.5 eq),

EtOH, reflux

(Bu2(AcO)Sn)2O (2 mol%),

PMHS (10% xs),

60-65°, 1 h

Et3SiH (1.5 eq), TFA, (13 eq),

Conditions

I

R3

R2

(98)

Product(s) and Yield(s) (%)

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

314, 357

316

393

Refs.

477

C6-15

R1

Ph Bn t-Bu Et2CH 4-MeOC6H4 Ph

Me Me Me Me Ph Ph

Ph

Ph

Ph

Ph

Ph

Ph

90:10 >99:1 78:22

(65)

(73) (82)

>99:1

(40) (87)

92:8 >99:1

(78)

90:10

4-O2NC6H4

Me

Ph

>99:1

>99:1

4-MeOC6H4

Me

Ph (59)

>99:1

(46)

4-MeOC6H4

Ph

Me (75)

>99:1

(40)

Ph

Me

Et

syn:anti (61)

4-MeOC6H4

OSiEt3

R3

O

R3

Me

R1

R2

R3CHO (1 eq), EtCN, –78° to rt, 1h

Et3SiH (1 eq), InBr3 (10 mol%),

Et

1.2 eq

R2

R1

O

R2 760

478

C7

O

O

I

+

II (74)

Et3SiH (1.2 eq), TiCl4 (2.4 eq),

II (100)

II (100)

CH2Cl2, –5°, 1 h

OH

+

II (97), II:I = 100:0

I

I

OH

I (73)

I (73)

O

PhSiH3 (1.01 eq), Ni, PPh3 (0.02 eq)

[(Ph3P)CuH]6 (5 mol%), MeC6H5, 18 h

PhSiH3 (1.5 eq),

(Ph3P)3RhCl (10 mol%), 0°, 340 min

Ph2SiH2 (1.1 eq),

(Ph3P)3RhCl (10 mol%), 50°, 30 h

Et3SiH (1.1 eq),

CH2Cl2, rt, 4 h

(Ph3P)4RhH (0.3 mol%),

Ph2SiH2 (1.3 eq),

CH2Cl2, –5°, 1 h

Et3SiH (1.2 eq), TiCl4 (2.4 eq),

CH2Cl2, –5°, 1 h

TMSH (1.2 eq), TiCl4 (2.4 eq),

(Ph3P)3RhCl (10 mol%), 45°, 4 h

Et3SiH (1.1 eq),

Conditions

II

II

OH

II (97), I:II = 0:100

I (90), I:II = 98:2

Product(s) and Yield(s) (%)

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

449

438

447

435

435

374

449

449

435

Refs.

479

C8

O

O

O

Cl

Pr-i

CO2H

CF3 OH

MeC6H5, 8 min

[(Ph3P)CuH]6 (5 mol%),

PhSiH3 (1.5 eq),

PhSiH3 (1.01 eq), Ni, PPh3 (0.02 eq)

NaOBu-t (0.1 mol%), MeC6H5, rt, 1 h

PMHS (1.6 eq), 209 (0.1 mol%),

Et3SiH (3 eq), TFA, rt, 48 h

2. n-C5H11CHO, TiCl4, CH2Cl2, –78°

MeC6H5, rt, 39 h

1/6 [(Ph3P)CuH]6 (5 mol%),

1. HMe2SiOSiMe2H (1.5 eq),

(0.5 mol%), CH2Cl2, 50°, 24 h

PhMe2SiH (1.1 eq), (Ph3P)4RhH

MeC6H5, rt, 24 h

1/6 [(Ph3P)CuH]6 (5 mol%),

HMe2SiOSiMe2H (1.5 eq),

I

O

O

Cl

I (85)

O

O

(98)

(81)

CO2H

CF3 OH

Pr-i

(89)

C5H11-n

OH

OSiMe2Ph

(72)

(82)

(85)

OSi(Me)2OSiMe2H

447

438

454

453

455

374

455

480

C8

O

O

MeC6H5, 46 h

[(Ph3P)CuH]6 (5 mol %),

PhSiH3 (1.5 eq),

CD3CN, DMI (0.5 eq), rt, 12 h

Cl3SiH (2 eq), CoCl2 (0.175 eq),

DMI, rt, 22 h

PhMe2SiH (4 eq), CuCl (2 eq),

–78°, 1 h

2. Aldehyde, BF3•OEt2, CH2Cl2,

MeC6H5, rt, 4 h

[(Ph3P)CuH]6 (18 mol%),

1. PhMe2SiH, (1.5 eq),

CHO

MeC6H5, rt, 4 h Ts N 2. , TiCl4, CH2Cl2, –78°

1/6 [(Ph3P)CuH]6 (5 mol%),

1. PhMe2SiH (1.5 eq),

CH2Cl2, rt, 4 h

(Ph3P)4RhH (0.3 mol%),

ClCH2Me2SiH (1.1 eq),

CH2Cl2, rt, 12 h

(Ph3P)4RhH (0.4 mol%),

PhMe2SiH (1.1 eq),

Conditions

O

I

R

OH

OH (82)

(100) cis:trans = 97:3

(68)

cyclohex-3-enyl (80)

R

4-O2NC6H4CHO 4-O2NC6H4

carbaldehyde

cyclohex-3-ene-

Aldehyde

N Ts

I (100), single isomer

I (50)

O

O

Product(s) and Yield(s) (%)

(96)

(80)

OSiMe2CH2Cl

OSiMe2Ph

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

447

451

445

455

455

374

374

Refs.

481

O

MePh2P, C6H6, 20°, 15 h,

Rh4(CO)12 (0.5 mol%),

PhCHO, Et2MeSiH,

(Ph3P)3RhCl (10 mol%), C6H6, rt, 1 h

Ph2SiH2 (1.1 eq),

C6H6, rt, 6 h

PMHS-Pd nanocomposite,

CHCl3, rt, 4 h

(Ph3P)4Pd (0.013 eq),

Ph2SiH2 (1.8 eq), ZnCl2 (0.38 eq),

(Ph3P)4Pd (0.013 eq), rt, 4 h

Ph2SiH2 (1.8 eq), ZnCl2 (0.38 eq),

THF, reflux, 4.5 h

Mo(CO)6 (3-5 mol%),

PhSiH3 (1.3-1.5 eq),

CD3CN, DMI (0.5 eq), rt, 2 h

Cl3SiH (2 eq), CoCl2 (0.175 eq),

C6H6, 50°, 5 h

(Ph3P)3RhCl (10 mol%),

Et3SiH (1.1 eq),

CH2Cl2, 50°, 24 h

(Ph3P)4RhH (0.5 mol%),

PhMe2SiH (1.1 eq),

O

III

(75)

+

O

Ph

OH

(69)

II

OH

(87) cis:trans = 92:8

I + II (96), I:II = 97:3

III (97)

III (85)

III (—)

III (100)

I

OSiEt3

OSiMe2Ph

I (95), I:II = 87:13

464

435

219

436

436

450

451

435

374

482

C9

C8-17

R

CH2Cl2, –78°

2. Me2CHCH2CHO, BF3•OEt2,

MeC6H5, rt, 3 h

1/6 [(Ph3P)CuH]6 (5 mol%),

1. PhMe2SiH (2.5 eq),

MeC6H5, 6 h

[(Ph3P)CuH]6 (0.5mol%),

PhSiH3 (1.5 eq),

DMI, rt, 20 h

PhMe2SiH (4 eq), CuCl (2 eq),

CH2Cl2, –5°, 1 h

Et3SiH (1.2 eq), TiCl4 (2.4 eq),

Pr-i

Pr-i O

O

I

OH

(73)

I (13)

(75)

2-C4H3S

CH2Cl2, –5°, 1 h

(68)

2-C4H3O O

(72)

2-C10H7

O

(87)

OH

4-CF3C6H5

I (53)

R

O

(38)

TMSH (1.2 eq), TiCl4 (2.4 eq),

Co(dpm)2 (5 mol%), rt

PhSiH3 (1.2 eq),

Ph

CHO

Me

R

Pr-i

O

O

Conditions

(99)

(66)

(89)

Product(s) and Yield(s) (%)

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

455

447

445

449

449

461

Refs.

483

n-C5H11

O

CH2Cl2, –78°

CHO, BF3•OEt2,

DMA, 0° to rt, 2 h

PPh3 (25 mol%), TBAF (20 mol%),

PhMe2SiH, CuCl (25 mol%),

2. Add enone, 0° to rt, 2.5 h

DMA, 0°, 0.5 h

(Ph3P)3CuF•2 EtOH,

1. PhMe2SiD (2 eq),

DMA, 0° to rt, 2 h

PPh3 (25 mol%), TBAF (20 mol%),

PhMe2SiH (1.2 eq), CuCl (25 mol%),

2. Add enone, 0° to rt, 2.5 h

0°, 0.5 h

(Ph3P)3CuF• 2 EtOH, DMA,

1. PhMe2SiH (2 eq),

(Ph3P)3CuF•2 EtOH (1 eq)

PhMe2SiH (2 eq), DMA,

2.

Bu3Sn

MeC6H5, rt, 2 h

1/6 [(Ph3P)CuH]6 (5 mol%),

1. PhMe2SiH (1.5 eq),

CH2Cl2, –78°

2. ClCH2CH2OCH2CHO, BF3•OEt2,

MeC6H5, rt, 2 h

1/6 [(Ph3P)CuH]6 (5 mol%),

1. PhMe2SiH (1.5 eq),

II (77)

n-C5H11

I (77)

I (91)

n-C5H11

Pr-i

O

Pr-i

O

D

OH

OH

II

I

O

O

O

(76)

(87)

(62) >99% D

(91)

SnBu3

Cl

444

444

444

444

446

455

455

484

C10

C9

O

O

n-C5H11

O

O

rt, 20 min

Ph2SiH2 (1.1 eq), (Ph3P)3RhCl (10 mol%),

C6H6, rt, 2 h

(Ph3P)3RhCl (10 mol%),

EtMe2SiH (1.1 eq),

Et2SiH2, (Ph3P)3RhCl

i-PrOH, DCE

PhSiH3 (1.3 eq), Mn(dpm)3 (3 mol%),

PhSiH3 (1.01 eq), Ni, PPh3 (0.02 eq)

3. Allyl bromide

2. Add enone, 0°, 45 min

DMA, 0°, 0.5 h

1. PhMe2SiH (2 eq), (Ph3P)3CuF•2 EtOH,

3. D2O

2. Add enone, 0°, 45 min

DMA, 0°, 0.5 h

1. PhMe2SiH (2 eq), (Ph3P)3CuF•2 EtOH,

Conditions

O

I

I

EtMe2SiO

OH

O

n-C5H11

n-C5H11 D O

O

+

+

(—)

O

(81.9)

(45)

II

II OH

OH

(67) 85% D

(74)

I (98), I:II = 0:100

I (97), I:II = 78:22

Product(s) and Yield(s) (%)

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

435

435

435

448

438

444

444

Refs.

485

O

50:50 50:50 0:100 0:100 I + II (—)

Et3Si (n-Pr)3Si Et2HSi Ph2HSi R3SiH (1.1 eq),

75:25 0:100 0:100

PhMe2Si Et2HSi Ph2HSi

Mo(CO)6 (3-5 mol%), THF, reflux, 3 h

PhSiH3 (1.3-1.5 eq),

Mo(CO)6 (3-5 mol%), THF, reflux, 15 h

Ph2SiH2 (1.3-1.5 eq),

I + II (100)

+

II

O

(90) cis:trans = 1:1

I + II (90), I:II = 4.5:1

I

II (—) O

50:50

(n-Pr)3Si

Et2SiH2, (Ph3P)3RhCl

50:50

Et3Si

R3Si I:II

75:25

PhMe2Si

(Ph3P)3RhCl (0.5 mol%), 50°, 2 h

I:II

I + II (—)

O

R3Si

R3SiH, (Ph3P)3RhCl

(Ph3P)4Pd (0.018 eq), CHCl3, rt, 3 h

Ph2SiH2 (1.55 eq), ZnCl2 (0.4 eq),

I:II = 4.5:1 450

450

435

437

452

436

486

C10

O

O

O

O

CH2Cl2, rt, 12 h

(Ph3P)4RhH (0.4 mol%),

Ph2SiH2 (1.3 eq),

THF, reflux, 11.5 h

Mo(CO)6 (3-5 mol%),

PhSiH3 (1.3-1.5 eq),

i-PrOH

PhSiH3 (2 eq), Mn(dpm)3 (3 mol%),

(Ph3P)4Pd (0.013 eq), CHCl3, rt, 2 h

Ph2SiH2 (1.7 eq), ZnCl2 (0.52 eq),

DMI, rt, 22 h

PhMe2SiH (4 eq), CuCl (2 eq),

DMA, 0° to rt, 4.5 h

PPh3 (160 mol%), TBAF (150 mol%),

PhMe2SiH, CuCl (160 mol%),

2. Add enone, 0° to rt, 24 h

(Ph3P)3CuF•2 EtOH, DMA, 0°, 0.5 h

1. PhMe2SiH (2 eq),

(Ph3P)3CuF•2 EtOH (1 eq)

PhMe2SiH (4 eq), DMA,

Conditions

O

I

I (0)

I (50)

O

(83)

(84) cis:trans = 65:35

(85)

(85) dr = 8:1

Product(s) and Yield(s) (%)

I (89) cis:trans = 1:4

I (87)

I

O

O

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

374

450

448

436

445

444

444

446

Refs.

487

Ph

O

(95) (49) (—)

(36) (—)

1 1

2 2

Ph2HSi PhCl2Si

(58) (49) (0)

(34) (36) (0)

1.5 h 3.5 h 18 h —

Et3Si (EtO)3Si Ph2HSi PhCl2Si

0° to rt, 6 h

Ph2SiH2 (1.1 eq), (Ph3P)3RhCl,

45°, 15 h I:II = 60:40

I:II = 37:63

(96)

(—)

2h

PhMe2Si

Et3SiH (1.1 eq), (Ph3P)3RhCl,

II (>99)

I (—)

Time

R3Si

DMA, 0° to rt, 0.5 h

(Ph3P)3CuF•2 EtOH (1.0 eq),

R3SiH (2 eq), I + II

(69)

(—)

1

2

Et3Si

(63)

(—) (trace)

1 0.05

PhMe2Si

2

PhMe2Si 1

2

II

x

R3Si PhMe2Si

(>99)

II I

Ph

(—)

+

I

1

I

I (100)

Ph

OH

y

(Ph3P)3CuF•2 EtOH (y eq)

R3SiH (x eq), DMA,

Ph2SiH2 (0.5 eq), CsF, rt, 30 min

(EtO)3SiH, CsF, rt, 30 min

O

(100)

435

435

444

446

319

83

488

C10

Ph

O

12 h 21 h 12 h

(CuOTf)2•C6H6 Cu2O CuCN

Temp

0° to rt

60°

0° to rt

0° to rt

0° to rt

0° to rt

Mo(CO)6 (3-5 mol%), THF, reflux, 7 h

Ph2SiH2 (1.3-1.5 eq),

rt, 30 min

Ph2SiH2 (2.3 eq), CsF (1 eq),

(Ph3P)4Pd (0.0009 eq), CHCl3, rt, 2 h

Ph2SiH2 (1.3 eq), ZnCl2 (0.3 eq),

2. TBAF, MeOH, rt, 30 min

MeC6H5, rt, 3 h

1/6 [(Ph3P)CuH)]6 (5 mol%),

1. HMe2SiOSiMe2H,

CH2Cl2, 0°, 1 h

Et3SiH (1.2 eq), TiCl4 (2.4 eq),

solvent, 0° to rt

(Ph3P)3CuF•2 EtOH (1.0 eq),

PhMe2SiH (2 eq),

4h 21 h

CuF(PPh3)3 CuCl

2h

Time CuF(PPh3)3•2 EtOH

PhMe2SiH (3 eq), DMA

Conditions

II (95)

II (100)

II (100)

II (82)

II (36)

II

II

(64)

(48)

(27)

(55)

(>99)

II

(57) (42) (80)

6h 2.5 h 12.5

MeC6H5

(40)

(92)

THF

2.5 h

2h

Time

NMP

DMF

DMA

Solvent

(trace) (trace)

(—)

(trace)

(—)

(—)

(—)

I

I + II

Product(s) and Yield(s) (%)

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

450

83

436

455

449

444

444

Refs.

489 O Ph

O

(Ph3P)3RhCl (10 mol%), 0°, 30 min

Et2SiH2 (1.1 eq),

(Ph3P)3RhCl (10 mol%), 80°, 25 h

Et3SiH (1.1 eq),

0° to rt, 6 h

Ph2SiH2 (1.1 eq), (Ph3P)3RhCl,

45°, 15 h

Et3SiH (1.1 eq), (Ph3P)3RhCl,

MePh2P, C6H6, 20°, 3.5 h

Rh4(CO)12 (0.5 mol%),

PhCHO, Et2MeSiH,

2. BnOCH2CHO, TiCl4, CH2Cl2, –78°

MeC6H5, rt

1/6 [(PPh3)CuH]6 (2 mol%),

1. PMHS (1.25 eq),

2. 4-O2NC6H4CH2Br, CH2Cl2, rt, 3 h

MeC6H5, rt, 2 h

OH

I

I

O

I

O

OBn

+

NO2

Ph

Ph

O + II

II

Et2MeSiO

(83)

(57)

I + II (88), I:II = 80:20

Bn

O

O

I (98), I:II = 3:97

I (—)

Ph

Et2MeSiO

Ph

Ph

1. HMe2SiOSiMe2H (0.55 eq), 1/6 [(Ph3P)CuH]6 (2 mol%),

II (96.9)

II (100)

PhSiH3 (1.01 eq), Ni, PPh3 (0.02 eq)

Mo(CO)6 (3-5 mol%), THF, reflux, 1.5 h

PhSiH3 (1.3-1.5 eq),

OH

Bn

O

I (96), I:II = 94:6

435

435

435

435

464

455

455

438

450

490

C11

O

TBSO

O

O

Ph O

O

O

O

CH2Cl2, 1 h

Et3SiH (1.2 eq), TiCl4 (2.4 eq),

MeC6H5, 10 min

PhSiH3 (1.5 eq), [(Ph3P)CuH]6 (5 mol%),

MeC6H5, rt, 1 h

NaOBu-t (0.1 mol%),

PMHS (1.6 eq), 209 (0.1 mol%),

NaOBu-t (0.1 mol%), MeC6H5, rt, 1 h

PMHS (1.6 eq), 209,

CH2Cl2, reflux, 30 min

NaI (10 mol%), TMSCl (10 mol%),

HMe2SiOSiMe2H (1.5 eq),

Et3SiH (5 eq), TFA (26 eq), 60-65°, 10 h

Et3SiH (4 eq), TFA (20 eq), 60-65°, 8 h

50°, 60 min

Et3SiH (1 eq), (Ph3P)3RhCl (0.5 mol%),

Conditions

O

TBSO

O

O

I (75)

Ph O

OH

OH

I

(70)

(95)

(92)

–78°

0°

Temp (50)

(53) cis:trans = 9:1

(85) dr = 4:1

(60)

(50)

OSiEt3

Product(s) and Yield(s) (%)

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

449

447

454

454

314

393

393

411

Refs.

491

C12

O

Ph

O

O

O

Ph

O

O

CHO

Cl

O

CO2Et

CO2Me

O

O

NaOBu-t (3 mol%), MeC6H5, rt, 3 h

PMHS (1.6 eq), 209 (0.1 mol%),

PhSiH3 (1.2 eq), Co(dpm)2 (5 mol%), rt

BF3•OEt2 (2 mol%), TFA, rt, 0.5 h

Et3SiH or EtMe2SiH (4 eq),

Et3SiH (xs), BF3•OEt2, 80-95°

Et3SiH (6 eq), BF3 (xs), 20°, 6 h

MeC6H5, 50°, 16 h

Et3SiH (2.1 eq), (Ph3P)3RhCl (1 mol%),

CH2Cl2, –78°

Et3SiH (2 eq), SnCl4 (0.1 eq),

CH2Cl2, –78°

Et3SiH (2 eq), BF3•OEt2 (1.1 eq),

DMI, rt, 21 h

PhMe2SiH (4 eq), CuCl (2 eq),

H

O

Ph

O

Ph

O

(71)

OH (70)

(94) dr = 5:1

Cl

OH (96)

(91)

+

O

(81) cis:trans = 98:2

(64)

CO2Me

OSiEt3

H

CO2Et

H H I

O

I (66-74)

I

I (61)

O

O

(14)

454

461

396

442

442

471

463

463

445

492

C13

C12

O

O

Bn

O

O

O

O

CH2Cl2, 0°, 1 h

Et3SiH (1.2 eq), TiCl4 (2.4 eq),

(95)

Et3Si

78:22

98:2 85:15

(95)

+

(94)

O

(60)

(87)

EtMe2Si

I

O

PhMe2Si

Bn

OH

(99)

I:II

I (78)

O

I (59)

I

O

II

Product(s) and Yield(s) (%)

I + II

R3Si

R3SiH (1.1 eq), (Ph3P)3RhCl

2. Allyl bromide, TBAT (1.2 eq)

MeC6H5, 0°, 2-3 h

NaOBu-t (5%), (S)-p-Tol-BINAP,

1. PMHS (0.53 eq), CuCl (10%),

2. P(OEt)3 (1.1 eq)

i-PrOH, DCE, O2

1. PhSiH3 (1.3 eq), Mn(dpm)3 (3 mol%),

2. P(OEt)3 (1.1 eq)

i-PrOH, DCE, O2

1. PhSiH3 (1.3 eq), Mn(dpm)3 (3 mol%),

i-PrOH, DCE

PhSiH3 (1.3 eq), Mn(dpm)3 (3 mol%),

Conditions

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

OH

449

435

459

465

465

448

Refs.

493

78:22 86:14

3h 12 h

none C6H6 (0.2 M)

0:100

Et2HSi Ph2HSi

2. P(OEt)3 (1.1 eq)

Mn(dpm)3 (3 mol%), i-PrOH, DCE, O2

1. PhSiH3 (1.3 eq),

i-PrOH, DCE

PhSiH3 (1.3 eq), Mn(dpm)3 (3 mol%),

(Ph3P)3RhCl (10 mol%), 50°, 2 h

Et3SiH (1.1 eq),

(Ph3P)3RhCl (10 mol%), C6H6, rt, 15 h

EtMe2SiH (1.1 eq),

[(Ph3P)CuH]6 (5 mol%), MeC6H5, 47 h

PhSiH3 (1.5 eq),

(Ph3P)3RhCl (10 mol%), rt, 30 min

Ph2SiH2 (1.1 eq),

(Ph3P)4Pd (0.019 eq), CHCl3, rt, 2 h

I (25)

OH

O

I (96), I:II = 100:0

I (94), I:II = 98:2

I (96)

I (98), I:II = 100:0

I (96)

0:100

Et3Si

Ph2SiH2 (2.5 eq), ZnCl2 (0.35 eq),

91:9 44:56

PhMe2Si

I:II

R3Si

I + II (—)

64:36

3h

none

R3SiH, (Ph3P)3RhCl

I:III

Time

I (—) +

Solvent

(10-20 mol%), solvent, 50°

Et3SiH (1.2 eq), (Ph3P)3RhCl,

(51)

III

OSiEt3 (—)

465

448

435

435

447

435

436

437, 452

435

494

C13

Ph

Ph

Ph

i-Pr

O

O

O

O

O

Pr-i

O

H

i-Pr

DCE, rt, 30 min

Co(dpm)2 (5 mol%),

PhSiD3 (120 mol%),

DCE, rt, 30 min

Co(dpm)2 (5 mol%),

PhSiH3 (120 mol%),

CH2Cl2, –78°

Et3SiH (2 eq), SnCl4 (0.1 eq),

CH2Cl2, –78°

Et3SiH (10 eq), BF3•OEt2 (1.1 eq),

CH2Cl2, –78°

Et3SiH (10 eq), BF3•OEt2 (1.1 eq), I

(18)

Pr-i

Ph

Ph

D

O

O

OH

OH

I (53) + II (9) +

I (19) + II (62)

Ph

O

(—)

(—)

Ph

+

+

O

Ph

Ph

II

O

5.7:1 epimer ratio

+

(24)

(96)

CH2Cl2, –78°

OSiEt3

O

D

O

i-Pr

Pr-i

OH

(12)

(59)

O

Product(s) and Yield(s) (%)

Et3SiH (10 eq), BF3•OEt2 (1.1 eq),

Et3SiH, (Ph3P)3RhCl

Conditions

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

463

(—)

460

460

463

463

463

2.6:1 epimer ratio

(69)

452

Refs.

495

C13-15

Ph

Cl

O

Ph

Ph2SiH2 THF

18 h

OTHP

(77)

(86)

(95)

R

10 h

OH

Ph

12 h

I

O

Bn

OBu-t

Ph

Cl

(86)

(88)

(86)

(87)

(88)

O

OAc

TBAF (5-10 mol%), HMPA, 0°

PhMe2SiH (1.1-1.2 eq),

[(Ph3P)CuH]6 (5 mol%), MeC6H5, 6 h

PhSiH3 (1.5 eq),

i-PrOH, DCE

PhSiH3 (1.3 eq), Mn(dpm)3 (3 mol%),

6h

1h

1h

1h

1h

Time

I I (—) 87% selectivity

OAc

I + II

R

O

0.1

THF

PMHS 0.005

0.1

Ph2SiH2 MeC6H5

MeC6H5

0.1

MeC6H5

PMHS

PMHS

0.1

Solvent

R3SiH x

NaOBu-t (0.1 mol%), solvent, rt

R3SiH (1.3 eq), 209 (x mol%),

Ph2MeSiH, TBAF

Ph

OH

Time

O

Ph

OAc

PhMe2SiH, TBAF

R

O

Bn

O

I:II

87:13

91:9

84:16

+

O

(50)

Ph

(97)

II

OH

(95) 84% selectivity

R

320

447

448

454

440

440

496

C14

O

Ph

O

Bn

CO2Me

Cl

O

CHO

NaOBu-t (6 mol%), MeC6H5, rt, 1 h

CuCl2•2H2O (1 mol%),

PMHS (3 eq), 209,

NaOBu-t (0.1 mol%), MeC6H5, rt, 1 h

PMHS (1.6 eq), 209 (0.1 mol%),

Co(dpm)2 (5 mol%), DCE, 35°

PhSiH3 (1.2 eq),

BF3•OEt2 (2 mol%), TFA, rt, 0.5 h

Et3SiH or EtMe2SiH (4 eq),

Ph

Bn

OH

I (87) dr = 4:1

I

O

O

CO2Me

Cl

(35)

(96)

(97)

(98)

Product(s) and Yield(s) (%)

(90) dr = 5:1

OH

CO2Me

NH2 O

BF3•OEt2 (2 mol%), TFA, rt, 12 h

Et3SiH or EtMe2SiH (4 eq),

O

CO2Me

O

CO2Me

NH2

O

BF3•OEt2 (2 mol%), TFA, rt, 12 h

Et3SiH or EtMe2SiH (4 eq),

NH2

O

O

CO2Me

O

NH2 O

Conditions

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

454

454

461

396

396

396

Refs.

497

C15

O

O

MeHN

CO2Me

R

O

BF3•OEt2 (2 mol%), TFA, rt, 24 h

Et3SiH or EtMe2SiH (4 eq), CO2Me

R

O

O

O

BF3•OEt2 (2 mol%), TFA, rt, 24 h

Et3SiH or EtMe2SiH (4 eq),

O

CO2Me

O

O

60-65°, 0.5 h

CO2Me

MeHN

O

O Et3SiH (10 eq), TFA (20 eq),

OH

OH

O

60-65°, 20 h

Et3SiH (5 eq), TFA (20 eq),

Bn

OSiEt3

O

O

NaOBu-t (0.1 mol%), MeC6H5, rt, 1 h

PMHS (1.6 eq), 209 (0.1 mol%),

O

Bn

TIPSO

O

Et3SiH, Pt[(vinylMe2Si)2O]2

TIPSO

O

OH

OH

(93)

(96)

Time OMe

8h

NHMe 24 h

R

(98)

(99)

(54)

(98)

(98)

396

396

393

393

454

456

498

C15

Ph

O Ph

Ph2SiH2 (2.3 eq), CsF (1 eq), 0°, 1 h

DMA, 0° to rt, 2 h

PPh3 (110 mol%), TBAF (100 mol%),

PhMe2SiH (1.2 eq), CuCl (110 mol%),

DMA, 0° to rt, 1 h

PPh3 (20 mol%), TBAF (10 mol%),

PhMe2SiH (1.2 eq), CuCl (20 mol%),

(1.0 eq), DMA, 0° to rt, 3 h

PhMe2SiH (2 eq), (Ph3P)3CuF•2 EtOH

(Ph3P)3CuF•2 EtOH (1 eq)

PhMe2SiH (2 eq), DMA,

0° to rt, 6 h

PhSiH3 (1.1 eq), (Ph3P)3RhCl,

0° to rt, 6 h

Ph2SiH2 (1.1 eq), (Ph3P)3RhCl,

C6H6, rt, 15 h

Et3SiH (1.1 eq), (Ph3P)3RhCl,

CHCl3, 60°, 7 h

Et3SiH (3 eq), TFA (6 eq),

Ph2SiH2 (0.5 eq), CsF, rt, 30 min

Conditions

I

(80)

+ Ph

Ph

+ Ph

I + II (95), I:II = 95:5

Ph

I (95) + II (5)

II (94)

II (25)

II (98)

II (98)

II (—)

II (—)

II (—)

Ph

Ph

OH

(17)

Ph

II

O Ph

Product(s) and Yield(s) (%)

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

Ph

83

444

444

444

446

435

435

435

434

319

Refs.

499

C16

C15-23

C15-16

Ph

Ph

Ph

O

OMe

O

n

O

OMe

Ar

Ar

O

O

O

H

Ar = 4-BrC6H4

60-65°, 20 h

Et3SiH (4 eq), TFA (10 eq),

CCl4, 50°, 6 h

Et3SiH (1 eq), TFA (10 eq),

rt, 30 min

Co(dpm)2 (5 mol%), DCE,

PhSiH3 (120 mol%),

(Ph3P)4Pd (0.014 eq), CHCl3, rt, 3 h

Ph2SiH2 (2.4 eq), ZnCl2 (0.77 eq),

CH2Cl2, –78°

2. Me2CHCH2CHO, BF3•OEt2,

MeC6H5, rt, 0.5 h

1/6 [(Ph3P)CuH]6 (5 mol%),

1. PhSiH3 (1.5 eq),

PMHS-Pd nanocomposite, C6H6, rt, 6 h

MeC6H5, 108 min

[(Ph3P)CuH]6 (5 mol%),

PhSiH3 (1.5 eq),

Ph

Ph

Ph O

i-Bu

Ph

O

II (95)

II (96)

OH

OH

O

n

OMe

OMe

Ar

Ar OH

O

OH

Ph

(75) (75) (75) (76) (79) (79) (77)

4-MeC6H4 4-EtC6H4 4-t-BuC6H4 4-n-C6H13C6H4 4-PhC6H4 4-BnCH2C6H4

(50)

(80) 4-FC6H4

(36)

(87)

Ph

Ar

2

1

n

(98)

(73)

393

439

460

436

455

219

447

500

C16-18

C16-17

C16

t-Bu

Ph

O

O

O

O

N

O

Ar

O

Time 7h 8h 7h 20 h 9h 9h

Ph 4-MeC6H4 4-EtC6H4 2-MeC6H4 4-MeOC6H4 4-ClC6H4

Et3SiH (5 eq), TFA (10 eq), CCl4, 50-55°

TFA, rt, 24 h

Et3SiH, BF3•OEt2,

CH2Cl2, –78°

Et3SiH (10 eq), BF3•OEt2 (1.1 eq),

Co(dpm)2 (5 mol%), 70°

PhSiH3 (2.4 eq),

Ar

n

O

Conditions

t-Bu

Ph

(78)

(67)

(68)

(53)

(74)

O

N

O

H

O

O

(54)

H

O

O

Ar

H

n

(47)

(81)

+

1

0

n (62)

(93)

O

O

Product(s) and Yield(s) (%)

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

Ph (15)

266

441

463

461

Refs.

501

C17

C16-23

C16-19

O

Ph

R1

R2

R2

O

O

O Ph

O O Co(dpm)2 (5 mol%), 50°

PhSiH3 (2.4 eq),

DMA, 0° to rt, 1.5 h

PPh3 (25 mol%), TBAF (20 mol%),

PhMe2SiH, CuCl (25 mol%),

2. Enone, 0° to rt, 2 h

(Ph3P)3CuF•2 EtOH, DMA, 0°, 0.5 h

1. PhMe2SiH (2 eq),

CCl4, 50°, 6 h

O

I (64)

Ph

Ph

O

OH

I

O

O

(46)

Ph

Ph

O

(40)

(0)

4-MeOC6H4

(65)

I II

(5)

Ph

R1

R1

+

(52)

(85)

R1 or R2

(50)

O

n

4-MeOC6H4

Et3SiH (6 eq), TFA (10 eq),

O

N

Me

R1 or R2

R2

R2

4-MeOC6H4

DCE, rt, 30 min

Co(dpm)2 (5 mol%),

PhSiH3 (120 mol%),

TFA, rt, 24 h

Ph

R1

Et3SiH, BF3•OEt2,

I

R2

n

R1

O

R2

O

O

R1

N

O

(52)

O

H

O

H

R2

II

(90)

OMe 1

Me

R1

(92)

(92)

1

1

H

(94)

0

n

Me

H

H

H H

R2

R1

461

444

444

393

460

441

502

C18

C17

O

O

Et3SiH or EtMe2SiH (4 eq),

CO2Me

NEt2

CO2Me O O

N

Et3SiH, TFA, CH2Cl2, 42 h

BF3•OEt2 (2 mol%), TFA, rt, 12 h

Et3SiH or EtMe2SiH (4 eq),

BF3•OEt2 (2 mol%), TFA, rt, 12 h

O

H

H

CO2Me

NEt2

CO2Me O

N

O

O

O

OH

O

+

H

OH

O

O

R

O

(65)

O

(60) +

(98)

(99)

H

H

NEt2

O

BF3•OEt2 (2 mol%), TFA, rt

R

H

O

1-pyrrolidinyl

O

24 h

8h

Time

O

Product(s) and Yield(s) (%)

Et3SiH or EtMe2SiH (4 eq),

DCE, rt, 30 min

Co(dpm)2 (5 mol%),

PhSiH3 (240 mol%),

CO2Me

O

O

O

CO2Me

R

O

O

Conditions

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

O

OH

(94)

(98)

(40)

(2)

242

396

396

396

460

Refs.

503

C19

O

Ph

Me N

Ph

O

O

O

O

Ph

O

O

O

O

OH

Me N

CH2Cl2, –78°

Et3SiH (2 eq), BF3•OEt2 (1.1 eq),

CH2Cl2, –78°

Et3SiH (10 eq), Et2AlCl (1.1 eq),

DCE, rt, 30 min

Co(dpm)2 (10 mol%),

PhMeSiH2 (400 mol%),

Co(dpm)2 (5 mol%), 50°

PhSiH3 (2.4 eq),

Et3SiH, TFA, CH2Cl2, 60 h

Et3SiH, TFA, CH2Cl2, 44 h

Ph I (49)

O

+

O

II (88) + III (10)

Ph

O

H

H

OSiEt3

O

Me N

Ph

O

O

Ph

O

O

(83) +

O

(86) +

O

(75)

Ph II (36)

O

Me N

Ph (27) +

O

OH

+ Ph

H

H

O

Ph III (8)

O

O

463

463

460

461

242

(14) 242

(17)

(27)

O

OH

504

C20-21

C20

C19

Ph

Ph

Ph

H

O

O

O

O

O

O

O

Y

O

O

OTr

OTBS

SPh

O

O

Ph

Ph

Ph

DDCE, 50°

R3SiH (x eq), Co(dpm)2 (y eq),

Co(dpm)2 (5 mol%), 50°

PhSiH3 (2.4 eq),

Co(dpm)2 (5 mol%), 50°

PhSiH3 (2.4 eq),

Mn(dpm)3 (3 mol%), i-PrOH, DCE

PhSiH3 (1.3 eq),

CH2Cl2, rt, 12 h

(Ph3P)4RhH (0.5 mol%),

Ph2SiH2 (1.3 eq),

Conditions

Ph

Ph

Ph

H

O

O

O

O

O

H

OH

SPh

I

O

H

O

O

O

Ph

Ph

Ph

OTr

OTBS

Y

O

+ Ph

(63)

(62)

(100)

(56)

O

II

Y

O Ph

Product(s) and Yield(s) (%)

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

462

461

461

448

374

Refs.

505

C21

Ph

Ph

O

O

O

O

Ph

H

O

H

Ph

DCE rt, 30 min

Co(dpm)2 (5 mol%),

PhSiH3 (120 mol%),

DCE, rt, 30 min

Co(dpm)2 (10 mol%),

PhMeSiH2 (400 mol%),

DCE, rt, 30 min

Co(dpm)2 (5 mol%),

PhSiH3 (240 mol%),

2. P(OEt)3 (1.1 eq)

Mn(dpm)3 (3 mol%), i-PrOH, DCE, O2

1. PhSiH3 (1.3 eq),

Mn(dpm)3 (3 mol%), i-PrOH, DCE

I

O

II (—)

I (11)

Ph

O

O

+

Ph

O

H

H

H

H

O

O

H

(70)

O OH

O

(72) (11)

(—) (73)

(38) (41)

H

Ph

H

H

0.10

4.0

PhMeHSi

CH2

PhSiH3 (1.3 eq),

0.05

2.4

PhH2Si

CH2

H

0.05

1.2

PhH2Si

CH2

O

(69)

0.10

4.0

PhMeHSi (9)

(—) (63)

0.05

2.4

PhH2Si

O

II

O

I (16) (31)

PhH2Si

O

y 0.05

x 1.2

R3Si

Y

II

Ph (72)

(85)

(99)

460

460

460

465

448

506

C23

AcO

AcO

O

AcO

H

H

O

O

O

O

O

CH2Cl2, rt, 1 h

Et3SiH (1.2 eq), TiCl4 (2.4 eq),

CH2Cl2, rt, 1 h

Et3SiH (1.2 eq), TiCl4 (2.4 eq),

Et3SiH, TFA, 30 h

Et3SiH, TFA, CH2Cl2, 48 h

CH2Cl2, rt, 0.5 h

Et3SiH (1.2 eq), TiCl4 (2.4 eq),

Conditions

H

H

AcO

AcO

H

I (96) + II (4)

O

AcO

I

I

O

O

O

O

O

(86)

O

H

(76)

(70-80)

+

(80)

Product(s) and Yield(s) (%)

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

II

O (14)

O

449

449

242

242

449

Refs.

507

C27

C26

O

H

OMe

OMe

t-BuPh2SiO

MeO

MeO

H

O

O

CF3

OEt

OEt

O

N

(50) (45) (75) (40) (75) (50)

0.5 h 0.5 h 0.6 h 0.4 h 0.5 h —

60° 60° 60° rt rt

MeCl2Si Me2ClSi Et2(EtO)Si Me(EtO)2Si HMe2SiOSiMe2

CH2Cl2, rt, 12 h

(Ph3P)4RhH (0.4 mol%),

Ph2SiH2 (1.3 eq),

Et3SiH, (Ph3P)3RhCl

CH2Cl2, rt, 48 h

Et3SiH (3.95 eq), BF3•OEt2 (19.8 eq),

OMe

OMe

H

t-BuPh2SiO

MeO

MeO

(70)

7h

160°

(n-Pr)3Si

[—(H)(Me)SiO—]4 60°

(80)

5h

150°

Et3Si

I

Temp Time

R3Si

R3SiH, H2PtCl6, MeC6H5

H

OSiEt3

CHO

O

N CF3

(32)

(64)

(76)

374

761

443

458

508

C29

C27

a

H

O

O

C8H17-n

3

NAc Co(dpm)2 (5 mol%), 50°

PhSiH3 (2.4 eq),

CH2Cl2, rt, 10 min

Et3SiH (1.2 eq), TiCl4 (2.4 eq),

(Ph3P)4Pd (0.067 eq), CHCl3, rt, 1 h

Ph2SiH2 (1.6 eq), ZnCl2 (0.90 eq),

(Ph3P)4Pd (7.2 mol%), CHCl3, rt, 1 h

Ph2SiD2 (4 eq), ZnCl2 (4 eq),

(Ph3P)4Pd (0.03 eq), CHCl3, rt, 1 h

Ph2SiH2 (1.6 eq), ZnCl2 (0.5 eq),

The yield was determined by NMR analysis.

AcN

O

O

O

3

Conditions

AcN

O

O

O

O D

H

H

H

O

O

(92)

(71)

(100)

NAc (68)

(81) 5α:5β = 3:1

C8H17-n

3

3

Product(s) and Yield(s) (%)

TABLE 16. ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued) Unsaturated Ketone

461

449

436

436

436, 457

Refs.

509

C4

O OMe

Unsaturated Ester

CH2Cl2, 45°, 3 h

[Rh(cod){P(OPh)3}2]OTf (1 mol%),

Et2MeSiH (1 eq), PhNCO (0.5 eq),

C6H6, 80°, 1 h

EtMe2SiH, (Ph3P)3RhCl (0.1 mol%),

C6H6, 60°, 12 h

PhMe2SiH, (Ph3P)3RhCl (0.1 mol%),

C6H6, 60°, 1 h

Et3SiH, (Ph3P)3RhCl (0.1 mol%),

100°, 1 min

(n-Pr)3SiH, (Ph3P)3RhCl (0.5 mol%),

N H

+

(90)

O

OMe

OMe

OMe

O

O

Et3Si

(31.6)

II

OMe

(78)

(80)

OMe

OSiEt3

(n-Pr)3Si

(90)

+

O

TMS

(23)

(26)

O

O

Product(s) and Yield(s) (%)

OMe (33) +

Et3Si

OMe

O

EtMe2Si

PhMe2Si

II (54)

Ph

+

O

TMS

OMe

OSi(Pr-n)3

I (42)

Et3SiH, H2PtCl6 (0.5 mol%)

I

I (22) +

I (96)

O

TMSH, H2PtCl6 (0.5 mol%)

C6H6, rt, 4 h

PMHS-Pd nanocomposite,

CD3CN, DMI (0.5 eq), 70°, 5 h

Cl3SiH (2 eq), CoCl2 (0.175 eq),

Conditions

TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS

OMe

OMe

(38.9)

(4)

475

466

466

466

467

467

467

219

451

Refs.

510

C4

O OMe

Unsaturated Ester

3h 14 h 10 h 47 h 47 h 68 h

[Rh(cod){P(OPh)3}2]OTf [Rh(cod)(PPh3)2]OTf [Rh(cod)(PPh2Me)2]OTf [Rh(cod)(dppb)]OTf Rh4(CO)12 None

O

(90) (93) (96) (73) (96) (96) (86) (94) (99) (85) (82) (82) (45) (43) (0)

3h 13 h 5h 15 h 13 h 13 h 12 h 6h 4h 12 h 14 h 15 h 61 h 24 h

4-BrC6H4 4-MeOC6H4 4-MeC6H4 3-MeC6H4 2-MeC6H4 2-ClC6H4 1-C10H7 2-C4H3O p-Ts Bz Bn c-C3H5 c-C6H11

O

3h

(0)

4-ClC6H4

O

(79)

(68)

(89)

(95)

(90)

(86)

Time

N H

N H

Ph

R

Ph

O

R

CH2Cl2, 45°

[Rh(cod){P(OPh)3}2]OTf (1 mol%),

Et2MeSiH (1 eq), RNCO (0.5 eq),

21 h

[Rh(cod){P(OPh)3}2]OTf

PhNCO (0.5 eq), CH2Cl2, rt Catalyst Time

Et2MeSiH (1 eq), catalyst (1 mol%),

Conditions

OMe

OMe

Product(s) and Yield(s) (%)

TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)

475

475

Refs.

511 (68) (49) (47) (20:1

er of I

+

OMe

OMe

(69) syn:anti = 23:1

(15) syn:anti = 15:1

I:II

O

O

OMe

BnOCH2

I

O

OH

Ph

OH

OMe

OMe

OH

O

O

I + II

R

Ph

Ph

OH

OH

R

RCHO, 97 (7.5 mol%), rt, 24 h

Et2MeSiH, [Ir(cod)Cl]2 (2.5 mol%),

1-naphthaldehyde, CH2Cl2, rt, 16 h

Me-DuPHOS (5.5 mol%),

Cl2MeSiH, [Rh(cod)Cl]2 (2.5 mol%),

(E)-PhCH=CHCHO, CH2Cl2, rt, 16 h

Me-DuPHOS (5.5 mol%),

Cl2MeSiH, [Rh(cod)Cl]2 (2.5 mol%),

CH2Cl2, rt, 16 h

Me-DuPHOS (5.5 mol%), PhCHO,

Cl2MeSiH, [Rh(cod)Cl]2 (2.5 mol%),

CH2Cl2, rt, 16 h

Me-DuPHOS (5.5 mol%), i-PrCHO,

Cl2MeSiH, [Rh(cod)Cl]2 (2.5 mol%),

601

762

762

762

762

512

C5

C4

O

O

OEt

OMe

Unsaturated Ester

70°, 12 h

ClMe2SiH, (Ph3P)3RhCl,

reflux, 12 h

EtMe2SiH, (Ph3P)3RhCl,

80°, 2 h

PhMe2SiH, (Ph3P)3RhCl,

CD3CN, DMI (0.5 eq), 70°, 5 h

Cl3SiH (2 eq), CoCl2 (0.175 eq),

CD3CN, DMI (0.5 eq), 80°, 10 h

PhMe2SiH (2 eq), CoCl2 (0.175 eq),

RhCl3•3H2O (0.009 mol%), acetone, rt

TMSH (1.3 eq),

OEt

OEt

SiMe2Cl

O

EtMe2Si

Me2PhSi

I

O

I (70)

OMe OTMS

O (24)

O

O

(65)

OEt

OEt

(85)

(83)

(85)

50:50 (14)

(62)

20 h

BnCH2

R III

OMe

50:50 (10)

O

(80)

R

OH

(E)-PhCH=CH 20 h

OMe

+

II I:II

I

O

I + II

R

OH +

Product(s) and Yield(s) (%)

Time

2. H3O+

RCHO, DCE, 20°

1. PhSiH3 (2 eq), Co(dpm)2 (0.05 mol%),

Conditions

TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)

R III

OH

466

466

466

451

451

473

475

Refs.

513

O OMe

acetone, rt

RhCl3•3 H2O (0.009 mol%),

TMSH (1.3 eq),

2. MeOH, rt

1. TMSH, H2PtCl6 (0.5 mol%), 60°, 3 h

rt, 72 h

(Ph3P)4Pd (0.02 eq), PPh3 (0.09 eq),

Ph2SiD2 (1.2 eq), ZnCl2 (1.74 eq), D

OMe

+

OMe

OMe

OTMS

O

O

O

+

O OMe

(54)

TMS

CO2Me

CO2Me

(89)

(28)

(90)

(17)

473

467

436

514

C5

O

OMe

OMe

O

Unsaturated Ester

TMSH (1.3 eq), RhCl3•3 H2O O (0.009 mol%), , rt R1 R2

THF, reflux, 20 h

Mo(CO)6 (3-5 mol%),

PhSiH3 (1.3-1.5 eq),

CH2Cl2, 80°, 24 h

[Rh(cod){P(OPh)3}2]OTf (1 mol%),

Et2MeSiH (1 eq), PhNCO (0.5 eq), N H

R2

R1

O

O

OMe

OMe

OTMS

O

O

O

(61)

5h

2-ClC6H4 (53)

(95)

14 h

2-MeC6H4

12 h

(84)

14 h

3-MeC6H4

p-Ts

(95)

12 h

4-MeC6H4

(83)

(92)

14 h

4-MeOC6H4

4h

(91)

13 h

4-BrC6H4

2-C4H3O

(80)

4h

15 h

(87)

13 h

4-ClC6H4

1-C10H7

(88)

Time

N H

O

Ph

Ph

Ar

Ar

CH2Cl2, 45°

[Rh(cod){P(OPh)3}2]OTf (1 mol%),

Et2MeSiH (1 eq), ArNCO (0.5 eq),

Conditions

(78) H

(66)

(91)

(95) —CH2CH(Me)(CH2)3—

Me Me

Et

R2 Me

Me

(26)

R1

(90)

OMe

OMe

Product(s) and Yield(s) (%)

TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)

473

450

475

475

Refs.

515

O

O

O

OMe

EtMe2SiH, (Ph3P)3RhCl, C6H6, 70°, 12 h

PhMe2SiH, (Ph3P)3RhCl, 60°, 2 h

100°, 1 min

(n-Pr)3SiH, (Ph3P)3RhCl (0.5 mol%),

Et3SiH, (Ph3P)3RhCl, C6H6, 70°, 2 h

(P h3P)4RhH (0.3 mol%), CH2Cl2, rt, 1.5 h

(EtO)3SiH (1.1 eq),

CH 2Cl2, rt, 12 h

(P h3P)4RhH (0.3 mol%),

(EtO)3SiH (1.1 eq),

RhCl 3•3H2O (0.009 mol%), acetone, rt

TMSH (1.3 eq),

O

OMe

OSiMe2Et

OMe

OSiMe2Ph

OMe

OSi(Pr-n)3

OMe

OSiEt3

OMe

(86)

(71)

(70)

+

+

+

(34)

(91)

(74)

(85)

O

OSi(OEt)3

O

OSi(OEt)3

TMSO

OMe

OSiMe2Et

OMe

(6)

(24)

(6)

OSiMe2Ph

OMe

OSiEt3

466

466

467

466

374

374

473

516

C6

C5

O

O

O OMe

OMe

OEt

Unsaturated Ester

100°, 1 min

n-Pr3SiH, (Ph3P)3RhCl (0.5 mol%),

TMSH, H2PtCl6 (0.5 mol%)

2. MeOH, rt

100°, 1 min

1. (n-Pr)3SiH, (Ph3P)3RhCl (0.5 mol%),

2. MeOH, rt

100°, 1 min

1. Et3SiH, (Ph3P)3RhCl (0.5 mol%),

2. MeOH, rt

60°, 10 min

1. TMSH, (Ph3P)3RhCl (0.5 mol%),

Et3SiH, (Ph3P)3RhCl, C6H6, 70°, 3 h

Conditions

Et3Si

OEt

OMe

OMe

OSi(Pr-n)3

+

O

OMe

OSi(Pr-n)3

OMe

OSiEt3

OMe

OTMS

O +

O

O

(25)

OMe

(28)

(3)

(8.6)

OEt

OSiEt3

OMe

TMS

TMS

Et3Si

CO2Me

CO2Me

+

+

(75.4)

(56)

(73.5)

(85.6)

(77)

(52)

Product(s) and Yield(s) (%)

TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)

467

467

467

467

467

466

Refs.

517

O

CN

O

OEt

OMe

OEt

OEt

O

O

Et3SiH (1 eq), TFA (3 eq), 0°, 25:1

21:1

—

4.3:1

11:1

dr

OH

CO2Me

(47)

2h

(EtO)3Si

OSiEt3

(0)

6h

Et3SiH (2.1 eq), (Ph3P)4RhCl (1 mol%),

(8)

15 h

Ph2ClSi

O

OH

CO2Me

O

PhMeClSi

H

(74)

O

1h

Time

N

S

MeCl2Si

R3Si

Me-DuPHOS (5 mol %), C6H6, rt

R3SiH, [Rh(cod)Cl]2 (2.5 mol%),

Me-DuPHOS (5 mol%), C6H6, rt, 4 h

MeCl2SiH, [Rh(cod)Cl]2 (2.5 mol%),

CH2Cl2, rt, 1.5 h

Et3SiH (3.15 eq), TFA (19.5 eq),

R

471

471

474

474

468

522

C9

O

O

H

OPh

O

OMe

Unsaturated Ester

RCHO (0.2 eq), rt, 12 h R

Et2MeSiH (0.35 eq), [Rh(cod){(R)-BINAP}] BF4 (5 mol%),

1. R3SiH (0.5 eq), [Rh(cod){(R)-BINAP}] BF4 (5 mol%), CH3CH2CHO (2.0 eq) 2. H3O+ R3Si Et2MeSi PhMe2Si (EtO)Me2Si

1. EtMe2SiH (1.0 eq), [Rh(cod)Cl]2 (2.5 mol%), CH3CH2CHO (0.83 eq), (R)-BINAP (6.5 mol%), rt, 24 h 2. H3O+

MeC6H5, 50°, 16 h

Et3SiH (2.1 eq), (Ph3P)4RhH (1 mol%),

Conditions

I

OH

PhO

(0)

I (23) (18) O

I + II

O

II

O II

O

er II 91:9 90:10 89:11

(6) dr = 4.6:1, er = 94:6

PhO

er I

+

91:9 90:10 —

(73) syn:anti = 7:1, ee syn = 81%

(90) syn:anti = 3:1, ee syn = 75%

(54) syn:anti = 6:1, ee syn = 71%

(86) syn:anti = 6:1, ee syn = 83%

R

OH

II (42) (48) (29)

(46) dr = 4.6:1, er = 94:6

PhO

O

+

OSiEt3 CO2Me

I + II (68), I:II = 2.5:1

I

OSiEt3 CO2Me

Product(s) and Yield(s) (%)

TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)

470

470

470

471

Refs.

523

C10

O

O

O

O

O

OMe

H

O OPh

OC6H11-c

O

O

OMe

CH3CH2CHO (0.83 eq), rt, 48 h

(S)-BINAP (6.5 mol%),

Et2MeSiH (5 eq), [Rh(cod)Cl]2 (5 mol%),

Mo(CO)6 (3-5 mol%), THF, reflux, 35 h

PhSiH3 (1.3-1.5 eq),

MeC6H5, 50°, 16 h

Et3SiH (2.1 eq), (Ph3P)4RhH (1 mol%),

MeC6H5, 50°, 16 h

Et3SiH (2.1 eq), (Ph3P)3RhCl (1 mol%),

MeC6H5, 50°, 16 h

Et3SiH (2.1 eq), (Ph3P)4RhH (1 mol%),

MeC6H5, 50°, 16 h

Et3SiH (2.1 eq), (Ph3P)3RhCl (1 mol%),

I

O

O

III

+

+

O

O

O

O

II

I:II:III:IV = 2:5.4:2:1

I + II + III + IV (65)

CO2Me

OSiEt3

CO2Me

OSiEt3

PhO

O

O

I (60)

I O

OMe

OH

OC6H11-c

O

IV

CO2Me

OSiEt3

CO2Me

OSiEt3

(76) syn:anti = 4.3:1, ee syn = 88%

(100)

(68)

I + II + III + IV (81), I:II:III:IV = 5.4:4:2:1

+

O

O

470

450

471

471

471

471

524

C11

C10

n-Pr

Ph

O

O

O

O

O

O

O

H

H

O

OPh

O

O

O

OMe

OMe

O

OMe

Unsaturated Ester

MeC6H5, 50°, 16 h

Et3SiH (2.1 eq), (Ph3P)4RhH (1 mol%),

MeC6H5, 50°, 16 h

Et3SiH (2.1 eq), (Ph3P)4RhH (1 mol%),

Me-DuPHOS (5 mol%), C6H6, rt, 15 h

MeCl2SiH, [Rh(cod)Cl]2 (2.5 mol%),

Me-DuPHOS (5 mol%), C6H6, rt, 4 h

MeCl2SiH, [Rh(cod)Cl]2 (2.5 mol%),

MeC6H5, 20 min

PhSiH3 (1.5 eq), [(Ph3P)CuH]6 (5 mol%),

rt, 48 h

(Ph3P)4Pd (0.02 eq), PPh3 (0.05 eq),

Ph2SiH2 (1.7 eq), ZnCl2 (0.76 eq),

CH3CH2CHO (0.83 eq), rt, 48 h

(S)-BINAP (6.5 mol%),

Et2MeSiH (5 eq), [Rh(cod)Cl]2 (5 mol%),

Conditions

O

I

O

OH

OMe

OH

(91) dr > 25:1

(88)

(81)

(50) dr = 23:1

O

(80)

(52) syn:anti = 3.9:1, ee syn = 88%

CO2Me

OSiEt3

O

OMe

OH

O

O

Et3SiO

n-Pr

I (95)

Ph

PhO

O

Product(s) and Yield(s) (%)

TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)

471

471

474

474

447

436

470

Refs.

525

C12

Ph

O

O

O

O

O

O

O

O OEt

OPh

H OMe

Me-DuPHOS (5 mol%), C6H6, rt, 15 h

MeCl2SiH, [Rh(cod)Cl]2 (2.5 mol%),

Me-DuPHOS (5 mol%), C6H6, rt, 15 h

MeCl2SiH, [Rh(cod)Cl]2 (2.5 mol%),

CD3CN, DMI (0.5 eq), 70°, 5 h

Cl3SiH (2 eq), CoCl2 (0.175 eq),

DMA, 0° to rt, 4.5 h

PPh3 (20 mol%), TBAF (10 mol%),

PhMe2SiH (1.2 eq), CuCl (20 mol%),

DMI, rt, 5 h

PhMe2SiH (2 eq), CuCl (x eq),

CH3CH2CHO (0.83 eq), rt, 48 h

(S)-BINAP (6.5 mol%),

Et2MeSiH (5 eq), [Rh(cod)Cl]2 (5 mol%),

MeC6H5, 50°, 16 h

Et3SiH (2.1 eq), (Ph3P)3RhCl (1 mol%),

MeC6H5, 50°, 16 h

Et3SiH (2.1 eq), (Ph3P)3RhCl (1 mol%), I

I (50)

I (54)

Ph

PhO

O

I

O OEt

OH

I (69) dr = 1:20

CO2Me

OSiEt3

O OH

(74)

(76) dr > 25:1

(0)

0.1

OH

(86)

0.2

O

(90)

(96)

0.5

1

x

(0)

(61) dr = 1.5:1

474

474

451

444

445

470

471

471

526

C13

C12

Ph

Ph

Ph

Ph

Et

O

O

O

OMe

O

OMe

OEt

OEt

OEt

OPr-i

O

O

H

O

CN

O

Unsaturated Ester Conditions

MeC6H5, rt, 4 h

NaOBu-t (0.1 mol%), t-BuOH (12 eq),

PMHS (12 eq), 209 (2 mol%),

MeC6H5, rt, 1 h

NaOBu-t (0.1 mol%), t-BuOH (4 eq),

PMHS (4 eq), 209 (0.3 mol%),

MeC6H5, rt, 1 h

NaOBu-t (1.8 mol%), t-BuOH (4 eq),

PMHS (4 eq), 209 (0.3 mol%),

MeC6H5, rt, 1 h

NaOBu-t (0.1 mol%), t-BuOH (4 eq),

PMHS (4 eq), 209 (0.3 mol%),

reflux, 24 h

Mo(CO)6 (3-5 mol%), THF,

PhSiH3 (1.3-1.5 eq),

50°, 16 h

(Ph3P)3RhCl (1 mol%), MeC6H5,

Et3SiH (2.1 eq),

50°, 16 h

(Ph3P)3RhCl (1 mol%), MeC6H5,

Et3SiH (2.1 eq),

Ph

Ph

Et

I (88)

Ph

Ph

O

O

O

O

CN

I

I

CO2Me

OEt

OEt

OEt

OPr-i

OMe

OSiEt3

O

+

(93) dr = 1.5:1

(97)

(91)

(90)

(91)

I + II (54), I:II = 2:1

OSiEt3

II

OSiEt3

Product(s) and Yield(s) (%)

TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)

CO2Me

454

454

454

454

450

471

471

Refs.

527

C15

C14

Ph

n-C6H13

BnO

O H

O

O

O

OPh

O

OPr-i

OMe

OC6H11-c

H

O

O

OPh

THF, reflux, 30 h

Mo(CO)6 (3-5 mol%),

PhSiH3 (1.3-1.5 eq),

CH3CH2CHO (0.83 eq), rt, 48 h

(S)-BINAP (6.5 mol%),

Et2MeSiH (5 eq), [Rh(cod)Cl]2 (5 mol%),

CH3CH2CHO (0.83 eq), rt, 48 h

(S)-BINAP (6.5 mol%),

Et2MeSiH (5 eq), [Rh(cod)Cl]2 (5 mol%),

MePh, 50°, 16 h

Et3SiH (2.1 eq), (Ph3P)4RhH (1 mol%),

MePh, 50°, 16 h

Et3SiH (2.1 eq), (Ph3P)4RhH (1 mol%),

MePh, 50°, 16 h

Et3SiH (2.1 eq), (Ph3P)3RhCl (1 mol%),

+ BnO

I BnO

CO2Me

+

+

II

I:II:III:IV = 1.7:1.5:1:1

Ph

n-C6H13

PhO

O

PhO

I

O

+

CO2Pr-i

OC6H11-c

471

471

471

(75)

450

470

(30) syn:anti = 4.4:1, —% ee syn 470

II

OSiEt3

CO2Me

(54) syn:anti = 4.2:1, 88% ee syn

OH

I + II (59), I:II = 1:2

CO2Pr-i

OH

O

OSiEt3

IV

OSiEt3

CO2Me

BnO

OSiEt3

I + II + III + IV (81),

III

OSiEt3

CO2Me

I + II + III + IV (72), I:II:III:IV = 1.2:1:1.2:1.7

BnO

OSiEt3

528

C19

C18

C16

EtO

Ph

TBSO

O

O

OEt Sn(Bu3-n)3

O

CO2Me

Ph

OC12H25-n

O

CH2Cl2, –78°, 1 h

Et3SiH (10 eq), TMSOTf (2 eq),

CH3CH2CHO (0.83 eq), rt, 48 h

(S)-BINAP (6.5 mol%),

[Rh(cod)Cl]2 (5 mol%),

Et2MeSiH (5 eq),

CH3CH2CHO (0.83 eq), rt, 48 h

(S)-BINAP (6.5 mol%),

[Rh(cod)Cl]2 (5 mol%),

Et2MeSiH (5 eq),

MeC6H5, 50°, 16 h

Et3SiH (2.1 eq), (Ph3P)3RhCl (1 mol%),

DMI, rt, 6 h

PhMe2SiH (4 eq), CuCl (2 eq),

Conditions

EtO

Ph

OEt

OH

OH

Sn(Bu3-n)3

O

O

PhO

O

CO2Me

Ph

OC12H25-n

PhO

TBSO

O

O

(72)

(74)

(95)

93% ee syn

(49) syn:anti = 3.9:1,

88% ee syn

(53) syn:anti = 3.8:1,

Product(s) and Yield(s) (%)

TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)

OPh

OPh

O

Unsaturated Ester

469

470

470

471

445

Refs.

529

C22

C21

PhS

Ph

Ph

O

O

O

OMe

H OPr-i

Sn(Bu3-n)3

O

O

Sn(Bu-n)3

OMe

(54)

TFA

Ph3Si

CH2Cl2, –78°, 1 h; 0° 1 h; rt, 4 h

Et3SiH (10 eq), TFA (2 eq),

CH2Cl2, –78°, 1 h; 0°, 5 h; rt, 5 d

Et3SiH (10 eq), TMSOTf (2 eq),

CH2Cl2, –78°, 1 h; rt, 5 d

Et3SiH (10 eq), BF3•OEt2 (2 eq),

MePh, 50°, 16 h

Et3SiH (2.1 eq), (Ph3P)4RhH (1 mol%),

CH2Cl2, –78°, 1 h; 0°, 1 h

I (24)

I (24)

PhS

Ph

Ph

O

I

+ Ph

Ph

OMe

(42)

I + II (68), I:II = 1:2.5

Sn(Bu3-n)3 I

O

(—)

CO2Pr-i

Sn(Bu-n)3

OMe

Sn(Bu-n)3

OMe

OSiEt3

(0) (74)

TMSOTf

Ph3Si

O

(98)

HOAc

Et3Si

D

(96)

TMSOTf

Et3Si

Et3SiH (10 eq), DOAc (2 eq),

(71)

BF3•OEt2 TFA

Et3Si

O

Et3Si

Acid

R3Si

CH2Cl2, –78°, rt, 4 h

R3SiH (10 eq), acid (2 eq),

O

II

OSiEt3 CO2Pr-i

469

469

469

471

469

469

530

C25

C24

O

O

O

OBn Sn(Bu3-n)3

O

Sn(Bu-n)3

OBn

Unsaturated Ester

CH2Cl2, –78°, 1 h

Et3SiH (10 eq), TFA (2 eq),

CH2Cl2, –78° to rt, 1 h; 0° 1 h

Et3SiH (10 eq), TMSOTf (2 eq),

Conditions

O

O

O

OBn Sn(Bu3-n)3

O

Sn(Bu-n)3

OBn

(64)

(61)

Product(s) and Yield(s) (%)

TABLE 17. ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued)

469

469

Refs.

531

C5

C4-10

C3-9

n-Pr n-Pr i-Pr

H

n-Pr

i-Pr

NMe2

H

H

O

R2

R1

R2

N

R

(80)

I:II 24:76 31:69 30:70 28:72 36:64

(78) (72) (93) (68) (75)

1-C10H7 4-MeC6H4 2-C10H7 4-O2NC6H4 4-ClC6H4

Ph

R

32:68

NMe2

+

(87)

O

R1

R1

R

OH

II

O NMe2

Product(s) and Yield(s) (%)

I + II

RCHO, CH2Cl2, rt, 45 h I

(70)

15 h

Cl3SiH (1.3 eq), (Ph3P)4Pd, (5 mol%),

(100)

4h OH

(100)

1.3 h

R2

N

1.7 h

Time

Mo(CO)6 (3-5 mol%), THF, reflux

PhSiH3 (1.3-1.5 eq),

0.2 h

i-Pr

i-Pr O

(95)

0.2 h

n-Pr

n-Pr

R1

(100)

1h 0.3 h

n-Pr

H

O

(80) (100)

Time

R2

N

H

O

R2

Mo(CO)6 (3-5 mol%), THF, reflux

PhSiH3 (1.3-1.5 eq),

H

R2

N

R1

Conditions

TABLE 18. ORGANOSILANE REDUCTION OF α,β−UNSATURATED AMIDES

R1

O

Unsaturated Amide

763

450

450

Refs.

532

C25

C11

C10

C5-6

Ph

Ph

R1

O

NHTs

NMe2

Sn(Bu-n)3

O

O

CH2Cl2, –78°, 1.5 h

Et3SiH (10 eq), TMSOTf (2 eq),

PPh3 (0.019 eq), CHCl3, rt, 10 h

(Ph3P)4Pd (0.011 eq),

Ph2SiH2 (3 eq), ZnCl2 (1.1 eq),

Mo(CO)6 (3-5 mol%), THF, reflux, 4 h

PhSiH3 (1.3-1.5 eq),

PPh3 (0.019 eq), rt, 10 h

(Ph3P)4Pd (0.011 eq),

Ph

O

I (80)

I

4h

(E)-PhCH=CH

Me

H

—

—

NHTs

NMe2

Sn(Bu-n)3

O

O

O

(70)

(50)

72:28

70:30

70:30

72:28

80:20

I:II

NHMe

5h

Ph

Me

H

Ph

4h

(E)-PhCH=CH

H

Me

NHMe

(72)

3h

Ph

H

Me

Ph2SiH2 (1.5 eq), ZnCl2 (1.0 eq),

(90)

6h

BnCH2

H

H

O

(96)

4h

(E)-PhCH=CH

H

H

(68)

(95)

2h

Ph

H

H

I

(41)

(78)

+

(14)

(31)

(12)

(10)

(trace)

O R2 R1

(trace)

(3)

III

OH

(78)

R3

O

II

NHTs

R3

Sn(Bu-n)3

O

NMe2 +

Product(s) and Yield(s) (%)

NMe2 +

I + II

R1

R2

O

Time

OH

R3

R3CHO, ClCH2CH2Cl, 20°

PhSiH3 (2 eq), CoX2 (0.05 mol%),

R3

R2

NMe2

Conditions

TABLE 18. ORGANOSILANE REDUCTION OF α,β−UNSATURATED AMIDES (Continued)

R1

R2

O

Unsaturated Amide

III

(0.5)

OH

469

436

450

436

478

Refs.

533

C16

C9

C8

C6

C5

C3-4

H H H Me

H

Me

Me

H

Fe

H

H

Ph

H

H

CN

CN

CN

CN

E:Z = 1:1

CN

R2

R2

CN

R1

R1

CN

Unsaturated Nitrile

Et3SiH (2 eq), TFA, rt, 3 h

PMHS-Pd nanocomposite, C6H6, rt, 5 h

Mo(CO)6 (3-5 mol%), THF, reflux, 12 h

PhSiH3 (1.3-1.5 eq),

rt, 72 h

(Ph3P)4Pd (0.013 eq), PPh3 (0.05 eq),

Ph2SiH2 (1.25 eq), ZnCl2 (0.66 eq),

Mo(CO)6 (3-5 mol%), THF, reflux, 4.5 h

PhSiH3 (1.3-1.5 eq),

Mo(CO)6 (3-5 mol%), THF, reflux, 9 h

PhSiH3 (1.3-1.5 eq),

Mo(CO)6 (3-5 mol%), THF, reflux, 12 h

PhSiH3 (1.3-1.5 eq),

I

Fe

I (90)

I (90)

CN

CN

(60)

24 h

20°

acac

CN

(83)

CN

(49)

CN

(100)

(0)

(5) (31)

(92)

12 h

20°

dpm

CN

(2) (25)

(72)

5h

70°

acac

(3)

(93)

20°

dpm

(42)

20°

acac 12 h

3h

70°

acac 24 h

Ph II

R1

+

(5)

I

CN R2

OH

(100)

II

Product(s) and Yield(s) (%)

I

Ph

Ph

OH

(70)

PhCHO, ClCH2CH2Cl Temp Time X

PhSiH3 (2 eq), CoX2 (0.05 mol%),

Conditions

TABLE 19. ORGANOSILANE REDUCTION OF α,β−UNSATURATED NITRILES

179

219

450

436

450

450

450

478

Refs.

534

C7

C6-8

C6

C5

O

O R1

OMe

OMe

O

O

OMe

Et3SiH, TFA, 55°, 15 h

TMSOTf (0.01 eq), CH2Cl2, 0°, 30 min

TMSH (1.1 eq),

Et3SiH, TFA, rt

I2SiH2 (3 eq), CHCl3, 22°, 12 h

CH2Cl2, 0°, 30 min

TMSH (1.1 eq), TMSOTf (0.01 eq),

2. I2

1. I2SiH2 (2 eq), CHCl3, 22°, 30 min

I2SiH2 (2 eq), CHCl3, 22°, 30 min

I2SiH2 (2 eq), CHCl3, 22°, 30 min

Conditions

I

(—)

S

OMe

I

OSiEt3

(100)a

(—)

CF3O2C (—)

(45)

OCHR1R2 + R1R2CHO

+

(100)

(100)

OCHR1R2

OMe

(100)

(100)

+ CF3O2C

HO

I

I (99)

I

I

Product(s) and Yield(s) (%)

TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS

2 O R R1,R2 = H, H; H, Me; Me,Me

O

OMe

S

OMe

OEt

OEt

MeO

O

MeO

Acetal/Ketal

(—)

764

260

480

OCHR1R2

O2CCF3

358

480

358

358

358

Refs.

535

C8

O

O

O

MeO

HO

O

OH

O OH HO

OH

OMe

O

OMe

OH

O

O

MeO OMe

HO HO

HO

CH2Cl2, –78°, 15 min

Ph2SiH2 (1.5 eq), TiCl4 (1.2 eq),

I2SiH2 (3 eq), CHCl3, 22°, 24 h

CH2Cl2, reflux, 4 h

Et3SiH (1.1 eq), Nafion®-H,

I2SiH2 (2 eq), CHCl3, 22°, 2 h

BF3•OEt2 (1.1 eq), 0°, 10 min

2. Et3SiH (1.5 eq),

1. i-Bu2AlH, hexanes, MeC6H5, –78°

TFA (12 eq), 0° to rt, 16 h

Et3SiH (30 eq), BF3•OEt2 (30 eq),

Et3SiH, TMSOTf, MeCN

I

O HO

O

OH

OH

O

(98)

(70)

(50)

OH

(91.7)

(90)

(50)

O

O

MeO OMe

OMe

I

HO

HO HO

HO

(82)

492

358

335

358

510

483

518

536

C8

O

O

O

O

O

O O

O

O Et3SiH, HOTf

CH2Cl2, –78°

Et3SiH (1.2 eq), SnCl4 (1.2 eq),

CH2Cl2, –78°, 15 min

Et3SiH (1.2 eq), TiCl4 (1.2 eq),

CH2Cl2, –78°

Et3SiH (1.5 eq), TiCl4 (1.2 eq),

CH2Cl2, –78°, 15 min

Ph2SiH2 (1.5 eq), TiCl4 (1.2 eq),

CH2Cl2, –78°

Et3SiH (1.5 eq), TiCl4 (1.2 eq),

Conditions

I

O +

O

IV

O

II

O

II

O

OH

OH

OH

OH

(51) single diastereomer

I + II (71), I:II = 63:36

OH

+

I + II (76), I:II = 7:93

OH

I + II (72), I:II = 76:24

I

O

+

II

O

I + II + III + IV (61),

OH

+

I:II:III:IV = 42.6:0.8:48.7:7.9

III

O

OH

I + II (82), I:II = 1:99

+

I

O

Product(s) and Yield(s) (%)

TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal

499

495

495

495

495

495

Refs.

537

C8-12

R2

R1

H H H H H Me H H H H Me

Ph

Ph

Ph

Ph

4-ClC6H4

Ph

3-MeOC6H4

3-MeOC6H4

4-MeC6H4

BnCH2

BnCH2

R2 H

—(CH2)5—

c-C6H11

R1

O

O

(93)

(81)

(70)

Bn

(80)

(93)

Bn

Bn

(86)

Bn

(86)

(80)

c-C6H11

Bn

(86)

allyl

(83)

(87)

n-C5H11

Bn

(82)

Bn

allyl

(87)

R2

Bn

R1

OR3

Bn

R3

Sn(OTf)2, MeCN, –20°, 3-6 h

TBSH (1.4 eq), R3OTMS (3 eq), 501

538

C9

C8

Ph

O

O

OMe

OMe

endo:exo = 40:60

OEt

OEt

OMe

OMe

O

O

CH2Cl2, reflux, 2 h

Et3SiH (1.1 eq), Nafion®-H,

CH2Cl2, 0°, 30 min; 29°, 16 h

Et3SiH (1.1 eq), TMSOTf (0.01 eq),

CH2Cl2, 0°, 30 min

TMSH (1.1 eq), TMSOTf (0.01 eq),

CH2Cl2, reflux, 2 h

Et3SiH (1.1 eq), Nafion®-H,

Et3SiH (1.2 eq), TFA (30 eq), 50°, 8-10 h

CH2Cl2, 0° to rt, 24 h

Et3SiH (10 eq), BF3•OEt2 (10 eq),

CH2Cl2, 0° to rt, 24 h

Et3SiH (10 eq), BF3•OEt2 (10 eq),

Conditions

I (96)

I (90)

Ph

+

(96)

(99)

(21)

(75)

+

I + II (85), I:II = 40:60

OEt

OH

OH

OMe

OMe I

O

I

O

O

II

O OH

Product(s) and Yield(s) (%)

TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal

(45)

335

480

480

335

327

485

485

Refs.

539

C9-12

C9-10

C9

Ph

R

(82) (77)

Ac

Ac

(96)

—(CH2)5—

(91)

—(CH2)4—

(89)

Br

NEt2

Et

Ph

R

Me

AcBr (2.2 eq), CH2Cl2, rt, 3 h

Et3SiH (1.56 eq), SnBr2 (0.056 mol%),

CH2Cl2, 0° to rt, 36 h

Et2NSiHMe2 (1.2 eq), TiCl4 (0.2 eq),

O MeO

Et

6

2. Ac2O (12 eq), rt, 24 h

O

MeO OMe

R2

O

AcO MeO

MeO

MeO

Me

MeO

TFA (12 eq), 0°

1. Et3SiH (30 eq), BF3•OEt2 (30 eq),

TFA (12 eq), 0° to rt, 16 h

Et3SiH (30 eq), BF3•OEt2 (30 eq),

I (97)

Et3SiH, FSO3H, TMSNHCONHTMS

R1

OR2

OR1

OMe

MeO

MeO O

OMe

MeO OMe

OMe

O

MeO

O

I (76)

I (46)

I (93)

Et3SiH, FSO3H, MeC(OTMS)=NHTMS

MeCN, reflux

Et3SiH (4 eq), TCNE (0.3 eq),

CH2Cl2, rt, 10 min

Et3SiH (5 eq), Sn-mont,

Bn

Ph

R (31)

(79)

(81)

(95)

506

359

483

483

487

487

500

353

540

C9-20

C9-13

Cl Br Cl Br Cl Br Cl

Ph

3-MeOC6H4

3-MeOC6H4

4-MeC6H4

4-MeC6H4

4-ClC6H4

Cl Br

2-C10H7

2-C10H7

R

Br

1-C10H7

CO2Me

0

0

0

0

rt

rt

rt

rt

rt

rt

rt

rt

rt

rt

Temp

3h

5h

1h

2h

7h

5h

2h

12 h

3h

3h

2h

3h

3h

3h

Time

CH2Cl2, –78° to rt, 4 h

Et3SiH, BF3•OEt2,

Cl

1-C10H7

R4

Br

4-BrC6H4

2

Cl

4-BrC6H4

O

Br

4-ClC6H4

R3

X

CH2Cl2

SnX2 (0.056 mol%), AcBr (2.2 eq),

Ph

OMe

Et3SiH (1.56 eq),

Ar

R1

HO

Ar

OMe

Conditions

R1 R

Ar

2

O

R4

R3

CO2Me

(94)

(91)

(96)

(92)

(97)

(92)

(87)

(79)

(86)

(89)

(99)

(97)

(89)

(76)

Br

Product(s) and Yield(s) (%)

TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal

512

506

Refs.

541

C9-16

R

1

Me

R1

(72) (81)

63:1 16:1 9:1

Me Ph Ph

Ph Et i-Pr

(82)

(83)

13:1

Ph

Me

(63)

(70)

7:1

Et

10:1

S R2

Me

trans:cis

H

Me

O

Me

CH2Cl2, –78°, 5 min

S

(40)

Ph

R2

OH

S R2

(48)

—(CH2)5— Ph

(79)

Ph

R1

O

S

Me

—(CH2)5—

Me

Ph3SiH (1 eq), TiCl4 (1.2 eq),

(51)

Me

H

(43)

Me

H

—(CH2)5—

(61)

Me

Me

Me

Me

Me

H

Me

Me

R4

R3

R2

R1

520

542

C10

Ph

Ph

Ph

O

O

HO

O

O

O

O

O

O

O

OEt

EtO

O

OH

OH

OMe

O O

CHO

Et3SiH, BF3•OEt2, –45°, 5 min

THF, 60°, 48 h

(Ph3P)3RhCl (0.025 mol%),

PhSiH3 (4 eq),

THF, rt, 48 h

(Ph3P)3RhCl (0.025 mol%),

PhSiH3 (3 eq),

Et3SiH, HOTf

I2SiH2 (1.2 eq), CH2Cl2, rt, 4 h

I2SiH2 (1.2 eq), CH2Cl2, rt, 4 h

HCl, CH2Cl2, rt, 1 h

Et3SiH (2 eq), AlCl3 (1 eq),

CH2Cl2, rt, 1 h

Et3SiH (2 eq), AlCl3 (1 eq),

HCl, 20°, 1 h

Et3SiH (2 eq), AlCl3 (1 eq),

50°, 8-10 h

Et3SiH (1.2 eq), TFA (30 eq),

Conditions

Ph

Ph

Ph

O

I

I (50)

I (93)

I (93)

OEt

O

O

O

O

I

O

OH

(89)

(75)

OH

OH

(39)b

I

CHO

(86)

(91)

(81)

(94)

Product(s) and Yield(s) (%)

TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal

510

493

493

499

505

505

136

136

146

327

Refs.

543

Bn

O

Br

Ph

O

O

OMe

MeO

MeO

O

O

OMe

OMe

O

O O

OMe

OMe

I2SiH2 (2 eq), CHCl3, 22°, 2 min

I2SiH2 (1 eq), CHCl3, 0°, 60 min

THF, rt, 48 h

(Ph3P)3RhCl (0.025 mol%),

PhSiH3 (3 eq),

2. LiAlH4, THF, rt, 2.5 h

CH2Cl2, rt, 2.5 h

1. Et3SiH, SnBr2-AcBr,

C6H6, reflux, 0.5 h

2. (n-Bu)3SnH, AIBN,

CH2Cl2, rt, 2.5 h

1. Et3SiH, SnBr2-AcBr,

I2SiH2 (2 eq), CHCl3, 0°, 99:1

R (92)

+

(100)

R

CH2OBn R3O

H

Ph

O I I:II

H

99:1

R1

HO

(91.2)

(59)

CH2Cl2, –78°, 3 min

Et3SiH (4 eq), TiCl4 (1.2 eq),

Ph

OMe

I + II

R

CH2Cl2, reflux, 2 h

Et3SiH (1.1 eq), Nafion®-H,

(13)

O

H

Product(s) and Yield(s) (%)

CO2Et

O

OMe

O

O

R3O R3O

R3O

H

Ph

MeO

Conditions

H

O II

TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal

Pr-i

R H

(11)

485

483

489

335

Refs.

545

MeO

Ph

H

MeO

HO

O

O H

HO

MeO MeO

O I

OMe

OMe

O

OMe

OH

OMe

H

O O

H

H

O

OMe

OMe O

MeCN, reflux

Et3SiH (4 eq), TCNE (0.3 eq),

Et3SiH, HOTf

Et3SiH, HOTf

Et3SiH, TFA, 70°, 8 h

TFA (12 eq), 0° to rt, 16 h

Et3SiH (30 eq), BF3•OEt2 (30 eq),

MeO

Ph

O

O H H

H

O

MeO MeO

O O

O O

I

OMe

OMe

H

O

OMe

(65)

(70)

(59)

(82)

(100)

500

499

499

515

483

546

C11

O

Br

Ph

Ph

O

O

O

O

OH

Ph

O

O

O

Ph

OEt

OEt

Ph

Ph

O

OMe

OMe

CH2Cl2, –78° to 0°

Et3SiH (3 eq), TFA (3 eq),

I2SiH2 (2 eq), CHCl3, 0°, 99:1

cis:trans

HO

(98)

(94)

(97)

(91)

OTBS

H

Me CH2CO2Et

(92)

CH2CO2Et OTBS

H

Me

R4

R3

R2

R1

(9)

510

479

295

295

496

556

C18-20

C18

C17

O

MeO

Ph

O

H

O

H

O

O

O

OR

9

R

O

O

N

O

OBn

H

H OMe

OMe

R = TMS

H

OH Cl

O

OR

O OMe H

H

O

O

OMe OH

O

RO

RO

Et2O:CH2Cl2 (1:1), rt, 12 h

PMHS, AlCl3 (1 eq),

CH2Cl2, –70°, 45 min

Et3SiH (8 eq), TMSOTf (2 eq),

Et3SiH (1.1 eq), TFA, rt, 18 h

Et3SiH, TMSOTf, CH2Cl2, 0°

CH2Cl2, –78°, 15 h

Et3SiH (4 eq), TiCl4 (1.2 eq),

MeCN, rt, 16 h

Et3SiH (5 eq), TMSOTf (5 eq),

Conditions

H

H

HO

OMe

OMe

O

HO

HO

O H

H

Cl

R

O

9

H

N

OH

O

OH

O (70)

O

OBn

HO

(69)

+ HO

(70)

(69)

O (1)

(82)

CO2Me

N3

R

OMe

OMe

(65)

H

(89)

O

H

OBn

(94)

Product(s) and Yield(s) (%)

TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal

OBn

496

339

486

481

488

503

Refs.

557

C18-28

C18-19

Ph

Ph

Ph

H

O

O

O

O

O

O

O

H

TBSO

TBSO

Ph

O

O

O

OR

O

OR

O

OR

O

OAc

O

R

OR

OMe

OR

OMe

OR

OMe

OH

CN

OH

NHAc

OMe

CH2Cl2, rt, 2-4 h

Et3SiH (5 eq), TFA (5 eq),

CH2Cl2, rt, 2-4 h

Et3SiH (5 eq), TFA (5 eq),

CH2Cl2, rt, 2-4 h

Et3SiH (5 eq), TFA (5 eq),

Et3SiH, BF3•OEt2, –78°, 30 min

–78°, 30 min

2. Et3SiH (1.5 eq), BF3•OEt2 (1.1 eq),

MeC6H5, –78°

1. (i-Bu)2AlH, hexanes,

CH2Cl2, rt, 2-4 h

Et3SiH (5 eq), TFA (5 eq),

TBSO

HO

BnO

HO

BnO

HO

BnO

H

H

TBSO

HO

BnO

OR

O

OR

O

OR

O

O

O

OAc

O

OR

OMe

OR

OMe

OR

OMe

R

CN

NHAc

OMe

SPh

CN

H

R

Bn

Ac

R

Bn

Ac

R

Bn

Ac

R

(60)

(75)

(81)

(75)

(94)

(81)

(98)

(80)

(95)

(—)

(—)

494

494

494

510

510

494

558

C19

OR

OMe

RO RO

RO

RO

O

OR OMe

R = TMS

R = TMS

Et3SiH (5 eq), TMSOTf (5 eq),

MeCN, rt, 16 h

Et3SiH (5 eq), TMSOTf (5 eq),

MeCN, rt, 16 h

HO

HO

HO

O

RO

OR

HO

R = TMS

MeCN, rt, 16 h

RO

OR

OMe

Et3SiH (5 eq), TMSOTf (5 eq),

OH

OH

O

OH

O

(72)

OH O

OH

OH

OH

HO O

OH

HO O

O HO HO OH HO

O

MeCN, rt, 16 h

Et3SiH (5 eq), TMSOTf (5 eq),

HO

RO

R = TMS

R = TMS

MeCN, rt, 16 h

Et3SiH (5 eq), TMSOTf (5 eq),

HO

HO

HO

OMe

OR

R = TMS

MeCN, rt, 16 h

Et3SiH (5 eq), TMSOTf (5 eq),

Conditions

RO

OR

OMe

OR

RO OMe O

OR

RO O

O RO RO

OR

RO

RO

RO

(19)

(78)

+ HO

HO

(100)

(97)

(97)

OH

OH

(9)

OH

+

+

OH

O

+

O OH HO HO HO

HO

Product(s) and Yield(s) (%)

HO

HO

OH O

OH

TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal

(19)

OH

OH

OH

O OMe

(3)

(19)

503

503

503

503

503

503

Refs.

559

C19-21

Ph

Ph

Ph Ph

Ph

H

R4

H

H

—(CH2)4—

Me

H

R3

Me

R2

Ph

O

Ph

O

CO2Me

Ph

R1

O

O

O

OH

S

R4 R3 R2

R1

O

S

(73) (76) (88)

EtAlCl2 AlCl3 TMSOTf

Ph3Si Ph3Si Ph3Si

Ph

(82)

Et2AlCl

Ph3Si

TiCl4

CH2Cl2, –70°, 45 min

Et3SiH (8 eq), TMSOTf (2 eq),

Et2O:CH2Cl2 (1:1), rt, 12 h

PMHS, AlCl3 (1 eq),

Et3Si

H

S Ph

R1

(53)

(42)

R3

O

CO2Me

R4

OH

OBn

7:1

30:1

34:1

17:1

11:1

18:1

28:1

10:1

82:1

16:1

15:1

trans:cis

(57)

R2

(75)

(79)

(86)

BF3•OEt2

Ph3Si

PhMe2Si TiCl4

(88)

TiCl4

Ph3Si

(70)

(87)

TiCl4

Ph2MeSi TiCl4

(76)

TiCl4

O

Ph3Si

Lewis acid

Ph

S

Ph3Si

R3Si

CH2Cl2, –78°, 5 min

R3SiH (1 eq), Lewis acid (1.2 eq),

(68)

339

496

520

560

C20

Ar

H

O

HO

O

O

O

O

O

O

O

Cl N

Ar = 3-MeO-4-HOC6H3

OH

H

Ar

CO2Me

Ph

Ph

O

OH

Ph

Et3SiH, BF3, Et2O

CH2Cl2, –78°, 45 min; rt, 3 h

Et3SiH (1.1 eq), BF3•OEt2 (1.1 eq),

Et3SiH (1.1 eq), TFA, rt, 18 h

CH2Cl2, –70°, 45 min

Et3SiH (8 eq), TMSOTf (2 eq),

Conditions

Ar

H

O

O

Ph

O H

Ar

CO2Me

Ph

Ph

O (47)

O

+

N

+

H

O

Ar

H

O

Ar

(88)

Cl

(97)

O

O

O (14)

O

(37)

(20)

H

H

H

Ar +

OH

OMe

H

O

Ar

Product(s) and Yield(s) (%)

TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal

O (19)

O

Ar H

766

765

468

339

Refs.

561

C21

H

O

O

OR

O

Ph

OR

O

OBn

Et3SiH, BF3•OEt2, –20°, 24 h O

(48)

MeO

H

O

H

CO2Et

OTBS

R = TMS

OBn

O

I2SiH2 (2 eq), CH2Cl2, rt, 2 h

CH2Cl2, –23°

Et3SiH (5 eq), TiCl4 (3.0 eq),

MeCN, rt, 16 h

Et3SiH (5 eq), TMSOTf (5 eq),

I

Ph

HO

O

EtO2C

EtO2C

H

O

CCl3

OH

H

O

(71)

+

O HO

OMe

+

MeO

(94) α:β = 3:1

OH

OH OH

(65)

OMe

(40)

O

+ Ph

(—)

OBn

MeO

(95)

+

MeO

CO2Et

O OH

O

AcO

O PhMe2SiH, BF3•OEt2

OH OPr-i

O

OH

H

MeO MeO

O

OH

TFA (12 eq), 0° to rt, 16 h

Et3SiH (30 eq), BF3•OEt2 (30 eq),

O

OMe

OMe

MeO

OH

O

OMe OMe O

OH

MeO

CCl3

O RO

EtO2C

EtO2C

AcO

O

MeO MeO

MeO

(5)

(10)

CO2Et

MeO

MeO O

(23)

OMe

505

306

503

767

510

482

562

C23

C22

HO

O

O

O

O

O

Ph

Ph

SPh

OH

CO2Me

O

H

N

H

O

OMe

OMe

S

MeO2C

H

H

O HO H

N

HO

H

TBSO

Me

H

MeO

OH

HN

O

O

H O

OMe 2

CH2Cl2, –78°, 45 min; rt, 3 h

Et3SiH (1.1 eq), BF3•OEt2 (1.1 eq),

–78°, 30 min

2. Et3SiH (1.5 eq), BF3•OEt2 (1.1 eq),

MeC6H5, –78°

1. (i-Bu)2AlH, hexanes,

Et3SiH, TFA

CH2Cl2, MeCN, 0°

Et3SiH, BF3•OEt2,

Et3SiH (2.5 eq), TFA, 0°, 2 h

Conditions

O

O

H

N

O

O

Ph

Ph

O

O

HN

H

SPh

+

H O

OMe

(60)

(70)

N

H

O

H

(58)

OMe O

MeO2C

H

H

O

S

CO2Me

HO

H

TBSO

Me

H

MeO

OH

O

HN

(—)

(83)

HS

Product(s) and Yield(s) (%)

TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal

O (56)

O OMe

765

510

770

769

768

Refs.

563

C27

C24

O

MeO

MeO

OH

H

O

MeO

MeO

H

OAc

HO

MeS

OAc

O Et3SiH, BF3•OEt2, rt, 3 h

–78°; rt, 48 h

BF3•OEt2 (1.5 eq), CH2Cl2,

O

O

O

Et3SiH (4.5 eq),

OH

OH

OAc

OBn

OMe

H

O

BF3•OEt2 (12 eq), CH2Cl2

Et3SiH (13 eq),

BnO

OAc

O

O

OH

OAc

MeS

MeO

O O

O O O

Ph

Ph

O

O H

OBn

OH

OBn

(88)

O

O

(64)

(89)

510

484

495

564

C29

C28

C27

Ph

BnO

OBn

Ph

Ph

BnO

OBn

BnO

OBn

O O BnO

O

O O BnO

O O BnO

O

O

O OMe

O PhthN OMe

OBn

OH

OMe

OBn O

BnO

OBn

OH

OBn

OH

CH2Cl2, rt, 4 h

Et3SiH (12 eq), BF3•OEt2 (2 eq),

–78° 1 h; –10°, 12 h

Et3SiH, BF3•OEt2, CH2Cl2,

CH2Cl2, rt, 4 h

Et3SiH (12 eq), BF3•OEt2 (2 eq),

CH2Cl2, rt, 4 h

Et3SiH (12 eq), BF3•OEt2 (2 eq),

–78° 1 h; –10°, 12 h

Et3SiH, BF3•OEt2, CH2Cl2,

–78° 1 h; –10°, 12 h

Et3SiH, BF3•OEt2, CH2Cl2,

Conditions

HO BnO

BnO

OBn

HO BnO

BnO

HO BnO

BnO

OBn

BnO

OBn

I

OMe

O

OBn

OMe

OBn

OMe

OBn O

BnO

O

OBn

OBn

OBn

PhthN

O

I

O

O

+

+

(85)

BnO

OBn

(59)

(83)

BnO

OBn

(53)

II

O

II

O

OBn

OBn

I + II (81), I:II = 5:1

I + II (76), I:II = 5:1

Product(s) and Yield(s) (%)

TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal

497

508

497

497

508

508

Refs.

565

C35

C34

C32

BnO BnO

BnO BnO

BnO BnO

BzO

O

O O

Ar

OH

O

O

OMe

OBn OBn O

BnO OMe

OBn

BnO

O

OH

OBz Ph

OBn

OBz

O

Ar = 2,6-dichloro-3-pyridinyl

TBDPSO

1 1 2

SnCl4 ZnBr2 ZnCl2•OEt2 rt

–5°

–5°

–5°

Temp

3h

1.5 h

1.5 h

1.5 h

Time

CH2Cl2, 0° to rt, 16 h

Et3SiH (3 eq), TMSOTf (2.25 eq),

CH2Cl2, 0° to rt, 16 h

Et3SiH (3 eq), TMSOTf (2.25 eq),

–78°, 1 h; rt, 3 h

2. Et3SiH, BF3•OEt2, CH2Cl2,

1. PhMgCl (1.5 eq), THF, –78°

Et3SiH, BF3•OEt2, MeCN, –40° to rt

2

x

BF3•OEt2

Catalyst

Et3SiH (x eq), catalyst

BnO BnO

BnO BnO

O

O

Ph

O

O

OBn OBn O

BnO

OBn

BnO

O

OBn

O OBz OBz

BnO BnO

BzO

TBDPSO

— 2:1

(68)

(80)

(77)

(88)

1:5

(—)

(—)

2.6:1

(30)

α-D:β-D

+

TBDPSO

(57)

β-D

Ph

Ar

O

O O

Ar

α−D

504

504

771

509

511

566

C37

C36 O

OBn

Et3SiH, TMSOTf

HO

BnO

HO

BnO

HO

BnO

O

OBn

O

OBn

O

OBn

OH OBn

OBn

OBn

OBn

OBn

OBn

Et3SiH, BF3•OEt2, MeCN, 0° to rt

Et3SiH, BF3•OEt2, MeCN, 0° to rt

Et3SiH, BF3•OEt2, MeCN, 0° to rt

BnO

BnO

O

I

O

OBn

I

O

OBn

O

OBn

OBn

OBn

BnO

BnO

O

BnO

O

OBn

OBn OBn BnO

OBn

Et3SiH, TMSOTf

BnO

BnO

OH OBn

OBn

OBn

BnO

Conditions

+

(85)

BnO

+

BnO

I + II (67), I:II = ca. 1:1

OBn

OBn

I + II (76), I:II > 10:1

OBn

OBn

OBn

OBn

(65)

(35)

II

O

OBn

II

O

OBn

Product(s) and Yield(s) (%)

TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal

OBn

OBn

OBn

OBn

507

507

507

519

519

Refs.

567

C38

C37-39

H

O

OBn

OAc

OBz

O

CO2Et

HO

BnO

OH

OAc OAc

OH

OBn

OH

OBn

OBn

OAc

Et3SiH, BF3•OEt2, MeCN, 0° to rt

Et3SiH, BF3•OEt2, MeCN, 0° to rt

BnO

EtO2C

BnO

EtO2C

AcO OAc

O I

OBn

O

OBn

+

BnO EtO2C

(72)

OAc

O II

OBn

(—)

OBn I + II (66), I:II = 3:1

OBn

OBn

OBn

OAc OAc

OH

(80)

(30)

(77)

CO2Me

O

Ph

3-C4H3O

CO2Me H

(87)

2-C4H3O

Ar

OH

O

O

N

O Et3SiH, BF3•OEt2, CH2Cl2, rt, 1 h

OBz

Ar

BnO OBn

O

O OBz BzO

BnO

OBz Et3SiH, BF3•OEt2, MeCN, –40° to rt

CH2Cl2, –78°, 1 h; 10°, 16 h

Et3SiH (2 eq), BF3•OEt2 (2 eq),

O OBz Ar

O

OBz

OH

OBn CO2Et OBn

HO

BnO

O

BnO OBn

AcO

O

HO

BzO

BnO

N

OBn

OBn 507

507

773

509

772

568

C42

C40

C39

O

BnO

O

OAc

O

BnO H

O

OH OBn

O

Ph

OAc

O

OAc

O

H

O H

O

OAc

O

OAc

O

H MeO

AcO

OAc

O

OH OBn

OBn

OBn

BnO

O

O

OBn

OBn

BnO

Ph

Ph

O

AcO

H

O

OAc

H

(CF3CO)2O (3 eq), CH2Cl2, rt, 2-4 h

Et3SiH (5 eq), TFA (5 eq),

H

H O

H O

H OH

Et3SiH, TMSOTf

Et3SiH, TMSOTf

OH

CH2Cl2, 0°

Et3SiH, TMSOTf

(CF3CO)2O (3 eq), CH2Cl2, rt, 2-4 h

Et3SiH (5 eq), TFA (5 eq),

OC10H21-n

OAc

OC10H21-n

Conditions

BnO

O

BnO

H

OBn

OBn OBn

BnO

O

O

OAc

O

AcO

OAc

O

OBn

OBn OBn

BnO

HO

BnO

HO

BnO

AcO

H

H

O

Ph

OAc

O

OAc

O

H

H

O

(83)

H (70)

H

O

OAc

H

H

O

H

(78)

OC10H21-n

OAc

OC10H21-n

(—)

(—)

OAc

O

OAc

O

Product(s) and Yield(s) (%)

TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal

O

H OH OH

482

519

519

494

494

Refs.

569

C57

C56

C44

MPMO

BnO

BnO

MPMO

BnO

BnO

BnO

BnO

OH

O

OBz

OH

O

O

O

OBn

OBn

O

O

O

OBn

OMe

OBn

H

OMe O HO

dr = 1:1

OBz

O

OBn

O

O

H

CH2Cl2, –20°, 20 min

PhMe2SiH (10 eq), TMSOTf,

MeCN, –20°, 20 min

R3SiH (10 eq), BF3•OEt2 (0.1 eq),

Et3SiH, TFA, CH2Cl2, –10°, 72 h

BnO

BnO

+

BnO

BnO

BnO

BnO

O

O

O

OBn

II

OBz

I

O

OBn

O

O

OMe O

OH

OBz

OH

BnO

BnO

OH

O

OBz

O

OBn

O

OBn

OMe

OBn

O

O

OBn

H

3:2

(80)

3:1 (—) PhMe2Si

7:1

I:II (—)

(82) Et3Si

n-Pr3Si

I + II

(86) dr = 1:1

R3Si

O

H

OBn

O

517

517, 774

513

570

C57

BnO OH

O

CH2Cl2, rt, 4 h

The product is a single isomer of undetermined configuration.

O BnO

Et3SiH (12 eq), BF3•OEt2 (2 eq),

The yield was determined by NMR spectroscopy.

BnO

O

OBn

b

O

a

BnO

O

Ph

Conditions

BnO

HO O BnO

OBn O BnO BnO

O

OBn (73)

Product(s) and Yield(s) (%)

TABLE 20. ORGANOSILANE REDUCTION OF ACETALS, KETALS, AND HEMIKETALS (Continued) Acetal/Ketal

497

Refs.

571

C8

C7

C6

C5

HO

O

N H

AcHN

O2N

Ph

Ph

N

Et2N

O

N H

N H

O

OH

N H

OH

OH

N H

OH O

OMe

N H

N H

O

O

O

N

Aminal

OH

OH

I (75)

CH2Cl2, 5° to rt, 2 h

Et3SiH (1.2 eq), TFA (3 eq),

O

N H

AcHN

O2N

Ph

Ph

N

Et2N

O

CH2Cl2, 5°, 2 h

Et3SiH (1.2 eq), BF3•OEt2 (1.2 eq),

CHCl3, rt, 1-4 h

Et3SiH (1.5 eq), TFA (10 eq),

CHCl3, rt, 1-4 h

Et3SiH (1.5 eq), TFA (10 eq),

CHCl3, rt, 1-4 h

Et3SiH (1.5 eq), TFA (10 eq),

CHCl3, reflux, 2 h

Et3SiH (1.5 eq), TFA (10 eq),

CHCl3, rt, 1-4 h

Et3SiH (1.5 eq), TFA (10 eq),

CHCl3, rt, 1-4 h

Et3SiH (1.5 eq), TFA (10 eq),

CHCl3, rt, 1-4 h

Et3SiH (1.5 eq), TFA (10 eq),

Conditions

I

NHMe O

NHMe

NHMe

O

NHMe

(94)

(85)

(88)

NHMe

(57)

(84)

NHMe

O

O

O

N Me

(84)

(92)

(86)

Product(s) and Yield(s) (%)

TABLE 21. ORGANOSILANE REDUCTION OF AMINALS AND HEMIAMINALS

521

521

526

526

526

526

526

526

526

Refs.

572

C11

C10

C9-15

C9

Ph

(90) (88)

Bn

N O

Et3SiH, HCO2H, CH2Cl2, rt, 10 h

HCO2

(96)

Ph

OH

(91)

n-C7H15

CHCl3, rt, 1-4 h

(55)

n-C5H11

O

(97)

i-Bu

Ph

(75)

n-Bu

Et3SiH (1.5 eq), TFA (10 eq),

(96)

OH

MeO

n-Pr

H N

CH2Cl2, –15° to rt, 16 h

Et3SiH (10 eq), BF3•OEt2 (3 eq),

CHCl3, rt, 1-4 h

Et3SiH (1.5 eq), TFA (10 eq),

(65)

OH

Et

R

NH

O

N H

Conditions

N

H

O

N Pr-n I

(85)

(91)

O

+

I + II (42), I:II = 3:5

+

NHMe

NHMe

Pr-n (29)

H

O

R

NH

O

O

Product(s) and Yield(s) (%)

TABLE 21. ORGANOSILANE REDUCTION OF AMINALS AND HEMIAMINALS (Continued)

Me

R

HO

Pr-n

MeO

O

Aminal

n-Bu

N

II

O

775

526

527

526

Refs.

573

C16

C13

C12

MeO

BocHN

TBSO

AcHN

N

O

OMe

OMe

OBn

Ac

N

OMe

OTBS

2. Et3SiH, 0°, 30 min

1. TiCl4, CH2Cl2, –78°, 30 min

2. Et3SiH, 0°, 30 min

1. TFA, CH2Cl2, 30 min

Et3SiH, TFA, CH2Cl2, 15 min

CH2Cl2, –40°, 1-2 h

Et3SiH (2 eq), BF3•OEt2 (2 eq),

CH2Cl2, –40°, 1-2 h

Et3SiH (2 eq), BF3•OEt2 (2 eq),

CH2Cl2, 5° to rt, 2 h

Et3SiH (1.2 eq), TFA (3 eq),

CH2Cl2, –40°, 1-2 h

Et3SiH (2 eq), BF3•OEt2 (2 eq),

N

BocHN

TBSO

I (42)

AcHN

H

N

N

O

O

O

(93)

(98)

(97)

(88)

AcHN

OBn

Ac

N

+

I

OTBS

(—)

(—)

OH (51)

524

524

524

521

521

521

521

574

C19-28

C18

C17

C16-17

O

N

R2

O

R1

OTMS

Fmoc N

CF3

Bn

N

MeO2C

AcHN

Rf

OTMS

Ph

Ph

O

O

OH

N

N H

NBn

OMe

Aminal

Et3SiH (3 eq), TFA, CHCl3, rt, 22 h

CH2Cl2, 50°, 24 h

Et3SiH (1 eq), BF3•OEt2 (1 eq),

CHCl3, rt, 20 h

Et3SiH (3 eq), TFA (xs),

CH2Cl2, 5° to rt, 2 h

Et3SiH (1.2 eq), TFA (3 eq),

CH2Cl2, 5°, 2 h

Et3SiH (1.2 eq), BF3•OEt2 (1.2 eq),

CH2Cl2, rt, 5 h

Et3SiH (1 eq), BF3•OEt2 (1 eq),

Conditions

N

R2

Fmoc N

CF3

Bn

N

O

Ph

Ph

N

N H I

O

O

NBn

OH

R1

Me

MeO2C

I (87)

AcHN

Rf

R1 Me Me Me Me i-Pr MeSCH2CH2 Bn BnOCH2 Ph(CH2)4 DNP N N CH2

(61)

(63)

(89)

(84)

(80)

CClF2 CF3CF2

(85)

CF3

Rf

(98) (91) (74) (95) (100) (22) (70) (96) (70) (67)

R2 H c-C6H11 Me Bn H H H H H H

Product(s) and Yield(s) (%)

TABLE 21. ORGANOSILANE REDUCTION OF AMINALS AND HEMIAMINALS (Continued)

528

522

525

521

521

522

Refs.

575

C30

C23

C22

C20 N

O HO

MeO2C

O

O

Cl

NH O OH O

Fmoc N

O

N

Me

MeO2C

MeO

+

O

N H

HO

N

O O

NH O

O Et3SiH, TFA

Et3SiH (3 eq), TFA, CHCl3, rt, 22 h

O

Et3SiH, TFA

2. Et3SiH

1. TiCl4, CH2Cl2, –78° to 0°

I

NH

H

N

O

O

N

+

O

Cl

N H

O O

II

NH O

(—)

(22) + Cl

O

(15)

MeO2C

I + II (95), I:II = —

O

O

MeO2C

Me OH

Fmoc N

O

N

Me

MeO2C

O

N

(37)

528

776

770

524

576

C12

C11

C10

C8

MeO

Cl

Ph

O

N

H N

N H

N H

CO2Et H N

H N CO2Et

Et3SiH (1.5 eq), TFA, –10°, 0.5 h

Et3SiH (1.5 eq), TFA, –10°, 0.5 h

Et3SiH (1.5 eq), TFA, –10°, 0.5 h

(i-Pr)3SiH (5 eq), TFA, CH2Cl2, rt, 2 h

MeO

Cl

Ph

I (4%)a

H N

CO2Et H N

H N

CO2Et

CO2Et

(92)

(85%)a

(99)

(94)

(80) cis:trans = 42:58

NH2 N I H

N H

(67)

NH2

O

N

Product(s) and Yield(s) (%)

CO2H Et3SiH (5 eq), TFA, CH2Cl2, rt, 2 h

Et3SiH (1.4 eq), TFA, 60°, 48 h

Et3SiH (5 eq), TFA (10 eq), 65°, 25 h

Conditions

TABLE 22. ORGANOSILANE REDUCTION OF ENAMINES

CO2H

CO2Et

Enamine

535

535

535

532

532

533

235

Refs.

577

C14-21

C14

C13

C12

R3

R2

Cl

O

OMe H H OBn

OMe

H

O R

OMe

H

H

4

CO2Et

CO2Et

OMe H

H

H

OMe

R

H

3

NH

R

2

H N

H N

CO2Me

N

OMe

R4

R1

O

1

R

MeO

Br

(95) (80) (80) (33)

5h 20 h

R4 H

R1

O

9h

R3

R2

Cl

O

MeO

Br

MeO

Br

6.5 h

Time

Et3SiH (3 eq), TFA, CH2Cl2, rt

CH2Cl2, 0°, 6 h; rt, 6 h

Et3SiH (1.05 eq), TFA (1 eq),

Et3SiH (1.5 eq), TFA, –10°, 0.5 h

Et3SiD (1.5 eq), TFA-d1, –10°, 0.5 h

Et3SiH (1.5 eq), TFA, –10°, 0.5 h

D H N

H N

O

NH

H

CO2Me

N

D

H N

(56)

CO2Et

CO2Et

CO2Et

(97)

(98)

(99)

538

536

535

535

535

578

C16-19

C16-17

C15

R1

R

1

Cl

N H

R2

N H

R2

R3

R3

i-Pr

N

O

CO2Bu-t

N

Cl

Enamine

Et3SiH (3 eq), TFA, 50°

Et3SiH (1 eq), TFA, 20°

Et3SiH, TFA, CH2Cl2, –42°

Et3SiH, TFA, CH2Cl2, 15 min

Conditions

R1

R1

Cl

N H

R2

N H

R2

R3

R3

i-Pr

N

O

CN CO2Me CO2Me CO2Me Ac EtO2C

3-O2NC6H4 Ph 2-O2NC6H4 2-CF3C6H4 3-O2NC6H4 3-O2NC6H4

CO2Me CO2Me CO2Me CO2Me Ac EtO2C

(72)

(60)

(56)

(94)

(55)

(89)

(64) Ac 3-O2NC6H4

Ac

R3

(69) CO2Me 2-CF3C6H4 CO2Me

R2

(66) CO2Me 2-O2NC6H4 CO2Me

R1

(58)

(63) CO2Me

CN

R3 Ph

3-O2NC6H4

R2

(70)

CO2Me

CO2Me

R1

CO2Bu-t

N

Cl

(74) dr = 1:1

Product(s) and Yield(s) (%)

TABLE 22. ORGANOSILANE REDUCTION OF ENAMINES (Continued)

529

529

777

524

Refs.

579

C21

C20

C18

C17

BnO

Br

OCO2Et

NHBn

O

O

OH

N

O

O

N

O

N

H N

O

CO2Et

O

Acid TFA TFA-d1 TFA

R1 D H H

Et3SiR (1.5 eq), acid, –10°, 0.5 h

1

Et3SiH, TFA, CHCl3, 20°, 24 h

Et3SiH, TFA, CHCl3, 20°, 24 h

Et3SiH (9 eq), TFA, CHCl3, 20°, 24 h

BnO

Br

H

D

H

R2

R3

O

O

O

H (94)

H (77)

D (63)

R3

OCO2Et

R2

NHBn

N

O

N

O

N

H N

O

CO2Et

(—)

(—)

O (75)

535

537

537

537

580

C27

C22

C21-23

R2

R1

H N

C11H23-n

N H EtO2C

H N

N H EtO2C

Boc

N

Cl

N H

Ph

Ph

N

Enamine

CO2Et

CO2Et

N

Ph

R3SiH (x eq), TFA, 20°

Et3SiH (2 eq), TFA, rt, 1 h

CH2Cl2, –42°, 4 h

(i-Pr)3SiH (6 eq), TFA (10 eq),

CH2Cl2, –42°, 4 h

Et3SiH (6 eq), TFA (10 eq),

Et3SiH (2 eq), TFA, 50°, 64 h

Conditions

Boc I

N

Cl + N

Cl

H N

N H EtO2C I

+

H N

N H EtO2C

Cl OMe

Cl OMe

C11H23-n

+

H

H

Br F

R2

R1

Ph

Ph

H N N H EtO2C III

CO2Et

+

CO2Et

(81)

Ph

II

CO2Et

N H EtO2C

Ph

Boc III

N

Cl

(80)

(14)

(32)

(25)

H N

Boc II I + II + III (79) I:II:III = 75:10:15

C11H23-n

N H

N

I + II + III (95), I:II:III = 78:9:13

R2

R1

N

Ph

Product(s) and Yield(s) (%)

TABLE 22. ORGANOSILANE REDUCTION OF ENAMINES (Continued)

CO2Et

530

530

531

C11H23-n

531

534

Refs.

581

C31

a

N H

N

H N

Ph

MeO N H

(—)

18 h

3

N

—

(—)

18 h

PhMe2Si 3

MeO

— 46:44:10

(—)

1h

2

Et3Si

Et3SiH (2 eq), TFA, 50°, 64 h

N

The yield was determined by NMR spectroscopy.

MeO

MeO

N

O

—

(—)

18 h

2

Et3Si

Ph3Si

19:17:64

(—)

1.5 h

2

Et3Si

I + II + III I:II:III

Time

x

R3Si

N

O

H N N

(52)

Ph 534

582

C8-20

C8-14

C8-13

C8

Ar

Ph

R

Ph

R1

R1

N

R2

N

N

N

Me Me Me Me n-Bu n-Bu Ph Ph Ph

H H H H H H H H Me

R2

R2

R1

Me

Imine

(Ph3P)3RhCl 50°

55°

55°

(Ph3P)3RhCl

(C6F5)3B (5-10 mol%), MeC6H5

55°

(Ph3P)3RhCl 100°

(Ph3P)3RhCl

PhMe2SiH (1.05 eq),

Et2HSi

Et3Si

Et2HSi

PhMeHSi (Ph3P)3RhCl

Et2HSi

PdCl2

Et3Si 55°

(Ph3P)3RhCl 100°

Et3Si

0°

30°

Temp

(Ph3P)3RhCl

(Ph3P)3RhCl

Et2HSi Ph2HSi

Catalyst

R33Si

C6H6, rt, 1 h

R3SiH (1.1 eq), catalyst (0.5 mol%),

Cl3SiH, MeCN, reflux, 4 h

THF, rt, 20 h

PhSiH3 (1 eq), catalyst (10 mol%),

Conditions

72 h

15 h

2h

0.5 h

1.5 h

24 h

20 h

3h

0.5 h

Time

Ar

Ph

R

Bn

R1

(85)

(91)

(96)

(93)

(96)

(90)

(65)

(92)

(95)

N H

R2

NH

R2

SiH2Ph

N H

R1

N

Me (2) +

N

(53)

Ph

(47)

Si

Ph

H

Me

n-Pr

R

Bn

N

Me Bn

Product(s) and Yield(s) (%)

TABLE 23. ORGANOSILANE REDUCTION OF IMINES

(95)

120

546

542

544

Refs.

583

C10

C9

H H Me

Ph

Ph

4-MeOC6H4

Ph

Ph

O

N

Pr-n

N

(96)

96 h

rt

Bn

H

Ph

PhH2Si

(95)

Bn

H

Ph

N

(95)

23 h

rt

Bn

H

Ph

R2

(97)

4h

rt

Bn

H

Ph

Ph

R1

(86)

2h 17.5 h

rt 70°

2-MeOC6H4

H

(0)

H

OMe

4-MeOC6H4

Bn 1.5 h

C6H6, reflux, 4 h

Cl3SiH (1.2 eq), BF3•OEt2,

C6H6, reflux, 4 h

Cl3SiH (1.2 eq), BF3•OEt2,

THF, rt, 20 h

PhSiH3 (1 eq), catalyst (10 mol%),

70°

70°

Ph

O

R2 Si

NHPr-n

(89)

OMe

(82)

(28) (43) n-C5H11 n-Pr

(89) (21) (64) n-C5H11

H N

R2 N H Ph II

N

i-Pr

I

R1

(3)

+ R2

R

1

n-C7H15 Me

N I R1

R2

(>95)

(91)

(95)

1h 3h

(93)

0.5 h

rt

SO2Ph rt

(60)

0.5 h

rt

Ph

(80)

0.5 h

rt

Boc

(57)

26 h

t-Bu

70°

48 h

Ph

Time

Ph

allyl

70°

H

Temp

Ph

Me

H

Ph

R2

R1

Ar

II

R1

545

545

544

584

C11-14

C11

C10-22

R1

Ph

Ph

S

(97) (88) (86)

Ph Ts Ph 4-MeOC6H4 Bn

2-C4H3O

Ph

Ph

Ph

(86)

(99)

(99)

Ph

R2

2-C4H3S

N H

2-C4H3O

CH2Cl2:DMF (4:1), 0°, 4 h

R1

H N Ph

NHBu-t

I

(77)

(54)

(56)

(22)

Product(s) and Yield(s) (%)

C5H11-n

SiH2Ph

N

NHPh

R2

Cl3SiH (1.5 eq),

Et3SiH (1 eq), TFA (3 eq), 70°, 30 h Ph

I (37)

C6H6, reflux, 4 h

Cl3SiH (1.2 eq), BF3•OEt2,

S I (93)

Ph

Et3SiH (1 eq), TFA, (3 eq), 70°, 6 h

HOAc, KU-1, 55°, 5 h

Et3SiH (1.1-1.2 eq), HCO2H,

THF, rt, 20 h

PhSiH3 (1 eq), 230 (10 mol%),

PhMe2SiH (1.1-1.2 eq), TFA, rt, 16 h

Conditions

TABLE 23. ORGANOSILANE REDUCTION OF IMINES (Continued)

R1

N

Bu-t

N Ph

C5H11-n

R2

N

Ph

N

N

Imine

318

541

545

541

208

544

276

Refs.

585

C12

t-Bu

Ph

N

N

Ph

O

R R = Ph, c-C6H11

Bn

C5H11-n

N

N

PMP N

N

PMP

Cl3SiH, MeCN, reflux, 4 h

PMHS, EtOH, n-butyltris(EH)tin, rt

THF, rt, 20 h

PhSiH3 (1 eq), 230 (10 mol%),

C6H6, reflux, 4 h

Cl3SiH (1.2 eq), BF3•OEt2,

P(OPh)3 (10 mol%), CH2Cl2, 18 h

[Ir(cod)Cl]2 (2.5 mol%),

OC6F5 (2.5 eq), Et2MeSiH, (2.5 eq),

O

P(OPh)3 (10 mol%), CH2Cl2, 18 h

[Ir(cod)Cl]2 (2.5 mol%),

OC6F5 (2.5 eq), Et2MeSiH, (2.5 eq),

O

t-Bu

PhH2Si

O

N

N

PMP

O

Ph

O

N H

N H

N

R

Bn

Bn

C5H11-n

N H

PMP

(48)

(75)

(52) +

Bn

Ph

N

n-C5H11

(81)

Si

H

N

Bn

C5H11-n

(78) trans:cis > 20:1

(60) trans:cis > 20:1

(35)

542

543

544

545

476

476

586

C13

C12-15

N

N

N

Ph

Ph

Ph

C6H11-c

C5H11-n

Bn

Ph

I (40)

Cl3SiH (1.2 eq), BF3•OEt2,

SiH2Ph

Bn

H

Ph Ph C5H11-n

N

(17)

545

545

542

544

541

Si

I (80)

n-C5H11

N

Et3SiH (1 eq), TFA (3 eq), 70°, 1.5 h

(17)

(60)

Ph

543

543

Ph

C6H11-c

(3) +

(84)

543

Refs.

I (82)

N H I

N H

C5H11-n

N

N H

R3

Product(s) and Yield(s) (%)

PMHS, EtOH, rt, n-butyltris(EH)tin

C6H6, reflux, 4 h

Ph

Ph

Cl3SiH (1.2 eq), C6H6, reflux, 4 h

Cl3SiH, MeCN, reflux, 4 h

THF, rt, 20 h

PhSiH3 (1 eq), 230 (10 mol%),

rt, 9 h

n-butyltris(EH)tin (0.1 eq),

PMHS, EtOH, rt,

(81)

N

(76)

6h

n-C6H13 Me Bn

Ph

(82)

H

Ph

(75)

20 h

N H

10 h

H

Ph

Time

R1

R2

Bn

Bn

H

t-Bu

EtOH, rt

n-BuSn[O2CCH(Et)Bu-n]3 (0.1 eq),

PMHS (3 eq),

Conditions

TABLE 23. ORGANOSILANE REDUCTION OF IMINES (Continued)

7h

R3

R2

R3

R1

N

Ph

R1

R2

Imine

587 10 10 10 — 10 5

P(OPh)3 P(OPh)3 P(OPh)3 none P(OPh)3 P(OPh)3

[Ir(cod)Cl]2

4-O2NC6H4 [Ir(cod)Cl]2 [Ir(cod)Cl]2 [Ir(cod)Cl]2 none [Ir(cod)Cl]2

C6F5 C6F5 C6F5 C6F5

dppe (5 mol%), 80°

OPh (2.5 eq), Et2MeSiH, [Rh(cod)Cl]2 (2.5 mol%),

I

Ph

Ph

Ph

(14) (13) (56) (68) (28) (0) (58)

rt rt rt rt rt rt

(20) dr > 20:1

(15) +

50°

Temp

N

Ph N SiPhH2

I (20) dr > 20:1

10

P(OPh)3

[Ir(cod)Cl]2

1-C10H7 Ph

O

x

Ligand

Catalyst

O

Ph

I (67)

I (67)

I (71)

R

ligand (x mol%), CH2Cl2, 18 h

OR (2.5 eq), Et2MeSiH, (1 eq) 230 (2.5 mol%),

O

THF, rt, 20 h

PhSiH3 (1 eq), 230 (10 mol%),

Et2O, rt, 10 h

PMHS (5 eq), ZnCl2 (2 eq),

Et2O, rt, 10 h

PMHS (5 eq), ZnCl2 (2 eq),

HOAc, KU-1, 55°, 5 h

Et3SiH (1.1-1.2 eq), HCO2H,

N Ph

Ph Si N Ph

H Ph

(47)

476

476

544

539

539

208

588

C13-15

C13-14

C13

R2

Ph

R1

H H Et Me H H

Ph

3-O2NC6H4

n-C5H11

Ph

4-MeC6H4

4-MeOC6H4

R2

N

Ph

H

—(CH2)5—

NTs

N

R2

N

c-C6H11

R1

R1

O2N

Ph

Ph

Imine

OC6F5 (2.5 eq),

Conditions

50 h

59 h

59 h

50 h

56 h

42 h

67 h

48 h

Time

LiOMe (4 mol%), THF, rt, 0.5 h

(MeO)3SiH (1.2 eq),

60-70°, 30-60 min

Et3SiH (1 eq), TFA (3 eq),

Et2O, rt, 12 h

PMHS (5 eq), ZnCl2 (2 eq),

P(OPh)3 (10 mol%), CH2Cl2, 18 h

[Ir(cod)Cl]2 (2.5 mol%),

Et2MeSiH, (2.5 eq),

O

R2

R1

Ph

Ph

NHTs

N

(80)

(97)

(63)

(80)

(92)

(100)

(84)

(62)

R1

O2 N

O

R2

NHBn

N H

Ph

Me (95) H

(86)

(78)

H

H

R2

Me

H

R1

(75)

(68) trans:cis = —

Product(s) and Yield(s) (%)

TABLE 23. ORGANOSILANE REDUCTION OF IMINES (Continued)

294

540

539

476

Refs.

589

C14

C13-16

S

OMe

n-C5H11

N

Bn

N

Ph

reflux, 4 h

Cl2SiH2 (1.2 eq), C6H6,

C6H6, reflux, 4 h

Cl3SiH (1.2 eq), BF3•OEt2,

P(OPh)3 (10 mol%), CH2Cl2, 18 h

[Ir(cod)Cl]2 (2.5 mol%),

OC6F5 (2.5 eq), Et2MeSiH (2.5 eq),

O

Et2O, rt, 10 h

PMHS (5 eq), ZnCl2 (2 eq),

EtOH, rt,

PMHS, n-butyltris(EH)tin,

S

I (90)

O

I (73)

Ph

N H

I

H N

Ph

Bn

Ph

Ar

OMe

N

N H I

(73)

N

(76)

4-(i-Pr)C6H4

Ph

(88)

3-MeOC6H4

Et2O, rt, 15 h

(78)

2-MeOC6H4

Ph

(62)

4-MeOC6H4

N

(69)

H N

2-ClC6H4

Ph

Ph (79)

PMHS (5 eq), ZnCl2 (2 eq),

Cl3SiH, MeCN, reflux, 4 h

4-ClC6H4

Ar

Ph

Ar

N

Ph

Ph

C5H11-n

(61)

(50) trans:cis > 20:1

(76)

(60)

545

545

476

539

543

539

542

590

C17

C16

C15

Ph

N

CO2Me

NHTs

N

N

Ph

n-C6H13

N

Ph

Ph

Bn

Ph

Ph

Imine

20° 20° 20° 40°

AlCl3 TiCl4 BF3•OEt2 ZnCl2

P(OPh)3 (10 mol%), CH2Cl2, 18 h

[Ir(cod)Cl]2 (2.5 mol%),

OC6F5 (2.5 eq), Et2MeSiH (2.5 eq),

O

Temp

Catalyst

Ph2SiH2 (1.2 eq), catalyst (1 eq), CH2Cl2

EtOH, rt

PMHS, n-butyltris(EH)tin,

Et2O, rt, 20 h

PMHS (5 eq), ZnCl2 (2 eq),

P(OPh)3 (10 mol%), CH2Cl2, 18 h

[Ir(cod)Cl]2 (2.5 mol%),

OC6F5 (2.5 eq), Et2MeSiH (2.5 eq),

O

Conditions

N

O

Ph

Ph

N H

N

Ph

(48)

(63)

(90)

(90)

(55)

(70) trans:cis = 5.2:1

(80) trans:cis > 20:1

Bn (81)

Ph

Ph

N H

CO2Me

NHTs

n-C6H13

Ph

O

Product(s) and Yield(s) (%)

TABLE 23. ORGANOSILANE REDUCTION OF IMINES (Continued)

476

373

543

539

476

Refs.

591

C19

C18

Ph

Ph

Ph

O

Ph

N

N

N

Bn

O

Bn

•

C5H11-n

N

N

Ph

Ph

Et3SiH, Cl3CCO2H

THF, rt, 20 h

PhSiH3 (1 eq), 230 (10 mol%),

Et2O, rt, 12 h

PMHS (5 eq), ZnCl2 (2 eq),

Et2O, rt, 24 h

PMHS (5 eq), ZnCl2 (2 eq),

EtOH, rt, 10 h

n-butyltris(EH)tin (0.1 eq),

PMHS (3 eq),

Ph

Ph

Ph

O

Ph

N H

Bn

SiH2Ph

N H

O

Bn

•

C5H11-n

N

H N

N H

(0)

Ph

N

Ph H

n-C5H11

(50)

(63)

(0) +

Ph

Ph

(82)

Si

Ph C5H11-n

N

Ph Ph (0)

778

544

539

539

543

592

C23-26

R1

(78) (69)

PhCH(OH)CHMe PhCH(OH)CHMe

Cl(CH2)4

allyl

(82)

3-O2NC6H4

(81)

N

Ph

R2

HN

N

O

Cl(CH2)4

CH2Cl2, rt, 16 h

Et2SiH2 (2.2 eq), (Ph3P)3RhCl,

R1

Cl(CH2)4

R2

N

N

R1

R2

N

O

Conditions

O R1

R2

NH

N

Product(s) and Yield(s) (%)

TABLE 23. ORGANOSILANE REDUCTION OF IMINES (Continued)

R1

R2

N

N

O

Imine

547

Refs.

593

C9

C8

C7

C5

Ph

N

O

Ph

O

N OH

OH

N

O

N

OH

N

OH

OH

OH

Ph

MeO

Ph

N

O

N

OH

Hydroxylimine

10% Pd-C, 40-50°, 3 h

PMHS (3 eq), (t-BuCO)2O (1.1 eq),

10% Pd-C, 40-50°, 4 h

PMHS (3 eq), (t-BuCO)2O (1.1 eq),

10% Pd-C, 40-50°, 6 h

PMHS (3 eq), (t-BuCO)2O (1.1 eq),

10% Pd-C, 40-50°, 5 h

PMHS (3 eq), (t-BuCO)2O (1.1 eq),

10% Pd-C, 40-50°, 4 h

PMHS (3 eq), (t-BuCO)2O (1.1 eq),

10% Pd-C, 40-50°, 3 h

PMHS (3 eq), (t-BuCO)2O (1.1 eq),

10% Pd-C, 40-50°, 3 h

PMHS (3 eq), (t-BuCO)2O (1.1 eq),

Conditions

Ph

O

I

O

H N

O

Boc

N H

(82)

(90)

(85)

Boc

Boc (65)

HN Boc

Boc

Boc

H N

I (75)

Ph

MeO

Ph

H N

O

H N

(80)

(85)

Product(s) and Yield(s) (%)

TABLE 24. ORGANOSILANE REDUCTION OF HYDROXYLIMINES

548

548

548

548

548

548

548

Refs.

594

C10

C9-15

MeO

MeO

OMe

N

OMe

OMe NOAc

OMe

OH

NOAc

0°

7

Me

t-Bu

2h

0°

1

Bn

10% Pd-C, 40-50°, 5 h

PMHS (3 eq), (t-BuCO)2O (1.1 eq),

CH2Cl2, rt, 9 h

Et3SiH (1.2 eq), TMSOTf (0.1 eq),

CH2Cl2, 0°, 2 h

Et3SiH (1.2 eq), TMSOTf (0.1 eq),

Et3SiH, TFA

2h

rt

3

Me

OBz

6h 10 h

0°

1

N

Time

Temp

n

CH2Cl2

Et3SiH (1.2 eq), TMSOTf (0.1 eq),

Me

n

NOAc

Conditions

n

MeO

MeO

OMe

t-Bu

(78)

(66)

(80)

(65)

OR

I

OMe

H N

OMe

CN

CN

+ t-Bu

OMe

Boc

CN

(81)

(82)

(82)

I + II (85), I:II = 5:1

H

NHOBz

II

Product(s) and Yield(s) (%)

TABLE 24. ORGANOSILANE REDUCTION OF HYDROXYLIMINES (Continued)

R

OR

Hydroxylimine

H NHOBz

548

552

552

550

552

Refs.

595

C12-13

C12

Me

N

R

n

O

OBz

Me

n-C7H15

O

OH

Me

Ph

N

H

Ph

—(CH2)5—

R2

Ph

N

OR3

R1

R1

AcON

R2

C10-16

Bn

Bz

Bn

Bn

Ac

R3 rt rt rt rt 50°

1.2 1.2 1.2 2

Time

5d

overnight

overnight

24 h

overnight

CH2Cl2

Et3SiH (1.2 eq), TMSOTf (0.1 eq),

Et3SiH, TFA

10% Pd-C, 40-50°, 7 h

PMHS (3 eq), (t-BuCO)2O (1.1 eq),

Temp

x 1.2

TFA or TFA-CH2Cl2 (1:1)

PhMe2SiH (x eq),

O

R

R2

O

n

NHOBz

(23)

(78)

(75)

(65)

H N

NHOR3

(67)

R1

CN

Boc

Et

Me

0°

rt

4h

6h

Temp Time

(95)

2

R

(85)

1

n

(80)

(81)

(61)

552

550

548

276, 551

596

C13-20

C13

C12-23

R

R2

OBz

Me Me

Ph

PhCH2

P

EtO

N

Ph

OH

OEt

O

t-Bu

Ph

(62) (79) (73) (79) (65) (54)

i-Bu Ph Bn BnCH2

OEt

O

i-Pr

EtO

P

(66)

R

(75)

NHOBn

Ph

Boc

Et

Et3SiH (2 eq), TFA (as solvent), 40°, 12 h

10% Pd-C, 40-50°, 7 h

HN

(85) cis:trans = 5:1

(82)

(90)

(0)

(54)

Product(s) and Yield(s) (%)

Me

R

—(CH2)11—

H

4-MeC6H4

(95)

R2

NHOBz

(85)

PMHS (3 eq), (t-BuCO)2O (1.1 eq),

R1

—(CH2)5—

R2

Et3SiH, TFA, 0.5-6 h

Conditions

TABLE 24. ORGANOSILANE REDUCTION OF HYDROXYLIMINES (Continued)

—(CH2)4—

R1

N

BnO

Ph

R1

N

Hydroxylimine

553

548

550

Refs.

597

C17

C16

C15

N

O

t-Bu

MeO

OBn

MeO

O

N

Cl

N

Ph N

Cl N

NOAc

H

OBz

OH

OBn

OMe

OH

O

OBz

OH

Et3SiH (2 eq), TFA

10% Pd-C, 40-50°, 6 h

PMHS (3 eq), (t-BuCO)2O (1.1 eq),

CH2Cl2, rt, 3 h

Et3SiH (1.2 eq), TMSOTf (0.1 eq),

10% Pd-C, 40-50°, 3 h

PMHS (3 eq), (t-BuCO)2O (1.1 eq),

Et3SiH (2 eq), TFA

10% Pd-C, 40-50°, 6 h

PMHS (3 eq), (t-BuCO)2O (1.1 eq),

t-Bu

MeO

N H

I

+

t-Bu I + II (85), I:II = 5:1

NHOBz

Cl

(80)

(90)

(54)

Boc

(90)

(80)

CN

H

Boc

OBn

OMe

Cl

Ph

NHOBz

O

Boc

O

HN

H N

O

OBn

MeO

II

NHOBz

550

548

552

548

550

548

598

C44

C35-42

C19

C18

R4

MsO

OBz H

R2

N

R

7

H

Me

R8

PhMe2SiH (2.3 eq), TFA, 60°, 40 min

CH2OBz H

OBz CH2OBz H

OBz OBz

OBz H

R

6

PhMe2SiH (2.3 eq), TFA

Et3SiH (2 eq), TFA

PhMe2SiH (1.2 eq), TFA, rt

PhMe2SiH (1.2 eq), TFA, rt

Conditions

R4

BzO

I

OH

+

+

NHOBn

R2

N OBz R1

(85) (90)

(88)

(82)

R2

OMs R1

R8

12

I NHOCOPh

OAc

NHOBn

R3

BzO

R

6

R5

R7

Ph

Ph

OAc

NHOBn

II

(73)

I + II (77), I:II = 25:75

OAc

(73)

OBz (70)

R2

I + II (73), I:II = 99:1

OAc

NHOBn

II

OBz H

H

R1

Ph

Ph

NHOBn

Product(s) and Yield(s) (%)

TABLE 24. ORGANOSILANE REDUCTION OF HYDROXYLIMINES (Continued)

OBz H

H

H

OTBDPS

OBz OBz H

OBz OBz R1

H

OBz H

OBz OBz H

R

5

OBz H

R

4

H

R

3

OBz H

R2

OBn

H

R

1

R2

N

OCOPh

OMs R1

R8

12

N

OAc

OAc

OBn

N

N

R3

BzO

R

6

R5

R7

Ph

Ph

BnO

Hydroxylimine

549

549

550

551

551

Refs.

599

C6-9

C6

R

ACHN (0.2 eq), MeC6H5, 110°, 5 h

2h 4h 2h 3h 3h 6h 2h 2h 2h 3h 3h 2h 2h 2h

3,4-Me2

2,4-Me2

2,6-Me2

3,5-Me2

2,4,6-Me3

4-MeO

4-Cl

4-Br

4-CHO

4-Ac

3-Ac

4-MeO2C

4-CN

2h

4-Me

Time

MeC6H5

Et3SiH (5 eq), (Ph3P)3RhCl (0.02 eq),

PMHS, Pd/C, EtOH, 80°

2. ACHN (0.3 eq), MeC6H5, 110°, 3 h

H

NO2

NO2

CN

1. PhSiH3 (0.5 eq), (n-Bu)3SnH (10%),

Conditions

R

(0)

(49)

(71)

(—)

(—)

(—)

(71)

(86)

(75)

(85)

(83)

(83)

(82)

(90)

(86)

NH2

NH2

CN

(89)

(67)

Product(s) and Yield(s) (%)

TABLE 25. ORGANOSILANE REDUCTION OF NITROALKANES

R

NO2

Nitro Compound

554

316

555

Refs.

600

C12

C10

C8

C7

O

CO2Et

NO2

NO2

NO2

NO2

NO2

TBSO

EtO2C

CO2Et

Nitro Compound

(78)

360 h 240 h 120 h

MeC6H5 MeC6H5 MeC6H5 MeC6H5, EtOAc 240 h

0.01 0.02 0.05 0.02

8.0 5.0 5.0 5.0

2. ACHN (0.3 eq), MeC6H5, 110°, 3 h

ACHN (0.2 eq), MeC6H5, 110°, 5 h

1. PhSiH3 (0.5 eq), (n-Bu)3SnH (10%),

2. ACHN (0.3 eq), MeC6H5, 110°, 3 h

ACHN (0.2 eq), MeC6H5, 110°, 5 h

1. PhSiH3 (0.5 eq), (n-Bu)3SnH (10%),

(89)

360 h

MeC6H5

0.01

8.0

O

TBSO

(82)

(—)

(76)

(—)

360 h

(73)

360 h

MeC6H5

0.01

5.0

Time

C6H6

Solvent

0.01

y

EtO2C

5.0

x

Et3SiH (x eq), (Ph3P)3RhCl (y eq)

2. ACHN (0.3 eq), MeC6H5, 110°, 3 h

ACHN (0.2 eq), MeC6H5, 110°, 5 h

1. PhSiH3 (0.5 eq), (n-Bu)3SnH (10%),

2. AIBN (0.3 eq), MeC6H5, 110°, 3 h

AIBN (0.2 eq), MeC6H5, 110°, 5 h

1. PhSiH3 (0.5 eq), (n-Bu)3SnH (10%),

Conditions

NH2

CO2Et

CO2Et

(76)

(78)

(67)

(76)

Product(s) and Yield(s) (%)

TABLE 25. ORGANOSILANE REDUCTION OF NITROALKANES (Continued)

555

555

554

555

555

Refs.

601

C18

C16

C13

BnO

O2N

MsO

MsO

NO2

O

OBn

O

NO2

O

OMs

2. ACHN (0.3 eq), MeC6H5, 110°, 3 h

ACHN (0.2 eq), MeC6H5, 110°, 5 h

1. PhSiH3 (0.5 eq), (n-Bu)3SnH (10%),

MeC6H5, reflux, 4 h

Et3SiH (5 eq), (Ph3P)3RhCl (2 mol%),

2. ACHN (0.3 eq), MeC6H5, 110°, 3 h

ACHN (0.2 eq), MeC6H5, 110°, 5 h

1. PhSiH3 (0.5 eq), (n-Bu)3SnH (10%),

BnO

H2N

MsO

MsO

O

OBn

O

(71)

O

OMs

(—)

(70)

555

554

555

602

C6

C5-10

c-C6H11 Ph Bn 3-MeC6H4 Ph

H

H

H

H

Me

Cl

O2N

Cl

n-C5H11

H

N3

N2+ BF4—

N2+ BF4—

Cl

N3

i-Pr

H

OH

R2 Me

R1

R2

Me

N H

N

R1

O

Et3SiH, MeCN, rt, 16 h

Et3SiH, MeCN, rt, 16 h

(Boc)2O (1.1 eq), EtOH, rt, 3 h

PMHS (3 eq), 10% Pd-C,

(Boc)2O (1.1 eq), EtOH, rt, 5 h

PMHS (3 eq), 10% Pd-C,

Et3SiH (2 eq), TFA, 0°, 4 h

Conditions

Cl

O N H R1

R2

Cl

NO2

Cl

(70)

(72)

(88)

(90)

NHBoc

NHBoc

OH

(56)

(84)

(85)

(89)

(94)

(74)

(95)

(86)

H N

Product(s) and Yield(s) (%)

TABLE 26. ORGANOSILANE REDUCTION OF MISCELLANEOUS NITROGEN COMPOUNDS Nitrogen Compound

563

563

557

557

561

Refs.

603

C7

C7-8

C6-13

O

+

n

MeO

N3

N3

reflux, 90-120 min

n-PrOH (2 eq), C6H6, AIBN (5 mol%),

PMHS (1.5-2 eq), [(n-Bu)3Sn]2O (0.025 eq),

reflux, 90-120 min

n-PrOH (2 eq), C6H6, AIBN (5 mol%),

O

HO2C

I (91)

MeO

PhSiH3 (1.5-2 eq), [(n-Bu)3Sn]2O (0.025 eq),

(Boc)2O (1.1 eq), EtOH, rt, 3 h

PMHS (3 eq), 10% Pd-C,

(Boc)2O (1.1 eq), EtOH, rt, 4 h

PMHS (3 eq), 10% Pd-C, Ph

(83)

N3

(84)

1-Ad

n

(41)

1-C10H7

2. Et3SiH

(90)

Bn

O

(61)

Ph

O

(71)

t-Bu

1. NOBF4, SO2

(85)

n-Bu

RCHO (79)

N3

Et3SiH (2 eq), CH2Cl2, rt, 0.5-6 h

c-C3H5

NEt BF4–

i-Pr

R

HO2C

Ph

R

I

NHBoc

NH2

(51)

(40)

(94)

(90)

(94)

NHBoc

2

1

n

556

556

557

557

779

28, 562

604

C7

C7-14

C7-9

MeO

R

R

+

N2+ BF4–

N2+ BF4–

NPr-i FeCl4–

CN R

Et3SiH, MeCN, rt, 16 h

Et3SiH, MeCN, rt, 16 h

rt, 0.5-6 h

Et3SiH (1.5 eq), CH2Cl2, RCHO

OMe

TMS

CO, –20°

(88) (53) (36) (73) (46)

4-Cl 4-NCCH2 4-Me2N 4-MeO2C

(42) (91)

2-EtO2CC6H4 1-Ad

(90)

(25)

(0) (56)

PhCH=CH

(78)a 4-OHCC6H4 4-AcC6H4

(57) (19)a

(88)

4-NCC6H4

(97)

4-MeC6H4 4-MeOC6H4

(53)

4-ClC6H4

(87)

4-O2NC6H4

Ph

(77)

(11)

4-MeO

c-C3H5

R

(57)

2-Me

(91)

4-Me 3-Me

(61)

H

R

Product(s) and Yield(s) (%) TMS

N

TMSH (10 eq), Co2(CO)8 (0.08-0.25 eq),

Conditions

TABLE 26. ORGANOSILANE REDUCTION OF MISCELLANEOUS NITROGEN COMPOUNDS (Continued) Nitrogen Compound

563

563

28

559

Refs.

605

C9-11

C9

C8

R

R

+

NEt BF4–

N3

Ph

H N

N3

N3

Ph

Ph

OH

CO2—

N2+

CO2H

N2+ Cl–

Et3SiH (1.2 eq), CH2Cl2, rt, 0.5-6 h

THF, rt, 3-5 h

PMHS (2 eq), (Ph3P)4Pd (0.01 eq),

(Boc)2O (1.1 eq), EtOH, rt, 4 h

PMHS (3 eq), 10% Pd-C,

(Boc)2O (1.1 eq), EtOH, rt, 4 h

PMHS (3 eq), 10% Pd-C,

(Boc)2O (1.1 eq), EtOH, rt, 4 h

PMHS (3 eq), 10% Pd-C,

Et3SiH, CH2Cl2, reflux, 2 h

Et3SiH, THF, reflux, 2 h

RCHO

RNH2

I (89)

Ph

Ph

OH

+

I

NHBoc

(0)

4-NCC6H4

(54)

(0) (60)

4-OHCC6H4 4-AcC6H4

(85)

4-MeOC6H4

PhCH=CH

(92)

4-MeC6H4

(88)

4-EtOC6H4

(21)

(92)

Bn

(61)

(90)

4-O2NC6H4

(89) Ph

(9)

CO2SiEt3

c-C6H11

R

(90)

(88)

4-ClC6H4

R

(78)

(29) +

NHBoc

SiEt3

CO2H

28

270

557

557

557

563

563

606

C11

C10-15

C10

Ph

(82) (78) (79) (46)

Bn 3-MeC6H4 Ph

H

H

Me

CO, –20°

(92)

Ph

H

CN

(80)

c-C6H11

H

(91)

n-C5H11

H

(86)

H N

i-Pr

N H

Me

Ph

O

NH Ts

H

TMSH (10 eq), Co2(CO)8 (0.08 eq),

Et3SiH (2 eq), TFA, 0°, 4 h

H N

R2

R1

R2

Et3SiH (2 eq), TFA, 0°, 1 h

I (96)

I

NH2

Me

N H

N

NH Ts

2. AIBN (5 mol%), reflux, 90-120 min

n-PrOH (2 eq), C6H6

[(n-Bu)3Sn]2O (0.025 eq),

1. PMHS (1.5-2 eq),

2. AIBN (5 mol%), reflux, 90-120 min

n-PrOH (2 eq), C6H6

[(n-Bu)3Sn]2O (0.025 eq),

1. PhSiH3 (1.5-2 eq),

R1

O

N

N3

Conditions

R1

TMS

(80)

TMS

N

R2

(99)

(64)

Product(s) and Yield(s) (%)

TABLE 26. ORGANOSILANE REDUCTION OF MISCELLANEOUS NITROGEN COMPOUNDS (Continued) Nitrogen Compound

559

561

560

556

556

Refs.

607

C12 NH Ts NH Ts

N

n-C8H17

NH Ts

N

n-C10H21

i-Pr

Et

N

N3

N3

2. AIBN (5 mol%), reflux, 90-120 min

n-PrOH (2 eq), C6H6

[(n-Bu)3Sn]2O (0.025 eq),

1. PMHS (1.5-2 eq),

2. AIBN (5 mol%), reflux, 90-120 min

n-PrOH (2 eq), C6H6

[(n-Bu)3Sn]2O (0.025 eq),

1. PhSiH3 (1.5-2 eq),

2. AIBN (5 mol%), reflux, 90-120 min

n-PrOH (2 eq), C6H6

[(n-Bu)3Sn]2O (0.025 eq),

1. PMHS (1.5-2 eq),

2. AIBN (5 mol%), reflux, 90-120 min

n-PrOH (2 eq), C6H6

[(n-Bu)3Sn]2O (0.025 eq),

1. PhSiH3 (1.5-2 eq),

Et3SiH (2 eq), TFA , 0°, 1 h

Et3SiH (2 eq), TFA, 0°, 1 h

Et3SiH (2 eq), TFA, 0°, 1 h

I (94)

n-C8H17

I (95)

H N

H N

n-C10H21

i-Pr

Et

H N

I

I

NH Ts

NH Ts

NH Ts

NH2

NH2

(89)

(30)

(79)

(92)

(94)

556

556

556

556

560

560

560

608

C15

C14

C12

PMP

Ph

Ph

EtO2C

N3

N NH Ts

N NH Ts

N NH Ts

N NH Ts

N NH Ts

OEt

N NH Ts

n-C6H13

Ph

Et3SiH (2 eq), TFA, 0°, 1 h

Et3SiH (2 eq), TFA, 0°, 1 h

Et3SiH (2 eq), TFA, 0°, 1 h

Et3SiH (2 eq), TFA, 0°, 1 h

Et3SiH (2 eq), TFA, 0°, 1 h

Et3SiH (2 eq), TFA, 0°, 1 h

n-PrOH, AIBN, 80°

PhSiH3, (n-Bu)3SnH (cat.),

Conditions

PMP

Ph

Ph

EtO2C

H N NH Ts

H N NH Ts

(81)

(51)

(82)

560

560

560

560

560

(82)

(84)

560

556

Refs.

(75)

(—)

H N NH Ts

H N NH Ts

H N NH Ts

NH

OEt

H N NH Ts

n-C6H13

Ph

Product(s) and Yield(s) (%)

TABLE 26. ORGANOSILANE REDUCTION OF MISCELLANEOUS NITROGEN COMPOUNDS (Continued) Nitrogen Compound

609

C19

C16

I

a

N3

Cl

N3

N H

O N

Bn

Cl

O

N NH Ts

CO2Et

Cl

Et3SiH, TFA, 0° to rt, 24 h

NH-Gly-Gly-OEt Et3SiH, 20% Pd(OH)2/C, (Boc)2O

(Boc)2O (1.1 eq), EtOH, rt, 5 h

PMHS (3 eq), 10% Pd-C,

Et3SiH (2 eq), TFA, 0°, 1 h

The yield was determined by gas chromatography.

NC

I

BocHN

NC

Cl

N H

O

NH

CO2Et

Cl

NHBoc

H N NH Ts

Bn

O

Cl

(97)

NH-Gly-Gly-OEt

(85)

(76)

(80)

780

558

557

560

610

C16-20

C11-12

C10

C8-14

C6

R

R

S

S

S

+

S

SAr

SMe

SH

R

S 2

2 BF4–

Sulfur Compound

(0) (74)

2,4-(O2N)2C6H3 4-MeOC6H4

R

CH2Cl2, 0°, 20 h

Et3SiH (3-5 eq), BF3•OEt2,

20 h 22 h

1-Np 2-Np

168 h

20 h Bn

Time

(70)

Ph

92 h

24 h

Ar

SMe

+ ArSH

(0)

2-O2NC6H4

(20)

(52)

Ph

Time

(45)

Ph

(13) +

(67)

n-Bu

R

(100)

CH2Cl2, 0°

I

I

S

H

R

RSH

S

S

(25)

(50)

(40)

(30)

% Conv.

(5.5)

Product(s) and Yield(s) (%)

Et3SiH (3-5 eq), BF3•OEt2,

CH2Cl2, rt, 6 h

Et3SiH (1.3 eq), BF3•OH2 (4-6 eq),

Et3SiH (1.4 eq), TFA, 60°, 25 h

Et3SiH (1 eq), MeCN, 9:1

(48)

— 1:1

(54)

1:3 (71)

(51)

cis:trans

CO2Me

1:1

R

3

R5

R4

(69)

(76)

(71)

Me

Me

R2

O

I (62)

Br

Br

PhMeCH H

H

Ph

I

I

I (76)

Ph

Ph

I

OH

I (69)

Ph

(54)

Me

Me

—(CH2)3—

Me

Me

Me

R4

CH2Cl2, –78°, 45 min; rt, 3 h

2. Et3SiH (1.1 eq), BF3•OEt2 (1.1 eq),

1. LDA/THF; R4R5CO; TBAF a

CH2Cl2, rt, 10 min

HMe2SiOSiMe2H (1.0 eq), I2 (1.6 eq),

NaI (1.3 eq), CH2Cl2, 5-10°, 45 min

HMe2SiOSiMe2H (1.0 eq),

TMSCl (1.5 eq), MeCN, reflux, 45 min

PMHS (1 eq), NaI (1.33 eq),

LiBr (1.3 eq), TFA, 5-10°, 1.5 h

HMe2SiOSiMe2H (1.0 eq),

LiBr (1.3 eq), TFA, 5-10°, 15 h

HMe2SiOSiMe2H (1.0 eq),

TMSCl (1.5 eq), HOAc, reflux, 15 min

PMHS (1 eq), LiBr (1.33 eq),

(69)

765

357

357

567

357

357

567

614

C17

C16

C15

C14

C11

C10

Ph

Ph

Ph

Ph

N

Ts

N

Ts

O

EtO2C

O

Ph

CO2Me

N

Ts

N

Ts

Small Ring Substrate

PMHS (xs), EtOH, Pd-C, rt, 6 h

PMHS (xs), EtOH, Pd-C, rt, 6 h

PMHS (xs), EtOH, Pd-C, rt, 6 h

Et3SiH (3.9 eq), BF3, CH2Cl2, 20°, 7 d

PMHS (xs), EtOH, Pd-C, rt, 6 h

TMSCl (1.5 eq), MeCN, reflux, 7 h

PMHS (1 eq), NaI (1.33 mol%),

NaI (1.3 eq), CH2Cl2, 5-10°, 20 min

HMe2SiOSiMe2H (1.0 eq),

Conditions

Ph

Ph

Ph

Ph

EtO2C

I (46)

Pr-i I

I

NHTs

(80)

I

I II

(34)

(95)

(60)

(96)

(100)

NHTs

NHTs

Ph

i-Pr

NHTs

CO2Me

+

+ I + II (80), I:II 57:43

Product(s) and Yield(s) (%)

TABLE 28. ORGANOSILANE REDUCTION OF SMALL RING COMPOUNDS (Continued)

568

568

568

566

568

567

357, 567

Refs.

615

C24

C23

C21

C20

C19

a

Ar

Ph

Ph

Ph

Ph

Ts N

N

Ts

N

Ts

Ph

N

Ts

O

OBn

CO2Et

Ar = 3-PhOC6H4

CO2Et

Ph

Ph

N

Ts

CO2Et

CO2Et

PMHS (xs), EtOH, Pd-C, rt, 6 h

PMHS (xs), EtOH, Pd-C, rt, 6 h

CH2Cl2, 20°, 30 h

Et3SiR (1.1 eq), TFA (2.6 eq),

PMHS (xs), EtOH, Pd-C, rt, 6 h

PMHS (xs), EtOH, Pd-C, rt, 6 h

PMHS (xs), EtOH, Pd-C, rt, 6 h

PMHS (xs), EtOH, Pd-C, rt, 6 h

Ar

Ph

Ph

Ph

Ph

PMP

O

O

R

NHTs

(93)

(90)

(75)

D

H

R

(97)

CO2Et

OBn

Ph

CO2Et

NHTs

Ph

Ph

NHTs

NHTs

CO2Et

NHTs

CO2Et

NHTs

(—)

(93)

(85)

(80)

These sequential steps generate the intermediate substituted tetrahydrofuran-2-ol, which is converted in the second sequence into the final product shown.

PMP

O

Ts N

568

568

781

568

568

568

568

616

C20

C19

C18-20

R2 Et Et Me

R1 n-Pr i-Pr Ph

(90)

(95)

(95)

R1

CO2R2

(i-Pr)3SiH, MeC6H5

H

Ph3C+ –Br5-CB9H5

Me

, C6H6, reflux, 4 h

Ph3CH +

Ph3CH +

Ph3CH (—)

Me

1-Np Si

Ph Cl

(71)

[(i-Pr)3Si][Br5-CB9H5] (—)

[(i-Pr)3Si-NCMe][Br5-CB9H5] (—)

+

46

46

60

62

Ph3CH (100) + Et2SiHF (100)

Et2SiH2 (0.80 eq), rt, 1.5 h Ph

62

Ph3CH (100) + Me2SiF2 (95)

Me2SiH2 (0.45 eq), rt, 8 h

Si

62

Ph3CH (100) + Me2SiHF (100)

Me2SiH2 (0.8 eq) rt, 0.5 h

1-Np

62

62

782

Refs.

Ph3CH (100) + Et3SiF (100)

Ph3CH (100) + Me3SiF (100)

MeS

N

Product(s) and Yield(s) (%)

Et3SiH (0.8 eq), rt, 1.5 h

TMSH (0.8 eq), rt, 0.5 h

Et3SiH, TFA, MeCN

(i-Pr)3SiH, MeCN

R1

Conditions

TABLE 29. MISCELLANEOUS ORGANOSILANE REDUCTIONS

Ph3C+ –Br5-CB9H5

Ph3CCl

Ph3C+ BF4–

TBSO

SMe NHCO2R2

Substrate

617

C43

Ph3C+ (C6F5)4B–

C6D6 C6D6 MeC6H5 MeCN C6D6 C6D6

Et3Si Et3Si Et3Si (i-Pr)3Si (TMS)3Si

Solvent

TMS

R3Si

R3SiH

Ph3CH (—)

+

R3Si+ B(C6F5)4 – (—) 45

618

C4-8

C4

O

O

R

O

Ketone

n-BuLi (1.14 mol%), THF, rt

Me(EtO)2SiH (3.75 eq), 197 (0.57 mol%),

MeLi (1.14 mol%), THF, rt

[—(Me)(H)SiO—]4 (1.43 eq), 197 (0.57 mol%),

MeLi (1.14 mol%), THF, rt

Me(EtO)2SiH (1.43 eq), 197 (0.57 mol%),

23 (1.1 mol%), 0°, DME, 26 h

Ph2SiH2 (4 eq), [Rh(cod)2]BF4 (1.0 mol%),

Conditions

R

OH

R

OH

R

OH

I

OH

OH

(100)

(100)

+

Conf.

Time

R

S R S R Conf.

5 38 45 41 % ee

12 h 72 h 12 h 12 h

n-Pr t-Bu s-Bu Ph

R S R S R

2 21 42 39 99

(100) (100) (75) (100) (100)

12 h 140 h 140 h 24 h

i-Pr t-Bu s-Bu Ph

Time

S

19 12 h i-Pr

1h Et

R

R % ee

12 h

Ph

R

S 47

12 h

s-Bu

7

R 50

72 h

t-Bu

1h

S

6 48

12 h

n-Pr

Et

S

R

Conf.

17

7

% ee

12 h

1h

Time

I = 96% ee

I + II (94), I:II 90:10,

i-Pr

Et

R

II

OH

OH

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES

583

583

583

577

Refs.

619

C4-10

R1

O

R2

>99

(100)

Ph

12 h

(EtO)3SiH

R1

44

(80)

Ph

120 h

MeSiH3

2. PhMgBr

R2 150 h 230 h 230 h

Me n-Bu n-Pr Et s-Bu t-Bu n-Pr Et2NCH2 Ph n-C5H9 n-Bu c-C6H11

MeOCH2 550 h BnCH2 c-C6H11

i-Pr Me Et i-Pr Me Me i-Pr Me Me Et i-Pr Et Ph Me i-Pr

70 37 8 15 11 (5)

(94) (75) (92) (84) (96) (68)

600 h 1200 h

25 h 1270 h

18 h

90 (90) 300 h

4

R (+)

S (+)

(–)

R (–)

R (–)

(+)

R (+)

(–)

R (–) (91)

60 (63) 680 h 300 h

R (–)

40 (87)

S (+)

R (–) 27

65 (91) (99)

R (–)

11 (97)

S (+)

S (+) 5

18 (96) (92)

S (+)

S (+)

Conf.

19

10

% ee (93)

(89)

230 h

230 h

18 h

18 h

18 h

Time

n-Pr

Et

R

R

R

S

S

R

Conf.

Me

Me

R2

53

(100)

Ph

24 h

PMHS

R1

17

i-Pr (100)

12 h

(EtO)3SiH

OH

15

i-Pr (100)

12 h

PMHS

1. R3SiH (1 eq), catalysta (0.1 eq), rt

2

Et

1h

% ee (100)

R

Time

PMHS

R

OH

R3SiH

n-BuLi (1.14 mol%), THF, rt

R3SiH (3.75 eq), 197 (0.57 mol%),

584

583

620

C5

C4-12

R1

O

O

O

O

OEt

O

R2

Ketone

23 (1.1 mol%), 0°, THF, 4 h

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),

23 (1.1 mol%), –30°, THF, 75 h

Ph2SiH2 (2.5 eq), [Rh(cod)2]BF4 (1.0 mol%),

107 (1.2 mol%)

Ph2SiH2 (1.1 eq), [Rh(cod)Cl]2 (0.5 mol%),

Conditions

R1

I

O

OH

OH

OEt

OH +

OH

(60) 80% ee

II

OH

(87)

24 h

80

89

6

3

64

83

I = 35% ee

I + II (45), I:II = 42:58,

0°

Me

2-C10H7

(81)

24 h

24 h 20°

i-Pr

Ph

0°

(87)

24 h 0°

Et

Ph

Me

(81)

24 h

20°

ClCH2

Ph

1-C10H7

(89)

24 h

0°

Me

Ph

(69)

68 (89)

24 h

0°

Me

c-C6H11

24 h

42 (82)

40 h

0°

Me

n-C6H13

20°

80

(89)

24 h

0°

EtO2C(CH2)2 Me

t-Bu

95

(86)

96 h

0°

Me

t-Bu

Ph

76

(—)

24 h

0°

Me

i-Pr

86

56

(—)

24 h

0°

Me

Et

% ee (—)

Time

Temp

R2

R1

R2

OH

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

577

577

575

Refs.

621

C6

C5-17

t-Bu

R1

N

O

S

O

R2

O

—

–78°

121

MeC6H5, rt, 29 h

PhSiH3 (1.2 eq), CuF2 (1%), (S)-BINAP (1%),

n-C6H14, 65°, 1 h

PhSiH3 (1.1 eq), (R)-195-2n-BuLi (5 mol%),

2. PMHS, ketone, MeOH (3-7 eq), 15°, 17 h

MeOH, 60°, pyrrolidine, MeOH, THF

1. PhSiH3 (0.1 eq), 197 (2 mol%),

THF, –20°

[Rh(cod)]SbF6 (1 mol%), 126 (1 mol%),

Ph(1-C10H7)SiH2 (1.5 eq),

85 (10 mol%), MeOH, rt, 12-14 h

PMHS, Sn(OTf)2 (10 mol%),

4h

–50°

124

Catalyst Temp Time

catalyst (0.05 mol%), MeC6H5, 4 h

PMHS (4 eq), CuCl/NaOBu-t (1 mol%),

(—) 90

I

OH

R2

t-Bu

OH

I (58) 2% ee

I (30) 53% ee

t-Bu

R1

% ee

OH

(97) 90

N

H

OH

S

CH2-N-phth CH2-N-phth CO2Et

4-ClC6H4 4-O2NC6H4 2-C4H3S

75% conversion, 20% eeb

(75) 98% ee

CH2-N-phth

4-MeC6H4

CO2Me

1-C10H7

CH2-N-phth

CO2Me

4-O2NC6H4

Ph

CO2Me

4-MeC6H4

CO2Me

CO2Me

4-MeOC6H4

2-C10H7

CO2Me CO2Et

Me

Ph Ph

CF3

CO2Et Ph

R2

R1

(98)

(50)

(89)

(88)

(98)

(96)

(98)

(98)

(96)

(99)

(99)

(99)

(98)

(75)

784

783

587

576

385

590

622

C6

O

O

O

O

O

O

R

O

O

O

O

O

OMe

OEt

O

Ketone

23 (1.1 mol%), –30°, DME, 30 h

Ph2SiH2 (2.5 eq), [Rh(cod)2]BF4 (1.0 mol%),

23 (1.1 mol%), –30°, THF, 31 h

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),

23 (1.1 mol%), –30°, THF, 14 h

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),

MeC6H5, rt, 24 h

(R,R)-ebpe (20 mol%), vitride (3%),

PMHS (1.1 eq), Et2Zn (20 mol%),

44 (0.4 mol%), THF, rt, 30 min

Ph2SiH2 (1 eq), [Rh(cod)Cl]2 (0.3 mol%),

108 (1.2 mol%), THF, 0°, 120 h

Ph2SiH2 (1.1 eq), [Rh(cod)Cl]2 (0.5 mol%),

5-50°, 3-48 h

Et2SiH2, [(–)-(S)-bmpp]2RhCl, C6H6,

Conditions

I

O

OH

OH

I

O

OH

HO O

O

OH

O

+

OH

II

(74) 88% ee

(43) 32% ee

(—) 66% ee

OH

I = 97% ee

I + II (97), I:II = 75:25,

S

39

(76) 84% ee

S

31

(95)

t-Bu

Opt. Yield Conf. (93)

n-Bu

R

OEt

I (68) 37% ee

O

R

OH

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

577

577

577

594

787

575

785, 786

Refs.

623

S

O

O

O

O

O

I

90 88 70 78 74 67

12.5 100 0 12.5 100

121 121 122 122 122

S

91

0

121

131 (2 mol%), MeC6H5, rt, 4 h

OH

% ee

0

PMHS (1.2 eq), Ph2Zn (2 mol%),

OH

I (—) 78% ee

I (—)

+

II

(>99) 78% ee

(85) 92% ee

I = 70% ee

OH

OH

I + II (63), I:II 77:23,

OH

I (—) 90% ee

O

I

OH

124

MeC6H5 [(100 – x)]% x Ligand

NaOBu-t (3 mol%), THF (x%),

PMHS (4 eq), ligand (3 mol%), CuCl (3 mol%),

122 (0.05mol%), MeC6H5, –78°

PMHS (4 eq), CuCl/NaOBu-t (1 mol%),

121 (0.05 mol%), MeC6H5, –78°

PMHS (4 eq), CuCl/NaOBu-t (1 mol%),

124 (0.05 mol%), MeC6H5, –50°, 5 h

PMHS (4 eq), CuCl/NaOBu-t (1 mol%),

23 (1.1 mol%), 0°, DME, 55 h

Ph2SiH2 (2.5 eq), [Rh(cod)2]BF4 (1.0 mol%),

788

590

590

590

590

577

624

C6-12

C6-11

Ar

Ar

O

O

Me Me Et CH2Cl CO2Me t-Bu

2-C4H3S

Ph

Ph

Ph

Ph

Ph

Me

4-ClC6H4

Me Me Et CH2Cl CO2Me t-Bu

2-C4H3S

Ph

Ph

Ph

Ph

Ph Me Me Me Me Me

4-O2NC6H4

4-ClC6H4

4-MeC6H4

4-MeOC6H4

2-C10H7

1-indanone

R

Ar

R

Me

4-O2NC6H4

1-indanone

R

Ar

R

Ketone

70 h

70 h

70 h

70 h

50 h

170 h

170 h

25 h

70 h

40 h

70 h

70 h

Time

29 (5 mol%), MeOH, 0°

Ph2SiH2 (1.5 eq), [Rh(cod)Cl]2, (2.5 mol%),

72 h

72 h

240 h

240 h

25 h

120 h

70 h

24 h

96 h

Time

29 (5 mol%), THF, 0°

Ph2SiH2 (1.5 eq), [Rh(cod)Cl]2 (2.5 mol%),

Conditions

Ar

Ar

(24)

(0)

(0)

(51)

(92)

(15)

(11)

(95)

(68)

(28)

(46)

(100)

R

OH

(41)

(45)

(5)

(5)

(31)

(85)

(14)

(3)

(100)

R

OH

37

—

—

22

25

31

95

41

25

31

48

43

% ee

74

76

42

85

60

88

58

85

78

% ee

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

790

789

Refs.

625

C6-12

C6-11

R1

R1

4 10 43

(94) (95) (90)

Et2HSi Ph2HSi Ph2HSi

c-C6H11 c-C6H11 c-C6H11

i-Pr

n-Pr

t-Bu O

R2 Me Me Me Me Me Me Et Me Me Me n-Pr Me Me Me Me

R1

EtO2CCH2

EtO2C(CH2)2

AcO(CH2)3

Me2C=CHCH2CH2

n-C6H13

2-ClC6H4

Ph

Bn

2-MeO2CC6H4

3-AcOC6H4

Ph

2-MeOBn

BnCH2

1-C10H7

2-C10H7

Time 24 h 7h 24 h 20 h 2h 4h 4h 5h 14 h 24 h 5h 4h 5h 5h 6h

Temp –5° 0° 20° 20° 0° 0° 5° 0° 0° 0° 0-5° –5° 0° –5° –5°

x 6.0 6.0 6.0 6.0 4.0 4.0 4.0 6.0 6.0 6.0 4.0 6.0 6.0 4.0 4.0

AgBF4 (0.02 mol%), THF

(93)

(87)

(92)

(95)

(82)

(81)

(95)

(95)

(73)

(74)

(85)

(94)

(85)

(91)

(60)

R2

93

94

66

82

82

92

96

71

91

94

63

70

68

95

27

% ee

11

(98)

Et2HSi

c-C6H11

n-Pr

R1

40

(92)

Ph2HSi

c-C6H11

Me

Ph2SiH2 (1.6 eq), 87 (x mol%), 99 (10 mol%),

9

(98)

Et2HSi

n-C6H13

Me

R2

12

Et2HSi

i-Bu

Me

OH

25

(99)

Ph2HSi

R

R

S

R

R

R

R

R

Opt. Yield Conf. (98)

R3Si

t-Bu

R2

OH

R2

5-50°, 3-48 h

R1

Me

R2

R3SiH, [(+)-(R)-bmpp]2RhCl, C6H6,

R1

O

580, 581

785

626

C7

C6-12

O

O

O

O

R

88

(99)

2-C10H7 Me

O

R

60

(92)

n-C7H15 Me

23 (1.1 mol%), –30°, THF, 94 h

Ph2SiH2 (2.5 eq), [Rh(cod)2]BF4 (1.0 mol%),

23 (1.1 mol%), –30°, THF, 75 h

Ph2SiH2 (2.5 eq), [Rh(cod)2]BF4 (1.0 mol%),

AgBF4 (2 mol%), THF, 0°, 1 d

Ph2SiH2 (1.3 eq), RhCl3 (1 mol%), 197 (5 mol%),

2. PMHS, ketone, MeOH (3-7 eq), 15°, 11 h

OH

OH

I

I

OH

II +

OH

OH

OH

I = 89% ee

II

OH

I = 35% ee

I + II (45), I:II = 42:58,

I + II (88), I:II = 41:59

II 1S,2R 89% ee

OH

I + II (75), I:II = 69:31,

OH

+

I 1S,2S 91% ee

OH +

S

23

(12)

Et

Ph

(92) 50% ee

S

8

(19)

ClCH2

Ph

OH

R

91

(100)

Me

Ph

pyrrolidine, MeOH, THF, 60°

R

89

(45)

c-C6H11 Me

1. PhSiH3 (0.1 eq), 197 (2 mol%),

R

87

O

Conf.

% ee

R2

OH

(100)

R1

Me

38 (0.5 mol%), Et2O, rt, 15-25 h

Ph2SiH2 (1.5 eq), [Rh(cod)Cl]2 (0.25 mol%),

t-Bu

R2

Product(s) and Yield(s) (%)

R2

O

Conditions

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

R1

R1

Ketone

577

577

390

587

571

Refs.

627

S

O

EtO

O

N

O

O

O

O

OMe

OEt

O

18 h 4h —

10° 10° 30°

101 103 104

NaOBu-t (1 mol%), THF/MeC6H5, –50°, 4 h

PMHS (4 eq), 124 (0.05 mol%), CuCl (1 mol%),

7h

Time

0°

100

Complex Temp

AgBF4 (0.02 mol%), THF

complex (10 mol%),

Ph2SiH2 (1.6 eq), 87 (4.0 mol%),

108 (1.2 mol%), THF, 0°, 24 h

Ph2SiH2 (1.1 eq), [Rh(cod)Cl]2 (0.5 mol%),

108 (0.4 mol%), THF, rt, 30 min

Ph2SiH2 (1 eq), [Rh(cod)Cl]2 (0.3 mol%),

126 (1 mol%), THF, –20°

[Rh(cod)]SbF6 (1 mol%),

Ph(1-Np)SiH2 (1.5 eq),

23 (1.1 mol%), –30°, THF, 425 h

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),

O

S N

HO

(0)

(80)

(79)

(82)

OH

O

OH

EtO

O

OH

(66) 52% ee

—

75

79

94

(94) 99% ee

(71) 74% ee

OEt

(74) 69% eeb

(80) 98% ee, syn:anti = 1:1

OMe

OEt

% ee

O

O

OH

O

590

580

575

787

576

577

628

C8

C7

O

N

N

N O

O

O

Ketone

1 (1.1 mol%), THF, –50°, 48 h

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1 mol%),

38 (0.5 mol%), Et2O, 0°, 25 h

Ph2SiH2 (1.5 eq), [Ir(cod)Cl]2 (0.25 mol%),

NaOBu-t (1 mol%), THF/MeC6H5, –78°, 6.5 h

PMHS (4 eq), 124 (0.05 mol%), CuCl (3 mol%),

NaOBu-t (1 mol%), THF/MeC6H5, –35°, 8 h

PMHS (4 eq), 124 (0.05 mol%), CuCl (3 mol%),

MeOH, rt, 12-14 h

PMHS, Sn(OTf)2 (10 mol%), 87 (10 mol%),

NaOBu-t (1 mol%), MeC6H5, –50°, 2 h

PMHS (4 eq), 124 (0.05 mol%), CuCl (1 mol%),

Conditions

N

I

OH

OH

OH

I (82) 77% ee

HO

N

N

N

OH (19) 19% ee

(97) 84% ee

(92) 75% ee

(99) 0% ee

(97) 90% ee

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

578

582

590

590

385

590

Refs.

629

O

II

37 33 50 49

0° 10° 27°

117 118 119

3. Add ketone, 4 d

2. PMHS (5 eq)

1. 197 (4.5 eq), n-BuLi (9 eq), C6H6

25 (1.1 mol%), THF, rt, 10 h

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1 mol%),

II (67) 24% ee

I (62) 80% ee

% ee

0°

I (—)

OH

I (90) 92% ee

Temp

Ligand

OH

I (>98) 23% ee

I

116

ligand (0.5 %), MeC6H5

Ph2SiH2 (1.25 eq), Rh[(NBD)Cl]2 (0.5 %),

46 (0.4 mol%), THF, rt, 30 min

Ph2SiH2 (1 eq), [Rh(cod)Cl]2, (0.3 mol%),

THF, –20°

[Rh(cod)]SbF6 (1 mol%), 126 (1 mol%),

Ph(1-Np)SiH2 (1.5 eq),

2. PMHS, ketone, MeOH (3-7 eq), 15°, 6 h

MeOH, THF, 60°

1. PhSiH3 (0.1 eq), 197 (2 mol%), pyrrolidine,

MeC6H5, rt, 24 h

(R,R)-ebpe (20 mol%), vitride (3%),

PMHS (1.1 eq), Et2Zn (20 mol%), (—) 20% ee

588

606

791

788

576

587

594

630

C8

Ph

O

O

O

O OEt

Ketone

none none THF THF THF CH2Cl2 CCl4 THF

41 41 41 41 40 40 39 51

Ligand Solvent

II

OH

I

O OEt

73 (79) (54) (86) (77) (70) (58) (45)

–40° 0° –78° –78° –78° 0° –78°

0

14

48

51

82

73

73

% ee (54)

0°

II

Product(s) and Yield(s) (%)

(85) 86% ee

(>99) 76% ee

(80) 98% ee

(70) 88% ee

I (94) 60% ee

Ph

Ph

OH

OH

OH

Temp

Ph2SiH2 (4 eq), [Rh(cod)Cl]2 (1 mol%), ligand

[Rh(cod)Cl]2 (0.5 mol%), 37 (0.5 mol%), 0°

Ph2SiH2 (1.5 eq),

[Rh(cod)Cl]2 (1 mol%), 41, THF, –78°

Ph(1-Np)SiH2 (4 eq),

131 (2 mol%), MeC6H5, rt, 48 h

PMHS (1.2 eq), (i-Pr)2Zn (2 mol%),

23 (1.1 mol%), –30°, THF, 24 h

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (0.5 mol%),

25 (1.1 mol%), –40°, THF, 26 h

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),

Conditions

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

792

570

792

788

577

577

Refs.

631

(78) (85)

11 h 48 h 9h

25 26 27

(97) (94) (95) (65) (93) (55) (56) (97) (33) (99) (99) (92) (85) (78)

10° 0° rt rt rt rt rt rt rt –40° rt rt rt

41 41 42 47 49 50 45 44 46 46 43 53 52

(92)

Ph

OH

rt

rt

Temp

1 15

3

0

26

86

79

17

69

4

2

52

40

82

81

73

44

R

—

R

R

R

S

R

S

R

R

R

R

R

R

R

% ee Conf.

II (91) 76% ee

41

40

Ligand

ligand (0.4 mol%), THF, 30 min

Ph2SiH2 (1 eq), [Rh(cod)Cl]2 (0.3 mol%),

6 (0.4 mol%), THF, rt, 30 min

Ph(1-Np)SiH2 (1 eq), [Rh(cod)Cl]2 (0.3 mol%),

92

(88)

5h 92

% ee (89)

Time

24

I

Ligand

ligand (1.1 mol%), THF, rt

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1 mol%),

787

787

606

632

C8

Ph

O

Ketone

2 4

50°

% ee 94 90 95 96

Time 5h 1h 6h 99)

(99)

(90)

PhSiH3

16 h

24 h

1h

40 h

2h

6h

2h

16 h

2h

8h

Time

I

I (94) 76% ee

I (100) 72% ee

Silane

Silane (1.5 eq), 126 (1 mol%), THF, rt

Ar

2

Ar

4

CuF(PPh3)3•MeOH

[(Ph3P)CuH]6

Ar

4

CuF(PPh3)3•MeOH, dppb

Ar

(—)

0.5

CuF2

1

air

1

CuF2

CuI, Ph3SiF2N(Bu-n)4

Ar

4

CuF2

air

air

2

CuF2, dppb

2

Ar

2

CuF2, dppb

CuF(PPh3)3•MeOH

atm

x

[Cu]

(S)-BINAP, MeC6H5, atmosphere, rt

PhSiH3 (1.2-1.5 eq), [Cu] (x mol%),

(S)-BINAP (4 mol%), MeC6H5, air, rt

Me(EtO)2SiH (1.5 eq), CuF2,

MeC6H5, Ar, rt

PMHS (5 eq), CuF2, (S)-BINAP (4 mol%),

576

784

784

784

638

C8

Ph

O

Ketone

(87) (85) (13) (86) (30) (18)

OPr-i OPr-i OPr-i F F F

51 59 62 59 60 61

62

(89) (50) (90)

128 129 130

86

20

51

% ee (36)

127

51

56

61

65

51

18

Ligand

ligand (1 mol%), THF, rt

I

(20)

Cl

57

Ph2SiH2 (1.5 eq), [Rh(cod)]SbF6 (1 mol%),

50

Cl 23

% ee (60)

X

I

51

Ph

OH

L

(EtO)3SiH, THF, Ti(L)2X2, 2-3 d

Conditions

R

R

S

S

Conf.

S

S

S

S

S

S

S

R

Conf.

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

576

793

Refs.

639

R R R R R S R

25 91 78 67 83 84

(30) (66) (56) (78) (>99) (>99)

216 h 288 h 40 h 44 h 18 h 72 h

147 138 151 136 149 150

93

(59) (46) (42) (38) (52) (34)

24 h 24 h 24 h 5h 36 h 24 h 70 h

Cu(OTf)2 — AgOTf Cu(OTf)2 AgOTf AgOTf

37 37 35 35 36 41

84

45

92

90

67

95

% ee (56)

Time

AgOTf

Ligand Additive 37

ligand (1 mol%), additive (1 mol%), Et2O, 0° Ph

R

37

(11)

48 h

137

OH

S

84

(56)

170 h

139

Ph2SiH2 (2 eq), (Ph3P)RuCl2 (1 mol%),

S

75

(99)

18 h

135

Conf.

88

18 h

% ee (98)

Time

131

Ph

OH

Ligand

ligand (2 mol%), MeC6H5, rt

PMHS (1.2 eq), Et2Zn (2 mol%),

569

794

640

C8

Ph

O

Ketone

rt rt rt rt rt 0° 0° 0°

none C6H6 Et2O DME CH2Cl2 MeCN THF THF THF

29 29 29 29 29 29 29 28 30

Time 20 h 144 h 4h 1h 24 h 24 h 20 h 144 h

Temp 15° 0° 40° 15° 0° –20° 15° 0°

Ligand 28 28 29 29 29 29 30 30

ligand (5 mol%), THF

Ph2SiH2 (1.5 eq), [Ir(cod)Cl]2 (2.5 mol%),

rt

Solvent

Ligand

Temp

[Rh(cod)2]BF4 (5 mol%), ligand (5 mol%)

Conditions

72 h

72 h

48 h

20 h

12 h

3h

2h

12 h

1h

Time

Ph

Ph

R 13 0 23 18 0 0 22

(43) (100) (100) (55) (40) (90) (81)

R

—

—

S

S

—

R

Conf. 15

R

R

R

—

S

—

R

S

R

Conf.

% ee

50

31

85

0

6

0

8

21

12

% ee

(82)

OH

(67)

(46)

(31)

(43)

(100)

(100)

(71)

(100)

(73)

OH

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

789

789, 795

Refs.

641

92 98 —

(2-MeC6H4)2HSi MesPhHSi Mes2HSi

95 — — —

(—) (—) (0) (0) (0)

Ph2SiH2 Ph(1-Np)SiH2 Ph(t-Bu)SiH2 Et3SiH PMHS

58 (78) (50) (30) (50)

93 87 88 94 96

58

44

13

54

% ee (95)

Ligand

ligand (10 mol%), MeOH, rt

OH

88

(—)

PhMeSiH2

PMHS, Sn(OTf)2 (10 mol%),

0 78

(—)

% ee

I (—)

PhSiH3

Silane

Ph

95

2-MeC6H4PhHSi

I

80

Ph2HSi

Silane (1.5 eq), 126 (1 mol%), THF, rt

1 66

PhMeHSi

8

Et2HSi

3

% ee

PhH2Si

Ph

OH

n-C8H17H2Si

R3Si

R3SiH{RhCl(cod)}2 (2.5 mol%), (–)-37, THF, rt

R

R

S

S

R

Conf.

385

576

586

642

C8

Ph

O

Ketone

16

(26) (30) (73) (81) (36) (25) (51) (39) (52) (44) (65) (73) (50) (73) (35) (83)

13 15 14 9 10 8 12 11 32 33 3 4 5 6 191 192

0

5

24

32

27

31

40

33

36

0

35

12

16

8

18

40

% ee (51)

II

7

Ph

OH

Ligand

ligand (1 or 2 mol%), THF, 0°, 20 h

Ph2SiH2 (1.5 eq), [Rh(cod)Cl]2 (0.5 mol%),

Conditions

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

789

Refs.

643

Time 70 h 40 h 40 h

Temp 0° 0° 0°

28 30

76

(76) (80) (76) (84)

2.4 2.4 2.4 4

THF Et2O MeC6H5 MeC6H5 94

93

91

85

% ee (64)

x

27

10

48

% ee

2.4

(72)

(56)

(46)

none

II

II

Solvent

48 (x mol%), 0°

Ph2SiH2 (2 eq), [Rh(cod)Cl]2 (1 mol%),

Ligand 29

ligand (5 mol%), MeOH

Ph2SiH2 (1.5 eq), [Rh(cod)Cl]2 (2.5 mol%),

585

790

644

C8

Ph

O

Ketone

218 218 218 218 218

RhClL2 [Rh(Cl)COL2] 1/2[RhCl(C2H4)2]2•2L + C2H4 1/2[RhCl(C2H4)2]2•4L 1/2[RhCl(C2H4)2]2•5L

218

1/2[RhCl(C2H4)2]2•2L

219

218

[RhCl(C2H4)•L]2

1/2[RhCl(C2H4)2]2•3L

218

1/2[RhCl(C2H4)2]2•L

218

217

1/2[Rh(Cl)(cod)]2•2L

1/2[RhCl(C2H4)2]2•3L

219

1/2[Rh(Cl)(cod)]2•2L

217

218

1/2[Rh(Cl)(cod)]2•2L

1/2[RhCl(C2H4)2]2•2L

219

[Rh(Cl)(cod)]•2L

219

218

[Rh(Cl)(cod)]•L

1/2[RhCl(C2H4)2]2•2L

Ligand

Catalyst

ligand, THF, rt, 24 h

Ph2SiH2 (1.3 eq), catalyst (1 mol%),

Conditions

Ph

S R R R R R R R

58.3 31.0 7.5 33.1 27.6 25.7

94 90 78 92 83 79

R

51.2

R

41.4

96

89

R

5.0

88 R

R

6.6

92

3.3

R

6.8

93

63

R

4.4

94

52.3

—

11.2

93

92

R

0

90

Conf.

4.4

86

% Conv. % ee

II

OH

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

796

Refs.

645

S R S S S S S S S S

CONHPh CONHPh CONHC10H7-1 CONHCHPh2 CONHC6H14-n CONHBu-t CO2Ph CO2Me CO2Bu-t CH2OBn

1:3 1:1 1:1

(S,S,S)-TRISPHOS (S,S,S)-TRISPHOS

[Rh(cod)Cl]2 [Rh(cod)Cl]2 (NBD)Rh(acac) (S,S,S)-TRISPHOS (NBD)RhClO4 (S,S,S)-TRISPHOS

1:2

1:2

TRISPHOS

[Rh(cod)Cl]2

Rh:Ligand

Ligand

Catalyst

Ph2SiH2 (1 eq), catalyst, ligand, C6H6, rt, 16 h

Conf.

R

CH2Cl2, 0° to rt, 24 h

R N Cl3SiH (1.5 eq), CHO (0.1 eq),

II

II

(65)

(67)

(53)

(38)

(60)

(29)

(88)

(39)

(53)

(80)

(82)

(69)

(78)

(93)

(90) 36:64 71:29 61:39 54:46 55:45 61:39 57:43 55:45 56:44

31 27 43 20 8 11 21 14 11 13

81

58

75

81

0

% ee

R:S 65:35

% ee

797

379

646

C8

Ph

O

Ketone

0° 0° 0°

Et2O/TMEDA 2:1 THF/TMEDA 2:1 Et2O, TMEDA

(EtO)3Si (EtO)3Si (EtO)3Si

87 87 88 87

103 99 99 102

Ligand 89 88 92 93 91

100 101 103 104 102

33 63

(52) (46)

31 62 84 87

(88) (94) (87)

2h 3h 7h

Time 10 h 18 h 2h 18 h 20 h

Temp –5° 0° 10° 20° 20°

91 83 54 19 —

(91) (92) (88) (82) (66)

% ee

22

(94)

2h

ligand (10 mol%), AgBF4 (0.02 mol%), THF Complex

64

(50)

% ee

0 31

(33)

% ee (88)

I

(94)

I

I

Ph

OH

3h

Time

Ph2SiH2 (1.6 eq), complex (4.0 mol%),

89

Ligand

99

Complex

24h

24 h

24 h

6 h; 16 h

6 h; 16 h

Time

ligand (10 mol%), AgBF4 (0.02 mol%), THF

Ph2SiH2 (1.6 eq), complex (4.0 mol%),

0°; 20°

Et2O

(EtO)3Si

Temp –78°; 20°

Solvent

(MeO)3Si THF

R3Si

R3SiH (1 eq), Li-(R)-BINOL (5 mol%)

Conditions

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

580

580

592

Refs.

647

52 55 54 56 55 82

10° 20° 20° 20° 20°

117 118 119 109 113

96 95 39 88 79 95 86 86 97 96

10° 20° –27° 0° 10° 0° 20˚ 10° 10° 10°

1:1 1:1 1:1 1:1 1:1 1:1 1:1 1:1 1:4 1:2

MeC6H5 THF THF THF C 6H 6 C6H6 MeC6H5 MeC6H5 MeC6H5

96

0°

1:1

MeC6H5 MeC6H5

57

–27°

1:1

MeC6H5

Solvent Rh[(NBD)Cl]2:117 Temp

Ph2SiH2 (1.25 eq), Rh[(NBD)Cl]2 (0.5%), 117

% Conv.

% ee

0°

Ligand

Temp

I

I

116

ligand (0.5%), MeC6H5

Ph2SiH2 (1.25 eq), Rh[(NBD)Cl]2 (0.5%),

56

56

54

49

46

49

52

15

51

55

53

17

% ee

791

791

648

C8

Ph

O

Ketone

Time — 26 h 4d

–5° to 0° 0° 0°

Ph2HSi PhMeHSi Ph(1-Np)HSi

50°

MeC6H5 40°

50°

Et2O none

Temp

Solvent

12 h

5h

5h

Time

(EtO)3SiH, 194 (10 mol%)

R3Si

Temp

99 (10 mol%), THF, –5° to 0°

R3SiH (1.6 eq), 87 (1.5 mol%),

Conditions

I

Ph

(>98)

(78)

% ee

54

48

55

% ee

62

14

76-78

(>98)

(62)

(32)

(—)

I

OH

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

378

580

Refs.

649

(90) (47) (47)

24 h 24 h 24 h

0° 0° 0° 0° 0° 0° 0°

Et2O/TMEDA 30:1d Et2O/TMEDA 30:1e Et2O/TMEDA 30:1f Et2OTMEDA 30:1f Et2O Et2O/TMEDA 30:1 Et2O/TMEDA 30:1g

Li-(R)-BINOL Li-(R)-BINOL Li-(R)-BINOL Li-(R)-BINOL Li-(R)-BINOL (R)-hydro-BINOL Li-(R)-BINOL

x 0.3 0.3 0.33 0.48 0.5 0.24

Catalyst CuOBu-t CuO2CPh CuO2CPh CuO2CPh CuO2CPh CuO2CPh

ligand (y mol%)

(–)-BPPFA

(+)-NORPHOS

(+)-NORPHOS

(–)-DIOP

0-20°

20°

20°

0-20°

0-20°

0-20°

(–)-DIOP (–)-DIOP

Temp

Ligand

18 h

120 h

95 h

16 h

23 h

15 h

Time

(100)

(67)

(51)

(100)

(100)

(100)

(22)

24 h

20°

Et2O/TMEDA 30:1

Li-(R)-methoxythio-BINOL

Ph

(87)

24 h

–20°

Et2O/TMEDA 30:1

Li-(R)-2,2'-Me2BINOL

Ph2SiH2 (1.7 eq), catalyst (x mol%),

(0)

24 h

20°

Et2O or THF

Al-BINOL complex

OH

(46)

24 h

20°

Et2O/TMEDA 30:1c

28.9

16.3

38.8

13.4

18.7

19.5

% ee

24 h

24 h

8h

8h

R

S

R

R

R

R

Conf.

(91)

(92)

(96)

(91)

(50)

S S

S 40 66

S

52

S

S

70

70

59

S

R

58

R

37

S

S

26

—

63

64

R

Li-(R)-BINOL

24 h

20°

Et2O/TMEDA 2:1c

Li-(R)-BINOL

(37)

S

48 h

–22°

THF

(R)-BINOL phosphoric acid

R

6

12 h

0°

Et2O/TMEDA 2:1c

Li-(R)-BINOL

Conf.

48

7

(53)

% ee

48 h

0°

Et2O (59)

Time

Temp

Solvent

Li-(R)-BINOL

Ph

OH

Catalyst

(MeO)3SiH (1 eq), catalyst

798

592

650

C8

Ph

O

Ketone

Li-phenylalanine

(EtO)3Si Ph2SiH2 (1.7 eq), catalyst (x mol%),

x 0.3 0.55 0.4 0.3 0.16 0.04 0.3 0.33 0.48 0.5 0.24

Catalyst CuOBu-t CuOBu-t CuOBu-t CuO2CPh CuO2CPh CuO2CPh CuO2CPh CuO2CPh CuO2CPh CuO2CPh CuO2CPh

0.39

0.15

0.08

0.19

0.30

0.44

0.34

(–)-BPPFA

0.27

(+)-NORPHOS 0.81

(+)-NORPHOS 0.71

(–)-DIOP

(–)-DIOP

(–)-DIOP

(–)-DIOP

(–)-DIOP

(–)-DIOP

(–)-DIOP

(–)-DIOP

0-20°

20°

20°

0-20°

0-20°

0-20°

–10°

0-20°

0-20°

0-20°

0-20°

18 h

120 h

95 h

16 h

23 h

40 h

23 h

16 h

15 h

20 h

15 h

Time

OH

Li2-histidine

(EtO)3Si

Temp

(25)

Li-histidine

(MeO)3Si

y

(26)

189

(EtO)3Si

0.35

(26)

190

(EtO)3Si

Ligand

(30)

none

Ph

(0) (26)

188

(MeO)3Si

ligand (y mol%)

(55)

Ligand

I

(EtO)3Si

Ph

OH

R3Si

R3SiH, ligand, THF/TMEDA, 0°, 10 min

Conditions

28.9

16.3

(67)h (100)

38.8

13.4

(100)h (51)

18.7

16.7

16.9

12.7

15.3

18.8

19.5

% ee

(100)

(100)

(100)

(100)

(100)

(100)

(100)

R

S

R

R

R

R

R

R

R

R

R

Conf.

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

493

798

593

Refs.

651

none CCl4 MeC6H5 dioxane THF none none

4.4 4.4 4.4 4.4 4.4 8.8

125 125 125 125 125 (R)-BINAP 87

12 21

(92) (24)

DME MeC6H5

x — 2.0 2.0 1.0 1.5 1.5

Additive none AgBF4 AgPF6 AgOTf BF3•OEt2 EtAlCl2

— 3h 5h 27 h 14 h 18 h

rt 0° –3° –5° 0° 0°

Temp Time

additive (x mol%), THF

(89)

(90)

(96)

(80)

(94)

(0)

67

82

89

87

95

—

% ee

12

(11)

CCl4

Ph2SiH2 (1.6 eq), 99 (10 mol%),

10

OH

63

(8)

% ee (—)

Ph

Ph

OH

(16)

(95)

(97)

(45)

(88)

(0)

(94)

MeCN

72 h

24 h

24 h

96 h

24 h

24 h

48 h

Time

I

THF

Solvent

Ph2SiH2, 207 (1 mol%), rt

Solvent

x 8.8

Ligand

ligand (x mol%), AgOTf (2 mol%)

[RuCl2(C6H6)]2 (0.5 mol%),

Ph2SiH2 (160 mol%),

R

R

S

R

R

Conf.

0

5 (R)

54

35

23

—

38

% ee

580, 581

800

799

652

C8

Ph

O

Ketone

39.8

(66) (60) (45) (48) (60) (51) (53) (71) (72) (76) (93) (63)

MeC6H5 C6H6 n-C5H12 PE Et2O THF dioxane CH2Cl2 ClCH2CH2Cl CHCl3 CCl4 MeCN 16.8

56.6

15.2

22.2

23.8

25.2

24.0

34.0

24.2

28.4

31.0

31.8

% ee (60)

none

Ph

OH

Solvent

66 (2.5 mol%), 0-20°, 18 h

Ph2SiH2 (1 eq), [Rh(cod)Cl]2 (0.5 mol%),

Conditions

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

801

Refs.

653

R S R S R R R R R

25.5 31.8 34.4 20.2 23.0 37.4 32.8 39.8 70.1 26.5 33.8 39.6 3.6 4.3 4.2 34.7 33.8 53.6 8.7 24.3 1.7

(66) (66) (40) (56) (77) (44) (63) (77) (63) (69) (58) (57) (19) (16) (66) (69) (68) (51) (69) (48)

65 66 67 69 68 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84

R

R

R

S

R

S

R

S

R

R

S

S

Conf.

% ee

Ligand (42)

Ph

OH

64

ligand (2.5 mol%), MeC6H5, 0-20°, 18 h

Ph2SiH2 (1 eq), [Rh(cod)Cl]2 (0.5 mol%), 804

654

C8

Ph

O

Ketone

R S S R R

40.7 56.6 52.6 53.2 62.2 69.8 71.6 83.4 66.6 50.0 62.4 42.9 5.6 9.0 49.6 50.8 65.6 10.4 46.5 7.6

(93) (75) (90) (85) (67) (89) (90) (70) (85) (95) (10) (27) (63) (90) (90) (89) (17) (49) (22)

66 67 69 68 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84

R

R

R

S

R

S

R

S

R

R

S

S

R

R

R

Conf.

% ee (80)

Ph

OH

Product(s) and Yield(s) (%)

64

Ligand

ligand (2.5 mol%), CCl4, 0-20°, 18 h

Ph2SiH2 (1 eq), [Rh(cod)Cl]2 (0.5 mol%),

Conditions

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

801

Refs.

655

MeC6H5 CCl4 CCl4 MeC6H5 CCl4 MeC6H5 CCl4

5 5 5 5 5 5

58 55 55 56 56

CCl4

6

54 2.5

MeC6H5

5

54

58

none

5

54

58

Solvent

x

Ligand or complex

ligand or complex (x mol%), rt

Ph2SiH2 (1.2 eq), [Rh(cod)Cl]2 (0.5 mol%), Ph

(—)

(72)

(21)

(68)

(59)

(—)

(48)

(—)

(61)

(36)

OH

33

50

3

9

84

15

5

55

1

7

% ee

802

656

C8

Ph

O

Ketone

(68) (15) (>99)

6h 4h 18 h

133 152 148

Time 24 h 5h 11 h 78 h 9h 21 h 168 h 4h 50 h

Solvent THF THF THF THF THF DME CH2Cl2 MeC6H5 THF

Ligand 23 24 25 26 27 25 25 25 25

ligand (1.1 mol%), –40° Ph

(14)

6h

132

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),

(94)

6h

134

(95)

(86)

(81)

(96)

(85)

(78)

(88)

(89)

(90)

OH

76

18 h

89

90

91

90

15

1

92

92

85

% ee

88

0

22

76

78

% ee (>99)

Time

131

Ph

OH

S

S

S

S

S

R

S

S

S

Conf.

R

—

S

S

S

S

Conf.

Product(s) and Yield(s) (%)

Ligand

ligand (2 mol%), MeC6H5, rt

PMHS (2 eq), Et2Zn (2 mol%),

Conditions

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

499

577

788

Refs.

657

C8-9

Ar

Ph

O2N

O

O

AgOTf AgBF4 none AgBF4

2 2 2 4

Rh(cot)Cl Rh(cot)Cl RhCl3 RhCl3

5°

rt

15°

15°

20°

I

I

CF3

OH

90

75

70

43

41

% ee

97 91 93 21

(97) (98) (99)

7h 3h 4h

4-ClC6H4 4-MeC6H4 4-MeOC6H4

% ee (98)

OH

CF3

7h

Ar

Ph

OH

I (9) 6% ee

Ph

O2N

(98)

(86)

(57)

(64)

(68)

I

Time

2h

2h

3h

3h

2h

Time

Ph

63 (0.5 mol%), THF, 0°

Ph2SiH2 (1.6 eq), [Rh(cod)Cl]2 (0.25 mol%),

161 (2 mol%), MeC6H5, rt, 1 h

PMHS (1.2 eq), Et2Zn (2 mol%),

MeC6H5, 65°, 1 h

PhSiH3 (1.1 eq), (R)-195-2n-BuLi (5 mol%),

MeC6H5, 65°, 1 h

PhSiH3 (1.1 eq), (S)-195-2n-BuLi (5 mol%),

(EtO)3SiH, 193 (10 mol%)

none

2

Rh(cot)Cl

Temp

Ph

OSiPh2H

Ar

CF3

O

AgX

x

Catalyst

95 (x mol%), AgX (2 mol%), THF

Ph2SiH2 (1.5 eq), catalyst (1 mol%), II

OSiPh2H

(—) 54% ee

Ph

(>99) 27% ee

(9) 5% ee

OH

(2)

(14)

(39)

(33)

(32)

II

+

579

788

783

783

378

572

658

C8-9

Ar

Ar

O

O

16 16 17 18 19 17 20 21

Me Et Me Me Me Me Me Me

Ph

Ph

Ph

Ph

4-ClC6H4

Ph

Ph

2h

98)

50°

5h

Temp

Ph

R

0

(87)

OH

14

(100)

5

12

% ee

7

(78)

(84) (77)

Ar

OH

R Time

(EtO)3SiH, 194 (10 mol%), Et2O

199

O

Catalyst

Ph

n-BuLi (0.010 eq to catalyst), THF, –78° to rt

(EtO)3SiH (2.5 eq), catalyst,

Ar

O

S

S

R

S

S

S

S

—

S

S

R

S

Conf.

378

806

668

C8-12

R1

R

(98)

24 h

2-C10H7

R2 Me Et Me Me Me Me

R2 Me Me Me Me Me Et Me

R1

Ph

Ph

(E)-PhCH=CH

c-C6H11

n-C6H13

1-C10H7

R1

Ph

4-MeOC6H4

4-CF3C6H4

2,4-Me2C6H3

2,4,6-Me3C6H2

Ph

1-C10H7

(–)-34, THF, rt

MesPhSiH2, [Rh(cod)Cl]2 (2.5 mol%),

48 (4 mol%), MeC6H5, rt

R1

(85)

30 h

1-C10H7

Ph2SiH2 (2 eq), [Rh(cod)Cl]2 (1 mol%),

(93)

48 h

4-BrC6H4

R2

(93)

72 h

3-BrC6H4

R2

92

98 97 96 95 98 98 99

(94) (97) (88) (97) (99) (96) (97)

R2 % ee

52

(90) OH

87

(90)

22

91

94

% ee

66

48

55

62

57

54

% ee

(85)

(83)

(91)

(84)

I

OH

(87)

72 h

2-BrC6H4

O

(97)

R1

R

OH

24 h

125 (2.2 mol%), AgOTf (2 mol %), THF, rt Time

Ph2SiH2 (160 mol%), [RuCl2(C6H6)]2 (0.5 mol%),

Conditions

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

Ph

R

O

Ketone

586

585

799

Refs.

669

C8-13

R

1

R

30 40 70 — — 30 5 5

(80) (89) (90) (90) (95) (82) (78)

Me Me Me Ph Ph Ph Ph

4-MeC6H4

4-MeOC6H4

Bn

Ph

4-CF3C6H4

4-MeC6H4

4-MeOC6H4

26

(86)

Me

Me

Ph

4-CF3C6H4

26

(85)

Me

% ee (70)

R2

R2

Ph

THF/TMEDA, 0°, 24 h

R1

R

96

OH

82

(92)

1-Ad

2

94

(98)

BnCH2

O

72

(91)

% ee

c-C6H11

R1

R

OH

(81)

(MeO)3SiH (1 eq), Li2-histidine (10 mol%),

34, THF, 0°

o-Tol2SiH2, [Rh(cod)Cl]2 (1.0 mol%),

n-C6H13

R

O

593

586

670

C8-14

C8-13

(90) (95)

PhMe2Si Et2HSi

c-C6H11

c-C6H11

R Me Me Me Me Me Me Me Me Me Et i-Bu Bn

Ar

Ph

2-MeC6H4

4-MeC6H4

2-MeOC6H4

4-MeOC6H4

2-ClC6H4

4-ClC6H4

1-C10H7

2-C10H7

Ph

Ph

Ph

126 (1 mol%), THF, –20°

Ar

(92)

PhMe2Si

t-Bu

R

(97)

EtMe2Si

t-Bu

Ar

(93)

PhMeHSi

i-Pr

(75)

(95)

(95)

(99)

(99)

(95)

(90)

(56)

(90)

(90)

(98)

(80)

R

OH

(96)

Ph2HSi

i-Pr

Ph(1-Np)SiH2 (1.5 eq),

(98)

Ph2SiH2

Et

O

1%

94

94

94

95

98

85

98

88

95

92

95

95

ee (%)

19%

58%

54%

56%

12%

16%

42%

Opt. Yield (97)

R

R3Si

Ph

Et2HSi

C6H6, 5-50°, 3-48 h

OH

R

S

S

R

S

S

R

R

Conf.

Product(s) and Yield(s) (%)

Me

R

R3SiH, [(+)-(R)-bmpp]2RhCl,

Conditions

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

R

Ph

O

Ketone

576

785

Refs.

671

C8-14

0 0

(74) (90)

24 h 24 h

Ph Ph

4-MeC6H4

4-CF3C6H4

(50) (60) (53) (50) (61) (58)

H Cl H Me OMe H Ph

4-BrC6H4

4-BrC6H4

4-EtC6H4

4-BrC6H4

4-BrC6H4

4-i-PrC6H4

4-BrC6H4

(61)

R

Ar

R

77

(67)

24 h

Me

1-C10H7

Ar

90

(57)

24 h

Me

2,4,6-Me3C6H2

(EtO)3SiH, THF, 198, 96 h

81

(60)

24 h

i-Bu

Ph

R

65

(63)

24 h

MeO2C(CH2)2

Ph

Ar

46

(74)

24 h

Me

BnCH2

OH

66

(91)

24 h

Me

2-BrC6H4

O

S

61

75

85

78

80

84

65

83

S

S

R

R

R

R

R

% ee Conf.

—

—

S

R

S

S

R

S

Conf.

% ee (80)

6h

R2

OH

Time

R

1

Me

Li-(R)-BINOL (5 mol%), 0°

(MeO)3SiH (1 eq), Et2O:TMEDA (30:1),

Ph

R2 R2

O

R1

R1

793

572

672

C9

C8-15

Ar

CF3

Ar

t-Bu Me i-Pr t-Bu Me i-Pr t-Bu

Ph

2-C10H7

2-C10H7

2-C10H7

1-C10H7

1-C10H7

1-C10H7

O

i-Pr

Ph

O

Me

Ph

O

R

R

Ar

O

Ketone

vitride (3%), MeC6H5, rt, 24 h

(R,R)-ebpe (20 mol%),

PMHS (1.1 eq), Et2Zn (2 mol%),

MeC6H5, or THF, or MeC6H5/THF, –78°

PMHS (5 eq), CuCl, t-BuONa, 121 (0.005 mol%),

vitride (3%), MeC6H5, rt, 24 h

(R,R)-ebpe (20 mol%),

PMHS (1.1 eq), Et2Zn (2 mol%),

vitride (3%), MeC6H5, rt, 24 h

(R,R)-ebpe (20 mol%),

PMHS (1.1 eq), Et2Zn (20 mol%),

(MeO)3SiH (1.2 eq), 178, THF, 0°, 20 h

Conditions

S S S S S S —

65 82 20 22 20 —

(93) (>95) (>95) (59) (50) (0)

Ar

CF3 OH (—)

OH

S

12

(59)

I

S

42

(95)

4-MeOC6H4

3-MeOC6H4

Ar

(85) 95% ee

(—) 71% ee

Conf.

28

II

R

(93)

Ar % ee

OH

+

OH

72

73

% ee

Product(s) and Yield(s) (%)

I + II

I

R

I (—) 66% ee

Ar

OH

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

594

589

594

594

807

Refs.

673

Ph

O

II

OH

I

% ee 37 35 45 46 56 66

0° 20° 0° 20° 20° 20°

117 118 119 109 113

Ligand

Temp

I (—)

I (99) 88% ee

II (96) 95% ee

Ph

Ph

OH

116

ligand (0.5%), MeC6H5

Ph2SiH2 (1.25 eq), Rh[(NBD)Cl]2 (0.5%),

1 (1.1 mol%), THF, –40°, 24 h

[Rh(cod)2]BF4 (1 mol%),

(3-FC6H4)2SiH2 (1.5 eq),

4. TBAF, THF

3. Add ketone, 1 d

2. PMHS (5 eq)

1. 197 (4.5 eq), n-BuLi (9 eq), C6H6

93 (10 mol%), MeOH, rt, 12-14 h

PMHS, Sn(OTf)2 (10 mol%),

vitride (3%), MeC6H5, rt, 24 h

(R,R)-ebpe (20 mol%),

PMHS (1.1 eq), Et2Zn (2 mol%),

(98) 48% ee

(—) 81% ee

791

578

588

385

594

674

C9

O

S

O

O

O

Ketone

41 (0.4 mol%), THF, rt, 30 min

Ph2SiH2 (1 eq), [Rh(cod)Cl]2 (0.3 mol%),

4. TBAF, THF

3. Add ketone, 1.6 d

2. PMHS (5 eq)

1. 197 (4.5 eq), n-BuLi (9 eq), C6H6

25 (1.1 mol%), –40°, THF, 3 h

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),

126 (1 mol%), THF, –20°

Ph(1-Np)SiH2 (1.5 eq),

126 (1 mol%), THF, –20°

Ph(1-Np)SiH2 (1.5 eq),

93 (10 mol%), MeOH, rt

PMHS, Sn(OTf)2 (10 mol%),

126 (1 mol%), THF, –20°

Ph(1-Np)SiH2 (1.5 eq),

108 (1.2 mol%), 0°, 24 h

Ph2SiH2 (1.1 eq), [Rh(cod)Cl]2 (0.5 mol%),

Conditions

O

I

OH

I (68) 92% ee

I (87) 87% ee

OH

S

O OH

OH

I (90) 95% ee

I

OH

(85) 50% ee

(90) 85% ee

(90) 92% ee

(77) 12% ee

(86) 87% ee

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

787

588

577

576

576

385

576

575

Refs.

675

C9-10

Ar

O

Ph

Ph

O

O

R Me Me i-Pr i-Pr i-Pr i-Pr i-Pr i-Pr

4-MeC6H4

4-MeC6H4

Ph

Ph

Ph

Ph

Ph

Ph

R

O

OH

Ar

O

N

Bu-n

O

O

CO2Me

n-BuOH

n-BuOH

i-PrOH

EtOH

MeOH

none

i-BuNH2

MeOH

Additive

7.0

3.8

5.5

5

5

—

4

4

x

32 h

14 h

5.5 h

6h

5h

39 h

4h

3h

Time

2. PMHS (6-10 eq), additive (x eq), rt

1. PhSiH3 (0.1 eq), 198 (0.2 eq), MeOH, 60°

NaOBu-t (1 mol%), THF/MeC6H5, –50°, 10 h

PMHS (4 eq), 124 (0.05 mol%), CuCl (1 mol%),

2. PMHS, ketone, MeOH (3-7 eq), 15°

pyrrolidine, MeOH, THF, 60°

Ar

HO

(95)

(92)

(65)

(96)

(94)

(17)

(50)

(97)

R

OH

N O

Bu-n

99

—

—

99

99

90

—

97

% ee

OH

48

OH

33

(31)

4h

Ph 1. PhSiH3 (0.1 eq), 198 (2 mol%),

28

(>99)

6h

i-Pr

% ee (>99)

6h

Et

O Time

Ph

Ph

OH

1S,2R 95% ee

I

CO2Me

R

131 (2 mol%), MeC6H5, rt, 6 h

PMHS (1.2 eq), R2Zn (2 mol%),

92 (5 mol%), AgBF4 (2 mol%), THF, 0°, 1 d

Ph2SiH2 (1.3 eq), RhCl3 (1 mol%),

OH + I + II (76), I:II = 54:46

CO2Me

(68) 83% ee

(50) 96% ee b

1S,2S 92% ee

II

OH

587

590

587

788

390

676

C10

C9-13

Ph

O

Me2C=CH(CH2)2

Ph

O

O

c-C6H11

Ph

BnO

i-Pr

Ph 10 h

8h

13 h

12 h

5h

Time

4. TBAF, THF

3. Add ketone, 0.8 d

2. PMHS (5 eq)

1. 197 (4.5 eq), n-BuLi (9 eq), C6H6

THF/TMEDA, 0°, 24 h

(MeO)3SiH (1 eq), Li2-histidine (10 mol%),

THF, –20°

Ph(1-Np)SiH2 (1.5 eq), 126 (1 mol%),

1

1

0.5

1

Et

x

Ph

R

2. PMHS, ketone, MeOH (3-7 eq), 15°

1

R

pyrrolidine, MeOH, THF, 60°

1. PhSiH3 (0.1 eq), 198 (x mol%),

Conditions

I

OH

OH

>98

99

98

98

98

% ee

R

I (88) 12% ee

Ph

O

(80)

(86)

(86)

(86)

(87)

BnO

Ar

OH

(91) 28% ee

(92) 46% ee

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

4-MeC6H4 Me

Ar

Ar

O

Ketone

588

593

576

587

Refs.

677

Ph

Ph

Ph

O

O

O

Pr-i

Pr-n

R

Pr-n I

OH

65 66 66

0° 20°

118 119

MeOH, rt, 12-14 h

PMHS, Sn(OTf)2 (10 mol%), 93 (10 mol%),

I (96) 44% ee

67

0°

117

Ligand

% ee

Pr-i

Pr-i

0°

I

OH

OH

116

Ph

Ph

Ph

OH

I (87) 97% ee

Ph

Ph

OH

Temp

ligand (0.5%), MeC6H5

Ph2SiH2 (1.25 eq), Rh[(NBD)Cl]2 (0.5%),

4. TBAF, THF

3. Add ketone, 4.5 d

2. PMHS (5 eq)

1. 197 (4.5 eq), n-BuLi (9 eq), C6H6

1 (1.1 mol%), THF, –40°, 24 h

(3-FC6H4)2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1 mol%),

MeC6H5, or THF, or MeC6H5/THF, –78°

PMHS (5 eq), CuCl, t-BuONa, 121 (0.005 mol%),

92, THF, –78°

Ph(1-Np)SiH2 (4 eq), [Rh(cod)Cl]2 (1 mol%),

1 (1.1 mol%), THF, –50°, 48 h

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1 mol%),

Cl

(—)

(79) 92% ee

R

H

R (99)

(93)

(70) 59% ee

88b

89

% ee

(94) 81% ee

385

791

588

578

589

792

578

678

C10

MeO O

OMe O

Ketone

I

OH

II

43 (76) (89) (84)

2.4 4 10

MeC6H5 MeC6H5 MeC6H5

89

89

59

% ee (68)

x 2.4

THF

II

I (39) 93% ee

OH

I (80) 43% ee

I (70) 48% ee

MeO

(92) 99% ee

(89) 94% ee

Product(s) and Yield(s) (%)

(97) 92% ee

OMe OH

Solvent

44 (x mol%), solvent, 0°

Ph2SiH2 (2 eq), [Rh(cod)Cl]2 (1 mol%),

Li-(R)-BINOL (10 mol%), 0°, 24 h

(MeO)3SiH (1 eq), Et2O/TMEDA (30:1),

(–)-44 (4 mol%), MeC6H5, rt

Ph2SiH2 (2 eq), [Rh(cod)Cl]2 (1 mol%),

93 (10 mol%), MeOH, rt

PMHS, Sn(OTf)2 (10 mol%),

92, THF, –78°

Ph(1-Np)SiH2 (4 eq), [Rh(cod)Cl]2 (1 mol%),

MeC6H5, or THF, or MeC6H5/THF, –78°

PMHS (5 eq), CuCl, t-BuONa, 121 (0.005 mol%),

MeC6H5, or THF, or MeC6H5/THF, –78°

PMHS (5 eq), CuCl, t-BuONa, 121 (0.005 mol%),

Conditions

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

585

592

585

385

792

589

589

Refs.

679

C10

Ph

O OMe

2. PMHS, ketone, MeOH (3-7 eq), 15°

pyrrolidine, MeOH, THF

1. PhSiH3 (0.1 eq), 198 (2 mol%), MeOH, 60°,

(–)-34, THF, rt

MesPhSiH2, [Rh(cod)Cl]2 (2.5 mol%),

vitride (3%), MeC6H5, rt, 24 h

(R,R)-ebpe (20 mol%),

PMHS (1.1 eq), Et2Zn (2 mol%),

MeC6H5, 65°, 1 h

PhSiH3 (1.1 eq), (R)-195-2n-BuLi (5 mol%),

MeC6H5, 65°, 1 h

PhSiH3 (1.1 eq), (S)-195-2n-BuLi (5 mol%),

4. TBAF, THF

3. Add ketone, 1.6 d

2. PMHS (5 eq)

1. 197 (4.5 eq), n-BuLi (9 eq), C6H6

25 (1.1 mol%), –40°, THF, 4 h

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),

126 (1 mol%), THF, –20°

Ph(1-Np)SiH2 (1.5 eq),

106 (1.2 mol%), 0°, 42 h

Ph2SiH2 (1.1 eq), [Rh(cod)Cl]2 (0.5 mol%),

38 (0.5 mol%), Et2O, rt

Ph2SiH2 (1.5 eq), [Rh(cod)Cl]2 (0.25 mol%),

AgBF4 (0.02 mol%), THF, 0°, 2 h

Ph2SiH2 (1.6 eq), 92 (4.0 mol%),

Ph

OH

I (95) 98% ee

I (—) 64% ee

I (94) 10% ee

OMe

II (94) 10% ee

I (92) 91% ee

I (83) 84% ee

I (90) 91% ee

I (70) 80% ee

II (95) 57% ee

I (92) 99% ee

(50) 98% ee b

587

586

594

783

783

588

577

576

575

571

580

680

C11

C10

Ph

Ph

Ph

N

O

O

O

S

Bu-t

C6H13-n

O

Ketone

OH

I

OH

86

0°

119

1 (1.1 mol%), THF, –40°, 24 h

(3-FC6H4)2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1 mol%),

4. TBAF, THF

3. Add ketone, 2.5 d

2. PMHS (5 eq)

Ph

86

–5°

117

OH

OH

84

–5°

1. 197 (4.5 eq), n-BuLi (9 eq), C6H6

% ee

Temp

Bu-t

Bu-t

(97) 90% ee

Product(s) and Yield(s) (%)

(90) 89% eeb

(96) 95% ee

(10) 5% ee

(9) 5% ee

C6H13-n

OH

116

Ph

I (—)

Ph

Ph

N

S

Ligand

ligand (0.5%), MeC6H5

Ph2SiH2 (1.25 eq), Rh[(NBD)Cl]2 (0.5%),

MeC6H5, 65°, 1 h

PhSiH3 (1.1 eq), (R)-195-2n-BuLi (5 mol%),

MeC6H5, 65°, 1 h

PhSiH3 (1.1 eq), (S)-195-2n-BuLi (5 mol%),

NaOBu-t (1 mol%), MeC6H5, –50°, 4h

PMHS (4 eq), 124 (0.05 mol %) CuCl (1 mol%),

Conditions

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

578

588

791

783

783

590

Refs.

681

Ph

O

Ph

O

O

O

C6H13-n

CO2Me

1 3 3

1 3 3

123 121 123

4. TBAF, THF

3. Add ketone, 1 d

2. PhSiH3 (1.5 eq)

—

–50° 77

(88) 82% ee

(—)

—

–78°

OH

81

(—)

12 h 70

% ee (98)

Time

OH

C6H13-n

CO2Me

–50°

Ph

O

Ph

OH

Temp

1. 197 (4.5 eq), n-BuLi (9 eq), C6H6

y

Ligand x

NaOBu-t (y mol%), MeC6H5

PMHS (4 eq), ligand (0.05 mol%), CuCl (x mol%),

MeC6H5, rt, 18 h

PMHS (1.2 eq), Et2Zn (2 mol%), 131 (2 mol%),

(0)

588

590

788

682

C12

C11

O

O

N

O

O O

C6H13-n

Ketone

126 (1 mol%), THF, –20°

Ph(1-Np)SiH2 (1.5 eq),

DIOP (1.1 mol%), THF, rt, 48 h

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1 mol%),

MeC6H5, 65°, 1 h

(R) or (S)-195-2n-BuLi (5 mol%),

PhSiH3 (1.1 eq),

126 (1 mol%), THF, –20°

[Rh(cod)]SbF6 (1 mol%),

Ph(1-Np)SiH2 (1.5 eq),

87 (10 mol%), MeOH, rt

PMHS, Sn(OTf)2 (10 mol%),

THF/TMEDA, 0°, 24 h

(MeO)3SiH (1 eq), Li2-histidine (10 mol%),

123 (0.05 mol%), MeC6H5, –50°, 10 h

PMHS (4 eq), CuCl/NaOBu-t (1 mol%),

Conditions

I

HO

HO

HO

N OH

O

I (98) >99% ee

HO

HO

C6H13-n

(92) 91% ee

(0)

(90) 98% ee

(5) 33% ee

(66) 30% ee

(68) 83% ee

Product(s) and Yield(s) (%)

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

576

606

783

576

385

593

590

Refs.

683

1-Np

1-Np

Ph

O

BnO

O

O

O

O

Ph

Br

CO2Et

O

Ph

OH

OH

I

I:II 80.5:19.5 82.5:17.5 79:21 92:8 90:10 93.5:6.5

(60) (56) (84) (95) (92)

110 112 113 114 115

II

(82)

1-Np I + II

+

HO

Ph

(64) 84% ee R

(98) 44% ee

II 1S,2S 96% ee

OH

(70) 70% ee

(—) 75% ee

109

I

+

CO2Et

Br

I (94) 28% ee

1-Np

HO

1-Np

Ph

OH

I 1S,2R 99% ee

OH

BnO

O

Catalyst

0-20°, 10-15 h

Ph2SiH2 (1.2 eq), C6H6, catalyst (0.01 eq),

MeC6H5, 65°, 3 h

PhSiH3 (1.1 eq), (S)-195-2n-BuLi (5 mol%),

MeC6H5, rt, 24 h

(S,S)-ebpe (20 mol%), vitride (3%),

PMHS (1.1 eq), Et2Zn (20 mol%),

(EtO)3SiH, THF, 198, 96 h

MeOH, rt, 12-14 h

PMHS, Sn(OTf)2 (10 mol%), 87 (10 mol%),

87 (5 mol%), AgBF4 (2 mol%), THF, 0°, 1 d

Ph2SiH2 (1.3 eq), RhCl3 (1 mol%),

126 (1 mol%), THF, –20°

[Rh(cod)]SbF6 (1 mol%),

Ph(1-Np)SiH2 (1.5 eq),

I + II (92), I:II = 51:49

804

783

594

794

385

390

576

684

C13

C12

Ph

O

2-Np

1-Np

O

O

Ketone

61

20°

109

4. TBAF, THF

3. Add ketone, 2.5 d

2. PhSiH3 (1.5 eq)

1. 197 (4.5 eq), n-BuLi (9 eq), C6H6

C6H5Me, 65°, 1 h

PhSiH3 (1.1 eq), (S)-195-2n-BuLi (5 mol%),

C6H5Me, 65°, 1 h

PhSiH3 (1.1 eq), (R)-195-2n-BuLi (5 mol%),

4. TBAF, THF

3. Add ketone, 3 d

2. PMHS (5 eq)

1. 197 (4.5 eq), 2 n-BuLi, C6H6

MeC6H5, rt, 24 h

(R,R)-ebpe (20 mol%), vitride (3%), I

Ph

II OH

2-Np

OH

Product(s) and Yield(s) (%)

(88) 82% ee

(100) 25% ee

(—) 80% ee

(—)

I (100) 62% ee

I (84) 95% ee

2-Np

OH

42

20°

119 84

29

0°

20° 113 PMHS (1.1 eq), Et2Zn (20 mol%),

% ee

Temp

116

1-Np

HO

Ligand

ligand (0.5%), MeC6H5

Ph2SiH2 (1.25 eq), Rh[(NBD)Cl]2 (0.5%),

Conditions

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

588

783

783

588

594

791

Refs.

685

C16

C14-20

R2

68:32 75:25

(21) (27)

CONHNp-1 CONHNp-1

i-Bu Bn

Ph

Ph

38 (0.5 mol%), Et2O, rt

Ph2SiH2 (1.5 eq), [Rh(cod)Cl]2 (0.25 mol%),

54:46

(76)

CONHNp-1

Me

BnCH2

O

61:39

(47)

CONHPh

Et

Ph

R:S

OH

64:36

(87)

CONHPh

R

R2

R1

OH

OH

Me

3

0° to rt, 24 h

BnO

O

4-ClC6H4

R1

R3 N Cl3SiH (1.5 eq), CHO (0.1 eq), CH2Cl2,

126 (1 mol%), THF, –20°

Ph(1-Np)SiH2 (1.5 eq),

R2

O

O

R1

BnO

O

(100) 90% ee

(80) >99% ee

571

379

576

686

C22

H

O

HO

I:II 67:33 64:36

Catalyst Rh-(+)-DIOP Rh-(–)-DIOP

I (—)

H

H

7:3

Rh-(–)-DIOP

Ph2SiH2, catalyst, C6H6, 22°

7:3

Rh-(+)-DIOP

H

H

10 mol% of the catalyst was employed.

20 mol% of the catalyst was employed.

An additional 5 mol% of BINOL was added.

10 mol% of cinchonidine was added.

1-Naphthylphenylsilane was used as the reducing silane.

e

f

g

h

c

d

The configuration of the product was not determined.

The reducing agent was (EtO)3SiH.

b

OH

H

H

HO

+

H II (—)

H

II (—)

H

OH

H +

H

OH

I:II

I (—)

H

Product(s) and Yield(s) (%)

Catalyst

Ph2SiH2, catalyst, C6H6, 22°

The catalyst is S,S-[1,2-bis(tetrahydroindenyl)ethane]titanium (IV) and derivatives.

H

H

H

O

Conditions

TABLE 30. ASYMMETRIC ORGANOSILANE REDUCTION OF KETONES (Continued)

a

O

H

Ketone

OH

573

573

Refs.

687

C6-12

C6

(64) (67) (69) O

rt rt rt

1.4 2.0 3.0

CH2Cl2/MeC6H5 CH2Cl2/MeC6H5 CH2Cl2/MeC6H5

BnCH2

BnCH2

BnCH2 O

80:20 85:15

(62) (52) (52) (42) (67) (64) (65)

BnBr BrCH2CO2Et 1-bromo-3-methyl-2-butene n-BuI BnBr allyl bromide MeI

Me

Me

Me

BnCH2

BnCH2

BnCH2

BnCH2

73:27

76:24

94:6

94:6

92:8

I + II

I:II

I

+

R2 X

1

R2

Bn

O

R

1

II

R2

Product(s) and Yield(s) (%)

(42) 94% ee

R1

rt, 24 h

2. R2X, TBAT (1.2 eq), CH2Cl2/MeC6H5 (1:1),

(S)-p-Tol-BINAP, MeC6H5, 0°, 2-3 h R

(60)

50°

1.2

CH2Cl2

BnCH2

R

(62)

rt

2.0

CH2Cl2/MeC6H5

Me

1

(53)

rt

2.0

1. Ph2SiH2 (0.53 eq), CuCl (5%), NaOBu-t (5%),

(62)

rt

2.0

CH2Cl2 THF

R

Me

O

O

Me

Temp

x

Solvent-2

R

2. BnBr (x eq), TBAT (1.2 eq), temp

(S)-p-Tol-BINAP, MeC6H5, 0°, 2-3 h

1. Ph2SiH2 (0.53 eq), CuCl (5%), NaOBu-t (5%),

–78°, 24 h

t-BuONa (5 mol%) (S)-p-Tol-BINAP (5 mol%),

PMHS (1.05 eq), CuCl (5 mol%),

Conditions

TABLE 31. ASYMMETRIC ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES

R

O

O

Enone

459

459

595

Refs.

688

C8

C7

C6

O

O

O

Enone

DIOP (1.1 mol%), THF, rt, 10 h

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1 mol%),

3. Add ketone, 3 d

2. PMHS (10 eq)

1. 197 (4.5 eq), n-BuLi (9 eq), C6H6

126 (1 mol%), THF, –20°

[Rh(cod)]SbF6 (1 mol%),

Ph(1-Np)SiH2 (1.5 eq),

25 (1.1 mol%), –40°, THF, 4 h

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),

124 (0.1-0.5 mol%), MeC6H5, 0°, 4.5 h

PMHS (2 eq), (Ph3P)CuH (1 mol%),

–78°, 24 h

t-BuONa (5 mol%), (S)-BIPHEMP (5 mol%),

PMHS (1.05 eq), CuCl (5 mol%),

(R)-38 (0.5 mol%), Et2O, 0°, 15 h

Ph2SiH2 (1.5 eq), [Ir(cod)Cl]2 (0.25 mol%),

Conditions

I

OH

I (71) 95% ee

I (70) 85% ee

(71) 95% ee

(96) 90% ee

(61) 92% ee

(100) 84% eea

I (85) 91% ee

O

O

OH

Product(s) and Yield(s) (%)

TABLE 31. ASYMMETRIC ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued)

606

588

576

577

597

595

582

Refs.

689

C9

O

O

O

Bu-n

O

CO2Me

O

95 98

dioxane/THF

0°, 12 h

t-BuONa (5 mol%), (S)-p-Tol-BINAP (5 mol%),

PMHS (1.05 eq), CuCl (5 mol%),

0°, 24 h

t-BuONa (5 mol%), (S)-p-Tol-BINAP (5 mol%),

PMHS (1.05 eq), CuCl (5 mol%),

124 (0.1-0.5 mol%), MeC6H5, –78°, 18 h

PMHS (2 eq), (Ph3P)CuH (1 mol%),

92

THF

O

O

O

90

MeC6H5

Bu-n

% ee

I I (>90)

O

CH2Cl2

124 (0.1-0.5 mol%), 0°, 6 h Solvent

PMHS (1 eq), (Ph3P)CuH (1 mol%),

124 (0.00036 mol%), MeC6H5, –35°, 3 d

PMHS (2 eq), (Ph3P)CuH (1 mol%),

(S)-p-Tol-BINAP (5 mol%), 0°, 3 d

t-BuONa (5 mol%),

PMHS (1.05 eq), CuCl (5 mol%),

(86) 92% ee

(84) 98% ee

CO2Me

CO2Me

(94) 97% ee

(88) 98.5% ee

(88) 94% ee

595

595

597

597

597

595

690

C11

C10

O

Ph

O

O

O

Bu-n

C5H11-n

Enone

15°, 24 h

t-BuONa (5 mol%), (S)-BINAP (5 mol%),

PMHS (1.05 eq), CuCl (5 mol%),

THF/TMEDA, 0°, 24 h

(MeO)3SiH (1 eq), Li2-histidine (10 mol%),

THF/TMEDA, 0°, 24 h

(MeO)3SiH (1 eq), Li2-histidine (10 mol%),

Li-(R)-BINOL (10 mol%), 0°, 24 h

(MeO)3SiH (1 eq), Et2O/TMEDA (30:1),

–78°, 2 d

t-BuONa (5 mol%), (S)-p-Tol-BINAP (5 mol%),

PMHS (1.05 eq), CuCl (5 mol%),

25 (1.1 mol%), THF, –40°, 4 h

Ph2SiH2 (1.5 eq), [Rh(cod)2]BF4 (1.0 mol%),

2. PMHS, ketone, MeOH (3-7 eq), 15°, 4 h

pyrrolidine, MeOH, THF, 60°

1. PhSiH3 (0.1 eq), 198 (2 mol%),

Conditions

O

Ph

Ph

Ph

O

OH

OH

OH

OH

OH

Bu-n

C5H11-n

C5H11-n

(87) 96% ee

(78) 70% ee

(91) 28% ee

(91) 57% ee

(82) 87% ee

(84) 87% ee

(90) 84% ee

Product(s) and Yield(s) (%)

TABLE 31. ASYMMETRIC ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued)

595

593

593

592

595

597

587

Refs.

691

C13

C12

O

O

O

O

O

Bn O

vitride (3%), MeC6H5, rt, 24 h

(R,R)-ebpe (20 mol%),

PMHS (1.1 eq), Et2Zn (20 mol%),

(S)-p-Tol-BINAP (5 mol%), 0°, 24 h

t-BuONa (5 mol%),

PMHS (1.05 eq), CuCl (5 mol%),

then TBAF

(S)-p-Tol-BINAP (10 mol%), MeC6H5;

PMHS (1.1 eq), CuCl/NaOBu-t,

124 (0.1-0.5 mol%), MeC6H5, 0°, 6 h

PMHS (2 eq), (Ph3P)CuH (1 mol%),

+

O

Bn OH

Ph

(—)

(—) 18% ee

(86) 94% ee

O

(90) 96% ee

(92) 97.3% ee

(97) 97.5% ee

(78) 96% ee

Ph 45% conv., 71.6% ee

O

Bn

C7H13-n

O

O

Bn

Bn

124 (0.1-0.5 mol%), MeC6H5, –78°, 36 h

PMHS (2 eq), (Ph3P)CuH (1 mol%),

124 (0.4 mol%), MeC6H5, –78°

NaOMe (0.5 mol%),

PMHS (2 eq), CuCl (1 mol%),

O

O

O

Ph

C7H13-n

Bn

(S)-p-Tol-BINAP (5 mol%), 0°, 24 h

t-BuONa (5 mol%),

PMHS (1.05 eq), CuCl (5 mol%),

+

O

Ph

(—)

594

595

596

597

597

597

595

692

C14-19

R2 I + II (89) (94) (94) (91) (95) (90)

Temp –50° –30° 0° –50° –50° –50°

BnCH2 BnCH2 BnCH2 BnCH2 i-Pr Ph

Me

i-Pr

t-Bu

t-BuO2CCH2

Bn

Me

I R2

R1

MeC6H5, temp, 26 h; then TBAF

t-BuONa (1.7 eq), t-BuOH (5.0 eq),

96.5:3.5

91.5:8.5

90:10

93.5:6.5

93:7

91:9

I:II

+

56.0

–50°

CH2CO2Bu-t

R2

50.7

0°

t-Bu

R1

53.2

–78°

n-Bu

PMHS (2.2 eq), CuCl/(S)-p-Tol-BINAP (10 mol%),

56.5

0°

O

55.6

–78°

i-Pr

Ph

R

Me

O

I

+

% Conv. I

R1

R

O

91

93

93

94

93

91

% ee I

II

O

95.3

91.0

90.6

97.4

94.6

% ee

O

R2

Ph

(—)

R +

Product(s) and Yield(s) (%)

Temp

Ph

MeC6H5, temp; then TBAF

(S)-p-Tol-BINAP (10 mol%),

PMHS (1.1 eq), CuCl/NaOBu-t,

Conditions

TABLE 31. ASYMMETRIC ORGANOSILANE REDUCTION OF α,β−UNSATURATED KETONES (Continued)

R

R1

R

O

Enone O

Ph

(—)

596

596

Refs.

693

C16

C15

a

O

O

Bn

Pr-i

Ph

OBn

The product is the (–) enantiomer.

O

Bn

O

124 (0.1-0.5 mol%), MeC6H5, –35°, 16 h

PMHS (2 eq), (Ph3P)CuH (1 mol%),

0°, 24 h

t-BuONa (5 mol%), (S)-p-Tol-BINAP (5 mol%),

PMHS (1.05 eq), CuCl (5 mol%),

(S)-BINAP (5 mol%), –78°, 4 d

t-BuONa (5 mol%),

PMHS (1.05 eq), CuCl (5 mol%),

MeC6H5; then TBAF

(S)-p-Tol-BINAP (10 mol%),

PMHS (1.1 eq), CuCl/NaOBu-t, +

Bn

O

O

O

Bn

O

Ph

(91) 94% ee

(95) 99.5% ee

OBn

+ (—) Pr-i

(82) 96% ee

Pr-i 56% conv., 95.6% ee

Bn

O Bn

O

Pr-i

(—)

597

595

595

596

694

C4

O

+

+

OMe Ph

PMBO

BnO

+

Ester

O

O

O

H

H

H

90 98 98 98

[Ir(cod)Cl]2 [Ir(cod)Cl]2 [Ir(coe)2Cl]2 Ir(cod)BF4

2. H3O+

98 (7.5 mol%), rt, 24 h

1. Et2MeSiH, [Ir(cod)Cl]2 (2.5 mol%),

2. H3O+

98 (7.5 mol %), rt, 24 h

1. Et2MeSiH, [Ir(cod)Cl]2 (2.5 mol%),

98

88

[Ir(cod)Cl]2

[Rh(cod)Cl]2

87

[Ir(cod)Cl]2

98

86

[Ir(cod)Cl]2

(CO)2Ir(acac)

Ligand

Catalyst

2. H3O+

ligand (7.5 mol%), CH2Cl2, rt, 24 h

1.Et2MeSiH , catalyst (5 mol%),

Conditions

PMBO

BnO

Ph

OH

I

O OMe

2.0:1

4.0:1

4.0:1

4.4:1

3.9:1

1.5:1

2.0:1

+

10

82

86

94

92

70

80

0

II

O

BnO

50

1:1.3

% ee I

I:II

Ph

OH

OH

OMe

I

OMe

+ PMBO

OH

I + II (76), I:II = 6:1, er I > 95:5

O

I III I + II (59), I:II = 9.5:1, er I = 98:2 OH

OH

(9)

(56)

(35)

(53)

(48)

(30)

(32)

(46)

( 95:5, (I + II):III + IV > 95:5 OH

+

OBn

OH

601

601

601

696

C5

C4-9

C4

OEt 2. H3O+

Ph

O OEt

OMe

+

Ph

OH

2R,3R

—

2R,3R

O OEt

34

38

88

—

—

2R,3S

Conf. syn % ee anti Conf. anti

I II I + II (68), I:II = 6.6:1, 94% ee I

OH

87

3.4:1 (72)

Ph

98 (7.5 mol%), CH2Cl2, rt, 45 h

58

O

II

O

+ anti diastereomer

syn:anti % ee syn

OR

1.4:1

H

Ph

(21)

1. Et2MeSiH, [Ir(coe)2Cl]2 (5 mol%),

2. H3O+

t-Bu

O

H

(R)-BINAP (6.5 mol%), CH2Cl2, rt, 24 h

—

82

—

96

96

96

91

Ph

Ph

—

(0)

(E)-PhCH=CH

O

2.7:1

(65)

BnOCH2CH2

OH

—

(99

48

7

34

% ee anti

+ anti diastereomer

(90) syn:anti = 3:1, 75% ee syn

(54) syn:anti = 6:1, 71% ee syn

(86) syn:anti = 6:1, 83% ee syn

Product(s) and Yield(s) (%)

% ee syn

OPh

3.4:1

Et2MeSiH (1.75 eq),

R

O

OH

OH

OH

syn:anti

(R)-BINAP (6.5 mol%), CH2Cl2, rt, 24 h

[Rh(cod)Cl]2 (2.5 mol%),

O

O

OH

PhO

PhO

PhO

O

Ph

H

Et2MeSiH (1.2 eq),

{Rh(cod)[(R)-BINAP)]}BF4 (5 mol%), rt, 12 h

Et2MeSiH (1.75 eq),

rt, 12 h

{Rh(cod)[(R)-BINAP)]}BF4 (5 mol%),

Et2MeSiH (1.75 eq),

rt, 12 h

{Rh(cod)[(R)-BINAP)]}BF4 (5 mol%),

Et2MeSiH (1.75 eq),

R

O

O

O

O

Conditions

TABLE 32. ASYMMETRIC ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued) Ester

470

470

603

470

470

470

Refs.

699

C11

O

O

n-Bu

O

O

Bn

O OEt

OPh

Ph

O +

O H

4h 3h

–40°

CuCl2•2H2O MeC6H5/C5H12/i-PrOH –20°

PMHS

THF/C5H12/EtOH

CuCl

5 min

rt

PMHS

24 h

–15°

C6H12/EtOH

48 h

CuCl

Time rt

(90)

(90)

(89)

(34)

(50)

(80) 95% ee

Temp

OEt

PMHS

MeC6H5

Additive

Bn

O

Ph

92

93

—

91

80

% ee

(52) syn:anti = 3.9:1, 88% ee syn

(96) 99% ee

DEE/C5H12

CuCl

PMHS

O

O

n-Bu

O

O

PhO

OH

Ph2SiH2 CuCl

Cu Salt

Silane

(S)-p-Tol-BINAP (5 mol%)

NaOBu-t (5-20 mol%), additive,

Silane (4 eq), Cu salt (5 mol%),

MeC6H5, 0°

124 (7.3 mol%), t-BuOH (1.13 eq),

PMHS (2 eq), (Ph3P)CuH (7.3 mol%),

124 (0.1 mol%), t-BuOH (1.1 eq), rt, 1 h

PMHS (2 eq), (Ph3P)CuH (0.5 mol%),

(S)-BINAP (6.5 mol%), rt, 48 h

Et2MeSiH (5 eq), [Rh(cod)Cl]2 (5 mol%),

O

599

598

598

470

700

C12

C11

Ph

O

O

O

CO2Et

CO2Et

OPh

+

O H

MeC6H5, rt, 24 h

(S)-p-Tol-BINAP (10 mol%),

NaOBu-t (5 mol %),

PMHS (4 eq) CuCl (5 mol%),

MeC6H5, 0°

124 (7.3 mol%), t-BuOH (1.13 eq),

PMHS (2 eq), (Ph3P)CuH (7.3 mol%),

MeC6H5, 0°

124 (7.3 mol%), t-BuOH (1.13 eq),

PMHS (2 eq), (Ph3P)CuH (7.3 mol%),

(S)-p-Tol-BINAP (0.1 mol%), C6H12, rt

NaOBu-t (0.2 mol%), t-AmOH,

PMHS (4 eq), CuCl2 (0.1 mol%),

t-BuOH, rt, 1 h

PMHS, CuH, 124 (0.2-0.4 mol%),

(S)-BINAP (6.5 mol%), rt, 48 h

Et2MeSiH (5 eq), [Rh(cod)Cl]2 (5 mol%),

Conditions

O

I

CO2Et

CO2Et

OH

I (84) 90% ee

I (94) 91% ee

I (92) 98% ee

Ph

O

PhO

O

(95) 86% ee

(91) 98% ee

(0)

Product(s) and Yield(s) (%)

TABLE 32. ASYMMETRIC ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued) Ester

600

598

598

599

598

470

Refs.

701

C14

C13

Ph

Ph

R

O

OEt

OEt

OEt

O

O

+

O

O

OPh

OEt

O H

t-BuOH, 0°, 1 h

PMHS, CuH, 124 (0.2-0.4 mol%),

MeC6H5, 0°

124 (7.3 mol%), t-BuOH (1.13 eq),

PMHS (2 eq), (Ph3P)CuH (7.3 mol%),

(S)-BINAP (6.5 mol%), rt, 48 h

Et2MeSiH (5 eq), [Rh(cod)Cl]2 (5 mol%),

MeC6H5, rt, 25 h

(S)-p-Tol-BINAP (10 mol%),

NaOBu-t (5 mol%),

PMHS (4 eq), CuCl (5 mol%),

t-BuOH, 0°, 1 h

PMHS, CuH, 124 (0.2-0.4 mol%),

MeC6H5, rt

(S)-p-Tol-BINAP (10 mol%),

NaOBu-t (5 mol%),

PMHS (4 eq) CuCl (5 mol%),

MeC6H5, rt, 25 h

(S)-p-Tol-BINAP (10 mol%),

NaOBu-t (5 mol%),

PMHS (4 eq) CuCl (5 mol%),

Ph

PhO

Ph

R

O

Ph

O

Ph

O

OEt

OH

OEt

OEt

OEt

OEt O

O

O 22 h

24 h

Time

(97) 99% ee

(97) 99% ee

92

81

% ee

— % ee syn

(30) syn:anti = 4.4:1,

(89)

(94)

(90) 85% ee

(90) 95% ee

c-C6H11

n-C6H13

R

OEt

(98) 91% ee

O

598

598

470

600

598

600

600

702

C15

C14

Ph

Ph

Ph

Ph

O

O

OEt

OEt

OEt

O

OEt

O

t-BuOH, rt, 1 h

PMHS, CuH, 124 (0.2-0.4 mol%),

t-BuOH, rt, 1 h

PMHS, CuH, 124 (0.2-0.4 mol%),

MeC6H5, rt, 18 h

(S)-p-Tol-BINAP (10 mol%),

NaOBu-t (5 mol%),

PMHS (4 eq), CuCl (5 mol%),

MeC6H5, rt, 20 h

(S)-p-Tol-BINAP (10 mol%),

NaOBu-t (5 mol%),

PMHS (4 eq), CuCl (5 mol%),

MeC6H5, 0°

124 (7.3 mol%), t-BuOH (1.13 eq),

PMHS (2 eq), (Ph3P)CuH (7.3 mol%),

MeC6H5, 0°

124 (7.3 mol%), t-BuOH (1.13 eq),

PMHS (2 eq), (Ph3P)CuH (7.3 mol%),

t-BuOH, 0°, 1 h

PMHS, CuH, 124 (0.2-0.4 mol%),

Conditions

II

I O

O

Ph

Ph

I (96) 83% ee

II (95) 84% ee

II (98) 99% ee

Ph

Ph

O

O

OEt

OEt

OEt

OEt

(94) 98% ee

(93) 99% ee

(96) 90% ee

(98) 99% ee

Product(s) and Yield(s) (%)

TABLE 32. ASYMMETRIC ORGANOSILANE REDUCTION OF α,β−UNSATURATED ESTERS (Continued) Ester

598

598

600

600

598

598

598

Refs.

703

C15-18

R

88 88 93

3.8:1 3.9:1

(53) (49)

Ph(CH2)3

R

TBSO(CH2)3

PhO

% ee syn

(S)-BINAP (6.5 mol%), rt, 48 h

[Rh(cod)Cl]2 (5 mol%),

OH

4.2:1

H

O

syn:anti

+

Et2MeSiH (5 eq),

(54)

OPh

O

n-C6H13

R

O 470

704

C18

C15

C12

PMPN

PMPN

PMPN

PMPN

O

O

O

O

Bu-n

Pr-n

Lactam

F

C6H5F, air, rt, 3 h

t-AmOH (16 eq), (R)-p-Tol-BINAP (0.5 mol%),

NaOBu-t (5 mol%),

PMHS (16 eq), CuCl2•2 H2O (2.5 mol%),

MeC6H5/C5H12, 0°, 3 h

t-AmOH, (S)-p-Tol-BINAP (20 mol%),

PMHS (4 eq), CuCl2•2 H2O (5 mol%), NaOBu-t (20 mol%),

MeC6H5/C5H12, 0°, 3 h

t-AmOH, (S)-p-Tol-BINAP (20 mol%),

PMHS (4 eq), CuCl2•2 H2O (5 mol%), NaOBu-t (20 mol%),

MeC6H5/C5H12, rt, 1 h

t-AmOH, (S)-p-Tol-BINAP (5 mol%),

PMHS (4 eq), CuCl2•2 H2O (0.1 mol%), NaOBu-t (20 mol%),

Conditions

PMPN

PMPN

PMPN

PMPN

O

O

O

O

Bu-n

Pr-n

F

(89) 90% ee

(94) 94% ee

(89) 91% ee

(90) 92% ee

Product(s) and Yield(s) (%)

TABLE 33. ASYMMETRIC ORGANOSILANE REDUCTION OF α,β−UNSATURATED LACTAMS

599

599

599

599

Refs.

705

C9

C8

Ph

N

N

Me

Pr-n

Imine

Et2O, 0°, 48 h

[Ir(cod)Cl]2 (10 mol%),

Ph2SiH2 (2 eq), 38 (10 mol%),

Et2O, 0°, 60 h

[Ir(cod)Cl]2 (10 mol%),

Ph2SiH2 (2 eq), 38 (10 mol%),

MeC6H5, 0°, 90 h

[(Ph3P)RuCl2]2 (10 mol%),

Ph2SiH2 (2 eq), 38 (10 mol%),

I (24) 16% ee

I (56) 89% ee

I (51) 73% ee

605

605

605

610

35°, 12 h

610

I (94) 97% ee I (95) 99% ee

PhSiH3 (4.5 eq), 198 (1 mol%), rt, 12 h

612

PhSiH3 (4.5 eq), 198 (0.02 mol%),

(100) 97% ee

611

611

612

I

(82) 99% ee

(80) 99% ee

Refs.

I (50) —% ee

Ph

Pr-n

Pr-n

NHMe

Boc

N

Boc

N

Product(s) and Yield(s) (%)

PMHS (10 eq), 198 (10 mol%), rt, 48 h

PhSiH3 (4 eq), 198 (1 mol%), rt, 12 h

2. (t-BuO2C)2O

MeOH (0.1 eq), THF, rt, 6 h

pyrrolidine (0.1 eq),

1. PhSiH3 (2 eq), S,S-198 (1 mol%),

2. (t-BuO2C)2O

MeOH (0.1 eq), THF, rt, 6 h

pyrrolidine (0.1 eq),

1. PhSiH3 (2 eq), R,R-198 (1 mol%),

Conditions

TABLE 34. ASYMMETRIC ORGANOSILANE REDUCTION OF IMINES

706

C10

C9

O

Ph

R

N

O

N

Me

N

N

N

Imine

H2 (80 psig), 45°, 23 h

PhSiH3 (2.5-3 eq), 198,

H2 (80 psig), 50°, 23 h

PhSiH3 (2.5-3 eq), 198,

H2 (80 psig), 65°, 16 h

PhSiH3 (2.5-3 eq), 198,

H2 (80 psig), 65°, 7 h

PhSiH3 (2.5-3 eq), 198,

198 (0.1 mol%), 35°, 12 h

PhSiH3 (4.5 eq),

35°, 12 h

PhSiH3 (4.5 eq), 198 (x mol%),

Conditions

O

Ph

Ph

R

O

N H

N H

NHMe

x 0.1

N H

N H

N H

(86) 99% ee

98

92

% ee

(72) 99% ee

(79) 99% ee

(82) 99% ee

(87)

0.02 (96)

(96) 98% ee

4-ClC6H4

c-C6H11

R

Product(s) and Yield(s) (%)

TABLE 34. ASYMMETRIC ORGANOSILANE REDUCTION OF IMINES (Continued)

613

613

613

613

610

610

Refs.

707

N

Ph

34

20 h

[Rh(cod)Cl]2

I

85

(75)

20 h

[Ir(cod)Cl]2

85

32 86

(>95) (75) (78) trace (>95) (17) (>95)

20 h 60 h 20 h 50 h 50 h 30 h 30 h 40 h

37 37 37 35 36 38 38 41

[Ir(cod)Cl]2 [Ir(cod)Cl]2 [Rh(cod)Cl]2 [Ir(cod)Cl]2 [Ir(cod)Cl]2 [Ir(cod)Cl]2 [Rh(cod)Cl]2 [Ir(cod)Cl]2

71

—

88

34

88

% ee (>95)

Time

Ligand

Metal Complex

ligand (5 mol%), Et2O, 0°

metal complex (10 mol%),

Ph2SiH2 (2 eq),

88

(>95)

40 h

% ee (60)

Time

I

Ph

(Ph3P)RuCl2

N H

Metal Complex

MeC6H5, 0°

metal complex (10 mol%),

Ph2SiH2 (2 eq), 38 (10 mol%),

605

605

708

C11

C10-13

2.2 2.2 2.0 2.0 2.24 2.24

Ph

Ph

4-BrC6H4 a

2-MeOC6H4

3,4-(MeO)2C6H3

3,4-(MeO)2C6H3 a

Ph

N

Ph

N

Me

0-20°

0-20° 72 h

20 h

48 h

0-20°

30 h

0-20° 48 h

69 h

0°

0-20°

32 h

0-20°

24 h

32 h

0-20°

0-20°

Time

Temp

H2 (500 psig), 65°, 24 h

PhSiH3 (2.5-3 eq), 198,

Et2O, 0°, 100 h

[Ir(cod)Cl]2 (10 mol%),

Ph2SiH2 (2 eq), 38 (10 mol%),

MeC6H5, 0°, 50 h

(Ph3P)RuCl2 (10 mol%),

Ph2SiH2 (2 eq), 38 (10 mol%),

PhSiH3 (4.5 eq), 198 (1 mol%), rt, 12 h

PhSiH3 (4.5 eq), 198 (1 mol%), rt, 12 h

2.0

2.6

Ph

3,4,5-(MeO)3C6H2 Me N

2.2

Ph

2. (CF3CO)2O x

N

(–)-DIOP (x mol%)

1. Ph2SiH2 (2 eq), [Rh(cod)Cl]2 (2 mol%),

Conditions

N H

CF3

I

O

Ph

I (78) 98% ee

31

33

33

31

60

64

61

59

59

(80) 96% ee

(91) 97% ee

(81)

(89)

(87)

(85)

(82)

(84)

(84)

(83)

(85)

H

Ar

% ee

+

(10) 25% ee

NHMe

NHMe

N

I (18) 7% ee

Ph

H

Ar

R

S

R

R

R

R

R

R

R

Conf.

N CF3

O

Product(s) and Yield(s) (%)

TABLE 34. ASYMMETRIC ORGANOSILANE REDUCTION OF IMINES (Continued)

Ar

Ar

Imine

613

605

605

610

610

606

Refs.

709

C12

Ph

MeO

MeO

Cl

HO

N

7

N N

N

E:Z = 20:1

E:Z = 15:1

Pr-n

H2 (80 psig), 65°, 30 h

PhSiH3 (2.5-3 eq), 198,

65°, 50 h

PhSiH3 (2.5-3 eq), 198, H2 (80 psig),

(+)-DIOP, C6H6, 1°

Ph2SiH2 (2 eq), [Rh(C2H4)2]2 (2 mol%),

i-BuNH2 (1.5 eq), 65°, 2.5 h

PhSiH3 (9 eq), 198 (0.05 mol%),

s-BuNH2 (1.5 eq), 65°, 2.5 h

PhSiH3 (9 eq), 198 (2 mol%),

i-BuNH2 (1.5 eq), 65°, 2.5 h

PMHS (9 eq), 198 (0.5 mol%),

H2 (500 psig), 65°, 8 h

PhSiH3 (1.1 eq), 198, 7

HN

N H

Ph

N

I (79) 9% ee

MeO

MeO

I

I (95) 98% ee

I (73) 93% ee

Cl

HO

I

(93) 5.7% ee

(95) 98% ee

(74) 97% ee

NH

Pr-n

(84) 99% ee

613

613

607

612

612

612

613

710

C13

C12-18

R1

N

N

N

R2

(50) (62) (57) (96) (36) (46) (43) (69) (50)

CHCl3 CH2Cl2 CHCl3 CHCl3 CH2Cl2 CHCl3 CHCl3 CH2Cl2 CHCl3

c-C6H11 Ph Ph 4-MeOC6H4 2-MeOC6H4 Bn Ph Ph Ph

Ph 4-MeOC6H4 4-MeOC6H4 Ph Ph Ph 4-CF3C6H4 2-C10H7 2-C10H7

PMP

3. i-BuNH2, slow addition, 60°

2. Add imine

1. PMHS, 198

H2 (80 psig), 50°, 27 h

4

87

80

87

8

22

85

80

76