Metallocenes in Regio- and Stereoselective Synthesis [Topics in Organometallic Chem. vol.8 ed.] 9783540016069, 3540016066

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Volume Editor Professor Tamotsu Takahashi Catalysis Research Center Hokkaido University Kita 21, Nishi 10, Kita-ku Sapporo 001-0021 Japan [email protected]

Editorial Board Prof. John M. Brown

Prof. Pierre H. Dixneuf

Dyson Perrins Laboratory South Parks Road Oxford OX1 3QY [email protected]

Campus de Beaulieu Université de Rennes 1 Av. du Gl Leclerc 35042 Rennes Cedex, France [email protected]

Prof. Alois Fürstner

Prof. Louis S. Hegedus

Max-Planck-Institut für Kohlenforschung Kaiser-Wilhelm-Platz 1 45470 Mühlheim an der Ruhr, Germany [email protected]

Department of Chemistry Colorado State University Fort Collins, Colorado 80523-1872, USA hegedus@lamar. colostate.edu

Prof. Peter Hofmann

Prof. Paul Knochel

Organisch-Chemisches Institut Universität Heidelberg Im Neuenheimer Feld 270 69120 Heidelberg, Germany [email protected]

Fachbereich Chemie Ludwig-Maximilians-Universität Butenandstr. 5–13 Gebäuse F 81377 München, Germany [email protected]

Prof. Gerard van Koten

Prof. Shinji Murai

Department of Metal-Mediated Synthesis Debye Research Institute Utrecht University Padualaan 8 3584 CA Utrecht, The Netherlands [email protected]

Faculty of Engineering Department of Applied Chemistry Osaka University Yamadaoka 2-1, Suita-shi Osaka 565, Japan [email protected]

Prof. Manfred Reetz Max-Planck-Institut für Kohlenforschung Kaiser-Wilhelm-Platz 1 45470 Mülheim an der Ruhr, Germany [email protected]

Preface

“Metallocenes” have been used for complexes which have sandwich structures with two cyclopentadienyl ligands since the discovery of ferrocene. Recently metal complexes having one cyclopentadienyl ligand have also been classified as a member of metallocene derivatives. One important discovery in this area is the olefin polymerization catalyzed by metallocene complexes of early transition metals such as zirconium and titanium. In particular, the structure of the metallocene catalyst has a remarkable effect on the structure of the polymers. This discovery has had a strong impact on the industry. The area of organic synthesis using metallocenes of early transition metals has been lagging behind synthesis using late transition metals. Many of the reactions have been stoichiometric for some time. Among them hydrozirconation of unsaturated compounds has been widely used. In the last two decades, however, a lot of catalytic reactions including asymmetric synthesis have been developed. Now this area has become quite attractive for many researchers in organic synthesis. This book is presented as a volume of Topics in Organometallic Chemistry, aiming at giving an overview of the chemistry of metallocenes. In particular, in this book we focused on, (i) hydrozirconation and its application to natural product synthesis, (ii) the asymmetric carboalumination reaction, (iii) the cyclization reaction using metallocenes, (iv) catalytic reactions using metallocenes, (v) olefin polymerization and (vi) carbon-carbon bond cleavage reactions using metallocenes. I would like to express my thanks to all contributors to this book. Sapporo, April 2004

Tamotsu Takahashi

Preface

Contents

Hydrozirconation and Its Applications P. Wipf · C. Kendall . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1

Construction of Carbocycles via Zirconacycles and Titanacycles Z. Xi · Z. Li . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Metallocene-Catalyzed Selective Reactions M. Kotora . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 Diastereoselective, Enantioselective, and Regioselective Carboalumination Reactions Catalyzed by Zirconocene Derivatives E. Negishi · Z. Tan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139 Stereospecific Olefin Polymerization Catalyzed by Metallocene Complexes N. Suzuki . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177 Carbon-Carbon Bond Cleavage Reaction Using Metallocenes T. Takahashi · K. Kanno . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217 Author Index Volumes 1–8 . . . . . . . . . . . . . . . . . . . . . . . . . . 237 Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241

Topics Organomet Chem (2004) 8: 1– 25 DOI 10.1007/b13144 © Springer-Verlag Berlin Heidelberg 2004

Hydrozirconation and Its Applications Peter Wipf (

) · Christopher Kendall

University of Pittsburgh, Department of Chemistry, Pittsburgh PA 15260, USA [email protected]

1

Introduction and Scope

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2

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Preparation of Cp2ZrHCl and Related Reagents . . . . . . . . . . . . . . . .

3

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Functional Group Compatibility of Hydrozirconation . . . . . . . . . . . .

4

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Alternative Methods for Generating Organozirconocenes . . . . . . . . . .

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Hydrozirconation Followed by Halogenation . . . . . . . . . . . . . . . . .

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6

Hydrogenation and Reduction . . . . . . . . . . . . . . . . . . . . . . . . .

7

7

Hydrozirconation Followed by C–C Bond Formation

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7.1 7.2 7.2.1 7.2.2 7.2.3

Silver-Catalyzed Ligand Abstraction . . . . . . . . Transmetalation . . . . . . . . . . . . . . . . . . . Zirconium Æ Palladium and Zirconium Æ Nickel Zirconium Æ Zinc . . . . . . . . . . . . . . . . . Zirconium Æ Copper . . . . . . . . . . . . . . . .

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10 12 12 15 17

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Miscellaneous Reactions of Organozirconocenes . . . . . . . . . . . . . . .

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Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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References

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Abstract Next to hydroboration and hydrostannylation, hydrozirconation is among the few general methods available for the stoichiometric conversion of readily available alkenes and alkynes into stable, strongly nucleophilic synthetic intermediates. More significantly, the sterically shielded carbon–zirconium bond of organozirconocenes can participate in transmetalation schemes that link zirconium chemistry with many other elements in the periodic table, in particular with the highly functional group tolerant late transition metals. The in situ conversion of alkenes and alkynes into chain-extended synthetic building blocks by sequential hydrozirconation and further metal-catalyzed or metal-mediated condensations with electrophiles is thus characterized by experimental convenience and considerable strategic flexibility. In addition, the number of synthetic protocols that use organozirconocenes directly for intra- or intermolecular carbon–carbon and carbon–heteroatom bond formations is steadily increasing. As an extension of our comprehensive treatment of the topic in 1996, this review concentrates on the developments in hydrozirconation and its applications in synthesis from 1996 through mid-2002. Keywords Zirconocenes · Transmetalation · Cationic complexes · Alkenes · Alkynes

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1 Introduction and Scope The hydrozirconation of alkenes and alkynes with Cp2ZrHCl, a.k.a. Schwartz reagent [1], is one of two common methods for forming organozirconocenes (Scheme 1). According to the Pauling electronegativity scale, the ionic character of the C–Zr bond (26%) is almost equivalent to the C–Mg bond (27%), but organozirconocene complexes are intrinsically considerably weaker nucleophiles than Grignard reagents due to steric shielding at the metal atom by the two cyclopentadienyl ligands.While the preparations of Grignard and organolithium reagents mainly originate from the corresponding halides, the opportunity to use the more readily available, synthetically versatile alkenes and alkynes as starting materials is a great asset of zirconocene chemistry. Subsequent activation of the C–Zr bond by addition of catalytic or stoichiometric metal salts benefits from the ease of formation of bridged bimetallic complexes of early transition metals such as zirconium and the broad functional group compatibility and extraordinary synthetic utility of late transition metals. Figure 1 illustrates the ability of zirconocene to participate in mixed-metallic complex formation, often assisted by bridging chloride or oxygen atoms [2, 3].

Scheme 1 Formation of alkyl- and alkenylzirconium reagents by the hydrozirconation of alkenes and alkynes

Organozirconocene complexes can also be activated by ligand substitution or abstraction. In addition, small electrophiles such as halogens, dioxygen, protons, and isonitriles can be directly added to the Zr–C bond. This review will present a survey of many recent examples of hydrozirconation in organic synthesis, mostly focusing on material published since our last comprehensive review [4] on this subject [5–7]. The majority of examples for synthetic applications utilize alkenylzirconocenes, since the reaction of Cp2ZrHCl with alkynes is fast, regioselective, and quite functional group tolerant. Alkenes are not as reactive as alkynes, and furthermore internal alkenes are rapidly isomerized into terminal alkylzirconocenes [8–10], thus limiting the usefulness of this transformation. Some recent reactions of alkylzirconocenes are also covered. Cp2ZrHCl was first prepared in 1970 [11] and used to hydrozirconate alkenes [12] and alkynes [13] by Wailes and coworkers. Subseqently, Schwartz and coworkers treated the resulting alkylzirconocene [14] and alkenylzirconocene

Hydrozirconation and Its Applications

3

Fig. 1 Crystal structures of two zirconocene complexes with heteroatoms and carbon bridges to alanes

[15] products with inorganic electrophiles and used transmetalation from Zr to Al in order to increase reactivity towards organic electrophiles [16]. Due to these pioneering synthetic applications, Cp2ZrHCl is commonly referred to as “Schwartz reagent”.

2 Preparation of Cp2ZrHCl and Related Reagents The commercially available reagent is typically prepared by reduction of Cp2ZrCl2 with an aluminum hydride. Wailes and Weigold originally used one equivalent of LiAl(Ot-Bu)3H as the reducing agent in THF [11]. The insoluble zirconocene hydrochloride was isolated in 90% yield. The more practical LiAlH4 was at first not recommended as a reducing agent since it could lead to formation of significant quantities of Cp2ZrH2, a much more insoluble (and thus less reactive) complex than Cp2ZrHCl. For a solubilized version of zirconocene dihydride, see [17]. Schwartz and coworkers used Na[AlH2(OCH2CH2OCH3)2] (Red-Al) as the reducing agent in THF; however, this protocol contaminated the Cp2ZrHCl with ca. 30% NaCl [14]. Buchwald and coworkers discovered that the reaction, first reported by Wailes and Weigold [11], of Cp2ZrH2 with CH2Cl2 (forming Cp2ZrHCl and CH3Cl) was very rapid at room temperature, whereas the analogous reaction between Cp2ZrHCl and CH2Cl2 was slower [18]. Thus, by adding a CH2Cl2 wash to the workup of the LiAlH4 reduction of Cp2ZrCl2, the problem of over-reducing to Cp2ZrH2 was minimized.An important practical aspect of this process is the use of a filtered Et2O solution of LiAlH4, which is slowly added to the solution of zirconocene. The reaction of Cp2ZrCl2 with one equivalent of t-BuLi in toluene can also be used to prepare Cp2ZrHCl [19]. Since the reagent does not have a very long shelf-life, methods for its in situ generation have been developed, including the treatment of Cp2ZrCl2 with t-BuMgCl in benzene/Et2O which forms i-BuZrCp2Cl, a Cp2ZrHCl equivalent [20, 21], and reduction of Cp2ZrCl2 with LiEt3BH in THF which forms the Schwartz reagent, Et3B and LiCl, two by-

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products that do not interfere with hydrozirconation [22] but can be a problem for further transmetalation. Bu2ZrCl2, prepared by treatment of ZrCl4 with two equivalents of BuLi, can also serve as a hydrozirconating agent in hexane or toluene, but not in THF [23]. Many cyclopentadiene ring-substituted derivatives of Cp2ZrHCl have been prepared and tested in hydrozirconation schemes [24, 25]. Cp2ZrHCl is a moderately air-, moisture-, and light-sensitive amorphous colorless solid that can be handled and weighed on a balance without special precautions. In our hands, storage in a polyethylene bottle under N2 extends the shelf life of the reagent to at least 20 days without significant decrease in reactivity. The hydrozirconation of terminal alkynes and alkenes proceeds rapidly (5–15 min) at room temperature in CH2Cl2 or THF, and much more slowly in benzene or toluene [8]. The reaction is also very easily monitored visually since the colorless Cp2ZrHCl is insoluble in most common organic solvents whereas the colored organozirconocenes are highly soluble. If the reaction is performed under kinetic control with a slight excess of alkyne, the regioselectivity of hydrozirconation is actually quite low. However, if excess Schwartz reagent is employed, thermodynamic equilibration via double hydrozirconation-b-elimination leads to the highly regioselective formation of the terminal, sterically less hindered vinyl organometallic. Procedure: Schwartz Reagent [26]

To a dry, 1 L Schlenk flask equipped with a magnetic stirring bar Cp2ZrCl2 (100 g, 0.342 mol) is added under argon, followed by dry THF (650 mL). Dissolution of the solid is accomplished by gentle heating. To the solution is added dropwise, over a 45 min period, a filtered, clear solution of LiAlH4 (3.6 g, 94 mmol) in Et2O (100 mL). The resulting suspension is stirred at room temperature for 90 min, then Schlenk-filtered under argon using a “D” frit. The white solid is washed with THF (4¥75 mL), CH2Cl2 (2¥100 mL with stirring and a contact time of no greater than 10 min per wash), and then with Et2O (4¥50 mL), and dried in the dark under reduced pressure to yield 66 g (75%) of Cp2ZrHCl as a white powder.

3 Functional Group Compatibility of Hydrozirconation True to its nature as an early transition metal, zirconium displays considerable Lewis acidity and binds to hard Lewis bases such as carbonyl groups, thus facilitating hydride transfer and reduction. In general, amides, ketones, aldehydes, and nitriles are not compatible with alkene and alkyne hydrozirconation conditions. Alkynes are selectively hydrozirconated in the presence of esters, but only sterically hindered triisopropylsilylesters survive the slower hydrozirconation of alkenes. Acylsilanes are also readily tolerated in hydrozirconation, and carbamates, acetals, epoxides, silylethers, alkyl- and phenylethers,

Hydrozirconation and Its Applications

5

Scheme 2 Hydrozirconation of an electrophilic and easily deprotonated substrate

halides, and sulfides are recovered unchanged after exposure to Schwartz reagent. Alcohols and sulfonamides undergo an acid-base reaction with one equivalent of zirconocene hydrochloride but otherwise do not significantly interfere with alkene and alkyne hydrozirconation. An example for the considerable functional group compatibility and low basicity of hydrozirconation is shown in Scheme 2.

4 Alternative Methods for Generating Organozirconocenes Other widely used reagents for the formation of organozirconium complexes are Cp2ZrEt2 and Cp2ZrBu2. These “Cp2Zr(II)” equivalents can react with alkenes and alkynes to form zirconacyclopentanes, -cyclopentenes, and -cyclopentadienes, which react very similarly to the acyclic organozirconocenes formed by hydrozirconation. For a recent review, see [27] and references cited therein. Cp2ZrR2 reagents can also be inserted into vinyl halides [28], 2,2-difluorovinyltosylate [29], methoxy enol ethers [30], enolsilanes [31], and vinyl sulfides, sulfoxides, and sulfones [32] to form internal and terminal as well as cyclic alkenylzirconocenes.

5 Hydrozirconation Followed by Halogenation One of the most widely used applications in organozirconium chemistry is the preparation of (E)-vinyl halides via hydrozirconation and halogenation. Recent applications of this method in natural product synthesis include (+)-amphidinolide J [33], tedonolide [34, 35], and the CP-molecules (CP-263,114 and CP-225,917) [36]. For a fragment needed for (+)-acutiphycin, hydrozirconation of alkyne 5 followed by bromination afforded bromides 6 and 7 as a 94:6 mixture of regioisomers [37] (Scheme 3).Vinyl bromide 6 was then converted in 3 steps into Grignard reagent 8, and added to aldehyde 9, installing all carbons necessary for completion of the total synthesis.

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Scheme 3 Synthesis of the (+)-acutiphycin precursor (E)-vinyl bromide 6 by the hydrozirconation and bromination of alkyne 5

Procedure: Hydrozirconation, bromination of internal alkynes [37]

A solution of alkyne 5 (1.51 g, 5.50 mmol) in benzene (36.7 mL) was treated with Cp2ZrHCl (4.30 g, 16.5 mmol) in one portion, warmed to 40 °C for 1 h, and cooled to room temperature. NBS (1.96 g, 11.0 mmol) was then added, and the reaction mixture was stirred for 15 min and quenched with saturated NaHCO3. The biphasic mixture was stirred vigorously for 5 min and extracted with hexane/ethyl acetate (9:1). The combined organic extracts were washed with brine, dried (MgSO4), filtered through a pad of SiO2, and washed with hexane/ethyl acetate (4:1). Concentration and chromatography on SiO2 (hexanes/ethyl acetate, 95:5) afforded a 16.4:1 mixture of 6 to 7 as a colorless oil. (Z)-Vinyl halides can also be prepared from terminal alkynes via the hydrozirconation of stannylacetylenes [38]. In their total synthesis of myxalamide A (Scheme 4), Mapp and Heathcock reduced the triple bond of stannylacetylene 12 with Cp2ZrHCl [39]. Due to the higher reactivity of the zirconocene substituent over the stannyl group, aqueous workup and TBDMS-deprotection afforded (Z)-vinylstannane 14. Replacement of the tributyltin group with iodine led to iodotriene 15, which was isolated as a 15:1 ratio of Z/E isomers at the terminal alkene. The strategy of using both stoichiometric zirconium and tin was

Hydrozirconation and Its Applications

7

Scheme 4 Synthesis of a (Z)-vinyl iodide intermediate in the total synthesis of myxalamide A

preferred because Wittig olefination of aldehyde 17 afforded 15 with a Z/E ratio of 5:1 (which could not be improved by purification). Panek and coworkers used a similar difference in the reactivity of gembimetallic alkenes for the stereoselective synthesis of trisubstituted alkenes [40] (Scheme 5). Silylacetylenes react with Schwartz reagent much like stannylacetylenes, and again the zirconium moiety is selectively transformed first when quenched with inorganic electrophiles [41]. Thus, iodosilane 20 was formed after treatment of zirconocene 19 with I2. Negishi coupling of 20 and EtZnCl was very high yielding and was followed by iododesilylation to install the second vinyl iodide. Stille coupling with vinylstannane 23 afforded the trisubstituted alkene 24, a potential synthetic intermediate for the C1–C12 fragment of callystatin A.

6 Hydrogenation and Reduction Regiospecific deuterium labeling can be achieved by quenching organozirconocenes with D2O or by using Cp2ZrDCl for hydrozirconation.A nice demonstration of this concept is the synthesis of three deuterium-substituted analogues of dimethyl hept-1,6-dienyl-4,4-dicarboxylate [42] (Scheme 6). These compounds were used for the study of the mechanism of the transition metal-

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Scheme 5 Rapid stereoselective synthesis of trisustituted alkenes from silylacetylenes

Scheme 6 Regiospecific 2H-labelling using hydrozirconation

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catalyzed 1,6-diene cycloisomerization. Diyne 25 was treated with sufficient Cp2ZrHCl to reduce both triple bonds, and quenched with D2O to afford 1,7(E,E)-bisdeuterodiene 26. A second regioisomer, 2,6-2H2-diene 27, was synthesized using Cp2ZrDCl for the hydrozirconation and quenching with H2O. The third regioisomer in this series, 1,7-(Z,Z)-2H2-diene 29, was prepared by a formal hydrogenation (hydrozirconation and H2O quench) of bisdeuterodiyne 28. A tritiated version of the Schwartz reagent has also been used for regioselectively labeling olefins with tritium [43]. In some cases, hydrozirconation and quenching with water is more selective and more efficient than catalytic hydrogenation protocols. For example, this strategy has been used for the hydrogenation of buckminsterfullerene C60 en route to organofullerenes [44]. Cp2ZrHCl has been used as a reducing agent by Ganem and coworkers for the deoxygenation of b-ketoesters to a,b-unsaturated esters [45], and for the reduction of amides to give imines [46]. Similarly, Schwartz reagent reduces N,Ndisubstituted amides to aldehydes [47]. This reagent has also been used by Majoral and coworkers for reducing phosphine oxides into phosphines [48] and dicyanophosphines into cyanophosphanes [49]. Trauner and Danishefsky used the Ganem reduction protocol in their synthesis of the spiroquinolizidine subunit of halichlorine [50] (Scheme 7).

Scheme 7 Deoxygenation of the lithium enolate of 30 using Cp2ZrHCl in the synthesis of a halichlorine fragment

7 Hydrozirconation Followed by C–C Bond Formation With the exception of direct insertion into CO and isocyanides [51], carbon–carbon bond formation from organozirconocenes requires the use of metal salts for transmetalation or (chloride) ligand abstraction. The former protocol has been successfully applied for many carbonyl additions and crosscouplings, whereas the latter strategy is particularly useful for conversions with electrophiles such as epoxides and aldehydes.

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7.1 Silver-Catalyzed Ligand Abstraction One way to increase alkenylzirconocene reactivity towards organic electrophiles is to reduce the steric congestion about zirconium by ligand (chloride) abstraction. Maeta et al. reported that cationic zirconocenes prepared in situ reacted rapidly with aldehydes to generate 1,2-addition products [52]. For example, when the product of the hydrozirconation of 1-hexyne was treated with hydrocinnamaldehyde in the presence of 5 mol% of AgClO4, alcohol 33 was isolated in 90% yield after a 10 min reaction time (Scheme 8). In the absence of the Ag(I) salt, only 17% conversion was observed after 2 h.AgAsF6 can also catalyze this transformation [53]; however, other Ag(I) salts such as AgOTf, AgSbF6, AgPF6, and AgBF4 were less effective. Wipf and Xu have shown that epoxides are rapidly activated by the cationic zirconocene obtained from treatment of the hydrozirconation product with catalytic amounts of AgClO4 [54]. After the cationic zirconocene-promoted epoxide rearrangement/[1,2]-H shift, carbon–ligand transfer to the resulting aldehyde provides access to secondary alcohols.

Scheme 8 Alkenylzirconocene addition to aldehydes catalyzed by AgClO4

Procedure: AgClO4-catalyzed alkenylzirconocene addition to aldehydes [52].

A mixture of Cp2ZrHCl (401 mg, 1.55 mmol) and 1-hexyne (132 mg, 1.61 mmol) in CH2Cl2 (4.0 mL) was stirred at room temperature for 10 min. To the resulting solution was added 3-phenylpropanal (174 mg, 1.30 mmol) in CH2Cl2 (4.0 mL) followed by AgClO4 (13 mg, 63 mmol, 5 mol%). The reaction mixture gradually turned dark brown. After stirring for 10 min, the mixture was poured into saturated NaHCO3. Extractive workup (EtOAc) followed by purification by preparative TLC (hexane/EtOAc, 80:20) gave allylic alcohol 33 as a colorless oil (255 mg, 90%). When epoxy ester 35 was subjected to these reaction conditions, acetal 36 was formed as a single diastereomer [55]. Hydrolysis of the acetal afforded an enone, thus the net transformation represented a new conversion of an ester into an a,b-unsaturated ketone. Wipf and Methot used this reaction in a synthesis of pyridazinones [56] (Scheme 9). The optimized conditions included addition of 5 mol% of triphenyl phosphite to the reaction mixture and adsorbing AgClO4 onto Celite to improve the stability and simplify the handling of the reagent. Conjugate addition to 36 followed by hydrolysis formed enone 37.A second cuprate addition, followed by cyclization using hydrazine and subsequent oxidation afforded pyridazinone 38 in 86% yield from 36.

Hydrozirconation and Its Applications

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Scheme 9 Synthesis of pyridazinones using the silver(I)-catalyzed addition of an alkenylzirconocene to epoxyester 35

The cationic zirconium-mediated aldehyde addition methodology has recently been used by Maier and coworkers in their study toward the taxol skeleton [57] (Scheme 10). The diene precursor to a planned cycloaddition was prepared by first adding zirconocene 40 to aldehyde 41 under silver(I)-catalysis, which afforded alcohol 42 as a 77:23 mixture of diastereomers. Protection of the

Scheme 10 Use of the silver(I)-catalyzed addition of alkenylzirconocene 40 to aldehyde 41 in the preparation of a potential precursor to a taxol-like skeleton

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newly formed alcohol followed by deprotection and elimination of the primary alcohol gave diene 43. The intramolecular Diels-Alder reaction of 44 to 45 was, however, unsuccessful. 7.2 Transmetalation While many other metals can be used for transmetalation from alkyl- and alkenylzirconocenes [4], the synthetically most important protocols include cross-couplings after zirconiumÆpalladium and zirconiumÆnickel transmetalations, and carbon–carbon bond formation after zirconiumÆzinc and zirconiumÆcopper transmetalations. Recent advances in these transformations and their synthetic scope are discussed in more detail below. 7.2.1 ZirconiumÆPalladium and ZirconiumÆNickel Negishi and coworkers discovered that alkenylzirconocenes could be coupled to aryl or alkenyl halides under Ni- [58] or Pd-catalysis [59]. The mechanism [60] is believed to be analogous to the cross-coupling cycles of organotin (Stille) [61] or organoboron (Suzuki-Miyaura) [62] coupling reactions.A recent total synthesis of lissoclinolide demonstrates a typical application of this methodology [63] (Scheme 11). Protected propargyl alcohol 47 was hydrozirconated with in situ generated i-BuZrCp2Cl and the resulting zirconocene was iodinated to afford vinyl iodide 49. Pd-catalyzed coupling of 49 with propargyl alcohol (46), Swern oxidation and then a Corey-Fuchs reaction gave 1,1-dibromoalkene 50. Pd-catalyzed coupling of 50 with zirconocene 48 occurred exclusively at the trans-position, and carboxylic acid 51 resulted from subsequent lithium–halogen exchange and a CO2 quench.Ag+-catalyzed lactonization of 51

Scheme 11 Total synthesis of lissoclinolide by use of the Pd-catalyzed cross-coupling of alkenylzirconocenes and vinyl halides

Hydrozirconation and Its Applications

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was quantitative, and finally deprotection gave the natural product in 9 steps and 32% overall yield from 46. Alkenylzirconocenes have also recently been coupled under Ni-catalysis with benzyl chlorides [64] and a-bromo-a,a-difluoro esters [65]. This group also found that the yield of Pd-catalyzed cross-couplings of sterically hindered alkenylzirconocenes and vinyl halides could be significantly improved by adding ZnCl2 to the reaction mixture [66]. A transmetalation from the bulky Cp2Zr to the sterically less demanding zinc salt was assumed to precede the normal catalytic coupling cycle. Negishi and Zeng used the combination of hydrozirconation and ZnCl2-mediated Pd-catalyzed cross-coupling to prepare all-E-oligoenes in a very selective and efficient fashion [67] (Scheme 12). For example, 1-octyne was converted into dienyne 53 and then tetraenyne 54 by repeated hydrozirconation-cross-coupling-deprotection operations, and similarly into trienyne 57 and pentaenyne 58 via enyne 56. The alkyne endgroup of the polyene was also converted into an ester function using known hydrozirconation methodology.

Scheme 12 Synthesis of all-E-oligoenes by iterative hydrozirconation and ZnCl2-mediated Pd-catalyzed cross-couplings

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Scheme 13 Successful and failed applications of the ZnCl2-mediated, Pd-catalyzed crosscoupling of alkenylzirconocenes with vinyl halides in the synthesis of N-Boc-ADDA

Panek and Hu further optimized this experimental protocol [68] and applied it towards the synthesis of the Adda amino acid side chain of the microcystin family of natural products [69] (Scheme 13). Hydrozirconation of alkyne 61 in THF at 50 °C gave zirconocene 62 as a single regioisomer. Pd-catalyzed coupling of 62 with vinyl iodide 63 in the presence of ZnCl2 afforded diene 64, which was deprotected and oxidized to yield the desired N-protected amino acid. In a second synthesis of Adda, coupling of 62 with vinyl iodide 65 (differing from 63 only in oxidation state) was not successful under ZnCl2-mediated Pd-catalysis [70]. Instead, 62 was iodinated and subjected to Stille coupling with the vinyl stannane derivative of 65. The Zr–Zn–Pd transmetalation has also been applied towards the total syntheses of (–)-motuporin [71], reveromycin B [72], pitiamide A [73], FR901464 [74], and eunicenone A [75]. Montgomery and coworkers found that ZnCl2 was an essential additive to promote their Ni-catalyzed inter- or partially intramolecular couplings of alkenylzirconocenes, alkynes, and either aldehydes or enones [76] (Scheme 14).

Scheme 14 ZnCl2 is crucial to promote the Ni-catalyzed cyclization of 66 and an alkenylzirconocene

Hydrozirconation and Its Applications

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Scheme 15 One-pot ZrÆZn transmetalation and addition to aldehydes

7.2.2 ZirconiumÆZinc Just as Pd-catalyzed cross-couplings of organozirconium reagents and vinyl or aryl halides can be greatly improved by addition of ZnCl2 to the reaction mixture, so can zinc reagents improve their reactivity towards other organic electrophiles. For a recent review of ZrÆZn transmetalation, see [77].Wipf and Xu have shown that addition of dialkylzincs (Me2Zn or Et2Zn) to alkenylzirconocenes promotes 1,2-addition to aldehydes [78] (Scheme 15). Presumably, a ZrÆZn transmetalation is followed by the zirconium-promoted carbonyl addition of the vinyl ligand of the mixed alkyl-alkenyl zinc reagent 70. ZnBr2 can also be used in this transformation [79]. Procedure: Zr–Zn transmetalation, aldehyde addition [80]

A Schlenk flask, fitted with a rubber septum and a magnetic stirring bar, was charged under N2 with alkyne 68 (5.55 g, 18 mmol) and dry CH2Cl2 (60 mL), immersed in a cold water bath and stirred. Within 20 min, Cp2ZrHCl (5.10 g, 19.8 mmol) was added in five portions. The water bath was removed and the reaction mixture was stirred at room temperature until a homogeneous solution formed. The resulting golden-yellow solution was stirred for another 20 min and then cooled to –60 °C. By syringe, Me2Zn (2.0 M solution in toluene, 10.4 mL, 20.8 mmol) was added dropwise over 45 min while the bath temperature was kept at –60 °C. The resulting orange-yellow solution was stirred for an additional 10 min at –60 °C, the reaction flask was immersed in an ice bath, and a solution of hexanal (2.16 g, 21.6 mmol) in dry CH2Cl2 (10 mL) was added via syringe over 45 min. The reaction mixture was stirred at 0 °C for another 6 h and poured slowly into an ice-cold aqueous 5% NaHCO3 solution.Vigorous stirring was continued at room temperature until the gas evolution subsided. The mixture was extracted with Et2O. The combined organic extracts were washed with brine, dried (Na2SO4), filtered through a pad of Florisil and concentrated. The residue was purified by chromatography on SiO2 (ethyl acetate/hexanes, 1:30 to 1:15) to yield 4.90 g (66%) of 71 as a colorless oil. MeLi can also be used in place of Me2Zn in this transformation; however, the reaction proceeds through a different mechanism [81] (Scheme 16). Treatment

16

P. Wipf · C. Kendall

Scheme 16 MeLi can promote the addition of alkenylchlorozirconocenes to aldehydes

of the alkenylzirconocene 40 with MeLi replaces the chloride with a methyl group. This complex loses methane upon heating thus forming an alkyne-zirconocene complex. Reaction with benzaldehyde affords oxazirconacyclopentene 77 with excellent regioselectivity. Protonolysis gives the allylic alcohol. Unbranched terminal alkynes give excellent regioselectivity in the aldehyde insertion step, however, the selectivity is reduced when unsymmetrical internal alkynes or trimethylsilylacetylene are used. Wipf and coworkers have used the Zr–Zn transmetalation, aldehyde addition methodology for the rapid, stereocontrolled preparation of all-(E)-polyenes [82] in the total syntheses of (+)-curacin A [83] and (±)-nisamycin [84]. Synthesis of the eastern side chain of (±)-nisamycin was accomplished in two steps from alkyne 79 (Scheme 17). Hydrozirconation of 79 followed by addition to cyclohexylcarboxaldehyde in the presence of dimethylzinc afforded the allylic alcohol 80. Elimination of the newly formed hydroxyl group was accomplished via the corresponding trifluoroacetate.Addition of alkenylzirconocenes

Scheme 17 Application of a one-pot hydrozirconation, ZrÆZn transmetalation, aldehyde addition toward the total synthesis of (±)-nisamycin

Hydrozirconation and Its Applications

17

to a,b-unsaturated aldehydes yields bis-allylic alcohols that are very easily eliminated to form all-(E)-trienes. The Zr–Zn transmetalation, aldehyde addition strategy has also been used in the total syntheses of (–)-ratjadone [85] and fostriecin. In the latter example, the substrate was a chiral epoxyketone, which was converted to a tertiary alcohol in excellent diastereoselectivity by chelation control [86]. More recently, the reaction scope has been extended to the addition to C=N electrophiles to form allylic amides [87] as well as allyl hydroxylamines [88], and to the preparation of trans-1,2-disubstituted cyclopropanes [87, 89]. Powell and Rychnovsky found that the BF3-mediated addition to in situ formed oxacarbenium ions led to a mixture of alkyl and alkenyl ligand transfers [90] (Scheme 18).

Scheme 18 Additions to oxacarbenium ions

Wipf and Ribe developed a catalytic asymmetric variant of the aldehyde addition process employing chiral aminoalcohols and aminothiols as catalytic ligands [91]. Danishefsky and coworkers used this methodology in a total synthesis of (+)-halichlorine [92], and Porco’s group applied it in a recent synthesis of the salicylate antitumor antibiotic lobatamide C [93]. 7.2.3 ZirconiumÆCopper Transmetalation from Zr to Cu is a highly beneficial process as it combines the ease of preparation of organozirconocenes from alkenes and alkynes with the wide scope of organocopper reagents in organic synthesis. Schwartz and coworkers were first to demonstrate transmetalation to Cu in their report on the reductive dimerization of alkenylzirconocenes [94]. Virgili et al. used this transformation to prepare dialkoxy-1,3-butadienes [95]. The copper-mediated coupling of alkenylzirconocene 85 and phenethynyl bromide was reported to yield 86 [96] (Scheme 19). The latter two reactions can also be mediated by oxovanadium complexes [97].

Scheme 19 Cu-mediated cross-coupling of alkynyl bromide 85 with an alkenylzirconocene

18

P. Wipf · C. Kendall

Wipf and coworkers reported the preparation of a,b-unsaturated ketones by the Cu(I)-catalyzed addition of alkenylzirconocenes to acid chlorides [98]. Analogously, saturated ketones were obtained from alkylzirconocenes. This group also developed a copper-catalyzed conjugate addition of alkylzirconocenes to enones [99] and a,b-unsaturated acyloxazolidinones [100]. Lipshutz and coworkers have worked extensively on the preparation of cyanocuprates by a hydrozirconation, transmetalation sequence [101]. These cuprate reagents can be alkylated with epoxides or activated (benzylic or allylic) halides [102]. They have also been used in conjugate additions to a,b-unsaturated ketones [103], and a large-scale, one-pot preparation of prostaglandins has been based on this process [104]. Lipshutz and Wood reported an elegant three-component coupling of cyanocuprates, prepared by transmetalation from alkenylzirconocenes, cyclopentenones and aldehydes or propargylic triflates for the synthesis of prostaglandin-like compounds [105] (Scheme 20). Disubstituted cyclopentanone 90 was prepared in one pot and 74% yield as a 12:1 mixture of stereoisomers using alkyne 87, 2-cyclopentene1-one and methyl 4-oxobutanoate. A solid-supported version of this sequence was recently reported [106].

8 Miscellaneous Reactions of Organozirconocenes After an initial discovery by Negishi and coworkers [107],Whitby and Kasatkin expanded the scope of the reaction of 1-lithio-1-haloalkenes and organozirconocenes [108] (Scheme 21). In this interesting process, the lithium reagent reacts with the zirconocene, presumably via an “ate-complex”, to generate a new alkenylzirconocene. 1-Lithio-1-chloroalkene 93 is formed by treatment of (Z)1-chloro-2-methyl-1-octene with LiTMP at –80 °C, and quenching of the alkenylzirconocene intermediate 94 provides a 93:7 ratio of trisubstituted alkenes 95 and 96. With (E)-1-chloro-2-methyl-1-octene as a starting material under the same conditions, the ratio of 95 to 96 is 63:37; however, if the corresponding (E)-iodide is used, the ratio is found to change to 16:84. Dienes are

Scheme 20 One-pot synthesis of prostaglandins by conjugate addition, enolate trapping

Hydrozirconation and Its Applications

19

Scheme 21 Insertion of vinyl lithium 93 into alkylzirconocene 92 to form an alkenylzirconocene

formed either by reacting 1-lithio-1-haloalkenes with alkenylzirconocenes, which results in poor E:Z selectivity in the insertion step, or by reacting 1lithio-1-halodienes with alkylzirconocenes, which can give much better selectivity. Trienes are formed by reacting the lithiohalodienes with alkenylzirconocenes, and alkynylzirconocenes, formed by treating zirconocene dichloride with alkynyl lithium reagents, can also be subjected to these reaction conditions to form enynes and dienynes. Similarly, homologation of alkenylzirconocenes into allylzirconocenes occurs when reagents such as LiCH(Cl)SiMe3 [109] or LiCH(Cl)OMe [110] are used in place of the lithioalkene, and lithioepoxynitriles are transformed into 2-cyano-1,3-dienes [111]. Wipf and Kendall have recently reported a multi-component allylation of aldimines in which the allylmetal species is generated in situ from a mixture of alkenylzirconocene, dimethylzinc and diiodomethane [112]. Suzuki and coworkers developed a method for the preparation of allylzirconocenes by hydrozirconation of allenes. The resulting allylzirconocenes readily converted aldehydes into homoallylic alcohols in high diastereoselectivities [113]. This group has also shown that allylzirconocenes can be used to carbometalate alkynes [114] (Scheme 22). The latter process was found to be very regiospecific; for example, the carbozirconation of alkyne 99 resulted in the isolation of naphthalene 103 as the sole product after protonolysis of the intermediate alkenylzirconocene 101. When iodoalkyne 100 was subjected to the same reaction conditions, a formal substitution took place and led to the formation of enyne 104 [115]. Alkylzirconocenes can also be used for the carbozirconation of alkynes if [Ph3C]+[B(C6F5)]– is used as the initiator in place of methylaluminoxane (MAO) [116]. Taguchi, Hanzawa and coworkers prepared cyclopropyl alcohols from vinyloxiranes by simply treating the substrate with Schwartz reagent in CH2Cl2 [117] (Scheme 23). This reaction was very diastereoselective (when R=Me) for cisvinyloxirane 105b since cyclopropyl alcohol 108b was the only diastereomer

20

P. Wipf · C. Kendall

Scheme 22 Carbozirconation of alkyne 99 catalyzed by MAO, and a spontaneous rearrangement of 102 into enyne 104

Scheme 23

Synthesis of cyclopropyl alcohols from vinyloxiranes

observed in the reaction mixture. When the corresponding trans-vinyloxirane was used, the diastereomeric ratio of the anti,trans-cyclopropane (vs. anti,cis) was 80:20.Allylic ethers were converted into cyclopropanes by the same mechanism; however, a Lewis acid was needed for deoxygenation [118].

Hydrozirconation and Its Applications

21

Scheme 24 Regioselective 1,2- or 1,4-addition of acylzirconocenes to a,b-unsaturated ketones

As initially reported by Schwartz and Bertelo [119], CO can be inserted into C–Zr bonds, resulting in acylzirconocenes. Hanzawa, Taguchi and coworkers have developed the synthetic utility of these complexes and demonstrated their reactivity in Lewis acid mediated additions to aldehydes [120], Pd-catalyzed cross-couplings with aryl halides, benzyl halides, acid chlorides and allylic acetates [121], and Pd-catalyzed conjugate or 1,2-additions to a,b-unsaturated ketones [122] (Scheme 24). The site of addition (1,4- vs. 1,2-) can be completely controlled by the choice of reaction conditions. For example, addition of acylzirconocene 110 to cyclohexenone afforded exclusively the 1,2-addition product a-hydroxyketone 111 under Pd-catalysis. Reaction of the same substrates under BF3·OEt2-mediated Pd-catalysis gave exclusively the 1,4-addition product. The yield and selectivity with acyclic ketone substrates is equally high. The use of chiral phosphine ligands for Pd under the 1,2-addition conditions afforded hydroxyl ketones with modest (up to 67%) enantiomeric excess [123]. Dupont and Donato have developed a synthesis of parasorbic acid and other 5,6–2H-pyran-2-ones by quenching an acylzirconocene intermediate with iodine followed by intramolecular lactonization [124]. Hypervalent aryl and vinyl iodonium salts have also been used as electrophiles for Pd-catalyzed coupling with acylzirconocenes [125]. Oxidation of the carbon–zirconium bond in organozirconocenes can be effected by a wide range of reagents and results in alcohols and carbonyl compounds in generally only moderate yields [126].

9 Conclusions As amply demonstrated by the success of the metathesis reaction [127], alkenes and alkynes are synthetically extraordinarily versatile functional groups for transition metal-mediated transformations. Hydrozirconation with readily available zirconocene hydrides allows the direct reductive conversion of

22

P. Wipf · C. Kendall

alkenes and alkynes into reactive nucleophiles under mild reaction conditions that are compatible with the presence of many functional groups. While in the past most synthetic uses of organozirconocenes have been limited to halide formation, transmetalation protocols provide for a far greater value by selective carbon–carbon bond formations. In particular, cross-coupling and multi-component reactions have greatly extended the scope of the sterically hindered organozirconocene complexes. As a consequence, use of alkenyl- and alkylzirconocenes in natural product synthesis has considerably increased in the past 10 years. Much of the incentive for future method development with hydrozirconation products is likely to derive from new reaction discovery and the evolution of older, racemic protocols into catalytic enantioselective transformations.

References 1. Schwartz J, Labinger JA (1976) Angew Chem, Int Ed Engl 15:333 2. Hartner FM, Clift SM, Schwartz J (1987) Organometallics:1346 3. Waymouth RM, Santarsiero BD, Coots RJ, Bronikowski MJ, Grubbs RH (1986) J Am Chem Soc 108:1427 4. Wipf P, Jahn H (1996) Tetrahedron 52:12853 5. Wipf P, Xu W, Takahashi H, Jahn H, Coish PDG (1997) Pure Appl Chem 69:639 6. Labinger JA (1991) In: Trost BM, Fleming I (eds) Comprehensive organic synthesis, vol 8. Pergamon, Oxford, p 667 7. Takacs JM (1995) In: Abel EW, Stone FGA, Wilkinson G (eds) Comprehensive organometallic chemistry II: A review of the literature 1982–1994, vol 12. Pergamon, Oxford, UK, p 39 8. Wipf P, Takahashi H, Zhuang N (1998) Pure Appl Chem 70:1077 9. Annby U, Karlsson S, Gronowitz S, Hallberg A, Alvhall J, Svenson R (1993) Acta Chem Scand 47:425 10. Chirik PJ, Day MW, Labinger JA, Bercaw JE (1999) J Am Chem Soc 121:10308 11. Wailes PC, Weigold H (1970) J Organomet Chem 24:405 12. Wailes PC, Weigold H, Bell AP (1972) J Organomet Chem 43:C32 13. Wailes PC, Weigold H, Bell AP (1971) J Organomet Chem 27:373 14. Hart DW, Schwartz J (1974) J Am Chem Soc 96:8115 15. Hart DW, Blackburn TF, Schwartz J (1975) J Am Chem Soc 97:679 16. Carr DB, Schwartz J (1979) J Am Chem Soc 101:3521 17. Wipf P, Wang X (2000) Tetrahedron Lett 41:8237 18. Buchwald SL, LaMaire SJ, Nielsen RB, Watson BT, King SM (1987) Tetrahedron Lett 28:3895 19. Pool JA, Bradley CA, Chirik PJ (2002) Organometallics 21:1271 20. Swanson DR, Nguyen T, Noda Y, Negishi E (1991) J Org Chem 56:2590 21. Makabe H, Negishi E (1999) Eur J Org Chem 969 22. Lipshutz BH, Keil R, Ellsworth EL (1990) Tetrahedron Lett 31:7257 23. Eisch JJ, Owour FA, Shi X (1999) Oganometallics 18:1583 24. Annby U, Gronowitz S, Hallberg A (1990) Acta Chem Scand 44:862 25. Luinstra GA, Rief U, Prosenc MH (1995) Organometallics 14:1551 26. Buchwald SL, LaMaire SJ, Nielsen RB, Watson BT, King SM (1993) Org Synth 71:77 27. Negishi E, Takahashi T (1998) Bull Chem Soc Jpn 71:755

Hydrozirconation and Its Applications

23

28. Takahashi T, Kotora M, Fischer R, Nishihara Y, Nakajima K (1995) J Am Chem Soc 117:11039 29. Ichikawa J, Fujiwawa M, Nawata H, Okauchi T, Minami T (1996) Tetrahedron Lett 37:8799 30. Liard A, Kaftanov J, Chechik H, Farhat S, Morlender-Vais N, Averbuj C, Marek I (2001) J Organomet Chem 624:26 31. Ganchegui B, Bertus P, Szymoniak J (2001) Synlett 123 32. Farhat S, Marek I (2002) Angew Chem Int Ed 41:1410 33. Williams DR, Kissel WS (1998) J Am Chem Soc 120:11198 34. Matsushima T, Mori M, Zheng BZ, Maeda H, Nakajima N, Uenishi J,Yonemitsu O (1999) Chem Pharm Bull 47:308 35. Zheng BP, Maeda H, Mori M, Kusaka S, Yonemitsu O, Matsushima T, Nakajima N, Uenishi J (1999) Chem Pharm Bull 47:1288 36. Nicolaou KC, Jung JK, Yoon WH, He Y, Zhong YL, Baran PS (2000) Angew Chem Int Ed 39:1829 37. Smith III AB, Chen SSY, Nelson FC, Reichert JM, Salvatore BA (1997) J Am Chem Soc 119:10935 38. Lipshutz BH, Keil R, Barton JC (1992) Tetrahedron Lett 33:5861 39. Mapp AK, Heathcock CH (1999) J Org Chem 64:23 40. Arefolov A, Langille NF, Panek JS (2001) Org Lett 3:3281 41. Xu X-H, Zheng W-X, Huang X (1998) Synth Commun 28:4165 42. Bray KL, Lloyd-Jones GC (2001) Eur J Org Chem 1635 43. Zippi EM, Andres H, Morimoto H, Williams PG (1994) Synth Commun 24:1037 44. Ballenweg S, Gleiter R, Krätschmer W (1993) Tetrahedron Lett 34:3737 45. Godfrey AG, Ganem B (1992) Tetrahedron Lett 33:7461 46. Schedler DJA, Li J, Ganem B (1996) J Org Chem 61:4115 47. White JM, Tunoori AR, Georg GI (2000) J Am Chem Soc 122:11995 48. Zablocka M, Delest B, Igau A, Skowronska A, Majoral J-P (1997) Tetrahedron Lett 38:5997 49. Maraval A, Igau A, Lepetit C, Chrostowska A, Sotiropoulos J-M, Pfister-Guillouzo G, Donnadieu B, Majoral J-P (2001) Organometallics 20:25 50. Trauner D, Danishefsky SJ (1999) Tetrahedron Lett 40:6513 51. Negishi E, Swanson DR, Miller SR (1988) Tetrahedron Lett 29:1631 52. Maeta H, Hashimoto T, Hasegawa T, Suzuki K (1992) Tetrahedron Lett 33, 5965 53. Suzuki K, Hasegawa T, Imai T, Maeta H, Ohba S (1995) Tetrahedron 51:4483 54. Wipf P, Xu W (1993) J Org Chem 58:825 55. Wipf P, Xu W (1993) J Org Chem 58:5880 56. Wipf P, Methot J-L (1999) Org Lett 1:1253 57. Richter F, Bauer M, Perez C, Maichle-Mössmer C, Maier ME (2002) J Org Chem 67:2474 58. Negishi E, Van Horn DE (1977) J Am Chem Soc 99:3168 59. Okukado N, Van Horn DE, Klima WL, Negishi E (1978) Tetrahedron Lett 1027 60. Negishi E, Takahashi T, Baba S, Van Horn DE, Okukado N (1987) J Am Chem Soc 109:2393 61. Stille JK (1986) Angew Chem Int Ed 25:508 62. Miyaura N, Suzuki A (1995) Chem Rev 95:2457 63. Xu CD, Negishi E (1999) Tetrahedron Lett 40:431 64. Lipshutz BH, Bülow G, Lowe RF, Stevens KL (1996) Tetrahedron 52:7265 65. Schwaebe MK, McCarthy JR, Whitten JP (2000) Tetrahedron Lett 41:791 66. Negishi E, Okukado N, King AO, Van Horn DE, Spiegel BI (1978) J Am Chem Soc 100:2254 67. Zeng F, Negishi E (2002) Org Lett 4:703

24 68. 69. 70. 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. 90. 91. 92. 93. 94. 95. 96. 97. 98. 99. 100. 101. 102. 103. 104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114. 115. 116.

P. Wipf · C. Kendall Panek JS, Hu T (1997) J Org Chem 62:4912 Panek JS, Hu T (1997) J Org Chem 62:4914 D’Aniello F, Mann A, Schoenfelder A, Taddei M (1997) Tetrahedron 53:1447 Hu T, Panek JS (1999) J Org Chem 64:3000 Drouet KE, Theodorakis EA (2000) Chem Eur J 6:1987 Ribe S, Kondru RK, Beratan DN, Wipf P (2000) J Am Chem Soc 122:4608 Thompson CF, Jamison TF, Jacobsen EN (2000) J Am Chem Soc 122:10482 Lee TW, Corey EJ (2001) J Am Chem Soc 123:1872 Ni YK, Amarasinghe KKD, Montgomery J (2002) Org Lett 4:1743 Wipf P, Kendall C (2002) Chem Eur J 8:1778 Wipf P, Xu W (1994) Tetrahedron Lett 35:5197 Zheng B, Srebnik M (1995) J Org Chem 60:3278 Wipf P, Xu W (1997) Org Synth 74:205 Maier ME, Oost T (1995) J Organomet Chem 505:95 Wipf P, Coish PDG (1997) Tetrahedron Lett 38:5073 Wipf P, Xu W (1996) J Org Chem 61:6556 Wipf P, Coish PDG (1999) J Org Chem 64:5053 Williams DR, Ihle DC, Plummer SV (2001) Org Lett 3:1383 Chavez DE, Jacobsen EN (2001) Angew Chem Int Ed 40:3667 Wipf P, KendallC, Stephenson CRJ (2001) J Am Chem Soc 123:5122 Pandya SU, Garçon C, Chavant PY, Py S, Vallée Y (2001) Chem Commun 1806 Yachi K, Shinokubo H, Oshima K (1998) Angew Chem Int Ed 37:2515 Powell NA, Rychnovsky SD (1999) J Org Chem 64:2026 Wipf P, Ribe S (1998) J Org Chem 63:6454 Trauner D, Schwarz JB, Danishefsky SJ (1999) Angew Chem Int Ed 38:3542 Shen R, Lin CT, Porco JA (2002) J Am Chem Soc 124:5650 Yoshifuji M, Loots MJ, Schwartz J (1977) Tetrahedron Lett 1303 Virgili M, Moyano A, Pericàs MA, Riera A (1997) Tetrahedron Lett 38:6921 Hara R, Liu Y, Sun W-H, Takahashi T (1997) Tetrahedron Lett 38:4103 Ishikawa T, Ogawa A, Hirao T (1999) J Organomet Chem 575:76 Wipf P, Xu W (1992) Synlett 718 Wipf P, Xu W, Smitrovich JH, Lehmann R, Venanzi LM (1994) Tetrahedron 50:1935 Wipf P, Takahashi H (1996) Chem Commun:2675 Lipshutz BH, Bhandari A, Lindsley C, Keil R, Wood MR (1994) Pure Appl Chem 66: 1493 Lipshutz BH, Kato K (1991) Tetrahedron Lett 32:5647 Lipshutz BH, Ellsworth EL (1990) J Am Chem Soc 112:7440 Babiak KA, Behling JR, Dygos JH, McLaughlin KT, Ng JS, Kalish VJ, Kramer SW, Shone RL (1990) J Am Chem Soc 112:7441 Lipshutz BH, Wood MR (1994) J Am Chem Soc 116:11689 Manzotti R, Tang S-Y, Janda KD (2000) Tetrahedron 56:7885 Negishi E, Akiyoshi K, O’Connor B, Takagi K, Wu G (1989) J Am Chem Soc 111:3089 Kasatkin A, Whitby RJ (1999) J Am Chem Soc 121:7039 Kasatkin AN, Whitby RJ (1999) Tetrahedron Lett 40:9353 Kasatkin AN, Whitby RJ (2000) Tetrahedron Lett 41:6211 Kasatkin AN, Whitby RJ (2000) Tetrahedron Lett 41:6201 Wipf P, Kendall C (2001) Org Lett 3:2773 Chino M, Matsumoto T, Suzuki K (1994) Synlett 359 Yamanoi S, Imai T, Matsumoto T, Suzuki K (1997) Tetrahedron Lett 38:3031 Yamanoi S, Matsumoto T, Suzuki K (1999) Tetrahedron Lett 40:2793 Yamanoi S, Seki K, Matsumoto T, Suzuki K (2001) J Organomet Chem 624:143

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117. Harada S, Kowase N, Tabuchi N, Taguchi T, Dobashi Y, Dobashi A, Hanzawa Y (1998) Tetrahedron 54:753 118. Gandon V, Szymoniak J (2002) Chem Commun 1308 119. Bertelo CA, Schwartz J (1975) J Am Chem Soc 97:228 120. Harada S, Taguchi T, Tabuchi N, Narita K, Hanzawa Y (1998) Angew Chem Int Ed 37:1696 121. Hanzawa Y, Tabuchi N, Taguchi T (1998) Tetrahedron Lett 39:6249 122. Hanzawa Y, Tabuchi N, Taguchi T (1998) Tetrahedron Lett 39:8141 123. Hanzawa Y, Tabuchi N., Saito K, Noguchi S, Taguchi T (1999) Angew Chem Int Ed 38:2395 124. Dupont J, Donato AJ (1998) Tetrahedron: Asymmetry 9:949 125. Kang S-K, Yoon S-K (2002) J Chem Soc, Perkin Trans I 459 126. Nagashima T, Curran DP (1996) Synlett:330 127. Trnka TM, Grubbs RH (2001) Acc Chem Res 34:18

Topics Organomet Chem (2004) 8: 27– 56 DOI 10.1007/b13143 © Springer-Verlag Berlin Heidelberg 2004

Construction of Carbocycles via Zirconacycles and Titanacycles Zhenfeng Xi (

) · Zhiping Li

Peking University, College of Chemistry, 100871 Beijing, China [email protected]

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

28

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29

1

Introduction

2

Preparative Methods for Metallacyclic Intermediates

2.1 2.2 2.3 2.4

Metallacyclopropanes and Metallacyclopropenes . . . . . . . . . . . . . . Metallacyclobutanes and Metallacyclobutenes . . . . . . . . . . . . . . . Metallacyclopentanes, Metallacyclopentenes, and Metallacyclopentadienes Six-Membered Metallacycles . . . . . . . . . . . . . . . . . . . . . . . . .

. . . .

29 31 32 34

3

Preparation of Carbocyclic Compounds via Metallacycles . . . . . . . . . .

36

3.1 3.2 3.3 3.3.1 3.3.2 3.3.3 3.3.4 3.4 3.4.1 3.4.2 3.4.3 3.5

Three-Membered Carbocycles . . . . . . . . . . . . . . . . . . . Four-Membered Carbocycles . . . . . . . . . . . . . . . . . . . . Five-Membered Carbocycles . . . . . . . . . . . . . . . . . . . . Carbon Monoxide as One-Carbon Unit Affording Cyclic Ketones Isocyanides as One-Carbon Unit . . . . . . . . . . . . . . . . . . Other One-Carbon Unit Equivalents . . . . . . . . . . . . . . . . Preparation of Five-Membered Heterocycles . . . . . . . . . . . Six-Membered Carbocycles . . . . . . . . . . . . . . . . . . . . Benzene Derivatives . . . . . . . . . . . . . . . . . . . . . . . . Pyridine Derivatives and Related Compounds . . . . . . . . . . Others . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Seven-Membered Carbocycles and Others . . . . . . . . . . . .

. . . . . . . . . . . .

36 38 40 40 43 44 46 47 47 50 50 52

4

Concluding Remark

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

53

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53

References

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Abstract Metal-mediated selective construction of useful carbocyclic compounds from multi-component reaction systems has attracted much attention in recent years. Zirconocene (containing a Cp2Zr unit) and titanocene (containing a Cp2Ti unit) mediated reactions have made significant contributions to the development of synthetically useful methodologies for construction of carbocyclic compounds from different components. This review surveys applications of zirconacycles and titanacycles on construction of useful carbocyclic compounds from multi-components. A brief introduction into preparative methods for zirconacycles and titanacycles is also given. Keywords Zirconacycle · Titanacycle · Carbocycles · Methodology · Selectivity

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1 Introduction The preparation and reaction chemistry of metallacyclic compounds have attracted much attention in recent years because many synthetically important transition-metal-assisted reactions proceed via metallacyclic intermediates.As a consequence, metallacyclic compounds have become a large family in organometallic chemistry, and are normally generated in situ in a reaction that involves reductive coupling of two unsaturated organic substrates on a low valent transition metal center. Metallacycles of group 4 metals, especially Zr and Ti with cyclopentadienyl (Cp) ligands, have proven very useful as reagents in synthetic chemistry (Fig. 1). Existence of the two identical or different M–C bonds in such metallacycles provides various opportunities to design and construct a large diversity of compounds. Carbocycles are important compounds in natural products and functional materials. The traditional preparative methods for cyclic compounds include the Diels–Alder addition reaction, and cyclization mediated by Lewis acid and base. With the aid of metallacycles, carbocycles are often prepared in high yields with high selectivity from different components (Scheme 1). Among many metallacycles, zirconacycles and titanacycles with Cp ligands have been most widely used in stoichiometric reactions to prepare carbocycles.

Scheme 1 Preparation of carbocyles mediated by stoichiometric amounts of metallacycles via intermolecular reaction patterns

Fig. 1

Some representatives of metallacycles of zirconocene and titanocene. M=Zr or Ti

Construction of Carbocycles via Zirconacycles and Titanacycles

29

There have been several excellent reviews and books dealing with preparation methods of zirconacycles and titanacycles, especially on the formation of 3- and 5-membered zirconacycles [1–5]. Therefore, this paper will not describe details of preparation of 3- and 5-membered zirconacycles, which are the most popular metallacycles of zirconocene and titanocene. In order for readers to find appropriate references, a brief introduction into preparative methods of these metallacycles is given. Applications of zirconacycles and titanacycles in the construction of useful carbocyclic compounds from multi-components are summarized.

2 Preparative Methods for Metallacyclic Intermediates Generation of zirconocene (II) and titanocene (II) species is a prerequisite since zirconocene (IV) and titanocene (IV) are the stable oxidation states. A ligand-free zirconocene (II) species, [Cp2Zr(II)], a 14-electron species with d2 configuration, has been well accepted as a highly reactive intermediate, although it has never been isolated as a discrete chemical compound. Zirconocene (II) complexes are generally prepared by the reduction of zirconocene (IV) dichloride in the presence of stabilizing ligands such as carbon monoxide, phosphines, alkenes, alkynes, and so on [1–5]. Either heterogeneous or homogeneous procedures have been reported. As reducing reagents, Na, Li, Mg, Mg/HgCl2, Na–Hg, and so on, had been commonly used before Negishi and coworkers reported the convenient method for generating Cp2Zr(II) species by treatment of Cp2ZrCl2 with two equivalents of n-BuLi (Eq. 1) [6].

(1)

2.1 Metallacyclopropanes and Metallacyclopropenes Excellent reviews or chapters in books have been published dealing with chemistry of metallocene–alkene complexes, metallocene–alkyne complexes, and their corresponding three-membered metallacyclic compounds of zirconocene and titanocene [1–5]. Zirconocene(II)–alkene complexes and zirconocene (II)–alkyne complexes are often also viewed as zirconocene (IV) comple-

30

Z. Xi · Z. Li

(2)

(3)

(4)

xes (resonance hybrids) [2a]; their corresponding three-membered zirconacyclopropanes and zirconacyclopropenes are shown below (Eqs. 2–4, M=Zr, Ti). The first X-ray structure of a zirconocene(II)-–alkene complex, zirconocene(II)–stilbene stabilized by phosphine, was reported by Takahashi and coworkers [7]. Basically, the formation of zirconocene alkene or alkyne complexes may be achieved in three different ways: (a) by a reductive elimination process starting from alkyl, alkenyl or aryl zirconocene(IV) complexes (Eq. 1, and Eqs. 5–6) [1–5, 8, 9], or (b) by ligand exchange reactions involving carbonyl or phosphine complexes (Eq. 7), or (c) by b,b¢-C–C bond cleavage of zirconacyclopentanes or zirconacyclopentenes (Eqs. 8–9) [10, 11].

(5)

(6)

(7)

Construction of Carbocycles via Zirconacycles and Titanacycles

31

(8)

(9)

Oxazirconacyclopropanes, silazirconacyclopropanes, and other three-membered zirconacycles containing heteroatoms have been prepared via transmetallation and migratory insertion (Eqs. 10–11) [12]. (10)

(11) 2.2 Metallacyclobutanes and Metallacyclobutenes Four-membered titanacycle intermediates have been often involved in titanium carbene mediated olefin metathesis and related reactions (Eqs. 12–13). Both titanacyclobutanes and titanacyclobutenes have been reported and are useful intermediates for the synthesis of various organic compounds. Since many reviews have appeared [13], no details will be described in the paper. (12)

(13)

Except the well-known olefin-metathesis protocol, generally, there is lack of preparative methods for four-membered metallacycles. Takahashi and coworkers reported formation of zirconacyclobutene–silacyclobutene fused ring compound via a novel skeletal rearrangement of zirconacycles (Eq. 14) [14]. The structure of this compound has been characterized by X-ray analysis [14b]. (14)

32

Z. Xi · Z. Li

Fig. 2

Rosenthal and coworkers reported a series of interesting reactions of bis(trimethylsilyl)acetylene–zirconocene and –titanocene complexes.A variety of metallacyclobutene derivatives were prepared via metallacycocumulenes from 1,3-diynes, linear tetraynes, and tetraalkynylsilanes (Fig. 2). Cleavage of C–C single bonds in conjugated diynes was observed [5]. 2.3 Metallacyclopentanes, Metallacyclopentenes, and Metallacyclopentadienes There have been many reports on the preparation and applications of fivemembered zirconacycles, namely, zirconacyclopentanes, zirconacyclopentenes and zirconacyclopentadienes [1–5]. For the preparation of 5-membered zirconacycles, although it is possible to use di-Grignard or dilithium reagents for the preparation of zirconacyclopentanes [10], the reductive coupling of unsaturated organic substrates, either intramolecular or intermolecular, on a zirconocene(II) species is the most common way. Generally, intramolecular coupling pattern can afford bicyclic metallacycles in excellent yield with perfect regioselectivity. Treatment of zirconocene(II) species, generated in situ either by Cp2ZrCl2/2 n-BuLi (Negishi reagent) or Cp2ZrCl2/Mg/HgCl2, with a diene, a nonconjugated enyne, or a diyne affords high yield formation of corresponding bicyclic zirconacyclopentane, zirconacyclopentene, and zirconacyclopentadiene, respectively (Eqs. 15–18) [10, 15–17]. Titanacyclopentadienes could be prepared in a similar way [18, 19]. It is noteworthy that terminal acetylenes are generally not applicable for this reaction. Messy mixtures are normally obtained.

(15)

(16)

Construction of Carbocycles via Zirconacycles and Titanacycles

33

(17)

(18)

Coupling reaction of an alkene with a zirconocene(II)–alkene complex may give a zirconocyclopentane (and regioisomers). Similarly, formation of zirconacyclopentenes can be expected when zirconocene(II)–alkene complexes are treated with alkynes or when zirconocnene(II)–alkyne complexes are treated with alkenes. Takahashi has reported a very convenient procedure for the preparation of zirconacyclopentenes by warming of Cp2ZrEt2 to 0 °C in the presence of an alkyne or a conjugated diyne (Eq. 19) [11]. Although titanacyclopentenes could be similarly prepared (Eq. 20) [18], the reaction should be carried out at –30 °C. When the reaction is done at 0 °C, as the case for zirconocene, low yields of titanacyclopentenes are obtained.

(19)

(20)

Compared with symmetrical metallacyclopentadienes, unsymmetrical metallacyclopentadienes from two different alkynes are not always easily prepared. Several methods have been reported for preparation of unsymmetrical zirconacyclopentadienes in which the key step is the addition of a second alkyne to zirconocene–alkyne complexes generated in situ [20]. Formation of homocoupling products from the same alkyne is often the biggest problem (Eq. 21).

(21)

34

Z. Xi · Z. Li

(22)

A highly selective and practical alkyne–alkyne cross-coupling using Cp2ZrBu2 and ethylene gas was developed by Takahashi and coworkers (Eq. 22) [20]. A first alkyne was added to zirconacyclopentanes, generated in situ from the reaction of Cp2ZrBu2 and ethylene gas, affording zirconacyclopentenes with high selectivities at room temperature under ethylene atmosphere. Subsequent addition of a second alkyne to the solution of zirconacyclopentenes at 50 °C gave unsymmetrical zirconacyclopentadienes selectively from two different alkynes. For unsymmetrical titanacyclopentadienes, there is still no selective preparative method. Cyclic gem-metallozirconocene compounds such as a-lithiated zirconacyclopentadienes, a-stannyl or gallio-zirconacyclopentenes, and a,a¢bis(trimethylstannyl) zirconacyclopentadienes have been prepared (Fig. 3) [21–25]. These multifunctionalized zirconacycles can be expected to have useful applications in organic synthesis. 2.4 Six-Membered Metallacycles Compared with five-membered metallacycles, relatively fewer reports are known on the preparative methods and reaction chemistry of six-membered metallacycles.Whitby and coworkers have systematically investigated insertion of carbenoids into five-membered zirconacycles and developed a number of interesting six-membered zirconacycles [17, 26]. Isonitriles, 1-halo-1lithioalkenes, allenyl carbenoids, allyl carbenoids, propargy carbenoids, benzyl carbenoids, and 1-nitrile-1-lithio epoxides can all insert into zirconacyclopentanes and zirconacyclopentenes to afford various six-membered zirconacycles (Eqs. 23, 24).

Fig. 3

Construction of Carbocycles via Zirconacycles and Titanacycles

35

(23)

(24)

Lithiated chloromethyltrimethylsilane was reported to insert into zirconacyclopentadienes to give zirconacyclohexadiene derivatives (Eq. 25) [27]. This has been so far the only example of carbenoid insertion into 5-membered metallacyclopentadienes.

(25)

The first example of intramolecular alkyne insertion into zirconacyclopentadienes was reported by Takahashi and coworkers (Eq. 26) [14b]. The structure of the zirconacyclohexadiene–silacyclobutene fused ring compound was determined by single crystal X-ray analysis. Xi and coworkers recently reported an alternative method for the preparation of analogous zirconacyclohexadiene–silacyclobutene fused ring compound via an unprecedented alkyne-induced C–C bond and C–Si bond cleavage pattern (Eq. 27) [14c].

(26)

(27)

In a similar manner, reactions of zirconocene–benzyne complexes with bis(phenylalkynyl)phosphine afforded benzocyclozirconacyclohexadiene derivatives (Eq. 28) [28].

36

Z. Xi · Z. Li

(28)

A dibenzotitanacyclohexadiene, the first example of this kind, was prepared in 1988 from the reaction of 2,2¢-dilithiobiphenyl and Cp2TiCl2 and structurally characterized (Eq. 29) [29].

(29) Obviously, titanocene analogues of six-membered metallacycles are very rare, due to lack of preparative methods. More preparative methods are desirable and interesting reaction chemistry can be expected of six-membered metallacycles.

3 Preparation of Carbocyclic Compounds via Metallacycles Construction of carbocycles from metallacycles is attractive. Theoretically, for example, reaction of a five-membered metallacycle with a one-carbon unit may afford a five-membered carbocycle. A six-membered carbocycle may be formed from insertion of a two-carbon unit into a five-membered metallacycle. However, in many cases, skeletal rearrangement of in situ generated metallacycles takes place, thus making prediction of structures of products very difficult. Accordingly, in this section, we focus on the carbocycles formed, regardless of the starting metallacycles. 3.1 Three-Membered Carbocycles Formation of three-membered carbocycles from the reaction of three-membered metallacycles (or metallocene–alkyne or –alkene complexes) with a onecarbon unit can be considered to be the most straightforward way (Scheme 2). However, such a preparative route has not been reported. Takahashi and coworkers have reported three types of formation of cyclopropane derivatives from five-membered zirconacycles. One is via reaction of carbenes or carbenoids with carbon–carbon double bond in zirconcyclopentadienes (Eq. 30) [30], the second via b-elimination from zirconacyclopentenes (Eq. 31) [31] and the third via intramolecular Michael addition (Eq. 32) [32].

Construction of Carbocycles via Zirconacycles and Titanacycles

37

Scheme 2

Both of the carbene species, :CX2 and :CH2, which were generated in situ by the standard procedures, could smoothly react with one a,b-C=C bond in zirconacyclopentadienes without interference with Zr–C bonds to give cyclopropane derivatives after hydrolysis (Eq. 30) [30]. This was the first example of reaction of the a,b-C=C bond in metallacyclopentadienes.

(30)

The reaction of zirconacyclopentenes with homoallyl bromides afforded allylcyclopropane derivatives with diastereoselectivity through intramolecular alkylation (Eq. 31) [31]. A a-substituted homoallylic bromide produced predominantly the cis-isomer for the disubstituted cyclopropane moiety, while a b-substituted one gave the trans-isomer as a main product.

(31)

38

Z. Xi · Z. Li

(32)

Titanacyclopentenes are formed from the reaction of Cp2TiEt2 and alkynes as described above (Eq. 20) [18]. However, interestingly, when a silylated acetylene such as 1-trimethylsilyl-1-propyne was used, 1-methyl-1-(trimethylsilyl)methyl cyclopropane, other than the expected titanacyclopentene, was formed (Eq. 33) [18]. This reaction chemistry is different from that of analogous zirconocene. Formation of a titanocene–carbene complex is proposed via Michael addition-type reaction in the titanacyclopentene intermediates.

(33)

3.2 Four-Membered Carbocycles Cyclobutadiene is one of the most attractive molecules.A conceptually new and simple method using intramolecular coupling of 1-metallo-4-halobutadiene was reported to form cyclobutadiene derivatives by Takahashi and coworkers (Eq. 34). 1-Zircona-4-halobutadiene derivatives, generated in situ by treatment of zirconacyclopentadienes with one equivalent of iodine, react in the presence

Construction of Carbocycles via Zirconacycles and Titanacycles

39

(34)

(35)

of CuCl to produce cyclobutadiene derivatives that afford their dimmers, or Diels–Alder adducts with dimethyl maleate or fumarate (Eq. 35) [33]. Following the same concept as described above, a convenient one-pot procedure to arylcyclobutenes from arylacetylenes via zirconacyclopentenes was reported (Eq. 36) [34]. By using this method, conjugated cyclobutenes such as 1,2-diarylcyclobutenes can be readily prepared.

(36)

Negishi and coworkers reported an alternative method for 1,2-disubstituted cyclobutene derivatives from the reaction of t-BuLi and 1,4-diiodo-1-alkenes (Eq. 37) [35], which are isolated from treatment of zirconacyclopentes with iodine. However, the use of t-BuLi does not tolerate other functional groups in the starting diiodides. As described in Eq. 14 and Eqs. 26 to Eq. 28, and Fig. 2, along with formation of metallacycles, silacyclobutene derivatives and the phosphorus analogues are formed. These methods represent general routes for silacyclobutene derivatives. Interesting reaction chemistry of such silacycles can be expected.

(37)

40

Z. Xi · Z. Li

3.3 Five-Membered Carbocycles Conversion of the five-membered metallacycles into five-membered carbocycles, where the metal is eventually replaced with one carbon atom, is an attractive method for the construction of five-membered carbocycles (Eq. 38). In fact, such transformation is very popular using five-membered metallacycles of titanocenes and zirconocenes [1–5].

(38)

3.3.1 Carbon Monoxide as One-Carbon Unit Affording Cyclic Ketones The carbonylation reactions are very important in synthesis and for industrial applications as well. The Pauson–Khand reaction, the well-known cobalt-mediated procedure, combines an alkyne, an alkene, and a carbon monoxide ligand into cyclopentenones (Eq. 39) [36].

(39)

Zirconocene or titanocene mediated intramolecular cyclization reactions of enynes followed by CO insertion into their corresponding five-membered metallacycles led to the formation of bicyclic cyclopentenones (Eqs. 40, 41) [37, 38]. Intermolecular coupling of alkynes, alkenes, and CO mediated by zirconocene or titanocene affording cyclopentenone derivatives have also been achieved (Eq. 39) [18, 39, 40]. It is noteworthy that, in order to obtain the desired cyclopentenones from the reaction of zirconacyclopentenes with CO, termination of the reaction mixture with I2 is necessary.Alcohols are normally formed if the reaction mixture is treated with aqueous acid. However, in case of titanacyclopentenes, quenching with 3 N HCl gave cyclopentenones exclusively [18]. Under pressure of CO, cyclopentenones can be obtained in good yields in the presence of a catalytic amount of the titanocene Cp2Ti(CO)2 (Eq. 42) [41]. By using an enantiomerically pure analogue, Buchwald was able to perform a highly enantioselective catalytic Pauson–Khand type reaction (Eq. 42) [42].

(40)

Construction of Carbocycles via Zirconacycles and Titanacycles

41

(41)

(42)

In addition to CO, isocyanides and bis(trichloromethyl)carbonate were also applied as a one-carbon unit to transform five-membered metallacycles into cyclopentenones [41–44]. Carbonylation of five-membered zirconacycles has been applied for synthesis of complexed and natural products. Stereocontrolled one-pot synthesis of tricyclic ketone with only cis isomer was achieved by Negishi and coworkers (Eq. 43) [45].

(43)

Mori and coworkers successfully synthesized the optically active alkaloid (–)-dedrobine by a short sequence using zirconocene-promoted carbonylation and reductive cyclization (Eq. 44) [46].

(44)

42

Z. Xi · Z. Li

Wender and coworkers had established a methodology for the synthesis of a family of simple tigliane–daphnane analogues, based on the zirconocene-mediated enyne carbocyclization, demonstrating both the extension of the carbocyclization methodology to cycloheptanoid synthesis and the control of stereochemistry from a pre-existing ring system with the zirconocene-mediated carbocyclization reaction (Eq. 45) [47].

(45)

g-Butyrolactones are ubiquitous in nature. An attractive route to this ring system is the [2+2+1] approach. Although a similar approach has been successfully employed for the construction of five-membered carbocycles, the application of this route to heterocycle synthesis is rare. Crowe and coworkers firstly reported a titanocene-mediated synthesis of g-butyrolactones that proceeds via the reaction sequence of reductive coupling-carbonylation-reductive elimination (Eq. 46) [48].

(46)

Cyclopentenones could be also prepared from the BuLi-mediated reaction of zirconacyclopentadienes with CO (Eq. 47) [49]. The work reported by Takahashi represents the first example of cyclopentenone formation from two alkynes and CO mediated by metallocenes.

(47)

Construction of Carbocycles via Zirconacycles and Titanacycles

43

3.3.2 Isocyanides as One-Carbon Unit Insertion of isocyanides into zirconacyclopentanes and zirconacyclopentenes affords the corresponding zirconocene h2-imine complexes. Cyclopentylamine derivatives could be prepared by trapping of the insertion intermediates using alkenes, alkynes, and carbonyl compounds [50]. For example, insertion of phenylisocyanide into bicyclic zirconacyclopentenes affords iminoacyl complexes that rearrange to give a, b-unsaturated zirconocene h2-imine complexes. These complexes react with alkenes or alkynes to give cyclopententylamines (Eq. 48) [51].

(48)

Isocyanides can also insert into metallacyclopentadienes [52]. Majoral and coworkers reported insertion of isocyanides into indenylzirconacyclopentadienes and proved the formation of h1-imine zirconocene complex, which is intramolecularly stabilized by a phosphino group. Elimination of the metal fragment “Cp2Zr” give the corresponding b-phosphino imine derivatives or the unexpected b-iminophosphine by hydrolysis with HCl (Eq. 49) [53].

(49)

44

Z. Xi · Z. Li

(50)

If a sterically hindered isocyanide was used, only iminocyclopentadienes were formed in the presence of CuCl or NiCl2(PPh3)2 (Eq. 50) [54]. 3.3.3 Other One-Carbon Unit Equivalents 1,1-Dihalo-1-lithio species (halogenocarbenoids) undergo double insertion into the carbon–zirconium bonds of a zirconacyclopentane to produce, after hydrolysis, bicyclo[3.3.0]octanes (Eq. 51) [55].

(51)

Allenyl carbenoids (3-chloro-1-lithioalk-1-ynes) insert into zirconacyclopentanes and zirconacyclopentenes to afford cyclic h3-allenyl/prop-2-ynyl zirconocene complexes which give cyclized-alcohol products on addition of aldehydes activated with boron trifluoride-diethyl ether (Eq. 52) [56].

(52)

Xi and coworkers reported a one-pot procedure for the preparation of highly substituted indenes, tetrahydroindenes, and cyclopentadienes via Lewis acid mediated reactions of zirconacyclopentadienes with aldehydes. The carbonyl groups of aldehydes were deoxygenated in the reaction and behaved formally as a one-carbon unit (Eq. 53) [57].

Construction of Carbocycles via Zirconacycles and Titanacycles

45

(53)

Acyl chloride was found to behave as a one-carbon unit when treated with zirconacyclopentanes and zirconacyclopentenes in the presence of CuCl. Cyclopentene and cyclopentadiene derivatives were obtained, respectively (Eqs. 54, 55) [58, 59].

(54)

(55)

Interestingly, propynoates and iodopropenoates can also behave as one-carbon unit equivalents to form 1,1-addition products. In the presence of CuCl, zirconacyclopentadienes react with iodopropenoatesto give cyclopentadiene derivatives (Eq. 56) [60, 61].

(56)

In conclusion, five-membered metallacycles of titanocene and zirconocene are convenient starting materials for the construction of five-membered carbocyclic compounds. The formation of five-membered carbocycles can be accomplished by addition reactions (or insertion reactions) of a variety of electrophiles, such as CO, RCN, RNC, bis(trichloromethyl)carbonate, allenyl carbenoids, halogencarbenoids, aldehyde, acyl chlorides, propynoates, and iodopropenoatesthe to the five-membered metallacycles.

46

Z. Xi · Z. Li

3.3.4 Preparation of Five-Membered Heterocycles Replacement of the Cp2Zr or Cp2Ti units in five-membered metallacycles by a different metal or by an atom such as N and S provides an important route to other five-membered metallacycles or five-membered heterocycles containing N or S and so on (Eq. 57) [62, 63].

(57)

Me2SiCl2 does not react with zirconacyclopentadienes. When MeHSiCl2 or H2SiCl2 is used as a silyl electrophile, the reaction proceeds at room temperature to give the corresponding siloles in high yields [64]. Tilley and coworkers have reported a general and efficient method for the synthesis of various functionalized thiophene-1-oxide derivatives, via the reaction of zirconacyclopentadienes with SO2 [65]. Thiophenes were also obtained by the reaction of zirconacyclopentadienes with S2Cl2 [66]. When nitrosobenzene was used, Lewis acids were found to be effective for the promotion of formation of pyrrole derivatives from the reaction of zirconacyclopentadienes with nitrosobenzene (Eq. 58) [67].

(58)

Homocoupling of a conjugated diyne proceeded to give the single titanacyclopentadiene, which was utilized for the preparation of a heterocyclic compound (Eq. 59) [68].

(59)

Construction of Carbocycles via Zirconacycles and Titanacycles

47

3.4 Six-Membered Carbocycles Insertion of a two-carbon unit into a five-membered metallacycle may afford formation of a six-membered carbocycle (Eq. 60), such as a benzene derivative via a formal [2+2+2] aromatization of three alkynes. Similarly, insertion of a C–X unit such as a nitrile into a five-membered metallacycle may afford formation of a six-membered heterocycle, such as a pyridine derivative (Eq. 60). In recent years, Takahashi laboratory and other laboratories have developed a number of synthetically useful methods for six-membered cyclic compounds by taking advantage of five-membered metallacycles of zirconocenes and titanocenes [1–5].

(60)

3.4.1 Benzene Derivatives In the presence of CuCl or NiBr2(PPh3)2, the unsymmetrically substituted zirconacyclopentadienes generated in situ react smoothly with a third alkyne to afford benzene derivatives of three different alkynes (Eq. 61) [69, 70]. As a whole, this is the first example of highly selective, one-pot and high-yield preparation of benzene derivatives from three different alkynes. It should be pointed out that in the case of CuCl-mediated reactions the third alkyne should have at least one electron-withdrawing group. In the case of NiBr2(PPh3)2, the third alkyne could be normal alkynes bearing both electron withdrawing groups and electron donating groups. Reaction of zirconacyclopentadienes with carbenes affords zirconacyclopentene–cyclopropane fused ring intermediates, which further react with CO to generate 1,2,3,5-tetrasubstituted benzenes via a novel skeletal rearrangement (Eq. 62) [30].

(61)

48

Z. Xi · Z. Li

(62)

Naphthalene derivatives could be prepared by the reactions of zirconaindenes with allyl halides in the presence of ZnX2 (X=Br or Cl) and a catalytic amount of Pd(PPh3)4 (Eq. 63) [71].

(63)

2,3,4,5-Tetraalkyl styrenes were obtained when zirconacyclopentadienes were treated with 1,4-dihalo-2-butyne in the presence of CuCl, representing the first example of construction of styrene derivatives from three molecules of alkynes (Eq. 64) [72].

(64)

Buta-2,3-diene-1-yl benezene derivatives were obtained when zirconacyclopentadienes reacted with two propargyl halides in the presence of CuCl (Eq. 65) [73].

(65)

Formation of multi-substituted arylalkynes was achieved via Ni-catalyzed coupling reaction of zirconacyclopentadienes with two alkynyl halides (Eq. 66) [74].

(66)

Construction of Carbocycles via Zirconacycles and Titanacycles

49

Scheme 3 Homologation

Fused aromatic compounds such as polyacenes have attracted much attention as organic conductive materials. However, established methods are very limited. Lack of general and convenient synthetic methods for fused aromatic compounds and their very poor solubility in organic solvents are the most serious problems that control further advances in this very important field. Takahashi and coworkers have recently developed a synthetically useful method for preparation of fused aromatic compounds, by using the zirconocene-mediated aromatization of alkynes. In order to solve the solubility problem, alkyl substituents are introduced into to the skeletons. In principle, two types of synthetic protocols have been used. Type I protocol is via the homologation starting from a functionalized benzene derivative (Scheme 3) [75]; the Type II protocol is via the intermolecular cycloaddition of two alkynes to an arene (Scheme 4) [76].

Scheme 4 Intermolecular cycloaddition

50

Z. Xi · Z. Li

3.4.2 Pyridine Derivatives and Related Compounds Six-membered heterocycles were obtained from two different alkynes and other unsaturated organic substrates involving C=O and C=N moieties. The Reppe-type cyclotrimerization can be also applied for preparation of pyridine derivatives when one of the alkynes is replaced by a nitrile. The pyridine formation from two alkynes and a nitrile with Co complexes was originated by Wakatsuki and Yamazaki [77].Although this method is effective, there is a critical problem for the selective intermolecular coupling of two different alkynes with a nitrile. As shown in Eq. 67, two isomers of pyridine derivatives are formed when a metallacyclopentadiene reacts with a nitrile, due to the two possible orientations of the nitrile in its coupling with the unsymmetrically substituted metallacyclopentadienes.

(67)

Takahashi and coworkers reported a novel coupling reaction of azazirconacyclopentadienes, which were prepared in situ from an alkyne and a nitrile, with a different alkyne in the presence of NiX2(PPh3)2 to afford only single isomer of pyridine (Eq. 68) [78]. Pyridine derivatives with five different substituents from two different unsymmetrical alkynes and a nitrile were prepared with high regioselectivity and in good to excellent yields [78].

(68)

This method could also be applied for the formation of iminopyridines and pyridones using carbodiimide derivatives and isocyanate instead of nitriles (Eq. 69) [78b]. 3.4.3 Others Cyclohexadiene derivatives were obtained in high yields via the reaction of zirconacyclopentadienes with dimethyl maleate, dimethyl fumarate or allylic chlorides in the presence of CuCl (Eq. 70) [69b, 79].

Construction of Carbocycles via Zirconacycles and Titanacycles

51

(69)

(70)

Highly substituted pyran derivatives were synthesized with high regioselectivity from the reaction of zirconacycloipentadienes with diethyl ketomalonate in the presence of two equivalents of BiCl3 (Eq. 71) [80]. When zirconacyclopentadienes were treated with azodicarboxylates in the presence of CuCl, dihydropyridazine derivatives could be prepared (Eq. 71) [80].

(71)

52

Z. Xi · Z. Li

3.5 Seven-Membered Carbocycles and Others There are fewer examples concerning the formation of higher ring compounds, such as seven-, eight- and nine-membered cyclic compounds, from metallacycles of titanocene and zirconocene. 3-Chloro-2-chlorometheyl-1-propene acted as a three-carbon unit building block that after the reaction with zirconacyclopentadienes afforded methylenecycloheptadienes (Eq. 72) [79].

(72)

The first example of cyclooctatetraene formation from metallacyclopentadienes was reported by Takahashi and coworkers [81]. Sequential treatment of zirconacyclopentadiene with two equivalents of CuCl and one equivalent of NBS afforded cyclooctatetraenes in good yields (Eq. 73).

(73)

In similar protocol, the coupling of certain bicyclic zirconacyclopentadienes with diiodo compounds also gave cyclooctatetraene derivatives (Eq. 74) [82]. This reaction depends on the size of the side ring of the bicyclic zirconacyclopentadiene. Both simple zirconacyclopentadienes and bicyclic zirconacyclopentsdienes with a six-membered side ring do not give the desired eightmembered ring compounds [82].

(74)

The formation of eight- and nine-membered cyclic compounds has been achieved by a copper-catalyzed intermolecular [4+4] and [4+5] coupling of zirconacyclopentadienes with bis(halomethyl)arenes (Eq. 75) [83].

Construction of Carbocycles via Zirconacycles and Titanacycles

53

(75)

4 Concluding Remark Metallacycles, mainly five-membered ones of zirconocene and titanocene, have contributed significantly to the development of synthetically useful methods for cyclic compounds, especially to the selective construction of complexed cyclic compounds from different components. More applications of these useful protocols can be expected. Five-membered metallacycles are very popular. However, on the contrary, six-membered metallacycles are very rare. General and practical methods for six-membered metallacycles are desirable, since interesting and rich reaction chemistry and applications of these metallacycles can be expected.

References 1. Wailes PC, Coutts RSP, Weigold H (1974) Organometallic chemistry of titanium, zirconium, and hafnium. Academic Press, New York 2. (a) Negishi E, Huo S (2002) Synthesis and reactivity of zirconocene derivatives. In: Marek I (ed) Titanium and zirconium in organic synthesis. Wiley-VCH, chap 1. (b) Negishi E, Takahashi T (1998) Bull Chem Soc Jpn 71:755. (c) Negishi E, Takahashi T (1994) Acc Chem Res 27:124. (d) Negishi E, Takahashi T (1988) Synthesis 1. (e) Negishi E (1987) Acc Chem Res 20:65. (f) Negishi E, Takahashi T (1985) Aldrichimica Acta 18:31 3. (a) Takahashi T, Li Y (2002) Zirconacyclopentadienes in organic synthesis. In: Marek I (ed) Titanium and zirconium in organic synthesis. Wiley-VCH, chap 2. (b) Takahashi T, Kotora M, Hara R, Xi Z (1999) Bull Chem Soc Jpn 72:2591. (c) Takahashi T, Xi Z, Kotora M (1998) Recent Res Devel in Pure Appl Chem 2:515. (d) Takahashi T, Xi Z, Hara R (1997) Res Trends 2:117 4. (a) Buchwald SL, Broene RD (1993) Science 1696. (b) Buchwald SL, Nielsen RB (1988) Chem Rev 88:1047 5. (a) Rosenthal U, Burlakov VV (2002) Organometallic chemistry of titanocene and zirconocene complexes with bis(trimethylsilyl)acetylene as the basis for applications in organic synthesis. In: Marek I (ed) Titanium and zirconium in organic synthesis. WileyVCH, chap 10. (b) Rosenthal U, Pellny PM, Kirchbauer FG, Burlakov VV (2000) Acc Chem

54

6. 7. 8. 9.

10. 11.

12. 13.

14.

15.

16.

17.

18. 19. 20. 21. 22. 23.

24. 25.

Z. Xi · Z. Li Res 33:119. (c) Ohff A, Pulst S, Peulecke N,Arndt P, Burlakov VV, Rosenthal U (1996) Synlett 111 Negishi E, Cederbaum FE, Takahashi T (1986) Tetrahedron Lett 27:2829 Takahashi T, Murakami M, Kunishige M, Saburi M, Uchida Y, Kozawa K, Uchida T, Swanson DR, Negishi E (1989) Chem Lett 761 Takahashi T, Seki T, Nitto Y, Saburi M, Rousset CJ, Negishi E (1991) J Am Chem Soc 113:6266 (a) Erker G (1977) J Organomet Chem 134:189. (b) Erker G, Kropp K (1979) J Am Chem Soc 101:3659. (c) Buchwald SL, Watson BT, Lum RT, Nugent WA (1987) J Am Chem Soc 109:7137 Takahashi T, Tamura M, Saburi M, Uchida Y, Negishi E (1989) J Chem Soc Chem Commun 852 (a) Takahashi T, Kageyama M, Denisov V, Hara R, Negishi E (1993) Tetrahedron Lett 34:687. (b) Takahashi T, Xi C, Xi Z, Kageyama M, Fischer R, Nakajima K, Negishi E (1998) J Org Chem 63:6802 (a) Mori M, Kuroda S, Dekura F (1999) J Am Chem Soc 121:5591. (b) Kempe R, Spannenberg A, Lefeber C, Zippel T, Rosenthal U (1998) Z Krist 213:791 Takeda T (2002) Titanium-based olefin metathesis and related reactions. In: Marek I (ed) Titanium and zirconium in organic synthesis. Wiley-VCH, chap 14 (and references therein) (a) Takahashi T, Xi Z, Obora Y, Suzuki N (1995) J Am Chem Soc 117:2665. (b) Xi Z, Fischer R, Hara R, Sun W, Obora Y, Suzuki N, Nakajima K, Takahashi T (1997) J Am Chem Soc 119:12842. (c) Yu T, Deng L, Zhao C, Li Z, Xi Z (2003) Tetrahedron Lett 44:677 (a) Rousset CJ, Swanson DR, Lamaty F, Negishi E (1989) Tetrahedron Lett 30:5105. (b) Nugent WA, Taber DF (1989) J Am Chem Soc 111:6435. (c) Gell I, Schwartz (1979) J Chem Soc Chem Commun 244 (a) Negishi E, Holmes SJ, Tour JM, Miller JA (1985) J Am Chem Soc 107:2568. (b) Negishi E, Sawada H, Tour JM, Wei Y (1988) J Org Chem 53:913. (c) Nugent WA, Thorn DL, Harlow RL (1987) J Am Chem Soc 109:2788. (d) Fagan PJ, Nugent WA (1988) J Am Chem Soc 110:2310. (e) Rajanbabu TV, Nugent WA, Taber DF, Fagan PJ (1988) J Am Chem Soc 110:7128 (a) Davis JM,Whitby RJ, Jaxa-Chamiec A (1992) Tetrahedron Lett 33:5655. (b) Davis JM, Whitby RJ, Jaxa-Chamiec (1994) Synlett 110. (c) Davis JM, Whitby RJ, Jaxa-Chamiec A (1994) Tetrahedron Lett 35:1445. (d) Probert GD,Whitby RJ, Coote SJ (1995) Tetrahedron Lett 36:4113 Sato K, Nishihara Y, Huo S, Xi Z, Takahashi T (2001) J Organomet Chem 633:18 Nugent WA, Calabrese JC (1984) J Am Chem Soc 106:6422 Xi Z, Hara R, Takahashi T (1995) J Org Chem 60:4444 (and references therein) Dembitsky VM, Srebnik M (2002) gem-Metallozirconocenes in organic synthesis. In: Marek I (ed) Titanium and zirconium in organic synthesis. Wiley-VCH, chap 7 (a) Barluenga J, Sanz F, Fananas F (1997) Chem Eur J 3:1324. (b) Barluenga J, Sanz F, Fananas F (1995) J Chem Soc Perk Trans 1 1009 (a) Negishi E, Holmes SJ, Tour JM, Miller JA, Cederbaum FE, Swanson DR, Takahashi T (1989) J Am Chem Soc 111:1136. (b) Negishi E, Swanson DR, Cederbaum FE, Takahashi T (1987) Tetrahedron Lett 28:917. (c) Fuchs PL, Hutchinson DK (1987) J Am Chem Soc 109:4755. (d) Negishi E, Takahashi T, Saba S, van Horn DE, Okukado N (1987) J Am Chem Soc 109:2393 Negishi E, Holmes SJ, Tour JM, Miller JA, Cederbaum FE, Swanson DR, Takahashi T (1988) J Am Chem Soc 110:5383 Oouchi K, Mitani M, Hayakawa M, Yamada T, Mukaiyama T (1996) J Organomet Chem 516:111

Construction of Carbocycles via Zirconacycles and Titanacycles

55

26. (a) Dixon S,Whitby RJ (2002) Elaboration of organozirconium species by insertion of carbenoids. In: Marek I (ed) Titanium and zirconium in organic synthesis.Wiley-VCH, chap 3 27. Xi Z, Huo S, Noguchi Y, Takahashi T (2000) Chem Lett 218 28. Dupuis L, Pirio N, Meunier P, Igau A, Donnadieu B, Majoral JP (1997) Angew Chem Int Ed 36:987 29. Mike CA, Nelson T, Graham J, Cordes AW, Allison NT (1998) Organometallics 7:2573 30. Takahashi T, Ishikawa M, Huo S (2002) J Am Chem Soc 124:388 31. Suzuki N, Kondakov DY, Kageyama M, Kotora M, Hara R, Takahashi T (1995) Tetrahedron 51:4519 32. Takahashi T, Xi Z, Kotora M, Xi C (1996) Tetrahedron Lett 37:7521 33. Ubayama H, Sun W, Xi Z, Takahashi T (1998) Chem Commun 1931 34. Takahashi T, Shen B, Nakajima K, Xi Z (1999) J Org Chem 64:8706 35. (a) Negishi E, Liu F, Choueiry D, Mohamud MM, Silveira A, Reeves M (1996) J Org Chem 61:8325. (b) Boardman LD, Bagheri V, Swada H, Negishi E (1984) J Am Chem Soc 106:6105 36. (a) Khand IU, Knox GR, Pauson PL (1973) J Chem Soc Perkin Trans 1:977. (b) Schore NE (1995) In: Abel EW, Stone FGA,Wilkinson G (eds) Comprehensive organometallic chemistry II. Pergamon, Oxford, vol 12:703. (c) Chung YK (1999) Coord Chem Rev 188:297. (d) Brummond KM, Kent JL (2000) Tetrahedron 56:3263 37. Negishi E (1991) In: Trost BM, Fleming I, Paquette LA (eds) Comprehensive organic synthesis. Pergamon, Oxford, vol 5:1163 (and references therein) 38. (a) Mori M, Uesaka N, Shibasaki M (1992) J Org Chem 57:3519. (b) Agnel G, Owczarczyk Z, Negishi E (1992) Tetrahedron Lett 33:1543. (c) Agnel G, Negishi E (1991) J Am Chem Soc 113:7424 39. Buchwald SL, Watson BT, Huffman JC (1987) J Am Chem Soc 109:2544 40. Takahashi T, Xi Z, Nishihara Y, Huo S, Kasai K, Aoyagi K, Denisov V, Negishi E (1997) Tetrahedron 53:9123 41. (a) Berk SC, Grossman RB, Buchwald SL (1993) J Am Chem Soc 115:4912. (b) Berk SC, Grossman RB, Buchwald SL (1994) J Am Chem Soc 116:8593. (c) Hicks FA, Kablaoui NM, Buchwald SL (1996) J Am Chem Soc 118:9450 42. (a) Hicks FA, Buchwald SL (1996) J Am Chem Soc 118:11688. (b) Hicks FA, Kablaoui NM, Buchwald SL (1999) J Am Chem Soc 121:5881. (c) Hicks FA, Buchwald SL (1999) J Am Chem Soc 121:7026. (d) Sturla SJ, Buchwald SL (1999) J Org Chem 64:5547 43. Geis O, Schmalz HG (1998) Angew Chem Int Ed 37:911 44. Zhao Z, Ding Y, Zhao G (1998) J Org Chem 63:9285 45. (a) Maye JP, Negishi E (1993) Tetronhedron Lett 34:3359. (b) Negishi E, Maye JP, Choueiry D (1995) Tetronhedron 51:4447 46. Uesaka N, Saitoh F, Mori M, Shibasaki M, Okamura K, Date T (1994) J Org Chem 59:5633 47. Wender PA, MacDonald FE (1990) Tetrahedron Lett 31:3691 48. Crowe WE, Vu AT (1996) J Am Chem Soc 118:1557 49. Takahashi T, Huo S, Hara R, Noguchi Y, Nakajima K, Sun W (1999) J Am Chem Soc 121:1094 50. (a) Davis JM,Whitby RJ, Jaxa-Chamiec A (1992) Tetrahedron Lett 33:5655. (b) Davis JM, Whitby RJ, Jaxa-Chamiec A (1994) Tetrahedron Lett 35:1445. (c) Davis JM, Whitby RJ, Jaxa-Chamiec A (1994) Synlett 110. (d) Probert GD, Whitby RJ, Coote SJ (1995) Tetrahedron Lett 36:4113 51. Davis JM, Whitby RJ, Jaxa-Chamiec A (1994) Synlett 110 52. (a) Buchwald SL, Nielsen RB (1988) Chem Rev 88:1047. (b) Negishi E, Swanson DR, Miller S (1988) Tetrahedron Lett 29:1631. (c) Cuny GD, Gutierrez A, Buchwald SL (1991) Organometallics 10:537. (d) Aoyagi K, Kasai K, Kondakov DY, Hara R, Suzuki N, Takahashi T (1994) Inorg Chim Acta 220:319

56

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53. Cadierno V, Zablocka M, Donnadieu B, Igau A, Majoral JP, Skowronska A (1999) J Am Chem Soc 121:11086 54. Takahashi T, Tsai F, Li Y, Nakajiama K (2001) Organometallics 20:4122 55. Vicart N, Whitby RJ (1999) Chem Commum 1241 56. Gordon GJ, Whitby RJ (1997) Chem Commum 1321 57. (a) Xi Z, Li P (2000) Angew Chem Int Ed 39:2950. (b) Zhao C, Li P, Cao X, Xi Z (2002) Chem Eur J 8:4292 58. Takahashi T, Kotora M, Xi Z (1995) J Chem Soc Chem Commun 1503 59. Takahashi T, Xi Z, Kotora M, Xi C (1996) Tetrahedron Lett 37:7521 60. Kotora M, Xi C, Takahashi T (1998) Tetrahedron Lett 39:4321 61. Takahashi T, Sun W, Xi C, Kotora M (1997) Chem Commun 2069 62. (a) Fangan PJ, Nugent WA (1988) J Am Chem Soc 110:2310. (b) RajanBabu TV, Nugent WA, Taber DF, Fangan PJ (1988) J Am Chem Soc 110:7128 63. (a) Buchwald SL, Qun F (1989) J Org Chem 54:2793. (b) Buchwald SL, Fisher RA, Foxman BM (1990) Angew Chem Int Ed 29:771. (c) Spence REV, Hsu DP, Buchwald SL (1992) Organometallics 11:3492. (d) Fangan PJ, Nugent WA, Calabrese JC (1994) J Am Chem Soc 116:1880. (e) Ura Y, Li Y, Xi Z, Takahashi T (1998) Tetrahedron Lett 39:2787. (f) Ura Y, Li Y, Tsai F, Nakajima, Kotora M, Takahashi T (2000) Heterocycles 52:1171 64. Kanno K, Kira M (1999) Chem Lett 1127 65. Jiang B, Tilley TD (1999) J Am Chem Soc 121:9744 66. Suh M, Jiang B, Tilley TD (2000) Angew Chem Int Ed 39:2870 67. Nakamoto M, Tilley TD (2001) Organometallics 20:5515 68. Burlakov VV, Peulecke N, Baumann W, Spannenberg A, Kempe R, Rosenthal U (1997) Collect Czech Chem Commun 62:331 69. (a) Xi Z, Takahashi T (2000) Acta Chimica Sinica 58:1177. (b) Takahashi T, Xi Z,Yamazaki Y, Liu Y, Nakajima K, Kotora M (1998) J Am Chem Soc 120:1672. (c) Takahashi T, Kotora M, Xi Z (1995) J Chem Soc Chem Commun 361 70. Takahashi T, Tsai FY, Li Y, Nakajima K, Kotora M (1999) J Am Chem Soc 121:11093 71. Duan Z, Nakajima K, Takahashi T (2001) Chem Commun 1672 72. Xi Z, Li Z, Umeda C, Guan H, Li P, Kotora M, Takahashi T (2002) Tetrahedron 58:1107 73. (a) Takahashi T, Kotora M, Kasai K, Suzuki N (1994) Organometallics 13:4183. (b) Kotora M, Noguchi Y, Takahashi T (1999) Collect Czech Chem Commun 64:1119 74. Wang H, Tsai F, Takahashi T (2000) Chem Lett 1410 75. Takahashi T, Kitamura M, Shen B, Nakajima K (2000) J Am Chem Soc 122:12876 76. (a) Takahashi T, Hara R, Nishihara Y, Kotora M (1996) J Am Chem Soc 118:5154. (b) Takahashi T, Li Y, Stepnicks P, Kitamura M, Liu Y, Nakajima K, Kotora M (2002) J Am Chem Soc 124:576 77. Wakatsuki Y, Yamazaki H (1973) J Chem Soc Chem Commun 280 78. (a) Takahashi T, Tsai FY, Kotora M (2000) J Am Chem Soc 122:4994. (b) Takahashi T, Tsai FY, Li Y, Wang H, Kondo Y, Yamanaka M, Nakajima K, Kotora M (2002) J Am Chem Soc 124:5059 79. Kotora M, Umeda C, Ishida T, Takahashi (1997) Tetrahedron Lett 38:8355 80. Takahashi T, Li Y, Ito T, Xu F, Nakajima K, Liu Y (2002) J Am Chem Soc 124:1144 81. Takahashi T, Sun W, Nakajima K (1999) Chem Commun 1595 82. Yamamoto Y, Ohno T, Itoh K (1999) Chem Commun 1543 83. Takahashi T, Sun W, Liu Y, Nakajima K, Kotora M (1998) Organometallics 17:3841

Topics Organomet Chem (2004) 8: 57– 137 DOI 10.1007/b96002 © Springer-Verlag Berlin Heidelberg 2004

Metallocene-Catalyzed Selective Reactions Martin Kotora (

)

Charles University, Department of Organic Chemistry, Faculty of Science, Hlavova 8 128 43 Prague 2, Czech Republic [email protected]

1

Introduction

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2.1 2.1.1 2.1.2 2.2 2.3 2.3.1 2.3.2 2.4 2.5 2.6 2.7 2.8 2.9 2.10 2.11

Carbometallation of Alkenes . . . . . . . . . . Carbomagnesation . . . . . . . . . . . . . . . Carboalumination . . . . . . . . . . . . . . . Carbometallation of Alkynes . . . . . . . . . . Dimerization of Alkenes and Alkynes . . . . . Dimerization of Alkenes . . . . . . . . . . . . Dimerization of Alkynes . . . . . . . . . . . . Conjugate Addition . . . . . . . . . . . . . . . Hydroacylation . . . . . . . . . . . . . . . . . Hydroboration . . . . . . . . . . . . . . . . . Hydrosilylation . . . . . . . . . . . . . . . . . Hydration of Alkynes . . . . . . . . . . . . . . Intramolecular Addition of Alcohols to Alkynes Allylic Amination . . . . . . . . . . . . . . . . Reaction of Diazocompounds with C=X Bonds

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60 60 67 69 72 72 74 74 75 77 78 79 79 80 81

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Coupling of Two or More Multiple Bonds . . . . . . . . . . . . . . . . . . .

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3.1 3.1.1 3.1.2 3.1.3 3.2 3.2.1 3.2.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9 3.10 3.11

Coupling of Alkenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hydridic Mechanism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Alkylative Mechanism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Metallacyclopentane Mechanism . . . . . . . . . . . . . . . . . . . . . . . . Coupling of Alkynes and Alkenes . . . . . . . . . . . . . . . . . . . . . . . Intramolecular Coupling . . . . . . . . . . . . . . . . . . . . . . . . . . . . Intermolecular Coupling . . . . . . . . . . . . . . . . . . . . . . . . . . . . Coupling of Alkenes with Carbonyl Group . . . . . . . . . . . . . . . . . . Coupling of Alkenes and Alkynes with Epoxides . . . . . . . . . . . . . . . [2+2+2] Cyclotrimerization of Alkynes . . . . . . . . . . . . . . . . . . . . [2+2+2] Cyclotrimerization of Alkynes with C–Heteroatom Multiple Bonds [2+2+2] Cyclotrimerization of Alkynes with Alkenes . . . . . . . . . . . . . [4+2] Cycloaddition (Diels–Alder Reaction) . . . . . . . . . . . . . . . . . [5+2] Cycloaddition Reaction . . . . . . . . . . . . . . . . . . . . . . . . . Coupling of Allenes with Alkenes . . . . . . . . . . . . . . . . . . . . . . . Multicomponent Couplings of Alkenes with Alkynes . . . . . . . . . . . . .

84 84 86 87 90 90 93 99 101 103 108 111 111 113 113 118

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4

C–C Bond Cleavage Reactions . . . . . . . . . . . . . . . . . . . . . . . . . 123

4.1 4.2

Alkene Metathesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 C–C Bond Cleavage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124

5

Substitution Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124

5.1 5.2

Allylic Substitution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 Propargylic Substitution . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125

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Isomerization Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . 128

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Isomerization of Allyl Alcohols . . . . . . . . . . . . . . . . . . . . . . . . . 128 Isomerization of Propargyl Alcohols . . . . . . . . . . . . . . . . . . . . . . 129

7

Other Reactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 131

7.1 7.2 7.3 7.4 7.5

Cyclization of Dienynes . . . . . . . . . . . . Annulation of Alkynes with Nitrosoaromatics Hydrodechlorination of Aryl Chlorides . . . Reductive Amination of Ketones . . . . . . . Oxidative Cyclization of Amino Alcohols . .

8

Conclusion

References

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131 131 131 132 132

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Abstract Transition metal cyclopentadienyl complexes constitute a large family of compounds that can be used as catalyst for a number of organic transformations such as additions of various organics to double and triple bonds, inter- and intramolecular coupling of double and triple bonds, substitution reactions, functional group interconversions, isomerizations, and C–C bond cleavage reactions. These reactions usually proceed with high degree of regio-, stereo- and enantioselectivity under mild reaction conditions. Moreover, they often display broad tolerance to the presence of other functional groups in the substrates. Keywords Cyclopentadiene · Metallocene · Homogenous catalysis · C–C bond formation

Abbreviations Ac Acetyl BINAP 2,2¢-Bis(diphenylphosphino)-1,1¢-binaphthyl Bn Benzyl Boc tert-Butyloxycarbonyl BTMSA Bis(trimethylsilyl)acetylene Bu Butyl i-Bu iso-Butyl t-Bu tert-Butyl cat Catalytic COD 1,4-Cyclooctadiene Cp Cyclopentadienyl CSA Camphorsulfonic acid

Metallocene-Catalyzed Selective Reactions Cy C5H5 C5Me5 D DMF dppe dppm dr E EBTH eq Et Hex c-Hex Ind Me Oct Ph Pr i-Pr TBS TBAF Tf TFA THF TIPS TMS Ts

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Cyclohexyl Cyclopentadienyl Pentamethylcyclopentadienyl Heat N,N-Dimethylformamide Bis(diphenylphosphino)ethane Bis(diphenylphosphino)methane Diastereoisomer ratio Electrophile Ethylenebis(4,5,6,7-terahydro-1-indenyl) Equivalent Ethyl Hexyl Cyclohexyl Indenyl Methyl Octyl Phenyl Propyl iso-Propyl tert-Butyldimethylsilyl Tetrabutylammonium fluoride Trifluoromethansulfonyl Trifluoroacetic acid Tetrahydrofuran Triisopropylsilyl Trimethylsilyl Tosyl, 4-toluensulfonyl

1 Introduction The discovery of the first cyclopentadienyl transition metal compound – ferrocene [1] – and the confirmation of its structure [2] opened a new era in chemistry. It showed the direct relationship between organic chemistry and inorganic chemistry of transition metals, and provided the necessary impetus for development of a new area: organometallic chemistry. Although, the cyclopentadienylmetal compounds seemed to be rather a chemical curiosity, further research soon revealed their useful potential in chemistry. Namely, it has been shown that many of them can be used as catalysts to facilitate a plethora of reactions and transformation under mild reaction conditions that would be otherwise difficult or even impossible to achieve by using classical organic processes. Cyclopentadienyl ligands have considerable advantage over other ligands based, e.g., on compounds with N- or P-coordination to the central metal atom in complexes, in that they usually remain for the most part uninvolved in the transformation mediated by the central metal atom. They can be considered as

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rather chemically inert ligands that do not interfere or react with reactants during the reaction. This is clearly a consequence of the strong h5-coordination mode between the cyclopentadienyl ring and the metal, and the energetic cost of disrupting this very stable unit. Also, it is possible to tune and change the properties of the metal center by careful changes to the structure of the corresponding cyclopentadienyl moiety. Various degrees of substitution on the cyclopentadienyl ring may change both electronic as well as steric properties of the metal complex. This provides delicate means to control the properties and behavior of the whole complex and also the environment in the close vicinity of the metal atom [3, 4, 5]. Both steric as well as electronic properties have a profound effect on the course of the reaction. These effects have been observed, e.g., in carboalumination of alkenes, [2+2+2]-cyclotrimerization of alkynes, hydroboration, etc. A number of other examples can be found as well. The main goal of this chapter is to give a brief overview of reactions that have been catalyzed by cyclopentadienylmetal complexes and to show their potential and application in organic synthesis. The reactions have been classified into seven types according to their similar features. The tables give some representative examples of chemical transformations. In some cases presumed reaction mechanisms are also shown for better understanding of the course of the reaction. It is necessary to emphasize that the list of the reactions and possible applications is by no means final and many new interesting applications and reactions can be expected to appear in the near future.

2 Additions to Multiple Bonds 2.1 Carbometallation of Alkenes Generally speaking, carbometallation of alkenes results in the formation of substituted alkanes. In this process two new bonds at each terminus of the double bond are formed. 2.1.1 Carbomagnesation One of the first practical reactions was the zirconocene (h5–C5H5)2ZrCl2 1 catalyzed carbometallation of simple alkenes with Grignard reagents. Simple alkenes such as 1-decene and styrene underwent ethylmagnesation in high yields to give the new Grignard reagent 2 that after the reaction with an electrophile gave 3 (Scheme 1). The key intermediate of this reaction is the zirconocene–ethylene complex 4 that reacts with the alkene to give the substituted zirconacyclopentane 5. Its transmetallation with another equivalent of EtMgBr

Metallocene-Catalyzed Selective Reactions

61

Scheme 1

Scheme 2

results in the transmetallation of the more sterically hindered Zr–C bond to 6, which decomposes into 2 with the regeneration of the zirconocene–ethylene complex 4 (Scheme 2) [6, 7, 8]. The use of higher alkyl Grignard reagents leads to alkylmagnesation [9]. Although this reaction is of considerable synthetic interest its applicability in organic synthesis is rather limited. Nevertheless, it has been recently shown that the zirconocene 1 catalyzed ethylzincation of alkenes with a mixture composed of Et2Zn/EtMgBr(cat) can be done with high yields of the products (Scheme 3). The reaction mechanism is the same as the above mentioned one. A stoichiometric amount of EtMgBr with respect to the amount of the zirconocene 1 is used only to generate the zirconocene–ethylene complex 4. The transmetallation itself proceeds with diethylzinc to the organozinc intermediate 7. A few examples of ethylzincation followed by iodonolysis are shown in Table 1 [10]. A considerable advance in this area was a discovery that styrene can be catalytically alkylated with various alkyl tosylates in the presence of (cyclohexyl)ethylmagnesium bromide to give the new Grignard reagent 8. Its reaction with oxygen furnishes after hydrolysis the alcohols 9 (Scheme 4).Authors claim that the reaction mechanism does not proceed through a metallacycle formation, instead that the ate-complex 10 is the species responsible for the alkylation (Scheme 5). This procedure enables addition of various linear, branched,

Scheme 3

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Table 1 Zr-catalyzed ethylmagnesation of allyl ethers followed by iodination

Alkene

a

Product

Yield (%) a

GC yields. Isolated yields are given in parentheses.

Scheme 4

Scheme 5

Metallocene-Catalyzed Selective Reactions

63

and cycloalkyl groups to alkenes [11]. The intramolecular variant has been developed as well and it allows preparation of various benzocycloalkenes [12]. The use of alkenes bearing a functional group in the near vicinity of the double bond opens new possibilities for the control of carbomagnesation. Ethylmagnesation of allylic alcohols with the terminal or internal double bond proceeds by different reaction pathways to give different kinds of products. Zirconocene-catalyzed ethylmagnesation of protected and unprotected allylic alcohols with the terminal double bond proceeds through the Grignard reagents 11 and 12 to give the diols 13 and 14 with the opposite diastereoselectivity in high yields (Scheme 6). The advantage of this reaction is that by simple means, such as the choice between the protected and unprotected allylic alcohol, it is possible to control diastereoselectivity in the products. The best diastereoselectivity for ethylmagnesation of unprotected allylic alcohols was achieved in Et2O; on the other hand, better yields of the products 13 and 14 were obtained in THF (Table 2). Ethylmagnesation of the protected allylic alcohols proceeded in both media with similar results (Table 3). Homoallylic alcohols undergo ethylmagnesation under the same conditions as well [13].

Scheme 6

Zirconocene-catalyzed carbomagnesation of internal allylic ethers proceeds by a different pathway. The carbometallation of allylic ethers with the internal double bond gives formally the Sn2¢ substitution product 15 with the loss of the ether moiety (Scheme 7). A few examples are given in Table 4. Especially interesting, from the synthetic point of view, is ethylmagnesation of cyclic ethers (the last entry in Table 4), because it opens a pathway to the synthesis of functionalized homoallylic alcohols [14]. An asymmetric variant of this reaction gives products with ees>90% [15]. Also the titanocene (h5-C5H5)2TiCl2 16 has proved to be an excellent catalyst for a number of various alkylation reactions of alkenes and dienes: such as regioselective double alkylation, Mizoroki–Heck type alkylation, carbosilylation, carbomagnesation, and double silylation [16]. Of special interest are the first

Scheme 7

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Table 2 Zr-catalyzed ethylmagnesation of allylic alcohols

Alkene

a

Major Product

dr

Yield (%) c

In Et2O. b In THF. c Isolated yields.

two cases: regioselective double alkylation and Mizoroki–Heck type alkylation. The regioselective double alkylation of vinylarenes enables functionalization of the double bond either by the same two alkyl chains (2 equivalents of alkyl bromide) or two different alkyl chains (two different alkyl bromides) to give 17 (Scheme 8) [17]. It is assumed that the reaction mechanism is series of oneelectron transfer reactions. Some typical examples are given in Table 5. The Mizoroki–Heck type reaction proceeds under similar reaction conditions to give 18 (Scheme 8). However, the change of the solvent from THF to Et2O is required for the successful course of the reaction [16]. Some typical examples are given in Table 6. A plausible reaction pathway for double alkylation of alkenes is outlined in Scheme 9. It is assumed that 16 reacts with RMgX to generate the titanium(III) complex 19. One-electron transfer from 19 to alkyl bromide leads to the cleav-

Scheme 8

Metallocene-Catalyzed Selective Reactions

65

Table 3 Zr-catalyzed ethylmagnesation of allylic ethers

Alkene

Major Product

Yield (%) c

dr

Table 1 Z

a

In Et2O. b In THF. c Isolated yields.

Table 4 Zr-catalyzed ethylmagnesation of allyl ethers

Alkene

Product

Yield (%)

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Scheme 9 Table 5 Ti-catalyzed double alkylation of alkenes

Alkene

a

R1-Br

R2-Br

Product

Yield (%) a

Isolated yields.

age of the C–Br bond to give alkyl radical along with the dibutyltitanocene 20, which readily forms 21 through b-hydrogen elimination. Addition of the formed alkyl radical to styrene affords a benzyl radical species, which recombines with 21 to give the benzyltitanium compound 22. Subsequent transmetallation of 22 with RMgX gives the corresponding benzyl Grignard reagent 23, which after the reaction with alkyl bromide gives the doubly alkylated product 18. The reaction mechanism of the Mizoroki–Heck reaction proceeds through a similar reaction pathway [16].

Metallocene-Catalyzed Selective Reactions

67

Table 6 Ti-catalyzed Mozoroki-Heck reaction

Alkene

a

R-Br

Product

Yield (%) a

Isolated yields. b 16 (20 mol%).

2.1.2 Carboalumination Another type of alkene functionalization is carboalumination. Cyclopentadienylamidotitanium dichlorides such as 24 catalyzed carboalumination of alkenes with triethylaluminium with subsequent oxygenation to furnish the 1,4-diols 25 (Scheme 10) [18]. Some representative examples are given in Table 7. It has been proposed that triethylaluminium initially reacts with 24 to give 26, which after b-hydrogen elimination affords the titanium(II)-ethylene complex 27. Its reaction with alkene gives the titanacycloalkane 28 that after transmetallation with triethylaluminium furnishes the ethyl-alkyl intermediate 29, which releases the catalytically active species 26 and the organoalumium intermediate 30. Its treatment with oxygen followed by acidic workup affords the diols 25 (Scheme 11). Zirconocene also catalyzes carboalumination of alkenes with trimethylaluminium and subsequent oxygenation affords the alcohols 31 (Scheme 12). The successful course of the reaction requires the use of sterically hindered zir-

Scheme 10

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M. Kotora

Scheme 11

Scheme 12

Table 7 Ti-catalyzed carboalumination of alkenes

Alcohol

Product

Yield (%) a

a

Isolated yields. b 24 (10 mol%), solvent CH3CHCl2. c dr 1/1. d dr 2/1.

a

Isolated yields. b 24 (10 mol%), solvent CH3CHCl2 . c dr 1/1. d dr 2/1.

Metallocene-Catalyzed Selective Reactions

69

Table 8 Ti-catalyzed methylalumination of alkenes

Alkene

a

Product

dr

Yield (%) a

Isolated yields.

conocene such as (h5-C5Me5)2ZrCl2 32 bearing pentamethylcyclopentadiene ligands [19]. In this instance the reaction mechanism proceeds by a somewhat different pathway: it is assumed that the reaction mechanism proceeds through the cationic methylzirconocene intermediate [(h5-C5Me5)2ZrMe+]. Some typical examples are given in Table 8. The use of other zirconocenes bearing bulky cyclopentadienyl ligand with chiral centers resulted in the development of an asymmetric variant of this reaction [19a, 20]. 2.2 Carbometallation of Alkynes Carbometallation of alkynes provides one of the possible routes to stereoselectively substituted alkenes. There is no doubt that one of the most useful functionalizations of alkynes is Negishi methylalumination of terminal alkynes [21]. This reaction is catalyzed by the zirconocene 1 and the addition of trimethylaluminium proceeds regioselectively through a stereoselective syn-addition to give the cismethylalkenylalanes 33, which can be used in further reactions with electrophiles or cross-coupling reactions (Scheme 13). This method will not be

Scheme 13

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M. Kotora

dealt with in this section and its scope and application will be presented in a separate chapter. Generally speaking, other cyclopentadienylmetal complex catalyzed carbometallations of alkynes are rather rare but a few interesting examples have been reported. The first one is the zirconocene 1 catalyzed ethylmagnesation of dialkyldiynes with ethylmagnesium bromide to afford a mixture of isomeric enynes 34 (Scheme 14). The ethylation proceeds regioselectively on the terminal carbon atom of the diyne moiety. However, the addition is not stereoselective: a mixture of cis and trans isomers is obtained [22].

Scheme 14

The key steps of the reaction mechanism (Scheme 15) follow those proposed for carbometallation of alkenes. It is noteworthy that the transmetallation with EtMgBr proceeds at the Zr–sp2C bond, which is a rare phenomenon, and at the end of the catalytic cycle vinylmagnesium bromide 35 is obtained, which after hydrolysis affords the enyne 34.

Scheme 15

Interesting carbometallation was reported for the vanadocene (h5C5H5)2VCl2 36 catalyzed addition of trimethylaluminium to bis(trimethylsilyl)butadiyne. The reaction resulted in the formation of the dimethylated enyne 37 (Scheme 16) [23]. Although, the reaction itself was unprecedented and afforded purely the Z-isomer, its synthetic applicability at the present state is negligible because of the low overall yield of the product (27%) and its limited scope. No reasoning for a possible reaction mechanism was given.

Metallocene-Catalyzed Selective Reactions

71

Scheme 16

A second one is the zirconocene 1 catalyzed reaction of chloroalkynes with ethylmagnesium bromide to give substituted the cyclobutenes 38 (Scheme 17). Some typical examples are given in Table 9. The reaction mechanism is outlined in Scheme 18. It is assumed that the first step is the formation of the zirconacyclopentene 39 by the reaction of ethylene-zirconocene complex with chloroalkyne followed by subsequent rearrangement to the chlorocyclobutenylzirconium intermediate 40.Alkylation of 40 with EtMgBr followed by b-hydrogen elimination affords the cyclobutene 38 [24].

Scheme 17

Scheme 18

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Table 9 Zr-catalyzed formation of cyclobutenes

Chloroalkyne

a

Product

Yield (%) a

GC yields.

2.3 Dimerization of Alkenes and Alkynes 2.3.1 Dimerization of Alkenes Transition metal complex catalyzed tail-to-tail dimerization of acrylates represents an attractive and alternative route to adipic acid and has received considerable attention. Among many catalytic systems the ones with substituted cyclopentadienyl or indenyl ligands exhibit high activity under mild reaction conditions.Acrylates are dimerized to a mixture of cis and trans isomers of the methyl hexenedioates 41 and 42 (Scheme 19). Turnover (TO) frequencies for different catalysts varied to a considerable extent: 43a (h5-C5Me5)Rh(CH2= CH2)P(OMe)3 (slow), 43b (h5-C5Me5)Rh(CH2=CH2)2 (6.6 TO/min), 43c (11 TO/min), 43d (11 TO/min), 43e (h5-C5H5)Rh(CH2=CH2)2 (0.1 TO/min), 43f (1 TO/min). The catalytically active species for acrylate dimerization were usually cationic hydride species generated from the corresponding neutral complexes by the reaction with H(Et2O)B(3,5-(CF3)2Ph)4 [25]. Iridium analogs were completely catalytically inactive. On the other hand, efficient catalytic dimerization of simple alkenes can be usually achieved by early transition metal alkene or diene complexes. For example the niobium-butadiene complexes 44 and 45 also showed good catalytic activity for dimerization of isoprene into a mixture of the head-to-tail and head-to-head dimers 46 and 47 (Scheme 20). The former catalyst gave products in 85:15 ratio and the latter one gave rise to 70:30 ratio [26].

Metallocene-Catalyzed Selective Reactions

73

Scheme 19

Scheme 20

The cycloolefin–tantalum complex (h5-C5Me5)Ta(cyclooctene)Cl 48 is capable of dimerization of various olefins into a mixture of the head-to-tail and head-to-head dimers 49 and 50 (Scheme 21) [27]. Some representative results are summarized in Table 10. It was shown that the dimerization process proceeds through series of reversible metallacycle formations such as tantalacyclopentanes and tantalacyclobutanes, and b-hydrogen eliminations. The dimerization ends in reductive elimination of the organyl moiety from the intermediate alkylhydridotantalum species.

Scheme 21

Selective dimerization of ethene to 1-butene was reported for the tantalum hydride 51 [28]. The reaction proceeds through hydrotantalation of ethene to give alkyl tantalum compound, followed by the insertion of another molecule of ethene and b-hydrogen elimination.

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Table 10 Ta-catalyzed dimerization of alkenes

Alkene

Ratio of 49/50

2.3.2 Dimerization of Alkynes Dimerization of terminal alkynes has been extensively explored with numerous transition metal catalysts. Nevertheless, tertiary propargyl alcohols can be dimerized in an unprecedented way into the dienones 52 under catalysis of [(h5-C5H5)Ru(MeCN)3]+PF6- 53 (Scheme 22). The course of the reaction depends on the solvent used, which influences the stereochemistry of the double bond as well as regioselectivity of the dimerization. The best results for the formation of Z-dienones were obtained in a mixture of THF/acetone at low temperatures (–20 to 0 °C). E-isomers were obtained by carrying out the reaction in acetone at 60 °C. Table 11 demonstrates the broad scope of this unusual dimerization. A number of functional groups is tolerated [29].

Scheme 22

2.4 Conjugate Addition The late transition metal hydrides may behave like mild redox Lewis acid and base catalysts. This makes them useful for the generation of carbon nucleophiles from protonucleophiles by activation of the a-C–H bond adjacent to electron withdrawing groups (CN, COR). One of such catalysts is the iridium hydride 54 that can reversibly abstract a proton from an active methylene compound and act as a catalyst for Michael addition. The reaction of ethyl acetoacetate and cyanoacetate with acrylonitrile

Metallocene-Catalyzed Selective Reactions

75

Table 11 Ru-catalyzed dimerization of propargyl alcohols

Propargyl alcohol

a

T (°C)

Product

Yield (%) a

Isolated yields.

Scheme 23

at room temperature afforded almost quantitatively the products of twofold addition 55 (Scheme 23) [30]. On the other hand, ruthenium hydrides selectively promote monoaddition. The ruthenium hydrides (h5-C5H5)RuH(PPh3)2 56 and (h5-C5Me5)RuH(PPh3)2 57 are efficient catalysts for conjugate addition of various carbonyl compounds to activated alkenes to furnish the polycarbonyl compounds such as 58 and 59 (Scheme 24) [31]. 2.5 Hydroacylation Hydroacylation of alkenes with aldehydes is convenient method for the construction of C–C bonds under mild and neutral reaction conditions. Both intra and intermolecular variants are known. Hydroacylation proceeds through activation of the C–H bond of the aldehyde moiety followed by the addition to the double bond.

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Scheme 24

Scheme 25

Table 12 Co-catalyzed hydroacylation of trimethylsilylethene

Aldehyde

a

TOF (TO/h)

Conversion of the starting material.

Con. (%) a

Metallocene-Catalyzed Selective Reactions

77

Intermolecular hydroacylation of the electron-rich alkene (trimethylsilylethene) with various aldehydes to give the ketones 60 was catalyzed by the cobalt complex 61 at 35 °C with high yields (Scheme 25 and Table 12) [32]. Cyclopentadienylrhodium complexes were used for tandem Claisen rearrangement-hydrocylation of the allylenolethers 62 to the pentenals 63, which were subsequently cyclized to the cyclopentanones 64 (Scheme 26). Activity of the monomeric (h5-C5H5)Rh(CO)2 65 and the polystyrene supported catalyst 66 was compared. The results clearly showed that the latter one gave the better results (Table 13) [33].

Scheme 26

Table 13 Rh-catalyzed rearrangement-hydroacylation of allylenolethers

Ether

Solvent

Cat. (mol%)

dppe (mol%)

Yield (%) a 63/64

62a 62a 62a 62ab 62b

PhCN DMF decane PhCN PhCN

1.5 1.5 1 2 1.5

3 1.5 1 2 1.5

2/96 8/68 97/ Mg > Zn > Al Electrophilicty: Al > Zn > Mg > Li

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E. Negishi · Z. Tan

it might also participate in Zr-catalyzed acyclic bimetallic carbozincation as well. With these simple notions in mind, the reaction of terminal alkenes with Et2Zn (0.5 molar equivalents) was carried out in THF in the presence of 10 mol% of Cl2ZrCp2, but the expected carbozincation was not observed. It was soon found, however, that addition of 20 mol% of EtMgBr to the above reaction mixture would induce a smooth carbozincation to produce diisoalkylzincs in good yields except with styrene with which the product yield was 58%. The representative experimental results are summarized in Scheme 21, and a plausible mechanism is shown in Scheme 22 [173]. It should be pointed out here that this carbozincation is generally significantly cleaner and higher yielding than the corresponding ethylmagnesation.

Scheme 21

Scheme 22

The products can be directly used as useful isoalkylating agents in the Pdcatalyzed cross-coupling (Scheme 23). Although not fully clarified, the requirement for EtMgBr indicates that Et2Zn most probably does not readily dialkylate Cl2ZrCp2. Nor does it participate in the Zr-catalyzed bimetallic carbometallation in a manner of Al. These facts may be explained in terms of its lower nucleophilicity relative to EtMgBr and lower electrophilicity relative to Et3Al, respectively. Once Et2ZrCp2 is generated by the

Diastereoselective, Enantioselective, and Regioselective Carboalumination

161

Scheme 23

reaction of EtMgBr with Cl2ZrCp2, however, Et2Zn must be capable of sustaining the catalytic cycle shown in Scheme 21 in a manner of EtMgBr. This has indeed been established by treating a preformed zirconacyclopentane containing a b-nOct group with one equivalent each of Et2Zn and PMe3 to produce the expected (CH2CH2)ZrCp2·PMe3 and 2-ethyldecyl(ethyl)zinc in good yields. Treatment of the latter with I2 gave 2-ethyldecyl iodide in 80% yield [173]. In fact, the first carbozincation promoted by Cp2Zr derivatives was reported as early as 1983 [174]. Some representative results are shown in Scheme 24. Unlike the Zr-catalyzed carbozincation of alkenes discussed above, this carbozincation proceeded with Me2Zn, suggesting an acyclic process at least for this case. The high regioselectivity figures shown in Eq. 2 and Eq. 3 in Scheme 24 are most likely due to competitive terminal zincation of alkynes favoring the formation of 1,1-dimetalloalkenes. The use of I2ZrCp2 in place of Cl2ZrCp2 was desirable, as it permitted a much faster and higher yielding reaction.Although the reaction did proceed with a substoichiometric amount of I2ZrCp2, its catal-

(1) (2)

(3) Scheme 24

162

E. Negishi · Z. Tan

ysis is still marginal. Despite various shortcomings presented above, the reaction clearly deserves to be further investigated. At this point, however, any mechanistic discussion is premature. 5.3 Carbozirconation Induced by Alkyllithiums Treatment of Cl2ZrCp2 with 2 equivalents of nBuLi gives at low temperatures n Bu2ZrCp2 that decomposes via b-H abstraction to give (1-butene)zirconocene, often called the Negishi reagent [158, 159, 175, 176]. This can, in turn, undergo cyclic carbozirconation with or without displacement of 1-butene to produce five-membered zirconacycles [19, 139, 142, 158, 159, 162, 177, 178, 179]. So, the ability of alkyllithiums to induce stoichiometric cyclic monometallic carbozirconation has been well established and used widely in both organic and organometallic syntheses. In this sense, alkyllithiums are often equivalent to the corresponding alkylmagnesium derivatives. The fact that either alkyllithium or alkylmagnesium derivatives can be used interchangeably to induce virtually the same stoichiometric cyclic carbozirconation is a clear indication that this carbozirconation must be monometallic with little or no influence of Li or Mg at the critical stage of carbometallation. In marked contrast with Mg, however, little or nothing appears to be known about Zr-catalyzed carbolithiation. To further probe this puzzle, Cl2ZrCp2 was treated with an excess (≥3 molar equivalents) of nHexLi to partially simulate catalytic conditions. With 3.3 molar equivalents of nHexLi, the reaction produced in nearly quantitative yield nHex3ZrCp (35). Thus, one of the two Cp groups was displaced as LiCp formed in 98% yield. Interestingly, addition of one equivalent of 1-hexene to the mixture of 35 and LiCp produced zirconacyclopentane (36) in ≥80% yield. Evidently, the mixture of 35 and LiCp must exist in equilibrium with small quantities of nHex2ZrCp2 and nHexLi and serve as a reservoir of nHex2ZrCp2 [175]. Even more intriguing was the reaction of 36

Scheme 25

Diastereoselective, Enantioselective, and Regioselective Carboalumination

163

prepared by the well-established reaction of nHex2ZrCp2 with 1-hexene [162], with two equivalents of nHexLi once again to partially simulate catalytic conditions. The reaction produced a formally 14-electron lithium zirconate, which could be represented only by a fluxional structure (37).Although it was not feasible to obtain its X-ray structure, its NMR data indicated the presence of two nonequivalent nHex groups and 2,3-dibutyl-1,4-butylidene moiety undergoing a rapid transmetallation to make the two halves equivalent on the NMR time scale. The results presented above are summarized in Scheme 25. 5.4 Summary of the Effects of Metal Countercations Regardless of which metal countercation is used, the crucial requirement for an empty valence-shell orbital of Zr is evident in all of the stoichiometric and catalytic carbozirconation reactions discussed in this chapter. With highly nucleophilic alkyllithium and alkylmagnesium reagents, dialkylation of Cl2ZrCp2 occurs readily to produce dialkylzirconocenes. These products are often thermally unstable and decompose via b-H abstraction leading to the formation of three-membered zirconacycles. These zirconacycles can undergo cyclic monometallic carbozirconation to produce five-membered zirconacycles. Alkylmagnesium reagents can then undergo exquisite metathetical ring opening of zirconacyclopentanes accompanied by b-H abstraction to regenerate three-membered zirconacycles, thereby permitting Zr-catalyzed carbomagnesation. This ring opening and b-H abstraction processes can also be induced by alkylzincs, but they are not sufficiently nucleophilic to undergo the initially required dialkylation of Cl2ZrCp2, which must therefore be performed with alkylmagnesiums or perhaps even with alkyllithiums, although the latter remains untested. Alkyllithiums are most probably too nucleophilic to sustain Zr-catalyzed carbometallation via dialkylzinconcene derivatives and five-membered zirconacycles, presumably because alkyllithiums can readily and strongly interact with such Zr species to convert them into catalytically inactive species through “ate” complexation and displacement of Cp and other ligands. In short, they tend to act as catalyst poisons. At present, the carbometallation reactions of Al–Zr reagents appear to be all bimetallic, whether they are acyclic or cyclic. The Zr-catalyzed acyclic bimetallic methylalumination is the only well-established Zr-catalyzed carbometallation reaction permitting introduction of a Me group in a satisfactory manner, although the reaction of the Zn–Zr combination appears to be promising. At present, alkylalanes are also the only class of compounds that undergo Zr-catalyzed cyclic bimetallic carbometallation. The reactivity profiles of Li, Mg, Zn, and Al have been reasonably well delineated. The experimental findings and interpretations presented above may now be extended and applied to the development of those carbometallation re-

164

E. Negishi · Z. Tan

actions involving other mono-, bi-, and multimetallic reagents as well as other related carbometallation reactions, such as the Zr-catalyzed enantioselective carboalumination of alkenes discussed in the following section.

6 Zr-Catalyzed Asymmetric Carboalumination of Alkenes 6.1 Discovery of Zr-Catalyzed Asymmetric Methyl-, Ethyl-, and Higher Alkylalumination of Alkenes 6.1.1 Zr-Catalyzed Asymmetric Alkylation with Alkylmagnesium Reagents via Cyclic Carbozirconation Shortly after the discovery of the Zr-catalyzed carboalumination of alkynes in 1978, attempts were made briefly to observe the corresponding carboalumination of alkenes, but no more than traces of the desired products were formed. This puzzle was soon resolved when the Zr-catalyzed hydrogen-transfer hydroalumination with i Bu3Al was discovered in 1980 [166]. Since the expected products of carboalumination of alkenes would be isoalkylalanes, they could then undergo hydrogen-transfer hydroalumination in competition with the desired carboalumination. With this rationalization, attempts to develop the Zrcatalyzed asymmetric carboalumination were postponed. In 1993, a Zr-catalyzed asymmetric carbometallation proceeding via cyclic carbozirconation induced by alkylmagnesium derivatives was disclosed [180]. This and related reactions sharing a common cyclic carbozirconation process have since been developed by various groups including those of Hoveyda [180, 181, 182, 183, 184, 185], Whitby [186, 187], and Mori [188]. As they are mostly outside the scope of this chapter on Zr-catalyzed carboalumination, no systematic discussion of them is intended here, and the interested readers are referred to recent reviews and references therein [189, 190]. It should however be noted here that the cyclic carbozirconation-based asymmetric C–C bond formation reactions suffer from two significant limitations. One is that highly enantioselective (> 90% ee) C–C bond formation has been observed exclusively with allylically hetrosubstituted alkenes. Although very little has been reported about the use of other simple alkenes, the enantioselectivity in these cases appears to be rather low (< 50% ee). Efforts to develop highly stereoselective procedures applicable to simple ordinary alkenes are clearly desirable. Another noteworthy limitation is that, whereas incorporation of Et by the use of ethylmagnesium derivatives is generally high yielding, that of Pr, Bu, and higher alkyls appears to be low-yielding, typically 35–40%.

Diastereoselective, Enantioselective, and Regioselective Carboalumination

165

6.1.2 Zr-Catalyzed Asymmetric Methylalumination of Ordinary Unactivated Alkenes With the goal of discovering and developing a Zr-catalyzed asymmetric methylmetallation of alkenes represented by Eq. 1 in Scheme 26, the reaction of terminal alkenes with Me3Al-Cl2ZCp2 was reinvestigated [191]. However, the reaction of 1-octene with 1 molar equivalent of Me3Al and 8 mol% of Cl2ZrCp2 yielded just a trace ( 0.99) was achieved using 3 (R1=Me, R2=1-naphthyl) [40]. Substituted cyclopentadienyl

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N. Suzuki

Fig. 5 C2-Symmetric ansa-metallocenes for isospecific olefin polymerization

ligands bridged by a silicon atom were found to be effective for the construction of isospecific ansa-metallocenes (4, [mmmm]=0.98) [41, 42].Yamazaki recently reported that furyl substituents on cyclopentadienyl rings greatly increase catalytic activity of the ansa-zirconocene and hafnocene complexes [43]. Some C1-symmetric ansa-metallocenes also produce isotactic polypropylene, although it is difficult to predict their stereoselectivity in the polymerization. For example, 5 reported by Marks [44] and 6 by Miyake [45] give highly isotactic polypropylene (Fig. 6, 5: M=Hf, [mmmm]=0.95; 6: [mmmm]>0.98).

Fig. 6 C1-Symmetric ansa-metallocenes and a non-bridged metallocene for isospecific polymerization

Stereospecific Olefin Polymerization Catalyzed by Metallocene Complexes

187

There are few examples of non-bridged metallocenes acting as isoselective catalysts. Erker reported metallocenes with chiral auxiliaries on cyclopentadienyl or indenyl ligands [46, 47]. The polymerization proceeds by catalyst control. However, large substituents and a low reaction temperature are necessary to suppress fast rotation of the Cp/indenyl ligands, otherwise tacticity decreases. This limitation also leads to low activity, and it is a drawback of this type of catalyst. It was reported that 1-methylfluorenyl ligands are more effective for isoselective polymerization even at 60 °C (7: [mmmm]=0.83) [48]. Isorich polymerization with the achiral catalyst, Cp2TiPh2, by chain-end control was reported, although a low polymerization temperature was needed and the tacticity was not satisfactory [37]. Of course, catalyst structure is very important for highly isoselective polymerization. However, tacticity of polyolefins depends not only on catalyst structures but also on co-catalysts, reaction conditions such as temperature, monomer concentrations and Al/metal ratios. For example, in the case of a certain catalyst, isotacticity of polymers can strongly depend on the temperature for pre-mixing MAO and a catalyst precursor. The effect of reaction pressure up to 1500 MPa was also reported in hexene polymerization [49]. Group 3 metallocene hydrides, which usually form dimers, are known to be “single-component” catalysts for ethylene polymerization [50]. The olefin inserted species, Cp¢2Ln-R, is isoelectronic to active cationic species of group 4 metallocenes, and it can catalyze polymerization without such co-catalysts as MAO and borane compounds. Examples of isospecific a-olefin polymerization catalysts are, however, rather rare. Bercaw and Yasuda independently reported ansa-yttrocene complexes with bulky substituents on Cp rings (8 and 9 in Fig. 7) that catalyze polymerization of propylene and a-olefins in a highly isospecific manner, although their activity and molecular weight are moderate (8: polypropylene, [mmmm]=0.97, Mn=4200) [51, 52]. It is interesting that achiral monocyclopentadienylaryloxyyttrium 10 gives isotactic polymerization of hexene ([mmmm]>85%), presumably by chain-end control [53]. Divalent ansa-samarocene analogues, on the other hand, exhibited poor activity, albeit with high isotacticity ([mmmm]>0.95) [54].

Fig. 7 Lanthanide complexes for isospecific propylene polymerization

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2.2 Stereo-Control Mechanism in Isospecific Polymerization In isospecific polymerization by catalytic-site control, the ligand-induced chiral environment in ansa-metallocene complexes is responsible for stereoselectivity. Theoretical studies have shed light on the mechanism of stereoselective insertion, as illustrated in Fig. 8 [55, 56, 57].An olefin approaches the metal from side A with its alkyl (R) group up, while it inserts with the substituents down from side B. Thus insertion occurs only at a si-face in this case. This is explained by steric repulsion between the R group and the propagating polymer chain, which rotates avoiding the sterically demanding ligand. Steric repulsion between the alkyl group and ligand are of little importance for stereoselectivity. This mechanism is supported by experimental work. Propylene inserts into a Zr–CH3 bond with no stereoselectivity at all (re/si=1:1), while insertion of butene occurs with 1:2 selectivity [58]. On the other hand, the selectivity in propylene insertion into Zr-CH2CH3 is excellent [59]. Experimental studies show that the face selectivity during polymerization is complete, and that stereoerrors observed in polypropylene are not due to misinsertion but rather to chain-end epimerization [60, 61, 62].

Fig. 8 Face selectivity in olefin approach

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2.3 Racemo-Selective Synthesis The usual preparative method of bridged group 4 metallocenes that involves a dimetallated (typically, dilithium salt) ligand and a metal halide often gives a mixture of racemi and meso isomers. The ansa-metallocenes for isospecific polymerization, however, must be racemic, and the concomitant meso isomer causes formation of atactic polymers. Separation of the racemic isomers from the racemo/meso mixtures often requires tedious operations. For example, group 4 metallocene chlorides barely survive the usual column chromatograph separation (although a column technique at low temperature under an inert atmosphere may give good results), and occasionally several recrystallizations are required. Introduction of bulky substituents on Cp/indenyl ligands or bridging moieties can improve the racemo/meso ratios in the synthesis of ansa-metallocenes [42, 63, 64, 65]. Exclusive synthesis of the racemic isomer was even achieved using tert-butyl and trimethylsilyl substituents. However, polymerization using the corresponding ansa-zirconocene was not described [66], although the ansa-yttrocene complex 8 produced isotactic polypropylene [51]. There are many examples of ansa-metallocenes designed for stereoselective synthesis [67, 68, 69, 70]. In order to construct a racemo-selective structure, rigid bridging moieties such as biaryl groups or double bridges were used, whereas it does not seem easy to satisfy both a highly racemo-selective structure and a high isospecific catalyst ability. The preparation of a single stereoisomer of the ligand prior to complexation can result in predominant formation of racemic metallocenes. Brintzinger reported an S4-symmtric silylene–stannylene double bridged bis(cyclopentadienyl) ligand, which reacts with zirconium chloride to give a C2-symmetric complex exclusively [71]. Jordan reported a new preparative method that starts with metal amides. Non-metallated ligands react with M(NR2)4 to give ansa-metallocene bisamide complexes [72, 73, 74]. The use of bulky amides results in racemo-rich formation of ansa-metallocene complexes due to steric repulsion, although it requires chlorination to obtain more stable dichlorides. Yamazaki reported meso-selective formation of binuclear m-oxo-ansa-metallocenes [75]. This can be a convenient method for separating meso and racemo-isomers of ansa-bis(substituted cyclopentadienyl)metallocenes, although it might be less effective for non-substituted ansa-bisindenyl complexes [76]. 2.4 Syndiotactic Polypropylene Syndiotactic polypropylene was prepared by a heterogeneous vanadium catalyst with low tacticity. Preparation of highly syndiotactic polypropylene

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Fig. 9 Cs-Symmetric metallocenes for syndiospecific catalysts

([rrrr]=0.86) using the homogeneous catalyst 11 was first reported by Ewen (Fig. 9) [77]. Complex 11 has a Cs-symmetric structure, and propylene inserts to a metal–carbon bond alternately by the re-face and si-face (Fig. 10). It is believed that the monomer approaches the metal with its methyl group down, to avoid repulsive interaction with the propagating polymer chain [78]. A stereoerror found in the metallocene-produced syndiotactic polyolefin is rmmr, which is due to insertion from the wrong face (or chain-end epimerization). Another error, rmr, is formed by “skipped insertion”, which results from migration of the polymer chain without monomer insertion. Although syndiotactic polypropylene is less attractive in industry because of its slow crystallization rate, it still has attracted many chemists for academic

Fig. 10 Formation of syndiotactic polyolefins

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Fig. 11 Catalyst system for iso-block polypropylene

reasons. There have appeared many Cs-symmetric metallocenes derived from 11, and some have succeeded in improving syndiotacticity. Bercaw reported doubly bridged biscyclopentadienyl zirconium 14, which serves as a highly syndiospecific catalyst ([rrrr]=0.99 at 0 °C) [79]. It was also reported that (C5Me5)2MCl2 (M=Zr, Hf) gives syndio-rich polypropylene at low temperature (Zr, [rr]=0.68; Hf, [rr]=0.77 at –20 °C) by chain-end control [80]. 2.5 Hemiisotactic and Iso-Block Polypropylene Metallocene catalysts that allow various ligand designs made possible novel stereoregular polymers that could not be prepared with heterogeneous catalysts. Hemiisotactic polyolefin produced by 12 is an example [81]. Isoselective and aspecific insertion occur alternately in 12. It is of interest that the catalyst without a methyl group (11) gives syndiotactic polymer and the one with a tertbutyl group (13) gives isotactic polymer. Waymouth et al. reported that the non-bridged complex 15 produces iso-block polymers that consist of isotactic sequences and atactic sequences [82]. One rotamer of 15 has C2-symmetry and is thus isospecific, while another is aspecific. Slow isomerization between the two rotamers brings about iso-block polymers. These polypropylenes contain crystalline and amorphous parts, and have an elastomeric character (Fig. 11). 2.6 Regioselectivity: 2,1- and 1,3-Insertion In metallocene-catalyzed propylene polymerization, propagation proceeds via 1,2-insertion of the monomer. 2,1-Insertion gives rise to a secondary alkyl species. This species is known to be much less active for the next insertion and tends to be involved in chain transfer or isomerization into 1,3-inserted species. As shown in Scheme 4, b-hydrogen elimination followed by rotation and re-in-

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Scheme 4 1,3-Insertion of propylene via 2,1-inserted species

sertion resulted in 1,3-insertion of propylene. This trimethylene unit decreases crystallinity of the polymer, and is responsible for the lower melting point compared with those produced by heterogeneous catalysts, despite the high [mmmm].

3 Polystyrene 3.1 Catalysts for Syndiotactic Polystyrene Commonly used polystyrene is produced by radical polymerization in industry and its stereochemistry is atactic. Isotactic polystyrene was achieved by Natta using traditional Ziegler–Natta catalysis in 1956 [83]. Isotactic polystyrene, however, is less interesting in industry because of its slow crystallization rate. Ishihara et al. reported highly syndiotactic polystyrene using halfmetallocene complexes of titanium [84, 85]. Since syndiotactic polystyrene is a highly crystalline polymer with a rather fast crystallization rate, it is a promising material, leading many polymer chemists to investigate the catalysts. Some reviews have appeared and may be consulted [13, 86, 87, 88, 89, 90, 91]. The syndiotactic index, which is a percentage of the insoluble part in refluxing 2-butanone or acetone, is also often used to estimate syndiotacticity of polymers as well as [rr] triad and [rrrr] pentad. Ishihara et al. reported that CpTiCl3– and Cp*TiCl3–MAO catalyst systems synthesize syndiotactic polystyrene [84, 85]. Various styrene derivatives that have alkyl groups or halogens give syndiotactic polymers using these catalysts. CpTiCl2, a Ti(III) species, also shows high catalytic activity and stereospecificity. Zirconium and hafnium complexes are not only less active than titanium but also produce atactic polystyrene. Many studies on the catalysts based on Cp¢TiX3 have appeared, where Cp¢ is a substituted (or non-substituted) cyclopentadienyl, indenyl or related h5-ligand and X can be halogens, alkoxy or

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Fig. 12 Precatalysts for stereospecific polymerization of styrene

alkyl groups.Among the complexes with substituted cyclopentadienyl ligands, the catalytic activity of Cp¢Ti(OMe)3 is in the order C5Me4Et>C5Me5>C5Me4H> C5H5 [89, 92]. Indenyl, benz[e]indenyl and their phenyl-substituted ligands increase activity and stability of the catalysts (16, 17 in Fig. 12) [93, 94]. Brintzinger et al. reported that cyclopenta[1]phenanthrene titanium trichloride 18 exhibits the highest activity among Cp¢TiCl3-type catalysts [95]. Kaminsky et al. showed that fluorinated complexes Cp¢TiF3 exhibit much higher activity than Cp¢TiCl3 [96]. The catalytic activity of Cp*TiX3 decreases in the order F>OMe>Cl. Although titanocene complexes are less active than half-titanocenes, Miyashita et al. showed that a methylene-bridged titanocene 19 is effective for syndiospecific styrene polymerization [97]. A large gap aperture is probably necessary for coordination of styrene. Boranes can be used as activators instead of MAO [98], while the use of dry trialkylaluminum led to atactic polystyrenes [85]. The TiX4-type compounds (X=halogen, alkoxy, alkyl, etc.) aldo can catalyze syndiospecific styrene polymerization, although their activities are lower than Cp¢TiX3. 3.2 Active Species Ti(IV), Ti(III), and even Ti(II) are employed as catalyst precursors, but it is most probable that Ti(III) is the active species [99]. MAO and/or trialkylaluminum

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contained in MAO has been believed to be responsible for reducing Ti(IV) to Ti(III). Recently, Waymouth et al. reported that Cp*Ti(CH2Ph)3/[NHMe2Ph] [B(C6F5)4] did not polymerize styrene in the dark, although it generated syndiotactic polystyrene in the light [100]. They suggested that the light plays an important role in reducing Ti(IV) to Ti(III), which is active for syndiospecific polymerization of styrene. Indeed, Cp*Ti(allyl)2/[NHMe2Ph][B(C6F5)4] is highly active in the dark. 3.3 Mechanism of Syndiospecific Polymerization The propagation of styrene polymerization can be illustrated as in Scheme 5. Contrary to the a-olefin polymerization, the initiation and propagation reactions of styrene proceed via 2,1-insertion of monomers into the Ti–C bond [89, 101, 102]. The monomer inserts with high regioselectivity, and b-hydrogen elimination that terminates the propagation also occurs on 2,1-inserted species. Zambelli showed that molecular weight does not strongly depend on monomer concentration, showing that b-hydrogen elimination to the metal is the predominant chain-transfer process [103]. Its stereochemistry is regulated in chain-end control [104]. p-Coordination of a phenyl group in the last-inserted styrene to titanium in an agostic fashion seems important to control the approach of the next monomer [91].

Scheme 5 Polymerization of styrene catalyzed by half-titanocene complexes

The Cp*TiMe3-B(C6F5)3 catalyst gives syndiotactic polystyrene, while it produced atactic polystyrene in halogenated solutions such as CH2Cl2 or 1,2dichloroethane [105]. In accord with these results, Baird et al. proposed a carbocationic mechanism for styrene polymerization.

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3.4 Isotactic Polystyrene by Metallocene Catalysts Recently, Arai et al. reported preparation of isotactic polystyrene using some ansa-zirconocene complexes [106, 107]. For example, 20 gives isotactic polystyrene with [mmmm]>0.90. Although the isotactic homopolymer of styrene is less attractive for practical use, the catalysts would be useful in the production of stereoregulated styrene–ethylene copolymer. 3.5 Other Catalyst Systems Emulsion polymerization that uses water as a reaction medium is commonly employed for radical polymerization of styrene. Recently, application of Cp*Ti(OR)3/NHMe2Ph+B(C6F5)–4 for emulsion polymerization was reported [108]. The use of transition metals other than group 4 metals is rather rare. Some half-metallocenes of lanthanides can catalyze styrene polymerization without co-catalysts, although atactic polystyrene is obtained [86, 109, 110, 111]. A few non-cyclopentadienyl lanthanocenes are known to be capable of syndio and iso-rich polymerization of styrene [112, 113], whereas activity and stereoregularity are inferior to Ti catalysts. Calcium half-metallocene for syndiospecific “living” polymerization of styrene has been recently reported, although activity and stereoselectivity are not very good [114].

4 Poly(Methyl Methacrylate) 4.1 Background Methyl methacrylate (MMA) is one of the most common polar monomers. Poly(MMA) as commonly used is manufactured by a radical polymerization process. Syndio-rich poly(MMA) ([rr]=0.5–0.7) is obtained by the radical process. This clear transparent polymer is versatile and widely used. Synthesis of highly stereoregular poly(MMA) was achieved by anionic polymerization using organometallic compounds such as alkylaluminum, alkyllithium, and Grignard reagents as initiators. Both isotactic and syndiotactic poly(MMA) can be prepared by careful choice of initiators, additives, solvents, and reaction conditions [115, 116, 117]. Some of these reactions proceed in a living polymerization. However, high molecular weight and high stereoregularity were difficult to simultaneously accomplish by a single initiator system. Yasuda first reported that organolanthanides could efficiently initiate syn-

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diospecific polymerization of MMA in a living manner [118]. Collins showed that cationic zirconocenes are capable of polymerizing MMA [119]. There are several reviews on lanthanocene-catalyzed polymerization of MMA and acrylates [120, 121, 122]. 4.2 Lanthanocene Catalysts Yasuda reported some classes of organolanthanide(III) complexes that efficiently initiate stereoregular polymerization of MMA [118, 124]. In their first report, they employed samarocene hydride dimer, [SmH(C5Me5)2]2 (21),

Fig. 13 Lanthanide complexes for stereospecific MMA polymerization

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monoalkyllanthanides, LnR(C5Me5)2 (22, 23), and their m-bridged complexes (24, 25), as shown in Fig. 13. These catalysts achieved the following features for the first time [124]: i. High molecular weight (Mn), greater than 1¥106 ii. Very narrow polydispersity (Mw/Mn 500 °C for poly(norbornene). This makes structural analysis difficult, and hydrooligomerization products are often used for determination of the stereochemistry.Although homopolymers of cycloolefins cause difficulty in industrial manufacturing because of their high melting points, their copolymers with ethylene are of interest as optical materials, such as compact disks [179]. The mechanism of 1,3-enchainment of cyclopentene is similar to that of propylene. After 1,2-insertion of the monomer, b-hydrogen elimination and reinsertion resulted in 1,3-insertion.An achiral catalyst Cp2ZrCl2 produces cisrich but atactic poly(cyclopentene) that is amorphous polymer [180, 181].A few chiral zirconocenes such as rac-Me2Si(Ind)2ZrCl2 (3, R1=R2=H) [181] and racC2H4(Ind)2ZrCl2 (1b) [180] give highly cis-isotactic polymer, while racC2H4(THInd)2ZrCl2 (2) gives cis- (60%) trans-mixed polymer [182, 183]. The Cs-symmetric complex Ph2C(Cp)(Flu)ZrCl2 (11)/MAO showed low stereoselectivity [181].

Fig. 22 Stereoregularity in cyclopolymers

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Fig. 23 Hydrotrimers of norbornenes

Studies on hydrooligomerization of norbornene revealed that 3 predominantly gave the meso,meso-isomer (66–71%), and 11 gave the rac,rac-trimer in 55–78% selectivity (Fig. 23) [184].

8 Post-Metallocene Catalysts Homogeneous polymerization catalysts that have non-metallocene structures, so-called “post-metallocene” catalysts, have been extensively explored. Stereoselective polymerization using these catalysts has also been reported, although most examples describe polypropylene. Complex 62, a so-called constrained geometry catalyst (CGC), which has a bridged half-metallocene structure and thus is usually not considered a postmetallocene catalyst, is of much interest in ethylene polymerization and copolymerization. Its Zr-enolate complex 49 gives isotactic poly(MMA) despite the Cs-symmetric structure, although it shows in principle no stereoselectivity in propylene polymerization. The titanium–bisamide complex 63 reported by McConville is capable of living polymerization of a-olefins [185]. Formation of isotactic polypropylene ([mmmm]=0.79) using a 63-Al-i-Bu3-[Ph3C][B(C6F5)4] system by catalytic-site control has been reported [186]. Recently Fujita et al. reported that bis(phenoxyimine) complexes 64 show a significant high catalytic activity [187, 188, 189, 190]. Although the complexes 64 have C2-symmetric structures, it was found that the fluorinated derivatives (M=Ti, R1=C6F5, R2=t-Bu, R3=H, t-Bu) produce syndiotactic polypropylene under chain-end control ([rr]=0.98 [191], [rrrr]=0.96 at 0 °C [192]). It is noteworthy that the propylene inserts in a 2,1-fashion [193, 194, 195]. Benzamidinate complexes 65 and 66 also give isotactic polypropylene (66, [mmmm]=0.95–0.98) [196, 197]. Late transition metal catalysts that are highly active and produce high molecular weight polyolefins were recently reported [198, 199]. For example, nickel and palladium–diimine catalysts 67 produce highly branched polyethylene that is totally different from those produced by conventional or homogeneous Ziegler–Natta catalysts [200]. On the other hand, iron and cobalt 2,6-pyridine bis(imine) complexes 68 give linear polyethylene [201, 202]. These catalysts are used with co-catalysts such as MAO, and the active species are cationic. Neu-

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Fig. 24 Post-metallocene catalysts for olefin polymeriation

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tral nickel catalyst 69 was also reported [203]. There have been some examples, albeit few, of stereospecific polymerization using them. Syndiotactic polypropylene is formed by the nickel(II)–diimine complex 67 (M=Ni) at low temperature ([rrrr]=0.80 at –78 °C, 0.65 at 0 °C) [204, 205]. Polymerization proceeds by 1,2-insertion and the stereochemistry is regulated under chain-end control. On the other hand, isotactic polypropylene can be prepared using the iron complexes 68 (M=Fe; [mmmm]=0.55–0.67 at –20 °C) despite the low molecular weight of the polymer [206]. Polymerization proceeds via a 2,1-insertion mechanism by chain-end control.

9 Conclusion It has been shown that a variety of metallocene complexes serve as effective homogeneous, stereoselective polymerization catalysts. They achieve unprecedented polymers that could not be produced by traditional catalysts. Many examples of non-metallocene catalysts have also been studied. In industry, however, conventional heterogeneous catalyst systems are still major processes for the production of polyolefins. In order to apply homogeneous catalysts for commercial processes, practical improvements are needed. Heterogenization of homogeneous catalysts by adsorption on solid supports such as silica gel is one strategy allowing the existing process to be used [207, 208]. Economic drawbacks also must be overcome; the cost of the precatalyst complex is reduced by improvement in its activity. Further, MAO is also expensive, and decreasing this co-catalyst or exploring other inexpensive co-catalysts is being pursued. These technologies will provide increasing numbers of metallocene-produced polyolefins to the market in the near future.

References 1. Ziegler K, Holzkamp E, Breil H, Martin H (1955) Angew Chem 67:541 2. Ziegler, K (1964) Angew Chem 76:545 3. Natta G, Pino P, Corradini P, Danusso F, Mantica E, Mazzanti G, Moraglio G (1955) J Am Chem Soc 77:1708 4. Reichert KH, Meyer KR (1973) Makromol Chem 169:163 5. Long WP, Breslow DS (1975) Liebigs Annal Chem 463 6. Andresen A, Cordes HG, Herwig J, Kaminsky W, Merck A, Mottweiler R, Pein J, Sinn H, Vollmer HJ (1976) Angew Chem 88:689 7. Sinn H, Kaminsky W, Vollmer H-J, Woldt R (1980) Angew Chem Int Ed Engl 19:390 8. Brintzinger HH, Fischer D, Mülhaupt R, Rieger B, Waymouth RM (1995) Angew Chem, Int Ed Engl 34:1143 9. Bochmann M (1996) J Chem Soc, Dalton Trans 255 10. Coates GW (2000) Chem Rev 100:1223 11. Imanishi Y, Naga N (2001) Prog Polym Sci 26:1147 12. Kaminsky W (1996) Macromol Chem Phys 197:3907

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13. Kaminsky W (2000) Catal Today 62:23 14. Kaminsky W, Laban A (2002) Appl Catal A: Gerenal 222:47 15. Fink G, Mülhaupt R, Brintzinger H-H (eds) (1995) Ziegler catalysts. Springer, Berlin Heidelberg New York 16. Scheirs J, Kaminsky W (eds) (2000) Metallocene-based polyolefins. Wiley, West Sussex 17. Arjunan P, McGrath JE, Hanlon TL (eds) (2000) Olefin polymerization emerging frontiers. American Chemical Society, Washington DC 18. Blom R, Follestad A, Rytter E, Tilset M,Ystenes M (eds) (2001) Organometallic catalysts and olefin polymerization: catalysts for a new millennium. Springer, Berlin Heidelberg New York 19. Shapiro PJ (2002) Coord Chem Rev 231:67 20. Jordan RF, Dasher WE, Echols SF (1986) J Am Chem Soc 108:1718 21. Jordan RF, Bajgur CS, Willett R, Scott B (1986) J Am Chem Soc 108:7410 22. Jordan RF (1991) Adv Organomet Chem 32:325 23. Sishta C, Hathorn RM, Marks TJ (1992) J Am Chem Soc 114:1112 24. Yang X, Stern CL, Marks TJ (1991) J Am Chem Soc 113:3623 25. Hlatky GG, Upton DJ, Turner HW, (1991) WO 9109882 26. Chen YX, Stern CL, Marks TJ (1997) J Am Chem Soc 119:2582 27. Chen EYX, Marks TJ (2000) Chem Rev 100:1391 28. Burger BJ, Thompson ME, Cotter WD, Bercaw JE (1990) J Am Chem Soc 112:1566 29. Watson PL (1982) J Am Chem Soc 104:337 30. Mashima K, Fujikawa S, Nakamura A (1993) J Am Chem Soc 115:10990 31. Mashima K, Fujikawa S, Urata H, Tanaka E, Nakamura A (1994) J Chem Soc, Chem Commun 1623 32. Mise T, Kageyama A, Miya S, Yamazaki H (1991) Chem Lett 1525 33. Watson PL, Roe DC (1982) J Am Chem Soc 104:6471 34. Matsuzaki K, Uryu T,Asakura T (1996) NMR Spectroscopy and stereoregularity of polymers. Japan Scientific Societies Press, Tokyo 35. Yamaguchi Y, Suzuki N, Mise T, Wakatsuki Y (1999) Organometallics 18:996 36. Resconi L, Cavallo L, Fait A, Piemontesi F (2000) Chem Rev 100:1253 37. Ewen JA (1984) J Am Chem Soc 106:6355 38. Wild FRWP, Zsolnai L, Huttner G, Brintzinger H-H (1982) J Organomet Chem 232: 233 39. Kaminsky W, Külper K, Brintzinger H-H, Wild RWP (1985) Angew Chem Int Ed 24:507 40. Spaleck W, Küber F,Winter A, Rohrmann J, Bachmann B,Antberg M, Dolle V, Paulus EF (1994) Organometallics 13:954 41. Mise T, Miya S, Yamazaki H (1989) Chem Lett 1853 42. Wiesenfeldt H, Reinmuth A, Barsties E, Evertz K, Brintzinger H-H (1989) J Organomet Chem 369:359 43. Yamazaki H, Kimura K, Nakano M, Ushioda T (1999) Chem Lett 1311 44. Giardello MA, Eisen MS, Stern CL, Marks TJ (1995) J Am Chem Soc 117:12114 45. Miyake S, Okumura Y, Inazawa S (1995) Macromolecules 28:3074 46. Erker G, Nolte R, Tsay YH, Kruger C (1989) Angew Chem Int Ed Engl 28:628 47. Erker G, Temme B (1992) J Am Chem Soc 114:4004 48. Razavi A, Atwood JL (1993) J Am Chem Soc 115:7529 49. Yamaguchi Y, Suzuki N, Fries A, Mise T, Koshino H, Ikegami Y, Ohmori H, Matsumoto A (1999) J Polym Sci, A: Polym Chem 37:283 50. Hou ZM, Wakatsuki Y (2002) Coord Chem Rev 231:1 51. Coughlin EB, Bercaw JE (1992) J Am Chem Soc 114:7606 52. Yasuda H, Ihara E (1995) Tetrahedron 51:4563 53. Schaverien CJ (1994) Organometallics 13:69

Stereospecific Olefin Polymerization Catalyzed by Metallocene Complexes

213

54. Ihara E, Nodono M, Katsura K,Adachi Y,Yasuda H,Yamagashira M, Hashimoto H, Kanehisa N, Kai Y (1998) Organometallics 17:3945 55. Koga N, Morokuma K (1991) Chem Rev 91:823 56. Kawamura-Kuribayashi H, Koga N, Morokuma K (1992) J Am Chem Soc 114:8687 57. Castonguay LA, Rappé AK (1992) J Am Chem Soc 114:5832 58. Sacchi MC, Barsties E, Incoronata T, Locatelli P, Brintzinger H-H, Stehling U (1997) Macromolecules 30:3955 59. Longo P, Grassi A, Pellecchia C, Zambelli A (1987) Macromolecules 20:1015 60. Busico V, Cipullo R (1994) J Am Chem Soc 116:9329 61. Resconi L, Fait A, Piemontesi F, Colonnesi M, Rychlicki H, Zeigler R (1995) Macromolecules 28:6667 62. Leclerc MK, Brintzinger H-H (1996) J Am Chem Soc 118:9024 63. Herrmann GS, Alt HG, Rausch MD (1991) J Organomet Chem 401:C5 64. Chen YX, Rausch MD, Chien JCW (1994) Organometallics 13:748 65. Huhn T, Suzuki N,Yamaguchi Y, Mise T, Chihara T, Wakatsuki Y (1997) Chem Lett 1201 66. Chacon ST, Coughlin EB, Henling LM, Bercaw JE (1995) J Organomet Chem 497:171 67. Halterman RL (1992) Chem Rev 92:965 68. Grossmann RB, Tsai JC, Davis WM, Gutiérrez A, Buchwald SL (1994) Organometallics 13:3892 69. Ellis WW, Hollis TK, Odenkirk W, Whelan J, Ostrander R, Rheingold AL, Bosnich B (1993) Organometallics 12:4391 70. Huttenloch ME, Diebold J, Rief U, Brintzinger H-H, Gilbert AM, Katz TJ (1992) Organometallics 11:3600 71. Huttenhofer M, Schaper F, Brintzinger H-H (1998) Angew Chem Int Ed 37:2268 72. Diamond GM, Rodewald S, Jordan RF (1995) Organometallics 14:5 73. Christopher JN, Diamond GM, Jordan RF (1996) Organometallics 15:4038 74. Diamond GM, Jordan RF (1996) Organometallics 15:4045 75. Koyama M, Kimura K, Nakano M, Yamazaki H (1998) Chem Lett 1139 76. Yamazaki H (personal communication) 77. Ewen JA, Jones RL, Razavi A, Ferrara JD (1988) J Am Chem Soc 110:6255 78. Cavallo L, Guerra G, Vacatello M, Corradini P (1991) Macromolecules 24:1784 79. Herzog TA, Zubris DL, Bercaw JE (1996) J Am Chem Soc 118:11988 80. Resconi L, Abis L, Franciscono G (1992) Macromolecules 25:6814 81. Ewen JA, Elder MJ, Jones RL, Halpeslagh L, Atwood JL, Bott SG, Robinson K (1991) Makromol Chem Macromol Sump 48/49:253 82. Coates GW, Waymouth RM (1995) Science 267:217 83. Natta G (1956) Angew Chem 68:393 84. Ishihara N, Seimiya T, Kuramoto M, Uoi M (1986) Macromolecules 19:2464 85. Ishihara N, Kuramoto M, Uoi M (1988) Macromolecules 21:3356 86. Okuda J, Arndt S, Beckerle K, Hultzsch KC, Voth P, Spaniol TP (2001) Pure Appl Chem 73:351 87. Pellecchia C, Grassi A (1999) Top Catal 7:125 88. Po R, Cardi N (1996) Prog Polym Sci 21:47 89. Tomotsu N, Ishihara N, Newman TH, Malanga MT (1998) J Mol Catal A: Chem 128:167 90. Tomotsu N, Ishihara N (1999) Stud Surf Sci Catal 121:269 91. Zambelli A, Pellecchia C, Proto A (1995) Macromol Symp 89:373 92. Campbell Jr. RE, Newman TH, Malanga MT (1995) Macromol Symp 97:151 93. Foster P, Chien JCW, Rausch MD (1996) Organometallics 15:2404 94. Ready TE, Day RO, Chien JCW, Rausch MD (1993) Macromolecules 26:5822 95. Schneider N, Prosenc M-H, Brintzinger H-H (1997) J Organomet Chem 545–546:291 96. Kaminsky W, Lenk S, Sholz V, Roesky HW, Herzog A (1997) Macromolecules 30:7647

214

N. Suzuki

97. Miyashita A, Nabika M, Suzuki T (1994) In: International symposium on synthetic, structural and industrial aspects of stereospecific polymerization. Milano, Italy 98. Pellecchia C, Longo P, Proto A, Zambelli A (1992) Makromol Chem, Rapid Commun 13:265 99. Chien JCW, Salajka Z, Dong S (1992) Macromolecules 25:3199 100. Mahanthappa MK, Waymouth RM (2001) J Am Chem Soc 123:12093 101. Ishihara N (1990) PhD thesis, Oxford University 102. Pellecchia C, Longo P, Grassi A, Ammendola P, Zambelli A (1987) Makromol Chem Rapid Commun 8:277 103. Grassi A, Lamberti C, Zambelli A, Mingozzi I (1997) Macromolecules 30:1884 104. Minieri G, Corradini P, Guerra G, Zambelli A, Cavallo L (2001) Macromolecules 34:5379 105. Quyoum R, Wang Q, Tudoret M-J, Baird MC, Gillis DJ (1994) J Am Chem Soc 116:6435 106. Arai T, Ohtsu T, Suzuki S (1998) Polym Prepr 39:220 107. Arai T, Ohtsu T, Suzuki S (1998) Macromol Rapid Commun 19:327 108. Manders B, Sciandrone L, Hauck G, Kristen MO (2001) Angew Chem Int Ed 40:4006 109. Tanaka K, Furo M, Ihara E, Yasuda H (2001) J Polym Sci, A: Polym Chem 39:1382 110. Hou Z, Tezuka H, Zhang Y, Yamazaki H, Wakatsuki Y (1998) Macromolecules 31:8650 111. Hou Z, Zhang Y, Nishiura M, Wakatsuki Y (2003) Organometallics 22:129 112. Baudry-Barbier D, Camus E, Dormond A, Visseaux M (1999) Appl Organomet Chem 13:813 113. Liu L, Gong Z, Zheng Y, Jing X (1997) Macromol Rapid Commun 18:859 114. Harder S, Feil F, Knoll K (2001) Angew Chem Int Ed 40:4261 115. Hatada K, Kitayama T, Ute K (1988) Prog Polym Sci 13:189 116. Hatada K, Ute K, Tanaka K, Okamoto Y, Kitayama T (1986) Polym J 18:1037 117. Wesslén B, Mattsson G (1990) J Polym Sci A: Polym Chem 28:1033 118. Yasuda H, Yamamoto H, Yokota K, Miyake S, Nakamura A (1992) J Am Chem Soc 114:4908 119. Collins S, Ward DG (1992) J Am Chem Soc 114:5460 120. Yasuda H (2002) J Organomet Chem 647:128 121. Yasuda H (2001) J Polym Sci A: Polym Chem 39:1955 122. Yasuda H, Ihara E (1997) Adv Polym Sci 133:53 123. Yasuda H, Ihara E (1995) Macromol Chem Phys 196:2417 124. Yasuda H,Yamamoto H,Yamashita M,Yokota K, Nakamura A, Miyake S, Kai Y, Kanehisa N (1993) Macromolecules 26:7134 125. Giardello MA, Yamamoto Y, Brard L, Marks TJ (1995) J Am Chem Soc 117:3276 126. Lee MH, Hwang JW, Kim Y, Kim J, Han Y, Do Y (1999) Organometallics 18:5124 127. Qian C, Nie W, Sun J (2000) Organometallics 19:4134 128. Qian CT, Nie WL, Chen YF, Sun J (2002) J Organomet Chem 645:82 129. Knjazhanski SY, Elizalde L, Cadenas G, Bulychev BM (1998) J Polym Sci A: Polym Chem 36:1599 130. Yasuda H, Ihara E, Nitto Y, Kakehi T, Morimot M, Nodono M (1998) ACS Symp Ser 704:149 131. Ihara E, Koyama K, Yasuda H, Kanehisa N, Kai Y (1999) J Organomet Chem 574:40 132. Ihara E, Morimoto M, Yasuda H (1995) Macromolecules 28:7886 133. Deng H, Shiono T, Soga K (1995) Macromol Chem Phys 196:1971 134. Shiono T, Saito T, Saegusa N, Hagihara H, Ikeda T, Deng H, Soga K (1998) Macromol Chem Phys 199:1573 135. Chen Y-X, Metz MV, Li L, Stern CL, Marks TJ (1998) J Am Chem Soc 120:6287 136. Bandermann F, Ferenz M, Sustmann R, Sicking W (2001) Macromol Symp 174:247 137. Cameron PA, Gibson VC, Graham AJ (2000) Macromolecules 33:4329 138. Stuhldreier T, Keul H, Höcker H (2000) Macromol Rapid Commun 21:1093

Stereospecific Olefin Polymerization Catalyzed by Metallocene Complexes 139. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 151. 152. 153. 154. 155. 156. 157. 158. 159. 160. 161. 162. 163. 164. 165. 166. 167. 168. 169. 170. 171. 172. 173. 174. 175. 176. 177. 178. 179. 180. 181.

215

Frauenrath H, Keul H, Höcker H (2001) Macromolecules 34:14 Hölscher, M, Keul H, Höcker H (2002) Macromolecules 35:8194 Soga K, Deng H, Yano T, Shiono T (1994) Macromolecules 27:7938 Deng H, Shiono T, Soga K (1995) Macromolecules 28:3067 Nguyen H, Jarvis AP, Lesley MJG, Kelly WM, Reddy SS, Taylor NJ, Collins S (2000) Macromolecules 33:1508 Bolig AD, Chen EYX (2001) J Am Chem Soc 123:7943 Bolig AD, Chen EYX (2002) J Am Chem Soc 124:5612 Deng H, Soga K (1996) Macromolecules 29:1847 Mashima K, Matsuo Y, Tani K (1998) Proc Japan Aced 74:217 Mashima K (2000) Macromol Symp 159:69 Matsuo Y, Mashima K, Tani K (2001) Angew Chem Int Ed 40:960 Taube R, Sylvester G (1996) In: Cornils B, Herrmann WA (eds) Applied homogeneous catalysis with organometallic compounds. VCH, Weinhiem, vol 1, pp 280 Taube R, Windisch H, Maiwald S (1995) Macromol Symp 89:393 Porri L, Ricci G, Shubin N (1998) Macromol Symp 128:53 Oliva L, Longo P, Grassi A, Ammendola P, Pellecchia C (1990) Macromol Rapid Commun 11:519 Ricci G, Panagia A, Porri L (1996) Polymer 37:363 Porri L, Giarrusso A, Ricci G (2000) In: Scheirs J, Kaminsky W (eds) Metallocene-based polyolefins. Wiley, West Sussex, vol 2, pp 115 Ricci G, Porri L, Giarrusso A (1995) Macromol Symp 89:383 Soga K, Asai M, Suzuki Y, Miyazawa A, Tsuchihara K, Murata M, Ozaki H, Kawabe M, Fukui Y, Jin J, Hagihara H, Kase T, (1999) WO Patent 9940133 Soga K, Asai M, Suzuki S, Miyazawa A, Tsuchihara K, Murata M, Ozaki H, Kawabe M, Fukui Y, Jiju J, Hagiwara H, Kase T, (2001) JP Patent 2001122920 Pragliola S, Milano G, Guerra G, Longo P (2002) J Am Chem Soc 124:3502 Kaita S, Hou Z, Wakatsuki Y (1999) Macromolecules 32:9078 Kaita S, Hou Z, Wakatsuki Y (2001) Macromolecules 34:1539 Hou Z, Kaita S, Wakatsuki Y (2001) Pure Appl Chem 73:291 Naga N, Shiono T, Ikeda T (1999) Macromol Chem Phys 200:1466 Hackmann M, Repo T, Jany G, Rieger B (1998) Macromol Chem Phys 199:1511 Resconi L, Waymouth RM (1990) J Am Chem Soc 112:4953 Coates GW, Waymouth RM (1991) J Am Chem Soc 113:6270 Coates GW, Waymouth RM (1992) J Mol Catal 76:189 Kesti MR, Waymouth RM (1992) J Am Chem Soc 114:3565 Coates GW, Waymouth RM (1993) J Am Chem Soc 115:91 de Ballesteros OR, Venditto V, Auriemma F, Guerra G, Resconi L, Waymouth RM, Mogstad A-L (1995) Macromolecules 28:2383 Mitani M, Oouchi K, Hayakawa M, Yamada T, Mukaiyama T (1995) Chem Lett 905 Jeremic D, Wang Q, Quyoum R, Baird MC (1995) J Organomet Chem 497:143 Kokko E, Pietikäinen P, Koivunen J, Seppälä JV (2001) J Polym Sci A: Polym Chem 39:3805 Pietikäinen P, Väänänen T, Seppälä JV (1999) Eur Polym J 35:1047 Naga N, Imanishi Y (2002) Macromol Chem Phys 203:2155 Naga N, Shiono T, Ikeda T (1999) Macromolecules 32:1348 Bonnet F, Visseaux M, Barbier-Baudry D, Dormond A (2002) Macromolecules 35:1143 Kaminsky W, Spiehl R (1989) Makromol Chem 515 Cherdron H, Brekner M-J, Osan F (1994) Angew Makromol Chem 223:121 Collins S, Kelly WM (1992) Macromolecules 25:233 Arndt M, Kaminsky W (1995) Macromol Symp 95:167

216

Stereospecific Olefin Polymerization Catalyzed by Metallocene Complexes

182. 183. 184. 185. 186. 187. 188.

Kelly WM, Taylor NJ, Collins S (1994) Macromolecules 27:4477 Kelly WM, Wang S, Collins S (1997) Macromolecules 30:3151 Arndt M, Kaminsky W (1995) Macromol Symp 97:225 Scollard JD, McConville DH (1996) J Am Chem Soc 118:10008 Jin J, Tsubaki S, Uozumi T, Sano T, Soga K (1998) Macromol Rapid Commun 19:597 Matsui S, Mitani M, Saito J, Tohi Y, Makio H, Tanaka H, Fujita T (1999) Chem Lett 1263 Matsui S, Tohi Y, Mitani M, Saito J, Makio H, Tanaka H, Nitabaru M, Nakano T, Fujita T (1999) Chem Lett 1065 Matsui S, Fujita T (2001) Catal Today 66:63 Makio H, Kashiwa N, Fujita T (2002) Adv Synth Catal 344:477 Saito J, Mitani M, Onda M, Mohri J-I, Ishii S-I, Yoshida Y, Nakano T, Tanaka H, Matsugi T, Kojoh S-I, Kashiwa N, Fujita T (2001) Macromol Rapid Commun 22:1072 Tian J, Hustad PD, Coates GW (2001) J Am Chem Soc 123:5134 Saito J, Mitani M, Mohri J-I, Ishii S-I,Yoshida Y, Matsugi T, Kojoh S-I, Kashiwa N, Fujita T (2001) Chem Lett 576 Hustad PD, Tian J, Coates GW (2002) J Am Chem Soc 124:3614 Lamberti M, Pappalardo D, Zambelli A, Pellecchia C (2002) Macromolecules 35:658 Averbuj C, Tish E, Eisen MS (1998) J Am Chem Soc 120:8640 Volkis V, Shmulinson M, Averbuj C, Lisovskii A, Edelmann FT, Eisen MS (1998) Organometallics 17:3155 Ittel SD, Johnson LK, Brookhart M (2000) Chem Rev 100:1169 Rieger B, Baugh L, Kacker S, Striegler S (eds) (2003) Late transition metal polymerization catalysis. Wiley-VCH, Weinheim Johnson LK, Killian CM, Brookhart M (1995) J Am Chem Soc 117:6414 Bristovsek GJP, Gibson VC, Kimberley BS, Maddox PJ, McTavish SJ, Solan GA,White AJP, Williams DJ (1998) Chem Commun 849 Small BL, Brookhart M, Bennet AM (1998) J Am Chem Soc 120:4049 Younkin TR, Conner EF, Henderson JI, Friedrich SK, Grubbs RH, Bansleben DA (2000) Science 287:460 Pellecchia C, Zambelli A (1996) Macromol Rapid Commun 17:333 Pellecchia C, Zambelli A, Oliva L, Pappalardo D (1996) Macromolecules 29:6990 Small BL, Brookhart M (1999) Macromolecules 32:2120 Hlatky, GG (2000) Chem Rev 100:1347 Fink G, Steinmetz B, Zechlin J, Przybyla C, Tesche B (2000) Chem Rev 100:1377

189. 190. 191. 192. 193. 194. 195. 196. 197. 198. 199. 200. 201. 202. 203. 204. 205. 206. 207. 208.

Topics Organomet Chem (2004) 8: 217– 236 DOI 10.1007/b96004 © Springer-Verlag Berlin Heidelberg 2004

Carbon–Carbon Bond Cleavage Reaction Using Metallocenes Tamotsu Takahashi (

) · Ken-ichiro Kanno

Hokkaido University, Catalysis Research Center, Kita 21, Nishi 10, Kita-ku 001-0021 Sapporo, Japan [email protected]

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Introduction

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C–C Bond Cleavage of the Cyclopentadienyl Ligand of Metallocenes . . . . 218

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C–C Single Bond Cleavage . . . . . . . . . . . . . . . . . . . . . . . . . . . 220

3.1 3.2 3.3 3.4 3.5

C–C Bond Cleavage of Alkyl Metal Compounds . C–C Bond Cleavage of Metallacyclic Compounds C–C Bond Cleavage of Olefin, Diene, and Arene . C–C Bond Cleavage of Alkynes . . . . . . . . . . C–C Bond Cleavage of Nitriles . . . . . . . . . .

4

C–C Double Bond Cleavage

4.1 4.2

C–C Double Bond Cleavage by the Multi-Metallic System . . . . . . . . . . 230 C–C Double Bond Cleavage in the Coupling with Alkyne (Enyne Cyclization) 231

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C–C Triple Bond Cleavage

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Conclusion

References

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Abstract Among a lot of transition metal mediated or catalyzed C–C bond cleavage reactions, metallocene mediated C–C bond cleavage reactions, in particular, are attractive since many cases show the intermediates or the C–C bond cleavage steps in the reactions. Organic compounds are classified into three groups by the bond order of the C–C bond: (1) C–C single bond, (2) C–C double bond, and (3) C–C triple bond. Keywords C–C bond cleavage · Metallacycles · Cyclopentadienyl ligand · b,g-C–C bond · Multi-metallic system

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1 Introduction Carbon–carbon bond cleavage is a new area in organic and organometallic chemistry [1]. It has been generally believed that once a carbon–carbon bond is formed, it cannot be easily cleaved. Therefore, introduction of selectivities, such as regio-, stereo-, and enantioselectivity has to be done when a new carbon–carbon bond is formed.After formation of the carbon–carbon bond there is almost no chance to introduce new selectivity into it. However, what if we can easily cleave the carbon–carbon bond in a molecule? This will widen the scope of organic chemistry and organometallic chemistry. (1) Some carbon–carbon bond cleavage reactions have already been known as classic chemistry, such as opening small ring strained molecules (three-membered ring or four-membered ring), decarboxylation, and retro-Diels–Alder reaction and so on. Also, some mechanisms of cleavage reactions such as metathesis have been elucidated [2]. Recently, new C–C bond cleavage reactions have been reported for unstrained molecules using transition metal complexes. In particular, the number of reports on C–C bond cleavage has increased since the 1980s. Such C–C bond cleavage reactions of unstrained molecules with transition metal complexes are interesting, mysterious, and attractive. The mechanisms for those reactions still remain unclear. What is the driving force of the C–C bond cleavage of unstrained molecules? This should be the target of study. In order to study the C–C bond cleavage step, the best way is by monitoring the cleavage reaction or investigating the structure of the starting complex and the final metal-containing product. This means that metallocenes or metal complexes with cyclopentadienyl or related ligands are quite useful. In many C–C bond cleavage reactions, some metal-containing intermediates have been isolated and the structures of those complexes with cyclopentadienyl ligands have been determined either before or after the C–C cleavage reaction. Therefore, this chapter focuses on the C–C bond cleavage using metallocenes or metal complexes with cyclopentadienyl ligands or related ligands.

2 C–C Bond Cleavage of the Cyclopentadienyl Ligand of Metallocenes The first question regarding the C–C bond cleavage using metallocenes is the following.“Is the C–C bond of a cyclopentadienyl ligand cleaved by itself?” The answer is yes in some cases.

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The first direct C–C-bond cleavage reaction of the cyclopentadienyl ligand on metal was reported by Rosenthal et al. [3]. As shown in Eq. 2, titanacyclopentadiene derivatives, which can be prepared from a low valent titanocene and 3,9-dodecadiyne, gave a dihydroindene titanium complex.When the structure of the product is checked carefully, it is found that one C–C bond of the cyclopentadienyl ligand was cleaved and three new C–C bonds were formed in this transformation. The structure of the dihydroindene titanium complex was determined by X-ray analysis.

(2)

An interesting C–C bond cleavage of Me-substituted Cp ligand was reported by Stryker et al. for a CpCo derivative as shown in Eq. 3 [4]. 2-Butyne was inserted into a Cp ligand to form a seven-membered ring compound. It is notable that the allyl group in the starting complex reacted with 2-butyne to be converted into a dimethylcyclopentadienyl ligand to stabilize the complex as shown below.

(3)

Takahashi, Xi, and coworkers reported double C–C bond cleavage of the cyclopentadienyl ligand [5]. As shown in Scheme 1, one cyclopentadienyl ligand was torn into two parts, a 2-carbon unit and a 3-carbon unit that were converted into two different cyclic compounds, a benzene derivative and a pyridine derivative. Addition of a nitrile to a titanacyclopentadiene gave a 1,2,3,4-tetrasubstituted benzene derivative and a pyridine derivative (Eq. 4). A labeling reaction using a 13C-enriched Cp2Ti species clearly indicated that two carbons of the

Scheme 1

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benzene derivative and three carbons of the pyridine derivative came from the cyclopentadienyl ligand. Monitoring the reaction revealed that the benzene derivative was formed first and that there was a time-lag for the pyridine formation.

(4)

Although the mechanism has not yet been elucidated and is now under investigation, a coupling of the Cp ligand and the titanacyclopentadiene moiety is the important step, as Rosenthal has shown above. The subsequent double C–C bond cleavage giving a benzene derivative is not clear yet, but the allyl-titanium species might be formed after the double C–C bond cleavage. Reaction of the allyl-titanium with two nitrile molecules produces a pyridine derivative and a titanium nitride derivative, which is converted into ammonia after hydrolysis. This is a tentative explanation for this reaction. Some reports have shown that Cp ligands were converted into cyclopentadiene derivatives on metal complexes and then the C–C bonds were cleaved on the metal. Such reactions are discussed later.

3 C–C Single Bond Cleavage In most cases, cyclopentadienyl ligands do not incorporate in the reactions. In the following sections, we classify the organic unstrained molecules by the bond order in the cleavage reaction: (i) C–C single bond,( ii) C–C double bond, and (iii) C–C triple bond in the starting molecules. For the C–C single bond cleavage reaction, compounds were classified by their functional groups such as alkyl-metals, metallacycles, olefins, dienes, arenes, alkynes, and nitriles. The C–C single bond cleavage reaction by transition metal complexes requires the interaction of the bond with the metal center; in other words, coordination of the functional group (an anchor) in the molecule to the metal center. The cleavage of the single C–C bond occurs very often at the b,g-C–C bond in the intermediate, as shown in Scheme 2, via three patterns where X is carbon or heteroatom. 3.1 C–C Bond Cleavage of Alkyl Metal Compounds The C–C bond cleavage of alkyl metal occurs on the b,g-carbon–carbon bond in the alkyl group. The C–C bond cleavage of alkyl metal compounds always

Carbon–Carbon Bond Cleavage Reaction Using Metallocenes

221

Scheme 2

competes with b-hydrogen elimination. Therefore, such C–C bond cleavage reaction was usually observed in neopentylmetal compounds which do not have the b-hydrogen. Trineopentylaluminum is not a metallocene but this compound is important to show an example of the b,g-C–C bond cleavage reaction [6]. Although it is slow, elimination of isobutene and formation of Al(CH2CCMe3)2Me were detected (Eq. 5). (5) In 1982,Watson et al. reported the carbon–carbon bond cleavage reaction of an isobutyl group on metallocene of Lu, as shown in Eq. 6 [7]. The b,g-carbon– carbon bond was cleaved and the methyl group stayed on Lu in this reaction. The metallocene compound is very powerful at showing the structure of the

(6)

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final product. The product Lu–Me complex was fully characterized by X-ray analysis. The Lu–Me complex was a dimer. The structure clearly showed that one Me group stayed on Lu metal after the cleavage. Another important point is the competition with b-hydrogen elimination. Both the C–C bond cleavage and the b-hydrogen elimination are in equilibrium with the starting compound. The isobutyl group has b-hydrogen. Generally, it is believed that b-hydrogen elimination is much more favorable compared with C–C bond cleavage. However, it is interesting to note that the total amount of Cp*2Lu-CH3 in the reaction mixture, which is formed by C–C bond cleavage, increased and the rate is faster than the formation of isobutene by b-hydrogen elimination. This type of C–C bond cleavage is important for olefin polymerization chemistry. Metallocenes are well known for olefin polymerization. In a polymerization reaction of propene, formation of vinyl end groups is sometimes observed [8]. This reaction can be explained by the carbon–carbon bond cleavage reaction with elimination of the terminal olefin. This fact suggests that such a C–C bond cleavage reaction over b-hydrogen elimination is not so special for the metallocenes. A similar type of C–C bond cleavage was also observed for zirconium cation compounds [9]. The complex, as shown in Eq. 7 with a neopentyl group, showed the elimination of isobutene and the formation of the methylzirconocene complex.

(7)

This type of reaction is called b-methyl elimination or b-alkyl elimination. The methyl group or alkyl group on b-carbon is eliminated. Therefore, it is called b-methyl elimination or b-alkyl elimination. These terms are related to “b-hydrogen elimination”. However, the term,“b-carbon elimination”, is not appropriate. It is very confusing, since the carbon that is eliminated is not the b-carbon but the g-carbon. Therefore, b,g-cleavage, b-alkyl elimination, and bmethyl elimination are better terms for this type of reaction. 3.2 C–C Bond Cleavage of Metallacyclic Compounds

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C–C bond cleavage reactions of titanacyclopentanes and titanacyclohexane were independently studied by Grubbs [10] and Whitesides [11]. In the case of titanacyclopentane, ethylene was eliminated via a titanocene-bis(ethylene) complex as shown in Eq. 8. According to the deuterium labeling reaction, the real mechanism is more complicated, since scrambling of D was observed (Eq. 9) [10].

(8)

(9)

This type of C–C bond formation was used for the formation of hafnacyclopentene and hafnacyclopentadiene by Erker and his coworkers [12]. Takahashi et al. introduced regioselective and stereoselective transformation in the C–C bond cleavage reaction [13]. As shown in Scheme 3, a,a’-dimethylzirconacyclopentane was prepared in situ starting from 2,5-dibromohexane. This compound was selectively converted into b,b¢-dimethylzirconacyclopentane at room temperature in THF within 1 h. Since this reaction was too fast, it could not be followed by NMR. However, the transformation of a Hf analogue was slow enough for monitoring the reaction by NMR. As shown in Fig. 1, Cp signals of dimethylhafnacyclopentane in its 1H NMR spectrum are gradually changed to b,b¢-dimethylhafnacyclopentane cleanly and the stereochemistry of the final product was completely controlled. Two methyl groups at the a position of hafnacyclopentane were converted stepwise into the b-position. Further application of the b,g-C–C bond cleavage of zirconacycles has been done for the formation of benzene derivatives [14] and pyridine derivatives

Scheme 3

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Fig. 1 Isomerization of hafnacyclopentadiene monitored by 1H NMR

[15] via zirconacyclopentenes and zirconacyclopentadienes, as shown in Scheme 4 and Eq. 10, respectively. By this method, the first example of benzene formation from three different alkynes in one-pot was achieved [14].

Scheme 4

(10)

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All substituted and all different substituted pyridine derivatives could be prepared by the C–C bond cleavage of the zirconacyclopentane reaction in onepot from two different alkynes and one nitrile with excellent selectivity and high yields [15]. This is the only method for the penta-substituted and all different substituted pyridine from two unsymmetrical internal alkynes and one nitrile so far. 3.3 C–C Bond Cleavage of Olefin, Diene, and Arene In 1974, Green reported a reversible C–C bond formation and cleavage of the cyclopentadienyl ligand of Cp2MoEtCl [16]. The ethyl group moved from Mo to a Cp ligand by addition of a phosphine to give h4-cyclopentadiene derivatives. The ethyl group of the cyclopentadiene ligand on molybdenum, in turn, was eliminated by the C–C bond cleavage which was initiated by abstraction of the Cl anion. Then the Et group moved back to Mo as shown in Eq. 11. One important factor is the formation of a cyclopentadienyl ligand. The cyclopentadienyl ligand itself can be formed by elimination of either Et or H. Elimination of H is energetically much more favorable than that of the Et group. The reason why the elimination of Et is more favorable than that of H is not clear but one possible mechanism is as follows. Probably, elimination of H occurs very rapidly and reversibly. On the other hand, the elimination of Et is irreversible, or its reversible reaction might be slow, even though the reaction itself is a minor reaction. Therefore, elimination of the Et group is observed as the total reaction.

(11)

A similar type of alkyl group elimination from alkyl-substituted cyclopentadienes giving cyclopentadienyl ligands has been reported for W [17], Mo [18], and Ir [19]. The starting compounds are not Cp complexes but the final products are CpM compounds. Non-alkyl substituted cyclopentadiene showed the ring-opening reaction. Suzuki et al. reported that cyclopentadiene reacted with a trinuclear Ru complex to open the ring and that a ruthenacyclopentadiene derivative is formed as a product (Eq. 12) [20]. Reaction of norbornadiene with a bimetallic Ru complex also gave a ringopening product (Eq. 13). In this reaction two C–C bonds were cleaved. The cleaved C–C bonds were both single bonds in the starting material [21]. There is a report for the C–C bond cleavage of cyclooctadiene on cobalt by treatment with HBF4 as shown in Scheme 5[22]. The first step of this reaction is protonation of one double bond which converts the complex to the corre-

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(12)

(13)

Scheme 5

sponding h3-(p-allyl) cobalt compound. The p-allyl cobalt complex was isolated and characterized. The C–C bond cleavage occurred from this p-allyl complex. The b,g–C–C bond was cleaved.

(14)

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This result suggests that diene itself is not involved in the cleavage reaction. A p-allyl-metal species with agostic interaction of H with Co is the key intermediate. The same type of reaction also proceeds in 5-membered ring compounds on Co (Eq. 14) [23].A simple cobalt p-allyl complex reacted with 2-butyne to give a 7-membered ring cobalt complex where one carbon and two carbons of the allyl moiety were separated in the final product [11]. The mechanism is not yet clear. Bercaw reported an interesting reversible branching reaction of 1,4-pentadiene derivatives catalyzed by a scandocene hydride complex as shown in Scheme 6 [24].

Scheme 6

The C–C bond cleavage of an unstrained single bond of olefins is difficult. Activated ofefins, such as dienes, and a p-allyl system are needed for the cleavage reaction. The following example in Scheme 7 is also C–C bond cleavage of enones. The driving force of the cleavage is aromatization of the 6-membered ring. And the methyl group on the ring is eliminated as shown below [25, 26]. This reaction was applied in the synthesis of a steroid derivative. Catalytic C–C bond cleavage of neohexene has been reported using the [Cp*Ru(OMe)2]/CF3SO3H system (Eq. 15) [27]. The products were 2,3-di-

Scheme 7

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(15) methyl-2-butene, 2,3-dimethyl-1-butene and a small amount of CH4. Migration of one methyl group is the major reaction. Although it is not an unstrained compound, it is noteworthy that a C–C single bond of biphenylene was cleaved by (C5Me5)RhPh(H)PMe3 to give Rh containing a 5-membered ring complex as shown in Eq. 16 [28, 29].

(16)

3.4 C–C Bond Cleavage of Alkynes

Mach and coworkers reported the single bond cleavage of 2,4-disilyldiyne in the presence of a low-valent titanium complex that was produced by the reduction of (C5Me4H)2TiCl2 with Mg (Eq. 17). The final product [(C5Me4H)2Ti (CCSiMe3)2][MgCl(thf)] was characterized by X-ray analysis [30]. (17)

Similarly, Rosenthal showed the selective cleavage of the C–C bond of octatetraynes with titanocene and zirconocene bis(trimethylsilyl)acetylene complexes. The final product was also characterized by X-ray analysis (Eq. 18) [31].

(18)

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229

3.5 C–C Bond Cleavage of Nitriles

C–C bond cleavage of a nitrile on metal proceeds at the b,g-bond of the nitrile. As shown in Eq. 19, photolysis of [Me2Si(C5Me4)2]MoH2 gives a very active species that reacts with acetonitrile to give the methyl-cyanide complex Me2Si(C5Me4)2Mo(Me)CN [32]. This product was characterized by X-ray analysis. The usual molybdocene analogue affords an h2-nitrile complex but not the C–C bond cleavage complex. This suggests the coordination of nitrile to Mo in a side-on mode is the first step.

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4 C–C Double Bond Cleavage Several reactions can be expected for the reaction of olefin with transition metals. For example: i. ii. iii. iv. v. vi.

Oxidative addition of a vinyl C–H bond Oxidative addition of allylic C–H bond b,g-C–C single bond cleavage of olefins g,d-C–C single bond cleavage of olefins Insertion reaction Coupling reaction

Direct cleavage of the C–C double bond of olefins is not usually observed. The C–C double bond coordinates to transition metals first and a formal metallacyclopropane derivative is produced. If the C–C bond is cleaved in the metallacyclopropane, two metal-carbene moieties are formed on one metal center. Due to the unstability of bis(carbene) compounds, the direct and simple cleavage reaction of the C–C double bond does not easily occur (Eq. 20). (20)

230

T. Takahashi · K. Kanno

The cleaved fragment should be stabilized somehow. One method is stabilization of the cleaved species by multi-metallic systems. Another method is a combination with other functional groups in the molecule. 4.1 C–C Double Bond Cleavage by the Multi-Metallic System The multi-metallic system was reported by Suzuki et al. as shown in Eq. 21.Advantages of the multi-metallic system over a mono-metallic system are the existence of a multi-coordination site, the possibility of multi-electron transfer, and the stabilization of the fragmented species. The tri-ruthenium system Suzuki et al. developed showed an interesting C–C double bond cleavage [33]. As shown in Scheme 8, the C–C double bond of methyl methacrylate was cleaved when it was treated with {(h5-C5Me5)Ru}3(m-H)3(m3-H)2 at 80°C for 48 h. The structure of the final product was determined by X-ray single crystal analysis. Under milder conditions a m-vinylidene complex was isolated and its structure was also determined by X-ray analysis. The first step of this cleavage reaction is oxidative addition of the two terminal C–H bonds of alkenes. The following elimination of allylic hydrogen of the m-vinylidene complex afforded a bimetallic bridged allyl system. The b,g-C–C bond was cleaved in the bimetallic system to give the final product.

(21)

Scheme 8

Carbon–Carbon Bond Cleavage Reaction Using Metallocenes

231

4.2 C–C Double Bond Cleavage in the Coupling with Alkyne (Enyne Cyclization) C–C double bond cleavage of an enyne derivative using a metallocene derivative was reported by Takahashi and coworkers [34]. When an alkyne was treated with Cp2ZrEt2 and vinyl bromide or vinyl ether in this order; after hydrolysis a 2,3-disubstituted diene derivative was obtained (Eqs. 22 and 23). Bissilyl acetylene, aryl-substituted acetylene or cyclohexyl-substituted alkyne could be used as internal alkynes. (22)

(23)

This reaction was applied for intramolecular reactions.As shown in Eq. 24, a diene was formed. The structure of the final product clearly showed that the C–C double bond of enyne was cleaved. The use of vinyl ether gave vinylzirconation of alkynes without C–C bond cleavage. Therefore, the key point for this reaction is the use of the vinyl halide moiety.

(24)

Following the reaction of diphenylacetylene with vinyl bromide suggested the formation of two kinds of cyclobutene derivatives as intermediates (Scheme 9). Table 1 shows the hydrolysis product of the intermediates during the reaction. First, a cyclobutene derivative was formed in high yield, which gradually decreased. The amount of the second cyclobutene derivative increased with a decrease in the amount of the first cyclobutene derivative.Again it also decreased and the final diene accumulated. The structure of one of the zirconium-containing cyclobutene intermediates with trimethylsilyl substituted Cp ligands was determined by X-ray analysis. Judging from the results, the mechanism in Scheme 10 is plausible. The coupling of one alkyne and vinyl bromide occurs on zirconocene to give a-bromozirconacyclopentene. Elimination of Br via 1,2-shift of the Zr–C bond affords the first cyclobutene derivative. The zirconium moiety attaches to the

232

T. Takahashi · K. Kanno

Scheme 9

Table 1 Formations of Cyclobutenes and Butadienes in Scheme 9

T/°C

rt rt 50 50 50 50 50

time/h

1 3 1 3 6 15 24

ratio (%)

Combined yields

I

II

III

IV

98 95 36 25 18 1 tr

tr 1 38 17 3 1 tr

tr 2 21 48 66 84 86

tr 1 5 10 13 13 13

84 93 93 90 89 90 87

allylic carbon with R2 substituent. Allylic rearrangement to the second cyclobutene derivative, of which the structure was determined, occurs. Ringopening of the cyclobutene proceeds to afford a dienyl zirconocene derivative. Deuterolysis and iodinolysis of the dienylzirconocene showed the stereochemistry of the diene moiety was completely controlled by this reaction.

Scheme 10

Carbon–Carbon Bond Cleavage Reaction Using Metallocenes

233

5 C–C Triple Bond Cleavage C–C triple bond cleavage has some similarity to the C–C double cleavage. Several examples are known for the C–C triple bond cleavage in the multi-metallic system. A C–C triple bond easily coordinates to transition metals giving an alkyne complex. The alkyne complex can also be formally described as a metallacyclopropene. The second coordination of the C–C double bond moiety of the metallacyclopropene to another transition metal center provides a more strained two metallacyclopropane fused ring system. When the C–C bond is cleaved, the fragment can be stabilized in the multi-metallic system. Most reported reactions of this type used the Cp ligand in the system. An acetylide cluster, CpWRu2(CO)8(CCPh), was treated with 1 equivalent of Ru3(CO)12 to give two carbido-alkylidyne cluster complexes, CpWRu4(m5C)(CO)12(m-CPh) and CpWRu5(m6-C)(CO)14(m-CPh), as shown in Scheme 11 [35]. It is interesting to note that this cleavage is reversible.

Scheme 11

A diiron polyyne complex, Cp*Fe(CO)2-(CC)n-Fe(CO)2Cp* (n=3 or 4) showed site-selective cleavage reaction of the C–C triple bond when it reacted with Fe2(CO)9 or Fe3(CO)12 (Eq. 25) [36]. The second C–C triple bond from the terminal was selectively cleaved at room temperature, although the yield was relatively low. The cleaved fragment was stabilized by three iron metals. Similar (25)

234

T. Takahashi · K. Kanno

C–C triple bond cleavage by the (h5-C5R5)M system has been reported for Co [37], Rh [38] and Fe [39]. Usually, the C–C triple bond is cleaved in multi-metal systems. An unusual example of the C–C triple bond cleavage by mononuclear metal complex has been reported [40]. This occurs when the alkyne is very bulky as shown in Eq. 26.

(26)

The following reaction of an alkyne with an Ir complex looks like the C–C triple bond cleavage (Eq. 27) [41]. It is not the direct C–C triple bond cleavage by the reaction with metals. The first step of this reaction is addition of water to the triple bond forming an aldehyde. Elimination of CO from the resulting acyl complex gives the product.

(27)

6 Conclusion Metallocene or metal complexes with Cp or related ligands provide considerable important information about the mechanistic aspects of C–C bond cleavage reactions. At the same time, metallocenes sometimes show catalytic reactions. We believe that development of novel types of C–C bond cleavage reactions and elucidation of their mechanism will be accomplished using metallocenes and their related complexes.

References 1. (a) Bishop KC (1976) Chem Rev 76:461; (b) Watson PL Parshall GW (1985) Acc Chem Res 18:1; (c) Crabtree RH (1985) Chem Rev 85:245; (d) Jennings PW, Johnson LL (1994) Chem Rev 94:2241; (e) Crabtree RH (1994) Organometallic chemistry of alkane activation. In: Patai S, Rappoport Z (eds) Chemistry of alkanes and cycloalkanes. Wiley, New York, p 653; (f) Rybtchinski B, Milstein D (1999) Angew Chem Int Ed Engl 38:870; (g) Takahashi T, Kotora, M Hara R, Xi Z (1999) Bull Chem Soc Jpn 72:2591; (h) Murakami M, Ito Y (1999) Cleavage of carbon–carbon single bonds by transition metals. In: Murai

Carbon–Carbon Bond Cleavage Reaction Using Metallocenes

2.

3. 4. 5. 6. 7. 8. 9. 10. 11.

12. 13. 14.

15.

16. 17. 18.

19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31.

235

S (ed) Activation of unreactive bonds and organic synthesis. Springer, Berlin Heidelberg New York, p 97 (a) Mori M (1998) Top Organomet Chem 1:133; (b) Mori M (1998) J Synth Org Chem Jpn 56:115; (c) Harvey DF, DM Sigano (1996) Chem Rev 96:271; (d) Fürstner A (2000) Angew Chem Int Ed 39:3012; (e) Trnka TM, Grubbs RH (2001) Acc Chem Res 34:18; (f) Armstrong SK (1998) J Chem Soc Perkin Trans 1:371; (g) Aubert C, Buisine O, Malacria M (2002) Chem Rev 102:813; (h) Grubbs RH, Chang S (1998) Tetrahedron 54:4413 Tillack A, Baumann W, Ohff A, Lefeber C, Spannenberg A, Kempe R, Rosenthal U (1996) J Organomet Chem 520:187 Older CM, Stryker JM (2000) J Am Chem Soc 122:2784 Xi Z, Sato K, Gao Y, Lu J, Takahashi T (2003) J Am Chem Soc 125:9568 Pfohl W (1960) Liebigs Ann Chem 629:207 Watson PL, Roe DC (1982) J Am Chem Soc 104:6471 Resconi L, Diemontesi F, Franciscono G,Abis L, Florani T (1992) J Am Chem Soc 114:1025 Horton AD (1996) Organometallics 15:2675 (a) Grubbs RH, Miyashita A (1978) J Am Chem Soc 100:1300; (b) Grubbs RH, Miyashita A (1978) J Am Chem Soc 100:7418 (a) McDermott JX, Whitesides GM (1974) J Am Chem Soc 96:947; (b) McDermott, JX, White JF,Whitesides, GM (1976) J Am Chem Soc 98:6521; (c) McDermott JX,Wilson ME, Whitesides GM (1976) J Am Chem Soc 98:6529 (a) Erker G, Czisch P, Krüger C, Wallis J M (1985) Organometallics 4:2059; (b) Erker G, Dorf U, Rheingold AL (1988) Organometallics 7:138 Takahashi T, Fujimori T, Seki T, Saburi M, Uchida Y, Rousset CJ, Negishi E (1990) J Chem Soc Chem Commun: 182 (a) Takahashi T, Kotora M, Xi Z (1995) J Chem Soc Chem Commun: 361; (b) Takahashi T, Xi, Z Yamazaki A, Liu Y, Nakajima K (1998) J Am Chem Soc 120:1672; (c) Takahashi T, Tsai FY, Li Y, Nakajima K, Kotora M (1999) J Am Chem Soc 121:11093 (a) Takahashi T, Tsai FY, Kotora M (2000) J Am Chem Soc 122:4994; (b) Takahashi T, Tsai FY, Li Y, Wang H, Kondo Y, Yamanaka M, Nakajima K, Kotora M (2002) J Am Chem Soc 124:5059 Benfield FWS, Green MLH (1974) J Chem Soc Dalton Trans: 1324 Chong KS, Green MLH (1982) J Chem Soc Chem Commun: 991 (a) Eilbracht P (1976) Chem Ber 109:1429; (b) Eilbracht P (1976) Chem Ber 109:3136; (c) Eilbracht P (1980) Chem Ber 113:542; (d) Eilbracht P (1980) Chem Ber 113:1033; (e) Eilbracht P (1980) Chem Ber 113:1420; (f) Eilbracht P (1980) Chem Ber 113:2211 Crabtree RH, Dion RP (1984) J Chem Soc Chem Commun: 1260 Suzuki H, Takaya Y, Takemori T (1994) J Am Chem Soc 116:10779 Ohki Y, Suzuki H (2000) Angew Chem Int Ed Engl 39:3463 Cracknell RB, Nicholls JC, Spencer JL (1996) Organometallics 15:446 Nicholls JC, Spencer JL (1994) Organometallics 13:1781 Bunel E, Burger BJ, Bercaw JE (1988) J Am Chem Soc 110:976 Randon D, Chaudret B, He XD, Labrome D (1991) J Am Chem Soc 113:5671 Urbanos F, Halcrow MA, Fernandez-Baeza J, Dahan F, Labroue D, Chaudret B (1993) J Am Chem Soc 115:3484 Carreno R, Chaudret B, Labroue D, Sabo-Etienne S (1993) Organometallics 12:13 Perthuiset C, Jones WD (1994) J Am Chem Soc 116:3647 Perthuiset C, Edelback BL, Zubris DL, Jones WD (1997) Organometallics 16:2016 Vargan V, Mach K (1993) Organometallics 12:2820 (a) Pellny PM, Penlecke N, Burlakov VV, Tillack A, Baumann W, Spannenberg A, Kempe R, Rosenthal U (1997) Angew Chem Int Ed 36:2615; (b) Pulst S, Arudt P, Heller, B Baumann W, Kempe R, Rosenthal U (1996) Angew Chem Int Ed 35:1112

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32. Churchill D, Shin JH, Hascall T, Hahn JM, Bridgewater BM, Parkin G (1999) Organometallics 18:2403 33. Takemori T, Inagaki A, Suzuki H (2001) J Am Chem Soc 123:1762 34. Takahashi T, Xi Z, Fischer R, Huo S, Xi C, Nakajima K (1997) J Am Chem Soc 119:4561 35. Hwang SF, Chi Y, Chiang SJ, Peng SM, Lee GH (2001) Organometallics 20:215 36. Akita M, Sakurai A, Moro-oka Y (1999) Chem Commun: 101 37. (a) King RB, Harmon CA (1976) Inorg Chem 15:879; (b) Yamazaki H, Wakatsuki Y, Aoki K (1979) Chem Lett:1041; (c) Fritch JR, Vollhardt KPC (1980) Angew Chem Int Ed Engl 19:559; (d) Tallison N, Fritch JR, Vollhardt KPC, Walborsky EC (1983) J Am Chem Soc 105:1384 38. Clauss AD, Shapley JR, Winker CN, Hoffmann R (1984) Organometallics 3:619 39. (a) Nuel D, Dahan F, Mathiu R (1985) Organometallics 4:1436; (b) Hriljac JA, Shriver DF (1987) J Am Chem Soc 109:6010; (c) Cabrera E, Daran JC, Jeannin Y (1988) J Chem Soc Chem Commun: 607 40. Hayashi N, Ho DM, Pascal Jr RA (2000) Tetrahedron Lett 41:4261 41. Chin CS, Chong D, Maeng B, Ryu J, Kim H, Kim M, Lee H (2002) Organometallics 21:1739

Author Index Volumes 1 – 8

Abdel-Magid AF see Mehrmann SJ (2004) 6: 153–180 Alper H see Grushin VV (1999) 3: 193–225 Anwander R (1999) Principles in Organolanthanide Chemistry. 2: 1–62 Armentrout PB (1999) Gas-Phase Organometallic Chemistry 4: 1–45 Beak P, Johnson TA, Kim DD, Lim SH (2003) Enantioselective Synthesis by Lithiation Adjacent to Nitrogen and Electrophile Incorporation. 5: 139–176 Bien J, Lane GC, Oberholzer MR (2004) Removal of Metals from Process Streams: Methodologies and Applications. 6: 263–284 Böttcher A see Schmalz HG (2004) 7: 157–180 Braga D (1999) Static and Dynamic Structures of Organometallic Molecules and Crystals. 4: 47–68 Brüggemann M see Hoppe D (2003) 5: 61–138 Chlenov A see Semmelhack MF (2004) 7: 21–42 Chlenov A see Semmelhack MF (2004) 7: 43–70 Clayden J (2003) Enantioselective Synthesis by Lithiation to Generate Planar or Axial Chirality. 5: 251–286 Dedieu A (1999) Theoretical Treatment of Organometallic Reaction Mechanisms and Catalysis. 4: 69–107 Delmonte AJ, Dowdy ED, Watson DJ (2004) Development of Transition Metal-Mediated Cyclopropanation Reaction. 6: 97–122 Dowdy EC see Molander G (1999) 2: 119–154 Dowdy ED see Delmonte AJ (2004) 6: 97–122 Fürstner A (1998) Ruthenium-Catalyzed Metathesis Reactions in Organic Synthesis. 1:37–72 Gibson SE (née Thomas), Keen SP (1998) Cross-Metathesis. 1: 155–181 Gisdakis P see Rösch N (1999) 4: 109–163 Görling A see Rösch N (1999) 4: 109–163 Goldfuss B (2003) Enantioselective Addition of Organolithiums to C=O Groups and Ethers. 5: 12–36 Gossage RA, van Koten G (1999) A General Survey and Recent Advances in the Activation of Unreactive Bonds by Metal Complexes. 3: 1–8 Gotov B see Schmalz HG (2004) 7: 157–180

238

Author Index

Gras E see Hodgson DM (2003) 5: 217–250 Grepioni F see Braga D (1999) 4: 47–68 Gröger H see Shibasaki M (1999) 2: 199–232 Grushin VV, Alper H (1999) Activation of Otherwise Unreactive C–Cl Bonds. 3: 193–225 Harman D (2004 Dearomatization of Arenes by Dihapto-Coordination. 7: 95–128 He Y see Nicolaou KC, King NP (1998) 1: 73–104 Hidai M, Mizobe Y (1999) Activation of the N–N Triple Bond in Molecular Nitrogen: Toward its Chemical Transformation into Organo-Nitrogen Compounds. 3: 227–241 Hodgson DM, Stent MAH (2003) Overview of Organolithium-Ligand Combinations and Lithium Amides for Enantioselective Processes. 5: 1–20 Hodgson DM, Tomooka K, Gras E (2003) Enantioselective Synthesis by Lithiation Adjacent to Oxygen and Subsequent Rearrangement. 5: 217–250 Hoppe D, Marr F, Brüggemann M (2003) Enantioselective Synthesis by Lithiation Adjacent to Oxygen and Electrophile Incorporation. 5: 61–138 Hou Z, Wakatsuki Y (1999) Reactions of Ketones with Low-Valent Lanthanides: Isolation and Reactivity of Lanthanide Ketyl and Ketone Dianion Complexes. 2: 233–253 Hoveyda AH (1998) Catalytic Ring-Closing Metathesis and the Development of Enantioselective Processes. 1: 105–132 Huang M see Wu GG (2004) 6: 1–36 Hughes DL (2004) Applications of Organotitanium Reagents. 6: 37–62 Iguchi M, Yamada K, Tomioka K (2003) Enantioselective Conjugate Addition and 1,2-Addition to C=N of Organolithium Reagents. 5: 37–60 Ito Y see Murakami M (1999) 3: 97–130 Ito Y see Suginome M (1999) 3: 131–159 Jacobsen EN see Larrow JF (2004) 6: 123–152 Johnson TA see Break P (2003) 5: 139–176 Jones WD (1999) Activation of C–H Bonds: Stoichiometric Reactions. 3: 9–46 Kagan H, Namy JL (1999) Influence of Solvents or Additives on the Organic Chemistry Mediated by Diiodosamarium. 2: 155–198 Kakiuchi F, Murai S (1999) Activation of C–H Bonds: Catalytic Reactions. 3: 47–79 Kanno K see Takahashi T (2005) 8: 217–236 Keen SP see Gibson SE (née Thomas) (1998) 1: 155–181 Kendall C see Wipf P (2005) 8: 1–25 Kiessling LL, Strong LE (1998) Bioactive Polymers. 1: 199–231 Kim DD see Beak P (2003) 5: 139–176 King AO, Yasuda N (2004) Palladium-Catalyzed Cross-Coupling Reactions in the Synthesis of Pharmaceuticals. 6: 205–246 King NP see Nicolaou KC, He Y (1998) 1: 73–104 Kobayashi S (1999) Lanthanide Triflate-Catalyzed Carbon–Carbon Bond-Forming Reactions in Organic Synthesis. 2: 63–118 Kobayashi S (1999) Polymer-Supported Rare Earth Catalysts Used in Organic Synthesis. 2: 285–305 Kodama T see Arends IWCE (2004) 11: 277–320 Kondratenkov M see Rigby J (2004) 7: 181–204 Koten G van see Gossage RA (1999) 3: 1–8 Kotora M (2005) Metallocene-Catalyzed Selective Reactions. 8: 57–137 Kumobayashi H, see Sumi K (2004) 6: 63–96

Author Index

239

Kündig EP (2004) Introduction 7: 1–2 Kündig EP (2004) Synthesis of Transition Metal h6-Arene Complexes. 7: 3–20 Kündig EP, Pape A (2004) Dearomatization via h6 Complexes. 7: 71–94 Lane GC see Bien J (2004) 6: 263–284 Larrow JF, Jacobsen EN (2004) Asymmetric Processes Catalyzed by Chiral (Salen)Metal Complexes 6: 123–152 Li Z, see Xi Z (2005) 8: 27–56 Lim SH see Beak P (2003) 5: 139–176 Lin Y-S, Yamamoto A (1999) Activation of C–O Bonds: Stoichiometric and Catalytic Reactions. 3: 161–192 Marr F see Hoppe D (2003) 5: 61–138 Maryanoff CA see Mehrmann SJ (2004) 6: 153–180 Maseras F (1999) Hybrid Quantum Mechanics/Molecular Mechanics Methods in Transition Metal Chemistry. 4: 165–191 Medaer BP see Mehrmann SJ (2004) 6: 153–180 Mehrmann SJ, Abdel-Magid AF, Maryanoff CA, Medaer BP (2004) Non-Salen Metal-Catalyzed Asymmetric Dihydroxylation and Asymmetric Aminohydroxylation of Alkenes. Practical Applications and Recent Advances. 6: 153–180 Mizobe Y see Hidai M (1999) 3: 227–241 Molander G, Dowdy EC (1999) Lanthanide- and Group 3 Metallocene Catalysis in Small Molecule Synthesis. 2: 119–154 Mori M (1998) Enyne Metathesis. 1: 133–154 Muñiz K (2004) Planar Chiral Arene Chromium (0) Complexes as Ligands for Asymetric Catalysis. 7: 205–223 Murai S see Kakiuchi F (1999) 3: 47–79 Murakami M, Ito Y (1999) Cleavage of Carbon–Carbon Single Bonds by Transition Metals. 3: 97–130 Nakamura S see Toru T (2003) 5: 177–216 Namy JL see Kagan H (1999) 2: 155–198 Negishi E, Tan Z (2005) Diastereoselective, Enantioselective, and Regioselective Carboalumination Reactions Catalyzed by Zirconocene Derivatives. 8: 139–176 Nicolaou KC, King NP, He Y (1998) Ring-Closing Metathesis in the Synthesis of Epothilones and Polyether Natural Products. 1: 73–104 Normant JF (2003) Enantioselective Carbolithiations. 5: 287–310 Oberholzer MR see Bien J (2004) 6: 263–284 Pape A see Kündig EP (2004) 7: 71–94 Pawlow JH see Tindall D, Wagener KB (1998) 1: 183–198 Prashad M (2004) Palladium-Catalyzed Heck Arylations in the Synthesis of Active Pharmaceutical Ingredients. 6: 181–204 Richmond TG (1999) Metal Reagents for Activation and Functionalization of Carbon– Fluorine Bonds. 3: 243–269 Rigby J, Kondratenkov M (2004) Arene Complexes as Catalysts. 7: 181–204 Rodríguez F see Barluenga (2004) 13: 59–121 Rösch N (1999) A Critical Assessment of Density Functional Theory with Regard to Applications in Organometallic Chemistry. 4: 109–163

240

Author Index

Schmalz HG, Gotov B, Böttcher A (2004) Natural Product Synthesis. 7: 157–180 Schrock RR (1998) Olefin Metathesis by Well-Defined Complexes of Molybdenum and Tungsten. 1: 1–36 Semmelhack MF, Chlenov A (2004) (Arene)Cr(Co)3 Complexes: Arene Lithiation/Reaction with Electrophiles. 7: 21–42 Semmelhack MF, Chlenov A (2004) (Arene)Cr(Co)3 Complexes: Aromatic Nucleophilic Substitution. 7: 43–70 Sen A (1999) Catalytic Activation of Methane and Ethane by Metal Compounds. 3: 81–95 Shibasaki M, Gröger H (1999) Chiral Heterobimetallic Lanthanoid Complexes: Highly Efficient Multifunctional Catalysts for the Asymmetric Formation of C–C, C–O and C–P Bonds. 2: 199–232 Stent MAH see Hodgson DM (2003) 5: 1–20 Strong LE see Kiessling LL (1998) 1: 199–231 Suginome M, Ito Y (1999) Activation of Si–Si Bonds by Transition-Metal Complexes. 3: 131–159 Sumi K, Kumobayashi H (2004) Rhodium/Ruthenium Applications. 6: 63–96 Suzuki N (2005) Stereospecific Olefin Polymerization Catalyzed by Metallocene Complexes. 8: 177–215 Takahashi T, Kanno K (2005) Carbon-Carbon Bond Cleavage Reaction Using Metallocenes. 8: 217–236 Tan Z see Negishi E (2005) 8: in preparation Tindall D, Pawlow JH, Wagener KB (1998) Recent Advances in ADMET Chemistry. 1: 183–198 Tomioka K see Iguchi M (2003) 5: 37–60 Tomooka K see Hodgson DM (2003) 5: 217–250 Toru T, Nakamura S (2003) Enantioselective Synthesis by Lithiation Adjacent to Sulfur, Selenium or Phosphorus, or without an Adjacent Activating Heteroatom. 5: 177–216 Uemura M (2004) (Arene)Cr(Co)3 Complexes: Cyclization, Cycloaddition and Cross Coupling Reactions. 7: 129–156 Wagener KB see Tindall D, Pawlow JH (1998) 1: 183–198 Wakatsuki Y see Hou Z (1999) 2: 233–253 Watson DJ see Delmonte AJ (2004) 6: 97–122 Wipf P, Kendall C (2005) Hydrozirconation and Its Application. 8: 1–25 Wu GG, Huang M (2004) Organolithium in Asymmetric Process. 6: 1–36 Xi Z, Li Z (2005) Construction of Carbocycles via Zirconacycles and Titanacycles. 8: 27–56 Yamada K see Iguchi M (2003) 5: 37–60 Yamamoto A see Lin Y-S (1999) 3: 161–192 Yasuda H (1999) Organo Rare Earth Metal Catalysis for the Living Polymerizations of Polar and Nonpolar Monomers. 2: 255–283 Yasuda N see King AO (2004) 6: 205–246

Subject Index

Acetylide cluster 233 Acrylates 72, 200, 204 Acutiphycin 5 Acylsilane 4 Acylzirconocene, ketone addition, asymmetric 21 Adda 14 Addition, cis/trans 78 –, Markovnikov 79, 84–86 –, Michael 74 Aldehyde vinylation, silver(I)-catalyzed 10, 11 Alkene polymerization, Ziegler-Natta 142 Alkenes, carboalumination 164 –, Dzhemilev ethylmagnesation 151 Alkenylalanes, (E)-b-methyl-substituted 144 Alkenylzirconocene, aldehyde addition 10, 15 –, homologation 19 –, imine addition 17 Alkyl metal compounds, C-C bond cleavage 220 Alkylation 61, 63, 64, 71, 85 –, double 63, 64 –, Mizoroki-Heck 63, 64 –, regioselective 64 Alkylmagnesation 61 Alkylzirconocene, isomerization 2 Alkynes, alkylalumination 152 –, C-C bond cleavage 228, 231 –, Normant’s carbocupration 140 –, Zr-catalyzed carboalumination 141 Allyl-titanium 220 Allylzirconocene, aldehyde addition 20 Ansa-metallocenes 177 Arenes, C-C bond cleavage 225

B(C6F5)3 167 Benzamidinate 209 Benzene derivatives 47–49 Bimetallic complex 2, 7 Bipyridines 108, 109 Buchwald, S. 2 Butadienes 232 2-Butyne 219 C1/C2-symmetric complexes 185, 186, 201 Callystatin A 7 Carboalumination 139 Carbolithiation, Zr-catalyzed 162 Carbometallation, controlled single-stage 140 Carbon mononoxide 20 Carbonylation 101 Carbosilylation 63 Carbotitanation 143 Carbozincation, Zr-catalyzed 158, 159 Carbozirconation 19, 139 –, alkyllithiums 162 – mechanism, Al-assisted 151 Catalysts, chiral 98 –, single-site 179 Catalytic-site control 184 C-C double bond cleavage 229 C-C triple bond cleavage 233 C-H bond, activation 74, 75 Chain-end control 184, 194, 197, 211 Chain-transfer 181 Chirality 69, 108, 111 Claisen rearrangement 77 Compounds, natural 93, 105, 113 Conjugate addition 18 Corey-Fuchs olefination 12 Coupling, four-component 123 –, three component 118–123

242

Cp2ZrII derivatives 152 Cumulene 110 Cyclization 84, 86–90, 101, 105, 131 –, enantioselective 88 –, oxidative 132 –, reductive 99 Cycloaddition, higher order 113 Cyclobutadienes 38–39 Cyclobutenes 39, 71, 208, 232 Cycloisomerization 79, 80 Cyclooctatetraenes 52 Cyclopentadienyl ligand 217, 218 Cyclopentene 208 Cyclopentenones 40–42 Cyclopropane 17–20 Deuterium labeling 7 Dewar-Chatt-Duncanson model 140 Diastereoselectivity 63 1,4-Diaza-1,3-butadiene 204 Dichlorobis(1-neomenthylindenyl)zirconium 166 Diels-Alder reaction 111, 113 Diene complexes, h4 180 Dienes, C-C bond cleavage 225 1,3-Dienes, polymerization 205 Diiron polyyne 233 Dimerization 17 –, head-to-head/head-to-tail 72, 73 Dimethylcyclopentadienyl ligand 219 3,9-Dodecadiyne 219 Dyad 182 Dzhemilev ethylmagnesation 151 Electronegativity 2 b-Elimination 90 –, b-allyl 124 –, b-hydrogen 66, 67, 71, 73, 85, 89, 90, 94, 97, 116, 129 Enantioselective reactions 92, 98, 113 Enantioselectivity 88, 92, 98, 112 Enyne cyclization 231 Epimerization 188 Ethylmagnesation 60, 63, 70, 151 Ethylzincation 61 Friedel-Crafts reaction 142

Subject Index

Ganem, B. 9 Gap aperture 193, 201 Grignard reagent 2, 5, 60–63, 66, 84 Hafnacyclopentadiene 223 Halichlorine 9, 17 Hanzawa, Y. 19, 20 Heathcock, C. 6 Helicene 105 1,6-Heptadiene 206 Heterocumulenes 110 1,5-Hexadiene 206 Hydroalumination 157 b-Hydrogen elimination 181, 194, 208 Hydrometallation, hydrogen-transfer 140, 165 Hydrooligomerization 209 Hydrozirconation 157 HZrCp2Cl 157 IBAO 167 Isobutene 222 Isobutylaluminoxane 167 Lactonization, silver(I)-catalyzed 12 Lanthanocene catalysts 196 Lewis acid 74, 81, 111, 113, 118, 121, 123 Ligand, chiral 111 Lipshutz, B. 18 Lissoclinolide 12 Lithium aluminum hydride 3 Living polymerization 195 Maeta, H. 10 Maier, M. 11 Majoral, J.-P. 9 MAO 19, 167, 178 Me2Zr(NMI)2 167 Metal countercations 163 Metalla-Claisen rearrangement 99 Metallacycles 61, 73, 90, 217 Metallacyclic compounds, C-C bond cleavage 222 Metallacyclopropane 233 Metallocenes, ansa- 177 –, C-C bond cleavage 217 –, Cs-symmetric 191

Subject Index

(S)-2-Methyl-1-alkanols 167 2-Methyl-1-cyclobutenylalanes 143 Methylalumination 142 Methylaluminoxane (MAO) 19, 167, 178 Methylenecycloheptadienes 52 Methylenecycloheptane 207 Methylzirconocene 222 Microcystin 14 Misinsertion 188 Mizoroki-Heck reaction 64, 65 MMA 195 Montgomery, J. 14 Multi-component reactions 21 Multi-metallic systems 217, 230 Myxalamide A 6 Negishi, E. 12, 13, 18 Negishi coupling 7, 12 Negishi reagent 162 Nisamycin 16 Nitriles, C-C bond cleavage 229 Norbornadiene 225 Norbornene 208 1,7-Octadiene 206 Olefin polymerization, stereospecific, metallocene-catalyzed 177 Olefins, C-C bond cleavage 225 Oxovanadium complex 18 Oxygenation 67 Panek, J. 7, 14 Pauling electronegativity 2 Pentad 182, 183 Phenoxyimine 209 Phytol 169 Pitiamide A 169 PMMA 195 all-E-Polyenes 13, 16, 17 Polyolefins 177 –, hemiisotactic 191 –, isotactic/syndiotactic 182 Polystyrene 192 Porco Jr., J. 17 Propagation 181 Prostaglandins 16 Pyridazinone 10 2,6-Pyridine bis(imine) 209 Pyridine derivatives 50

243

Reaction, asymmetric 69 Rearrangement 71 –, Claisen 77 –, metalla-Claisen 99 Regioisomer 115 Regioselectivity 70, 74, 99, 109 Rychovsky, S. 17 Samarocene 187, 196, 206 Scandocene 227 Schwartz reagent 3, 4, 12 Schwartz, J. 2, 3, 17, 20 Selectivity 77, 106, 110, 129, 132 Silver perchlorate 10 – – on Celite 10 Silylacetylene 7, 16 Skipped insertion 190 Spiroquinolizidine 9 Stannylacetylene 6, 7 Stereoerrors 188, 190 Stereoselectivity 82 Steroids 227 Stille coupling 7, 12, 14 Suzuki, L. 19 Suzuki-Miyaura coupling 12 Swern oxidation 12 Taguchi, T. 19, 20 Taxol 11 Tebbe reagent 142, 156 Titanacyclopentadienes 32, 220 Titanacyclopentenes 33, 38, 41 Titanocene-bis(ethylene) 223 Transmetallation 60, 61, 66, 67, 70, 88 Triad 182 Trineopentylaluminum 221 Tritium labeling 9 Tunning, electronic 104 Vinyl halides 5, 6 Vinyl oxiranes 19, 20 Virgili, M. 17 Vitamin E 169 Wailes, P. 2, 3 Whitby, R. 18 Wipf, P. 10, 15–19 Wittig olefination 7

244

Yttrocene 187, 189 Ziegler-Natta catalysts 278 Zirconacycles, three-membered 163 Zirconacyclobutenes 31 Zirconacyclohexadienes 35 Zirconacyclopentadienes 32–35, 46–53

Subject Index

Zirconacyclopentanes 32–34 Zirconacyclopentenes 32–45, 51, 224 Zirconacyclopropanes/zirconacyclopropenes 30 Zirconocene(II)-alkene/ and -alkyne complexes 29 ZnEt2 201