Chlorobis(cyclopentadienyl)methylzirconium1

[1291-48-8]  · C11H13ClZr  · Chlorobis(cyclopentadienyl)methylzirconium  · (MW 271.90)

(used to generate zirconocene complexes with stable and unstable organic molecules;2 catalyzes the carboalumination of R3Al to terminal alkynes3)

Physical Data: pale yellow crystals.

Solubility: sol aromatic solvents.

Analysis of Reagent Purity: 1H NMR (benzene-d6) d 5.73 (s, C5H5), 0.32 (s, CH3) in a ratio of 10:3.

Preparative Methods: can be prepared by the reaction of Cp2ZrMe2 with Dichlorobis(cyclopentadienyl)zirconium. A 0.5 M solution of each reagent in toluene is heated to 130 °C for 35 h. Cp2ZrMeCl is isolated in >90% yield by recrystallization from toluene/hexanes.4 Alternatively, it can be prepared in pure form by the treatment of (Cp2ZrCl)2O with Trimethylaluminum.5 Although Cp2ZrMeCl is available in a reasonable quantity as mentioned, it is often convenient to generate an analog of Cp2ZrMeCl in the reaction media and use it in situ. Thus treatment of Cp2ZrCl2 with t-Butyllithium generates Cp2Zr(i-Bu)Cl through b-hydride elimination and insertion. Cp2Zr(i-Bu)Cl shows a comparable reactivity to Cp2ZrMeCl.6

Handling, Storage, and Precautions: the dry solid is highly sensitive to moisture, forming (Cp2ZrCl)2O, and should be kept tightly sealed to preclude moisture. Use of this reagent immediately following preparation is recommended.

Formation of Cp2Zr Complex.

Cp2ZrMeCl is a convenient reagent to produce mixed dialkylzirconocenes in the reaction with RLi (eq 1).7 By the application of this method, zirconocene complexes of either unstable or stable organic molecules can be generated from Cp2ZrMeCl.8 The formation of zirconocene complexes is achieved by substituting the halogen atom of Cp2ZrMeCl with an alkyl or a vinyl organometallic reagent which possesses at least one b-hydrogen atom. Thermolysis then results in the concomitant generation of methane. This procedure is complementary to Cp2Zr-butene (zirconocene equivalent) promoted zirconocene complex formation of unsaturated molecules,9 since the zirconocene equivalent does not allow the isolation of Cp2Zr complexes from very unstable or very reactive organic molecules. This b-hydrogen abstraction process is reported to involve an interaction of a b-C-H bond with the empty orbital of the zirconium valence shell.10 The general scheme for the formation of complexes of unstable organic molecules and the organic precursor required for their syntheses is shown in eqs 2-8.

In each case, a metal-halogen exchange with an organolithium reagent followed by the addition of Cp2ZrMeCl produces the precursor for the zirconocene complex. Thermolysis of these precursors at temperatures ranging between 20-100 °C causes the evolution of methane to give the desired zirconocene complexes, which can be isolated as their trimethylphosphine adducts or trapped with an unsaturated compound. Through this procedure, Cp2Zr complexes of arynes with a variety of substitution patterns (eq 3),8a,11 cyclic alkynes containing five to eight membered rings (eq 4), cyclic alkenes (eq 5),8b,c benzdiynes (multiply unsaturated aromatic species) (eq 6),12 imines (eq 7),13 and thioaldehydes (eq 8)14 have all been reported. Interestingly, methyl(2-norbornenyl)zirconocene is known to exist as a thermally stable complex (eq 9).15 This stability is attributed to the strain and the bulkiness of the 2-norbornenyl ligand. Thermolysis of methyl(2-furyl)zirconocene, derived from Cp2ZrMeCl and 2-furyllithium, yields a ring-enlarged and methyl-migrated compound instead of a Cp2Zr-heteroaryne complex (eq 10).16

The reactions of Cp2Zr complexes toward unsaturated molecules reveal their usefulness for preparing many functionalized compounds (eq 11). Thus the Cp2Zr-benzyne complexes react with many unsaturated compounds to give benzo-fused compounds (eq 12).8,17 A cyclopentyne-zirconocene complex has been used for the preparation of an optically active cyclopentenone derivative.18 In this reaction the addition of an optically active allylic ether to the cyclopentyne complex proceeds with ~100% asymmetric induction (eq 13).

Reaction of Cp2ZrMeCl with lithium amide derivatives and the subsequent extrusion of methane through b-hydrogen elimination is a very efficient way of generating imine-zirconocene complexes, zirconaaziridines.13 Zirconaaziridines, which can be isolated as trimethylphosphine adducts or THF adducts, have proven to be valuable intermediates in organic synthesis. These complexes react with carbonyl compounds or alkynes to give amino alcohols or allylic amines. When the azazirconacyclopentene prepared from zirconaaziridine and alkyne is treated with Carbon Monoxide under high pressure, di- and trisubstituted pyrroles are obtained in synthetically viable yields (eq 14).13b In a similar manner, reaction of the lithium amide of an allylic amine with Cp2ZrMeCl when heated to 60 °C gives an azazirconacyclopentene, which is converted to a pyrrole when treated with an isocyanide.13d Notable and efficient application of the benzyne complex chemistry derived from Cp2ZrMeCl has been seen in the effective synthesis of the pharmacophore of potent antitumor antibiotics.19

Hydroamination.

Imidozirconocene complexes20 can be generated in situ by treating Cp2ZrMeCl with a lithium amide (which does not have b-hydrogen) followed by elimination of methane upon heating. This transient species reacts with an alkyne derivative to give an azazirconacyclobutene derivative which can be converted to a carbonyl compound via an enamine. Carbonyl compounds also react with imidozirconocene complexes giving imine compounds (eq 15).

Carbometalation.

In the chemistry of carbometalation of alkylaluminum compounds mediated by zirconocene derivatives,21 reaction of a stoichiometric amount of Cp2ZrMeCl with 1-pentynyldimethylalane is known to give an alkenylmetal species, which is converted to diiodo or 2-methyl-1-pentene in good yields upon treatment with excess iodine or water. This process is an Al-assisted direct addition of the Zr-carbon bond to the alkyne (eq 16). It is interesting to note that the Cp2ZrMeCl-catalyzed R3Al addition to alkyne is a Zr-assisted Al-carbon bond addition (eq 17).


1. (a) Buchwald, S. L.; Nielsen, R. B. CRV 1988, 88, 1047. (b) Buchwald, S. L.; Fisher, R. A. CS 1989, 29, 417. (c) Negishi, E.; Takahashi, T. S 1988, 1.
2. Buchwald, S. L.; Watson, B. T.; Lum, R. T.; Nugent, W. A. JACS 1987, 109, 7137.
3. Negishi, E.; Van Horn, D. E.; Yoshida, T. JACS 1985, 107, 6639.
4. (a) Walsh, P. J.; Hollander, F. J.; Bergman, R. G. JACS 1988, 110, 8729. (b) Jordan, R. F. JOM 1985, 294, 321.
5. Wailes, P. C.; Weigold, H.; Bell, A. P. JOM 1971, 33, 181.
6. (a) Barr, K. J.; Watson, B. T.; Buchwald, S. L. TL 1991, 32, 5465. (b) Swanson, D. R.; Nguyen, T.; Noda, Y.; Negishi, E. JOC 1991, 56, 2590.
7. Surtees, J. R. CC 1965, 567.
8. (a) Buchwald, S. L.; Nielsen, R. B. CRV 1988, 88, 1047. (b) Buchwald, S. L.; Fisher, R. A. CS 1989, 29, 417. (c) Negishi, E.; Takahashi, T. S 1988, 1.
9. (a) Negishi, E. CS 1989, 29, 457. (b) Jensen, M.; Livinghouse, T. JACS 1989, 111, 4495. (c) Ito, H.; Taguchi, T.; Hanzawa, Y. TL 1992, 33, 4469. (d) Davis, J. M.; Whitby, R. J.; Jaxa-Chamiec, A. CC 1991, 1743.
10. Negishi, E.; Nguyen, T.; Maye, J. P.; Choueiri, D.; Suzuki, N.; Takahashi, T. CL 1992, 2367.
11. (a) Buchwald, S. L.; Watson, B. T.; Lum, R. T.; Nugent, W. A. JACS 1987, 109, 7137. (b) Buchwald, S. L.; Sayers, A.; Watson, B. T.; Dewan, J. C. TL 1987, 28, 3245. (c) Erker, G. JOM 1977, 134, 189. (d) Cuny, G. D.; Gutiérrez, A.; Buchwald, S. L. OM 1991, 10, 537.
12. Hsu, D. P.; Lucas, E. A.; Buchwald, S. L. TL 1990, 31, 5563.
13. (a) Buchwald, S. L.; Watson, B. T.; Wannamaker, M. W.; Dewan, J. C. JACS 1989, 111, 4486. (b) Buchwald, S. L.; Wannamaker, M. W.; Watson, B. T. JACS 1989, 111, 776. (c) Coles, N.; Whitby, R. J.; Blagg, J. SL 1990, 271. (d) Davis, J. M.; Whitby, R. J.; Joxa-Chamiec, A. CC 1991, 1743.
14. Buchwald, S. L.; Nielsen, R. B.; Dewan, J. C. JACS 1987, 109, 1590.
15. Erker, G.; Noe, R.; Albrecht, M. JOM 1993, 450, 137.
16. Erker, G.; Petrenz, R. OM 1992, 11, 1646.
17. (a) Cuny, G. D.; Gutierrez, A.; Buchwald, S. L. OM 1991, 10, 537. (b) Cuny, G. D.; Buchwald, S. L. OM 1991, 10, 363. (c) Buchwald, S. L.; King, S. M. JACS 1991, 113, 258. (d) Buchwald, S. L.; Fang, Q. JOC 1989, 54, 2793. (e) Buchwald, S. L.; Lucas, E. A.; Davis, W. M. JACS 1989, 111, 397.
18. Buchwald, S. L.; Lum, R. T.; Fisher, R. A.; Davis, W. M. JACS 1989, 111, 9113.
19. Tidwell, J. H.; Buchwald, S. L. JOC 1992, 57, 6380.
20. (a) Walsh, P. J.; Baranger, A. M.; Bergman, R. G. JACS 1992, 114, 1708. (b) Walsh, P. J.; Hollander, F. J.; Bergman, R. G. OM 1993, 12, 3705.
21. Negishi, E.; van Horn, D. E.; Yoshida, T. JACS 1985, 107, 6639.

Takeo Taguchi & Yuji Hanzawa

Tokyo College of Pharmacy, Japan



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