[80005-41-0]  · C18H28Zr  · Di-n-butylbis(cyclopentadienyl)zirconium  · (MW 335.64) (n-BuLi)

[109-72-8]  · C4H9Li  · Di-n-butylbis(cyclopentadienyl)zirconium  · (MW 64.06) (n-BuMgCl)

[693-04-9]  · C4H9ClMg  · Di-n-butylbis(cyclopentadienyl)zirconium  · (MW 116.87) (Cl2ZrCp2)

[1291-32-2]  · C10H10Cl2Zr  · Di-n-butylbis(cyclopentadienyl)zirconium  · (MW 292.32)

(a reagent generated in situ as a ZrCp2 equivalent useful for the preparation of ZrCp2 p-complexes containing alkynes,1,2 alkenes,1,2 dienes,5 aldehydes,14 and nitriles as well as five-membered zirconacycles and their bicyclic and polycyclic derivatives)

Alternate Name: di-n-butylzirconocene.

Physical Data: Cl2ZrCp2; mp 245 °C.

Form Supplied in: n-BuLi: solutions in cyclohexane, hexanes and pentane. n-BuMgCl: solutions in diethyl ether and THF. Cl2ZrCp2: colorless crystals. All are commercially available.

Preparative Methods: generated in situ by the addition of 2 equiv of n-Butyllithium in hexanes or pentane, or n-BuMgCl in diethyl ether or THF, to Dichlorobis(cyclopentadienyl)zirconium dissolved in THF at -78 °C in an inert atmosphere of N2 or Ar.

Handling, Storage, and Precautions: n-butyllithium and n-butylmagnesium chloride are sensitive to air, moisture, and a wide variety of heterofunctional and carbofunctional compounds. They must be used and stored under an inert atmosphere of N2 or Ar. Zirconocene dichloride may be handled in air, but it is advisable to avoid extensive exposure to air, moisture, and light. Use in a fume hood.

Reaction of n-Butyllithium with Cl2ZrCp2.

The reaction of Cl2ZrCp2 with 2 equiv of n-BuLi in THF at -78 °C cleanly produces n-Bu2ZrCp2 (1) in essentially quantitative yield within 1 h.1 At or above 0 °C, (1) decomposes smoothly to form thermally unstable (1-butene)zirconocene (2), which can be stabilized with PMe3 and other phosphines to give the corresponding 1-butene-zirconocene-phosphine complex (eq 1). Some such complexes, e.g. (EtCH=CH2)ZrCp2(PMe3) (3), have been isolated and fully identified.1c,2 Detailed studies of the decomposition reaction of dialkylzirconocenes indicate that the reaction is first-order, unimolecular,3 and nondissociative.4 Thus neither free ZrCp2 nor free alkene is formed during the conversion of dialkylzirconocenes into alkene-zirconocene complexes. In the absence of any other reagents, (EtCH=CH2)ZrCp2(PMe3), which exists as an 80:20 to 90:10 mixture of the distal and proximal stereoisomers (3a and 3b), respectively, further decomposes at 50 °C to give a dimeric species (4), which is relatively stable and inert to various compounds.2 Unstabilized alkene-zirconocene complexes are even more prone to a similar dimerization. Consequently, the generation and use of these compounds, e.g., (2) and (3) is best carried out in the presence of additional reagents that can react with alkene-zirconocene derivatives in a synthetically desirable manner before decomposition of the zirconocene complexes occurs.

Alkene Displacement Reactions.

The 1-butene-zirconocene complexes (2) and (3) can react with alkynes,1,2 alkenes,1,2 and conjugated dienes5 to give the corresponding p-complexes with concomitant expulsion of 1-butene. Even some single-bonded reagents, e.g. silanes,6 allyl ethers,7 and propargyl ethers,8 can react similarly with (2) or (3) to give oxidative addition products with extrusion of 1-butene. Some representative examples are shown in Scheme 1. The complexes (4), (5),1b (6),10 (7),2,9 (8),6 and (9)11 have been fully identified by spectroscopic and other analytical methods, including X-ray analysis.

Synthesis of Five-Membered Zirconacycles via (1-Butene)zirconocene.

Depending on substrate structures, quantities, and whether or not other reagents, such as phosphines, are present, the reactions of (1-butene)zirconocene with p-compounds, such as alkynes, alkenes, dienes, aldehydes, and nitriles, may give either displacement products as discussed above or five-membered zirconacycles with or without incorporation of 1-butene. Although the exact courses of these reactions depend on various kinetic and thermodynamic factors and often are difficult to predict, the following results indicate some general trends for prediction. In general, 1-butene is a relatively weak and readily displaceable ligand, as shown above. However, in cases where the 1-butene displacement products are relatively unhindered, 1-butene may ultimately be incorporated to give five-membered zirconacycles. Some reagents may be capable of directly interacting with (2) to give the corresponding five-membered zirconacycles with incorporation of 1-butene. Some of these reactions are shown in Scheme 2. The reactions of (2) with alkenes have been shown to give thermodynamically equilibrated products,12,13 In the thermally equilibrated products, alkyl groups prefer to be b to the Zr atom, while aryl and alkenyl groups end up in the a-position, as in (10)-(12). In the aldehyde reaction, the sterically less hindered C-Zr bond must selectively react with aldehydes to produce (13) in an irreversible manner.14

Synthetically more useful are those reactions in which five-membered zirconacycles are formed with extrusion of 1-butene. Particularly attractive are the bicyclization reactions of nonconjugated enynes,15-17 diynes,1,18,19 and dienes20-22 as well as related heterocycle-producing reactions (Scheme 3).23 These products can be readily converted to a variety of organic derivatives via various reactions including protonolysis, iodinolysis, and carbonylation (Scheme 4).1,12-23 The intermolecular versions of these reactions are more difficult to control. Nonetheless, some highly favorable and clean results have been obtained with selected alkenes.24 In some of these reactions (Scheme 3), zirconacyclopentanes are undoubtedly the initial products which then undergo ring contraction and reexpansion to give the final zirconacyclopentenes and other products.

The Zr-promoted bicyclization reactions of enynes and dienes have been applied to the efficient synthesis of some complex natural products, e.g. phorbol (14),25 pentalenic acid (15),26 iridomyrmecin (16),27 and dendrobine (17).28

Zirconocene derivatives derived from n-BuMgCl and Cl2ZrCp2 effectively catalyze cyclic29,30 and acyclic31 dimerization of alkenes, as exemplified by eq 2. Significant differences between Et2ZrCp230,32-34 and higher dialkylzirconocenes such as (n-Bu)2ZrCp2 have been noted.

1. (a) Negishi, E.; Cederbaum, F. E.; Takahashi, T. TL 1986, 27, 2829. (b) Takahashi, T.; Swanson, D. R.; Negishi, E. CL 1987, 623. (c) Negishi, E.; Holmes, S. J.; Tour, J. M.; Miller, J. A.; Cederbaum, F. E.; Swanson, D. R.; Takahashi, T. JACS 1989, 111, 3336.
2. (a) Binger, P.; Müller, P.; Benn, R.; Rufínska, A.; Gabor, B.; Krüger, C.; Betz, P. CB 1989, 122, 1035. (b) See also Buchwald, S. L.; Watson, B. T.; Huffman, J. C. JACS 1987, 109, 2544.
3. Negishi, E.; Nguyen, T.; Maye, J. P.; Choueiri, D.; Suzuki, N.; Takahashi, T. CL 1992, 2367.
4. Negishi, E.; Swanson, D. R.; Takahashi, T. CC 1990, 1254.
5. Maye, J. P.; Negishi, E. CC 1995, in press.
6. Takahashi, T.; Hasegawa, M.; Suzuki, N.; Saburi, M.; Rousset, C. J.; Fanwick, P. E.; Negishi, E. JACS 1991, 113, 8564.
7. (a) Ito, H.; Taguchi, T.; Hanzawa, Y. TL 1992, 33, 1295. (b) Ito, H.; Taguchi, T.; Hanzawa, Y. JOC 1993, 58, 774.
8. Ito, H.; Nakamura, T.; Taguchi, T.; Hanzawa, Y. TL 1992, 33, 3769.
9. Kool, L. B.; Rausch, M. D.; Alt, H. G.; Herberhold, M.; Thewalt, U.; Honold, B. JOM 1986, 310, 27.
10. Takahashi, T.; Murakami, M.; Kunishige, M.; Saburi, M.; Uchida, Y.; Kozawa, K.; Uchida, T.; Swanson, D. R.; Negishi, E. CL 1989, 761.
11. Binger, P.; Müller, P.; Herrmann, A. T.; Philipps, P.; Gabor, B.; Langhauser, F.; Krüger, C. CB 1991, 124, 2165.
12. Swanson, D. R.; Rousset, C. J.; Negishi, E.; Takahashi, T.; Seki, T.; Saburi, M.; Uchida, Y. JOC 1989, 54, 3521.
13. Negishi, E.; Miller, S. R. JOC 1989, 54, 6014.
14. Takahashi, T.; Suzuki, N.; Hasegawa, M.; Nitto, Y.; Aoyagi, K.; Saburi, M. CL 1992, 331.
15. Negishi, E.; Swanson, D. R.; Cederbaum, F. E.; Takahashi, T. TL 1987, 28, 917.
16. RajanBabu, T. V.; Nugent, W. A.; Taber, D. F.; Fagan, P. J. JACS 1988, 110, 7128.
17. Lund, E. C.; Livinghouse, T. JOC 1989, 54, 4487.
18. Nugent, W. A.; Thorn, D. L.; Harlow, R. L. JACS 1987, 109, 2788.
19. Van Wagenen, B. C.; Livinghouse, T. TL 1989, 30, 3495.
20. Rousset, C. J.; Swanson, D. R.; Lamaty, F.; Negishi, E. TL 1989, 30, 5105.
21. Nugent, W. A.; Taber, D. F. JACS 1989, 111, 6435.
22. Davis, J. M.; Whitby, R. J.; Jaxa-Chamiec, A. TL 1992, 33, 5655.
23. Jensen, M.; Livinghouse, T. JACS 1989, 111, 4495.
24. Takahashi, T.; Xi, Z.; Rousset, C. J.; Suzuki, N. CL 1993, 1001.
25. Wender, P. A.; McDonald, F. E. JACS 1990, 112, 4956.
26. Agnel, G.; Negishi, E. JACS 1991, 113, 7424.
27. Agnel, G.; Owczarczyk, Z.; Negishi, E. TL 1992, 33, 1543.
28. Mori, M.; Uesaka, N.; Shibasaki, M. JOC 1992, 57, 3519.
29. Negishi, E.; Rousset, C. J.; Maye, J. P.; Choueiry, D.; Suzuki, N.; Takahashi, T. JACS Submitted for publication.
30. Knight, K. S.; Waymount, R. M. JACS 1991, 113, 6268.
31. Rousset, C. J.; Negishi, E.; Suzuki, N.; Takahashi, T. TL 1992, 33, 1965.
32. Takahashi, T.; Seki, T.; Nitto, Y.; Saburi, M.; Rousset, C. J.; Negishi, E. JACS 1991, 113, 6266.
33. Hoveyda, A. H.; Xu, Z. JACS 1991, 113, 5079.
34. Lewis, D. P.; Muller, P. M.; Whitby, R. J.; Jones, R. V. H. TL 1991, 32, 6797.

Ei-ichi Negishi

Purdue University, West Lafayette, IN, USA

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