Titanocenemethylene-Zinc Halide Complex1

Cp2Ti=CH2.ZnX2

(methylenation reagent of unsaturated carbonyl groups1)

Solubility: sol THF, toluene.

Preparative Methods: the reaction of Diiodomethane with Zinc dust in THF at 45 °C produces CH2(ZnI)2 in ca. 45% yield. Its reaction with Dichlorobis(cyclopentadienyl)titanium (25 °C, 30-60 min) affords a deep red solution of the titanocenemethylene-zinc halide complex (ca. 45-55% yield).2

Handling, Storage, and Precautions: should be handled and stored under an inert atmosphere.

Methylenation of Unsaturated Carbon Centers.

The titanocenemethylene-zinc halide complex reacts rapidly with ketones in good yields (eq 1).2 The alkenation of an a,b-unsaturated ketone gives the corresponding diene (eq 2).2 Whereas no clean reaction is observed with acid chlorides, the addition of the titanocenemethylene complex to a nitrile provides, after a workup with D2O, an a-deuterated ketone (eq 3).2 The reaction with alkynes is less straightforward and moderate regio- and chemoselectivity is observed (eq 4).2

Alternative titanium-based reagents can be used and have found more applications than the titanocenemethylene-zinc halide complex.1 The Tebbe reagent m-Chlorobis(cyclopentadienyl)(dimethylaluminum)-m-methylenetitanium, although involving the use of pyrophoric Trimethylaluminum, has found broader application in synthesis.1,3 A related reagent prepared from zinc, a dihalomethane, and Titanium(IV) Chloride (Takai reagent)4 proved also to be a useful methylenation reagent of aldehydes and ketones. After a modification, this reagent is also able to perform a methylenation (and alkylidenation) of various carboxylic acid derivatives (eq 5).5 The preparation modification reported by Lombardo provides a mild, nonbasic method for the methylenation of ketones. The Lombardo reagent is compatible with a wide variety of functional groups. Compared to the original procedure of Takai, the modification of Lombardo involves the preformation of the reagent, which was found to be stable at low temperature (eq 6).6 Finally, Nysted reported the preparation of the alkenation reagent [XZnCH2ZnCH2ZnX.THF] which, in the absence of titanium salts, proved to be highly efficient for the methylenation of steroids (eq 7).7


1. Review of titanium-based reagents for carbonyl methylenation: Pine, S. H. OR 1993, 43, 1.
2. Eisch, J. J.; Piotrowski, A. TL 1983, 24, 2043. For a Zr analog see: Tour, J. M.; Bedworth, P. V.; Wa, R. TL 1989, 30, 3927.
3. (a) Tebbe, F. N.; Parshall, G. W.; Reddy, G. S. JACS 1978, 100, 3611. (b) Pine, S. H.; Zahler, T.; Evans, D. A.; Grubbs, R. H. JACS 1980, 102, 3270.
4. Takai, K.; Hotta, Y.; Oshima, K.; Nozaki, H. TL 1978, 2417.
5. (a) Okazoe, T.; Takai, K.; Oshima, K.; Utimoto, K. JOC 1987, 52, 4410. (b) Takai, K.; Fujimura, O.; Kataoka, Y.; Utimoto, K. TL 1989, 30, 211. (c) Takai, K.; Kataoka, Y.; Okazoe, T.; Utimoto, K. TL 1988, 29, 1065. (d) Takai, K.; Tezuka, M.; Kataoka, Y.; Utimoto, K. SL 1989, 27.
6. (a) Lombardo, L. TL 1982, 23, 4293. (b) Lombardo, L. OS 1987, 65, 81.
7. (a) Nysted, L. N. U.S. Patent 3 865 848, 1975 (CA 1975, 83, 10 406q). (b) Nysted, L. N. U.S. Patent 3 960 904, 1976 (CA 1976, 85, 94 618n).

Paul Knochel

Philipps Universität, Marburg, Germany



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