t-Butyl 2-Chloro-2-trimethylsilylacetate

[66406-43-7]  · C9H19ClO2Si  · t-Butyl 2-Chloro-2-trimethylsilylacetate  · (MW 222.79)

(alkenation of enolizable ketones leading to functionalized, tetrasubstituted alkenes (a,b-unsaturated esters) via a Peterson alkenation)

Physical Data: bp 55 °C/1.4 mmHg.

Solubility: sol THF.

Preparative Method: prepared from t-Butyl Chloroacetate by sequential reaction with Lithium Diisopropylamide and Chlorotrimethylsilane followed by aqueous workup and distillation.1

Handling, Storage, and Precautions: as this material is an activated alkyl halide, it must be considered a potential alkylating agent and lachrymator and handled with care and suitable protective clothing (e.g. gloves) in a fume hood.

The classical method for alkenation of an aldehyde utilizes Wittig reagents (phosphorus ylides) or related species such as the Wadsworth-Emmons reagent. These reagents do not generally give useful yields in the alkenation of ketones because of problems of steric hindrance between the ketone and the phosphorus reagent and because of competing enolization of the ketone. a-Silyl carbanions are generally less basic and less subject to steric encumbrance than the corresponding phosphorus ylides.2 Therefore the Peterson alkenation2 of ketones by a-silyl carbanions frequently provides superior results to the phosphorus reagents such as in the alkenation of cyclopentanone (eq 1).3

If the a-silyl carbanion is also functionalized with a leaving group such as chloride, condensation with carbonyl compounds can lead to epoxysilanes (eq 2).4

If the carbanion is further substituted with a t-butoxycarbonyl group, the epoxysilane reaction pathway is suppressed and Peterson alkenation is the normal reaction course. Thus the reaction of t-butyl 2-chloro-2-lithio-2-trimethylsilylacetate, derived from t-butyl 2-chloro-2-trimethylsilylacetate by reaction with LDA, with aldehydes (eq 3) and ketones (eq 4) leads to tri- and tetrasubstituted functionalized alkenes, a-chloro-a,b-unsaturated esters.1

In the case of unsymmetrical ketones, moderate (eq 5) to good (eq 6) degrees of stereoselection are observed in the alkenation process, although yields are typically low.

Chloro t-butoxycarbonylalkenes are of use as functional intermediates in, for example, the total synthesis of prostaglandins.5 More general is the interest in these products as herbicides,6 insecticides,7 and antibiotics.8 In the latter case, the Peterson alkenation was utilized to prepare C(2)-substituted monic acid esters (eq 7).

1. Chan, T. H.; Moreland, M. TL 1978, 515.
2. Ager, D. J. S 1984, 384.
3. Shimoji, K.; Taguchi, H.; Oshima, K.; Yamamoto, H.; Nozaki, H. JACS 1974, 96, 1620.
4. Burford, C.; Cooke, F.; Ehlinger, E.; Magnus, P. JACS 1977, 99, 4536.
5. Goldstein, S.; Vannes, P.; Houge, C.; Frisque-Hesbain, A. M.; Wiaux-Zamar, C.; Ghosez, L.; Germain, G.; Declercq, J. P.; Van Meerssche, M.; Arrieta, J. M. JACS 1981, 103, 4616.
6. Rueb, L.; Eicken, K.; Westphalen, K. O.; Wuerzer, B.; BASF A.-G. Eur. Pat. Appl. 1991 (CA 1991, 115, 29 347x; CA 1991, 114, 185 266e).
7. Milner, D. J.; Spinney, M. A.; Robson, M. J.; Imperial Chemical Industries PLC. Eur. Pat. Appl., 1990 (CA 1991, 114, 82 191x); Tessier, J.; Teche, A.; Demoute, J. P.; Roussel-UCLAF. Eur. Pat. Appl., 1984 (CA 1984, 101, 110 414z).
8. Crimmin, M. J.; O'Hanlon, P. J.; Rogers, N. H. JCS(P1) 1985, 541; Rogers, N. H.; Crimmin, M. J.; Beecham Group PLC. Eur. Pat. Appl. 1983 (CA 1983, 99, 158 139f).

Michael A. Brook

McMaster University, Hamilton, ON, Canada

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