Ethyl Trimethylsilyl Malonate1-3

(R = Et)

[18457-03-9]  · C8H16O4Si  · Ethyl Trimethylsilyl Malonate  · (MW 204.30) (R = Me)

[51849-23-1]  · C7H14O4Si  · Methyl Trimethylsilyl Malonate  · (MW 190.27)

(synthesis of b-keto esters1-3)

Physical Data: R = Et, bp 75 °C/0.5 mmHg, d 1.000 g cm-3; R = Me, bp 105-110 °C/19 mmHg.

Preparative Methods: ethyl trimethylsilyl malonate is commercially available, or it may be easily prepared from the potassium salt of Ethyl Malonate.1,2,6 Methyl trimethylsilyl malonate has been prepared from t-butyl methyl malonate by treatment with Trimethylsilyl Trifluoromethanesulfonate,4 or from Meldrum's acid (2,2-Dimethyl-1,3-dioxane-4,6-dione) and methyl trimethylsilyl ether.5 The preparation and use of t-butyl trimethylsilyl malonate has been reported, although it has not been isolated and characterized.7,8

Handling, Storage, and Precautions: the ethyl derivative is reported to be moisture sensitive.

Ethyl trimethylsilyl malonate is a useful alternative to other malonates in the synthesis of b-keto esters. Trimethylsilyl 2-lithio-2-ethoxycarbonylacetate (1) adds smoothly to a variety of acid chlorides to provide intermediates which undergo spontaneous decarboxylation upon aqueous hydrolysis at room temperature. However, since the first report of its preparation and use,1 it has seen only limited application in organic synthesis. The reagent has been utilized in the synthesis of g,d-unsaturated b-keto esters (Nazarov reagents), which are themselves useful annulating agents.2a Ethyl trimethylsilyl malonate undergoes deprotonation with n-Butyllithium at low temperature to provide the lithio derivative (1). Treatment with crotonyl chloride furnishes ethyl crotonylacetate (eq 1).

The scope of the reaction has been expanded to provide a general synthesis of b-keto esters. A variety of acid chlorides (alkyl, cycloalkyl, aromatic, and heteroaromatic) undergo the reaction (eq 2).2b,9 The method is applicable to the preparation of bis-b-keto esters from diacid chlorides (eq 3).2b

More recently, the mixed anhydride (2) has been shown to undergo efficient homologation under these conditions to give keto ester (3), a highly functionalized intermediate in the synthesis of members of the acomonine family of diterpene alkaloids (eq 4).8

In the synthesis of corynomycolic acid derivatives,10 a key b-keto ester intermediate has been prepared from a substituted malonate derivative (eq 5). In this case, higher yields are obtained when Lithium Diisopropylamide is employed in the deprotonation step instead of n-BuLi.

Related Reagents.

Bis(trimethylsilyl) Malonate; Diethyl Ethoxymagnesiomalonate; Diethyl Malonate; Ethyl 3,3-Diethoxyacrylate; Ethyl Malonate; Magnesium Ethyl Malonate; Malonic Acid; Methyl Cyanoformate.

1. Schmidt, U.; Schwochau, M. M 1967, 98, 1492.
2. (a) Pichat, L.; Beaucourt, J.-P. S 1973, 537. (b) Taylor, E. C.; Turchi, I. J. OPP 1978, 10, 221.
3. For a review of the synthesis of b-keto esters from malonates, see: Pollet, P. L. J. Chem. Educ. 1983, 60, 244.
4. Borgulya, J.; Bernauer, K. S 1980, 545.
5. Rigo, B.; Fasseur, D.; Cauliez, P.; Couturier, D. TL 1989, 30, 3073.
6. Bruynes, C. A.; Jurriens, T. K. JOC 1982, 47, 3966.
7. Cambie, R. C.; Clark, G. R.; Jones, T. C.; Rutledge, P. S.; Strange, G. A.; Woodgate, P. D. AJC 1985, 38, 745.
8. van der Baan, J. L.; Barnick, J. W. F. K.; van Beek, G.; Bickelhaupt, F.; Spek, A. L. T 1992, 48, 2773.
9. Turchi, I. J.; Cullen, T. G. H 1984, 22, 2463.
10. Dobner, B.; Nuhn, P.; Buge, A. ZC 1988, 28, 299.

Gary L. Bolton

Parke-Davis/Warner-Lambert Company, Ann Arbor, MI, USA

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