Ethyl (Methyldiphenylsilyl)acetate1

(R = Et)

[13950-57-7]  · C17H20O2Si  · Ethyl (Methyldiphenylsilyl)acetate  · (MW 284.46) (R = Me)

[89266-73-9]  · C16H18O2Si  · Methyl (Methyldiphenylsilyl)acetate  · (MW 270.43) (R = i-Pr)

[87776-13-4]  · C18H22O2Si  · Isopropyl (Methyldiphenylsilyl)acetate  · (MW 298.49) (R = t-Bu)

[77772-21-5]  · C19H24O2Si  · t-Butyl (Methyldiphenylsilyl)acetate  · (MW 312.52)

(vinyl 1,1-dication synthetic equivalent in reactions with Grignard reagents;2 reagent for Peterson synthesis of a,b-unsaturated esters3)

Physical Data: clear to light yellow liquids. R = Et, n25D 1.5381; R = i-Pr, n26D 1.5398; R = t-Bu, n24D 1.5324.

Preparative Method: whereas the direct silylation of the lithium enolate of an ester normally results in the formation of a mixture of the a-silyl ester and the corresponding silyl ketene acetal, the same reaction with Methyldiphenylchlorosilane gives exclusively the a-methyldiphenylsilyl ester.2d,4 This direct C-silylation is the best general route to a-silyl esters.

Purification: best purified by silica gel chromatography. The esters can be distilled through a suitable short path apparatus.

Handling, Storage, and Precautions: the esters desilylate in acid or alkaline medium. They desilylate very slowly with water or alcohols under neutral conditions.

Alkene Synthesis.

The first synthetically successful conversion of an a-silyl ester to an alkene was accomplished by the reaction of ethyl trimethylsilylacetate with 2 equiv of the Grignard reagent formed from high purity Magnesium and a primary or aryl halide, followed by elimination of the b-hydroxy silane formed (eq 1).2a Although the same reaction has never been reported for ethyl a-(methyldiphenylsilyl)acetate, use has been made of the ready C-methyldiphenylsilylation of the lithium enolates of esters to form ethyl a-alkyl-a-(methyldiphenylsilyl)acetates.4a These a-silyl esters react with primary or aryl Grignard reagents to provide, after elimination, trisubstituted alkenes (eqs 2-5).2c,d Improved results are often obtained when the first addition is carried out with a Grignard reagent and the second with an organolithium reagent. The use of a Grignard reagent followed by an organolithium reagent allows the preparation of mixed trisubstituted alkenes (eq 5). The stereoselectivity is excellent when the elimination step is accomplished under basic conditions, but only moderate when carried out under acidic conditions.

Tetrasubstituted alkenes can be prepared in an analogous fashion from a,a-dialkyl-a-(methyldiphenylsilyl)acetate, prepared by alkylation of the corresponding a-alkyl-a-silyl ester (eqs 6 and 7).4b These reactions are, however, strongly influenced by the steric demands of the highly substituted a-carbon and therefore tend to give ketones even with an excess of the Grignard reagent. Alkenes are obtained only with the Grignard/organolithium reagent combination, and even this sequence sometimes succumbs to steric strain. No reports of the use of cerium reagents in these transformations have appeared.

Synthesis of a,b-Unsaturated Esters.

Yamamoto and co-workers3c and others3d,e have shown that a-trimethylsilyl acetates effect Peterson alkenation of ketones and aldehydes. The lithium enolates of a-(methyldiphenylsilyl) esters react similarly with ketones and aldehydes to give a,b-unsaturated esters (eq 8).3a,b In the case of a-silyl acetates, no particular advantage of either the trimethylsilyl or methyldiphenylsilyl group over the other is apparent. In the case of a-substituted a-silylacetates, the methyldiphenylsilyl group has the distinct advantage of being directly prepared by methyldiphenylsilylation of the lithium enolate of the ester.1b The (E)/(Z) stereoselectivity of the a,b-unsaturated ester synthesis shows no correlation with the steric bulk of the alcohol portion of the a-(methyldiphenylsilyl)acetates. However, the (E)/(Z) ratio is affected by the temperature and mode of addition. It appears that the elimination step in the process leads to a mixture of diastereomeric alkenes.3a,b

A Michael addition of the silyl enolate was employed in a short synthesis of (±)-methyl jasmonate from cyclopentenone (eqs 9 and 10).5 This convergent scheme was carried out in three steps: conjugate addition of methyl a-(methyldiphenylsilyl)lithioacetate to cyclopentenone, alkylation of the resulting enolate with (Z)-1-bromopent-2-ene, and desilylation with Potassium Fluoride. (±)-Ethyl jasmonate was prepared in a similar fashion. In the conjugate addition step, the a-(methyldiphenylsilyl)ester gave superior results to those obtained with the a-trimethylsilyl esters.

Related Reagents.

t-Butyl Trimethylsilylacetate; N,N-Dimethyl-2-(trimethylsilyl)acetamide; Ethyl 2-(Methyldiphenylsilyl)propanoate; Ethyl Trimethylsilylacetate; Trimethylsilylacetic Acid; Trimethylsilylacetone.

1. Larson, G. L. PAC 1990, 62, 2021.
2. (a) Larson, G. L.; Hernández D. TL 1982, 23, 1035. (b) Hernandez, D. Doctoral Dissertation, University of Puerto Rico, 1984. (c) Hernández, D; Larson, G. L. JOC 1984, 49, 4285. (d) Cruz de Maldonado, V.; Larson, G. L. SC 1983, 13, 1163. (e) Larson, G. L.; Lopez-Cepero, I. M.; Mieles, L. R. OSC 1993, 8, 474.
3. (a) Larson, G. L.; Fernandez de Kaifer, C.; Seda, R.; Torres, L. E.; Ramirez, J. R. JOC 1984, 49, 3385. (b) Larson, G. L.; Quiroz, F.; Suárez, J. SC 1983, 13, 833. For related papers on the use of a-trimethylsilylacetates in the synthesis of a,b-unsaturated esters, see: (c) Shimoji, K.; Taguchi, H.; Oshima, K.; Yamamoto, H.; Nozak, H. JACS 1974, 96, 1620. (d) Hartzell, S. L.; Sullivan, D. F.; Rathke, M. W. TL 1974, 1403, (e) Larcheveque, M.; Debal, A. CC 1981, 877.
4. (a) Larson, G. L.; Fuentes, L. M. JACS 1981, 103, 2418. (b) Larson, G. L.; Cruz de Maldonado, V.; Fuentes, L. M.; Torres, L. E. JOC 1988, 53, 633.
5. Oppolzer, W.; Modao, G.; Baettig, K. HCA 1983, 66, 2140.

Gerald L. Larson

Hüls America, Piscataway, NJ, USA

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