Ethyl 2-(Methyldiphenylsilyl)propanoate1

[77772-22-6]  · C18H22O2Si  · Ethyl 2-(Methyldiphenylsilyl)propanoate  · (MW 298.49)

(precursor to 1,1-disubstituted 1-propenes;1c,2 reacts with primary Grignard reagents to give 2-(methyldiphenylsilyl)-3-alkanones,3 which in turn lead to regioselectively derived methyldiphenylsilyl enol ethers4 or to 3-alkanones; reagent for the synthesis of a-methyl-a,b-unsaturated esters5)

Alternate Name: ethyl 2-(methyldiphenylsilyl)propionate.

Physical Data: clear to pale yellow liquid; n24D 1.5407.

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 reaction of lithium ester enolates with methyldiphenylchlorosilane gives exclusively the a-methyldiphenylsilyl ester.1b,c This direct C-silylation is the best general route to a-silyl esters.

Purification: can be purified by silica gel chromatography, eluting with ethyl acetate/hexane (2:98 v/v), or by short path distillation.

Handling, Storage, and Precautions: this compound and other a-silyl carbonyl compounds are hydrolyzed under acidic or basic conditions to give the parent desilylated esters.

1,1-Disubstituted 1-Propenes.

The reaction of ethyl (methyldiphenylsilyl)propanoate (1) with primary or aryl Grignard reagents results in the formation of the a-silyl ketone or a 1,1-disubstituted 1-propene.1c,2 For example, the reaction with Phenylmagnesium Bromide in refluxing THF for several hours leads to 1,1-diphenyl-1-propene in good yield (eq 1). In general, the more sterically demanding the Grignard reagent, the lower the yield of the alkene. The synthesis of alkenes from other more sterically hindered a-(methyldiphenylsilyl) esters requires a sequential reaction of the ester with a Grignard reagent followed by an organolithium reagent (eq 2).

a-Silyl Ketones, Silyl Enol Ethers, and Ketones.

The reaction of (1) with Grignard reagents leads to the corresponding 2-(methyldiphenylsilyl)-3-alkanone (eq 3).3 This reaction is favored when the acid portion of the ester is larger than propionyl. The reaction proceeds through formation of a magnesium enolate on the side of the a-silyl ketone opposite to that of the bulky methyldiphenylsilyl group (eq 4). The direct conversion of a-(methyldiphenylsilyl) esters to ketones can be accomplished by treatment of the ester with a Grignard reagent followed by protiodesilylation with Potassium Fluoride/methanol (eq 5).

The a-(methyldiphenylsilyl) ketones isomerize to the corresponding silyl enol ether regioselectively simply by mild thermolysis at about 150 °C (eq 6). This reaction can also be done in a stereoselective fashion to give the (Z)-enol silyl ether when the thermolysis is carried out in acetonitrile (eq 7).4

a-Methyl-a,b-unsaturated Esters.

Deprotonation of (1) and related compounds followed by reaction of the resulting enolate with aldehydes provides a-methyl(alkyl)-a,b-unsaturated esters in good yields.5 The (Z) diastereomer predominates, with (Z)/(E) ratios between 90:10 and 79:21. Acrolein reacts in a similar manner, undergoing 1,2-alkenation to give a 77:23 mixture of (Z)- and (E)-ethyl 2-methyl-2,4-pentadienoates (eq 8).

Related Reagents.

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

1. (a) Larson, G. L. PAC 1990, 62, 2021. (b) Larson, G. L.; Fuentes, L. M., JACS 1981, 103, 2418. (c) Larson, G. L.; Lopez-Cepero, I. M.; Mieles, L. R. OSC 1993, 8, 474.
2. Hernández, D; Larson, G. L. JOC 1984, 49, 4285.
3. Larson, G. L.; Cruz de Maldonado, V.; Fuentes, L. M.; Torres, L. E. JOC 1988, 53, 633.
4. Larson, G. L.; Berrios, R.; Prieto, J. A. TL 1989, 30, 283.
5. Larson, G. L.; Fernandez de Kaifer, C.; Seda, R.; Torres, L. E.; Ramirez, J. R. JOC 1984, 49, 3385.

Gerald L. Larson

Hüls America, Piscataway, NJ, USA

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