[144-79-6]  · C13H13ClSi  · Methyldiphenylchlorosilane  · (MW 232.80)

(protecting group for alcohols; reacts with carboxylic acids and sulfoximes; C-silylates lithium ester enolates)

Physical Data: bp 295 °C/760 mmHg; d 1.128 g cm-3; n20D 1.5742.

Form Supplied in: clear or transparent, pale yellow liquid.

Analysis of Reagent Purity: gas chromatography on a nonpolar column such as SE-30.

Solubility: sol most organic solvents; reacts with protic solvents such as alcohols, acids, amines, water.

Purification: vacuum distillation is preferred method.

Handling, Storage, and Precautions: chlorosilanes react with water and even moisture in the air to generate HCl and siloxanes, care should be taken to minimize contact with air. Use in a fume hood.

Protecting Group for Alcohols.

The reaction of methyldiphenylchlorosilane with alcohols in the presence of imidazole provides the methyldiphenylsilyl-protected alcohol. The protection of primary, secondary, and tertiary alcohols proceeds with high yields. The methyldiphenylsilyl-protected alcohols are intermediate in stability between those of the trimethylsilyl- and t-butyldimethylsilyl-protected ones.1 It has been shown that, in general, the phenyl-substituted silyl groups are more readily removed by base, where electronic factors are more important, than the trialkylsilyl protecting groups. On the other hand, with acid hydrolysis steric factors play a more significant role and the phenyl-substituted silyl groups are more stable than the trimethylsilyl group, but less stable than the more sterically hindered triethylsilyl and other trialkylsilyl groups.2 The methyldiphenylsilyl ethers can be oxidized by the chromium reagents Dipyridine Chromium(VI) Oxide, Pyridinium Chlorochromate, and Pyridinium Dichromate (eq 1). 1

A primary alcohol was readily methyldiphenylsilylated by the reaction of methyldiphenylchlorosilane in the presence of an amine. In eq 2 the amine is also the reagent being silylated.3

The methyldiphenylsilyl esters of carboxylic acids can be prepared by the reaction of the chlorosilane with the acid in the presence of Triethylamine or with the potassium salt of the acid (eqs 3 and 4).4

Sulfoximes can be silylated with methyldiphenylchlorosilane. The resulting methyldiphenylsilylated sulfoximes can be deprotonated at the methyl group and the anion condensed with aldehydes. The diastereospecificity is greater with the methyldiphenylsilyl group than with the t-butyldimethylsilyl group (eqs 5 and 6).5

C-Silylation of Lithium Ester Enolates.

A very useful asset of methyldiphenylchlorosilane is its ability to directly provide a-(methyldiphenylsilyl) esters (eq 7).6 These a-(methyldiphenylsilyl) esters have themselves proved to be precursors to alkenes, ketones, a-(methyldiphenylsilyl) ketones, and enol silyl ethers and have been used in the synthesis of some natural products.6b An elegant use of the methyldiphenylsilyl group in synthesis (eq 8) is that reported by Villanueva and Prieto,7 who methyldiphenylsilylated the protected ethyl 4-oxolevulinate to give the a-silyl ester (1). This was then treated with 3-phenylpropylmagnesium bromide to give ketone (2), a reaction made possible by the presence of the bulky methyldiphenylsilyl group. This ketone was then regioselectively deprotonated on the side opposite to the methyldiphenylsilyl group and the resulting enolate trimethylsilylated to give enol silyl ether (3), which was subjected to an intramol ecular Mukaiyama reaction to give cyclopentanone (4). Deprotonation and reaction with Formaldehyde produces a methylenomycin B derivative, (5).

Other Methyldiphenylsilylations.

Methyldiphenylchlorosilane was used to form 6-silyluracils and uridines.8 The yields were better than those obtained with Chlorotrimethylsilane (eq 9). The methyldiphenylsilylation of the lithium anion of 3-triethylsilyloxy-1,4-pentadiene occurs to place the methyldiphenylsilyl group on the 1-position, providing, after deprotection, the b-methyldiphenylsilyl ketone (6) (eq 10).9

Related Reagents.

t-Butyldimethylchlorosilane; t-Butyldiphenylchlorosilane; Ethyl 2-(Methyldiphenylsilyl)propanoate.

1. Denmark, S. E.; Hammer, R. P.; Weber, E. J.; Habermas, K. L. JOC 1987, 52, 165.
2. Sommer, L. H. Stereochemistry, Mechanism and Silicon, McGraw-Hill: New York, 1965; 127.
3. (a) Tacke, R.; Wannagat, U. M 1975, 106, 1005. (b) Friedrich, G.; Bartsch, R.; Ruehlmann, K. Pharmazie 1977, 32, 394.
4. (a) Verweij, J. Ger. Patent 2 166 561, 1974 (CA 1974, 81, 152 216k). (b) Rutherford, K. G.; Seidewand, R. J. CJC 1975, 53, 67.
5. Hwang, H. J.; Logusch, E. W.; Brannigan, L. H.; Thompson, M. R. JOC 1987, 52, 3435.
6. (a) Larson, G. L.; Fuentes, L. M. JACS 1981, 103, 2418. (b) Larson, G. L. PAC 1990, 62, 2021.
7. Villanueva, O.; Prieto, J. A. JOC 1993, 58, 2718.
8. Ikehira, H.; Matsuura, T.; Saito, I. TL 1984, 25, 3325.
9. Kim, S.; Emeric, G.; Fuchs, P. L. JOC 1992, 57, 7362.

Gerald L. Larson

Hüls America, Piscataway, NJ, USA

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