Silyl enol ethers methylmagnesium bromide

Friedel-Crafts acylation of 4-bromoindole led to 67, which, after protection by N-tosylation to give 68, was treated with methylmagnesium bromide and afforded compound 66, which contains the welwistatin C3-C16 bond as well as its gem-dimethyl substituent at C(16). A Lewis-acid catalyzed displacement of the tertiary hydroxyl in 66 by a cyclohexanone silyl enol ether afforded intermediate 69, which was then deprotected and N-mclhylalcd to 70 (Scheme 13). 

Preparative Method the best procedure for the preparation of trimethylsilylacetone is the reaction of trimethylsilyl-methylmagnesium chloride or bromide with acetic anhydride. Other useful preparative methods for a-trimethylsilyl ketones involve the reaction of trimethylsilylmethylmagnesium chloride with acid chlorides, or with aldehydes followed by oxidation of the resulting /3-hydroxysilane to the ketone. When the trialkylsilyl group is very large, particularly the triisopropylsilyl group, a rearrangement from the silyl enol ether to the a-silyl ketone is possible. ... 

An example of this strategic approach is a six step synthesis of ( S)-( — )-ipsenol (207), a constituent of the sex pheromone of the bark beetle, which is outlined in Scheme 29 [75]. L-Lactic acid is activated through formation of mixed anhydride 203, and subsequent addition of methylmagnesium bromide furnishes methyl ketone 204. Aldol condensation of enol silyl ether 205 with isovaleraldehyde gives the adduct 206 (89% ds). 

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