Lewis Base Catalyzed, Enantioselective Aldol Addition of Methyl Trichlorosilyl Ketene Acetal to Ketones

Abstract
The catalytic enantioselective addition of an acetate enolate equivalent to ketones is described. Methyl trichlorosilyl ketene acetal reacts with a wide range of ketones in the presence of pyridine N-oxide to afford the aldol addition products in excellent yields. Chiral 2,2‘-pyridyl bis-N-oxides bearing various substituents at the 3,3‘- and 6,6‘-positions also provide excellent yields of the aldol products with variable enantioselectivities ranging from 94/6 er for aromatic ketones to nearly racemic for aliphatic ketones. An X-ray crystal structure of the complex between a catalyst and silicon tetrachloride (((P)-(R,R)-19·SiCl4)) has been obtained. Extensive computational analysis provides a stereochemical rationale for the observed trends in enantioselectivities.

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