Lewis Base Activation of Lewis Acids: Catalytic, Enantioselective Addition of Glycolate-Derived Silyl Ketene Acetals to Aldehydes

Abstract

A catalytic system involving silicon tetrachloride and a chiral, Lewis basic bisphosphoramide catalyst is effective for the addition of glycolate-derived silyl ketene acetals to aldehydes. It was found that the sense of <i>diastereoselectivity</i> could be modulated by changing the size of the substituents on the silyl ketene acetals. In general, the trimethylsilyl ketene acetals derived from methyl glycolates with a large protecting group on the α-oxygen provide enantiomerically enriched α,β-dihydroxy esters with high <i>syn</i>-diastereoselectivity, whereas the <i>tert</i>-butyldimethylsilyl ketene acetals derived from bulky esters of α-methoxyacetic acid provide enantiomerically enriched α,β-dihydroxy esters with high <i>anti</i>-diastereoselecitvity.