Asymmetric nucleophilic alkylation of aldehydes via 1,1-heterodisubstituted alkenes

Aldehydes are asymmetrically acylated by a two step sequence that is initia ted by a homologation step to 1,1-heterodisubstituted alkenes followed by a symmetric dihydroxylation. Thus, ketene O,S-acetals are efficiently prepare d from aldehydes by a Peterson olefination with lithiated methoxy-phenylthi otrimethylsilyl methane 14 as the C-1 source. Although they are dihydroxyla ted with the Sharpless catalyst with moderate to good enantioselectivity (6 2-80% ee), the process is not efficient owing to the low chemical yields of the desired alpha-hydroxy methyl esters (7-37%). Use of the corresponding sulfoxide 24 or sulfon 25 led to an improved chemical yield of alpha-hydrox y methyl ester 19, but the stereoselectivity was diminished. In contrast, i ntermediate ketene O,O-acetals are prepared by a Horner-Wittig reaction wit h phosphine oxide 31 and are dihydroxylated both with good chemical and ste reochemical yield. The concept is applicable to aromatic, aliphatic, and ch iral aldehydes. For example, this short sequence allows exclusive and indep endent preparation of both diastereomeric heptoses 69a and 69b.