Non-thiazolidinedione antihyperglycaemic agents. Part 5: Asymmetric aldol synthesis of ( S)-(−)-2-oxy-3-arylpropanoic acids

Abstract

Boron-mediated asymmetric aldol reactions of substituted benzaldehyde 5 with 2-oxyethanoyloxazolidinones 4a– e, containing electron withdrawing, chelating, and bulky alkoxy and aryloxy groups, gave variable yields of syn-aldol adducts 6a– e in high diastereoisomeric excess. Dehydroxylation of these adducts afforded 7a– e in a sequence which complements the traditional Evans asymmetric alkylation strategy. Cleavage of the auxiliary from 7a– e afforded antihyperglycaemic ( S)-(−)-2-oxy-3-arylpropanoic acids 3a– e in excellent enantiomeric excess.