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

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.