Highly Stereoselective Aldol Reaction of meso-Glutaraldehyde Derivatives

Abstract

Enantioselective aldol reaction is one of the most useful methods in order to synthesize the family of macrolides and ionophore antibodies which have a deoxypolypropionate skelton. As 2,4-dimethylglutaraldehyde also contains the deoxypolypropionates, enantioselective aldol reaction of meso-2,4-dimethylglutaraldehyde would efficiently construct the macrolides. We have investigated the stereoselective anti-aldol reaction of meso-2,4-dimethylglutaldehyde with propionyl ester bearing (1R,2S)-(−)-norephedrine derivatives to construct stereo tetrads building blocks with good stereoselectivities in one step. Large amounts of meso-2,4-dimethylglutaldehyde was prepared by Swern oxidation with a microflow system, and the asymmetric aldol reaction afforded the lactol in 72% yield. Diastereomeric ratio of the lactone, converted by oxidation of the lactol, was measured by HPLC with a chiral column to be 6:1. Observed diastereoselectivities could be rationalized by Zimmerman-Traxler model.