Polyol Synthesis with β-Oxyanionic Alkyllithium Reagents: Syntheses of Aculeatins A, B, and D

Synthesis of ketone aldol products using a non-aldol route was developed. The beta-phenylthio alcohols were prepared from optically pure oxiranes. Deprotonation and reductive lithiation generated the key intermediate, a beta-oxyanionic alkyllithium reagent. Addition to a Weinreb amide produced the beta-hydroxy ketone in >90% yield using only 1.5 equiv of the phenylthio alcohol. Stereoselective reduction of the ketone led to either the syn- or anti-1,3-diol. This simple, convergent sequence was used to prepare aculeatins A, B, and D from a common intermediate.