A new synthesis of (2S)-4-oxopipecolic acid by thermal rearrangement of enantiopure spirocyclopropaneisoxazolidine

Abstract

A novel synthesis of (2S)-4-oxo-pipecolic acid is reported. The synthetic route employs as a key step the diastereoselective cycloaddition of the N-glycosylnitrone 7 to methylenecyclopropane followed by thermal rearrangement of the spirocyclopropaneisoxazolidine 8a. Stereoselective reduction of the N-BOC methyl ester of 4-oxopipecolic acid by L-selectride® gives the protected cis-4-hydroxy-pipecolic acid 14.