A new synthesis of alkaloid (S)-3-hydroxypiperidin-2-one and its O-TBS protected derivative

Abstract

From the known lactone (S)-4, easily derived from L-glutamic acid, a scalable approach to chiral building block O-silylated 3-hydroxypiperidin-2-one 3 and alkaloid 1 was achieved in five and six-steps respectively. The key steps are a chemoselective amidation of lactone-ester 5 and a one-pot reductive borane-decomplexation, N-debenzylation and cyclization.