A short and efficient formal synthesis of (R)-pipecolic acid from the ring expansion of chiral aziridine

Abstract

Ring expansion of 4-(R)-1-(R)-1-phenylethyl)aziridin-2-yl)butyl 4-tosylate obtained from tosylation of 4-(R)-1-(R)-1-phenylethyl)aziridin-2-yl)butan-1-ol via formation of 1-azabicyclo[4.1.0]heptane tosylate gives substituted piperidine. The ring openings of azabicycloheptane tosylate with acetate nucleophiles proceeded in highly regio-and stereoselective manner with release of the ring-strain of the three-member aziridine ring through the breakage of either C-N bond. This ring expansion streategy of aziridine provides a short route for asymmetric synthesis of biologically active natural alkaloid such as R-Pipecolic acid.