Access to Optically Active 3‐Aminopiperidines by Ring Expansion of Prolinols: Thermodynamic versus Kinetic Control

Abstract

Abstract 3‐Aminopiperidines are of great interest because they can possess a wide range of biological activity depending on the nitrogen substituents. Different approaches their synthesis are presented and the most efficient is a ring expansion of prolinols induced by XtalFluor‐E (diethylaminodifluorosulfinium tetrafluoroborate) in the presence of tetrabutylammonium azide, via an aziridinium intermediate, followed by the reduction of the corresponding azide. Under kinetic conditions, a 2‐(azidomethyl)pyrrolidine/3‐azidopiperidine ratio of 0:100 can be attained depending on the substituents present on the prolinol.