Memory of Chirality in the Asymmetric Synthesis of Piperidines with Vicinal Stereocenters by Intramolecular Sn2′ Reaction

Abstract

Intramolecular Sn2' cyclization of α-amino ester enolates provided piperidine derivatives with vicinal quaternary-tertiary stereocenters with excellent diastereo- and enantioselectivity via memory of chirality and the Thorpe-Ingold effect. DFT calculations provided a mechanistic rationale for the increase in chirality preservation via the Thorpe-Ingold effect. This new method has the potential to be integrated into concise asymmetric synthesis of bioactive molecules containing multisubstituted piperidine moieties.