Stereoselective Two-Carbon Ring Expansion of Allylic Amines via Electronic Control of Palladium-Promoted Equilibria

Abstract

Despite their potential value within drug discovery, general methodologies enabling the two-carbon homologation of pyrrolidine and piperidine systems have yet to be developed. Herein we report that palladium-catalysed allylic amine rearrangements enable efficient two-carbon ring expansion of 2-vinyl pyrrolidine and piperidines to their azepane and azocane counterparts. Conditions are mild, tolerant of a range of functional groups and the process can occur with a high degree of enantio-retention. The products formed undergo a range of orthogonal transformations, making them ideal scaffolds for the creation of compound libraries.