Organo-catalyzed enantioselective [4+2] Annulation of glutaraldehyde and c3-indolyl-imines to access indol-3-yl-piperidines

Abstract

A simple and straightforward method is developed for the enantioselective synthesis of indol-3-yl-piperidine. The reaction proceeds through a proline-catalyzed direct Mannich reaction between glutaraldehyde and C3-indolyl-imines, followed by intramolecular reductive cyclization as an overall [4+2] annulation in one-pot fashion. A series of indol-3-yl-piperidine have been accessed with good yields up to 71 % and high enantioselectivity up to >99 % ee.