Methanesulfonic acid mediated cyclization and meyer-schuster rearrangement of γ-amino-ynones: Access to enantiopure pyrrolidine exocyclic vinylogous amides

Abstract

α- and β-Amino-ynones have been largely used to prepare heterocyclic rings in the presence of various electrophiles such as protic acids or gold(I). Herein we disclose the unprecedented formation of pyrrolidine exocyclic vinylogous amides, in place of the expected azepinones or piperidinones, starting from γ-amino-ynones derived from amino acids. The process involves a tandem 1,2-addition of the protected nitrogen to the carbonyl group followed by a Meyer-Schuster rearrangement, which efficiently afforded enantiopure pyrrolidine exocyclic vinylogous amides. The sequence is poorly catalyzed by gold salts, but proved to be very efficient in the presence of methanesulfonic acid. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.