Regioselective Metal-Free Decarboxylative Multicomponent Coupling of α-Amino Acids, Aldehydes and Isonitriles Leading to <i>N</i>-Substituted Azacyclic-2-carboxamides with Antithrombotic Activity

Abstract

An atom-economical regioselective synthesis of N-substituted prolinamides or N-substituted piperidine-2-carboxamides via a metal-free decarboxylative multicomponent coupling between l-proline or pipecolic acid, aldehydes, and isonitriles is described. The cascade event involves sequential imine formation, decarboxylation, isonitrile insertion, and hydrolysis to afford the product in one-pot. Two of the prolinamides were found to display appreciable antithrombotic activity via inhibition of platelet aggregation.