Copper-catalyzed decarboxylative three-component reactions for the synthesis of imidazo[1,2-a]pyridines

Abstract

Imidazo[1,2-a]pyridine derivatives were synthesized through multicomponent coupling reactions of 2-aminopyridines, aldehydes, and alkynecarboxylic acids in the presence of 10 mol-% CuI/Cu(OTf) 2. Both aryl- and alkyl-substituted alkynecarboxylic acids, including propiolic acid, were good alkyne sources and afforded the desired imidazo[1,2-a]pyridines in good yields through the decarboxylative coupling reactions. Arylalkynecarboxylic acids were synthesized through palladium-catalyzed coupling reactions between aryl iodides and propiolic acid and reacted with 2-aminopyridine and aldehydes, with or without a purification step. In both cases the desired imidazo[1,2-a]pyridines were obtained in good yields. Mechanistic studies suggested that in the case of propiolic acid the decarboxylative addition predominates over terminal alkyne addition. Imidazo[1,2-a]pyridine derivatives were synthesized through three-component coupling reactions of 2-aminopyridines, aldehydes, and alkynecarboxylic acids in the presence of 10 mol-% CuI/Cu(OTf) 2 Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.