Copper‐Catalyzed Decarboxylative Three‐Component Reactions for the Synthesis of Imidazo[1,2‐a]pyridines

Abstract

AbstractImidazo[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.