Copper(II)-Mediated Aerobic Synthesis of Imidazo[1,2-a]pyridines via Cascade Aminomethylation/Cycloisomerization of Alkynes

• Published in: Journal of organic chemistry Vol. 80; no. 21; pp. 11212 - 11218
• Main Authors: Rassokhina, Irina V, Shirinian, Valerii Z, Zavarzin, Igor V, Gevorgyan, Vladimir, Volkova, Yulia A
• Format: Journal Article
• Language: English
• Published: United States 06-11-2015
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.5b02102

A single copper(II)-catalyzed three-component cascade aminomethylation/cycloisomerization of propiolates to form imidazo[1,2-a]pyridines was explored. A straightforward method was developed for the practical synthesis of functionalized imidazo[1,2-a]pyridines from benzaldehydes, 2-aminopyridines, and propiolate derivatives catalyzed by Cu(OAc)2 hydrate in the presence of air. The protocol is marked by excellent yields, functional group tolerance, and, above all, adaptability to synthesize imidazo[1,2-a]pyridine-based drug molecules such as Alpidem.