Copper-Catalyzed Domino Three-Component Benzannulation: Access to Isoquinolines

We report herein the synthesis of isoquinolines through a copper(I)-catalyzed domino reaction. During this transformation, three molecules of terminal alkynes, 2-bromoaryl aldehydes (ketones), and acetamide react together, in a sequence including Sonogashira coupling, condensation, 6-endo-dig cyclization, elimination of acetic acid, and hydrolysis. In this reaction, isoquinolines with broad functional group tolerance were successfully obtained by using acetamide as nitrogen source, which provides an alternative to odorous and toxic amines.