Zn-Catalyzed Multicomponent KA2 Coupling: One-Pot Assembly of Propargylamines Bearing Tetrasubstituted Carbon Centers

Abstract

Tetrasubstituted propargylamines comprise a unique class of highly useful compounds, which can be accessed through the multicomponent coupling between ketones, amines, and alkynes (KA2 coupling), an underexplored transformation. Herein, the development of a novel, highly efficient, and user-friendly catalytic system for the KA2 coupling, based on the environmentally benign, inexpensive, and readily available zinc acetate, is described. This system is employed in the multicomponent assembly of unprecedented, tetrasubstituted propargylamines derived from structurally diverse, challenging, and even biorelevant substrates. Notable features of this protocol include the demonstration of the enhancing effect that neat conditions can have on catalytic activity, as well as the expedient functionalization of hindered, prochiral cyclohexanones, linear ketones, and interesting molecular scaffolds such as norcamphor and nornicotine.