Three-Component Coupling of Aldehydes, Amines, and Alkynes Catalyzed by Oxidized Copper Nanoparticles on Titania

Copper nanoparticles (mainly as Cu2O) on titania have been shown to catalyze the multicomponent synthesis of propargylamines from aldehydes, amines, and alkynes (A3 coupling) effectively at 70 degrees C under solvent-free conditions. Both aromatic and aliphatic aldehydes and alkynes have been combined with secondary amines to provide a wide range of propargylamines in moderate to excellent yields. Two examples of ketone/amine/alkyne (KA2) coupling are also included. The catalyst is easy to prepare, reusable at a low copper loading (0.5 mol-%), and exhibits higher catalytic activity than some commercially available copper sources. Some mechanistic aspects of the reaction have also been examined, which have unveiled the participation of copper(I) acetylides in a heterogeneous process.