Synthetic and Mechanistic Studies on the Solvent-Dependent Copper-Catalyzed Formation of Indolizines and Chalcones

Abstract

Copper nanoparticles supported on activated carbon have been found to catalyze the multicomponent synthesis of indolizines from pyridine-2-carbaldehyde derivatives, secondary amines, and terminal alkynes in dichloromethane; in the absence of solvent, however, heterocyclic chalcones are formed. We provide compelling evidence that both processes take place through aldehyde–amine–alkyne coupling intermediates. In contrast to other well-known mechanisms for chalcone formation from aldehydes and alkynes, a new reaction pathway involving propargyl amines as intermediates that do not undergo rearrangement is presented. The formation of indolizines or chalcones is driven by inductive and solvent effects, with a wide array of both being reported. In both reactions, the nanoparticulate catalyst has been shown to be superior to some commercially available copper catalysts, and it could be recycled in the case of the chalcone synthesis.