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

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.