Copper(II) chloride catalyzes the three-component coupling of cyclohexanone, amines, and alkynes to produce tetrasubstituted propargylamines. As a wide range of substrates react without solvent, excess starting material, or other additives, water is the sole by-product. Studies demonstrate that this reaction is first order in copper, cyclohexanone, amine, and alkyne. These mild conditions allow for the first direct, catalytic synthesis of silyl-protected tetrasubstituted propargylamines.

Difficult-to-access alkyl-substituted quinolines are formed directly from commercially available anilines, aldehydes, and alkynes bearing a variety of substituents. Copper(II) triflate catalyzes this three-component coupling without ligand, cocatalyst, solvent, or inert atmosphere. In addition, a two-component Povarov reaction forms 2,3-dialkyl quinolines under the same green conditions that enable the selective three-component synthesis of 2-alkyl quinolines as well as more common aryl quinolines.

A high-yielding three-component reaction proceeds under mild, solvent-free conditions for access to a wide variety of fully-substituted propargylamines. Inexpensive copper(II) chloride catalyzes the coupling of equimolar amounts of amines, alkynes, and cyclohexanone such that the only by-product is one equivalent of water.

A single Cu(II) catalyst without the addition of ligand or base couples a diverse range of nitrogen sources with alkynes and aldehydes bearing alkyl, halogenated, silyl, aryl, and heteroaryl groups. The first example of a copper-catalyzed alkynylation involving p-toluenesulfonamide provides high yields of N-Ts-protected propargylamines. The superior activity of copper(II) triflate also allows this three-component alkynylation to incorporate a ketone.