Condensation Versus Hydroamination for the Direct, Catalytic Synthesis of Tetrasubstituted Propargylamines

Abstract

Multicomponent couplings of carbonyls, amines, and nucleophiles provide a wide array of trisubstituted carbons bearing amines but tetrasubstituted products are rarely formed. Cooperative copper/titanium catalysis under solvent-free conditions is required to overcome the barrier to condensation of a ketone with an amine and subsequent alkynylation. An alternative mode of accessing ketimines is the Markovnikov hydroamination of alkynes. Heating a simple copper salt with an amine and a terminal alkyne rapidly produces tetrasubstituted propargylic amines via tandem hydroamination-alkynylation.