Copper-Catalyzed Three-Component Coupling of Terminal Alkyne, Dihalomethane and Amine to Propargylic Amines

The direct C-H and C-halogen activation for C-C bond formation is one of the most interesting reactions in organic chemistry. C-C bond formation using alkynes as a carbon nucleophilic source is a very useful method in synthesis. Herein, a copper(I) chloride catalyzed three-component coupling reaction of alkynes, dihalomethanes and amines through C-H and C-halogen activation to form propargylic amines under mild conditions has been established. The reaction can be conducted in water, in neat or in common organic solvents and it was applicable to both aromatic and aliphatic alkynes with good functional groups tolerance. It represents an excellent example of multi-component reactions (MCRs), provides an elegant method for the synthesis of propargylic amines which are frequent skeletal components and synthetically versatile key intermediates for the preparation of many nitrogen-containing biologically active compounds. From the mechanism point of view, this chemistry offers not only a new approach to propargylic amines with new C-C and C-N bonds formation through C-H and C-halogen activation, but also provides valuable mechanistic insight into the novel multi-component reactions.