Enantioselective A3‑Coupling Reaction Employing Chiral CuI‑iPrpyboxdiPh/N‑Boc‑(l)‑Proline Complex under Cooperative Catalysis: Application in the Synthesis of (Indol-2-yl)methanamines

An efficient route to enantioenriched propargylamines via a three-component alkynylation reaction using cooperative catalysis with a CuI-iPrpyboxdiPh complex and N-Boc-(l)-proline has been accomplished. A variety of functionalized amines, aldehydes, and 2-ethynyl anilines were reacted smoothly at ambient temperature to furnish a wide range of propargylamines in high yields (up to 94%) and excellent enantioselectivities (up to 98% ee). Synthetic utility of the methodology has been demonstrated by transforming the products into various synthetically useful intermediates. Finally, propargylamines were transformed into biologically important (indol-2-yl)­methanamines over two steps in good yields (up to 88%) with an excellent level of enantioselectivities (up to 95%).