Cu-Catalyzed Cycloaromatization and Amination of 2-Bromoaryl Nitriles, Terminal Alkynes, and Amines for 1-Aminoisoquinoline Synthesis

We report a copper-catalyzed 6-endo-dig cycloaromatization and amination of 2-bromoaryl nitriles, terminal alkynes, and amines for efficient and selective synthesis of 1-aminoisoquinolines, which involves difunctionalization of the cyano group with amination of its carbon atom. A variety of 1-aminoisoquinolines, as well as derivatives of modified amino-containing drug molecules, are readily achieved in water. Cu(III)-acetylide serves as intermediate and governs the exclusive 6-endo-dig selectivity, suppressing undesired 5-exo-dig byproducts.