Gold Catalyzed Photoredox C1‐Alkynylation of N‐Alkyl‐1,2,3,4‐tetrahydroisoquinolines by 1‐Bromoalkynes with UVA LED Light

Abstract A synthetic method that combines [Au 2 (μ‐dppm) 2 ]Cl 2 (dppm=bis(diphenylphosphanyl)methane) and UVA LED (LED=light emitting diode) light (365 nm) to catalyze the regioselective C1‐alkynylation of N ‐alkyl‐1,2,3,4‐tetrahydroisoquinolines (THIQs) with alkynyl bromides is described. The reaction mechanism was delineated to involve a reductive quench pathway to generate the two posited radical species of the nitrogen‐containing heterocycle and organic halide. In contrast, radical formation via an oxidative quench pathway was suggested to be operative in analogous control experiments with a 1‐iodoalkyne. The usefulness of this carbon‐carbon bond forming strategy was also exemplified by its application to the formal synthesis of the opioid analgesic drug methopholine and synthesis of a protoberberine alkaloid derivative. magnified image