Mn(acac)3/Hydrazide-Catalyzed Aerobic Oxidative Cross-Dehydrogenative Couplings of 1,2,3,4-Tetrahydroisoquinolines and Their Mechanistic Studies

Abstract

Aerobic oxidative cross-dehydrogenative couplings of 1,2,3,4-tetrahydroisoquinolines were developed using a Mn(acac)3 and ethyl 2-(4-nitrophenyl)hydrazine-1-carboxylate cocatalytic system. Nucleophiles, including nitroalkanes, dialkyl malonates, acetophenones, indoles, phosphonates, and phosphine oxides, were successfully employed to produce α-functionalized 1,2,3,4-tetrahydroisoquinolines. Control experiments revealed that radical species are not involved in the mechanism. Additionally, 1H NMR and HRMS analyses in the stoichiometric reaction identified an aminal structure as a crucial intermediate. Computational studies further support the plausibility of a hydride transfer process in the oxidation of 1,2,3,4-tetrahydroisoquinolines instead of the triazane pathway, which was predominantly proposed in the DEAD-mediated reaction.