Flavin-Catalyzed Aerobic α-Functionalization of 1,2,3,4-Tetrahydro-isoquinolines: Application to C=O and C–O Bond Formation

Under metal- and light-free conditions, cationic flavin catalysts enable the aerobic α-functionalization of 1,2,3,4-tetrahydroisoquinolines: (i) α-oxygenation to 3,4-dihydroisoquinolones (C=O formation) and (ii) α-alkoxylation (C-O formation) via cross-dehydrogenative coupling with alcohols. The aerobic α-C=O and C-O bond formations occur via two complementary α-C-H activation pathways catalyzed by flavins with tunable redox properties. These reactions proceed in molecular oxygen or air atmospheres (1 atm) without any additional sacrificial reagents (e.g., external reductants) and without light, unlike conventional flavin-catalyzed aerobic oxidation reactions.