Aerobic oxidative C–C bond formation through C–H bond activation catalysed by flavin and iodine†

We report a metal/light-free aerobic oxidative C–C bond formation using sp³ C–H bond activation of tetrahydroisoquinolines catalyzed by flavin and iodine. The dual catalytic system enabled the oxidative Mannich and aza-Henry reactions by the cross-dehydrogenative coupling between two sp³ C–H bonds. Furthermore, the flavin–iodine-coupled catalysis was applied to the synthesis of pyrrolo[2,1-a]isoquinolines through the sequential oxidative 1,3-dipolar cycloaddition and dehydrogenative aromatization. The biomimetic flavin catalysis efficiently activates molecular oxygen; thus the non-metal dual catalytic system enables green oxidative transformation using molecular oxygen as an environmentally friendly terminal oxidant which generates benign water.