A Dual Cobalt-Photoredox Catalytic Approach for Asymmetric Dearomatization of Indoles with Aryl Amides Via C-H Activation

In this study, we unveil a novel method for the asymmetric dearomatization of indoles under cobalt/photoredox catalysis. By strategically activating C-H bonds of amides and subsequent migratory insertion of π-bonds present in indole as reactive partner, we achieve syn-selective tetrahydro-5H-indolo[2,3-c]isoquinolin-5-one derivatives with excellent yields and enantiomeric excesses of up to >99 %. The developed method operates without a metal oxidant, relying solely on oxygen as the oxidant and employing an organic dye as a photocatalyst under irradiation. Control experiments and stoichiometric studies elucidate the reversible nature of the enantiodetermining C-H activation step, albeit not being rate-determining. This study not only expands the horizon of cobalt-catalyzed asymmetric C-H bond functionalization, but also showcases the potential synergy between cobalt and photoredox catalysis in enabling asymmetric synthesis of complex molecules.