Enantioselective Radical Cyclization of Tryptamines by Visible Light-Excited Nitroxides

Nitroxides can absorb both ultraviolet (UV) and visible light, and their electron can be excited from the π-bonding orbital to the antibonding π* orbital or the n-bonding orbital to the antibonding π* orbital, respectively. Despite the reported UV-induced hydrogen atom transfer (HAT) process, the potential of nitroxides for visible light-excited photosynthesis is underexplored. Here we demonstrate that nitroxide can convert indole to its radical through a visible light-induced HAT process. A chiral phosphoric acid-catalyzed cyclization of the in situ-formed imine radical, followed by trapping by another molecule of nitroxide, provides the product in high yield and enantioselectivity. To highlight the novelty and efficiency of this strategy, an asymmetric total synthesis of natural product (-)-verrupyrroloindoline was accomplished in 5 steps.