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.