Ynamide Smiles Rearrangement Triggered by Visible-Light-Mediated Regioselective Ketyl–Ynamide Coupling: Rapid Access to Functionalized Indoles and Isoquinolines

In the past decades,
significant advances have been made on radical
Smiles rearrangement. However, the eventually formed radical intermediates
in these reactions are limited to the amidyl radical, except for the
few examples initiated by a N-centered radical. Here, a novel and
practical radical Smiles rearrangement triggered by photoredox-catalyzed
regioselective ketyl–ynamide coupling is reported, which represents
the first radical Smiles rearrangement of ynamides. This method enables
facile access to a variety of valuable 2-benzhydrylindoles with broad
substrate scope in generally good yields under mild reaction conditions.
In addition, this chemistry can also be extended to the divergent
synthesis of versatile 3-benzhydrylisoquinolines through a similar
ketyl–ynamide coupling and radical Smiles rearrangement, followed
by dehydrogenative oxidation. Moreover, such an ynamide Smiles rearrangement
initiated by intermolecular photoredox catalysis via addition of external
radical sources is also achieved. By control experiments, the reaction
was shown to proceed via key ketyl radical and α-imino carbon
radical intermediates.