Benzylic C(sp3)–H Functionalization via Copper-Catalyzed [3+3] Radical Cycloaddition

The development of benzylic C(sp3)–H functionalization
methods
for the assembly of benzylic derivatives has been extensively explored
in recent years. However, the engagement of benzylic carbon and its
adjacent C=C bond as a C3 synthon in the cycloaddition reaction via
direct benzylic C–H activation is rare. Herein, we report a
copper-catalyzed [3+3] radical cycloaddition reaction through benzylic
C–H bond functionalization to construct six-membered cyclohexane-type
rings. In this reaction, the 2-benzylic C–H bond of an indole
is selectively activated and the indole serves as a C3 synthon that
reacts through highly chemoselective intermolecular self-[3+3] and
cross-[3+3] cycloaddition pathways. Multiple symmetric and nonsymmetric
polycyclic hexahydrocarbazole scaffolds with hexacyclic 6/5/5/6/5/5/6
and pentacyclic 6/5/5/6/5/6 ring systems are synthesized with high
efficiency and chemoselectivity using this strategy. Inspired by the
unique radical addition pathway of cross-[3+3] cycloaddition, a highly
controllable benzylic C–H functionalization for the construction
of C3a-alkylated pyrroloindolines was also developed.