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.