Synthesis of Indole-Fused Oxepines via C-H Activation Initiated Diastereoselective [5+2] Annulation of Indoles with 1,6-Enynes

A rhodium-catalyzed diastereoselective formal [5 + 2] annulation of indoles with cyclohexadienone-containing 1,6-enynes has been established via indole 2,3-difunctionalization. The reaction, probably proceeding through tandem indole C2-H alkenylation and intramolecular Friedel-Crafts alkylation relay, provides rapid construction of indole-fused oxepines in good to excellent yields with a broad substrate scope. This method also features concomitant construction of cis-hydrobenzo[b] oxepine scaffolds, a core unit found in numerous natural products of important biological activities.

Automated summary

A rhodium-catalyzed diastereoselective formal [5 + 2] annulation of indoles with cyclohexadienone-containing 1,6-enynes has been successfully established via indole 2,3-difunctionalization. This method allows for rapid construction of indole-fused oxepines with a broad substrate scope and simultaneous formation of cis-hydrobenzo[b] oxepine scaffolds, which are core units found in natural products with important biological activities.