Enantioselective Synthesis of Indole-Fused Polycycles Bearing Four Consecutive Stereocenters via Rhodium Catalysis

Indole-fused polycycles are common in natural products and bioactive molecules, yet their concise and efficient synthesis remains challenging, especially for compounds with multiple stereocenters. Herein, we report the application of a chiral Cp^xRh^III catalyst in the enantioselective C-H activation/[4+2] annulation of indoles with bicyclic alkenes. This chiral catalytic system exhibits high enantioselectivity and broad functional group tolerance and operates under benign conditions. The scope of this methodology encompasses a variety of substrates, delivering novel polycyclic compounds with four consecutive stereocenters and a bridged ring in good to excellent yields and remarkable enantioselectivities (≤1:99 er). This approach facilitates the synthesis of structurally diverse molecules that retain their bicyclic integrity while introducing chirality. More importantly, chiral <b>3ab</b> significantly inhibited the proliferation of CESS and Kasumin-1 cells with IC₅₀ values of 0.76 and 0.28 μM, respectively. In addition, <b>3ab</b> has been demonstrated as an effective agent for promoting apoptosis in CESS cells.