Synthesis of Semi-Saturated Heterocycles via Photocatalytic Intramolecular [2 + 2] Cycloaddition/Dearomatization

Intramolecular [2 + 2] cycloaddition/dearomatization could be an ideal pathway to construct semi-saturated polycycles in a "one-pot" manner. However, such a reaction is considered as thermodynamically infeasible due to the instability of the cyclobutane-fused rings and the higher triplet-excited-energy barrier of substrates. Herein, we successfully achieved an array of semi-saturated alkaloid analogues─cyclobutane-fused indolizidines─in up to 98% yield for 33 examples through intramolecular [2 + 2] cycloaddition of indoles via high-energy diradical intermediates. This reaction was initiated by a visible-light-induced energy transfer strategy, exhibited excellent chem-, regio-, and stereoselectivity (>99:1 dr), and provided an easy access for rapid late-stage saturation of pharmaceutical indole-containing molecules.