Enantioselective Synthesis of Cyclobutane‐fused Heterocycles via Lewis Acid‐Catalyzed Dearomative [2+2] Photocycloaddition of Indoles, Benzofurans, and Benzothiophenes with Alkenes

Cyclobutane-fused heterocycles are important motifs in biologically active molecules, yet their enantioselective synthesis remains a significant challenge. We report a broadly applicable and modular strategy for constructing these strained architectures through a visible-light-mediated, Lewis acid-catalyzed dearomative [2+2] photocycloaddition of indoles, benzofurans, and benzothiophenes with alkenes. The method employs a simple catalytic system based on commercially available rare-earth Lewis acids and chiral pyridine-2,6-bis(oxazoline) (PyBox) ligands. A wide array of heteroarenes and styrenes bearing diverse functional groups participate efficiently, delivering cyclobutane-fused products in up to 96% yield, >20:1 dr, and >99% ee. The synthetic utility is further demonstrated by gram-scale synthesis and facile removal of the directing group to access functionalized amino acid derivatives. Mechanistic investigations, including ultraviolet-visible (UV-vis) spectroscopy, nonlinear effect studies, kinetic isotope effects, and density functional theory (DFT) calculations, reveal that a triplet-state heteroarene engages in regio- and enantio-selective C─C bond formation under mild photochemical conditions. This study highlights the potential of excited-state Lewis acid catalysis in unlocking enantioselective dearomatization pathways for complex molecular architectures.