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Abstract Hybrid fused two-dimensional/three-dimensional (2D/3D) rings are important pharmacophores in drugs owing to their unique structural and physicochemical properties. Preparation of these strained ring systems often requires elaborate synthetic effort and exhibits low efficiency, thus representing a limiting factor in drug discovery. Here, we report two types of energy-transfer-mediated cascade dearomative [2 + 2] cycloaddition/rearrangement reactions of quinoline derivatives with alkenes, which provide a straightforward avenue to 2D/3D pyridine-fused 6−5−4−3- and 6−4−6-membered ring systems. Notably, this energy-transfer-mediated strategy features excellent diastereoselectivity that bypasses the general reactivity and selectivity issues of photochemical [2 + 2] cycloaddition of various other aromatics. Tuning the aza-arene substitutions enabled selective diversion of the iridium photocatalysed energy transfer manifold towards either cyclopropanation or cyclobutane-rearrangement products. Density functional theory calculations revealed a cascade energy transfer scenario to be operative. 

Dearomative cycloaddition reactions represent an ideal means of converting flat arenes into three-dimensional architectures of increasing interest in medicinal chemistry. Quinolines, isoquinolines, and quinazolines, despite containing latent diene and alkene subunits, are scarcely applied in cycloaddition reactions because of the inherent low reactivity of aromatic systems and selectivity challenges. Here, we disclose an energy transfer–mediated, highly regio- and diastereoselective intermolecular [4 + 2] dearomative cycloaddition reaction of these bicyclic azaarenes with a plethora of electronically diverse alkenes. This approach bypasses the general reactivity and selectivity issues, thereby providing various bridged polycycles that previously have been inaccessible or required elaborate synthetic efforts. Computational studies with density functional theory elucidate the mechanism and origins of the observed regio- and diastereoselectivities.