A d e ‐ n ovo Approach Towards Divergent [3+2π/σ] Photocycloadditions of Nitrones via Assembly‐Controlled Kinetic Electron Transfer Gating

ABSTRACT Three‐dimensional, conformationally rigid molecular architectures are increasingly valued in chemical biology and drug discovery, yet their syntheses often rely on step‐intensive or metal‐mediated methods. Herein, we report a metal‐free, redox‐neutral photocatalytic approach that enables otherwise challenging divergent [3+2π/σ] photocycloadditions of nitrones under mild conditions. Visible‐light excitation of an acridinium photocatalyst promotes cycloaddition of nitrones with alkynes to furnish densely substituted 4‐isoxazolines, prototypical “Flatland” heterocycles, while engagement of bicyclo[1.1.0]butanes triggers rapid skeletal reorganization to deliver oxa–aza–bicycloheptanes that escape flatland into three‐dimensional chemical space. Both product classes are synthetically challenging under conventional thermal or metal‐catalyzed conditions. The transformation tolerates a wide range of functional groups and provides access to bioisosterically relevant structural motifs. Synthetic photocatalysis is typically designed around thermodynamic considerations, yet the role of electron transfer kinetics in controlling reactivity remains underdeveloped. We establish kinetic electron transfer gating as a general design principle whereby substrate assembly directs charge transfer toward otherwise disfavoured partners, overriding thermodynamic preferences. Mechanistic investigations, in conjunction with density functional theory (DFT) calculations, support a unified photocatalytic manifold and clarify the origin of the divergent reactivity, thereby providing a platform for various downstream transformations.