Dual Cobalt/Photoredox Catalysis for the Synthesis of α,β-Unsaturated γ-Lactams and α-Enaminones

Single-atom exchange skeleton editing serves as a central strategy for molecular reconstruction, yet achieving precise control over ring opening and atom substitution remains a significant challenge. Herein, we present a novel cobalt/photoredox dual catalytic system that enables O to N atom transmutation skeleton editing. The transformation commences with the <i>in situ</i> condensation of furanones and anilines to form enamine intermediates. A desaturation process, driven by sequential single-electron transfer (SET) and hydrogen atom transfer (HAT), then forges the critical O-β-aminated furan intermediates. Subsequently, under the promotion of Sc(OTf)₃, nucleophilic addition and ring opening of anilines to the furan-derived intermediates occur, followed by proton transfer tautomerization and intramolecular cyclization and oxidation to afford α,β-unsaturated γ-lactams. This method precisely orchestrates a one-pot sequential O-heterocycle ring opening, O to N atom transmutation, and skeletal reorganization, enabling modular access to otherwise challenging α,β-unsaturated γ-lactams. Furthermore, the reaction operates under mild conditions with commercially available substrates. The density functional theory (DFT) calculations demonstrate that the 1,3-H shift leading to an O-β-amino-substituted furan intermediate and controllable furan nucleophilic addition-ring opening direction are pivotal to the success of this transformation.