Migrating Group Strategy for Remote Functionalization of Seven-Membered Rings

Seven-membered rings are essential structural components in bioactive compounds, yet their precise synthesis remains challenging compared to smaller ring systems. While traditional approaches rely on ring assembly strategies, direct functionalization of simpler cyclic precursors offers an attractive alternative to substituted building blocks. We report a photocatalytic transannular ketone migration strategy that converts 1,1-disubstituted acylcycloheptanes into 1,4-disubstituted products under mild conditions, promoted by sodium decatungstate and thiol cocatalysts under light-emitting diode (LED) irradiation. The process operates via reversible hydrogen atom abstraction and donation at multiple sites within the ring, followed by site-selective migration via radical addition and β-scission at the exocyclic carbonyl group. This dynamic kinetic approach to site-selective C–H functionalization provides regioselective access to densely substituted seven-membered rings, addressing a longstanding gap in synthetic methodology.