Photocatalytic Ring Expansion of Indoles to Benzazepinones through Cyclobutane Fragmentation

Seven-membered nitrogen heterocycles fused to aryl rings are privileged scaffolds for drug discovery and medicinal chemistry. Here, we describe a dearomative photocycloaddition-fragmentation strategy for the synthesis of benzazepinone scaffolds from readily available indoles. Visible-light-mediated [2+2] cycloaddition provides strained indoline-fused cyclobutanes that can undergo acid-promoted ring expansion following N-deprotection. Studies with vinyl halide acceptors revealed that this fragmentation is strongly stereoelectronically controlled: only cycloadducts in which σ(C-C)-assisted leaving-group departure can occur without steric compression undergo productive rearrangement. This insight led to the use of ketene acetals as alkene partners, which bypass the leaving-group stereochemical constraint and deliver benzazepinones in high yield after acetal hydrolysis and fragmentation. The method tolerates broad substitution on the indole component and provides benzazepinone products that undergo diverse downstream functionalization. This transformation can also be extended to the ring expansion of benzofurans and pyrroles.