Divergent Skeletal Editing of Pyridinium Salts to Azepinones and Pyrrolidinones via Formal Carbonyl Insertion

Skeletal editing offers a powerful strategy for rapid diversification of molecular frameworks without requiring de novo synthesis, yet most existing methods enable only a single, unidirectional scaffold transformation from a given substrate. Here, we report a divergent skeletal editing platform for pyridinium salts that enables sequential ring expansion and contraction from a common heteroaromatic precursor. Formal carbonyl insertion into pyridines proceeds with good efficiency at either the para or ortho position to afford azepinones under mild conditions. Subsequent photochemical [2 + 2] cycloaddition triggers two-carbon exocyclic transposition, delivering pyrrolidinone scaffolds not readily accessible through direct pyridine editing. This sequence constitutes a rare example of bidirectional ring-size editing (6 → 7 → 5) from a single core structure. The method exhibits a broad substrate scope, excellent functional group tolerance, and compatibility with late-stage modifications of drug molecules. This work establishes pyridines as versatile substrates for divergent skeletal editing and provides a practical framework for scaffold hopping in medicinal chemistry.