2026/05/04 by Yi Luo, Lin Zhou, Xiaotian Qi +1 · 1 voice
Chemistry · #Advanced Synthetic Organic Chemistry #Cyclopropane Reaction Mechanisms #Radical Photochemical Reactions
paper · doi:10.1021/jacs.6c03052
openalex publication_date 2026/05/04 · openalex created_date 2026/05/05 · openalex updated_date 2026/07/25
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.