Controlled Epoxide-Enabled Formal Oxygen Insertion of Indenones to Isocoumarins

Abstract Regioselective oxygen insertion into sp2-rich carbonyl scaffolds remains challenging because Baeyer–Villiger oxidation relies on migratory aptitude. Here, we translate an aziridine-based nitrogen-insertion platform to an epoxide-enabled oxygen-insertion manifold for indenones. H2O2/NaOH epoxidation followed by MeSO3H-promoted rearrangement affords isocoumarins as single observed regioisomers in a two-step sequence. The method tolerates diverse substituents, enables orthogonal and sequential editing of distinct carbonyl motifs, and circumvents incomplete conversion and overoxidation encountered under direct m-CPBA conditions.