Skeletal Editing of Hydroxyl Oxindoles via Organoiodine‐Catalyzed Oxygen Atom Insertion Reaction

Abstract In the field of skeleton editing, the development of catalytic single‐atom insertion into five‐membered rings is highly desirable and holds significant synthetic value. While numerous transition‐metal‐catalyzed strategies have been established, organocatalytic single‐atom insertions into five‐membered rings remain scarce due to persistent challenges such as the development of competent organocatalytic systems and the identification of suitable five‐membered heterocyclic substrates. To address this gap, we have developed a novel organoiodine‐catalyzed single‐oxygen atom insertion reaction employing hydroxyl oxindoles and N ‐centered nucleophiles such as triazoles, indazoles, and purine derivatives to access a broad range of structurally diverse six‐membered N , O ‐heterocycles. Control experiments and theoretical calculations provide deep insight into the reaction mechanism and the activation mode underlying this organoiodine‐catalyzed transformation. Notably, theoretical studies reveal that hexafluoro‐2‐propanol (HFIP) plays a critical role by forming multiple hydrogen‐bonding and C─H•••π interactions with the reactants, thereby facilitating the single‐oxygen atom insertion. This work constitutes the first example of organocatalytic oxygen atom insertion in molecular skeletal editing and marks the first use of hydroxyl oxindoles as substrates in this context, enabling skeletal editing of five‐membered non‐aromatic heterocycles. Moreover, this study presents a successful case of catalytic intermolecular oxidation within organoiodine chemistry, thereby contributing substantially to related research areas.