Water-Phase Synthesis of 2,5-Methanobenzo[ d ][1,3,6]oxadiazocine with Low Catalyst Loading

Herein, we report a novel strategy to construct bridged benzo[1,3,6]oxadiazocine scaffold from γ-hydroxy enals and o-phenylenediamine, a transformation that diverges from the conventional benzimidazole formation via aldehyde 1,2-addition. This protocol features unprecedented reactivity, green conditions (water solvent, 1 mol % catalyst, room temperature), simple operations, broad substrate scope, and versatile product derivatization, providing a practical and sustainable route to three-dimensional scaffolds of potential value in medicinal chemistry.