Lewis Acid-Catalyzed Domino Inverse Electron-Demand Diels–Alder/Thermal Ring Expansion Reaction for the Synthesis of Arene-Annulated Eight-Membered Nitrogen Heterocycles

A domino inverse electron-demand Diels-Alder reaction/thermal ring expansion sequence was developed to enable the one-step synthesis of arene-annulated eight-membered nitrogen heterocycles from readily available aromatic 1,2-diazines. A boron-based, bidentate Lewis acid catalyst facilitates the initial cycloaddition of Boc-protected 2-azetine with various electron-poor and electron-rich phthalazines. The subsequent electrocyclic ring expansion furnishes azocines fused to differently substituted aromatics, a structural motif that holds vast potential for further derivatization.