Efficient construction of pyrrolo[1′,2′:1,2]azocino[4,5-c]quinolines via cascade cycloaddition and annulation reaction

Novel polysubstituted pyrrolo[1′,2′:1,2]azocino[4,5-c]quinolines were efficiently synthesized by a one-pot three-component reaction of proline, isatins and chalcones in refluxing methanol and by a sequential domino annulation reaction with methyl propiolate in refluxing acetonitrile. The reaction with isatins without an N-protecting group afforded hexahydropyrrolo[1′,2′:1,2]azocino[4,5-c]quinolines, while the reaction with N-benzylisatins gave octahydropyrrolo[1′,2′:1,2]azocino[4,5-c]quinolones with an additional propiolate unit connecting to a dihydropyridyl ring. The reaction mechanism with domino [3 + 2]cycloaddition, ring-expansion and annulation processes was rationally proposed for the formation of polycyclic products.