Copper-Catalyzed Synthesis of Aza-Fused Polycyclic Quinolines

Significance

Reported here is the synthesis of benzimidazo[1,2-a]quinolines as well as imidazo- and pyrrolo-fused quinolines via a copper-catalyzed cascade reaction. Using 2-iodobenzaldehyde and 2-(1H-benzo[d]imidazole-2-yl)aceto­nitrile (R^¹ = CN) as starting materials, a screening of conditions showed that CuI as catalyst, l-proline as ligand, and K₂CO₃ as base gave the optimal yield (91%). The scope was then extended to a variety of 2-iodo- and 2-bromobenzaldehydes as well as bromo heteroaromatics to afford benzimidazo[1,2-a]quinolines in good to excellent yields, although it is necessary to heat at 50 ˚C for electron-rich benzaldehydes and at 80 ˚C for bromobenzaldehydes. The less reactive chloro­benzaldehydes required heating at 110 ˚C to achieve modest yields. Imidazoles and pyrroles ­afforded the corresponding aza-fused quinolines in low to good yields.