Synthesis of Tetrahydroquinolines via CAN-Catalyzed Povarov Reaction

Significance

The synthesis of tetrahydroquinolines via the one-pot cerium(IV) ammonium nitrate catalyzed Povarov reaction is described. Both cyclic and acyclic ethers were utilized to rapidly prepare fused and nonfused tetrahydroquinolines in good to excellent yield. Although cyclic ethers give an almost equimolar mixture of cis and trans products 4 and 5, a strong preference for the cis isomer 9 is observed with acyclic vinyl ethers. The resulting diastereoselectivity may be rationalized by a three-step mechanism involving imine formation, addition of the vinyl ether to give an oxonium ion and cyclization to give the observed products. Proof for the intermediate oxonium ion was obtained by a trapping experiment using ethanol as the reaction solvent to give an acetal.