Asymmetric Catalytic Synthesis Of Chiral Benzoazepinoindole Derivatives

Chiral isoquinolines and indole alkaloids often occur in the molecular skeleton of natural products and clinical drugs. The efficient and high enantioselective synthesis of them has become one of the hotspots and difficulties for current organic chemistry. It is well known that asymmetric catalytic Pictet-Spengler reaction is one of the most economical and effective ways to synthesis the isoquinolines and indole alkaloids. To begin with, this dissertation pays close attention on the research summary of the asymmetric Pictet-Spengler reaction from the points of chiral auxiliary induction and chiral catalysis. Futhermore, we conduct the asymmetric catalytic Pictet-Spengler-type reaction to synthesize the optically active benzoazepinoindole derivatives. And the following creative outcomes have been achieved.First, we developed a new method for optically active tetrahydrobenzo[6,7]azepino[3,4-b]indole derivatives which were catalyzed by the chiral SPINOL-derived phosphoric acids. Through screening of reaction conditions such as catalysts, solvents, temperature, and additives, we synthesized a series of chiral tetrahydrobenzo[6,7]azepino[3,4-b]indole derivatives with moderate yield and moderate to good enantioselectivity at4℃by using chiral SPINOL-derived phosphoric acids(2.4d) as the catalyst, CHCl3as the solvent、4A molecular sieves as the additive.Second, we developed a new method for chiral tetrahydrobenzo[6,7]azepino[4,3-b]indole derivatives which were catalyzed by the chiral SPINOL-derived phosphoric acids. Through screening of reaction conditions such as catalysts, solvents, temperature, and additives, we synthesized several chiral tetrahydrobenzo[6,7]azepino[3,4-b]indole derivatives with moderate to good yield and moderate to good enantioselectivity at4℃by using chiral SPINOL-derived phosphoric acids(2.4d) as the catalyst,1,2-dichloroethane as the solvent、4A molecular sieves as the additive.