Chiral Phosphoric Acid Catalyzed Asymmetric Synthesis Of Tetrahydroquinolines

Chiral tetrahydroquinolines are important class of nitrogen-containing heterocycles,and are important structural moieties found in a variety of biologically active natural products and pharmaceuticals.Accordingly,the development of efficient synthetic routes to chiral tetrahydroquinolines has attracted great interest over the past decades.To date,a number of elegant synthetic methods based on asymmetric catalysis have been reported.However,there are few reports on the construction of functional chiral tetrahydroquinolines by organocatalysis.In this thesis,we developed the asymmetric synthesis of tetrahydroquinoline catalyzed by chiral phosphoric acid and realized the construction of a variety of functional chiral tetrahydroquinolines.In the first part of our work,we have developed an efficient organocatalytic intermolecular tandem reductive amination/asymmetric transfer hydrogenation of2-quinolinecarboxaldehydes and aromatic amines,realizing the highly enantioselective synthesis of tetrahydroquinoline-fused chiral 1,2-diamines.In the precence of a chiral phosphoric catalyst,the ta ndem reaction preformed well under mild conditions,providing a wide range of chiral 1,2-diamines with high yields and excellent enantioselectivities.This protocol features broad substrate scope,good functional group compatibility,and easy gram-scale preparation.Moreover,several products were readily converted into chiral carbine and thiourea ligands,which were initially used in asymmetric catalytic reactionsIn the second part of our work,we developed an efficient asymmetric tran sfer hydrogenation reaction of quinoline-2-carboxamides catalyzed by a chiral phosphoric acid,realizing the highly enantioselective synthesis of tetrahydroqui noline-2-carboxamides.We investigated the effects of catalyst,solvent,temper ature,and catalyst loading on the re action.With the optimal reaction condition s in hand,we examined the substrate scope,providing various substituted tetra hydroquinolines-2-carboxamides with high yields and enantioselectivities.In the third part of our work,we realized the asymmetric s ynthesis of2-heteroaryl-substituted tetrahydroquinolines catalyzed by a chiral phosphoric acid.By screening the effects of catalysts,solvents,temperature,and additives on the reaction,we identified the optimal reaction conditions.The substrate scope was examined,and the desired products were obtained with good yields and excellent enantioselectivities.