Chiral Phosphoric Acid Catalyzed Asymmetric Hydrogenolysis And Friedel-crafts Alkylation Of N,O-hemiaminals

Chiral amines are important structural units in many drugs and biologically active molecules,and widely applied as chiral catalysts,chiral reagents and chiral ligands in asymmetric synthesis.Consequently,the synthesis of chiral amine has been a focused interest for organic chemists.The asymmetric nucleophilic addition of imine has been an effective means to access chiral amines.However,most of the imines are difficult to prepared and prone to decompose.The asymmetric hydrogenolysis of 3-aryl-3-hydroxyisoindolin-1-ones catalyzed by chiral phosphoric acid is studied in this thesis.After scanning the chiral phosphoric acids with different substituted groups at 3,3’-positions of binaphthyl,as well as the tests of solvents and temperature,the optimal condition is discovered.With 10 mol%of(S)-9-phenanthryl substituted chiral phosphoric acid as catalyst,the reaction proceeds efficiently in CHCl3 solvent at room temperature,with the enantioselectivity up to 91%ee.The Friedel-Crafts alkylation reaction of 3-methyleneisoindolin-1-one and indole catalyzed by chiral phosphoric acid was also studied.With(S)-a-naphthyl substituted chiral phosphoric acid as catalyst,the reaction proceeds efficiently in DCM solvent at room temperature,with the enantioselectivity up to 64%ee.