Application Of N-bearing Bisphosphine Ligands In Asymmetric Catalytic Reactions

In the field of asymmetric catalysis research, development Chiral phosphine ligands makes asymmetric catalysis technology has made considerable progress. At present, Chiral phosphine ligands have been widely used in various reactions, and some excellent ligands successfully achieve the industrial production applications, it has made remarkable achievements. Therefore, We having designed and synthesized chiral bisphosphine ligands of high catalytic activity and optically active is a very important and significant research issue. This dissertation contains four parts:Firstly, a new type of chiral bidentate phosphine ligands that chiral 6,6’-bis(diphenylphosphino)-5, 5’-biquinoline(BIQAP) was synthesized by two step reactions used optical pure BIQOL as raw material.Secondly, chiral BIQAP was used in asymmetric allylic alkylation reaction which got excellent catalytic effect. We selected acetonitrile as a solvent,[Pd(?3-C3H5)Cl]2 as the Pd source, metal ligand ratio Pd/L of 1: 2, the amount of catalyst 5 mol%, K2CO3 as the base, at room temperature for 24 h. When we expanded the indole substrates, the substrate is found that when the reaction of2-phenyl indole, the ee value up to 99%.Thirdly, Application of BIQAP ligands in asymmetric hydrogenation of quinoline and indole. In the hydrogenation of Quinoline, We selected in THF as a solvent, [Ir(COD)Cl]2 as a metal source, I2 content of 5 mol%, the substrate with the catalyst optimum ratio S/C is 10000, the hydrogen pressure is 5 MPa, at 0 ℃reaction conditions 12 h. You can get more than 99% yield and 91% ee value of the product. In the asymmetric hydrogenation of simple research indole, Using Pd(OCOCF3)2 /(R)-BIQAP catalyst, DCM/TFA(1/1) as the reaction solvent, reaction activator Bronsted acid is L- camphorsulfonic acid, The hydrogen pressure of 5 MPa,The reaction is room temperature completed in 24 h. Finally obtained 91% conversion and 72% ee value of the product stereoselectivity.Fourth, the asymmetric hydrogenation of the antidepressant duloxetine intermediates reduction synthesis Expand detailed study. The results showed thatwhen the chiral ligand is(S)-P-Phos, aid chiral diamine [(S)-daipen], the metal source [Ru Cl2(benzene)] complex formation of chiral catalysts trans-Ru Cl2[(S)-P-Phos] [(S)-daipen], then through a series of research and exploration, and KOH as base to determine the hydrogen pressure of 3 MPa, the reaction solvent is isopropanol, and the substrate catalyst molar ratio(S/C) of 100, 24 h at room temperature the reaction conditions, It can catalytic hydrogenation of duloxetine key intermediate 3-(dimethylamino)-1-(2-thienyl)-1 acetone.