Synthesis Of Electronically Deficient Atropisomeric Bisphosphine Ligands And Their Application In Asymmetric Hydrogenation Of Quinolines

The development progress of asymmetric reaction is also the development progress of chiral ligand. Design and synthesis of new ligands is the important research focus in asymmetric catalysis. A series of electronically deficient atropisomeric bisphosphine ligands have been synthesized in this paper. We mainly applied them in the asymmetric hydrogenation of quinolines. We also made a preliminary investigation to the effectiveness of the ligand in the asymmetric hydrogenation of simple indoles and asymmetric1,4-addition of phenylboronic acid to2-cyclohexenone.1. The synthesis of electronically deficient atropisomeric bisphosphine ligands bearing ester group and their application in asymmetric hydrogenation of quinolinesThe electronically deficient atropisomeric diphosphine ligands (S)-L2a-e and L3were obtained with condensation of (S)-OH-BiPhep and the corresponding acyl chloride or PhNTf2in the action of alkali via a simple one-step route. These chiral ligands were characterized by1H NMR,13C NMR,31P NMR, HRMS. The optical rotation of these chiral ligands was also recorded.We investigated the application of the electronically deficient atropisomeric diphosphine ligands in the Ir-catalyzed asymmetric hydrogenation of quinolines. It was found that [Ir(COD)Cl]2/(S)-L/I2catalytic system could be successfully applied in asymmetric hydrogenation of the2-substituted quinolines. The electronically deficient atropisomeric diphosphine ligands (S)-L2a-e and L3could achieve higher enantioselectivity than the electronically rich ligand (S)-MeO-BiPhep and the highest enantio selectivity was achieved by ligand L3bearing the strongest electron-withdrawing trifluoromethanesulfonyl group with ee up to95%. Further evaluating the catalytic efficiency of the L3in asymmetric hydrogenation, TON could be up to14600.2. The synthesis of electronically deficient atropisomeric bisphosphine ligand bearing trifluoromethoxy group and their application in asymmetric hydrogenation of quinolines and indolesA new electronically deficient atropisomeric diphosphine ligand L4bearing trifluoromethoxy group was synthesized from l-bromo-3-(trifluoromethoxy)benzene in high yield and the main steps included Grignard reaction, oxidative coupling, optical resolution and reduction reaction. These chiral ligands were characterized by!H NMR,13C NMR,31P NMR,19F NMR, HRMS. The optical rotation of the chiral ligands was also recorded. The absolute configuration of (-)-5was defined to be S by X-ray analysis. Therefore, the absolute configuration of the ligand was assigned.Firstly, we investigated the effectiveness of (5)-L4in the Ir-catalyzed asymmetric hydrogenation of quinolines. The ligand could successfully applied in asymmetric hydrogenation of the2-substituted quinolines with good reactivity and enantioselectivity via [Ir(COD)Cl]2/(S)-L4/I2catalytic system. The ee value was up to92%and TON was up to25000. Then, we made an investigation to the effectiveness of the ligand in other reactions. Our ligand was successfully applied in the Pd-catalyzed asymmetric hydrogenation of simple indoles with ee up to87%using a Bransted acid as an activator and Rh-catalyzed asymmetric1,4-addition of phenylboronic acid to2-cyclohexenone with92%yield and97%ee.