Highly efficient asymmetric synthesis of novel diphosphine ligands with additional chiral centers on the backbone and their applications in asymmetric hydrogenation reactions

Abstract

Asymmetric catalysis is an important subject in science and technology.This thesis focused on the development of novel C2-symmetric diphosphine ligands possessing additional chiral centers on the backbones and their applications in asymmetric hydrogenation reactions. Diastereomeric biaryl diphosphine ligands (S)- or (R)-[5,5',6,6'-bis(2R,4R-pentadioxy)]-(2,2')-bis(diphenylphosphino)-(1,l')-biphenyl with added chiral centers on the backbone were synthesized. Substrate-directed asymmetric synthesis occurred in the Ullmann coupling step for the preparation of the diastereomeric diphosphine oxides. The diastereomeric diphosphine oxides were easily by column chromatography with silica gel. Ruthenium catalysts containing these ligands were more effective than the BINAP catalytic systems in the hydrogenation of 2-(6'-methoxy-2'-naphthyl)propenoic acid (up to 97% ee) and B-ketoesters (up to > 99% ee). The additional chiral centers exhibited a significant influence on the enantioselectivity and activity of the catalysts. C2-symmetric biphenyl phosphine ligand (S)-[6,6'-(2R,4R-pentadioxy)]-(2,2')-bis (diphenylphosphino)-(1,l')-biphenyl possessing a chiral bridge to link the biphenyl groups was prepared. Complete atropdiastereoselectivity was realized for the first time in the preparation of biaryl diphosphine oxide via asymmetric intramolecular Ullmann coupling with central-to-axial chirality transfer. The effect of precise chiral recognition was also clearly revealed in a related asymmetric ring closure reaction. Ligands (S)-[6,6'-(2R,5R-hexadioxy)]-(2,2')-bis(diphenylphosphino)-(1,1')-biphenyl and (R)-[6,6'-(2S,3S-butadioxy)]-(2,2')-bis(diphenylphosphino)-(l,l')-biphenyl were prepared via the ring closure route, too. The stereorecognition abilities of the corresponding Ru complexes for the three ligands compared favorably with Ru(BINAP) or Ru(MeO-BIPHEP) complex in the same model reactions. The introduction of additional chiral centers offered opportunities for structurally fine-tuning this type of ligand. The product configuration in the studied reactions was controlled by the axial chirality and independent of the additional central chirality of all of the five synthesized ligands. MM2 modeling was used to simulate the steric energies of the diastereomeric diphosphine oxides and ligands' dihedral angle values. It successfully explained why only single diastereomer was produced in the asymmetric intramolecular Ullmann coupling and ring closure reaction by the difference of the steric energies between the two diastereomers. The calculation and experimental results suggested that rigidity of ligand might be more important than the dihedral angle in the asymmetric induction. The relationship of ee in the model reactions with the dihedral angle of the ligand was discussed.