Polymer Supported Chiral Catalysts In The Asymmetric Synthesis Of Chiral Secondary Alcohols

Chiral is the basic phenomenon of the nature. Recently, with the evolution of asymmetric catalysis, asymmetric synthesis for achieving optical active products (such as optical pure secondary alcohols) has got a significant development. However, the high cost of the chiral catalyst and the metal contamination of the product remain to be surmounted. The search for recyclable chiral catalysts with low leaching level of metals has been constantly recognized as one of the prime concerns from both academic and industrial perspectives. Using polymer-supported chiral catalysts can simplify the chiral catalyst's separation, as well as recovery and recycling, which is prospective to meet the tendency of green asymmetric synthetic chemistry.In this thesis, we mainly discuss two parts of work. 1. Preparation of polymer-supported chiral diphosphine-Ru complexes and their use in catalyzed asymmetric hydrogenation of pre-chiral ketones. 2. Preparation of polymer-supported chiral proline-derivedβ-aminoalcohol ligands and their use in the catalyzed asymmetric diethylzinc addition to aldehydes.In the first part, we have synthesized two kinds of modified chiral diphosphine ligands (NH₂-BINAP 53 and HO-BIPHEP 61), which were used for preparation of polymer supported chiral diphosphine-Ru catalysts. Nafion-membrane, reinforced with poly(tetrafuoroethylene) fiber, was first used as an efficient support for the preparation and application of heterogeneous chiral Nafion-NH-BINAP-Ru catalysts (55 and 56). The supported chiral catalysts exhibit high activity and stability in the asymmetric hydrogenation ofβ-ketoesters. We also found that: The restriction of the Nafion matrix had different influence with different substrates; and the electronic affection of Nafion influenced the enantioselectivity of ruthenium complexes.Three kinds of soluble polymer supported chiral diphosphine-Ru catalysts (78, 79 and 80) were prepared using HO-BIPHEP 61 as initial chiral ligand. These supported catalysts were used in the asymmetric hydrogenation ofβ-ketoesters and the best results were achieved with the novel chiral MeO-PEG-O-BIPHEP-RuBr₂ catalyst (78), which catalysed the hydrogenation ofβ-ketoesters in up to 98% yield and 99% ee under atmospheric pressure. The accelerating effects exerted by the PEG linkage were dramatic as compared to the unsupported analogue MeO-Biphep-RuBr₂ 77. Furthermore, the catalyst could be recovered easily and the recycled catalysts were shown to maintain their efficiency in two consecutive runs. One of the reduced products, i.e. (S)-ethyl 3-hydroxy-3-phenylpropanoate, was useful in the preparation of optical pure (S)-fluoxetine. The procedure spared the cost of the chiral catalyst and avoids the plausible contamination of fluoxetine by the toxic transition metal species, which maybe useful in the industry.A soluble polymer (MeO-PEG) supported BIPHEP-Ru/chiral diamine (DPEN) complex (99), in which the polymer is attached to the two phenyl rings of BIPHEP ligand, has been prepared, and shown to be highly active (0.1% mol cat.) with good enantioselectivity for the catalyzed asymmetric hydrogenation of unfunctionalized aromatic ketones. Especially for 4'-tert-butyl-acetophenone and 1-acetonaphthone, excellent ee values up to 96.5% and 95.9% have been obtained which are comparable to or even higher than the enantioselectivity achieved with BINAP-Ru-DPEN catalyst under similar conditions. The supported chial catalyst showed high air stability and could be recovered easily and the recycled catalysts were shown to maintain their efficiency in several consecutive runs.In the second part, polymer (Aminomethylated polystyrene resin and MeO-PEG) supported proline-derivedβ-aminoalcohol ligands (125 and 126), in which the polymer were attached to the 4-hydroxy posotion of theβ-aminoalcohol ligand using succinic acyl as the linkage, have been prepared smoothly, and shown to be highly active with good enantioselectivity (up to 90% ee) for the catalyzed asymmetric diethylzinc addition to aldehydes. Particularly, the insoluble polymer supported catalyst was able to be reused several catalytic runs without loss of enantioselectivity after readily recoverble procedure.