Asymmetric Hydrogen Transfer Reaction In The Emulsion Reaction System And The Fluorine-containing Branched Molecules Catalysts Synthesis And Applications

Asymmetric transfer hydrogenation (ATH) has been used widely as an efficient and practical method for preparation of optically pure secondary alcohols. Since the first introduction by Noyori and co-workers in the 1990's, asymmetric transfer hydrogenation with (1S,2S)- or (1R,2R)-N-(p-tolylsulfonyl)-1,2-diphenyl-ethylenediamine (TsDPEN) in combination with [RuCl2(p-cymene)]2 as the catalyst has witnessed great success in enantioselective reduction of prochiral ketones. The protocol constitutes an efficient and practical method for preparation of optically pure secondary alcohols that belongs to a large family of key intermediates for the enantioselective synthesis of bioactive products. Recently, the interest in developing asymmetric transfer hydrogenation in aqueous medium has been significantly surged. The catalytic organic transformation using water as medium is particularly desirable because of the environmental concerns.Although asymmetric transfer hydrogenation in water has been proved to work well for an array of ketones, there is still much room for improvement both in substrate scope and enantioselectivity that can match or outperform the original organic solvent version. In many cases, inferior results were always achieved when performing the asymmetric transfer hydrogenation on water-insoluble ketones. Another limitation of the methodology in drug synthesis is that the Ru-TsDPEN catalyst cannot be easily separated from products and metals (Ru) would be leached in the products. The search for recyclable catalysts for asymmetric transfer hydrogenation with low leaching level of metals has been constantly recognized as one of the prime concerns from both academic and industrial perspectives.In the present dissertation, the research work has been in connection with the following two themes.1. Highly efficient asymmetric transfer hydrogenation of ketones in emulsions and application in the enantioselective synthesis of Sitagliptin. 2. Fluorinated dendritic catalysts for asymmetric transfer hydrogenation in water.In the first part, we disclosed that the readily formed emulsion system is an ideal medium for performing the asymmetric transfer hydrogenation by HCO2Na in water, which provides greatly enhanced activity and enantioselectivities.Many significant chiral secondary alcohols become easily accessible with high conversion and optical purity via asymmetric transfer hydrogenation of prochird ketones in emulsions. Solid ketones that worked poorly in liquid medium gave much better results, demonstrating the benefits by using this new medium. This new system was also used in the asymmetric synthesis of Sitagliptin.In the second part, we report a highly efficient fluorinated dendritic catalyst for the asymmetric transfer hydrogenation of prochiral ketones in aqueous medium. This new catalyst has exhibited high catalytic activities, excellent enantioselectivities, and unprecedented recycling ability up to twenty-six times.The required fluorinated dendritic chiral ligand 61 was prepared with a nine-step protocol starting from 3,5-dihydroxybenzoic acid, bromopentafluorobenzene and p-hydroxyphenylsulfonamido modified chiral ligand.One of the most important objectives of designing the fluorinated dendritic catalyst was to facilitate catalyst/product separation via the solvent precipitation method. To our delight, the recycling use of the fluorinated dendritic catalyst was quite successful. The catalyst can be reused more than twenty-six times with no significant decline both in selectivity and activity for asymmetric transfer hydrogenation of acetophenone. Toward the beginning of the recycle (runs 1th-9th), excellent conversion and enantioselectivity were obtained with no extension of the reaction time. Even in the 24th run, the reaction also afforded a conversion of 93%and an ee of 91% in 18 h. ICP analysis showed that nearly no ruthenium had leached into the organic phase (hexane). And the ee's remained almost unchanged until the 26th run (93% conversion and 88% ee, in 24 h).