Asymmetric Hydrogenation Of Ketoamides And Study Of New Catalyst On Asymmetric Hydrogenation Of Simple Ketones

In this dissertation,we have studied the asymmetric hydrogenation of?/?/?ketoamides with high reactivities and enantioselectivities.We also developed a new type of Ru-diphosphine-diimine catalyst by using achiral bipyridine as the diamine and this catalyst was applied to the asymmetric hydrogenation of unfunctionalized ketones with ee values up to 94%.1.Asymmetric hydrogenation of?-keto Weinreb amides has been realized with[Ru??S?-Sunphos??benzene?Cl]Cl as the catalyst and CeCl₃·7H₂O as the additive.A series of enantiopure?-hydroxy Weinreb amides?up to 97%ee?have been obtained.Catalytic amount of CeCl₃·7H₂O is essential for the high reactivity and enantioselectivity and the ratio of CeCl₃·7H₂O to[Ru??S?-Sunphos??benzene?Cl]Cl plays an important role in the hydrogenation reaction.2.In order to enhance the coordinating ability of?-keto acid derivatives,?-keto amide was used in the asymmetric hydrogenation.A series of?-hydroxy amides were synthesized with high enantioselectivities?up to 99%?in the presence of Ru-Xyl-SunPhos-Daipen catalyst,providing key building blocks for a variety of naturally occurring and biologically active compounds.3.?-Ketoesters and?-ketoamide were hydrogenated by Ru-diphosphine and Ru-diphosphine-diamine catalyst.An efficient asymmetric hydrogenation of?-keto Weinreb amides catalyzed by Ru-Xyl-SunPhos-Daipen bifunctional catalyst has been achieved while ketoesters could not be hydrogenated under the same conditions.This method afforded a series of enantioenriched?-hydroxy Weinreb amides in good yields?up to 93%?and enantioselectivities?up to 99%?with high tolerance of electronic property and steric hindrance of substrates.The enantiomerically pure product can be transformed easily to the key intermediate for the synthesis of?+?-Centrolobine.4.An efficient Ru catalyst was synthesized by using bipyridine and enantiopure diphosphine,which was applied to the asymmetric hydrogenation of unfunctionalized ketones with full conversion and good enantioselectivities.This study represents the synthesis of chiral cis-Ru?diphosphine??bipyridine?catalyst and a possible mechanism was proposed to explain the hydrogenation procedure by using the achiral“non N-H”diamine,which is different from the traditional“outer-sphere”six-membered ring mechanism.