Asymmetric Hydrogenation of Ketoamides and Study of New Catalyst on Asymmetric Hydrogenation of Simple Ketones

Author:Zhao Meng Meng

Supervisor:zhang zhao guo


Degree Year:2015





In this dissertation,we have studied the asymmetric hydrogenation ofα/γ/δketoamides 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 ofα-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 enantiopureα-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 ofγ-keto acid derivatives,γ-keto amide was used in the asymmetric hydrogenation.A series ofγ-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.δ-Ketoesters andδ-ketoamide were hydrogenated by Ru-diphosphine and Ru-diphosphine-diamine catalyst.An efficient asymmetric hydrogenation ofδ-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 enantioenrichedδ-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.