Rhodium Or Nickel Catalyzed Asymmetric Hydrogenation To Synthesize Functional Chiral Amines

Chiral amines play an very important role in organic compounds and natural product,as an organic intermediate which has been widely used in chiral pharmaceutical synthesis.With the concept of sustainable development and green been proposed and developed,developing highly efficient,economical andconvenient,environmentally friendly methodology to synthesize pharmaceuticals,especially containing chiral amine fragments,has been widely studied by science researchers.Transition metal catalyzed homogeneous asymmetric hydrogenation has been recognized as one of the most efficient,convenient and atom economic method for preparation of various chiral compounds.In the past several decades,the remarkable achievements have been made.However,drawbacks exist all the time and need to be solved in necessary:asymmetric hydrogenation of alkenes bearing sulfur substituent is hard;Often Ru-,Rh-,Ir-,and Pd-based catalysts are used in asymmetric hydrogenation,cheap metal catalysts for asymmetric hydrogenation is in the necessaries of study.In this thesis,we decoumented the Ru,Rh,Pd,Ir and Ni-catalyzed asymmetric hydrogenation to synthesize all kinds of chiral amines containing functionalization groups.Then,our work focuses on the development of Rh-catalyzed asymmetric hydrogenation to prepare two knids chial amines with high yieds and enantioselsctivity.Besides,we make a study on the cheap metal Ni-catalyzed asymmetric hydrogenation to synthesize chiral amines.The research contents are as follows:1.In conclusion,we have made a study about regioselective asymmetric hydrogenation of conjugated enamides,developed a new strategy to synthesize P-substituted chiral allylic amines by Rh/DuanPhos catalyzed asymmetric hydrogenation under very mild reaction conditions.[Rh(cod)(Sc,Rp)-DuanPhos]BF4 exhibited high regioselectivity and good to excellent enantioselectivity with a broad substrate scope(up to 97%ee,TON up to 1 000).2.We have successfully developed an efficient approach to generate chiral?-acetylamine sulfide.Rh/DuanPhos,overcome the drawbacks of S atom extremely tends to coordinating with the transition metal which results in the catalyst deactivation,could asymmetric hydrogenation of ?-acetylamino vinylsulfide.In addition,an effective and concise synthetic route to Apremilast was developed.3.We have made a study of Nickel-catalyzed asymmetric hydrogenation,Nickel-catalyzed asymmetric hydrogenation of ?-acylamino nitroolefins has been achieved,affording chiral ?-amino nitroalkanes with high yields and excellent enantioselectivities(96->99%ee,TON up to 574)under a mild conditions.Moreover,the deuterium labeling studies and theoretical calculation was performed to explore the possible mechanism.