Ni-H Catalyzed Asymmetric Hydroalkylation Of Unsaturated Hydrocarbons To Construct ?-Nitrogen And Sulfur Chiral Carbon Centers

As an important property of organic compounds,asymmetry exists widely in various natural products and drug molecules.The different enantiomers of chiral compounds often have different physiological activities,and in most cases only one of them can have positive physiological effects.Therefore,obtaining chiral-specific organic compounds is one of the goals of contemporary organic chemists.In recent years,transition metal-catalyzed stereoselective construction of asymmetric carbon-carbon bonds has been developed rapidly.Among them,nickel catalysts have attracted extensive attention from chemists due to their unique catalytic activity and chemical selectivity.In the first chapter of this paper,the research progress of nickel-catalyzed asymmetric C-C bond construction was introduced in the form of a literature review,including nickel-catalyzed asymmetric cross-coupling,nickel-catalyzed asymmetric reductive cross-coupling,nickel-catalyzed asymmetric olefin hydrogenation and nickel-catalyzed asymmetric olefin difunctionalization.The asymmetric C-C bond formation reactions involving unsaturated hydrocarbons are mainly introduced.Unsaturated hydrocarbons are widely exist in natural products and drug molecules,easy to be prepared.Through the migratory-insertion of Ni-H intermediates to unsaturated hydrocarbons,the catalytic amount of alkyl-Ni intermediates can be produced in situ and coupled with electrophilic reagents,which can effectively avoid the use of stoichiometric organometallic reagents.It provides a modular synthesis method with easy operation and good functional group compatibility for the synthesis of chiral compounds.Optically pure chiral aliphatic amines and their derivatives are important skeletons of many natural products and pharmacologically active molecules,chemists are committed to developing methods for the synthesis of these chiral compounds for a long time.In the second chapter of this paper,we report a Ni-H catalyzed asymmetric hydroalkylation of enamides with alkyl halides.Through this method,chiral aliphatic amines can be obtained from simple and easily available reactants under mild reaction conditions.The success of this reaction is mainly attributed to the stereoselective migratory-insertion of Ni-H intermediate to enamide.The reaction can be applied to the efficient synthesis and modification of a variety of natural products and drug molecules.Through the asymmetric hydroalkylation of enamide and racemic ?-haloboronates,?-aminoboronates with two chiral centers can be prepared.Considering the abundant conversion ability of organic boron compounds,this method will be helpful to develop complex heteroatom-containing chiral molecules.Sulfur-containing compounds often have special physiological and pharmacological activities and are widely used in drug molecules.Sulfonamides are the first antibiotics to be used.However,it is difficult to synthesize ?-sulfur chiral compounds by traditional synthesis methods.In the third chapter of this paper,We introduce the functionalized ?-sulfur alkyl bromide into the asymmetric hydroalkylation strategy.The chiral C(sp3)-C(sp3)bond can be constructed at the ?-position of the sulfur atom through the asymmetric hydroalkylation between non-activated olefins and ?-sulfur alkyl bromide.This method shows a direct route for the synthesis of ?-sulfonamide/sulfone chiral compounds based on readily available non-activated olefins.We believe that this reaction will have a broad application prospect in the synthesis of sulfur-containing drug molecules and fine chemicals.