Synthesis Of P-and S-Stereogenic Compounds By Nickel-catalyzed Asymmetric Hydrofunctionalization

In recent years,heteroatom-stereogenic compounds have attracted more and more attention due to their unique structural characteristics and physicochemical properties.However,compared with carbon-stereogenic compounds,the synthesis and application of heteroatom-stereogenic compounds are lagging behind.P-stereogenic compounds and chiral sulfoxide compounds are common ligand types and organocatalysis.In addition,they have certain applications in medicine,materials and other fields.At present,the preparation of these compounds mainly relies on traditional synthesis methods.Asymmetric synthesis catalyzed by transition metal has become the most direct and efficient strategy to obtain chiral compounds.We are committed to the construction of P-and S-stereogenic compounds from simple and readily available raw materials by using inexpensive nickel catalyst.In Chapter 1,the types and research significance of chiral compounds are briefly introduced,followed by a summary and analysis of the development of nickel-catalyzed asymmetric hydrofunctionalization reactions of alkenes and alkynes.Combining the research status of heteroatom-stereogenic compounds and the understanding of nickel catalyst,a reasonable project design is proposed.Chapter 2 illustrates the significance of the research from the importance of chiral phosphine compounds and existing synthesis strategies.Asymmetric hydrofunctionalization catalyzed by transition metal has become the main method for constructing of chiral phosphine compounds due to its advantages of simplicity,high efficiency and high atom economy.By reason of the difficulty in obtaining prochiral secondary phosphines and racemizing secondary phosphine oxides(SPOs),most studies can only obtain carbon chiral phosphine compounds.The Ni(0)/(S,S)-BDPP catalyzed asymmetric hydrophosphinylation of enynes was achieved with readily prepared SPO as raw material.The reaction was performed under mild conditions and tolerated various functional groups,affording the P-stereogenic tertiary phosphine oxides with high yields,enantioselectivities and excellent regioselectivities.The mechanism studies revealed a mechanism different from the traditional Chalk-Harrod type.The mechanism of the reaction was investigated by NMR tracking and controlled experiments,and a mechanism different from the traditional Chalk-Harrod type was revealed,which provided a design idea for nickelcatalyzed hydrogen-functional group reaction of unsaturated bonds.In Chapter 3,the synthesis of chiral sulfoxide compounds from asymmetric hydrosulfenation of alkynes catalyzed by nickel is described.Chiral sulfoxide structure is the pharmacophore of many drugs and a common ligand type.Chiral auxiliaries induction and asymmetric catalytic oxidation are commonly strategies to synthesize chiral sulfoxides.Sulfenic acid is an extremely unstable organic sulphur oxoacid with active chemical properties and is considered to be a key intermediate in many reactions.At present,there are few researches on synthesis of chiral sulfoxide compounds by catalyzing asymmetric hydrosulfenation.Based on previous studies on the asymmetric hydrophosphinylation of nickel-catalyzed conjugated enyne,we have designed and realized the nickel-catalyzed asymmetric hydrosulfenation of alkynes.By exploring the reaction conditions,we found that using(R,R)-Ph-BPE as ligand with strong electrondonating ability can realize this kind of reaction and obtain excellent chirality control.In addition to obtain chiral alkenyl sulfoxides with excellent yield and enantioselectivity from common alkynes,chiral sulfoxides can also be introduced into many drug derivatives.The chiral alkenyl sulfoxide can be converted into a variety of complex compounds as synthons.The control experiment and NMR tracking experiment show that the reaction is also carried out by protonation mechanism,which further shows the application value of nickel catalyst in the asymmetric hydrofunctionalization reaction.In Chapter 4,the paper is summarized and analyzed as a whole,and the current problems and possible solutions are proposed according to the existing research results.