Study On Selective Coupling Reaction Of Alkyl Halide And Arylboric Acid By Palladium

Biaryl structure and diaryl methane results because of its important skeleton structure and widely exists in various structures of organic compounds and in synthetic organic chemistry and functional materials such as synthetic chemistry science and medicine synthesis and chemical production plays a very important role and application prospect.This paper first summarizes the development of transition metal catalyzed cross coupling reaction in recent years,and focuses on the classical reaction types such as Negishi reaction,Ullmann reaction and Suzuki reaction.Among them,the Suzuki coupling reaction has easily obtained raw materials,organic boron reagent with low toxicity,mild reaction conditions,good stability and wide application range of substrates,and has the advantages of easy product processing,so through this method to construct the carbon carbon bond（C-C）has been one of the important methods for synthesis of biaryls junction structure,and because the Suzuki coupling reaction with the stereo and regioselectivity characteristics make it widely attention and become one of the focuses of current research.As we all know,Suzuki coupling reaction is widely used in the construction of C（sp²）-C（sp²）bond,and the C（sp³）-C（sp²）bond has been gradually received widespread attention through Suzuki coupling reaction.On the basis of previous studies,this paper mainly uses different catalytic systems or changing some reaction conditions,so that the two halogenated aromatics containing C（sp²）-X and C（sp³）-X bonds can be selectively controlled with aryl boronic acid to construct C（sp²）-C（sp²）or C（sp³）-C（sp²）bonds.The main research results of this paper are summarized as follows:（1）The basis of previous work,selection of halogenated benzyl halide as the substrate for the reaction research,method of constructing selective Suzuki coupling reaction of different C-C bond successful development of a Pd catalytic activation of aryl halides and aryl boric acid such as Pd（OAc）₂/PCy₃·HBF₄catalyze the efficient and selective coupling of chloromethylbromobenzene with arylboronic acid to construct C（sp²）-C（sp²）bond,Pd（PPh₃）₄ catalyzes 1-bromo Selective coupling of 4-bromo（chloro）methylnaphthalene with arylboronic acid constructs C（sp³）-C（sp²）bond.The catalytic system of Suzuki selective coupling of halogenated benzyl halides was perfected by previous studies.（2）Pd（OAc）₂/PCy₃·HBF₄catalyzestheselectiveSuzukicouplingreactionof chloromethylbromobenzene with arylboronic acid by selecting different reaction substrates such as p-bromobenzyl chloride,m-bromobenzyl chloride,o-bromobenzyl chloride was reacted with arylboronic acid to form C（sp²）-C（sp²）bond.Thirty-five kinds of chloromethylbiphenyls were obtained,and then asymmetric biarylation of p-bromobenzyl chloride was carried out under this catalytic system,and four kinds of asymmetric methylene chain diaryl derivatives were synthesized with the yield between 47%and 98%.The results show that the occurrence of selective coupling is not affected by the halogen substitution position in the dihalogenated aromatic hydrocarbon,and the electron effect of the aryl boronic acid substituent has little effect on the reaction process and the synthesis of the target compound.At the same time,the intermolecular and intramolecular competitive reactions demonstrate the good efficiency and selectivity of this catalytic system.（3）Pd（PPh₃）₄ catalyzes the selective coupling of 1-bromo-4-bromo（chloro）methylnaphthalene with arylboronic,during the study,both 1-bromo-4-bromomethyl naphthalene and 1-bromo-4-chloromethyl naphthalene both undergo selective Suzuki coupling reaction with aryl boronic acid and construct C（sp³）-C（sp²）bond.The coupling results indicate that the selectivity in the reaction is not affected by the halogen electronic properties of C-X bonds in the dihalo-aromatic hydrocarbons,and the arylboronic acids containing different electronic effects can interact with both substrates during the process of substrate application.A very good selective coupling reaction was performed and 38 compounds were synthesized with yields ranging from 52%to 91%.At the same time,we have also carried out the amplification reaction and a series of substrate derivatization experiments,in which the amplified reaction yield reaches the gram scale（1.35 g）,and the coupling compound G1 can also perform some derivatization experiments to further synthesize other target compounds（H1-H3）,with a high yield between 76%and 97%,further proves the importance of this catalytic system in the functionalization of 1-bromo-4-bromo（chloromethyl）naphthalene and its derivatives.In summary,based on the Suzuki cross coupling of halogenated aryl halides and aryl boronic acids,a series of biaryl hydrocarbons and aryl methane compounds were synthesized through the optimization of conditions and the applicability of the substrates.The experiments show that the Suzuki selective coupling reactions have better functional group tolerance and substrate applicability under different catalytic systems,and the method of selectively construct C（sp²）-C（sp²）and C（sp³）-C（sp²）with Suzuki coupling reaction.bond has been supplemented and refined.