Metal-free Selective Borylation And Its Derivative Reaction

In the field of synthesis,boron compounds are a very important class of synthons,which can not only realize the construction and modification of functional molecules through metal-catalyzed coupling reactions but also can be widely used in the fields of materials science and medicinal chemistry as carboxylic acid analogs.Traditional aryl boron compounds can be prepared by metal transfer of highly reactive organolithium or organomagnesium reagents with electrophilic boron species,but their harsh reaction conditions make their compatibility poor.Alkyl boron compounds can be prepared from olefins by hydroboration.Although this type of reaction has been industrialized,it has poor regioselectivity for certain internal enes.With the development of organometallic chemistry,C-H borylation systems have been continuously developed,but the excessive cost of transition metals and the problem of metal residues have severely limited their applications in industrial production and drug development.Because of this,this paper has developed a series of metal-free borylation systems and has obtained a series of products with high selectivity.Part 1.Metal-free synthesis of C3-borylated indolesThe indole ring skeleton is an important part of many active natural products and potential drug molecules,and its synthesis method has attracted wide attention from researchers.Through the nucleophilic cyclization reaction of alkynyl groups promoted by boron trichloride,using o-alkynylamine substrates as raw materials,we achieved the synthesis of C3-boronic acid ester substituted indole.The reaction system is simple and easy to operate,and it can complete the corresponding conversion in a short time without ligands and additives.At the same time,this reaction system has better tolerance of functional groups,such as halogens,heterocycles,olefins,and so on.Besides,we applied the reaction system to the construction of the isoquinolinone borate skeleton.Part 2.Metal-Free Cross-Coupling of C3-borylated indole Intermediate and Diazo CompoundsThe indole unit exists ubiquitously in biologically active molecules and natural products.Transition metal-catalyzed functionalization of indole by carbene transfer is one of the most notable advances in synthetic chemistry during the past decade,which has been widely employed in the preparation of C3-substituted indoles.Considering the cost of using metal catalysts,researchers have turned more attention to the C-C bond construction with metal-free Here,we described an efficient example of catalyst-and metal-free aminoboration of alkynes and C-C bond formation with diazo compounds to produce C3-substituted indoles.Diverse alkynylanilines and diazo compounds can be utilized for this tandem transformation under mild reaction conditions,resulting in broad functional group compatibility.Additionally,this metal-free strategy can be extended to construct substituted benzofurans.Part 3.Metal-free direct C7 selective Csp2-H borylation of indoles and its derivatizationThe indole ring is a special aromatic heterocyclic compound,and it has the highest electron cloud density at the C3 position and has high reactivity,while the selective C-H bond activation functionalization of the benzene ring region is more difficult.Using the combination of the metal characteristics of the boron atom and with the help of the guide group,we have developed the metal-free indole C7 selective C-H boronation reaction for the first time and efficiently prepared a series of indole boronation products.The reaction conditions are simple and mild,and the resulting compound can undergo further derivatization reaction to realize the construction of the C-C bond,C-O bond,and C-N bond at the C7 position of indole.Through control experiments,we captured the key intermediates in the reaction,combined with DFT theoretical calculations,proposed a reasonable reaction mechanismPart 4.Metal-free direct C4 selective Csp2-H borylation of indoles and its derivatizationThe predecessors have provided us with a lot of experience in the arylation and alkylation of the Csp2-H bond at the indole C4 position.Given this,we hope to achieve the borylation of the C sp2-H bond at the C4 position of indole.A series of C4-boronic acid ester substituted indole derivatives and C4 hydroxy-substituted indole derivatives were prepared with high regioselectivity using this reaction system and this method was applied to the key of complex molecules in the synthesis of intermediates.It provides a new method for the modification of the C4 position of the indole skeleton.Part 5.Metal-free directed ortho Csp2-H borylation of aromatic amine and its derivatizationAromatic amines and their derivatives are an important class of organic intermediates.The conversion of C-H bonds in arylamines to C-B bonds provides a convenient way to convert to more types of bonds in the future.In previous reports of metal-free amine boronation reactions,due to the effect of the electronic effects of the substituents,only para-boronated products were obtained.The metal-free boronization system we established in this chapter can achieve the selective boronization of the ortho-Csp2-H bond of aromatic amide,and a series of ortho-boronated amine derivatives can be obtained with high selectivity.After the research,the one-pot method can also be used to construct a variety of phenol derivatives.