Study On The Free Radical Difunctionalization And Suzuki Coupling Reaction By Using Bromo(2)Chloromethane

Organic halogen compounds are important.They are not only important building blocks and synthetic intermediates in organic transformation,but also precursors of most organometallic reagents such as Grignard reagents,organic zinc reagents and organic copper reagents.In addition,organic halides are also extremely important synthetic molecules in the fields of medicine,agriculture and materials science.Therefore,it is necessary to develop an effective and convenient method for the synthesis of chlorinated compounds with diverse structures.The dissertation based on our group’s early dichloromethyl radical chemistry research,using stoichiometric bromodichloromethane/bromochloromethane as the source of chloromethyl radicals,based on the strategy of free radical relay,we have developed copper-catalyzed chloromethylation/azidation tandem reactions of alkene to synthesize a series of chloromethyl compounds containing azide groups that can be derivatized.Using bromochloromethane as the methylene reagent,this dissertation have also developed a nickel catalyzed double cross-coupling reaction system,in which a series of diarylmethane compounds were synthesized through two suzuki couplings by step.The dissertation includes four parts:Chapter 1:Research backgroundFirstly,we introduced the application of chlorinated alkanes in organic synthesis,including their role as valuable organic compound and in the field of medicine.After that,several methods of introducing dichloromethyl and monochloromethyl into the molecule were introduced.Finally,we reviewed the difunctionalization of alkene with azide under metal and metal-free systems.Chapter 2:Copper-catalyzed dichloromethylazidation of alkeneUsing stoichiometric BrCCl2H as a source of dichloromethyl overcomes the limitation of using methylene chloride or chloroform as a solvent in reported article.We have developed a copper-catalyzed dichloromethylazidation of alkene.This reaction has demonstrated mild conditions,a broad substrate scope,high reactivity,and excellent functional-group tolerance.This method has been successfully used for the modification of the biologically active molecule estrone derivative and the product could be further transformed into dichloromethyltriazole and dichloromethylamine,which proves its potential synthetic application value.Chapter 3:Copper-catalyzed monochloromethylazidation of alkeneUsing stoichiometric bromochloromethane as the monochloromethyl source,we developed a copper-catalyzed monochloromethylazidation of alkene through radical tandem reactions to synthesize terminal alkyl chlorides.The reaction has demonstrated high catalytic efficiency,a broad substrate scope and good functional group compatibility.The terminal alkyl chlorides containing azide groups can be derivatized in various ways,and a series of nitrogen-containing multifunctional products can be synthesized efficiently,which indicates the potential application value of synthetic methodology in organic synthesisChapter 4:Nickel-catalyzed Suzuki coupling reaction of bromochloromethane and arylboronic acidUsing stoichiometric bromochloromethane as the methylene source and arylboronic acid as the aryl source,the diversified and efficient synthesis of diarylmethane compounds is realized under the catalysis of nickel.The reaction is carried out by a nickel-catalyzed stepwise suzuki coupling reaction.The reaction has demonstrated high mild conditions,a broad substrate scope and good functional group compatibility.