Study On Transition-metal-catalyzed Radical Difluoroalkylation

The incorporation of a fluorine atom or fluoroalkyl groups into organic compounds has a profound effect on their physical,chemical and physiological properties of parent molecules.Difluoromethylene(-CF₂-)can be regarded as the bioisostere of oxygen atom,carbonyl and methylene.Incorporation of(-CF₂-)into organic molecules can significantly improve the lipophilicity and metabolic stability of parent molecules,so it is widely used in the design of drugs and bioactive molecules.Difluoroalkylation has attracted much attention of chemists due to the important properties of difluoromethylene.In recent years,due to the development of new difluoroalkylation reagents and methodologies,significant progress has been made in the field of transition-metal-catalyzed difluoroalkylation.However,the fluorine-containing groups introduced in these reactions are mainly limited to-CF₂H?-CF₂FG(FG=COOR,CONR,COPOR,Ar,etc.).In this thesis,transition-metal-catalyzed radical difluoroalkylation of heteroarenes and alkenes were studied to synthesize compounds containing other significant difluoroalkyl groups-CF₂FG'(FG'=OAr,SAr,COAr,CF₂R),and consists of the following three parts:Part I:The decarboxylative C-H aryloxydifluoromethylation and arylthiodifluoromethylation of heteroaromatic compounds were disclosed by using easily accessible aryloxydifluoroacetic acids and arylthiodifluoroacetic acids as difluoroalkylating reagents,respectively.These reactions were promoted by the combination of catalytic sliver salt and oxidant,to give ArOCF₂-and Ar SCF₂-substituted heteroaromatic compounds in moderate to excellent yields.Part II:An iron-catalyzed coupling of readily available difluoroenol silyl ethers and cyclobutanone oxime esters to access novel gem-difluoromethylenated ketonitriles was developed.This reaction proceeds under mild conditions with excellent functional group tolerance.Due to the increasing importance of fluorine-containing compounds and synthetic utility of carbonyl and nitrile groups,this protocol might find applications in drug discovery and material science.Part III:A visible-light induced coupling of readily available difluoroenol silyl ethers and radical difluoroalkylating reagents to construct a series of structurally diverse tetrafluoroethylene-bridging structure(R-CF₂CF₂-R')was developed.This reaction proceeds under mild conditions with excellent functional group tolerance.In addition,the resulting carbonyl-containing products can be converted to various useful functional groups,and the tetrafluoroethylene-containing compounds might have potential applications in both agrochemical and material science.