Study On The C-H Functionalization And Derivatization Reaction Mediated By Chlorodifluoroethyl Hypervalent Iodine

In recent years,high-valent iodine chemistry has entered the golden age of development.As a low-toxic,environmentally friendly and versatile reagent,high-valent iodine compounds were widely applicated in difunctionalization,oxidation,carbon-carbon and carbon-heteroatom bonding,phenol dearomatization and rearrangement.The introduction of fluorine-containing functional groups into the organic framework could change its biological or chemical properties and played an important role in the field of drug development and materials.Therefore,it was of great significance to explore the meaning of high-valent iodine reagents introduce fluorine-containing functional groups into the organic framework.In this paper,a new type of 2-chloro-2,2-difluoroethyl high-valent iodonium salt reagent was designed and synthesized.First,ICH₂CF₂CI was synthesized from ICl and CF₂=CH₂,then ICH₂CF₂CI was oxidized to generate（2-chloro-2,2-difluoro-ethyl）-λ³-iodobis（2,2,2-trifluoroacetate）.Finally,a ligand exchange reaction occured in the presence of Tf OH to obtain 2-chloro-2,2-difluoroethyl high-valent iodonium salt reagent.The synthesis of the chlorodifluoroethyl hypervalent iodine has the characteristics of readily available raw materials,more simple preparation and large-scale preparation.We explored the ortho-position C-H functionalization reaction of the chlorodifluoroethyl high-valent iodine reagent prepared in this paper with benzamide substrates under Pd catalysis.It was found that 26 kinds of novel 2-（2-chloro-2,2-difluoroethyl）-benzamide derivatives could be obtained at room temperature.The mechanism of this reaction was asssumed as insertion reaction,deprotonation,oxidation reaction,reduction and elimination reaction.This reaction is compatible with-CH₃,-OCH₃,-CH₂Cl,-^tBu,-Ph,-F,-Cl,-Br,-CF₃ and other functional groups.This reaction has diverse substituents and universal substrates.The 2-（2-chloro-2,2-difluoroethyl）benzamide derivatives synthesized by the chlorodifluoroethyl high-valent iodine reagent could be treated with the organic base DBU to prepare 8 kinds of 1,1-difluoroethylenes compounds,including-CH₃,-OCH₃,-^tBu,-Ph,-Br and other functional groups,the yield was 62-91%.The prepareation of vinylidene fluoride compounds via elimination reaction could broaded its methodological.Compounds including-CH₃,-OCH₃,-^tBu,-CH₂Cl,-F,-Cl and other functional groups substituted 2-（2-chloro-2,2-difluoroethyl）benzamide derivatives could also be used to prepare 13 kinds of fluorinated isoquinolines by ring-closing reaction at room temperature in the presence of ^tBu OK,the yield was 64-97%.The 2-chloro-2,2-difluoroethyl（alkyl）periodonium salt reagent prepared in this paper could not only enrich the types of alkyl periodide reagents,but also offered new ideas for introduce fluorined functional groups into the ortho position of the benzamide substrates.Moreover,the introduction of-Cl could provide reaction sites for further derivatization,so the chlorodifluoroethyl hypervalent iodine reagent designed and synthesized in this paper was of great significance in the field of organic chemistry.