Copper-catalyzed Three-component Reaction Of Iodo-gem-difluoromethyl Ketones,with Alkynes/Olefins And Trimethylsilyl Cyanide

Organofluorine compounds have been widely used in medicine,pesticide,materials and other fields because of their C-F bond makes them show unique properties.In recent years,substantial efforts have been made on the development of fluoroalkylation reactions for the construction organofluorine compounds on drug synthesis methods.Among them,the difluoroalkylation reaction is currently gaining significant attention.As we know,alkynes were vital industrial raw materials,and their excellent performance in functionalization was widely concerned.In this thesis,a Cu-catalyzed three-component reaction of iodo-gem-difluoromethyl ketones,unsaturated hydrocarbons,and TMSCN was described.The method offers several advantages including mild reaction conditions,broad fluorinated substrate scope and good yields of products.This thesis is divided into three parts.In the first part,twenty iodo-gem-difluoromethyl ketones were obtained through the process optimization and amplification test.In the second part introduces copper catalyzed three component reactions of iodo-gem-difluoromethyl ketones,alkynes and TMSCN.The types of catalyst,ligand,free radical initiator,reaction solvent,temperature and reaction time involved in the system were screened to get the optimal conditions.Ultimately,the optimized conditions for the generation of difluoroacyl-substituted nitriles were determined as iodo-gem-difluoromethyl ketones,alkynes with TMSCN in the presence of Cu(CH₃CN)₄PF₆,?,?,?-terpyridine,and LPO in Me OH at 70 ? for 5?7 hours.And twenty-seven difluoroalkylated acrylonitrile products were synthesized.In the third part,the copper catalyzed three component reactions of iodo-gem-difluoromethyl ketones,olefins and TMSCN were developed.The types of catalyst,ligand,solvent involved in the system were screened to obtain the optimal conditions.Secondly,under the protection of nitrogen,Cu Tc was used as a catalyst,dtbbpy was used as a ligand,LPO and CH₂Cl₂ was used as a initiator and a solvent respectively,and iodo-gem-difluoromethyl ketones,olefins and TMSCN were carried out at room temperature for 5?7 hours.Twenty-four novel cyanodifluoroalkylated compounds were synthesized.