Synthesis Of Organofluorine Compounds Based On Copper Catalysis Strategy

Organofluorine compounds have been widely applied in medicinal,agricultural,and material sciences.The unique physical and biological properties of fluorinated compounds are attributed to their metabolic stability,lipophilicity,and electron-withdrawing nature of the fluorinated substituent.Copper,as a highly efficient and cheap transition metal,is of of star metals whic are widely used in catalytic reactions.Therefore,copper-catalyzed synthesis of small molecules of organic fluorides has gained more and more organic scientists'attention,which has made considerable achievements.In this sense,we have developed two systems for the synthesis of organofluorine compounds:fluorine-containing copper intermediates and catalysis of trace copper.The content of this paper will be divided into three parts.?1?Copper-Catalyzed synthesis of Indol-3-yl ?-?Difluoromethyl?-a-?trifluoromethyl?carbinols:Construction of Difluoromethylated sp3 Carbon Centers:1-methyl-lH-indole was used as the substrate in combination with 1,1,3,3,3-pentafluoro-2-trimethylsiloxypropene as a fluorinating reagent,The use of CuI as a catalyst and wet dichloroethane?DCE?as the solvent at 80? allowed the formation of the target product.The synthetic utility of the carbinol products was then explored through a range of derivatizations.Treatment of carbinols with 1.5 equiv of t-BuOK in CH3CN at 100 ? led to the isolation of difluoromethylated dinitrile indol-3-yl derivatives in good to excellent yields.We conducted a deuteration labeling reaction to examine the crucial role of H2O for this transformation,We found hydrolysis of enolate with DZO?4 equiv?produced the active species 1,1,1,3,3-pentafluoroacetone,which readily underwent a Friedel-Crafits-type reaction with indole to afford the desired carbinol.This method is superior to many of the others for its high efficiency,simple operation and good substrate scope.?2?Fluorine anion-promoted synthesis of 1,2,2-trifluorovinyl sulphides and selenides:Fluorine anion is uesd to initiate the reaction,because of the strong fluorophilicity of silicon.A variety of aryl and alkyl thiocyanates were used as the substrate reacted with trifluorovinyl trimethylsilane to afford 1,2,2-trifluorovinyl sulphides.This methodology is simple and mild.?3?Development of multigram scale synthesis of trifluoromethythiolating reagent:?bpy?CuSCF₃ and synthesis of trifluoromethylthiolated pyrones:Firstly,we synthesized trifluoromethythiolating reagent:?bpy?CuSCF₃.And then expand its scale under the optimal conditions,we chose 3-iodo-4-isopropoxy-6-methyl-2H-pyran-2-one as a model substrate to determine the reaction conditions.The best condition is using?bpy?CuSCF₃ as the trifluoromethylthiolating reagent in toluene at 100 ?.This methodology has the advantages of excellent efficiency,simple operation and good fuction group tolerance.