Investigation On Copper Catalyzed Perfluoroalkylation Of Aliphatic Organohalides

Organo-fluorine compounds have received increasing attention in the fields of medicinal chemistry,agrochemistry,and organic material science because of their unique chemical,biological,and physical properties.Particularly,difluoromethylated compounds can be widely employed as bioisosteres of thiol and amino groups due to their similar hydrogen bond acidity.Deoxyfluorination of aldehydes was powerful methods for the installation of CF₂H into organic molecules.However,despite their utility,these strategies limited by thermal instability,high toxic reagent,and limited substrate scope.For these reasons,transition metal catalyzed difluomethylation have been developed by using this expensive metal such as Pd,Ag,Au.To address these challenges,copper,with its well-established ability to efficiently capture CF₂H,has been extensively used to mediate bond formation.However stoichiometric copper is required for this transformation.Therefore,it is highly desirable for developing a catalytic copper to realize difluoromethylation reaction.The properties of trifluoromethyl and difluoromethyl are similar.The introduction of trifluoromethyl groups into the compounds can significantly improve the physicochemical properties such as acidity,lipophilicity,polarity,and metabolic stability of the compounds.Previously,the introduction of trifluoromethyl groups into aryls has been widely developed,while methods for the catalytic synthesis of trifluoromethylated alkane（sp³C-CF₃）remain rather limited.This thesis is divided into the following three sections:In the first chapter,the latest research progress in this field was summarized.Based on the literatures report,we proposed research program.In the second chapter,we successfully achieved the difluoromethylation of alkyl halides using a catalytic amount of copper and 0.6equivalent of zinc difluoromethyl reagent.This method has mild reaction conditions,excellent yield,good selectivity and good functional group tolerance.In the third chapter,we realized the copper-catalyzed perfluoroalkylation of alkyl halides with a wide range of substrates and mild reaction conditions.Finally,we studied on the mechanism,base on the experiments,we showed that the reaction involved a radical process.And we also proposed the possible mechanism.