Study Of The Incorporation Of Fluorine-containg Group Via Radical Process

Recently,radical chemistry has been one of most hot topics in the field of organic synthesis.It has a wide range of applications in organic chemistry due to its advantages,such as high efficiency,relatively short reaction time,avoiding the prolix protection and deprodection steps.In this paper,our subject was focus on the incorporation of fluorous groups via radical processes.The initial study was about oxidative fluorination of benzylic compounds.Then trifluoromethylation had attracted great attention mainly including C-CF₃ and S-CF₃ bonds formation.Moreover,other fluoroalkylation radicals had been introduced into terminal alkynes,as well as alkynyl carboxylic acids and α,β-unsaturated carboxylic acids.Firstly,an operationally simple and selective method for the direact conversion of benzylic C-H bond to C-F bond without the aid of transition metal catalysts was developed.According to the study,persulfate was a nice radical initiator,which homogenously produced SO4^-radical in the presence of transition metal,heat or light.And then the SO4^-radical could selectively abstracted benzylic hydrogen to give rise to benzylic radical,which resulted in the formation of C-F bond with Selectfluor as fluorination reagent.By controlling the reaction temperature and the amount of persulfate,the mono-and difluoromethyl arenes were selectively obtained.The yields of corresponding mono-and difluorinated products were up to 93%and 96%,respectively.Next,a metal-free decarboxylative trifluoromethylation of α,β-unsaturated carboxylic acids for the synthesis to Cvinyl-CF₃ compounds had been developed.DMF was a kind of good solvent,which could promote the generation of trifluoromethyl radical in the presence of heated Togni（II）reagent.The radical then coordinated to the carboxylic acids with the removing of carbon dioxide,which led to the desired decarboxylative trifluoromethylated products under an addition elimination process.The reaction was found to be high stereoselectivity with only E isomer.Furthermore,this methodology had been extended to the denitrative trifluoromethylation of aryl-substituted nitroethenes with the help of cheap iron catalysts.Followed by the formation of C-CF₃ bond,we were interested in the trifluoromethylation of thiols for synthesis of S-CF₃ bond with the yield up to 99%.Sodium trifluoromethanesulfinate（CF₃SO₂Na）was a solid and stable trifluoromethylating source,which could produce CF₃ radical by the activated of iodine pentoxide.Further study was concentrated on the other sodium fluoroalkanesulfinates with the assistance of catalytic silver and persulfate to obtain SCF₃ groups,as well as SCF₂H and SRfmoties.Finally,copper-catalyzed atom-transfer radical addition（ATRA）reaction of alkynes for introduction of fluoroalkyl groups and halides was studied.After screening,bis（2-dimethylaminoethyl）methylamine was an effective ligand with copper catalyst,which could generate fluoroalkyl radicals without the help of other initiators.A variety of perfluoroalkyl halides including BrCF₂CO₂Et,ICF₂CO₂Et and IRf could be employed with the yield up to 91%.Additionally,this strategy has been extended to the decarboxylic fluoroalkylation of alkynyl carboxylic acids,as well as α,β-unsaturated carboxylic acids.The method provided a streamlined access to di-and perfluoroalkylated organic compounds with a broad substrate scope and high region-and stereoselectivity.