Study Of Transition-metal-free Difluoromethylthiolation And Perfluoroalkanesulfonylation Reactions

Fluorine has the highest eletron electronegativity,small atomic size,and good lipophilicity.The introduction of fluorine and fluorine-containing groups into pharmaceutical molecules could desirably modulate the pharmacological activity,metabolic stability,lipid solubility,and bioavailability.With the broad application of fluorine-containing organic compounds in life science,it remains very important to develop efficient methods of importing fluorine or fluorine-containing groups into organic molecules.Difluoromethyl and perfluoroalkyl group are two kinds of significant fluorine-containing groups.This dissertation introduces the studies on transition-metal-freedifluoromethylthiolationandperfluoroalkanesulfonylation reactions.In the first part,the reaction of RSSR and TMSCF₂H was described,which gave RSCF₂H and/or RSCF₂SR selectively.When CsF was used as the base,RSCF₂H was obtained as the main product,while if t-BuOK was used as the base,RSCF₂SR was formed dominantly.Various disulfides applied in this reaction provided a series of RSCF₂H or RSCF₂SR in moderate to good yield.In addition,PhSX with different leaving groups?X?were also investigated in this reaction.Based on the mechanistic studies,a possible mechanism was proposed for this reaction.Our method could produce difluoromethylthioethers and RSCF₂SR in good yields under mild and transition-metal-free conditions without using expensive and less accessible starting materials by other means.In the second part,we developed a methodology for the synthesis of perfluoroalkanesulfonyl alkynes from alkynyl?phenyl?iodonium tosylate and cheap andreadilyaccessiblesodiumperfluoroalkanesulfinateinadditive-and transition-metal-free reaction conditions.Perfluoroalkanesulfonyl alkynes are important building blocks in organic synthesis.However,the previous synthetic methods for perfluoroalkanesulfonyl alkynes are very limited,and could only produce a narrow scope of perfluoroalkanesulfonyl alkynes.In our protocol,sodium perfluoroalkanesulfinates was used as perfluoroalkanesulfonylation reagents affording perfluoroalkanesulfonyl alkynes in good yields.The reaction does not need strong bases and provides a broad scope of perfluoroalkanesulfonyl alkynes.In addition,we found that the reaction of[?2-methoxyphenyl?ethynyl]?phenyl?iodonium tosylate with CF₃SO₂Na afforded 3-?trifluoromethanesulfonyl?benzofuran.The proposed mechanism might involve the interaction between alkylidene carbene and the oxygen from the ortho-OCH₃ group,followed by demethylation,which could be supported by the control experiments.