Aryldifluoro(chloro)methylation Of Activated Alkenes: Synthesis Of Difluoro(chloro)methyl Oxindoles

Organofuloro(chloro)compounds have attracted extensive attension because of their special biological activity.In recent years,the incorporation of fluorine(or chlorine)-containing functional groups into organic molecules catalyzed by transition metals has been extensively studied,especially for trifluoromethylation and trichloromethylation.However,the methods of introducing related difluoromethyl and dichloromethyl groups into organic compounds are still limited.Due to their broad appilication in the biology and medicine,In this dissertation,we focused our research interest on the development of new methodologies of difluoromethylation and dichloromethylation,and developed Pd(0)-and Fe-catalyzed difluoromethylation,as well as Pd(0)-catalyzed dichloromethylations.This dissertation consists of four chapters.Chapter 1:Review of Organofluoro(chloro)Compounds and Research Progress of Synthesis of Oxindoles.This chapter gives an overview of organofluoro(chloro)compounds in regard of their development,property,synthetic methods and application in organic synthesis,biology,medicine,agriculture and material and so on.The research status of the synthesis of oxindoles was also summarized in this part.Chapter 2:Pd(0)-Catalyzed Aryldifluoromethylation of Activated Alkenes.Difluoromethyloxindoles were constructed using activate alkene and PhSO2CF2I catalyzed by Pd(0)through radical addition cascade reaction.And desulfonylation of the product mediated by Mg can proceed smoothly to provide the different substituted difluoromethyloxindoles.On the basis of previous reports and our experimental results,the radical addition cascade mechanism is hypothesized.Chapter 3:Fe-Catalyzed Aryldifluoromethylation of Activated Alkenes.As a solution to the problems of Pd(0)catalytic system,such as harsh conditions,substrate scope limitation,toxicity,etc.,Fenton reagent was applied to the aryldifluoromethylation of activated alkenes,which afforded a variety of difluoromethyloxindoles in high yields via Iron-catalyzed difluoromethyl radical induction.The possible mechanism was proposed on the light of the previous reports and experimental details.Chapter 4:Pd(0)-Catalyzed Aryldichloromethylation of Activated Alkenes.The synthesis of dichloromethyloxindoles was firstly developed through a Pd(0)-catalyzed radical cascade reaction with high yields,in which BrCCl2H was crucial to be usd as the CCl2H-source.The corresponding products could be further transformed to monochloroalkenyloxindoles.The possible mechanism,including the induction of dichloromethyl radical by Pd(0),has also been proposed.