Nickel-Catalyzed Reductive Cross-coupling Of(Hetero) Aryl Halides With Mono-/Di-fluoromethyl Halides

The introduction of fluorine or fluorine-containing groups into organic compounds will greatly change their physiochemical properties and biological activities,making organic fluorine compounds widely used in the fields of medicine,pesticides and material development.Therefore,organic fluorine chemistry has gradually become a current topic in the field of research.It is of great academic value to find and develop efficient,green and safe fluorination or fluorinated group reaction methods.In recent years,nickel catalyzed reductive cross-coupling method has attracted more and more attention and research because of its high efficiency,mild conditions and step economy.Herein,we use abundant mono/difluorobromomethane as coupling blocks with this strategy,and the method of direct monofluoromethylation and difluoromethylation of(hetero)aryl halides have been successfully established.This dissertation includes three chapters.Chapter 1:Review of monofluoromethylation and difluoromethylationIn this part,we systematically summed up the methods of introducing mono-and di-fluoromethyl,including their research process and progress,and the corresponding reaction methodologies were classified and summarized.Chapter 2:Direct monofluoromethylation of(hetero)aryl halidesUsing monofluorobromomethane as the coupling block,the reductive coupling monofluoromethylation of(hetero)aryl halides catalyzed by nickel was realized.The reaction conditions are mild and the substrates are suitable for a wide range of applications.The mechanism study shows that there may be monofluoromethyl radicals in the catalytic cycle.Chapter 3:Direct difluoromethylation of(hetero)aryl halidesUsing difluorobromomethane as the coupling block,we also realized the reductive coupling difluoromethylation of(hetero)aryl halides catalyzed by nickel.For different substrates,good reaction results can be achieved by adjusting reaction conditions.The mechanism study shows that there may be difluoromethyl radicals in the catalytic cycle.