Nickel-Catalyzed Cross-Coupling Of Aryl Halides With Fluoroalkylating Reagents

In contrast to traditional cross-coupling,reductive coupling can directly use electrophilic partners as coupling partners instead of nucleophilic partners which are frequently synthesized when needed and required special care to exclude oxygen and moisture,thus has the advantages of mild conditions and and good functional group compatibility.At the same time,nickel-catalyzed fluoroalkylation reactions have received considerable attention and been developed significantly.Based on nickel-catalyzed reduction coupling strategy,this dissertation mainly described some efficient and highly selective aryl halide fluoroalkylation reaction systems.The concept,innovation,difficulty and development process of reductive coupling have been briefly described in Chapter One.Based on the importance of organic fluorine-containing compounds,related reports on nickel-catalyzed reductive cross-coupling fluoroalkylation have been systematically described in the order of the number of fluorine atoms in the fluorine-containing functional group.In Chapter Two,the importance and preparation methods of trifluoroethyl aryl compounds have been introduced firstly,then a nickel-catalyzed direct trifluoroethylation of aryl iodides with an industrial raw material 1,1,1-trifluoro-2-iodoethane via reductive coupling was reported.Using the insitu-generated catalysts by combination of nickel with various nitrogen and phosphine ligands,this method demonstrates high efficiency,excellent functionalgroup compatibility,especially with large sterically hindered groups.The powerful potential of this strategy was further elaborated by the late-stage modification of several derived bioactive molecules.Then,various mechanism control experiments were carried out.According to the results,the speculation that the phosphine ligands promote the conversion process by accelerating the reduction step of the nickel salt and a possible Ni(0)/Ni(II)reductive cross-coupling catalytic cycle through a radical process were proposed.In Chapter Three,the concept of pseudohalides,development of related reactions have been introduced firstly,then nickel-catalyzed reductive couping of aryl bromides and pseudohalides was reported.This catalytic system owns the advantages of easy operation,high catalytic efficiency and excellent functionalgroup compatibility,especially with large sterically hindered groups.According to the results of mechanism control experiments,the speculation that a trifluoroalkyl radical may be generated in the reaction and a possible Ni(0)/Ni(?)reductive cross-coupling mechanism have been proposed.In Chapter Four,after detailed introduction of the importance and preparation method of ?-aryl-?-fluorocarboxylic acid derivatives,a combinatorial nickel-catalyzed monofluoroalkylation of aryl bromides with the industrial raw regent ethyl chlorofluoroacetate was reported.According to the experimental results of condition screening,it is pointed out that the key factors to realize this reaction are the combination of nickel with readily available nitrogen and phosphine ligands and the using of a mixture of different solvents.Mechanistic studies indicated an in-situ-formed fluoroalkyl zinc reagent was involved in the catalytic cycle,and magnesium dichloride played a key role to activate chlorofluoroacetate to generate the zinc species.All the reports and the significance of this dissertation were summarized in Chapter five.