Transition-metal-catalyzed Synthesis Of Fluorinated Heterocycles From Fluoroalkylimidoyl Halide Derivatives

Due to its special biological activity, fluorinated compounds have been widely used in pharmaceuticals, agricultural chemicals, materials and so on. Thus, developing new and efficient synthetic methods and synthesizing fluorinated compounds with potential application value are of great significance. This dissertation is mainly focused on the study of synthesizing a series of fluorinated compounds starting from fluorinated N-aryl acetimidoyl halides. This work has been divided into three parts:Part I:Rhodium-catalyzed intramolecular difluoromethylenation1. In the presence of n-BuLi,2-aryl indoles,2-aryl pyrroles and2-aryl imidazoles can react with fluorinated N-aryl acetimidoyl halides to obtain substrates with a CF2Br group. Under Wilkinson’s catalyst, these substrates underwent intramolecular sp2C-H bond difluoromethylenation, offering a series of functionalized difluoromethylenative products with isolated yield as high as97%. Preliminary studies suggested that this reaction might not via a pure radical mechanism and further mechanism studies need to be carried out.2. Based on fluorinated N-aryl acetimidoyl halides, diynes can be synthesized through multistep reaction. These diynes could react with other alkynes to occur alkyne [2+2+2] cycloaddition reactions under the Wilkinson’s catalyst. The obtained phenanthridines with a CF2Br group could then occur tandem intramolecular sp2C-H bond difluoromethylenation to offer fluorine-containing multisubstituted polycyclic phenanthridines with isolated yield as high as85%. This method provides a convenient route to fluorine-containing polycyclic compounds.3. Based on fluorinated N-aryl acetimidoyl halides, phenols and indoles with a CF2Br group can be synthesized through multistep reaction. Under rhodium catalysis, intramolecular difluoromethylenative dearomatization of phenols or indoles with a CF2Br group has been developed. This methodology allows a wide range of functional group tolerance fluorinated azaspirocyclohexadienones bearing all-carbon quaternary centers to be prepared with isolated yield as high as95%. Part Ⅱ:Copper-catalyzed synthesis of2-trifluoromethylquinolinesBased on fluorinated N-aryl acetimidoyl halides, a series of alkylimines substrates were synthesized. Under copper catalysis, azide-alkyne cycloaddition (CuAAC) between these alkylimines substrates and sulfonyl azides occur. Then after intramolecular tandem cyclization reaction,2-trifluoromethylquinolines were synthesized with isolated yield as high as96%. This method has a broad scope and good functional-group compatibility.Part Ⅲ:Primary exploration on the direct heptfluoroisopropylation via hexafluoropropene(HFP)Silver fluoride can react with HFP in CH3CN to form a solution of heptfluoroisopropyl silver. Aryl boronic acids can react with the heptfluoroisopropyl silver reagent under copper to obtain heptfluoroisopropylated arenes with isolated yield as high as85%. This method provides a new way of introducing heptfluoroisopropyl group into molecule.