Carbon-Carbon/Carbon-Nitrogen Bond Formation Of Polyfluoroarenes Or β,β-Difluoroalkene

Because of the unique physicochemical properties and potential bioactivity, fluorinated compounds have been wide applications in pharmaceuticals, agrochemicals and materials science, and it has been received increasing attention in recent years. To date, only a few organofluoride natural products have been found and isolated, so the building blocks used to generate organofluoride containing pharmaceuticals and materials must be obtained through synthesis. Highly selective C-F bond cleavage/activation of fluorinated compounds have become current subjects of active investigation from the viewpoint of effective synthesis of fiuoroorganic compounds. In this dissertation, simple and efficient methods of highly selective C-F bond cleavage/activation and further transformation to form new C-C/C-N bonds from fluorinated compounds such as polyfluoroarenes or β,β-difluoroalkenes have been developed. The main contents in this dissertation are as follows:1) synthesis of 2-polyfluoroaryl arylacetates via a one-pot three-component reaction of poly-fluoroarenes, ethyl 2-chloropropionate and ortho-substituted nitrobenzenes; 2) Kumada cross coupling reaction of polyfluoroarenes with Grignard reagents via pyridinyl-directed C-F bond cleavage; 3) synthesis of (E)-N-(a-fluorovinyl)azoles by the reaction of β,β-difluoroalkenes with various N-H-containing heterocycles; 4) Suzuki-Miyaura coupling reaction of gem-difluoroalkenes via C-F activation.1. We developed a novel method for the synthesis of 2-polyfluoroaryl arylacetates via a one-pot three-component VNSAr-SNAr reaction of poly-fluoroarenes, ethyl 2-chloropropionate, and ortho-substituted nitrobenzenes in the presence of NaH. The strong electron-withdrawing group in polyfluoroarenes is essential for activation of the C-F bond and allows the formation of the product in good yields.2. We have developed ortho-selective cross coupling of polyfluoroarenes with Grignard reagents via pyridinyl-directed C-F bond cleavage in the absence of metal catalyst. We also suggested a possible pyridyl mediated C-F bond cleavage mechanism.3. We have described a facile and straightforward method for the stereoselective synthesis of (E)-N-(α-fluorovinyl)azoles by the reaction of (β,β-difluoroalkenes with various N-H-containing heterocycles in the absence of metal catalyst under very mild reaction conditions via vinylic nucleophilic substitution reaction (SNV) in the presence of K3PO4. Notably, the a-hetaryl-substituted monofluoroalkenes could further react with another 7c-electron-rich nitrogen heterocycle, affording the N,N’-α,α’-dihetaryl-substituted alkenes in excellent yields and tunable stereoselectivities. This method can be considered as a valuable strategy for direct access to various N-functionalized fluoroolefins and poly substituted olefins. Thirty compounds were synthesized and the bactericidal activities were tested, some of the compounds showed good bactericidal activities at 50 ug/mL.4. We have developed an efficient method for the stereoselective synthesis of polysubstituted fluoroalkenes. Fourteen novel Z-polysubstituted fluoroalkenes were synthesized by C-F bond activation via NiCl2(PCy3)2 catalyzed Suzuki reaction of β,β-difluoroalkenes and aryl boronic acids in good yields. The cell toxicity of 11 compounds were tested, compound Ⅳ-(Z)-3o showed good biological activity to MCF-7 cells, the IC50 value is 736.2 ng/mL.