Transition Metal-Catalyzed Deca- Rboxylative Difluoroalkylation Of α,β-Unsaturated Carboxylic Acids

The incorporation of fluorine atoms or fluoroalkyl groups into organic compounds is a consequence of the alteration of their physicochemical characteristics and bioavailability of the parent molecules. In the past decades, the chemists have paid more attention to transition-metal-mediated fluoroalkylation, which is a hot research topic in organofluorine chemistry. It is emergency to highly efficient introduce fluorine atoms or fluoroalkyl groups into organic compounds. As we known, decarboxylative cross-coupling reactions are broadly used in organic reactions. However, there are less reports about transition-metal-catalyzed decarboxylative fluoroalkylation of α,β-unsaturated carboxylic acids. In this dissertation, we mainly reported transition-metal-catalyzed decarboxylative difluoroalkylation of α,β-unsaturated carboxylic acids, which contained decarboxylative difluoroalkylation, decarboxylative atom transfer radical addition and decarboxylative aryldifluoroalkylationThis dissertation consisted of five chapters.Chapter one:Research backgroundWe described the application of fluorine-containing organic compounds in many fields, including pharmaceuticals, agrochemicals and materials fields. Then we reviewed the references about transition-metal-mediated difluoroalkylation reactionsChapter two:Nickel-catalyzed decarboxylative difluoroalkylation of α,β-unsaturated carboxylicacidsA new approach for nickel-catalyzed decarboxylative fluoroalkylation of α,β-unsaturated carboxylic acids was developed. This novel method has demonstrated excellent stereoselectivity, mild reaction conditions, broad substrate scope and excellent functional-group tolerance. Mechanistic investigations showed that a fluoroalkyl radical is involved in the catalytic cycle. The method was applied to the late-stage decarboxylative difluoroalkylation of bioactive estrone derivative, and demonstrated the potential prospect of this approach.Chapter three:Copper-catalyzed decarboxylative atom transfer radical addition of α,β-unsaturated alkynyl carboxylic acidsA new approach for copper-catalyzed decarboxylative atom transfer radical addition of α,β-unsaturated alkynyl carboxylic acids was developed. This new transformation has demonstrated broad substrate scope and excellent functional-group tolerance. The approach was also been applied to the late-stage atom transfer radical addition of bioactive estrone derivative. The novel method provided a facile pathway for application in drug discovery and development.Chapter four:Palladium-catalyzed decarboxylative aryldifluoroalkylation of α,β-unsaturated carboxylic acids.A new approach for palladium-catalyzed decarboxylative aryldifluoroalkylation of α,β-unsaturated alkynyl carboxylic acids was developed. Preliminary mechanistic studies indicated that a fluoroalkyl radical is involved in the catalytic cycle. The reaction conditions should be further optimized.Chapter five:SummaryWe summarized all the experiments, gave a positive attitude towards transition-metal-catalyzed decarboxylative difluoroalkylation of α,β-unsaturated carboxylic acids in this dissertation and finally suggested further work in the future.