New access to trifluoromethyl acrylates and acrylic acids and their subsequent use in organometallic chemistry

Owing to the unique properties of the trifluoromethyl (CF₃) group, CF₃-substituted alkenes play important roles in pharmaceuticals, agrochemicals, and materials science. Among various trifluoromethyl alkene derivatives, CF₃-containing acrylates and acrylic acids have great application potential. Despite obvious interest in such kinds of scaffolds, the methods for their synthesis as well as their substrate scope remain relatively limited. In this Ph.D. thesis, we mainly focused on the synthesis of 3-aryl-2-(trifluoromethyl)acrylates and acrylic acids. Subsequent transformations of these compounds were further investigated. In the first part of this thesis, we reported the synthesis of diverse methyl and tert-butyl 3-aryl-2-(trifluoromethyl)acrylates from aryl iodides and the corresponding 2-(trifluoromethyl)acrylates by Mizoroki-Heck reaction in the presence of palladium catalyst and silver(I) additive. The one-pot synthesis of 3-trifluoromethyl coumarin derivatives was further achieved starting from ortho-iodophenols and methyl 2-(trifluoromethyl)acrylate by tandem Mizoroki-Heck reaction and intramolecular cyclization. In the second part of this thesis, we demonstrated that the palladium-catalysed silver(I) additive-mediated Mizoroki-Heck reaction could be extended to the synthesis of 3-aryl-2-(trifluoromethyl)acrylic acids. Similarly, the reaction between ortho-iodophenols and 2-(trifluoromethyl)acrylic acid could also give access to 3-trifluoromethyl coumarin derivatives. Furthermore, we achieved the construction of more complex alkyl 3-aryl-2-(trifluoromethyl)acrylates by three-component reactions between aryl iodides, 2-(trifluoromethyl)acrylic acid, and alkyl iodides. In the last part of this thesis, we developed a method for palladium-catalysed copper(I)-mediated oxidative decarboxylative cross-coupling of heteroarenes with (Z)-3-aryl-2-(trifluoromethyl)acrylic acids. Diverse trisubstituted CF₃-alkenes were generated in relatively low yields but with high E/Z selectivity.