Recent advances in radical-based C-F bond activation of polyfluoroarenes and gem-difluoroalkenes

The direct employment of polyfluoroarenes and gem-difluoroalkenes as building blocks is regarded as one of the most effective and straightforward strategies for the introduction of fluorine-containing moieties into organic skeletons. Accordingly, for the activation of their C-F bonds, radical chemistry has gradually become a mild and powerful method. The radical-based transformations of polyfluoroarenes and gem-difluoroalkenes can be primarily categorized into three types based on specific intermediates involved: 1) multifluoroaryl radical anions, 2) monofluoroalkenyl radicals and 3) other radicals. Compared with the more established multifluoroaryl radical anion pathway, monofluoroalkenyl radical-involved cross-coupling reaction can proceed through C-radical cross-coupling, radical addition/elimination or hydrogen atom transfer process. For the presented examples in this review, the typical reaction modes, substrate scopes, radical-involved mechanisms, and late-stage applications in the modification of bioactive molecules are discussed, aiming to provide a comprehensive view of the recent advances of the radical-based transformations of polyfluoroarenes and gem-difluoroalkenes.