C–F bond activation under transition-metal-free conditions

The unique properties of fluorine-containing organic compounds make fluorine substitution attractive for the development of pharmaceuticals and various specialty materials, which have inspired the evolution of diverse C–F bond activation techniques.Although many advances have been made in functionalizations of activated C–F bonds utilizing transition metal complexes,there are fewer approaches available for nonactivated C–F bonds due to the difficulty in oxidative addition of transition metals to the inert C–F bonds. In this regard, using Lewis acid to abstract the fluoride and light/radical initiator to generate the radical intermediate have emerged as powerful tools for activating those inert C–F bonds. Meanwhile, these transition-metal-free processes are greener, economical, and for the pharmaceutical industry, without heavy metal residues. This review provides an overview of recent C–F bond activations and functionalizations under transition-metal-free conditions. The key mechanisms involved are demonstrated and discussed in detail. Finally, a brief discussion on the existing limitations of this field and our perspective are presented.