CC BY 4.0 UnportedAi, Han-JunMa, XingxingSong, QiulingWu, Xiao-Feng2022-04-142022-04-142021https://oa.tib.eu/renate/handle/123456789/8697https://doi.org/10.34657/7735The 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.enghttps://creativecommons.org/licenses/by/4.0/540C-F activationcouplingfluorinated compoundstransition-metal-freeArticle