Picking One out of Three: Selective Single C-F Activation in Trifluoromethyl Groups

The introduction of a trifluoromethyl (CF3) group into an organic molecule can modify its chemical behavior and lead to changes in its physicochemical and pharmacological properties. The CF3 group is often chosen for its chemical inertness and stability, which are related to the strong C-F bonds. In recent years, the potential of gaining straightforward access to difluorinated compounds through selective single C-F activation in CF3 groups has been unveiled. This review describes the latest methodologies for the synthesis of difluoromethylated arenes, difluoroalkenes and difluorinated aldol products of potential synthetic and/or biological interest, employing low-valent metals, transition metal catalysis, FLP and Lewis acid mediated transformations as well as photoredox catalysis.