A broadly applicable [ 18 F]trifluoromethylation of aryl and heteroaryl iodides for PET imaging

Molecules labelled with the unnatural isotope fluorine-18 are used for positron emission tomography. Currently, this molecular imaging technology is not exploited at its full potential because many 18 F-labelled probes are inaccessible or notoriously difficult to produce. Typical challenges associated with 18 F radiochemistry are the short half-life of 18 F (<2 h), the use of sub-stoichiometric amounts of 18 F, relative to the precursor and other reagents, as well as the limited availability of parent 18 F sources of suitable reactivity ([ 18 F]F – and [ 18 F]F 2 ). There is a high-priority demand for general methods allowing access to [ 18 F]CF 3 -substituted molecules for application in pharmaceutical discovery programmes. We report the development of a process for the late-stage [ 18 F]trifluoromethylation of (hetero)arenes from [ 18 F]fluoride using commercially available reagents and (hetero)aryl iodides. This [ 18 F]CuCF 3 –based protocol benefits from a large substrate scope and is characterized by its operational simplicity.