A broadly applicable [18F]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 F-18-labelled probes are inaccessible or notoriously difficult to produce. Typical challenges associated with F-18 radiochemistry are the short half-life of F-18 (<2 h), the use of sub-stoichiometric amounts of F-18, relative to the precursor and other reagents, as well as the limited availability of parent F-18 sources of suitable reactivity ([F-18]F- and [F-18]F-2). There is a high-priority demand for general methods allowing access to [F-18]CF3-substituted molecules for application in pharmaceutical discovery programmes. We report the development of a process for the late-stage [F-18]trifluoromethylation of (hetero)arenes from [F-18]fluoride using commercially available reagents and (hetero) aryl iodides. This [F-18]CuCF3-based protocol benefits from a large substrate scope and is characterized by its operational simplicity.