Arene radiofluorination enabled by photoredox-mediated halide interconversion

Positron emission tomography (PET) is a powerful imaging technology that can visualize and measure metabolic processes in vivo and/or obtain unique information about drug candidates. The identification of new and improved molecular probes plays a critical role in PET, but its progress is somewhat limited due to the lack of efficient and simple labelling methods to modify biologically active small molecules and/or drugs. Current methods to radiofluorinate unactivated arenes are still relatively limited, especially in a simple and site-selective way. Here we disclose a method for constructing C-F-18 bonds through direct halide/F-18 conversion in electron-rich halo(hetero)arenes. [F-18]F- is introduced into a broad spectrum of readily available aryl halide precursors in a site-selective manner under mild photoredox conditions. Notably, our direct F-19/F-18 exchange method enables rapid PET probe diversification through the preparation and evaluation of an [F-18]-labelled O-methyl tyrosine library. This strategy also results in the high-yielding synthesis of the widely used PET agent L-[F-18]FDOPA from a readily available L-FDOPA analogue.

Automated summary

PET is a powerful imaging technology used to visualize and measure metabolic processes and obtain unique information about drug candidates. The development of new and improved molecular probes in PET is crucial, but progress is restricted by the lack of efficient and simple labeling methods. This study introduces a method for constructing C-F-18 bonds through direct halide/F-18 conversion in electron-rich halo(hetero)arenes, enabling rapid diversification of PET probes.