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- ¹⁸ F bonds through direct halide/ ¹⁸ F conversion in electron-rich halo(hetero)arenes. [ ¹⁸ F]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 ¹⁹ F/ ¹⁸ F exchange method enables rapid PET probe diversification through the preparation and evaluation of an [ ¹⁸ F]-labelled O-methyl tyrosine library. This strategy also results in the high-yielding synthesis of the widely used PET agent L-[ ¹⁸ F]FDOPA from a readily available L-FDOPA analogue.
(© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)