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 bonds through direct halide/F conversion in electron-rich halo(hetero)arenes. [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 F/F exchange method enables rapid PET probe diversification through the preparation and evaluation of an [F]-labelled O-methyl tyrosine library. This strategy also results in the high-yielding synthesis of the widely used PET agent L-[F]FDOPA from a readily available L-FDOPA analogue.