Aryl and Alkyl Radiotrifluoromethylation via Metallaphotoredox-Mediated Radical Cross-Coupling

Given the short half-life of radionuclides used for positron emission tomography (PET), such as fluorine-18 (t_1/2 = 109.8 min), efficient and mild methods for the radiolabeling of PET tracers are highly sought after. Previous studies have shown how photoredox catalysis can be used to unlock unique reactivity by enabling radiofluorinations via radical formation of either non-radioactive substrates or carbon-centered ¹⁸F-labeled reagents. However, the cross-coupling of two different radical species, one of which is radiolabeled, remains thus far elusive. Herein, we report the metallaphotoredox-mediated radiotrifluoromethylation of arenes and alkanes via radical cross-coupling reactions (RCCR). All protocols proceed under mild conditions and use a commercially available Ru-based photoredox catalyst and copper(I) iodide to mediate the radical coupling. The reactions are operationally simple and can be set up without the use of a glovebox or Schlenk line. The good functional group tolerance and applicability to PET tracer synthesis is demonstrated by the radiotrifluoromethylation of a range of substrates, incl. bioactive boscalid and PET tracer [¹⁸F]SL25.1188. In a broader context, this work sets the stage for the further exploration of RCCR for radiolabeling reactions beyond radiotrifluoromethylation.