Sequential Ir/Cu-Mediated Method for the -Selective C-H Radiofluorination of (Hetero)Arenes.

This article describes a sequential Ir/Cu-mediated process for the selective C-H radiofluorination of (hetero)arene substrates. In the first step, Ir-catalyzed C(sp)-H borylation affords (hetero)aryl pinacolboronate (BPin) esters. The intermediate organoboronates are then directly subjected to copper-mediated radiofluorination with [F]tetrabutylammonium fluoride to afford fluorine-18 labeled (hetero)arenes in high radiochemical yield and radiochemical purity. This entire process is performed on a benchtop without Schlenk or glovebox techniques and circumvents the need to isolate (hetero)aryl boronate esters. The reaction was automated on a TracerLab FX module with 1,3-dimethoxybenzene and a tyrosine derivative. The products, [F]1-fluoro-3,5-dimethoxybenzene and an F-labeled tyrosine derivative, were obtained in 37 ± 5% isolated radiochemical yield and >99% radiochemical purity and 25% isolated radiochemical yield and 99% radiochemical purity, and 0.52 Ci/μmol (19.24 GBq/μmol) molar activity (), respectively.