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

This article describes a sequential Ir/Cu-mediated process for the meta-selective C-H radiofluorination of (hetero)arene substrates. In the first step, Ir-catalyzed C(sp(2))-H borylation affords (hetero)aryl pinacolboronate (BPin) esters. The intermediate organoboronates are then directly subjected to copper-mediated radiofluorination with [F-18]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 FXFN module with 1,3-dimethoxybenzene and a meta-tyrosine derivative. The products, [F-18]1-fluoro-3,5-dimethoxybenzene and an F-18-labeled meta-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/mu mol (19.24 GBq/mu mol) molar activity (A(m)), respectively.

Automated summary

This article presents a novel method for the meta-selective C-H radiofluorination of (hetero)arene substrates. The process can be conducted on a benchtop without the need for Schlenk or glovebox techniques, resulting in higher yields and purity of the products.