A General Copper-Mediated Nucleophilic 18F Fluorination of Arenes

Molecules labeled with fluorine-18 are used as radiotracers for positron emission tomography. An important challenge is the labeling of arenes not amenable to aromatic nucleophilic substitution (SNAr) with [F-18]F-. In the ideal case, the F-18 fluorination of these substrates would be performed through reaction of [F-18]KF with shelf-stable readily available precursors using a broadly applicable method suitable for automation. Herein, we describe the realization of these requirements with the production of F-18 arenes from pinacol-derived aryl boronic esters (arylBPin) upon treatment with [F-18]KF/K-222 and [Cu(OTf)(2)(py)(4)] (OTf = trifluoromethane-sulfonate, py = pyridine). This method tolerates electron-poor and electron-rich arenes and various functional groups, and allows access to 6-[F-18] fluoro-l-DOPA, 6-[F-18] fluoro-m-tyrosine, and the translocator protein (TSPO) PET ligand [F-18]DAA1106.