A General Copper‐Mediated Nucleophilic 18F Fluorination of Arenes

Abstract

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 (S_NAr) with [¹⁸F]F⁻. In the ideal case, the ¹⁸F fluorination of these substrates would be performed through reaction of [¹⁸F]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 ¹⁸F arenes from pinacol-derived aryl boronic esters (arylBPin) upon treatment with [¹⁸F]KF/K₂₂₂ and [Cu(OTf)₂(py)₄] (OTf=trifluoromethanesulfonate, py=pyridine). This method tolerates electron-poor and electron-rich arenes and various functional groups, and allows access to 6-[¹⁸F]fluoro-L-DOPA, 6-[¹⁸F]fluoro-m-tyrosine, and the translocator protein (TSPO) PET ligand [¹⁸F]DAA1106.