A General Copper‐Mediated Nucleophilic 18F Fluorination of Arenes

Abstract

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 N Ar) with [ 18 F]F − . In the ideal case, the 18 F fluorination of these substrates would be performed through reaction of [ 18 F]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 18 F arenes from pinacol‐derived aryl boronic esters (arylBPin) upon treatment with [ 18 F]KF/K 222 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‐[ 18 F]fluoro‐ L ‐DOPA, 6‐[ 18 F]fluoro‐ m ‐tyrosine, and the translocator protein (TSPO) PET ligand [ 18 F]DAA1106.