Publication
Broad‐scope Syntheses of [11C/18F]Trifluoromethylarenes from Aryl(mesityl)iodonium Salts
Publisher:
Wiley
Date:
20-03-2023
DOI:
10.1002/CHEM.202204004
Abstract: Efficient methods for labeling aryl trifluoromethyl groups to provide novel radiotracers for use in biomedical research with positron emission tomography (PET) are keenly sought. We report a broad‐scope method for labeling trifluoromethylarenes with either carbon‐11 ( t 1/2 =20.4 min) or fluorine‐18 ( t 1/2 =109.8 min) from readily accessible aryl(mesityl)iodonium salts. In this method, the aryl(mesityl)iodonium salt is treated rapidly with no‐carrier‐added [ 11 C]CuCF 3 or [ 18 F]CuCF 3 . The mesityl group acts as a spectator allowing radiolabeled trifluoromethylarenes to be obtained with very high chemoselectivity. Radiochemical yields from aryl(mesityl)iodonium salts bearing either electron‐donating or electron‐withdrawing groups at meta ‐ or para ‐ position are good to excellent (67–96 %). Ortho ‐substituted and otherwise sterically hindered trifluoromethylarenes still give good yields (15–34 %). Substituted heteroaryl(mesityl)iodonium salts are also viable substrates. The broad scope of this method was further exemplified by labeling a previously inaccessible target, [ 11 C] p ‐trifluoromethylphenyl boronic acid, as a potentially useful labeling synthon. In addition, fluoxetine, leflunomide, and 3‐trifluoromethyl‐4‐aminopyridine, as ex les of small drug‐like molecules and candidate PET radioligands, were successfully labeled in high yields (69–81 %).