Broad‐scope Syntheses of [<sup>11</sup>C/<sup>18</sup>F]Trifluoromethylarenes from Aryl(mesityl)iodonium Salts
Sanjay Telu, Susovan Jana, Mohammad B. Haskali, Bo Yeun Yang, Jimmy E. Jakobsson, Qunchao Zhao, Karla M. Ramos‐Torres, Pedro Brugarolas, Victor W. Pike
Abstract
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 examples of small drug‐like molecules and candidate PET radioligands, were successfully labeled in high yields (69–81 %).