Rapid and Efficient Synthesis of [C]Trifluoromethylarenes from Primary Aromatic Amines and [C]CuCF.

Prior studies have shown that trifluoromethylarenes can be labeled in high molar activities ( > 200 GBq/μmol) with positron-emitting carbon-11 ( = 20.4 min) by the reaction of the copper(I) derivative of [C]fluoroform [C]CuCF, with several types of precursors, such as aryl iodides, arylboronic acids, and aryldiazonium salts. Nonetheless, these precursors can be challenging to synthesize, and in the case of diazonium salts, are unstable. Methods that reduce challenges in precursor preparation for the synthesis of [C]trifluoromethylarenes are desirable to enhance possibilities for developing biologically relevant C-labeled compounds as radiotracers for biomedical imaging with positron emission tomography (PET). Here, we explored the production of no-carrier-added [C]trifluoromethylarenes from commercially available primary aromatic amines through reactions of [C]CuCF with diazonium salts that were generated . Moderate to high isolated decay-corrected radiochemical yields (RCY) (32-84%) were obtained rapidly (within 2 min) for many para-substituted and meta-substituted primary aromatic amines bearing a halo, methoxy, thiomethyl, hydroxy, nitro, nitrile, carboxyl, ethylcarboxy, or trifluoromethyl substituent. Null to low RCYs (0-13%) were observed only for ortho bromo-, nitro-, or nitrile-substituted precursors. This new radiosynthetic method usefully expands options for producing PET radiotracers bearing a [C]trifluoromethyl group, especially from aryl amine precursors.