Nuclear fluorination of 3,5-diarylisoxazoles with Selectfluor®

C-4 Fluorination of a series of 3,5-diarylisoxazoles has been accomplished using the N-F reagent Selectfluor®. With substrates containing neutral or activating substituents on the 5-phenyl ring, acetonitrile at room temperature or at reflux could be used as solvent. However, when deactivating substituents were present, a higher reaction temperature was required for which sulfolane was found to be a good solvent. At this higher temperature, a unique trifluorination of the isoxazole nucleus by an addition mechanism occurred as a side reaction.