Multiple Approaches to the In Situ Generation of Anhydrous Tetraalkylammonium Fluoride Salts for SAr Fluorination Reactions.

This article focuses on the development of practical approaches to the in situ generation of anhydrous fluoride salts for applications in nucleophilic aromatic substitution (SAr) reactions. We report herein that a variety of combinations of inexpensive nucleophiles (e.g., tetraalkylammonium cyanide and phenoxide salts) and fluorine-containing electrophiles (e.g., acid fluoride, fluoroformate, benzenesulfonyl fluoride, and aryl fluorosulfonate derivatives) are effective for this transformation. Ultimately, we demonstrate that the combination of tetramethylammonium 2,6-dimethylphenoxide and sulfuryl fluoride (SOF) serves as a particularly practical route to anhydrous tetramethylammonium fluoride. This procedure is applied to the SAr fluorination of a range of electron-deficient aryl and heteroaryl chlorides as well as nitroarenes.