Tetramethylammonium Fluoride Alcohol Adducts for S<sub>N</sub>Ar Fluorination
María T. Morales-Colón, Yi Yang See, So Jeong Lee, Peter J. H. Scott, Douglas C. Bland, Melanie S. Sanford
Abstract
Nucleophilic aromatic fluorination (SNAr) is among the most common methods for the formation of C(sp2)–F bonds. Despite many recent advances, a long-standing limitation of these transformations is the requirement for rigorously dry, aprotic conditions to maintain the nucleophilicity of fluoride and suppress the generation of side products. This report addresses this challenge by leveraging tetramethylammonium fluoride alcohol adducts (Me4NF·ROH) as fluoride sources for SNAr fluorination. Through systematic tuning of the alcohol substituent (R), tetramethylammonium fluoride tert-amyl alcohol (Me4NF·t-AmylOH) was identified as an inexpensive, practical, and bench-stable reagent for SNAr fluorination under mild and convenient conditions (80 °C in DMSO, without the requirement for drying of reagents or solvent). A substrate scope of more than 50 (hetero) aryl halides and nitroarene electrophiles is demonstrated.