Theoretical study on the mechanism of the benzaldehyde deoxyfluorination by sulfuryl fluoride and tetramethylammonium fluoride

Abstract

AbstractOrganic fluoride compounds have a potential widely application in pharmaceutical, chemical, and material industries. The deoxyfluorination of C=O bonds is one of important ways to synthesize the organic fluorides. Recently, one efficient aldehyde deoxyfluorination strategy by sulfuryl fluoride (SO2F2) and tetramethylammonium fluoride (TMAF) under mild condition was proposed with low cost and high yield, and SO2F2 was produced by the reaction of 1,1′‐sulfonyldiimidazole (SDI) and KF in formic acid solvent. Herein, a density functional theory (DFT) study was performed to investigate the nature of this reaction including the SO2F2 formation and the aldehyde deoxyfluorination. The calculated results indicate that in the SO2F2 formation, the formic acid plays an important role and participates in the reaction with SDI and KF to transfer proton and convert imidazole cation into imidazole, and in the aldehyde deoxyfluorination by SO2F2 and TMAF, this study points out that there are two C–F coupling steps in this process, and the second one along a SN2 pathway is the rate‐determining step with a free energy barrier of 9.6 kcal/mol. The fluoride anions (F−) come from TMAF as fluorination reagent, which agree well with experimental results. And SO2F2 acts as deoxidization reagent. In comparison with the benzaldehyde deoxyfluorination by diethylaminosulfur trifluoride (DAST), the aldehyde deoxyfluorination strategy by SO2F2 and TMAF owns thermodynamic and kinetic advantages. This theoretical study could provide theoretical insights to design new reagent for the deoxyfluorination of C=O bonds.