Study of Intramolecular SNAr Mechanism with Fluorophenols Substrates

The nucleophilic aromatic substitution (S_NAr) reaction is a widely used strategy for the derivatization of aromatic rings,^1,2 typically occurring in electron-deficient aryl fluorides due to the presence of electron-withdrawing groups. However, this type of reaction can also take place in the absence of such activating groups, proceeding through either concerted or stepwise mechanisms.³ The formation of 1,4-benzodioxanes from mono-, di- and trifluorophenols and cyclohexene oxide was selected as a model reaction and investigated using a one-pot methodology. The reaction mechanism was investigated through a combination of NMR experiments and DFT calculations to elucidate the S_NAr process and its associated energy profile. Analysis of the ¹⁹F{¹H} NMR spectra revealed that the reaction did not proceed when the monofluorinated phenol was employed. This behaviour can be rationalized by the reaction energy profile and conformational preferences predicted by the DFT calculations.