The influence of electronic perturbations on the Sulfur–Fluorine Gauche Effect

•Solution phase conformer populations determined using NMR.•A gauche arrangement predominates over the anti.•The gauche conformer molar fractions notably depend on the para-phenyl substituent.•Average gauche populations increase in the order sulfide, sulfone and sulfoxide.

Herein, a solution phase NMR conformer population analysis is employed to probe the effect of remote electronic perturbations on the conformational equilibria of a series of para-substituted β-fluorosulfides (1), sulfoxides (2) and sulfone derivatives (3). Conformations that allow for stabilizing stereoelectronic (σC–H → σ*C–F) and electrostatic (Fδ−…Sδ+) interactions predominate: this is consistent with the Sulfur–Fluorine Gauche Effect. The molar fractions (χ) of the two possible gauche conformers correlate linearly with the electron-withdrawing aptitude of the para-substituent, rendering the system ideally suited for a Hammett-type analysis. Despite the clear influence that the remote para-substituents have on conformer population, this is superseded by the oxidation state on sulfur (II, IV, VI), where an increased preference for the gauche conformer follows the trend: sulfide < sulfone < sulfoxide. It is envisaged that this proof of concept in controlling conformer population, either by proximal (oxidation state) or remote tuning (para-substituent), will find application in molecular design.

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