There and back again: the role of hyperconjugation in the fluorine gauche effect

Abstract

The origin of the fluorine gauche effect has been debated for decades and recently different interpretations have been raised in the scientific community as new computational methods emerged and were...

Regioselective Fluorohydrin Synthesis from Allylsilanes and Evidence for a Silicon–Fluorine Gauche Effect

“…This was also true for the triphenylsilyl fluorohydrin 2 (calculated energy minimum at Ø Si–F ∼ 50° for Ø F–OH = 60°), which is in fairly good agreement with results from X-ray analysis (e.g., Ø Si–F = 38°) when accounting for potential crystal forces , and the small energy differences calculated between the different conformations (Δ E ∼ 2 kJ/mol for Ø Si–F 50° vs Ø Si–F 60°). Our working hypothesis is that the gauche–gauche conformation has the lowest energy due to a combination of hyperconjugation (e.g., σ C–H → σ C–F *) and electrostatics (e.g., Si δ+ → F δ− ) …”

“…This was also true for the triphenylsilyl fluorohydrin 2 (calculated energy minimum at Ø Si−F ∼ 50°for Ø F−OH = 60°), which is in fairly good agreement with results from X-ray analysis (e.g., Ø Si−F = 38°) when accounting for potential crystal forces 52,53 and the small energy differences calculated between the different conformations (ΔE ∼ 2 kJ/ mol for Ø Si−F 50°vs Ø Si−F 60°). Our working hypothesis is that the gauche−gauche conformation has the lowest energy due to a combination of hyperconjugation (e.g., σ C−H → σ C−F *) 54 and electrostatics (e.g., Si δ+ → F δ− ). 55 Given not only the value of fluorine-containing compounds for drug discovery 1−7 but also an emerging interest in organosilanes for this purpose, 56 silicon-substituted fluorohydrins could present a novel platform for designing conformationally restricted biologically active structures.…”

Structural, Electronic, Reactivity, and Conformational Features of 2,5,5-Trimethyl-1,3,2-diheterophosphinane-2-sulfide, and Its Derivatives: DFT, MEP, and NBO Calculations

“…Further, the results indicate that the values of GAE are more vital for analyzing the conformational preferences of these compounds than the electrostatic effects, which are Since the hyperconjugation of two electrons and orbitals occurs, stabilization is significant [40]. The effect of the molecule geometry on the energy gap, the ability of the empty orbital to receive, and the ability of the filled orbital to donate are essential parts of this scenario [41,42].…”

“…conformations decrease from compound (1) to compound (3). Since the hyperconjugation of two electrons and orbitals occurs, stabilization is significant [40]. The effect of the molecule geometry on the energy gap, the ability of the empty orbital to receive, and the ability of the filled orbital to donate are essential parts of this scenario [41,42].…”

Revisiting the Conformational Isomerism of Dihaloethanes: A Hybrid Computational and Experimental Laboratory for the Undergraduate Curriculum

“…Indeed, the described laboratory program was inspired, in part, by previous literature using NMR or Raman , spectroscopy to determine populations of 1,2-dichloroethane (DCE) and 1,2-dibromoethane (DBE). We note the importance of conformational isomerism in 1,2-difluoroethane (DFE) with regards to the gauche effect; however, this laboratory program is designed to encourage students to think critically about the effect of intermolecular interactions, in liquid and solvent, on conformation. In addition, DFE is not studied directly in this experiment due to the inherent difficulties associated with handling low boiling liquids.…”