Evaluation of the Alicyclic Gauche Effect in 2-Fluorocyclohexanone Analogs: a Combined NMR and DFT Study

Daniela Rodrigues Silva, Lucas A. Zeoly, Rodrigo A. Cormanich, Célia Fonseca Guerra*, Matheus P. Freitas

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Herein, we have investigated the effect of an endocyclic group (forming the N–C–C–F fragment) on the conformational preferences of 2-fluorocyclohexanone analogs. A combined approach of nuclear magnetic resonance and density functional theory calculations was employed to assess the conformational equilibrium in several media. In turn, natural bond orbital analysis and the conformational behavior of other 2-halocyclohexanone analogs were used to get more insights about the intramolecular interactions governing the conformer stabilities. Our results reveal that any stabilization from interactions featured in the gauche effect is overcome by a short-range interaction of the fluorine substituent with the carbonyl group. Consequently, the gauche effect in heterocyclic compounds is not as stabilizing as in their acyclic counterparts. Only the electrostatic gauche effect takes place even in polar solvents owing to an attraction between the axial fluorine and an endocyclic quaternary ammonium group.

Original languageEnglish
Pages (from-to)884-890
Number of pages7
JournalEuropean Journal of Organic Chemistry
Issue number7
Early online date14 Jan 2020
Publication statusPublished - 21 Feb 2020


  • Axial–equatorial equilibrium
  • Conformation analysis
  • Fluorine gauche effect
  • Heterocycles
  • Stereoelectronic effects


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