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Evaluation of the Alicyclic Gauche Effect in 2‐Fluorocyclohexanone Analogs: a Combined NMR and DFT Study
Author(s) -
Silva Daniela Rodrigues,
Zeoly Lucas A.,
Cormanich Rodrigo A.,
Guerra Célia Fonseca,
Freitas Matheus P.
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201901815
Subject(s) - chemistry , conformational isomerism , alicyclic compound , intramolecular force , gauche effect , substituent , fluorine , natural bond orbital , density functional theory , stereochemistry , computational chemistry , polar , crystallography , organic chemistry , molecule , medicine , physics , surgery , astronomy
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.