TY - JOUR
T1 - Evaluation of the Alicyclic Gauche Effect in 2-Fluorocyclohexanone Analogs
T2 - a Combined NMR and DFT Study
AU - Silva, Daniela Rodrigues
AU - Zeoly, Lucas A.
AU - Cormanich, Rodrigo A.
AU - Guerra, Célia Fonseca
AU - Freitas, Matheus P.
PY - 2020/2/21
Y1 - 2020/2/21
N2 - 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.
AB - 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.
KW - Axial–equatorial equilibrium
KW - Conformation analysis
KW - Fluorine gauche effect
KW - Heterocycles
KW - Stereoelectronic effects
UR - http://www.scopus.com/inward/record.url?scp=85079429898&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85079429898&partnerID=8YFLogxK
U2 - 10.1002/ejoc.201901815
DO - 10.1002/ejoc.201901815
M3 - Article
AN - SCOPUS:85079429898
VL - 2020
SP - 884
EP - 890
JO - European Journal of Organic Chemistry
JF - European Journal of Organic Chemistry
SN - 1434-193X
IS - 7
ER -