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

doi:10.1002/ejoc.201901815

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

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Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

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 language	English
Pages (from-to)	884-890
Number of pages	7
Journal	European Journal of Organic Chemistry
Volume	2020
Issue number	7
Early online date	14 Jan 2020
DOIs	https://doi.org/10.1002/ejoc.201901815
Publication status	Published - 21 Feb 2020

Funding

The authors acknowledge the Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) for the scholarships to D.R. S. and L.A. Z. (grant numbers 140955/2017-8 and 142476/2018-8, respectively) and the fellowship to M.P. F. (grant number 301371/2017-2), the Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) for the visiting student scholarship to D.R. S. (grant number 88881.190436/2018-01), the Funda??o de Amparo ? Pesquisa do Estado de Minas Gerais (FAPEMIG, grant numbers CEX?APQ?00383/15 and CEX?APQ?00344/17), as well as the Netherlands Organization for Scientific Research (NWO) for the financial support.

Funders	Funder number
Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico
Netherlands Organization for Scientific Research
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior	88881.190436/2018‐01
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Conselho Nacional de Desenvolvimento Científico e Tecnológico	142476/2018‐8, 301371/2017‐2, 140955/2017‐8
Fundação de Amparo à Pesquisa do Estado de Minas Gerais	CEX–APQ–00383/15, CEX–APQ–00344/17

Keywords

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

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

abstract = "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.",

keywords = "Axial–equatorial equilibrium, Conformation analysis, Fluorine gauche effect, Heterocycles, Stereoelectronic effects",

author = "Silva, {Daniela Rodrigues} and Zeoly, {Lucas A.} and Cormanich, {Rodrigo A.} and Guerra, {C{\'e}lia Fonseca} and Freitas, {Matheus P.}",

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doi = "10.1002/ejoc.201901815",

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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

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

Abstract

Funding

Keywords

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