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 |
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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 | |
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 |
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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