Conformational impact of structural modifications in 2-fluorocyclohexanone

Francisco A Martins,Matheus P Freitas,Josué M Silla

doi:10.3762/bjoc.13.172

Francisco A Martins, Matheus P Freitas + Show 1 more

Open Access

https://doi.org/10.3762/bjoc.13.172

Copy DOI

Abstract

2-Haloketones are building blocks that combine physical, chemical and biological features of materials and bioactive compounds, while organic fluorine plays a fundamental role in the design of performance organic molecules. Since these features are dependent on the three-dimensional chemical structure of a molecule, simple structural modifications can affect its conformational stability and, consequently, the corresponding physicochemical/biological property of interest. In this work, structural changes in 2-fluorocyclohexanone were theoretically studied with the aim at finding intramolecular interactions that induce the conformational equilibrium towards the axial or equatorial conformer. The interactions evaluated were hydrogen bonding, hyperconjugation, electrostatic and steric effects. While the gauche effect, originated from hyperconjugative interactions, does not appear to cause some preferences for the axial conformation of organofluorine heterocycles, more classical effects indeed rule the conformational equilibrium of the compounds. Spectroscopic parameters (NMR chemical shifts and coupling constants), which can be useful to determine the stereochemistry and the interactions operating in the series of 2-fluorocyclohexanone derivatives, were also calculated.

Highlights

Organofluorine compounds are of special interest in materials, pharmaceutical and agricultural sciences, as the C–F bond is the most polar bond in organic chemistry, which can be useful in the design of performance organic molecules [1]
A fluorine substituent in organofluorine compounds affects conformational properties, since it can induce stereoelectronic effects, such as σC–H to σ*C–F hyperconjugative interactions in case of an antiparallel oriented C–H bond. This is the origin of the so-called 'gauche effect', because electronegative C–X bonds do not participate in such hyperconjugative interactions and often give way to the C–H bond in occupying the antiperiplanar orientation relative to the C–F bond [2,3,4,5,6]
Hyperconjugation plays a secondary role as dictating interaction of the conformational isomerism of 2-fluorocyclohexanone derivatives investigated in this study

Summary

Introduction

Organofluorine compounds are of special interest in materials, pharmaceutical and agricultural sciences, as the C–F bond is the most polar bond in organic chemistry, which can be useful in the design of performance organic molecules [1]. A fluorine substituent in organofluorine compounds affects conformational properties, since it can induce stereoelectronic effects, such as σC–H to σ*C–F hyperconjugative interactions in case of an antiparallel oriented C–H bond. This is the origin of the so-called 'gauche effect', because electronegative C–X bonds do not participate in such hyperconjugative interactions and often give way to the C–H bond in occupying the antiperiplanar orientation relative to the C–F bond [2,3,4,5,6].

Methods

Results

Conclusion