title: A computational study of vicinal fluorination in 2,3-difluorobutane: implications for conformational control in alkane chains.
abstract: A comprehensive conformational analysis of both 2,3-difluorobutane diastereomers is presented based on density functional theory calculations in vacuum and in solution, as well as NMR experiments in solution. While for 1,2-difluoroethane the fluorine gauche effect is clearly the dominant effect determining its conformation, it was found that for 2,3-difluorobutane there is a complex interplay of several effects, which are of similar magnitude but often of opposite sign. As a result, unexpected deviations in dihedral angles, relative conformational energies and populations are observed which cannot be rationalised only by chemical intuition. Furthermore, it was found that it is important to consider the free energies of the various conformers, as these lead to qualitatively different results both in vacuum and in solvent, when compared to calculations based only on the electronic energies. In contrast to expectations, it was found that vicinal syn-difluoride introduction in the butane and by extension, longer hydrocarbon chains, is not expected to lead to an effective stabilisation of the linear conformation. Our findings have implications for the use of the vicinal difluoride motif for conformational control.
authors.affiliation: Department of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ (UK).
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Fox
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gourdain
authors.forename: Anton
authors.initials: A
authors.lastname: Coulthurst
authors.forename: Clare
authors.initials: C
authors.lastname: Fox
authors.forename: Ilya
authors.initials: I
authors.lastname: Kuprov
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Essex
authors.forename: Chris-Kriton
authors.initials: CK
authors.lastname: Skylaris
authors.forename: Bruno
authors.initials: B
authors.lastname: Linclau
mesh_terms: D000473:Alkanes / Q000737:chemistry; D002073:Butanes / Q000737:chemistry*; D005461:Fluorine / Q000737:chemistry*; D054879:Halogenation; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism
chemical_list: C492641:2-fluorobutane; D000473:Alkanes; D002073:Butanes; D005461:Fluorine
keywords: NMR spectroscopy; computational chemistry; conformational analysis; organofluorine chemistry; stereoelectronic effects