Conformation of tri- and tetra-substituted 2-fluoro cyclohexanones: proton non-equivalence, F–H and F–C coupling constants, conformational dependence of 3JFH and 4JFH

The main conformation in solution (C6D6) of monofluorinated 2,2′,5-tri- and 2,2′,5,5′-tetra-substituted cyclohexanones have been studied using 1D and 2D NMR. It has been shown that for tri-substituted ketones the two possible diastereomers differ by the orientation of the fluorine atom which is axial or equatorial and that, similarly, the diastereomers of the tetra-substituted ketones having a methyl and a benzyl at C5 differ by the axial or equatorial position of the fluorine atom (the benzyl group remaining equatorial). However, the diastereomers of the tetra-substituted ketone having a methyl and a phenyl at C5 differ by the orientation of the phenyl group which is either axial or equatorial while the fluorine atom is axial in both cases. A conformational dependence of 3JFH (with 3JFH axial/axial=35–40 Hz>3JFH equatorial/axial=13–13.5 Hz>3JFH axial/equatorial=10–12 Hz≫3JFH equatorial/equatorial=3–4 Hz) and Δδ6e–6a (positive when the fluorine atom is equatorial but negative when the fluorine atom is axial) has been found for ketones 1–5 as well as a clear geometrical dependence of 4JFH (with 4JFH axial/axial=6 Hz>4JFH equatorial/equatorial=3–4 Hz>4JFH axial/equatorial=1.5 Hz>4JFH equatorial/axial=0 Hz) for ketones 1–4.