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 (3)J(FH) (with (3)J(FH) axial/axial=35-40 Hz>(3)J(FH) equatorial/axial=13-13.5 Hz>(3)J(FH) axial/equatorial=10-12 Hzmuch greater than(3)J(FH) equatorial/equatorial=3-4 Hz) and (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 (4)J(FH) (with (4)J(FH) axial/axial=6 Hz>(4)J(FH) equatorial/equatorial=3-4 Hz>(4)J(FH) axial/equatorial=1.5 Hz>(4)J(FH) equatorial/axial=0 Hz) for ketones 1-4. (C) 2002 Elsevier Science Ltd. All rights reserved.