Three-Center CF···HN Intramolecular Hydrogen Bonding in the 2,6-Bis(2,6-difluorophenyl)piperidine Systems¹

¹H, ¹³C, and ¹⁹F NMR spectroscopy provided evidence for an interaction between the NH proton and the neighboring fluorine atoms in 2,6-bis(2,6-difluorophenyl)piperidin-4-ones, which can be qualified as a three-center hydrogen bonding. This was confirmed by the X-ray crystal structures of two compounds revealing the axial orientation of the amino hydrogen and its short contacts to two fluorine atoms. Surprisingly, the IR spectra exhibited shift of the NH stretching frequency to higher instead to lower wavenumbers in the 2,6-difluorophenyl derivatives. The variable temperature ¹⁹F NMR spectra showed enhanced C−C rotation barriers of the aryl substituents in the 2,6-difluorophenyl derivatives, due to the intramolecular hydrogen bonding.