Noncovalent Interactions of Fluorine with Amide and CH₂ Groups in <i>N</i>-Phenyl γ-Lactams: Covalently Identical Fluorine Atoms in Nonequivalent Chemical Environments

Abstract

We designed and synthesized N-phenyl γ-lactam derivatives possessing two covalently identical ortho-F nuclei on the N-phenyl group. The F nuclei sited in different chemical environments where they were spatially adjacent to amide and alkyl groups due to hindered rotation around the central N-Ar bond. ¹⁹F NMR spectroscopic and X-ray crystallographic methods were used to distinguish the axially prochiral F nuclei and provide structural insights for through-space interactions between F and amide/CH₂ groups. Direct spectroscopic evidence for multipolar interactions in F···amide and F···CH₂ pairs were provided.