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

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.