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

We designed and synthesized N-phenyl gamma-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. F-19 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 center dot center dot center dot amide and F center dot center dot center dot CH2 pairs were provided.