Lone-Pair-Induced Topicity Observed in Macrobicyclic Tetra-thia Lactams and Cryptands: Synthesis, Spectral Identification, and Computational Assessment

The synthesis of a rigid macrobicyclic N,S lactam <b>L1</b> and a topologically favored in/in N,S cryptand <b>L2</b> are reported with X-ray structure analysis, dynamic correlation NMR spectroscopy, and computational analysis. Lactam <b>L1</b> exhibits two distinct rotameric conformations (plus their enantiomeric counterparts) at 25 °C, as confirmed via NMR spectroscopy and computational analysis. Coalescence of the resonances of <b>L1</b> was observed at 115 °C, allowing for complete nuclei to frequency correlation. Combining computational investigations with experimental data, topological equilibria and relative energies/strain relating to the perturbation of the pore were determined. Due to the increased conformational strain of the N₂S₂ template, the nitrogen lone pairs in <b>L2</b> elicit a unique transannular interaction, resulting in a thermodynamically favored in/in nephroidal racemate. The combination of preferred topology, steric relief, and electronic localization of <b>L2</b> induces a chiral environment imparted through the amine with a computed inversion barrier of 10.3 kcal mol^–1

Lone-Pair-Induced Topicity Observed in Macrobicyclic Tetra-thia Lactams and Cryptands: Synthesis, Spectral Identification, and Computational Assessment

The synthesis of a rigid macrobicyclic N,S lactam <b>L1</b> and a topologically favored in/in N,S cryptand <b>L2</b> are reported with X-ray structure analysis, dynamic correlation NMR spectroscopy, and computational analysis. Lactam <b>L1</b> exhibits two distinct rotameric conformations (plus their enantiomeric counterparts) at 25 °C, as confirmed via NMR spectroscopy and computational analysis. Coalescence of the resonances of <b>L1</b> was observed at 115 °C, allowing for complete nuclei to frequency correlation. Combining computational investigations with experimental data, topological equilibria and relative energies/strain relating to the perturbation of the pore were determined. Due to the increased conformational strain of the N₂S₂ template, the nitrogen lone pairs in <b>L2</b> elicit a unique transannular interaction, resulting in a thermodynamically favored in/in nephroidal racemate. The combination of preferred topology, steric relief, and electronic localization of <b>L2</b> induces a chiral environment imparted through the amine with a computed inversion barrier of 10.3 kcal mol^–1

Lone-Pair-Induced Topicity Observed in Macrobicyclic Tetra-thia Lactams and Cryptands: Synthesis, Spectral Identification, and Computational Assessment

The synthesis of a rigid macrobicyclic N,S lactam <b>L1</b> and a topologically favored in/in N,S cryptand <b>L2</b> are reported with X-ray structure analysis, dynamic correlation NMR spectroscopy, and computational analysis. Lactam <b>L1</b> exhibits two distinct rotameric conformations (plus their enantiomeric counterparts) at 25 °C, as confirmed via NMR spectroscopy and computational analysis. Coalescence of the resonances of <b>L1</b> was observed at 115 °C, allowing for complete nuclei to frequency correlation. Combining computational investigations with experimental data, topological equilibria and relative energies/strain relating to the perturbation of the pore were determined. Due to the increased conformational strain of the N₂S₂ template, the nitrogen lone pairs in <b>L2</b> elicit a unique transannular interaction, resulting in a thermodynamically favored in/in nephroidal racemate. The combination of preferred topology, steric relief, and electronic localization of <b>L2</b> induces a chiral environment imparted through the amine with a computed inversion barrier of 10.3 kcal mol^–1