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

Abstract

The synthesis of a rigid macrobicyclic N,S lactam L1 and a topologically favored in/in N,S cryptand L2 are reported with X-ray structure analysis, dynamic correlation NMR spectroscopy, and computational analysis. Lactam L1 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 L1 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 NS template, the nitrogen lone pairs in L2 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 L2 induces a chiral environment imparted through the amine with a computed inversion barrier of 10.3 kcal mol.

Synthesis, Characterization, and Copper(II) Chelates of 1,11-Dithia-4,8-diazacyclotetradecane

“…Mixed N, S-containing macrocyclic ligands continue to be of significant interest due to their metal chelate coordination and redox properties with d-block elements . The property of the [14]­aneN 2 X 2 series (X = S or O) to chelate both hard and soft metals has been reported throughout the literature with recently reporting as biological CO 2 - and proton-reducing agents, MRI contrast agents, positron emission tomography imaging, anticancer agents, nitric oxide sensors, and as a scaffold for cryptand formation . Many copper­(II) chelates within the [14]­aneN 2 S 2 series have been previously investigated by both Rorabacher and Siegfried with binding constants and comparisons to other mixed [14]­ane systems including S 4 and N 4 .…”

“…1 The property of the [14]aneN 2 X 2 series (X = S or O) to chelate both hard and soft metals has been reported throughout the literature 2 with recently reporting as biological CO 2 -and proton-reducing agents, 3 MRI contrast agents, 4 positron emission tomography imaging, 5 anticancer agents, 6 nitric oxide sensors, 7 and as a scaffold for cryptand formation. 8 Many copper(II) chelates within the [14]aneN 2 S 2 series have been previously investigated by both Rorabacher and Siegfried with binding constants and comparisons to other mixed [14]ane systems including S 4 and N 4 . 9 Practical pathways leading to the synthesis of [14]aneN 2 S 2 L2 10 and L3 11 heteroconstitutional isomers (Figure 1) have been previously reported in moderate and reproducible yields.…”