Probing Noncovalent Interactions in [3,3]Metaparacyclophanes

Arene-arene interactions are fundamentally important in molecular recognition. To precisely probe arene-arene interactions in cyclophanes, we designed and synthesized (2,6-phenol)paracyclophanes and (2,6-aniline)paracyclophanes that possess two aromatic rings in close proximity. Fine-tuning the aromatic character of one aromatic ring by fluorine substituents enables investigations on the intramolecular interactions between the electron-rich phenol and aniline with tetra-H- and tetra-F-substituted benzene. pK_a measurements revealed that the tetra-F-template increases the acidity of the phenol (ΔpK_a = 0.55). X-ray crystallography and computational analyses demonstrated that all [3,3]metaparacyclophanes adopt cofacial parallel conformations, implying the presence of π-π stacking interactions. Advanced quantum chemical analyses furthermore revealed that both electrostatic interactions and orbital interactions provide the key contribution to the structure and stability of [3,3]metaparacyclophanes.