Transannular Hydrogen Bonding in Planar-Chiral [2.2]Paracyclophane-Bisamides

A series of [2.2]paracyclophane-bisamide regioisomers and alkylated comparators were designed, synthesized, and characterized in order to better understand the transannular hydrogen bonding of [2.2]paracyclophane-based molecular recognition units. X-Ray crystallography shows that transannular hydrogen bonding is maintained in the solid-state, but no stereospecific self-recognition is observed. The assignment of both transannularly and intermolecularly hydrogen bonded N-H stretches could be made by infrared spectroscopy, and the effect of transannular hydrogen bonding on amide bond rotation dynamics is observed by H-1-NMR in nonpolar solvents. The consequences of transannular hydrogen bonding on the optical properties of [2.2]paracyclophane is observed by comparing alkylated and non-alkylated pseudo-ortho 4,12-[2.2]paracyclophane-bisamides. Finally, optical resolution of 4-mono-[2.2]paracyclophane and pseudo-ortho 4,12-[2.2]paracyclophane-bisamides was achieved through the corresponding sulfinyl diastereoisomers for circular dichroism studies. Transannular hydrogen bonding in [2.2]paracyclophane-amides allows preorganization for self-complementary intermolecular assembly, but is weak enough to allow rapid rotation of the amides even in nonpolar solvents.