Stereochemical inversion in difunctionalised pillar[5]arenes

Pillar[5]arenes constitute a class of macrocycles which display planar chirality on account of the methylene bridges that link five disubstituted para-phenylene rings together. Dynamic H-1 NMR spectroscopy indicates that A1/A2-dihydroxypillar[5]arene undergoes conformational inversion between its enantiomers with an energy barrier of 11.9kcalmol(-1). This process involving an oxygen-through-the-annulus rotation by all five hydroquinone rings is associated with the breaking of two intramolecular hydrogen bonds between phenolic hydroxyl and methoxyl groups on neighbouring phenylene rings. A combination of molecular mechanics and quantum mechanical calculations reveals that the conformational inversion undergone by A1/A2-dihyroxypillar[5]arene involves the breaking of one of these hydrogen bonds in the rate-limiting step of the process. Not only does the calculated energy of activation (13.8kcalmol(-1)) using density functional theory agree well with the experimentally determined value (13.0 kcal mol(-1)), it also leads to the identification of the lowest energy pseudorotational pathway involving four intermediates and five transition states. While replacing the two hydroxyl groups in A1/A2-dihydroxypillar[5]arene with carbonyl groups leads to much more rapid conformational inversion, placing bromine atoms ortho to the two phenolic hydroxyl groups increases the strength of the intramolecular hydrogen bonds, raising the energy barrier to inversion by 3.9kcalmol(-1).