Stereochemical inversion in difunctionalised pillar[5]arenes

AbstractPillar[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 1H NMR spectroscopy indicates that A1/A2-dihydroxypillar[5]arene undergoes conformational inversion between its enantiomers with an energy barrier of 11.9 kcal mol− 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 (13.8 kcal mol− 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 3.9 kcal mol− 1.Keywords:: dynamic NMR spectroscopymolecular symmetrypillararenesstereochemical inversiontopic relationships AcknowledgementsThe research at Northwestern University (NU) is a result of a collaboration with the National Center for Nano Technology Research at the King Abdulaziz City for Science and Technology (KACST) in Saudi Arabia. We thank Dr Amy Sarjeant and Charlotte Stern for performing the single-crystal X-ray crystallography data collection, Saman Shafaie for collecting high-resolution mass spectrometric data and the QUEST high-performance computing center at NU for allocation of computer time. NLS thanks the National Science Foundation (NSF) for a Graduate Research Fellowship and STS thanks the International Institute for Nanotechnology (IIN) at NU for a postdoctoral fellowship.