Supramolecular Catalysis of a Catalysis-Resistant Diels-Alder Reaction: Rapid Dimerization of Cyclopentadiene inside Cucurbit[7]uril

In contrast to Diels-Alder reactions involving heteroatom-containing substrates, the endo dimerization of cyclopentadiene responds only very weakly to changes in microenvironment or the presence of potential catalysts (less than factor of 10 variation), although this pure hydrocarbon reaction has been used as an early model to predict the maximum possible catalytic effect (kcat/kuncat ca. 106 M) due to entropic contributions of a transition-state confinement (Page, M. I.; Jencks, W. P. Proc. Natl. Acad. Sci. USA 1971, 68, 1678). In the presence of cucurbit[n]uril homologues the reaction is selectively and almost maximally (kcat/kuncat ca. 4 × 105 M) accelerated by the intermediary sized cucurbit[7]uril in aqueous solution, while the other macrocyclic homologues display no acceleration or an inhibitory effect. The expected product inhibition due to the strong binding of the dicyclopentadiene reaction product can be overcome by addition of 10% methanol, which affords catalytic turnover numbers above 10. The reaction was monitored using 1H NMR spectroscopy as well as UV spectrophotometry. The analysis of the kinetic data, combined with packing coefficient considerations, modelling of Lennard-Jones potentials, and dispersion-corrected DFT calculations, suggest that the catalysis is due to an entropy-dominated transition-state stabilization in the tightly packed ternary complex.