Supramolecular Catalysis of a Catalysis-Resistant Diels–Alder Reaction: Almost Theoretical Acceleration of Cyclopentadiene Dimerization inside Cucurbituril
journal contributionposted on 31.01.2022, 17:37 by Foad N. Tehrani, Khaleel I. Assaf, Robert Hein, Casper M. E. Jensen, Thomas C. Nugent, Werner M. Nau
In contrast to Diels–Alder reactions involving heteroatom-containing substrates, the endo dimerization of cyclopentadiene responds only very weakly to changes in the microenvironment or the presence of potential catalysts (less than a factor of 10 variations). 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 transition-state confinement [Page, M. I.; Proc. Natl. Acad. Sci. U.S.A. 1971, 68, 1678−1683]. In the presence of different cucurbit[n]uril homologues, the reaction is selectively and almost maximally (kcat/kuncat ca. 4 × 105 M) accelerated by the intermediary-sized cucurbituril 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 and UV spectrophotometry. The analysis of the kinetic data, combined with packing coefficient considerations, modeling of Lennard-Jones potentials, and dispersion-corrected density functional theory (DFT) calculations, suggests that catalysis is due to an entropy-dominated transition-state stabilization in the tightly packed ternary complex.
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packing coefficient considerationsmacrocyclic homologues displayh nmr spectroscopyalmost maximally (<different cucurbit [<pure hydrocarbon reactiondicyclopentadiene reaction product>] uril homologues4 × 1010 variations ).uncat </ sub6 </ sup5 </ sup1 </ supalmost theoretical acceleration7 ] uriln </k </sized cucurbit>< subuv spectrophotometrystrong bindingstate stabilizationstate confinementpotential catalystsmonitored usingkinetic datajones potentialsinhibitory effectentropic contributionsendo dimerizationearly modelcyclopentadiene respondscontaining substratesaqueous solution.; proc