Issue 23, 2024

Investing in entropy: the strategy of cucurbit[n]urils to accelerate the intramolecular Diels–Alder cycloaddition reaction of tertiary furfuryl amines

Abstract

Cucurbit[n]urils, renowned for their host–guest chemistry, are becoming versatile biomimetic receptors. Herein, we report that cucurbit[7]uril (CB[7]) accelerates the intramolecular Diels–Alder (IMDA) reaction for previously elusive and unreactive tertiary N-methyl-N-(homo)allyl-2-furfurylamines by up to 4 orders of magnitude under mild conditions. Using 1H NMR titrations and ITC experiments, we characterize the dissimilar thermodynamic and kinetic properties of the complexes. We also determine the activation parameters (ΔG, ΔH and ΔS) leading to the transition state of the IMDA reactions, both in the bulk and included in CB[7], to shed light on the key role of the receptor on the acceleration observed. CB[7] acts as an “entropy trap” utilizing guest binding to primarily pay the entropy penalty for reorganizing the substrate in a high-energy reactive conformation that resembles the geometry of the highly ordered transition state required for the IMDA reaction. This study underscores the potential of cucurbit[n]urils as artificial active sites, emulating specific aspects of enzymatic catalysis.

Graphical abstract: Investing in entropy: the strategy of cucurbit[n]urils to accelerate the intramolecular Diels–Alder cycloaddition reaction of tertiary furfuryl amines

Associated articles

Supplementary files

Article information

Article type
Edge Article
Submitted
18 Mar 2024
Accepted
02 May 2024
First published
03 May 2024
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2024,15, 8841-8849

Investing in entropy: the strategy of cucurbit[n]urils to accelerate the intramolecular Diels–Alder cycloaddition reaction of tertiary furfuryl amines

K. de la Vega-Hernández, M. G. Suero and P. Ballester, Chem. Sci., 2024, 15, 8841 DOI: 10.1039/D4SC01816H

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