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.

中文翻译：

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熵的研究：葫芦[n]脲加速糠胺叔胺分子内狄尔斯-阿尔德环加成反应的策略

葫芦[ n ]urils以其主客体化学而闻名，正在成为多功能的仿生受体。在此，我们报道了葫芦[7]脲（CB[7]）将先前难以捉摸且不反应的叔N-甲基-N-（同）烯丙基-2-糠胺的分子内狄尔斯-阿尔德（IMDA）反应加速了高达4倍温和条件下的数量级。使用¹ H NMR 滴定和 ITC 实验，我们表征了配合物不同的热力学和动力学性质。我们还确定了导致 IMDA 反应过渡态的激活参数（Δ G ^≠、Δ H ^≠和 Δ S ^≠），无论是在本体中还是在 CB[7] 中，以阐明受体上观察到的加速度。 CB[7]充当“熵陷阱”，利用客体结合主要支付以高能反应构象重组底物的熵损失，该构象类似于IMDA反应所需的高度有序过渡态的几何形状。这项研究强调了葫芦[ n ]脲作为人工活性位点的潜力，模拟酶催化的特定方面。