Spotlight on Mechanosterics: A Bulky Macrocycle Promotes Functional Group Reactivity in a [2]Rotaxane

Macrocycles typically hinder the reactivity of adjacent functional groups in mechanically interlocked molecules due to steric shielding. Herein, we report a [2]rotaxane in which a bulky macrocycle in fact accelerates deprotection of a Fmoc-derived stopper by 36-fold compared to a non-interlocked control. We rationalize this by a preorganization of the macrocycle and the stopper, exposing its reactive site for base abstraction. This is evidenced by extensive NMR, SC-XRD, and DFT studies, revealing highly directional CH−π interactions and hydrogen bonding between the interlocked components. Our findings highlight and structurally rationalize how entanglement can instead promote reactivity through precise spatial control. This concept paves the way for designing molecular machines with functional, reactivity-enhancing components.大环通常会通过空间位阻屏蔽效应，阻碍机械互锁分子（mechanically interlocked molecules）中相邻官能团的反应活性。本文报道了一种[2]轮烷（[2]rotaxane），其体积庞大的大环反而使Fmoc保护基衍生的封端基团的脱保护反应速率相较于非互锁对照体系提升了36倍。我们通过大环与封端基团的预组织效应对该现象进行合理化阐释：该预组织方式暴露出了可被碱夺取的反应位点。该结论得到了大量核磁共振（NMR）、单晶X射线衍射（SC-XRD）以及密度泛函理论（DFT）研究的证实，结果揭示了互锁组分之间存在高度定向的CH-π相互作用与氢键。我们的研究结果凸显并从结构层面阐释了分子缠结如何通过精准的空间调控反而促进反应活性。这一概念为设计具备功能性且可提升反应活性组分的分子机器开辟了全新路径。