Department of Chemistry, University of Sheffield , Sheffield S3 7HF, U.K.
Department of Chemistry, University of Warwick , Coventry CV4 7AL, U.K.
J Am Chem Soc. 2018 Feb 28;140(8):2821-2828. doi: 10.1021/jacs.7b11334. Epub 2018 Feb 15.
The Kemp elimination (reaction of benzisoxazole with base to give 2-cyanophenolate) is catalyzed in the cavity of a cubic ML coordination cage because of a combination of (i) benzisoxazole binding in the cage cavity driven by the hydrophobic effect, and (ii) accumulation of hydroxide ions around the 16+ cage surface driven by ion-pairing. Here we show how reaction of the cavity-bound guest is modified by the presence of other anions which can also accumulate around the cage surface and displace hydroxide, inhibiting catalysis of the cage-based reaction. Addition of chloride or fluoride inhibits the reaction with hydroxide to the extent that a new autocatalytic pathway becomes apparent, resulting in a sigmoidal reaction profile. In this pathway the product 2-cyanophenolate itself accumulates around the cationic cage surface, acting as the base for the next reaction cycle. The affinity of different anions for the cage surface is therefore 2-cyanophenolate (generating autocatalysis) > chloride > fluoride (which both inhibit the reaction with hydroxide but cannot deprotonate the benzisoxazole guest) > hydroxide (default reaction pathway). The presence of this autocatalytic pathway demonstrates that a reaction of a cavity-bound guest can be induced with different anions around the cage surface in a controllable way; this was confirmed by adding different phenolates to the reaction, which accelerate the Kemp elimination to different extents depending on their basicity. This represents a significant step toward the goal of using the cage as a catalyst for bimolecular reactions between a cavity-bound guest and anions accumulated around the surface.
由于（i）疏水性作用驱动苯并异恶唑在笼腔中结合，以及（ii）离子配对作用驱动在 16+笼表面周围积累氢氧根离子，Kemp 消除（苯并异恶唑与碱反应生成 2-氰基苯酚盐）在立方 ML 配位笼的空腔中被催化。在这里，我们展示了在存在其他阴离子的情况下，空腔结合的客体的反应如何被修饰，这些阴离子也可以在笼表面周围积累并取代氢氧根离子，从而抑制基于笼的反应的催化。加入氯离子或氟离子会在很大程度上抑制与氢氧根离子的反应，从而出现新的自动催化途径，导致反应呈 S 形曲线。在这个途径中，产物 2-氰基苯酚盐本身在阳离子笼表面周围积累，作为下一个反应循环的碱。因此，不同阴离子对笼表面的亲和力为 2-氰基苯酚盐（产生自动催化）> 氯离子 > 氟离子（均抑制与氢氧根离子的反应，但不能使苯并异恶唑客体去质子化）> 氢氧根离子（默认反应途径）。这种自动催化途径的存在表明，通过在笼表面周围存在不同的阴离子，可以以可控的方式诱导空腔结合的客体的反应；通过向反应中添加不同的酚盐来证实这一点，这会根据其碱性在不同程度上加速 Kemp 消除。这是朝着使用笼作为空腔结合的客体与在表面周围积累的阴离子之间的双分子反应的催化剂的目标迈出的重要一步。
