Ludden Michael D, Taylor Christopher G P, Tipping Max B, Train Jennifer S, Williams Nicholas H, Dorrat Jack C, Tuck Kellie L, Ward Michael D
Department of Chemistry, University of Warwick Coventry CV4 7AL UK
Department of Chemistry, University of Sheffield Sheffield S3 7HF UK.
Chem Sci. 2021 Oct 25;12(44):14781-14791. doi: 10.1039/d1sc04887b. eCollection 2021 Nov 17.
An octanuclear ML coordination cage catalyses the Kemp elimination reaction of 5-nitro-1,2-benzisoxazole (NBI) with hydroxide to give 2-cyano-4-nitrophenolate (CNP) as the product. In contrast to the previously-reported very efficient catalysis of the Kemp elimination reaction of unsubstituted benzisoxazole, which involves the substrate binding inside the cage cavity, the catalysed reaction of NBI with hydroxide is slower and occurs at the external surface of the cage, even though NBI can bind inside the cage cavity. The rate of the catalysed reaction is sensitive to the presence of added anions, which bind to the 16+ cage surface, displacing the hydroxide ions from around the cage which are essential reaction partners in the Kemp elimination. Thus we can observe different binding affinities of anions to the surface of the cationic cage in aqueous solution by the extent to which they displace hydroxide and thereby inhibit the catalysed Kemp elimination and slow down the appearance of CNP. For anions with a -1 charge the observed affinity order for binding to the cage surface is consistent with their ease of desolvation and their ordering in the Hofmeister series. With anions that are significantly basic (fluoride, hydrogen carbonate, carboxylates) the accumulation of the anion around the cage surface accelerates the Kemp elimination compared to the background reaction with hydroxide, which we ascribe to the ability of these anions to participate directly in the Kemp elimination. This work provides valuable mechanistic insights into the role of the cage in co-locating the substrate and the anionic reaction partners in a cage-catalysed reaction.
一种八核ML配位笼催化5-硝基-1,2-苯并异恶唑（NBI）与氢氧根发生肯普消除反应，生成产物2-氰基-4-硝基苯酚盐（CNP）。与之前报道的对未取代苯并异恶唑肯普消除反应的高效催化不同，之前的反应涉及底物在笼腔内部的结合，而NBI与氢氧根的催化反应较慢，且发生在笼的外表面，尽管NBI能够在笼腔内结合。催化反应的速率对添加阴离子的存在很敏感，这些阴离子会与带16 +电荷的笼表面结合，将笼周围的氢氧根离子取代，而氢氧根离子是肯普消除反应中必不可少的反应伙伴。因此，我们可以通过阴离子取代氢氧根的程度以及由此抑制催化的肯普消除反应并减缓CNP出现的程度，来观察阴离子在水溶液中与阳离子笼表面的不同结合亲和力。对于带 -1电荷的阴离子，观察到的与笼表面结合的亲和力顺序与它们的去溶剂化难易程度及其在霍夫迈斯特序列中的排序一致。对于碱性较强的阴离子（氟离子、碳酸氢根、羧酸盐），与氢氧根的背景反应相比，笼表面周围阴离子的积累加速了肯普消除反应，我们将此归因于这些阴离子直接参与肯普消除反应的能力。这项工作为笼在笼催化反应中共同定位底物和阴离子反应伙伴的作用提供了有价值的机理见解。
