Department of Organic Chemistry, University of Geneva , Geneva, Switzerland.
J Am Chem Soc. 2014 Feb 5;136(5):2101-11. doi: 10.1021/ja412290r. Epub 2014 Jan 23.
The introduction of new noncovalent interactions to build functional systems is of fundamental importance. We here report experimental and theoretical evidence that anion-π interactions can contribute to catalysis. The Kemp elimination is used as a classical tool to discover conceptually innovative catalysts for reactions with anionic transition states. For anion-π catalysis, a carboxylate base and a solubilizer are covalently attached to the π-acidic surface of naphthalenediimides. On these π-acidic surfaces, transition-state stabilizations up to ΔΔGTS = 31.8 ± 0.4 kJ mol(-1) are found. This value corresponds to a transition-state recognition of KTS = 2.7 ± 0.5 μM and a catalytic proficiency of 3.8 × 10(5) M(-1). Significantly increasing transition-state stabilization with increasing π-acidity of the catalyst, observed for two separate series, demonstrates the existence of "anion-π catalysis." In sharp contrast, increasing π-acidity of the best naphthalenediimide catalysts does not influence the more than 12 000-times weaker substrate recognition (KM = 34.5 ± 1.6 μM). Together with the disappearance of Michaelis-Menten kinetics on the expanded π-surfaces of perylenediimides, this finding supports that contributions from π-π interactions are not very important for anion-π catalysis. The linker between the π-acidic surface and the carboxylate base strongly influences activity. Insufficient length and flexibility cause incompatibility with saturation kinetics. Moreover, preorganizing linkers do not improve catalysis much, suggesting that the ideal positioning of the carboxylate base on the π-acidic surface is achieved by intramolecular anion-π interactions rather than by an optimized structure of the linker. Computational simulations are in excellent agreement with experimental results. They confirm, inter alia, that the stabilization of the anionic transition states (but not the neutral ground states) increases with the π-acidity of the catalysts, i.e., the existence of anion-π catalysis. Preliminary results on the general significance of anion-π catalysis beyond the Kemp elimination are briefly discussed.
引入新的非共价相互作用来构建功能系统至关重要。我们在此报告实验和理论证据，表明阴离子-π 相互作用可以有助于催化。Kemp 消除被用作发现具有阴离子过渡态的反应的概念创新催化剂的经典工具。对于阴离子-π 催化，羧酸根基和增溶剂通过共价键连接到萘二酰亚胺的π-酸性表面上。在这些π-酸性表面上，发现过渡态稳定化高达ΔΔGTS = 31.8 ± 0.4 kJ mol(-1)。这对应于过渡态识别 KTS = 2.7 ± 0.5 μM 和催化效率 3.8 × 10(5) M(-1)。对于两个独立系列，观察到随着催化剂的π-酸性增加而显著增加过渡态稳定性，这表明存在“阴离子-π 催化”。与此形成鲜明对比的是，最佳萘二酰亚胺催化剂的π-酸性增加不会影响超过 12000 倍的弱底物识别（KM = 34.5 ± 1.6 μM）。与在苝二酰亚胺的扩展π-表面上消失的米氏动力学一起，这一发现支持π-π 相互作用的贡献对于阴离子-π 催化不是很重要。π-酸性表面和羧酸根基之间的连接体强烈影响活性。长度和灵活性不足会导致与饱和动力学不兼容。此外，预组织连接体并不能大大提高催化作用，这表明羧酸根基在π-酸性表面上的理想定位是通过分子内阴离子-π 相互作用而不是通过连接体的优化结构来实现的。计算模拟与实验结果非常吻合。它们除其他外证实，特别是阴离子过渡态的稳定化（而不是中性基态）随着催化剂的π-酸性增加而增加，即存在阴离子-π 催化。简要讨论了阴离子-π 催化在 Kemp 消除之外的一般意义的初步结果。
