Kim Soo Bok, Koo Byeong Jun, Lee Sun Bu, Kim Woo Hee, Bae Han Yong
Department of Chemistry, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
Acc Chem Res. 2025 Jul 1;58(13):1997-2015. doi: 10.1021/acs.accounts.5c00187. Epub 2025 Jun 17.
ConspectusWater, an environmentally friendly and benign reaction medium, has traditionally been underestimated for its use in organic synthesis because it offers limited substrate solubility and can lead to undesired side reactions. However, recent studies have demonstrated that water can actively participate in catalysis, significantly enhancing reactivity and selectivity. The unique physicochemical properties of water can unlock reactivity paradigms that are inaccessible using conventional organic solvents.Since 2022, our research group has been systematically examining the impact of bulk water on catalytic performance, particularly in super Brønsted acid/base catalysis, -heterocyclic carbene (NHC) catalysis, energy transfer (EnT) photocatalysis, and single electron transfer (SET) photocatalysis. By investigating the water-induced rate acceleration and selectivity enhancement, we developed a series of catalytic systems that take advantage of the hydrophobic-effect-induced high-pressure-like effects at aqueous interfaces.This Account summarizes our recent efforts in water-enhanced catalysis and showcases how different catalytic systems benefit from aqueous conditions. Our studies on superacid catalysis revealed that water not only stabilizes key reactive intermediates but also promotes the selective formation of α-tertiary amines through Petasis-type allylation reactions. Similarly, superbase catalysis has enabled exceptional reactivity in SuFEx click chemistry, facilitating C-C and C-S bond formation with ppm-level catalyst loadings. Expanding beyond classical organocatalysis, we also explored NHC catalysis, in which water enhances aza-Michael additions. In addition, EnT photocatalysis has been developed in which aqueous-phase photocatalysis facilitates dearomative cycloadditions through a Dexter-type triplet energy transfer mechanism. Furthermore, photocatalysis in water has emerged as a powerful tool for SET processes, accelerating radical-mediated Giese-type transformations in bulk water with remarkable efficiency. The implications of these findings extend far beyond synthetic methodology. Water-enhanced catalysis offers a sustainable approach to catalysis, reduces reliance on toxic organic solvents, and improves reaction outcomes. Additionally, their ability to mediate high-efficiency transformations in aqueous media opens new opportunities in chemical biology, materials science, hydrometallurgy, and sustainable synthesis. Our research aims to expand the scope of water-enhanced catalytic systems, including their applications in diverse catalysis and biorelevant chemistry, further solidifying the role of bulk water as an active participant in modern catalytic processes.
综述
水，作为一种环境友好且温和的反应介质，传统上因其在有机合成中底物溶解度有限且可能导致不期望的副反应，而在有机合成中的应用一直被低估。然而，最近的研究表明，水能够积极参与催化过程，显著提高反应活性和选择性。水独特的物理化学性质能够开启使用传统有机溶剂无法实现的反应模式。
自2022年以来，我们的研究团队一直在系统地研究大量水对催化性能的影响，特别是在超强布朗斯特酸/碱催化、氮杂环卡宾（NHC）催化、能量转移（EnT）光催化和单电子转移（SET）光催化方面。通过研究水诱导的速率加速和选择性增强，我们开发了一系列利用水相界面处疏水效应诱导的类似高压效应的催化体系。
本综述总结了我们在水增强催化方面的近期工作，并展示了不同的催化体系如何从水相条件中受益。我们对超酸催化的研究表明，水不仅能稳定关键的反应中间体，还能通过Petasis型烯丙基化反应促进α-叔胺的选择性形成。同样，超强碱催化在硫氟交换点击化学中展现出卓越的反应活性，以ppm级别的催化剂负载量促进碳-碳和碳-硫键的形成。除了经典的有机催化，我们还探索了NHC催化，其中水增强了氮杂-Michael加成反应。此外，还开发了EnT光催化，其中水相光催化通过Dexter型三重态能量转移机制促进脱芳构化环加成反应。此外，水中的光催化已成为SET过程的有力工具，能在大量水中高效加速自由基介导的吉斯型转化反应。
这些发现的意义远远超出了合成方法学的范畴。水增强催化提供了一种可持续的催化方法，减少了对有毒有机溶剂的依赖，并改善了反应结果。此外，它们在水介质中介导高效转化的能力为化学生物学、材料科学、湿法冶金和可持续合成开辟了新的机遇。我们的研究旨在扩大水增强催化体系的范围，包括其在各种催化和生物相关化学中的应用，进一步巩固大量水作为现代催化过程中积极参与者的作用。
