Water-Enhanced Catalysis: A Broadly Applicable Strategy for Promoting Reactivity and Selectivity in Diverse Chemical Reactions.

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.