Rendering Solubility Irrelevant: Interfacial Cooperative Catalysis by La2NiO4 Enables Aquachemical Knoevenagel Condensation

Achieving carbon–carbon bond formation in water without relying on substrate solubility remains a fundamental challenge in sustainable chemistry. Herein, we report an “aquochemical” Knoevenagel condensation catalyzed by a layered lanthanum nickelate (La2NiO4) under interfacial (Type IIIc) conditions. The reaction proceeds efficiently even for immiscible liquids and insoluble solids, demonstrating that catalytic turnover is governed by surface interactions rather than bulk dissolution. A wide range of active methylene compounds and challenging electrophiles, including electron-rich and heteroaromatic substrates, are well tolerated. Notably, efficient conversion is achieved even under fully heterogeneous solid–solid–solid conditions. These results highlight interfacial cooperative catalysis as a powerful strategy to transcend solubility limitations in aqueous C–C bond formation.