A 2D Chemically Stable Cu‐MOF for Green Synthesis of Bioactive 4H‐Pyran Derivatives

Abstract Metal–organic frameworks (MOFs) are widely used as heterogeneous catalysts, offering high densities of tunable active sites for multicomponent organic transformations. However, the development of catalytically efficient and chemically robust 2D MOFs remains a significant challenge, especially under harsh reaction conditions. Herein, we report the green synthesis of a 2D robust mixed‐ligand based Cu(II)‐MOF, IITKGP‐54 , demonstrating exceptional chemical stability in water and across a wide range of aqueous pH‐solutions (pH = 2–10). Owing to the accessible Lewis acidic open metal sites (OMSs), IITKGP‐54 exhibits superior catalytic activities toward rarely explored three‐component condensation reaction to produce pharmacologically important 2‐amino‐3‐cyano‐4H‐pyran derivatives, offering several advantages including low catalyst loading, operation in green solvent, broad substrate compatibility and excellent recyclability without structural degradation, which highlights its superiority as environmentally benign heterogeneous catalyst for this transformation over other homogeneous and heterogeneous catalysts used earlier. IITKGP‐54 expands the utility of 2D MOF catalysts for one‐pot sustainable synthesis of bioactive 4H‐pyran derivatives.