Establishing Structure–Activity Relationships in Heterogeneous Catalysis of Three-Component Organic Coupling Reactions by Lewis Acidic Metal Sites and Polar Moieties

The postpandemic surge in demand for antimicrobial drugs has accelerated the customization of suitable catalysts, fostering a synergy between their structure and activity in promoting the multicomponent organic coupling reactions. In this work, we have successfully constructed two new polar metal-organic frameworks, viz., <b>Co-bpaipa</b> and <b>Ni-bpaipa</b>, where bpaipa^2- = 5-(bis(pyridin-2-ylmethyl)amino)isophthalate, embedded with catalytically active Co/Ni Lewis acidic metal sites and polar moieties (such as O/N heteroatoms) for a critical evaluation of their role in the synthesis of an important category of antimicrobial drugs, oxazolidinones, from a three-component coupling reactions. Both frameworks feature a rare 2D <i>fes</i> topology and possess high thermal (up to 380 °C) and water stability. Microscopic analysis revealed block- and octagon-shaped surface images of Co and Ni analogs, respectively, at the micrometer scale. Their chemical state and elemental composition were further examined using X-ray photoelectron spectroscopy. For the solvent-free synthesis of 2-aryl oxazolidinones, the use of CO₂ gas as a direct feedstock ensures a sustainable process that also involves epoxides and aromatic amines. The vital aspect of this study is to optimize conditions that are critical for high yields of products under a comparatively milder temperature, a lower catalyst loading, and a shorter reaction time. Interestingly, depending on the metal center, the epoxide-to-aniline ratio influences the formation of oxazolidinones such that the maximum conversion (∼90%) is obtained with <b>Co-bpaipa</b> and <b>Ni-bpaipa</b> using 3:1 and 1:1 ratios, respectively. Such an outcome through a comparison of two catalysts with a difference in the single metal site conducted for the first time is fully supported by investigating the nature and strength of interactions between the reactants and catalysts through comprehensive theoretical simulations, including QTAIM and CBMC analysis. A wide spectrum of substrates with diverse electronic, steric, and polarizing effects is tested to obtain bioactive precursors, particularly tedizolid and delpazolid, achieving high conversion rates (65-94%) and turnover numbers. The postcatalysis analysis of both <b>Co-bpaipa</b> and <b>Ni-bpaipa</b> demonstrates their structural stability and nonleachability, even after multiple catalytic runs.