Unravelling the mechanistic ‘Black Box’ of heterogeneous condensation reactions catalyzed by aminosilicas

Primary amino-functionalized silicas (H₂N-SiO₂) are well known acid-base cooperative catalysts for many organic transformations, including carbon–carbon (C–C) bond forming condensation reactions, and much attention has been devoted to the elucidation of their action mode. However, to our surprise, the mechanism of Henry reactions and Knoevenagel condensations catalyzed by H₂N-SiO₂ is still paradoxical, and the identity of the actual base species, transition states, reactivity, and product selectivity, remain as debatable topics of discussion. Herein we propose a brand-new reaction mechanism for H₂N-SiO₂-catalyzed Henry reactions that overcomes all prior inconsistencies. With the aid of Hammett analysis and density functional theory (DFT) calculations, we have effectively identified several critical transition states and are able to explain reactivity and product selectivity. This study revealed that H₂N-SiO₂ catalyzed Henry reactions of aldehydes and nitro compounds follow the imine mechanism to afford olefin adducts as only possible products. In addition, we utilized our findings to comprehend the mechanism of Knoevenagel condensation, a comparable reaction, dispelling a more than two-decade old misconception regarding the nature of the active base involved.