(352e) Understanding Intramolecular Cooperativity in Acid-Base Silica-Supported Organocatalysts

Carbon-carbon coupling reactions are essential steps in many chemical syntheses including pharmaceutical production and biomass valorization. Highly selective carbon-carbon bond formation steps are commonly performed with expensive homogeneous transition metal-complex catalysts, which suffer from process and scaling limitations. Heterogeneous organocatalysts, a class of enzyme-inspired catalysts which may be synthetically tuned and can incorporate multiple functionalities, are being investigated as possible immobilized and robust alternatives for various transformations. Weakly acidic mesoporous silica may be readily grafted with functional groups such as amines to form acid-base catalysts. Motivated by evidence that intramolecular cooperativity in bifunctional chemical moieties could provide additional benefit over catalysts with solely intermolecular cooperative interactions between grafted and surface species, this project studies how the alkyl linker length between the amine and alcohol moieties of the grafted alkanolamine silanes affect their intramolecular cooperativity. In order to isolate this activity, a parallel series of catalysts were synthesized with HMDS-capped surface silanols, removing the potential for intermolecular cooperativity between grafted amines and surface silanols. Kinetic studies of the acid-base catalyzed aldol condensation of 4-nitrobenzaldehyde and acetone were performed to determine relative catalyst activities and site-specific rates. Alkanolamine catalyst activity showed minimal dependence on alkyl linker length beyond 2 carbons, with comparable rates across 3-5 carbon spacings. Capped catalysts with solely intramolecular cooperative capabilities, however, were found to have activities strongly dependent on linker length. The capped 5 carbon linker catalyst was at least as active as the best uncapped catalyst, indicating effective catalytic cooperativity with a single bifunctional moiety.