Synthesis of Organosilanes and Investigation of Their Catalytic Activity for Direct Amide Bond Formation

Abstract

<p>Amide synthesis is a fundamental reaction in synthetic chemistry due to the abundance of amides in biologically active molecules, synthetic polymers, and commercial products. Coupling reagents that activate the carboxylic acid have become the most well-studied method to direct amide bond formation. Amongst these, carbodiimides, uronium and phosphonium salts, and benzotriazoles are the most common. These reactions, however, are often limited by poor atom economy, and toxic and expensive reagents. Therefore, synthetic chemists need a better method to form amides safely and efficiently. Organosilanes have been reported as greener, efficient alternative amide coupling reagents. Current work in this field often requires a stoichiometric (or more) amount of the silane. While stoichiometric amide coupling reactions are generally the methods of choice for their efficiency and practicality, catalytic amide coupling can present a new step toward greener methodologies to make amides. This thesis explores novel organosilanes that are investigated as catalysts for direct amidation. The silane catalysts are designed to have enhanced reactivity by incorporating a hydrogen bond donor (HBD) to facilitate the formation of a silyl ester intermediate and nucleophilic attack at the carbonyl by the amine coupling partner. The synthesis of various organosilanes have been investigated, including silanes that have an amide or urea, hydroxy, or protonated amine as a HBD. The silanes that have been successfully synthesized were tested as catalysts in direct amidation. Aryl and alkyl silanes, and di- and trisubstituted silanes were used in stoichiometric silane-mediated amide synthesis to study how the substitution on the silicon effects amidation.</p>