Charge-Enhanced Organocatalysts: Synthesis and Application Toward Symmetric and Asymmetric Reactions

Abstract

Hydrogen bonds are ubiquitous in Nature and are the principal interaction through which enzymes catalyze reactions. Brønsted acid organocatalysts mimic this process and present a greener alternative to metal-based species as the former do not contribute to the consumption of limited metal resources or the production of toxic metal wastes. Despite these benefits, organocatalysts have remained underutilized in industrial processes because they typically have low activity compared to their inorganic counterparts. In 2015, the Kass group demonstrated that Brønsted acidity and organocatalytic activity could be significantly enhanced in low-polarity media through the incorporation of formal positive charges. This principle has since been extended to common organocatalyst scaffolds such as thioureas and phosphoric acids. This dissertation details the further enhancement of Brønsted acidity in low-polarity solvents by the concerted action of positive charges and electron-withdrawing groups and a study on the implications of catalyst acidity on the rate of Friedel–Crafts alkylation reactions. In addition, the interactions of charged thioureas and Brønsted acidic co-catalysts are explored and the charge-enhanced acidity approach is extended to asymmetric TADDOL organocatalysis.