Selective Hydroxyl Functionalization Using Novel Bifunctional Macrocyclic Catalysts and SuFEx-Based Methodologies

The research behind this dissertation explores innovative strategies for the functionalization of alcohols. Alcohols are abundant in biologically relevant molecules and pharmaceutical drugs, so designing new methods for modifying them has gained significant interest over the years. The first and second chapters of this dissertation focus on the selective functionalization of a particular class of alcohols, amino alcohols, a well-represented functional handle in biomolecules. The hydroxyl functionalization of amino alcohols often demands multiple synthetic steps. We developed a new class of macrocyclic catalysts to enable precise and efficient transformations of amino alcohols, advancing the scope and efficiency of amino alcohol functionalization. The third chapter focuses on using Sulfur(VI) Fluoride Exchange (SuFEx) chemistry to directly deoxy-functionalize alcohols under a mild condition. This SuFEx approach leverages sulfonyl fluoride reagents to enable diverse nucleophilic substitutions on alcohols, particularly in settings where conventional activation methods are inefficient or produce wasteful byproducts. Collectively, this research provides insights into the role of macrocyclic catalysts and SuFEx reagents in selectively functionalizing alcohols and presents a promising, sustainable approach for broadening the synthetic toolkit for alcohol functionalization.