UC Berkeley

Chapter 1. An overview of enantioselective catalysis in supramolecular hosts is presented. A brief background of the main principles of supramolecular cage catalysis and types of hosts commonly utilized is given to provide context for an overview of the state of homogenous enantioselective supramolecular catalysis. This discussion outlines work towards catalysis approaches during the 21st century of thermally catalyzed reactions. The potential for supramolecular catalysts to complement existing state-of-the-art organocatalysts and transition metal catalysts for difficult synthetic transformations is noted and opportunities to advance the field toward this goal are highlighted.Chapter 2. A brief description of the state of enantioselective reductions of oximes to hydroxylamines is presented. An introduction to oximes and hydroxylamines as relevant functional groups is given before state-of-the-art approaches towards enantioselective oxime reductions to hydroxylamines and outstanding challenges are discussed. Chapter 3. The development and application of an enantiopure Ga4L6 host catalyst system for enantioselective oxime reductions is presented. Particular emphasis in this work is directed toward gaining insight into the interactions and features relevant for enantioinduction in the host with these substrates. Application of the supramolecular host system enabled an expanded range of reducible oximes. Reaction scope and mechanistic study informed resulting data science analysis of potential interactions in the catalytic system. In addition to steric effects, exhibited through a high degree of size and shape recognition, electronic effects were also found to be important for enantioinduction of some substrates. This work serves as proof-of-concept for supramolecular hosts’ potential to complement existing catalytic scaffolds and helps lay the foundation for future study into the mechanism of enantioinduction in these hosts. Chapter 4. Initial results towards an expanded reaction scope and improved understanding of enantioselective reductions in a supramolecular M4L6 system are presented. This work is designed to further build on the findings of Chapter 3. The ability to modulate and improve enantioselectivity of oximes by tuning host scaffold, namely host metal identity and spacer group, is explored. The use of pyridine borane reductant to tune enantioselectivity is also discussed. These findings are used to inform ongoing work towards the enantioselective reductions of ketones and indoles, both poorly selective substrate classes under initial conditions. Enantiodivergent behavior of substrates based on both host and pyridine borane identity is revealed.