Abstract

Phase-Transfer Deracemization, Development of Reagents for Electrophilic Trifluoromethylation, and Hydrogen-Mediated Deoxydehydration

by

Andrew Vivek Samant

Doctor of Philosophy in Chemistry

University of California, Berkeley

Professor F. Dean Toste, Chair

As is often the case in the chemical sciences, the research presented here represents a path that followed naturally from one step to the next in the laboratory while ending up in seemingly disparate areas of focus at the end of each project.

Chapter 1 describes the development of a purely chemical deracemization system. Typical asymmetric reactions fall into two categories: those where the starting material must be transformed into a new compound, and those where enantioenriched starting materials can be recovered in a maximum of 50% yield. Deracemization is an alternate strategy which can generate enantioenriched starting material in 100% maximum yield. The major challenge to implementing a successful chemical deracemization is that, on its own, solution-phase deracemization is always thermodynamically unfavorable. In order to circumvent this, we developed a system where the deracemization process could be chemically pumped by coupling it to the quenching of a strong oxidant and a strong reductant. In particular, we used a phase-transfer strategy to promote selective reaction of the substrate with both a cationic, water-soluble oxidant and a highly insoluble reductant, rather than having the oxidant and reductant react directly with one another.

An interest in cationic reagents similar to the oxidant used to accomplish deracemization led (albeit quite indirectly) to the development of the reagents described in Chapter 2. Widely used iodine(III)-based electrophilic trifluoromethyling agents (e.g. Togni reagents) are typically neutral species, which require activation by a Lewis acid in order to trifluoromethylate nucleophiles such as alcohols and imidazoles. In contrast, we have developed a new class of trifluoromethyliodonium chlorides, which possess a high degree of cationic character and are capable of accomplishing these trifluoromethylations in the absence of an activator. Furthermore, we have demonstrated that these iodonium chlorides serve as good surrogates for reactive intermediates produced during acid-mediated trifluoromethylation. This equivalence has allowed us to gain a better understanding of these systems and has led to observations that could aid in the development of even more effective classes of reagent in the future.

Chapter 3 describes a new and promising method for the conversion of biomass into commodity chemicals. Most modern commercial biomass conversion relates to the transformation of lipids (e.g. triglycerides) into chemically simple biofuels. Carbohydrate-based feedstocks, which include abundant natural resources such as glucose and cellulose, have the potential to be converted into more complex monomers and fine chemicals. In the course of our research, we developed a system capable of reducing sugar-derived compounds, such as glucaric acid and its derivates, directly to commercially relevant starting materials such as adipate esters using hydrogen gas as the reductant. This dual-catalytic system uses palladium on carbon to activate hydrogen gas and high-valent soluble rhenium catalysts to deoxygenate polyols. Additionally, we have investigated the unusual alpha,beta-selectivity that this deoxydhydration system provides, and used to selectively convert ribonolactone and gluconolactone into compounds which retain a high degree of chemical complexity but are less highly oxygenated than the starting materials.