Date of Award

2020

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Graduate Group

Chemistry

First Advisor

Marisa C. Kozlowski

Abstract

Part I: A simple monomeric vanadium species combined with a Brønsted or Lewis acid additive is found to effect the asymmetric oxidative ortho−ortho coupling of simple 2-hydroxycarbazoles with good to excellent levels of conversion and enantioselectivity. Diverse substitution patterns and functionality are well tolerated. mechanistic studies suggest a radical-radical coupling facilitated by a vanadium (V) complex.

Part II: A method for the manganese catalyzed oxidative coupling of ortho-tert-butyl activated tyrosine was developed. High throughput experimentation was utilized to quickly optimize the reaction; isolated yields of up to 90% were obtained. The subsequent de-tert-butylation reactions to afford dityrosine were highly successful. Finally, several attempts to synthesize natural products or biologically active compounds that contain a dityrosine subunit were undertaken. However, to date, none of these attempts have yielded any positive results.

Part III: Attempts to develop a method for the direct oxidative C-O coupling of tyrosine were also unsuccessful. Stoichiometric oxidant and metal salen/an catalyst screens did not reveal the formation of any desired product nor did attempts to form the ether via metalloporphyrins. However, when applied to simpler methoxy phenols, metalloporphyrins and some metal salen catalysts engendered the diaryl ether bond effectively in yields up to 50%.

Part IV: The first, oxidative photocatalytic method for phenol-phenol homo-coupling and cross-coupling is described with isolated yields of up to 97% obtained. Measured oxidation potentials and computed nucleophilicity parameters are consistent with a nucleophilic attack of one partner onto the oxidized radical form of the other partner. Understanding of this model permitted the development of cross-coupling reactions between nucleophilic phenols/arenes. Importantly, easily oxidized phenols proceeded with high selectivity and efficiency. A highlight of this method is that one equivalent of each coupling partner is utilized. Building on these findings, the first non-enzymatic, catalytic method for coupling tyrosine was developed.

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