Date of Award

5-2-2024

Author's School

Graduate School of Arts and Sciences

Author's Department

Chemistry

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

In chapter 1 we will explore the essential background on electrochemistry and anodic cyclization reactions, laying the foundation for understanding the subsequent chapters. In chapter 2, we will explore the mechanistic model established for anodic olefin coupling reactions and the importance of the second oxidation step in the success of these reactions. We showed how a fast second oxidation step can be used to push an anodic cyclization down a kinetic pathway. We will also explore how this step impacts the generation of product in photoelectron-transfer initiated radical cation reactions. It is evident that a fast second oxidation step alone is insufficient to guide a reaction with a slow cyclization to the desired product. The decomposition of the initial radical cation takes place first. Therefore, when planning a cyclization reaction, both steps must be considered and employed to devise a successful process. In chapter 3, we will be examining how a fast second electron oxidation can be used to channel a reaction down a new synthetic pathway. We will examine one such application that reverses the normal reactivity of an imine group to make cyclic proline derivatives. Through including a chiral imine, we showed that we can induce asymmetry into an anodic cyclization. In chapter 4, we will briefly outline the history of our efforts to perform a tandem anodic cyclization along with our most recent efforts to carry out this transformation. This latest effort utilized a fast second oxidation step to drive the first cyclization down a kinetic pathway, ensuring the first ring generated stayed shut. This bought time for the subsequent cyclization to take place and allowed us to successfully perform a tandem cyclization on a model substrate. Efforts to extend this idea to using an imine as a relay group in these transformations proved unsuccessful. We will also explore cyclizations that utilized an acetylene trapping group. By adding a TMS group the acetylene we were able to successfully channel it down a cationic pathway to an allene product. In chapter 5, we will be exploring anodic cyclizations to make a key nitrogen-carbon bond in the alkaloid backbone of the chrysosporazine family of natural products. We will explore how lowering the pKa of N-H of the amide by converting it into a thioamide allowed for deprotonation of this coupling partner so that it could be selectively oxidized to a radical that then triggered the subsequent cyclizations. The cyclizations leading to five-membered rings used ferrocene as the oxidative mediator. However, in the six-membered ring example that directly targeted the chrysosporazine ring skeleton the oxidative mediator was changed to copper acetate. This modification enabled the six-membered ring cyclization to occur with yields comparable to those of the five-membered ring cyclizations. At the end of this chapter, I propose further experiments that need to be carried out in order to successfully synthesize the chrysosporazine family of natural products.

Language

English (en)

Chair and Committee

Kevin Moeller

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