Graduate Studies

 

First Advisor

Patrick H. Dussault

Degree Name

Doctor of Philosophy (Ph.D.)

Committee Members

Andrej Rajca, Barry Cheung, James Checco, Kenneth Nickerson

Department

Chemistry

Date of this Version

8-2025

Document Type

Dissertation

Citation

A dissertation presented to the Graduate College of the University of Nebraska in partial fulfillment of requirements for the degree of Doctor of Philosophy

Major: Chemistry

Under the supervision of Professor Patrick H. Dussault

Lincoln, Nebraska, August 2025

Comments

Copyright 2025, Amber Marie Schuster. Used by permission

Abstract

I. SET CLEAVAGE OF PEROXIDES: INFLUENCE OF REDUCTANT AND PEROXIDE ON THE RATE AND MODE OF ALKOXY RADICAL FORMATION

The reductive cleavage of organic peroxides to generate alkoxy radicals is frequently accomplished via single-electron transfer (SET) from a reductant. Previous reports employ either symmetrical peroxides or peroxides with predictable cleavage behavior, such as peresters. We were interested in how the structure of the peroxide and the nature of the reducing system combine to impact the rate of reaction and the selectivity for alkoxy radical formation during cleavage of unsymmetric peroxides. In this dissertation, one will find the reactions of a family of peroxides (dialkyl peroxides, peroxyacetal, perester, alkyl/silyl peroxide, hydroperoxide) based upon a shared radical clock skeleton with a number of reductants, including three photoredox systems of varying potential. The observed outcomes demonstrate clear substrate- and reductant-dependent differences in the rate and selectivity of SET cleavage. These findings will allow researchers to selectively form desired alkoxy radicals by altering the reaction conditions.

II. INVESTIGATIONS OF A MODULAR SYNTHETIC ROUTE TO DT3 AND GT3 TOCOTRIENOLS AS RADIOPROTECTIVE TARGETS

With the increased risk of nuclear warfare attacks across the world, it is critical to have both a safe and potent radioprotective agent for nuclear emergencies. Both γ-tocotrienol (GT3) and δ-tocotrienol (DT3) have been shown to act as effective radioprotectants. Isolation of GT3 and DT3 from natural sources can be achieved, but the resulting yield is very low due to a low natural abundance. Furthermore, the current synthetic approaches are lengthy, costly, and yield products with multiple stereoisomers. This dissertation chapter discusses the key features in the tocotrienol structure that are important for total synthesis and outlines previous synthetic approaches towards GT3 and DT3 tocotrienols.

III. INVESTIGATIONS INTO THE REDUCTIVE CLEAVAGE OF PEROXIDES WITH ORGANOCOPPER REAGENT

Ethers are important functional groups found widely in natural products and man-made materials. Approaches towards ether formation most commonly rely on the reaction of a nucleophilic oxygen with an electrophilic carbon. The polarity-reversed version of this transformation involves generation of ethers through the reaction of nucleophilic carbon with electrophilic oxygen. organomagnesium nucleophiles; the synthesis of tertiary ethers (containing a tertiary C-O bond) through reaction of Grignard reagents with tertiary peresters remains an important synthetic method. It was later discovered that ethers could be generated from reactions of dialkyl peroxides and organolithium compounds, but good yields were restricted to unhindered substrates. Our lab has explored the reactivity of peroxides towards organomagnesium and organolithium compounds and found that monoperoxyacetals exhibit enhanced reactivity compared to dialkyl and alkyl/silyl peroxides, efficiently transferring primary, secondary, and tertiary alkoxides to form ethers. However, these transformations rely upon strongly basic organolithium and organomagnesium nucleophiles. This dissertation work aims to expand this methodology to allow efficient ether formation using less basic organometallic nucleophiles, with an initial emphasis on organocopper reagents.

Advisor: Patrick H. Dussault

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