Dissertation

Investigations into the Development of New Methodologies for Organic Electrochemistry

Seastram, Alex

2022

Overview

This thesis describes investigations into the development of new electrochemical methodologies applicable to organic synthesis. Initial investigations were focused on the development of new strategies for the generation and utilisation of alkoxy radicals under electrochemical conditions. To this end, a new procedure for an electrochemical manganese-catalysed deconstructive chlorination of cycloalkanols was developed. In this study, tertiary cyclopropanols and cyclobutanols were conveniently converted into synthetically useful distally chlorinated ketones via alkoxy radical intermediates. This methodology utilises an inexpensive manganese (II) pre-catalyst to facilitate the synthesis of a diverse range of β- and γ-chloroketones (40 examples, 30-90% yield). Facile scale-up was also performed by employing a recirculating flow-electrochemistry system and mechanistic investigations, including the use of cyclic voltammetry, allowed the proposal of alkoxy radical intermediates. Further work on the electrochemical generation of alkoxy radicals was then performed to overcome the limitations associated with the manganese-catalysed method. This work centred around the use of cerium (III) or (IV) salts to generate alkoxy radicals under electrochemical conditions. Following these unsuccessful investigations, the development of a photoelectrochemical system for the cerium-mediated generation of alkoxy radicals was subsequently explored. Chapter 4 of this thesis then describes investigations into an electrochemical alkene hetero-difunctionalisation procedure that proceeds via a 1,4-nitrile migration. In this study, cyanohydrin substrates bearing a distal alkene were converted into synthetically useful 1,2-azidonitriles using a manganese (II) salt as an azide transfer reagent (28 examples, 27-75% yield). This methodology was then extended to perform electrochemical alkene sulfonylcyanation and trifluoromethylcyanation, as well as to access a trifunctionalised hexanenitrile from a functionalised malononitrile starting material. The utility of the products formed was demonstrated through orthogonal derivatisation, and mechanistic investigations, including cyclic voltammetry studies and a radical clock experiment, allowed the proposal of radical intermediates within the reaction mechanism.

• Publisher: ProQuest Dissertations & Theses
• Subject: Voltammetry