Photochemical Methods for the Construction of C-C and C-X Bonds

Abstract

This thesis encompasses photochemical methods for the construction of C-C and C-X bonds. Following an introduction on the challenges with photochemistry, early work in photoredox catalysis and the application of continuous processing for photochemical reactions are three research chapters. Chapter 2 discloses the development of a photoredox-catalysed dehydrogenative cross-coupling reaction between aldehydes and alkylarenes in continuous flow. In the process, the reaction was adapted to a flow set-up, further optimised and expanded to prepare a range of α-aryl ketones including drug derivatives. Furthermore, the application of flow reactors towards multi-gram scale-up was investigated and in doing so, a previously unreported method to recycle the iridium photocatalyst was established. Chapter 3 contains a new method to prepare β-spiropyrrolidines using visible-light-driven photocatalysis. By adapting and re-optimising a photocatalytic pyrrolidine ring forming reaction developed within the Ley group, a range of β-spiropyrrolidines were prepared. In addition, the reaction was shown to be well-suited to a flow set-up and was successfully executed on a decagram scale. The products were then derivatised at the halomethyl substituent formed on the pyrrolidine ring. Finally, a brief investigation into the preparation of piperidine rings with this strategy was made. Chapter 4 investigates new methods to access sulfonyl compounds via sulfinate salts. This began with the development of a photoredox-catalysed sulfinate preparation using a previously unexplored piperidine-SO2 surrogate. With this reaction, a variety of alkyl and aryl sulfones were prepared by quenching of the generated sulfinates, including drug derivatives. Following this, a pilot study into a new nitro-sulfinate reductive coupling strategy was conducted to access sulfonamides directly from sulfinates. In doing so, two sets of general conditions were established that enabled access to a selection of N-heteroaryl sulfonamides, that were previously inaccessible with alternative reductive coupling methods.