Thesis
Single electron transfer reactions mediated by photoredox catalysis or potassium metal
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2024
- Thesis identifier
- T17040
- Person Identifier (Local)
- 202066179
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- This thesis consists of four chapters of background chemistry, results and discussion, conclusions and future work. The aim of the work presented in these chapters is to investigate either the photoredox catalysed functionalisation of aryl alkyl ethers or the potassium metal-mediated reductive coupling of arenes. Chapter 1 – Photoredox-Mediated Giese-Type Coupling of Aryl Alkyl Ethers Photoredox catalysis is a rapidly expanding area of chemical research. Furthermore, within this area a relatively new and exciting prospect is the use of organic photoredox catalysts to replace traditional metal complexes which tend to contain expensive precious metals such as ruthenium and iridium. In particular, acridinium-based salts have emerged as extremely capable and efficientcatalysts for reactions involving photooxidation. The work reported in Chapter 1 demonstrates the use of a particular acridinium photocatalyst (Acr) to oxidise aryl ether substrates (i) with the aim of functionalising in the α-carbon position relative to the ether oxygen atom (Scheme 1). Oxidation of the aryl ether ring facilitates deprotonation of the α-carbon to afford an α-aryloxyalkyl radical iii. This radical is then trapped by an appropriately electron-poor alkene substrate thereby forming a new C(sp3)–C(sp3) bond to give product iv. This chemistry has been successfully applied to an array of electronically and sterically different aryl ethers and alkene substrates to afford new C–C bonded compounds, most of which are novel. Further studies provide evidence to support the proposed oxidation/deprotonation reaction pathway. Scheme 1: Photoredox-mediated alkylaon of aryl alkyl ethers with Giese acceptors. Chapter 2 – Application to Late-Stage Functionalisation The late-stage diversification of complex drug molecules is a very important practice as it enables the rapid development of compound libraries for testing through efficient and selective functionalisation of existing intricate compounds. Late-stage C–H bond modification in particular has received much interest recently due to the prevalence of C–H bonds across chemistry. Thus, the work presented in Chapter 2 addresses the attempts made to apply the photoredox catalysed C–H functionalisation process developed in Chapter 1 to the late-stage alteration of marketed drug compounds which contain a suitable aryl alkyl ether moity (Scheme 2). Linker chains were synthesised which contained an electron-poor alkene group at one end and a functionalisable handle at the other and then these were tested in couplings under the developed conditions. It was found that large complex drug molecules were not successfully functionalised but smaller, simpler drug compounds (v) could be effectively modified under the established procedure using a simple electron-deficient radical acceptor, vi, albeit with varying selectivity in relation to the functionalisation process. Scheme 2: General structure of linker chains synthesised and reaction of drug compounds with alkene vi. Chapter 3 – Photoredox-Mediated Cyanation and Allylation of Aryl Alkyl Ethers Both nitrile and allyl groups are very versatile functional handles and can be found in a vast array of pharmaceutically relevant molecules. Therefore, the development of new approaches to the installation of nitrile and allyl moieties is of great importance to synthetic chemistry. With this in mind, the work discussed in Chapter 3 shows the application of our established photoredox catalysed protocol to the cyanation and allylation of aryl alkyl ethers (i) utilising aryl sulfones as the nitrile/allyl source (Scheme 3). This allowed for the successful cyanation and allylation of an array of aryl ether substrates. Furthermore, the utility of the allylation reaction was demonstrated through further functionalisation of the installed allyl group. Scheme 3: Photoredox-mediated cyanation and allylation of aryl alkyl ethers using aryl sulfones. Chapter 4 – Potassium Metal-Mediated Coupling of Benzene Following on from work carried out by a previous PhD student in the Murphy group who found that heating K metal, KOtBu in benzene (ix) at 150 °C produced a significant amount of biphenyl (x), the work shown in Chapter 4 expands on these initial findings. Deuterium studies produced insights into the mechanism of the reductive coupling and provided evidence for the free exchange of H− and D− throughout the reaction (Scheme 4). Moreover, the addition of other arene compounds to the reaction showed that these also participate in H/D exchange and in some cases fragmentation and also coupling to benzene. Scheme 4: Reaction of benzene (ix) and benzene-d6 (ix-d6) producing a mixture of isotopologues of biphenyl (x).
- Advisor / supervisor
- Murphy, John
- Resource Type
- DOI
- Embargo Note
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File | 2024-09-04 | Embargo |