New catalytic methods for the derivatisation and functionalisation of electron deficient heteroaromatic compounds

Thesis

Introduction

The first part of Chapter 1 provides a brief review on the reactivity of pyridines and quinolines. Additionally, several well-established methods for the derivatisation and functionalisation of these electron-deficient heterocycles are highlighted.

The second part of Chapter 1 introduces the general principles of Transfer Hydrogenation (TH) and highlights how TH and related processes could be used in modern catalysis.

“Interrupted Transfer Hydrogenation” (ITH)

Chapter 2 introduces a novel reactivity mode for quinolinium salts. The first part of the chapter focuses on the initial reaction development. This is followed by a comprehensive substrate scope and attempts to induce enantioselectivity on privileged substrates. Finally, the focus was shifted towards mechanistic investigations that allowed us to propose a mechanism of action for this novel methodology.

Chapter 3 presents how the ITH methodology was extended to encompass electron-deficient pyridines. The substrate scope for pyridiniums that bear an electron-withdrawing group at the 4- position was investigated. Additionally, preliminary attempts to extend the ITH methodology to the less reactive 4-aryl pyridiniums are also highlighted in this chapter. Mechanistic investigations revealed a similar reaction pathway to that of quinoliniums. Additionally, preliminary findings lead to the discovery and development of a new reactivity mode for 4- substituted pyridines.

3,5-Dimethylation of 4-substituted pyridines

Chapter 4 introduces a rhodium catalysed 3,5-dimethylation of 4-substituted pyridines with methanol and formaldehyde. The reaction development, as well as a preliminary substrate scope and detailed mechanistic studies are presented. Additionally, the effect of the simple iodide ion on the catalytic system was also qualitatively assessed.

Experimental details

Chapter 5 contains detailed procedures and spectroscopic characterisation data for the compounds synthesised in this thesis.

Authors: Grozavu, A

• DOI: 10.5287/ora-r8dexmdz4
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford