Azaarenes are of widespread chemical significance, being present in numerous chiral, biologically active natural products, and serving as building blocks for the discovery of new medicines, agrochemicals, and functional molecules. Consequently, the development of new methods to prepare chiral azaarene-containing compounds is an important goal. The Lam group and others have previously demonstrated the synthetic utility of azaarenes as activating groups in a variety of catalytic asymmetric processes, which are summarised in Chapter 1. Chapter 2 presents a recent achievement in this area: the development of a mild and highly enantioselective conjugate addition of acetylazaarenes to nitroalkenes, under nickel catalysis, to afford densely functionalised products. The reaction scope includes a broad range of acetylazaarenes as well as (hetero)aromatic and aliphatic nitroalkenes. When α-nitroacrylate esters are employed as conjugate acceptors, products bearing a quaternary stereogenic centre are formed in high yield and with excellent enantioselectivity. The methodology is easily scalable, allowing multigram preparations to be carried out with catalyst loadings of 1 mol% without loss of yield or enantioselectivity. Further transformations of the products, including diastereoselective transfer hydrogenation, are briefly described. Finally, Chapter 3 gives an overview of unsuccessful efforts to develop routes to α-sulfonyl organoboron compounds, for subsequent use in ate complex homologation chemistry, via catalytic asymmetric conjugate addition processes.

Chapter 1 is a brief review on some of the recents developments in palladium-catalysed C-H functionalisation chemistry. The synthesis and functionalisation of heterocycles using these methodologies was particularly emphasised. Chapter 2 presents our efforts to identify a new catalytic system to promote the intramolecular coupling of vinyl bromides with unfunctionalised aryl C-H bonds for the formation of benzofurans. Dihydrobenzofurans were obtained efficiently under mild conditions in the presence of Pd(OAc)₂, X-Phos and K₂CO₃ in DMA at 80 °C and a subsequent one-pot isomerisation under acidic conditions afforded the desired benzofurans. A new strategy has also provided access to more complex benzofurans by functionalisation of the exocyclic alkene isomer in both a chiral and achiral manner. In Chapter 3, mechanistic studies were performed on the benzofuran formation reaction. The analysis of substituent effects on the aromatic ring is in accordance with an electrophilic aromatic substitution mechanism (SEAr); however, the existence of both intra and intermolecular kinetic isotope effects suggest a SE3 type pathway rather than a pure SEAr. In Chapter 4, the intramolecular coupling of vinyl bromides with unfunctionalised aryl C-H bonds was further extended to the synthesis of six-membered heterocycles by direct arylation of alkenyl bromide derivatives in the presence of Pd(OAc)₂, dppf and K₂CO₃ in DMA at 120 °C. The synthetic utility of this methodology was exemplified by the synthesis of substituted isoquinolines in six steps. Moreover, we have applied our methodology to the direct arylation of sulfonamides, leading to an interesting synthesis of widely used sultams. Both these new routes are currently being investigated and should provide access to a variety of differently substituted cyclic sulfonamides and isoquinolines. Finally, Chapter 5 presents a new strategy for the synthesis of benzo[b]furan was briefly investigated. It consists in consecutive Tsuji-Trost and C-H functionalisation reactions. This methodology requires simpler and more versatile substrates, allowing access to various heteroaromatics in a single step. We successfully proved the viability of this reaction through the synthesis of a range of benzofurans in modest yields. To our knowledge, this is the first example of a single palladium catalyst performing these different reactions in tandem in a simple procedure.

This work describes the extension of rhodium-catalysed intermolecular hydroacylation to encompass some tandem catalytic processes, wherein a further catalytic process is enacted on the product of an intermolecular hydroacylation reaction in “one pot”. Chapter 1 entails an overview of the development of hydroacylation chemistry, with a focus on the different types of catalytic systems which have been used to facilitate this transformation. A brief description of some precedented examples of tandem catalytic processes which include a hydroacylation reaction is also included. Chapter 2 describes the intermolecular hydroacylation of chelating aldehydes and propargylic alkynes to form γ-hydroxy-α,β-enones, and their subsequent acid-catalysed cyclisation to form substituted furans in a "one-pot" procedure. Additionally, a tandem intermolecular hydroacylation/double-bond isomerisation protocol for the synthesis of 1,4-dicarbonyl compounds is detailed, and the subsequent transformation of this class of compounds to heterocycles is included. Chapter 3 focuses on the development of tandem catalytic hydroacylation/reductive processes, wherein a hydroacylation product undergoes a reduction which is catalysed by the hydroacylation catalyst. Chapter 4 describes an attempt to utilise the rhodium-catalysed conjugate addition of arylmetal species to enomes to create a tandem alkyne hydroacylation/conjugate addition process. Chapter 5 encompasses the use of a small range of different solvents in rhodium-catalysed hydroacylation, in an attempt to find higher-boiling alternatives to acetone and a "green" alternative to the commonly used DCE.