Investigations on the use of amidic ligands in copper-catalysed arylation reactions

This thesis reports investigations on the use of amidic ligands, in particular picolinamide ligands, in copper-catalysed arylation of nucleophiles with aryl halides. An introduction to the field of copper-catalysed arylations of nucleophiles, mostly focusing on the mechanistic aspects of these processes, from the early investigations to the most recent developments, is reported in Chapter 1. Following this introduction, the results of this research are presented in three chapters, each dealing with a different topic. Chapter 2 reports on the synthesis of a range of differently substituted picolinamide ligands and their use in the copper-catalysed arylation of phenols and amides. The catalytic screenings reported in this chapter are the basis for the mechanistic investigations reported in Chapter 4. A range of phenols, amides and aryl halides were tested under optimised conditions to assess the validity of the method. All the coupling products were isolated and characterised. Chapter 3 describes the synthesis of copper complexes with picolinamide ligands, to be used for mechanistic investigations. Five different types of complexes, with differently substituted ligands, were obtained, and their structural features in the solid state are summarised in this chapter. Discussion on the mechanism of formation of these complexes, and on the role of the base in the process is also included. Investigations on the mechanism of the coupling reaction between phenols and aryl halides, facilitated by picolinamide ligands, are reported in Chapter 4. The complexes synthesised in Chapter 3, used as pre-catalysts for the coupling process, and electrochemical measurements on these complexes, are employed to investigate the role of the electronic properties of the ligands in the reaction, and its influence on the metal centre. Other miscellaneous experiments, such as radical clock experiments, are also reported. The final two chapters of this thesis, Chapters 5 and 6, contain general conclusions and suggestions for further investigation topics (Chapter 5), and detailed experimental procedures and characterisation data for all of the compounds prepared in Chapters 2-4 (Chapter 6)