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)

Visible light-promoted iron-catalyzed C(sp2)-C(sp3) Kumada cross-coupling in flow

X.-J.W., I.A., J.A., and T.N. would like to acknowledge the European Union for a Marie Curie ITN Grant (Photo4Future, Grant No. 641861). C.S. acknowledges the European Union for a Marie Curie European post-doctoral fellowship (FlowAct, Grant No. 794072). We would like to thank the Engineering and Physical Sciences Research Council for financial support (EP/M02105X/1). C. L. thanks the Prof. & Mrs Purdie Bequests Scholarship and AstraZeneca for his PhD Studentship.A continuous‐flow, visible‐light‐promoted method has been developed to overcome the limitations of iron‐catalyzed Kumada–Corriu cross‐coupling reactions. A variety of strongly electron rich aryl chlorides, previously hardly reactive, could be efficiently coupled with aliphatic Grignard reagents at room temperature in high yields and within a few minutes’ residence time, considerably enhancing the applicability of this iron‐catalyzed reaction. The robustness of this protocol was demonstrated on a multigram scale, thus providing the potential for future pharmaceutical application.Publisher PDFPeer reviewe

Synthesis of heterocycles via aerobic oxidation

Research in the field of aerobic oxidation has recently gained much attention from both academia and industry. The main reason for this has to be found in the inherent greenness of such methods. Although much investigation has been undertaken to develop new methods and reactions and to elucidate the mechanistic aspects of this chemistry, its applications in the synthesis of heterocycles have been relatively limited. In this review, the recent developments in this field are summarized

Flow photochemistry: shine some light on those tubes!

Continuous-flow chemistry has recently attracted significant interest from chemists in both academia and industry working in different disciplines and from different backgrounds. Flow methods are now being used in reaction discovery/methodology, in scale-up and production, and for rapid screening and optimization. Photochemical processes are currently an important research field in the scientific community and the recent exploitation of flow methods for these methodologies has made clear the advantages of flow chemistry and its importance in modern chemistry and technology worldwide. This review highlights the most important features of continuous-flow technology applied to photochemical processes and provides a general perspective on this rapidly evolving research field

Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts

A ruthenium-catalyzed photoredox coupling of substituted N-aryltetrahydroisoquinolines (THIQs) and different bench-stable pyridinium salts was successfully developed to give fast access to 1-benzyl-THIQs. Furthermore, secondary alkyl and allyl groups were also successfully introduced via the same method. Additionally, the typically applied N-phenyl group in the THIQ substrate could be replaced by the cleavable p-methoxyphenyl (PMP) group and successful N-deprotection was demonstrated

Continuous-Flow Synthesis of Pyrylium Tetrafluoroborates: Application to Synthesis of Katritzky Salts and Photoinduced Cationic RAFT Polymerization

Katritzky salts have emerged as effective alkyl radical sources upon metal- or photocatalysis. These are typically prepared from the corresponding triarylpyrylium ions, in turn an important class of photocatalysts for small molecules synthesis and photopolymerization. Here, a flow method for the rapid synthesis of both pyrylium and Katrizky salts in a telescoped fashion is reported. Moreover, several pyrylium salts were tested in the photoinduced RAFT polymerization of vinyl ethers under flow and batch conditions