New methods for the synthesis of N-heteroaromatics and imines

Abstract: This thesis is divided in four chapters, containing the work realised in two universities and has as the aim the synthesis of nitrogen-containing compounds. The first chapter describes the project realised at The University of Sheffield. In this part, the scope of alkynylboronate cycloadditions with aromatic substrates was explored, to obtain highly functionalised heteroaromatic compounds. The aza-Diels-Alder cycloaddition reactions of 1,2,4-triazines with alkynes offered a rapid synthesis of highly substituted pyridineboronic esters. With these substrates, the possibility of controlling axial chirality through chiral tethers favouring one atropisomer over the other was envisaged. The scope was explored to establish empirical selectivity data relating the importance of the interaction between the functional group on the alkyne and the chiral boronic ester on the diastereomeric excess. In the second chapter of this thesis, the work done at Stockholm University is described. In this project, an efficient method for the oxidative coupling of a diverse variety of benzylamines with other nucleophilic partners was developed. This process is catalysed by a transition-metal functionalized MOF (Metal-organic framework), namely PCN-222(Pd), under light irradiation. Importantly, the self-condensation of two identical molecules of benzyl amine was avoided. This increased the scope of the reaction, as well as the usefulness of the process. Catalytic conditions to achieve this goal were found, and the substrate scope was investigated. The third part described the work done during the industrial secondment at AstraZeneca. Joseph Harrity’s group has recently developed a Ni-catalysed benzannulation method forthe mild and selective synthesis of functionalised phenols. During the secondment, the bestconditions have been investigated for the formation of heterocyclic compounds resulting from the Ni-catalysed coupling of cyclobutenone with different groups such aldehydes, imines and nitriles. Finally, the last chapter would include the synthesis of Pyrimidines derivatives. Pyrimidinesare amongst the most widely represented class of heterocycles in biological systems and asignificant proportion of marketed pyrimidines contain a 2-amino group. Based on this, the Harrity group worked on the synthesis of pyrimidines via the condensation of stable boronicacid derivative as ynone (potassium (3-oxo-3-phenylprop-1-yn-1-yl)trifluoroborate) with various guanidines to have access to aryl-, heteroaryl-, and alkyl- substitutedaminopyrimidines.