New methods for the synthesis of N-heteroaromatics and imines

This thesis is divided into four chapters containing the work conducted at two universities, and it
describes new methods for the synthesis of nitrogen-containing compounds.
The first chapter describes the project undertaken 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 ortho to the
biaryl axis 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, a side reaction arising from 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 describes the work done during the industrial secondment at AstraZeneca. This was
focused on a recently developed Ni-catalysed benzannulation method for the mild and selective
synthesis of functionalised phenols. During the secondment, the optimisation of the formation of
heterocyclic compounds resulting from the Ni-catalysed coupling of cyclobutenone with different
substrates such aldehydes, imines and nitriles was explored.
Finally, the last chapter describes a new approach to an unusual class of pyrimidine derivatives.
Pyrimidines are amongst the most widely represented class of heterocycles in the chemical
sciences. Based on this, we explored the synthesis of pyrimidine boronates via the condensation
of stable ynone trifluoroborates with various guanidines to have access to aryl-, heteroaryl-, and
alkyl- substituted aminopyrimidines containing the valuable boron functional handle.