Towards the synthesis of imines and iminiums and their reactions in situ

Functionalised amines are important targets for organic chemists. Various methods are used to functionalise amines, however often these reactions will involve the use of toxic or expensive reagents and therefore must be controlled, especially when used as active pharmaceutical ingredients (API). These reagents could potentially increase the cost associated with API and fine chemical synthesis. There has been an impetus to directly activate the C-H bonds adjacent to amine groups, thus increasing the reactivity of the group.
Metal complexes have been used to stoichiometrically activate amines, however catalytic methods would be more favourable due to potential cost reduction. Metal complexes are used widely for hydrogen transfer reaction, which have provided a new methodology to activate non-electrophilic substrates by forming their electrophilic analogues. This methodology has been used extensively with alcohols, however there remains the opportunity to form imines by amine activation.
The research disclosed in this thesis discusses efforts toward the formation of imines or iminium ions from their amine precursors. Analysis of the N-alkylation of several amines has been carried out, with discussion of methods to inhibit N-alkylation to form more of the desired imine. Mechanistic analysis of the various species in the reactions has given information including a potential pathway for N-alkylation, amine iridium binding and a potential inhibition product.
The optimisation of an indole cyclisation reaction has been probed, with different a range of conditions investigated. A discussion of an attempted telescoped reaction has been given as well, together with a study on the expansion of the methodology to include diverse structural motifs. The attempted incorporation of different nucleophiles has also been disclosed with a discussion of the results and potential improvements to these reactions. Finally, an overview of the future for this research has been presented with potential new avenues for exploitation.