1,3-Dipolar cycloadditions are invaluable reactions that offer a convenient synthetic route for the preparation of a large variety of heterocycles. Their main advantages include convergence, high atom economy and great versatility. While the formation of triazoles via the azide–alkyne cycloaddition has been extensively studied, an analogous azide–alkene cycloaddition that produces triazolines has received relatively little attention. This phenomenon can be explained by the typically high thermal instability of the latter class of compounds under the reaction conditions that they are generated in. However, triazolines are promising biologically active heterocycles that serve as useful synthons in organic chemistry and developing an accessible methodology for their formation would be highly desirable. Cleaner, safer and more sustainable processes are becoming very important and therefore we investigated the use of deep eutectic solvents for this transformation. Such solvents are made of two or three inexpensive components that produce benign mixtures with interesting physico-chemical properties. In addition, they are water-soluble, biodegradable and recyclable which is making their use in organic synthesis increasingly popular. This thesis describes the multi-gram preparation of a wide range of triazolines via the azide–alkene cycloaddition in a deep eutectic solvent. Moreover, formation of other useful heterocyclic motifs such as aziridines, pyrazolines, pyrrolines and triazoles is also reported.
Chapter 1 is an introductory chapter and provides a general overview of 1,3-dipolar cyclo-additions and traditional methods for the preparation of triazolines and aziridines. It also discusses the reactivity of triazolines and characteristic properties of deep eutectic solvents. Chapter 2 then focuses on the optimisation of reaction conditions of the azide–alkene cycloaddition in a deep eutectic solvent and explores the scope with a range of azides, alkenes and dienes. Later sections of this chapter outline how triazolines can be employed as synthons to generate 1,4- and 1,5-disubstituted triazoles, and the synthesis and reactivity of 1,4-disubstituted triazolines to form pyrazolines and aziridines is also described. While Chapter 3 investigates the use of a deep eutectic solvent in nitrile ylide– and nitrilimine–alkene cycloadditions, Chapter 4 includes the copper(I)-mediated azide–alkyne cycloaddition reaction promoted by ring-expanded N-heterocyclic carbene ligands to generate 1,4-regioisomeric triazoles. The final parts of the thesis contain general conclusions, future work, experimental procedures as well as characterisation and X-ray crystallographic data.