Synthesis, structure and functionalisation of 1,2-diazetidines

Abstract

The four-membered cyclic hydrazine, 1,2-diazetidine, has received little attention from the scientific community. This system has useful potential applications in medicine and synthetic chemistry, but very few compounds of this class are known. This thesis describes the synthesis, structure and functionalisation chemistry of new simple 1,2- diazetidine derivatives. Synthetic studies show a Hard−Soft Acids and Bases controlled ring closure is necessary to effect acceptable to good yields in cyclisations to saturated N−carboxyalkyl and N−sulphonyl diazetidines. Functionalisation of these systems via C−H activation was unsuccessful due to protecting group participation. Synthetic studies toward the parent 1,2-diazetidine molecule (C2N2H6) using chloramine mediated N−N ring closure or deprotection strategies were also unsuccessful. Further studies show a wide range of simple 3-alkylidene-1,2-diazetidines and functionalised derivatives are accessible from commercial materials in two steps using an efficient Cu(I)-catalysed cyclisation. The scope of this cyclisation method is assessed. Pd(0)-catalysed Heck chemistry of 3-methylene-1,2-diazetidines allows a stereoselective route to arylated derivatives in moderate yields. Furthermore, diastereoselective reduction of these systems provides an efficient route to 1,2-diamines. Structural studies of a range of synthesised 1,2-diazetidines by X-ray crystallography and dynamic nuclear magnetic resonance spectroscopy are presented. Together these studies present the potential these molecules hold in synthetic chemistry