1-Azetines, 1,2-Thiazetin-1,1-dioxides and Isothiazol-1,1-dioxides as Building Blocks in Heterocyclic Synthesis: the Attempted Synthesis of Bicyclic β-Sultams

This thesis is concerned with the synthesis of β-sultams and the development of new routes for the synthesis of bicyclic versions of these molecules as potential anti-bacterials. The synthesis of 1-azetines, 1,2-thiazetin-1,1-dioxides and isothiazol-1,1-dioxides as precursors of bicyclic heterocycles is described.

1-Azetines were synthesised from azetidin-2-ones prepared via the [2+2] cycloaddition of alkenes with N-chlorosulfonyl isocyanate (CSI). They reacted with diphenylcyclopropenone or nitrile oxides to afford bicyclic systems whose reactivity was explored and afforded a range of heterocycles such as 1,2,4-oxadiazoles, pyridines or pyrimidines via novel reaction pathways.

The synthesis of 1,2-thiazetin-1,1-dioxide through two routes will be discussed: the alkylation of 3-oxo-β-sultams to afford 3-ethoxy-1,2-thiazetin-1,1-dioxides, and the ring contraction of an isothiazol-1,1-dioxide to afford a 3-diethylamino-1,2-thiazetin 1,1-dioxide. The reactivity of these 1,2-thiazetin-1,1-dioxides towards diphenylcyclopropenone, 1,3-dipoles and dienes was studied and is fully described.

In the course of chemistry mentioned above, a series of isothiazol-1,1-dioxides was synthesised. Their reaction with 1,3-dipoles to yield the corresponding bicyclic heterocycles is described.