Exploration of the Synthesis, Reactivity and Applications of 1,2-Oxathiine 2,2-Dioxides

This thesis constitutes an investigation of the synthesis, reactivity and photochromic applications of the 1,2-oxathiine 2,2-dioxide heterocyclic ring system.

An extensive series of substituted 1,2-oxathiine 2,2-dioxides was obtained using a two-step synthetic route comprising of a sulfene addition to the enaminone substrates Ito afford the 4-dimethylamino-3,4-dihydro-1,2-oxathiine 2,2-dioxide intermediates II(Scheme A1). A mild and highly efficient Cope elimination reaction was employed to introduce the C3-C4 oxathiine ring double bond leading to the unsaturated 1,2-oxathiine 2,2-dioxidesIIIwith full chemo-and regio-selectivity.

The preparation of the enaminone precursors was accomplished in generally high yields through the reaction of α-methylene-containing ketones IV with DMFDMA. The crystal structures of two unique, stable, organic salts(Va,b)resulting from the action of DMFDMA on benzoylacetonitrile were obtained. The subsequent addition of sulfene derivatives, derived from the action of Et3N on methanesulfonyl chlorides, proceeded in fair to very good yields and the main structural features of the 3,4-dihydro-1,2-oxathiine 2,2-dioxides II were mapped out using extensive NMR experiments and X-ray crystallography. The mechanism, regioselectivity and stereoselectivity of the sulfene additions were also explored, with the enaminone motif found to direct the addition of the sulfene fragment through a concerted process that afforded a thermodynamic and akinetic product which constitute a pair of anti/syn diastereomers. The foregoing two step transformation to afford the 1,2-oxathiine 2,2-dioxidesIIIwas further developed into a convenient “one-pot” method.

The efficient synthesis of α-methylene ketones with either phenyl or 2,5-dimethylthienyl groups appended on their structure allowed access tothe1,2-oxathiine 2,2-dioxide analogues VI which exhibited photochemically reversible photochromism as a consequence of the thiophene rings adopting an antiparallel conformation which was established by X-ray crystallography(Scheme A2). The ring-closed photo-isomers VII, established by NMR spectroscopy, afforded yellow → red coloured species with maxat circa410 -510 nm. UV-Vis spectroscopic studies revealed that, at a photostationary state, the 3,4-dihydro-1,2-oxathiine 2,2-dioxides exhibited less intensely coloured, hypsochromically shifted absorption maxima than their unsaturated derivatives.

The reactivity of the 1,2-oxathiine 2,2-dioxide system was probed by their use as substrates in various transformations(Scheme A3). Ring bromination (structures VIII) revealed a clear bias towards bromination at the 3-position of the heterocycle, whereas the 5-position reacted much more slowly and the 4-position was completely inactive towards Br2. Lithium-bromine exchange of the foregoing brominated products led to their degradation, thus Pd-catalysed methods were explored as means of functionalisation.

The Suzuki cross-coupling reaction of the brominated 1,2-oxathiines VIII with a selection of boronic acids afforded the target coupled products IX in moderate yields with the concomitant formation of homo-coupled, bis-1,2-oxathiine 2,2,2',2'-tetraoxide, side-products X. Homo-coupling of was found to be the exclusive result of a Miyaura borylation protocol. The requirement for brominated 1,2-oxathiine 2,2-dioxides VIII was avoided by the use of an efficient C-H activated cross-coupling protocol which afforded a small library of diversely substituted 1,2-oxathiine 2,2-dioxides IX.

Cycloaddition reactions of 6-styryl substituted 1,2-oxathiine 2,2-dioxides with PTAD afforded novel tricyclic adducts,1H-[1,2]oxathiino[5,6-c][1,2,4]triazolo[1,2-a]pyridazine-1,3(2H)-dione 8,8-dioxidesXI, that rearranged upon contact with silica to afford more stable regioisomers (XII). Benzyne addition to mono-, di-and tri-substituted 1,2-oxathiine 2,2-dioxides afforded low yields of substituted naphthalenes XIII as a consequence of cycloaddition across the fixed diene unit of the 1,2-oxathiine 2,2-dioxide ring with concomitant retro-Diels Alder elimination of SO3leading to the aromatised product.