Cyclic Thiosulfinates and Thiosulfonates from Oxidation of the 2-Thiacephem Ring System. Synthesis of (5R)-Penems by Stereospecific SO2 Extrusion

Article abstract of DOI:10.1021/jo00368a002

The MCPBA oxidation of 2-thiacephems afforded regioisomeric pairs of cyclic thiosulfinates; the 6,7-trans substrates yielded 1-oxides as the main product, while 6,7-cis-2-thiacephems were preferentially oxidized at the sulfur atom furthest removed from the azetidinone ring.On further MCPBA oxidation, the 6,7-trans-2-thiacephem 1-oxides underwent an apparent 'straightforward' oxidation at the sulfinyl sulfur with formation of the 1,1-dioxides, whereas the 6,7-cis 1-oxides and all of the 2-oxides gave similar mixtures (ca. 3:1) of the two possible thiosulfonates, thus implying the intermediacy of vic-dioxides and O,S-sulfenyl sulfinates.Sodium periodate readily reacted with the 2-oxides but not with the 1-oxides or the parent disulfides, affording the 2,2-dioxides regioselectively.Stereospecific extrusion of SO2 occurred from the 1,1-dioxides upon storage or mild heating; (5R)-penems were obtained even in cases where the biologically inactive 5S epimers had been anticipated as a consequence of the trans-directing effect of the C7 substituent.