Diastereoselective synthesis of 3-acetoxy-4-(3-aryloxiran-2-yl)azetidin-2-ones and their transformation into 3,4-oxolane-fused bicyclic β-lactams

cis-3-Acetoxy-4-(3-aryloxiran-2-yl)azetidin-2-ones were prepared through a Staudinger [2+2]-cyclo-condensation between acetoxyketene and the appropriate epoxyimines in a highly diastereoselective way. Subsequent potassium carbonate-mediated acetate hydrolysis, followed by intramolecular ring closure through epoxide ring opening, afforded stereodefined 3-aryl-4-hydroxy-2-oxa-6-azabicyclo[3.2.0]heptan-7-ones as a novel class of C-fused bicyclic beta-lactams. Selective benzylic oxidation of bicyclic N-(4-methoxybenzyl)-beta-lactams with potassium persulfate and potassium dihydrogen phosphate provided the corresponding N-aroyl derivatives as interesting leads for further beta-tactamase inhibitor development.