Total synthesis of analogues of the β-lactam antibiotics. Part 5. 3-Thiacepham-4-exo-carboxylates and their 1,1,3,3-tetraoxides

Abstract

t-Butyl hydroxy{4-[(Z)-2-(methoxycarbonyl)vinylthio]-2-oxoazetidin-1-yl}acetate (19a) was transformed into t-butyl 2-endo-methoxycarbonylmethyl-3-thiacepham-4-exo-carboxylate (20a) by sequential reactions involving thionyl chloride, potassium thioacetate, and cyclohexylamine. Oxidation of compound (20a) with potassium permanganate gave the 1,1,3,3-tetraoxide (23a), the structure of which was established by X-ray crystallography. The exceptional acidity of the 2- and 4-hydrogen atoms of compound (23a) was revealed by their replacement with deuterium atoms in the presence of deuterium oxide and with methyl groups in the presence of diazomethane. Cleavage of the t-butyl ester function of the thiacepham tetraoxide (23a) was effected by trifluoroacetic acid but the resultant acid (23b) underwent a rapid decarboxylation in water to give 2-endo-methoxycarbonylmethyl-3-thiacepham 1,1,3,3-tetraoxide (26a).