Synthesis of 4-Thioxo-2-azetidinones

Article abstract of DOI:10.1021/jo01296a026

4-Thioxo-2-azetidinones, which are C- and N-substituted imides of monothionomalonic acid, have been prepared by a thermal rearrangement of 4-(2-methoxycarbonylethylsulfinyl)-2-azetidinones through the intermediacy of β-lactam 4-sulfenic acids.The 4-sulfinyl-2-azetidinones have been obtained by total synthesis, or from penicillin sulfoxides.The former approach, which allows the choice of variegated arrays of substituents, was employed in the synthesis of (+/-)-1-(1-methoxycarbonyl)-2-methylprop-1-enyl)-3-phthalimido-4-thioxo-2-azetidinone (8) (a didehydrovaline derivative), (+/-)-1-(1-(tert-butoxycarbonyl)-2-tert-butoxyethyl)-3- phthalimido-4-thioxo-2-azetidinone (19) (a serine derivative), and 1,3,3-triphenyl-4-thioxo-2-azetidinone (20).Compound 27, which is the levorotatory enantiomer of the racemic 8, has been obtained by the degradation of methyl 6-(β-phthalimido)penicillanate sulfoxide (21).