ALKYLATION OF PENICILLANATES - ASPECTS OF THE CHEMISTRY OF PENICILLANATE SULFONIUM SALTS

Methyl (6S)-6-chloro-, (6S)-6-phthalimido- and 6,6-dibromo-penicillanates (4)-(6) were converted into sulfonium salts (7)-(12) using trimethyloxonium tetrafluoroborate, methyl fluorosulfonate and triethyloxonium tetrafluoroborate. Methyl 6,6-dibromo-1-methylpenicillanate tetrafluoroborate (9) was assigned the 1 .alpha.-configuration. Treatment of sulfonium salts (7)-(12) with sodium carbonate gives the corresponding methyl 2-[(2R)-2-alkylthio-4-oxoazetidin-1-yl]-3-methylbut-2-enoates (22)-(25) in high yield. Methanolysis of methyl (6S)-6-chloro-1-methylpenicillanate tetrafluoroborate (7) gives a mixture of methyl (2S)-2-[(2S,3R)-3-chloro-2-methoxy-4-oxoazetidin-1-yl]-3-methyl-3-methylthiobutanoate (29), its C-2'' epimer (30) and methyl (2S)-2-[(2R)-2-chloro-3,3-dimethoxypropionamido]-3-methyl-3-methylthiobutanoate (32), whereas treatment with sodium carbonate in methanol gives methyl (2S)-2-(trans-2-chloro-cis-2-methoxycarbonylvinylamino)-3-methyl-3-methylthiobutanoate (36). Similar reactions were observed with ethanol. A sulfonium salt could not be isolated from the reaction between methyl (6R)-6-phthalimidopenicillanate (3) and trimethyloxonium tetrafluoroborate, but treatment of the mixture with anhydrous sodium carbonate gave a mixture of methyl 3-methyl-2-[(2R,3R)- and -[(2S,3R]-2-methylthio-4-oxo-3-phthalimidoazetidin-1-yl]-but-2-enoates (39) and (46). Complex product mixtures were obtained from the reaction between methyl (6R)-6-pnenylacetamidopenicillanate (2) and trimethyloxonium tetrafluoroborate.