2-(Alkylthio)penem-3-carboxylic acids. IV. Synthesis of (hydroxyethyl)azetidinone precursors to 1-thia analogs of thienamycin.

The synthesis of hydroxyethylazetidinone precursors to 1-thia analogs of thienamycin is described. An N-protected azetidinone 4 was hydroxyethylated via an aldol reaction to give four diastereomers 5-8, which were converted to the diastereomeric pair of racemic 8R and 8S trans azetidinones 9b and 10b. Stereochemical assignment was achieved by correlation of 9b with the optically active azetidinone 16 which was obtained from the hydroxyethylpenicillanate 14a with known stereochemistry. The optically active 8R and 8S azetidinones 16 and 27 were synthesized more efficiently starting from the penicillinderived bromo compound 19 in a series of steps including stereochemical inversion at the C-8 position.