Anhydropenicillin: a key intermediate for the stereocontrolled introduction of the 6-R-hydroxyethyl side chain of the penem and carbapenem antibiotics

Aldol condensation of the magnesium enolate derived from anhydro-6,6-dibromopenicillin with acetaldehyde allows for the stereospecific introduction of a 1-R-hydroxyethyl substituent at C-6. Protection of the hydroxy group followed by reductive dehalogenation provides anhydro-6(α)-[(1-R)-(tert;-butyldimethylsilyloxy)-ethyl]-penicillin, an intermediate in the synthesis of thienamycin. A high yield conversion of this anhydro derivative to (4-R)-acetoxy-(3-S)-[(1-R)-(tert-butyldimethylsilyloxy-ethyl]-azetidin-2-one (5) is also reported.