Nuclear analogs of β-lactam antibiotics. XVII. Stereospecific synthesis of penem and carbapenem precursors

Abstract

The transformation of methyl 6-.alpha.-bromopenicillanate to N-methoxalyl-(3S)-bromo-(4R)-chloro-2-azetidinone (8) is described. Azetidinone 8 was converted, in a stereoselective manner, to (3S)-bromo-(4R)-tritylthio-2-azetidinone. Subsequent reduction of the 4-bromo substituent with Zn afforded the chiral (4R)-tritylthio-2-azetidinone, a useful intermediate for the synthesis of penems. Azetidinone 8 was also converted to the reactive (3S)-bromo-(4R)-chloro-2-azetidinone (11). Treatment of the (4R)-chloroderivative 11 with n-butyl or allylcuprate afforded the (4R)-butyl and (4R)-allylazetidinones as the predominant diastereomers. An improved synthesis of 11 to the (4R)-allylazetidinone using tetraallyltin is also described.