Simple and condensed β-lactams. Part 7. Side chain extensions of some azetidin-2-one derivatives, and the formation of melillo's lactone, a strategic intermediate in the total synthesis of thienamycin, from 3-acetyl-1-benzyl-4-cyanomethylazetidin-2-one

Abstract

The oxoazetidinecarboxylic acids (2a) and (2b) and the homologous acid (8b) were converted by treatment of their chlorides with ethyl diazoacetate into the diazo esters (4a, b), and (10b), respectively. Irradiation of the diazo ester (4b) afforded the diethyl and ethyl hydrogen malonates (17) and (18), respectively. Attempted thermal decarboxylation of the latter resulted in profound degradation to give a mixture of the isomeric compounds (19a, b). NaBH₄ reduction at –78 °C of the diazo ester (4d) gave mixtures of the diastereoisomers of the diazo esters (4e) and (20). The (hydroxymethyl)-azetidinone (6b) was converted via the aldehyde (5b) and the nitroethyl derivative (22) into the acetals (23) and (25). Attempts to convert the nitrile (7a) into either the acid (8a) or the ester (9a) in acceptable yields, failed. The nitriles (7g) and (7e)[obtained in two steps from the nitrites (7c) and (7b), respectively] were converted by refluxing hydrochloric acid into Melillo's lactone (28)(the key intermediate of a practical synthesis of the carbapenem antibiotic thienamycin) and its N-unsubstituted analogue (30), respectively.