Simple and condensed β-lactams-I : The application of diketene in β-lactam synthesis. The synthesis and functional group manipulations of diethyl 3-acetyl-4-oxoazetidine-2,2-dicarboxylates

Acylation of the N-substituted diethyl aminomalonates 3a– 3d with diketene furnished the ring tautomers 6a– 6d of the expected acetoacetyl derivatives 5. By treatment with iodine and sodium ethoxide compounds 6a– 6d are smoothly converted into the β-lactam derivatives 2a– 2d. Deethoxycarbonylation of the ethylene ketals 7a– 7d of the latter furnishes mixtures of the corresponding diastereomeric monoesters 8 and 10. The ethoxycarbonyl groups of the trans esters 8 are more reactive than those of the cis isomers 10. This permits, under appropriate conditions, selective alkaline hydrolysis and NaBH 4 reduction of the trans esters 8 in the presence of the cis esters 10. Reduction of the cis ester 10c under more forceful conditions furnishes the trans hydroxymethyl derivative 11c.