PREPARATION OF ALPHA-METHYLENE AND ALPHA-ETHYLIDENE BETA-LACTAMS VIA THE ESTER ENOLATE IMINE CONDENSATION USING BETA-(DIALKYLAMINO) ESTERS AS STARTING MATERIALS - SCOPE AND SYNTHETIC APPLICATIONS

A new, simple procedure for the preparation of appropriately substitut ed alpha-methylene and alpha-ethylidene beta-lactams via the ester eno late-imine condensation is described. The method is based on the use o f lithium 3-(dialkylamino) ester enolates as synthetic equivalents of the corresponding acrylate alpha-anions. Thus, the reaction of lithium enolates of 3-(dialkylamino) esters with imines produced alpha-[(dial kylamino)alkyl] beta-lactams stereoselectively and in high yield. Upon dehydroamination the latter furnished a variety of alpha-alkylidene b eta-lactams. The synthesis of 3-alkylidene-4-formyl-2-azetidinones is a particularly significant feature of this work. Preparation of functi onalized alpha-keto beta-lactams and beta-lactam-furan hybrids through a dihydroxylation-oxidation process starting from different alpha-alk ylidene derivatives is also described. In addition, reduction of vario us 4-functionalized (Z)- and (E)-3-ethylidene-2-azetidinones yielded t he corresponding 3-ethylideneazetidines as advanced precursors of poly oximic acids.