ASYMMETRIC-SYNTHESIS OF BETA-LACTAMS VIA THE ZINC-MEDIATED GLYCINE ESTER ENOLATE IMINE CONDENSATION REACTION USING ALPHA-AMINO ESTERS AS THE CHIRAL AUXILIARY

Imine esters of glycine, (R)-phenylglycine, (R)-(1,4-cyclohexadienyl)g lycine and (S)-valine have been employed in the ester enolate-imine co ndensation via double activation with ZnCl2. The reaction of the chlor ozinc enolate (1b) of ethyl ,5-tetramethyl-1-aza-2,5-disilacyclopentyl )acetate with (R)-methyl N-benzylidene-2-phenylglycinate (2a) afforded the trans-beta-lactam 3a in 79% yield with excellent asymmetric induc tion (de >97%). Other imine esters also afforded trans-beta-lactams di astereoselectively, albeit in lower conversions (37-70%). Methyl silyl )-2-propyn-1-ylidene]amino]-3-methylbutanoate (2e) afforded a mixture of four diastereoisomers (68% conversion). The products were isolated as 3-phthalimido beta-lactams 5b-e and as 3-[(methoxycarbonyl)amino]-b eta-lactam 6b. The reactivity of the zinc enolates and the diastereose lectivity of the reactions are discussed in terms of the coordination of the imine esters to ZnCl2 (template effect) and the stability and a ggregation equilibria of the zinc enolates.