THE SYNTHESIS OF 3-ALKYL-BETA-LACTAMS AND 3-ARYL-BETA-LACTAMS FROM ZINC ENOLATES AND IMINES

Chlorozinc enolates of (hetero)aryl-, alkyl- and silyl-substituted ace tates were reacted with imines and alpha-diimines. The zinc-mediated r eaction of (hetero)aryl-substituted acetates with imines afforded tran s-beta-lactams in good yields and with excellent selectivity. Zinc eno lates of non-functionalized alkanoates yielded the corresponding 3-alk yl-beta-lactams (predominantly trans) in moderate yields. Bulky substi tuents increase the rate and enhance the cis-trans selectivity of the reaction. Methyl 2-(trimethylsilyl)acetate does not afford 3-(trimethy lsilyl)-beta-lactams via the zinc-mediated reaction with imines, but N -(trimethylsilyl)-beta-amino esters, which are formed via an intramole cular silyl shift. The desilylated beta-amino esters were obtained fro m the zinc enolate of methyl acetate, albeit in moderate conversion, a nd careful control of the reaction conditions was necessary to avoid s ide-reactions. The substituent effects are discussed in terms of pre-e quilibria involving the enolate and six-membered cyclic transition sta tes.