The synthesis of 3-alkyl- and 3-aryl-β-lactams from zinc enolates and imines

✍ Scribed by Hendrik L. van Maanen; Henk Kleijn; Johann T. B. H. Jastrzebski; Gerard van Koten

• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 658 KB
• Volume: 113
• Category: Article
• ISSN: 0165-0513
• DOI: 10.1002/recl.19941131207

✦ Synopsis

Abstract

Chlorozinc enolates of (hetero)aryl‐, alkyl‐ and silyl‐substituted acetates were reacted with imines and α‐diimines. The zinc‐mediated reaction of (hetero)aryl‐substituted acetates with imines afforded trans‐β‐lactams in good yields and with excellent selectivity. Zinc enolates of non‐functionalized alkanoates yielded the corresponding 3‐alkyl‐β‐lactams (predominantly trans) in moderate yields. Bulky substituents increase the rate and enhance the cis‐trans selectivity of the reaction. Methyl 2‐(trimethylsilyl)acetate does not afford 3‐(trimethylsilyl)‐β‐lactams via the zinc‐mediated reaction with imines, but N‐(trimethylsilyl)‐β‐amino esters, which are formed via an intramolecular silyl shift. The desilylated β‐amino esters were obtained from the zinc enolate of methyl acetate, albeit in moderate conversion, and careful control of the reaction conditions was necessary to avoid side‐reactions. The substituent effects are discussed in terms of pre‐equilibria involving the enolate and six‐membered cyclic transition states.