Stereoselective synthesis and Lewis acid mediated functionalization of novel 3-methylthio-β-lactams

A proficient etiquette for the stereoselective synthesis of novel 3-methylthio-β-lactams and their Lewis acid mediated functionalization is described. Treatment of 2-methylthioethanoic acid and appropriate imines in the Staudinger reaction leads to the stereocontrolled synthesis of novel trans-3-methylthio-β-lactams in excellent yields. cis-3-Chloro-3-methylthio-β-lactams, obtained from stereoselective chlorination of trans-3-methylthio-β-lactams using N-chlorosuccinimide (NCS) and AIBN, were subjected to Lewis acid (TiCl4 or SnCl4) mediated functionalization using various active aromatic, heterocyclic and aliphatic compounds (nucleophiles). This reaction provides an easy access to novel, stereoselective cis-3-monosubstituted-3-methylthio-β-lactams, which further undergo smooth desulfurization with Raney-nickel to afford C-3 cis- and trans-monosubstituted-β-lactams. The cis or trans configuration of the hydrogen/chloro/nucleophile substituent at C-3 was assigned with respect to C4–H.