J. E. Vincent

Vinyl-β-lactams as Efficient Synthons. Eco-friendly Approaches via Microwave Assisted Reactions

Abstract Vinyl-β-lactams are efficient synthons for a variety of compounds of biomedical interest—such as isocephalosporins, carbapenem and thienamycin intermediates, and pyrrolidine alkaloids. Convenient methods are described for obtaining both enantiomers of some of these synthons. Microwave-induced Organic Reaction Enhancement (MORE) chemistry techniques allow highly accelerated synthesis of variously substituted vinyl-β-lactams using limited amounts of solvents and with efficient stereocontrol—thus achieving high ‘atom economy’. The effect (if any) of microwaves on bond angles and bond lengths and the geometry of transition states are not well understood yet. Nonetheless, reactions under microwave irradiation in open systems are rapid, safe, and cost-effective for synthetic approaches that are much more friendly to the environment than conventional processes.

A CONVENIENT SYNTHESIS OF α-AMINO-β-LACTAMS

Abstract A safe and convenient method is described for the synthesis of α-amido-β-lactams starting with glycine and an azomethine. The amino group of glycine is protected by reaction with a β-dicarbonyl compound following the method of Dane et al. and the carboxyl group is activated through the formation of a mixed anhydride or an active ester. Condensation between these glycine derivatives and acyclic or cyclic imino compounds (including thioimidates) in presence of triethylamine leads to stereospecific synthesis of 3-(β-carbonyl-vinylamino)-2-azetidinones in 40–60% yield. The vinylamino side chain can be hydrolyzed under mild acid conditions to form 3-amino-2-azetidinones which can be acylated to α-amido-β-lactams. Alternatively, the vinylamino side chain can be converted to an amido side chain by ozonolysis. The molecular parameters of a 3-(β-carbonyl-vinylamino)-2-azetidinone were determined by X-ray crystallography. Usefulness of this α-amido-β-lactam synthesis is illustrated by the preparation of isotopelabeled β-lactams and intermediates for some β-lactam antibiotics.

Non-hazardous synthesis of isocephosphorin intermediates via α-vinylamino-β-lactams☆

Abstract The reaction of a Schiff Base derived from veratrylamine and cinnamaldehyde with (α-methyl-β-alkoxycarbonyl)-vinylamino acetic acid (from glycine and an acetoacetate ester) in presence of a chloroformate ester and triethylamine constitutes a safe synthesis of α-vinylamino β-lactams that can be converted by literature methods to known intermediates for the synthesis of isocephalosporins and analogs.