Stereospecific cyclization of β-hydroxy aryl amides to β-lactams

Abstract

N-Aryl-β-lactams can be prepared conveniently by an intramolecular reaction of β-hydroxyarylamides under the influence of diethyl azodicarboxylate (DEAD) and triphenylphosphine (TPP). Optically active 3-amino-2-azetidinone derivatives can be prepared by this method starting with a suitably protected α-amino-β-hydroxy carboxylic acid amide. This cyclization involves the retention of configuration at C2 and complete inversion at C3 of the starting acid. In some cases diamides of azodicarboxylic acid have been used by replacing TPP with the more reactive tributyl phosphine. Other phosphorus reagents such as phosphite esters and hexamethyl phosphorus triamide could also be used.