Microwave-Assisted Iodine-Catalyzed Diastereomeric Synthesis of 3-Pyrrole Substituted β -Lactams

Microwave-assisted reaction of achiral α-keto-β-lactams with optically active and commercially available trans-4-hydroxy-L-proline, using a catalytic amount of iodine in EtOH, resulted in a diastereoisomeric mixture of C-3 pyrrole-substituted β-lactams. We hypothesize that iodine in a polar protic solvent such as EtOH plays a crucial role by first coordinating with the ketone carbonyl to form an iodonium ion, which subsequently undergoes spontaneous rearrangement, releasing molecular iodine. This represents a novel method for synthesizing optically active pyrrole-substituted β- lactams in excellent yields. There are very few reports available on the synthesis of C-3 pyrrolesubstituted β-lactams. Our investigation shows that various aromatic substituents at N-1 and C-4 predominantly form cis-β-lactams over trans-β-lactams. The methodology is rapid and provides efficient access to diastereoisomeric β-lactams as both cis and trans isomers.