Asymmetric Synthesis of 3-Pyrrole Substituted β-Lactams Through p-Toluene Sulphonic Acid-catalyzed Reaction of Azetidine-2,3-diones with Hydroxyprolines

Abstract

Aims: The aim of this study is to investigate the p-toluene sulphonic acid (p-Ts.OH)- catalyzed reaction of racemic-azetidine-2,3-diones with enantiomerically pure cis and trans-4- hydroxy-L-proline in refluxing ethanol culminating in a synthesis of substituted novel 3-(pyrrol-1- yl)-azetidin-2-ones at the C-3 position. Methods: This work describes an alternative synthetic route enabling the tandem transformation of proline to pyrrole, followed by intramolecular chirality transfer to the β -lactams ring. Results: All four diastereomers of 3-(pyrrol-1-yl)-azetidin-2-ones could be achieved in good to excellent yield with high diastereoselectivity in a single-pot operation. Conclusion: This method can be applied to other activated carbonyl compounds and functionalized pyrroles can be obtained through an expeditious process.