Phosphoric Acid Catalyzed Asymmetric [2+2] Cyclization/Penicillin-Penillonic Acid Rearrangement

Abstract

Enantioselective synthesis of imidazolidin-5-ones through a phosphoric acid catalyzed reaction between azlactones and N-substituted β-carbolines is reported. The reaction takes place via an initial formal [2+2] cycloaddition to generate an α-amino-β-lactam, which subsequently undergoes an acid-catalyzed asymmetric penicillin-penillonic acid (PPA) rearrangement with high diastereo- and enantioselectivity. To the best of our knowledge, this represents the first [2+2] cyclization of azlactones with imines and the first asymmetric PPA rearrangement, which are linked together by the phosphoric acid catalyst.

Keywords: PPA rearrangement; asymmetric cyclization; azlactones; carbolines; chiral phosphoric acids.