Chiral BrOnsted Acid-Catalyzed Asymmetric Synthesis of N-Aryl-cis-aziridine Carboxylate Esters

We report a multi-component asymmetric BrOnsted acid-catalyzed aza-Darzens reaction which is not limited to specific aromatic or heterocyclic aldehydes. Incorporating alkyl diazoacetates and, important for high ee's, ortho-tert-butoxyaniline our optimized reaction (i.e. solvent, temperature and catalyst study) affords excellent yields (61-98%) and mostly >90% optically active cis-aziridines. (+)-Chloramphenicol was generated in 4 steps from commercial starting materials. A tentative mechanism is outlined.