3 years ago

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

Chiral Brønsted Acid-Catalyzed Asymmetric Synthesis of N-Aryl-cis-aziridine Carboxylate Esters
Sean P. Bew, Paolo Pesce, David L. Hughes, Sean M. Thurston, John Liddle
We report a multi-component asymmetric Brønsted 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. Nice and easy: An efficient one-pot synthesis of chiral non-racemic aziridines was achieved by using 1 mol % of a readily available Brønsted acid catalyst. The introduction of an ortho-tert-butoxy group on the N-aryl ring was critical to inducing high levels of optical activity in the products. By using this protocol a simple 4-step synthesis of the antibiotic (+)-chloramphenicol was realized.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201611990

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