N,N-DIIsopropyl-N-phosphonyl imines lead to efficient asymmetric synthesis of aziridine-2-carboxylic esters

Org Biomol Chem. 2013 May 28;11(20):3400-8. doi: 10.1039/c3ob40251g.

Abstract

Highly diastereoselective asymmetric synthesis of chiral aziridine-2-carboxylic esters is reported for 20 examples with good yields (51-87%) and excellent diastereoselectivities (>99:1 dr for most cases). The modified N-phosphonyl imines have proven to be superior to previous imine auxiliaries for the aza Darzens reaction by using a secondary isopropyl group to replace the primary benzyl group for N,N-diamino protection. In the meanwhile, a special operation by slowly adding the pre-cooled imine solution at -78 °C into the preformed β-bromo lithium enolate mixture at this temperature in the presence of 4 Å molecular sieves was found to be crucial in terms of yields and diastereoselectivity. The present method can provide an easy and general access to β-hydroxy α-amino acids and other important amino building blocks.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aziridines / chemical synthesis*
  • Aziridines / chemistry
  • Esters / chemical synthesis*
  • Esters / chemistry
  • Imines / chemistry*
  • Molecular Structure

Substances

  • Aziridines
  • Esters
  • Imines
  • aziridine-2-carboxylic acid