Carbamoyl anion addition to N-sulfinyl imines: highly diastereoselective synthesis of α-amino amides

J Am Chem Soc. 2013 Apr 17;135(15):5565-8. doi: 10.1021/ja402647m. Epub 2013 Apr 9.

Abstract

Carbamoyl anions, generated from N,N-disubstituted formamides and lithium diisopropylamide, add with high diastereoselectivity to chiral N-sulfinyl aldimines and ketimines to provide α-amino amides. The methodology enables the direct introduction of a carbonyl group without the requirement of unmasking steps as with other nucleophiles. The products may be converted to α-amino esters or 1,2-diamines. Iterative application of the reaction enabled the stereoselective synthesis of a dipeptide. Spectroscopic and computational studies support an anion structure with η(2) coordination of lithium by the carbonyl group.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry*
  • Chemistry Techniques, Synthetic
  • Dipeptides / chemical synthesis
  • Dipeptides / chemistry
  • Imines / chemistry*
  • Models, Molecular
  • Molecular Conformation
  • Stereoisomerism
  • Substrate Specificity

Substances

  • Amides
  • Dipeptides
  • Imines