Enantioselective synthesis of (-)-dihydrocodeine and formal synthesis of (-)-thebaine, (-)-codeine, and (-)-morphine from a deprotonated α-aminonitrile

Org Lett. 2014 Oct 17;16(20):5282-5. doi: 10.1021/ol5023849. Epub 2014 Oct 1.

Abstract

The α-benzylation of a deprotonated bicyclic α-aminonitrile, followed by Noyori's asymmetric transfer hydrogenation combined with the Grewe cyclization onto a symmetrical A-ring precursor, are the key steps of a short and high-yielding enantioselective synthesis of the morphinan (-)-dihydrocodeine. This compound can be converted to (-)-thebaine in high yield by known transformations, while (-)-codeine and (-)-morphine are available from an advanced intermediate.

MeSH terms

  • Codeine / analogs & derivatives*
  • Codeine / chemical synthesis
  • Codeine / chemistry
  • Hydrogenation
  • Molecular Structure
  • Morphine / chemical synthesis*
  • Morphine / chemistry
  • Nitriles / chemistry*
  • Stereoisomerism
  • Thebaine / chemical synthesis*
  • Thebaine / chemistry

Substances

  • Nitriles
  • Thebaine
  • Morphine
  • dihydrocodeine
  • Codeine