Enantioselective synthesis of (-)-dihydrocodeinone: a short formal synthesis of (-)-morphine

J Org Chem. 2006 Jan 20;71(2):449-55. doi: 10.1021/jo0513008.

Abstract

[reaction: see text] The radical cyclization approach to the morphine alkaloids has been applied in an asymmetric synthesis of (-)-dihydrocodeinone. A chiral cyclohexenol (R-32), from the CBS reduction of the enone, is the source of chirality. The first key step, tandem closure in which stereochemistry is controlled by geometric constraints, (-)-15b --> (+)-16, was followed by an unprecedented reductive hydroamination, completing the synthesis of (-)-dihydroisocodeine ((-)-17) in 13 steps from commercially available materials.

Publication types

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

MeSH terms

  • Hydrocodone / chemical synthesis*
  • Hydrocodone / chemistry*
  • Models, Molecular
  • Molecular Conformation
  • Morphine / chemistry*
  • Morphine Derivatives / chemical synthesis
  • Morphine Derivatives / chemistry
  • Stereoisomerism

Substances

  • Morphine Derivatives
  • Hydrocodone
  • Morphine