Scalable synthesis of enantiomerically pure bicyclo[2.2.2]octadiene ligands

J Org Chem. 2012 May 18;77(10):4765-73. doi: 10.1021/jo3005638. Epub 2012 May 2.

Abstract

An operationally simple and scalable synthesis of enantiomerically pure bicyclo[2.2.2]octadiene (bod*) ligands relying on an organocatalytic one-pot Michael addition-aldol reaction with cheap 2-cyclohexenone and phenylacetaldehyde is presented. The crystalline bicyclic product 4a (6-hydroxy-5-phenylbicyclo[2.2.2]octan-2-one) is transformed into phenylbicyclo[2.2.2]oct-5-en-2-one 2, a versatile starting material for the 2-step synthesis of both symmetrical, such as Hayashi's Ph-bod* ligand, as well as novel unsymmetrical chiral dienes.

MeSH terms

  • Acetaldehyde / analogs & derivatives*
  • Acetaldehyde / chemistry
  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / chemistry*
  • Catalysis
  • Cyclohexanones / chemistry*
  • Ligands
  • Molecular Structure
  • Stereoisomerism

Substances

  • 6-hydroxy-5-phenylbicyclo(2.2.2)octan-2-one
  • Bridged Bicyclo Compounds
  • Cyclohexanones
  • Ligands
  • 2-cyclohexen-1-one
  • Acetaldehyde
  • phenylacetaldehyde