High-pressure Diels-Alder cycloadditions between benzylideneacetones and 1,3-butadienes: application to the synthesis of (R,R)-(-)- and (S,S)-(+)-Delta8-tetrahydrocannabinol

J Org Chem. 2010 Jun 18;75(12):4251-60. doi: 10.1021/jo100785w.

Abstract

High-pressure Diels-Alder reactions of various alkoxy/alkyl-substituted benzylideneacetones with methyl-1,3-butadienes are reported. Activation by high pressure (8-11 kbar) in combination with the mild Lewis acid HfCl(4).2THF allows these reactions to efficiently and regioselectively produce a series of ortho-substituted cyclohexenyl-benzene cycloadducts, that are useful precursors for the expeditious construction of the privileged 6,6-dimethyltetrahydro-6H-benzo[c]chromene skeleton. Application to the synthesis of Delta(8)-trans-THC in both enantiomeric pure forms is based on the successful resolution of selected cycloadduct by the SAMP-hydrazone method.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzylidene Compounds / chemistry*
  • Butadienes / chemistry*
  • Cannabidiol / chemical synthesis*
  • Cannabidiol / chemistry
  • Cyclization
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Stereoisomerism

Substances

  • Benzylidene Compounds
  • Butadienes
  • Cannabidiol