Practical stereoselective synthesis of an alpha-trifluoromethyl-alpha-alkyl epoxide via a diastereoselective trifluoromethylation reaction

J Org Chem. 2007 Jan 5;72(1):292-4. doi: 10.1021/jo061839l.

Abstract

A practical stereoselective synthesis is reported for an alpha-trifluoromethyl-alpha-alkyl epoxide (1), which is an important pharmaceutical intermediate. The key step involves a chiral auxiliary-controlled asymmetric trifluoromethylation reaction for the introduction of the unique trifluoromethyl-substituted tertiary alcohol stereogenic center in the target molecule. The fluoride-initiated CF3 addition to chiral keto ester 6a proceeded with a diastereoselectivity up to 86:14. The major diastereomer was readily obtained with a >99.5:0.5 dr through a simple crystallization of the crude product mixture.

MeSH terms

  • Alkylation
  • Epoxy Compounds / chemical synthesis
  • Epoxy Compounds / chemistry*
  • Esters / chemistry
  • Fluorine / chemistry*
  • Methylation
  • Molecular Structure
  • Stereoisomerism

Substances

  • Epoxy Compounds
  • Esters
  • Fluorine