An efficient and general route to gem-difluoromethylenated alpha,beta-unsaturated delta-lactones: high enantioselective synthesis of gem-difluoromethylenated goniothalamins

J Org Chem. 2006 Sep 15;71(19):7261-7. doi: 10.1021/jo061012r.

Abstract

An efficient and general strategy to gem-difluoromethylenated alpha,beta-unsaturated delta-lactones in high yields from various aldehydes (including aliphatic, aromatic, alpha,beta-unsaturated, and sterically hindered aldehydes) has been developed. This methodology was successfully applied for the preparation of two enantiomers of gem-difluoromethylenated goniothalamins (S)-1 and (R)-1. gem-Difluoropropargylation of cinnamaldehyde followed by the resolution of resulting homopropargylic alcohols mediated by lipase from Pseudomonas (AK) gave alcohols (R)-6 and (S)-6. Selective hydrogenation of the triple bond of (S)-6 and (R)-6 to double bond with Lindlar catalyst in the presence of quinoline afforded the expected product (S)-8 and (R)-8, respectively. Deprotection of (S)-8 and (R)-8 followed by oxidation of the resulting 1,5-diols with catalytic 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) and excess bis-acetoxyiodobenzene (BAIB) provided the target molecules gem-difluoromethylenated goniothalamins (S)-1 and (R)-1 in high yields, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Furans / chemical synthesis*
  • Furans / chemistry
  • Hydrocarbons, Fluorinated / chemical synthesis*
  • Hydrocarbons, Fluorinated / chemistry
  • Lactones / chemical synthesis*
  • Lactones / chemistry
  • Molecular Structure
  • Stereoisomerism

Substances

  • Furans
  • Hydrocarbons, Fluorinated
  • Lactones
  • goniothalamicin