Reactivity umpolung in intramolecular ring closure of 3,4-disubstituted butenolides: diastereoselective total synthesis of paeonilide

Org Lett. 2013 Nov 15;15(22):5826-9. doi: 10.1021/ol4028804. Epub 2013 Oct 31.

Abstract

Remarkable reactivity reversal stratagem in 3,4-disubstituted butenolides under acidic conditions is described. Design of a suitably substituted multifunctional butenolide followed by an acid-catalyzed chemo- and diastereoselective intramolecular ring closure via the reactivity umpolung has been demonstrated to accomplish a concise total synthesis of paeonilide. Overall, the present protocol involves one-pot reduction of an α,β-unsaturated carbon-carbon double bond and intramolecular nucleophilic insertion of oxygen function at the electron-rich γ-position of butenolide. The involved mechanistic aspects have also been discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemistry
  • Cyclization
  • Molecular Structure
  • Stereoisomerism
  • Terpenes / chemical synthesis*
  • Terpenes / chemistry

Substances

  • Terpenes
  • paeonilide
  • butenolide
  • 4-Butyrolactone