Palladium-Catalyzed Trimethylenemethane Cycloaddition of Olefins Activated by the σ-Electron-Withdrawing Trifluoromethyl Group

J Am Chem Soc. 2015 Sep 16;137(36):11606-9. doi: 10.1021/jacs.5b07573. Epub 2015 Sep 8.

Abstract

α-Trifluoromethyl-styrenes, trifluoromethyl-enynes, and dienes undergo palladium-catalyzed trimethylenemethane cycloadditions under mild reaction conditions. The trifluoromethyl group serves as a unique σ-electron-withdrawing group for the activation of the olefin toward the cycloaddition. This method allows for the formation of exomethylene cyclopentanes bearing a quaternary center substituted by the trifluoromethyl group, compounds of interest for the pharmaceutical, agrochemical, and materials industries. In the diene series, the cycloaddition operates in a [3 + 4] and/or [3 + 2] manner to give rise to seven- and/or five-membered rings. This transformation greatly improves the scope of the TMM cycloaddition technology and provides invaluable insights into the reaction mechanism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkenes / chemistry*
  • Catalysis
  • Cycloaddition Reaction*
  • Electrons
  • Methane / analogs & derivatives*
  • Methane / chemistry
  • Palladium / chemistry*

Substances

  • Alkenes
  • trimethylenemethane
  • Palladium
  • Methane