Collective Synthesis of Illudalane Sesquiterpenes via Cascade Inverse Electron Demand (4 + 2) Cycloadditions of Thiophene S, S-Dioxides

J Am Chem Soc. 2022 Jun 8;144(22):10017-10024. doi: 10.1021/jacs.2c03304. Epub 2022 May 24.

Abstract

Thiophene S,S-dioxides are underutilized tools for the de novo construction of benzene rings in organic synthesis. We report a collective synthesis of nine illudalane sesquiterpenes using bicyclic thiophene S,S-dioxides as generalized precursors to the indane core of the natural products. Exploiting furans as unusual dienophiles in this inverse electron demand Diels-Alder cascade, this concise and convergent approach enables the synthesis of these targets in as little as five steps. Theoretical studies rationalize the reactivity of thiophene S,S-dioxides with both electron-poor and electron-rich dienophiles and reveal reaction pathways involving either nonpolar pericyclic or bifurcating ambimodal cycloadditions. Overall, this work demonstrates the wider potential of thiophene S,S-dioxides as convenient and flexible precursors to polysubstituted arenes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cycloaddition Reaction
  • Electrons*
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes*
  • Thiophenes

Substances

  • Illudalane
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes
  • Thiophenes