A new route to furanoeremophilane sesquiterpenoids. Synthesis of Senecio metabolites (±)-6-hydroxyeuryopsin, (±)-1,10-epoxy-6-hydroxyeuryopsin, (±)-toluccanolide A and (±)-toluccanolide C

Abstract

A new strategy for the synthesis of sesquiterpenoids of the furanoeremophilane family was developed in which the tricyclic nucleus was assembled in an A + C → A–C → A–B–C sequence. The A–C connection was made via coupling of a cyclohexenylmethyl bromide with a stannylfuran under “ligandless” Stille conditions, and the key cyclization which closed ring B was accomplished with complete stereocontrol by intramolecular formylation of a 2-silylfuran in the presence of trimethylsilyl triflate. This route was used to complete the first total syntheses of the furanoeremophilane 6-hydroxyeuryopsin and the eremophilenolides toluccanolide A and toluccanolide C, as well as a formal synthesis of 1,10-epoxy-6-hydroxyeuryopsin.