Stereoselective Synthesis of 1,4,5-Tri-cis-guaiane Sesquiterpene: First Total Synthesis of (−)-Dendroside C Aglycon

The first total synthesis of (−)-dendroside C aglycon, consisting of a 1,4,5-tri-cis-guaiane skeleton, from a versatile hydroazulene intermediate has been accomplished. The key features of the syntheses include the stereoselective preparation of the unusual cis-hydroazulene core via a sequence of a unique Dieckmann condensation of the bicyclic lactone system, which was concisely prepared by the tandem conjugate addition and intramolecular allylic alkylation of a butenolide precursor, and construction of the characteristic tricyclic skeleton by a carbene-mediated cyclopropanation.