Total Synthesis of Avenaol

Avenaol is a terpene with a unique all-cis cyclopropane in which all bulky substituents are oriented in the same direction. It is categorized into a non-canonical strigolactone. We have synthesized alkylidenecyclopropanes by Rh-catalyzed intramolecular cyclopropanation of allenes, followed by iridium-catalyzed diastereoselective double bond isomerization to construct all-cis cyclopropanes. Subsequently, distinction of the two hydroxymethyl groups of 1,3-diol by an intramolecular SN1-type reaction, followed by cleavage of the tetrahydropyranyl ring by regioselective C–H oxidation, led to the desired stereochemistry at the C-ring lactone. Using these key steps, the first racemic total synthesis of avenaol was achieved, and the proposed relative configuration of avenaol was proved synthetically. Furthermore, we developed a stereoselective introduction of D-ring butenolide via chiral thiourea-quaternary ammonium salt-catalyzed dynamic kinetic optical resolution. Then, by applying this method to synthetic intermediates, (+)-avenaol was successfully synthesized. This chapter details the total synthesis of avenaol, including failed attempts.