Total Synthesis of (±)-Methyl Atis-16-en-19-oate via Homoallyl−Homoallyl Radical Rearrangement

Abstract

Total synthesis of (±)-methyl atis-16-en-19-oate (5c), a tetracyclic diterpenoid possessing a bicyclo[2.2.2]octane ring system, was accomplished. Intramolecular Diels−Alder reaction of tetraene 14 was employed in a construction of kaurene skeleton 13. The pivotal step involved a homoallyl−homoallyl radical rearrangement process of (±)-methyl 12-hydroxykaur-16-en-19-oate monothioimidazolide 12, which led to 5c in good yield. Interestingly, treatment of methyl 12-oxo-kaur-16-en-19-oate 30 with hydrazine monohydrate in the presence of KOH in bis(ethylene glycol) at 200 °C resulted in cyclopropanation to furnish, directly, trachyloban-19-oic acid (4b), together with kaur-16-en-19-oic acid (6b).