Synfacts 2019; 15(11): 1226
DOI: 10.1055/s-0039-1691055
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of (±)-Isocomene

Erick M. Carreira
Moritz Hönig
Pirrung MC. * University of California, Berkeley, USA
Total Synthesis of (±)-Isocomene.

J. Am. Chem. Soc. 1979;
101: 7130-7131
Further Information

Publication History

Publication Date:
18 October 2019 (online)



Isolated from rayless goldenrod (Isocoma wrightii) in 1977, (±)-isocomene possesses an intriguing tricyclic carbon skeleton containing four adjacent stereocenters, three of which are quaternary. These structural features render the natural product a challenging target for synthesis. Pirrung was able to access isocomene in seven steps starting from commercially available 2-methylcyclohexa-1,3-dione. His strategy features an intramolecular [2+2] photocycloaddition to install three contiguous quaternary stereocenters and a Wagner–Meerwein rearrangement to furnish the tricyclic core.



Starting from commercially available 2-methylcyclohexa-1,3-dione (A), cyclohexenone E was accessed using a Stork–Danheiser transposition. Irradiation of the enone effected intramolecular [2+2] photocycloaddition to furnish cyclobutane F containing three adjacent quaternary stereocenters. Treatment of intermediate G with acid effected a Wagner–Meerwein rearrangement to give (±)-isocomene in excellent yield.