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Synthesis of (±)-Isocomene
Total Synthesis of (±)-Isocomene.
J. Am. Chem. Soc. 1979;
18 October 2019 (online)
Key words(±)-isocomene - Stork–Danheiser transposition - [2+2] photocycloaddition - Wittig olefination - Wagner–Meerwein rearrangement
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.