Synthesis of (±)-Isocomene

Key words

(±)-isocomene - Stork–Danheiser transposition - [2+2] photocycloaddition - Wittig olefination - Wagner–Meerwein rearrangement

Significance

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.

Comment

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.