Reactive species from aromatics and oxa-di-π-methane rearrangement: a stereoselective synthesis of (±)-hirsutene from salicyl alcohol

A total synthesis of hirsutene, a triquinane sesquiterpene, from salicyl alcohol is reported. Oxidation of salicyl alcohol in the presence of cyclopentadiene gave 9-spiroepoxy-endo-tricyclo5.2.2.0^2,6]undeca-4,10-dien-8-one which was elaborated to the 3-hydroxy-2-methyl-endo-tricyclo5.2.2.0^2,6]undeca-10-en-8-one containing major structural and functional features of hirsutene. Photochemical sigmatropic 1,2-acyl shift in 3-hydroxy-2-methyl-endo-tricyclo5.2.2.0^2,6]undeca-10-en-8-one followed by radical induced cleavage of peripheral cyclopropane bond, olefination and Simmon-Smith reaction furnished 11-hydroxy-1-methyl-4-spirocyclopropanetricyclo6.3.0.0^2,6]undecane that upon treatment with hydrogen on PtO₂ and PCC oxidation gave 1,4,4-trimethyltricyclo6.3.0.0^2,6]undecan-11-one, a known precursor. Wittig methylenation on this precursor gave hirsutene.