Synthesis based on cyclohexadienes. Part 15. Total synthesis of (±)-prezizaene, (±)-prezizanol and (±)-jinkohol II

Abstract

A new methodology for the synthesis of the complex ring system tricyclo[6.2.1.01,5]undecane, present in the zizaene group of sesquiterpenes, is described. Acid-catalysed rearrangement of the endo alcohol 20 afforded the enone 12, which was transformed stereoselectively into the key intermediate, (±)-norprezizanone 10. The features of the synthesis are the transformation of a bicyclo[2.2.2]octane framework into a bicyclo[3.2.1]octane system by an acid-catalysed rearrangement and a stereoselective conjugate addition of a methyl group on an α,β-unsaturated keto ester at –100 °C. Norprezizanone was converted into the sesquiterpenes (±)-prezizanol 5 and (±)-prezizaene 4. The first total synthesis of (±)-jinkohol II 6 is also presented.