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

A new methodology for the synthesis of the complex ring system tricyclo[6.2.1.0(1.5)]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 bicycle[2.2.2] octane framework into a bicycle[3.2.1] octane system by an acid-catalysed rearrangement and a stereoselective conjugate addition of a methyl group on an alpha,beta-unsaturated keto ester at -100 degrees C. Norprezizanone was converted into the sesquiterpenes (+/-)-prezizanol 5 and(+/-)-prezizaene 4. The first total synthesis of (+/-)-jinkohol II 6 is also presented.

Synthesis of chiral bicyclo[2.2.2]oct-5-en-2-ones via an intramolecular alkylation reaction

Generation of the thermodynamic dienolate of 9-bromocarvone derivatives 5, 7 and 11 furnished the chiral bicycle[2.2.2] octenones 6, 8 and 9 and 12 and 13 containing a bridgehead methyl group via an intramolecular alkylation reaction. In an analogous manner intramolecular alkylation reaction of the bromo enones 15a-e, obtained from carvone 2 by 1,3-alkylative enone transposition (-->14) followed by a regiospecific bromoetherification reaction, furnished the bicyclo[2.2.2]oct-5-en-2-ones 16a-e and 17a-e.