Challenging the Molecular Parameters of Vetiver: Can 4,5-Dimethyl-3-(3′-methylbut-1′-en-2′-yl)-4-phenylcyclopent-2-en-1-one Mimic Zizaenones in Structure and Odor?

In order to investigate the molecular parameters of vetiver odorants and scrutinize the significance of ziza-6(13)-en-3-ones as structural templates in the design of new vetiver odorants, 4,5-dimethyl-3-(3 '-methylbut-1 '-en-2 '-yl)-4-phenylcyclopent-2-en-1-one (10) was synthesized in 6 steps from cyclopentane-1,3-dione (20) following a Stork-Danheiser strategy after synthetic approaches by Ni-catalyzed [3+2] annulation and enyne metathesis had failed. Addition of EtOH, alpha-methylation of the resulting vinylogous ester 18, Pd-catalyzed alpha-arylation, and CeCl3 center dot 2LiCl mediated alkylation with (3-methylbut-1-en-2-yl)lithium, generated by Shapiro reaction from the corresponding hydrazone 23, furnished after a concluding alpha-methylation the target compound that possessed only a weak woody odor devoid of typical vetiver characteristics. While the design approach utilizing London dispersion forces could not reveal the secret of vetiver, it showed that the molecular parameters are far more complex than initially expected.