A Practical Synthesis of α-Asarone via Iodine-catalyzed Isomerization of α/β-Asarone

α-Asarone (1), isolated from the Guatteria guameri plant growing in southeast Mexico, is reported to be an anti-platelet and hypolipidemic agent.1,2 In addition, it is known to have sedating, neuroleptic, spasmolytic, anti-ulcerogenic and anti-atherogenic activity.3,4 Due to its low availability from natural sources, several synthetic approaches have been developed for α-asarone (trans-isomer, 1), which involve Grignard, Wittig, Aldol-Grob, Friedel-Crafts reactions.5–9 However, in the above methods, some of the unwanted toxic β-asarone (cis-isomer, 2) was always formed, along with the desired α-asarone, which is difficult to separate by column chromatography due to similarities in Rf values. β-Asarone can be converted to α-asarone by fusion with KOH in good yield.10 However, this reaction requires an excess amount of KOH (37 equiv.) and high temperature (200–220◦C). Selenium dioxide, which can effectively convert β-asarone to α-asarone,10 is not a good choice due to its toxicity. A recently developed palladium (II) catalyzed isomerization of cis-arylalkenes can also be applied to the preparation of α-asarone,11,12 however, industrial applications of this reaction on synthesis of α-asarone are challenging because the catalyst is expensive,