Domino Double Michael-Claisen Cyclizations: A Powerful General Tool for Introducing Quaternary Stereocenters at C(4) of Cyclohexane-1,3-diones and Total Synthesis of Diverse Families of Sterically Congested Alkaloids.

[摘要]：Reactions of substituted acetone derivs., RCH2COMe (R = Me, Et, allyl, PhCH2, etc.), with acrylic acid esters, e.g. H2C:CHCO2CMe3, (>200 mol %) in the presence of t-BuOK (200 mol %) in t-BuOH-THF (1:1 by vol.) turned out to proceed as a cascade process consisting of the first Michael addn., the second Michael addn., and the last Claisen reaction to afford 4,4-disubstituted cyclohexane-1,3-diones I. Only more substituted enolates play the role of a Michael donor in this cascade process, and therefore the ketone took up two alkoxycarbonylethyl groups on the same carbon bearing more substituents. Such intermediates were followed by intramol. Claisen reactions leading to cyclohexane-1,3-diones bearing quaternary stereogenic centers at C(4), which bears an alkoxycarbonylethyl group and the substituent of the starting acetone derivs. Thus-obtained 4,4-disubstituted cyclohexane-1,3-diones were successfully employed for total syntheses of intricate alkaloids of biol. interest such as (+)-aspidospermidine, (?-galanthamine, (?-lycoramine, and (?-mesembrine, all featuring quaternary stereogenic centers. DFT calcns. provided us with clear-cut explanations for the obsd. chemoselectivity of the cascade process involving ketone-based enolates under thermodynamically controlled conditions.

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