Concise Total Syntheses of (±)-Joubertiamine, (±)-O-Methyl­joubertiamine, (±)-3′-Methoxy-4′-O-methyljoubertiamine, (±)-Mesembrane, and (±)-Crinane

Abstract

A method to access cis-3a-aryloctahydroindole alkaloids has been developed through a key strategy involving Eschenmoser–Claisen rearrangement of allylalcohol. This approach gives us an opportunity to access the all-carbon quaternary center required for cis-3a-aryloctahydroindole alkaloids. Subsequent simple allylic oxidation of Eschenmoser–Claisen products and synthetic elaborations (reductions/oxidations) enabled the total syntheses of the title compounds to be completed in good yields in a few steps. The strategic viability was further tested in the total syntheses of Amaryllidaceae alkaloids (±)-mesembrane and (±)-crinane. Towards this end, we synthesized advanced intermediate keto-aldehydes from Eschenmoser–Claisen rearrangement products through iodolactonization followed by elaboration involving reduction and oxidation steps.

Keywords

Eschenmoser–Claisen rearrangement - all-carbon quaternary centers - allylic oxidation - alkaloids

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