Synthesis of marine brominated alkaloid amathamide F: a palladium-catalyzed enamide synthesis

Synthesis of brominated marine natural product amathamide F is described. Various strategies to construct the enamide functionality required for its synthesis have been explored. Finally, we succeeded in constructing the enamide moiety under a palladium-catalyzed condition. Facile transformation of 2,3,4-tribromo-5-methoxybenzaldehyde to the reported structure of amathamide F involved initial one-carbon-elongation of the aldehyde group followed by its conversion to corresponding enol acetate derivative prior to crucial Pd(II)-catalyzed cross-coupling with (S)-1-methylpyrrolidine-2-carboxamide. However, due to nonconformity of its NMR spectral data to that of the reported natural isolate, we have confirmed its actual structure through a synthesis.

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