Synthetic Approach to Chromone and Flavonoid Piperidine Alkaloids.

Despite the enormous importance of chromone and flavonoid piperidine alkaloids, a general method for their synthesis has not been described. Accordingly, from simple tetrahydro-3-pyridinemethanols ( A ) and phenol derivatives ( B ), a synthetic approach to chromone and flavonoid piperidine alkaloids is presented. The access to a novel chromone and flavonoid alkaloid precursors 4-(2-hydroxyphenyl)-3-methylenepiperidines ( C ) is achieved in only two steps: Mitsunobu reaction followed by an intramolecular C-H phenolization via an aromatic Claisen rearrangement of the respective Mitsunobu adducts ( D ). Consequently, the simultaneous installation of the functionalized phenol group and the exo-methylene group within the piperidine skeleton, permits, not only the easy construction of the chromone or flavonoid cores but also the simultaneous installation of the hydroxyl group with the required cis -orientation. Additionally, the synthetic utility of this novel approach is showcased in the formal synthesis of flavopiridol, rohitukine, and their N -Moc analogues.