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 (<b>A</b>) and phenol derivatives (<b>B</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 (<b>C</b>) 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 (<b>D</b>). 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 <i>cis</i>-orientation. Additionally, the synthetic utility of this novel approach is showcased in the formal synthesis of flavopiridol, rohitukine, and their <i>N</i>-Moc analogues.