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 () and phenol derivatives (), 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 () 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 (). 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 -orientation. Additionally, the synthetic utility of this novel approach is showcased in the formal synthesis of flavopiridol, rohitukine, and their -Moc analogues.