Synthesis of lycorines by intramolecular aryne cycloadditions

Intramolecular Diels-Alder reactions between the aryne and azadiene derivatives result in the formation of lycorine alkaloids. Aryne-azadiene can be obtained by base-activated dehydrohalogenation of an haloarene and enolization of an amide. Alterations in the nature or position of the substituents provide different products due to change in regioselectivity. Cyclization involves a two-step ionic mechanism initiated by nucleophilic attack on the benzyne by the nitrogen atom followed by intramolecular addition of the phenyl carbanion to the promoted benzene ring.