Addition–Migration Cascade for Ortho ‐Selective Carbon Functionalization of Phenols

Ortho ‐ and para ‐carbon‐disubstituted phenols are prevalent in natural products and pharmaceuticals, yet their selective synthesis remains challenging. The strong resonance‐donating effect of the hydroxyl group renders phenols electron‐rich, activates both ortho and para positions, and limits their direct functionalization with external nucleophiles. Herein, we report an addition–migration–rearomatization strategy for the ortho ‐selective carbon functionalization of phenols using readily accessible para ‐quinol carbonates and diverse organometallic nucleophiles. The transformation proceeds through nucleophilic 1,2‐addition to the dienone carbonyl, followed by C1‐to‐C2 group migration and rearomatization, thereby enabling the formal installation of carbon nucleophilic substituents at the enone α‐position. A broad range of sp 3 ‐, sp 2 ‐, and sp ‐hybridized nucleophiles, including alkyl, vinyl, aryl, heteroaryl, polyaromatic, and alkynyl reagents, participate efficiently under mild conditions. DFT calculations identify syn ‐methyl facial attack as kinetically preferred over syn ‐Boc facial attack by 24.72 kcal mol − 1 , establish that both S N 2′ manifolds are noncompetitive, and show that aromatization proceeds via a Mg‐assisted decarboxylation/deprotonation pathway rather than an unassisted route. Synthetic utility is demonstrated through a concise five step synthesis of the bioactive natural product honokiol from commercially available allyl anisole.