Palladium‐Catalyzed Asymmetric Migratory Allylic Alkylation of Allylic Alcohols

Comprehensive Summary Directing‐group (DG)‐free enantioselective functionalization of C(sp 3 )–H bond has emerged as a powerful tool for the late‐stage diversification in synthetic and medicinal chemistry. Herein, we have developed an enantioselective triple C–H bond functionalization method via asymmetric migratory allylic substitution of 1,2‐enols enabled by palladium catalysis. The robust nature of the migratory allylic substitution strategy is reflected by a broad scope of both electrophiles and nucleophiles with the control of chemo‐, regio‐ and enantioselectivity. This migratory alkylation method is redox‐neutral, with three C(sp 3 )–H bonds being oxidized for the alkylative functionalization and the original enol unit being reduced simultaneously. Mechanistic studies suggest that each one‐carbon migration consists of the sequential β‐H elimination and migratory insertion to form a new π‐allylpalladium species with the intermediacy of the diene‐palladium complex. This method was successfully applied for the synthesis of biologically active substances, (+)‐Phenoxanol, (+)‐Citralis, and (−)‐Citralis Nitrile.