Palladium-Catalyzed Asymmetric Migratory Allylic Alkylation of Allylic Alcohols

Abstract

Directing-group (DG)-free enantioselective functionalization of C(sp³)–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(sp³)–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.

Keywords

Asymmetric allylic alkylation / π-Allylpalladium / Migration / Triple C–H bond / Regioselectivity / Alcohols / Homogeneous catalysis / C–C coupling

RIGHTS & PERMISSIONS

2025 SIOC, CAS, Shanghai, & WILEY-VCH GmbH