Direct Catalytic Asymmetric Conjugate Addition of Benzofuran‐3(2H)‐ones to α,β‐Unsaturated Thioamides: Stereodivergent Synthesis of Rocaglaol

Rocaglaol, a representative flavagline, has attracted significant attention because of its unique chemical structure and biological activities. This paper reports a mild and scalable copper‐catalyzed enantioselective conjugate addition of benzofuran‐3(2H)‐one to α,β‐unsaturated thioamides. This method allows for the concise synthesis of all possible stereoisomers of a key intermediate of rocaglaol and its derivatives in a highly diastereo‐ and enantioselective manner using different chiral phosphine ligands. Theoretical insights into the reaction mechanism and the origin of ligand‐dependent diastereodivergence were obtained using density functional theory calculations.