Synergistic Pd/Cu‐Catalyzed Stereodivergent Controlling of the Z/E and R/S Configurations: Synthesis of Non‐Natural α‐Amino Acids Containing Trisubstituted Olefin

Abstract The synthesis of non‐natural α‐amino acids containing trisubstituted olefins with controlled Z/E and R/S configurations represents a significant challenge in organic synthesis. Herein, we report a synergistic Pd/Cu‐catalyzed approach that enables stereodivergent control over both central chirality and olefin geometry. By leveraging orthogonal catalytic cycles, this method allows for the independent and precise manipulation of these stereochemical elements within a single catalytic system. Specifically, the palladium catalyst governs the olefin configuration through ligand‐directed chemoselectivity, while the copper catalyst dictates the stereochemical outcome at the α‐carbon of the nucleophile. This dual catalytic strategy achieves a stereodivergent synthesis of olefin‐containing unnatural amino acids (UAAs), providing access to all four stereoisomers ( Z/R , Z/S , E/R , E/S ) through deliberate catalyst combinations.