Ligand- and Temperature-Controlled Stereodivergent Nickel-Catalyzed Hydrophenoxylation of Ynamides

The controlled synthesis of both <i>E</i>- and <i>Z</i>-stereoisomers remains a long-standing challenge in organic synthesis, yet it is important for accessing structurally and functionally diverse enamides. This study demonstrates the synthesis of <i>E</i>- and <i>Z</i>-hydrophenoxylated enamides using a nickel(II)-catalyst alongside phenols. The stereochemical outcome is controlled by the ligand environment and temperature. Ligands promote <i>syn</i>-addition via a keteniminium intermediate to afford the <i>E</i>-isomer, and elevated temperatures enable efficient <i>E→Z</i> isomerization to deliver the <i>Z</i>-isomer with excellent selectivity. This efficient and versatile strategy exhibits a broad substrate scope and functional group tolerance, including acids, bioactive estrone derivatives, sesamol, and related compounds.