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

The controlled synthesis of both E-
and Z-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 E- and Z-hydrophenoxylated enamides using
a nickel(II)-catalyst alongside phenols. The stereochemical outcome
is controlled by the ligand environment and temperature. Ligands promote syn-addition via a keteniminium intermediate to afford the E-isomer, and elevated temperatures enable efficient E→Z isomerization to deliver the Z-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.