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.
Joshi et al. (Thu,) studied this question.