Stereodivergent Construction of Enamides via a Radical-Mediated Isodesmic Reaction

Stereodivergent synthesis from the same starting materials is highly attractive but challenging in chemistry. Here, an unprecedented radical-mediated isodesmic reaction between aryl methylenemalononitriles and N-methyl amides is described. This integrated photochemical strategy enables the divergent synthesis of both (E)- and (Z)-enamides under very mild conditions. Particularly, it can prepare modularly (E)-α-deuterium enamides with >95% deuterium incorporation, representing a highly valuable addition to the research toolkit for enamide production. The utility of this protocol is also demonstrated by the synthesis of natural product alatamide and its deuterium-labeled analog. Mechanistic studies reveal that two sequential alkyl radical generations via photoinduced hydrogen atom transfer (HAT) in the presence of a sodium decatungstate (NaDT) catalyst are essential for this isodesmic reaction, and E/Z selectivities are adjusted by cocatalysts.