Decarbonylative Phosphorylation of Amides by Palladium and Nickel Catalysis: The Hirao Cross‐Coupling of Amide Derivatives

Abstract Considering the ubiquity of organophosphorus compounds in organic synthesis, pharmaceutical discovery agrochemical crop protection and materials chemistry, new methods for their construction hold particular significance. A conventional method for the synthesis of C−P bonds involves cross‐coupling of aryl halides and dialkyl phosphites (the Hirao reaction). We report a catalytic deamidative phosphorylation of a wide range of amides using a palladium or nickel catalyst giving aryl phosphonates in good to excellent yields. The present method tolerates a wide range of functional groups. The reaction constitutes the first example of a transition‐metal‐catalyzed generation of C−P bonds from amides. This redox‐neutral protocol can be combined with site‐selective conventional cross‐coupling for the regioselective synthesis of potential pharmacophores. Mechanistic studies suggest an oxidative addition/transmetallation pathway. In light of the importance of amides and phosphonates as synthetic intermediates, we envision that this Pd and Ni‐catalyzed C−P bond forming method will find broad application.