Nickel-catalyzed domino annulation coupling to construct oxindole analogues: A mechanistic and synthetic investigation

Nickel-catalyzed reductive coupling reactions are widely used to construct molecular scaffolds; however, the mechanisms of these reactions remain less studied. Here, we present a nickel-catalyzed reductive cyclization method to construct oxindole bearing new formed C-X (X = CN, I, and P) bonds. To investigate the detailed mechanism, different types of ligand-chelated σ-alkyl-Ni(II) complexes were isolated, characterized, and allowed to conduct relevant stoichiometric and catalytic reactions. Our collected data indicated that <i>N</i>-ligands promoted the oxidative addition and subsequent migratory insertion of the nickel complex with substrates. <i>P</i>-ligated catalysts facilitated the reductive elimination of the σ-alkyl-Ni(II)-CN intermediate to generate annulation products and suppressed byproduct formation. Further investigations elucidated that the C-CN bond was activated by zinc with the assistance of trifluoroacetic anhydrides. Ultimately, each step of nickel catalyzed annulations was clarified and these series of mechanistic studies settle the controversy of nickel catalytic cycle.