Oxidative Ring‐Opening of 1H‐Pyrazol‐5‐amines and Its Application in Constructing Pyrazolo–Pyrrolo–Pyrazine Scaffolds by Domino Cyclization

Herein, an oxidative ring‐opening of 1H‐pyrazol‐5‐amines to form 3‐diazenylacrylonitrile derivatives under mild and transition‐metal‐free conditions is described. In addition, the nucleophilic addition of deprotonated 1H‐pyrrole‐2‐carbaldehydes to the vinyl moiety of the yielded 3‐diazenylacrylonitriles could trigger domino cyclization to afford the 3H‐pyrazolo[3,4‐e]pyrrolo[1,2‐a]pyrazine derivatives. Computational studies suggest that the oxidation of 1H‐pyrazol‐5‐amines in the presence of PhIO is through the formation of a hydroxylamine intermediate followed by elimination of H2O to result in the ring‐opening product. The detailed domino cyclization pathway leading to the pyrazolo–pyrrolo–pyrazine scaffolds is revealed. A concise approach to synthesize 3H‐pyrazolo[3,4‐e]pyrrolo[1,2‐a]pyrazine derivatives via oxidative ring‐opening of 1H‐pyrazol‐5‐amines under mild and transition‐metal‐free conditions is described herein.