A copper-catalyzed aerobic domino process for the synthesis of isoindolin-1-ylidene derivatives

A convenient and efficient copper-catalyzed aerobic cascade reaction has been developed for the synthesis of the pharmacologically relevant isoindolin-1-ylidene scaffold. We discovered that various ortho-formyl cinnamates could react smoothly with different amines in the presence of a commercially available copper catalyst under mild aerobic conditions. Isoindolin-1-ylidene derivatives were assembled in one pot in moderate to good yields. This method features amine annulation and double dehydrogenation, representing high atomic efficiency. Its product could be further converted to the privileged isoindolinone pharmacophore.

Figure optionsDownload as PowerPoint slide