GIBH Makes Significant Progress in Dioxygen Activation

Very recently, a research group led by Dr. Qiang Zhu at GIBH made significant progress in copper-catalyzed dioxygen activation. The study shows that molecular dioxygen could be activated and incorporated into small molecules, forming formyl-substituted aromatic N-heterocycles very efficiently from simple and acyclic substrates. The results were published in Angew. Chem. Int. Ed. as a communication and the article was honored as “hot paper” selected by the editors.

This research has developed an unprecedented intramolecular dehydrogenative aminooxygenation (IDA) reaction catalyzed by 20 mol % CuII under a dioxygen atmosphere. Two privileged N-heterocycles substituted with aldehydes are obtained in moderate to good yields with broad substrate scope and good functionality tolerance. The aldehyde oxygen is derived from dioxygen by copper-mediated dioxygen activation and no additional organic or inorganic oxidants are required. The process, featuring high bond-forming efficiency, environmental benignity, and feasibility in scaffold diversification, will find its application in medicinal chemistry and chemical industry as well.  

In the article, the authors also demonstrated the effectiveness of this transformation by the fast assembly of Necopidem, an anxyolytic drug. Using the current process as the key step, the overall yield was improved dramatically from 21% to 50%.