Chen Yu, Yuan Ruyi, Zheng Tongtong, Guo Qingting, Yao Yingming, Zhang Li
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, China.
Nat Commun. 2025 Mar 16;16(1):2584. doi: 10.1038/s41467-025-57855-x.
Late-stage deuteration of aryl halides with deuterium oxide is a highly desirable but challenging transformation, primarily due to the difficulty of activating inert carbon-halogen bonds and the umpolung of deuterium oxide in the presence of various functional groups. To achieve this transformation, efforts have been made to develop photo-chemical, electro-chemical, or mechano-chemical strategies. However, these approaches often require specialized setups or activated substrates. Despite the well-known functional group tolerance of palladium catalysis, which makes it valuable in late-stage functionalization, a palladium-catalyzed deuteration of aryl halides with deuterium oxide has remained elusive. Herein, a deuteration reaction of aryl bromides, chlorides, and triflates with deuterium oxide has been developed, through palladium catalysis. Chemical equivalent amount of DO is required for inert substrates like aryl chlorides. The reaction features high functional group tolerance, making it suitable for late-stage deuteration.
利用氧化氘对芳基卤化物进行后期氘代是一种非常理想但具有挑战性的转化反应，主要是因为活化惰性碳 - 卤键存在困难，并且在各种官能团存在的情况下氧化氘会发生极性反转。为了实现这种转化，人们已经努力开发光化学、电化学或机械化学策略。然而，这些方法通常需要专门的装置或活化的底物。尽管钯催化对官能团具有众所周知的耐受性，这使其在后期官能团化中很有价值，但钯催化利用氧化氘对芳基卤化物进行氘代反应一直难以实现。在此，通过钯催化，已开发出一种利用氧化氘对芳基溴化物、氯化物和三氟甲磺酸酯进行氘代的反应。对于像芳基氯化物这样的惰性底物，需要化学计量的氧化氘。该反应具有高官能团耐受性，适用于后期氘代。
