Oxygen-Free Csp3-H Oxidation of Pyridin-2-yl-methanes to Pyridin-2-yl-methanones with Water by Copper Catalysis

• Published in: Molecules (Basel, Switzerland) Vol. 28; no. 22; p. 7587
• Main Authors: Zeng, Ming, Chen, Jia-Le, Luo, Xue, Zou, Yan-Jiao, Liu, Zhao-Ning, Dai, Jun, Jiang, Deng-Zhao, Li, Jin-Jing
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 14.11.2023
• Subjects: Antifungal agents; By products; Catalysis; Chromatography; Copper; copper catalysis; Csp3-H oxidation; mechanism study; Oxidation; pyridin-2-yl-methanones; water
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules28227587

Aromatic ketones are important pharmaceutical intermediates, especially the pyridin-2-yl-methanone motifs. Thus, synthetic methods for these compounds have gained extensive attention in the last few years. Transition metals catalyze the oxidation of Csp3-H for the synthesis of aromatic ketones, which is arresting. Here, we describe an efficient copper-catalyzed synthesis of pyridin-2-yl-methanones from pyridin-2-yl-methanes through a direct Csp3-H oxidation approach with water under mild conditions. Pyridin-2-yl-methanes with aromatic rings, such as substituted benzene, thiophene, thiazole, pyridine, and triazine, undergo the reaction well to obtain the corresponding products in moderate to good yields. Several controlled experiments are operated for the mechanism exploration, indicating that water participates in the oxidation process, and it is the single oxygen source in this transformation. The current work provides new insights for water-involving oxidation reactions.