Jie Gao, Subhajit Bhunia, Kailiang Wang, Lu Gan, Shanghua Xia and Dawei Ma*
*Interdisciplinary Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 26 Qiuyue Lu, Shanghai 201210, China, Email: madw
J. Gao, S. Bhunia, K. Wang, L. Gan, S. Xia, D. Ma, Org. Lett., 2017, 19, 2809-2812.
DOI: 10.1021/acs.orglett.7b00901
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Abstract
A class of N-(naphthalen-1-yl)-N’-alkyl oxalamides are powerful ligands in Cu-catalyzed coupling reactions of (hetero)aryl iodides and bromides with primary amines or ammonia. A wide range of coupling partners work well under these conditions.
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Details
This study introduces N-(naphthalen-1-yl)-N’-alkyl oxalamides as highly effective ligands for Cu-catalyzed aryl amination reactions. These ligands enable coupling of (hetero)aryl iodides with primary amines at 50 °C using only 0.01 mol % Cu2O and ligand, achieving over 10,000 turnovers. Similarly, coupling of (hetero)aryl bromides with primary amines and ammonia proceeds at 80 °C with 0.1 mol % Cu2O and ligand. The method demonstrates broad compatibility with various (hetero)aryl halides and amines, offering high yields and excellent chemoselectivity. Functionalized amines and heteroaryl bromides also perform well under these conditions, showcasing tolerance to diverse functional groups.
The study highlights MNBO as the optimal ligand, achieving complete conversion in 12 hours. Ethanol and tert-butyl alcohol are effective solvents, and the reaction is scalable, producing large quantities with minimal catalyst. Additionally, the method facilitates the synthesis of primary arylamines and cyclic secondary amines, which are crucial in drug discovery. The mild, environmentally friendly conditions and high turnover numbers make this approach promising for large-scale production of aryl amines. This work represents a significant advancement in Cu-catalyzed aryl amination, with ongoing investigations into its application in other coupling reactions.
CuI/Oxalic Diamide Catalyzed Coupling Reaction of (Hetero)Aryl Chlorides and Amines
W. Zhou, M. Fan, J. Yin, Y. Jiang, D. Ma, J. Am. Chem. Soc., 2015, 137, 11942-11945.
CuI/DMPAO-Catalyzed N-Arylation of Acyclic Secondary Amines
Y. Zhang, X. Yang, Q. Yao, D. Ma, Org. Lett., 2012, 14, 3056-3059.
Assembly of Biaryl Amines via Mild Copper-Catalyzed Coupling of Anilines with (Hetero)aryl Chlorides/Bromides
S. Li, L. Xu, B. An, D. Ma, Org. Lett., 2025, 27, 1498-1503.
Key Words
Ullmann reaction, amination