Bidentate Diamine Ligands for Cu-Catalyzed C-N Coupling

Amination of aromatic rings is an important reaction for the synthesis of functional compounds such as pharmaceuticals.¹⁾ Palladium catalysts have previously been used for amination, but there have been studies on the use of copper catalysts, which have low cost, low toxicity, and are easy to remove. It was reported that C-N coupling of aryl bromides with amines is possible using diamine bidentate ligands 1 and 2 with copper salts.²⁾ C-N coupling of aryl bromides and primary or secondary amines proceeds at room temperature in the presence of copper iodide, 1 or 2, and a base. Aryl bromides are also applicable to drug-like compounds containing heterocyclic rings. Ligands 1 and 2 are anionic and their high electron density accelerates oxidative addition. The catalytically active species 3 is stabilized by π-interactions with the central metal. When using aryl bromides with substituents in the ortho-position or bulky amines, 2 is more effective than 1 at preventing deactivation by N-arylation of the ligand. Furthermore, 1 has also been reported to be applicable to C-O coupling.³⁾

References

• 1) Transition-metal catalysed C–N bond activation
  • Q. Wang, Y. Su, L. Li, H. Huang, Chem. Soc. Rev. 2016, 45, 1257.
• 2) Room-Temperature Cu-Catalyzed Amination of Aryl Bromides Enabled by DFT-Guided Ligand Design
  • S. T. Kim, M. J. Strauss, A. Cabré, S. L. Buchwald, J. Am. Chem. Soc. 2023, 142, 6966.
• 3) Room-Temperature Copper-Catalyzed Etherification of Aryl Bromides
  • M. J. Strauss, M. E. Greaves, S.-T. Kim, C. N. Teijaro, M. A. Schmidt, P. M. Scola, S. L. Buchwald, Angew. Chem. Int. Ed. 2024, 63, e202400333.

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