Cu-Mediated Amination of (Hetero)Aryl C-H bonds with NH Azaheterocycles

Angew Chem Int Ed Engl. 2019 Dec 9;58(50):18141-18145. doi: 10.1002/anie.201910395. Epub 2019 Nov 8.

Abstract

Direct synthesis of N-(hetero)arylated heteroarenes has been realized through Cu-mediated C-N coupling of NH azaheterocycles with aryl C-H bonds under aerobic conditions. This method features a broad scope of both heterocyclic arenes (pyridine, quinoline, pyrazole, imidazole, furan, thiophene, benzofuran, and indole) and NH azaheterocycles (imidazole, pyrazole, indole, azindole, purine, indazole, benzimidazole, pyridone, carbazole), providing a versatile method for the synthesis of pharmaceutically important N-(hetero)arylated heteroarenes. The versatility of this reaction was further demonstrated through late-stage modification of marketed drugs and the synthesis of a key intermediate for accessing a class of angiotensin II receptor 1 antagonists.

Keywords: C−H amination; azolation; copper; heterocycles; homogeneous catalysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amination
  • Aza Compounds / chemistry*
  • Carbon / chemistry
  • Copper / chemistry*
  • Heterocyclic Compounds / chemical synthesis
  • Heterocyclic Compounds / chemistry*
  • Hydrogen / chemistry
  • Imidazoles / chemistry
  • Oxadiazoles / chemistry
  • Telmisartan / chemistry

Substances

  • Aza Compounds
  • Heterocyclic Compounds
  • Imidazoles
  • Oxadiazoles
  • Carbon
  • Copper
  • imidazole
  • Hydrogen
  • ataluren
  • Telmisartan