A direct intramolecular C-H amination reaction cocatalyzed by copper(II) and iron(III) as part of an efficient route for the synthesis of pyrido[1,2-a]benzimidazoles from N-aryl-2-aminopyridines.
A novel and efficient synthesis of pyrido[1,2-a]benzimidazoles through direct intramolecular aromatic C-H amination of N-aryl-2-aminopyridines has been developed. The reaction, cocatalyzed by Cu(OAc)(2) and Fe(NO(3))(3)·9H(2)O, is carried out in DMF under a dioxygen atmosphere. Diversified pyrido[1,2-a]benzimidazoles containing various substitution patterns are obtained in moderate to excellent yields by using this procedure. The results of mechanistic studies suggest that a Cu(III)-catalyzed electrophilic aromatic substitution (S(E)Ar) pathway is operating in this process. The unique role of iron(III) is believed to lie in its ability to facilitate formation of the more electrophilic Cu(III) species. In the absence of iron(III), a much less efficient and reversible Cu(II)-mediated S(E)Ar process takes place.
Wang
Honggen
H
State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Avenue, Guangzhou 510530, China.
Wang
Yong
Y
Peng
Changlan
C
Zhang
Jiancun
J
Zhu
Qiang
Q
D000586:Amination; D000631:Aminopyridines / Q000138:chemical synthesis*; D001562:Benzimidazoles / Q000138:chemical synthesis*; D002244:Carbon / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D005290:Ferric Compounds / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry*
D000631:Aminopyridines; D001562:Benzimidazoles; D005290:Ferric Compounds; D002244:Carbon; D003300:Copper; D006859:Hydrogen; C032439:alpha-aminopyridine