ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
Cobalt- and Iron-Catalyzed Redox
Condensation of o‑Substituted
Nitrobenzenes with Alkylamines:
A Step- and Redox-Economical
Synthesis of Diazaheterocycles
Thanh Binh Nguyen,* Julie Le Bescont, Ludmila Ermolenko, and Ali Al-Mourabit
Centre de Recherche de Gif-sur-Yvette, Institut de Chimie des Substances Naturelles,
CNRS, 91198 Gif-sur-Yvette Cedex, France
Received October 24, 2013
ABSTRACT
A wide variety of functionalized 2-aryl benzimidazoles can be prepared by a solvent-free cobalt- or iron-catalyzed redox condensation of
2-nitroanilines and benzylamines. The cascade including benzylamine oxidation, nitro reduction, condensation, and aromatization occurs without
any added reducing or oxidizing agent. The method can be extended to other alkylamines as reducing components or 2-nitrobenzamides as
oxidizing components when using an iron/sulfur catalyst to afford various diazaheterocycles.
Redox condensation of the nitro group with other
reducing components provides a direct, step-, atom-, and
redox-economical approach to nitrogen containing com-
pounds, including amides and aza-heterocycles. Most of
the reported methods for redox condensation of the nitro
group employ expensive metals and/or ligands1 with a
large excess of the reducing components or external oxidiz-
ing agents.2 In this context, we are interested in developing
such methods using low-cost and readily available simple
salts of the first-row transition metals in association with
ligands within reach. Recently, we reported ironꢀsulfur
catalyzed methods for redox condensation between
o-nitroanilines and 2- or 4-methylhetarenes3 or 2-phene-
thylamines4 as an efficient route to aza-heterocycles. In
continuing our study, we report here a general method for
iron- and cobalt-catalyzed redox condensation between
o-substituted nitrobenzenes and amines.
Our initial efforts were focused on identifying the cata-
lytic activity of the first row transition metal salts. For this
(4) Nguyen, T. B.; Retailleau, P.; Al-Mourabit, A. Org. Lett. 2013,
15, 5238.
(5) For some selected recent examples, see: (a) Li, J.; Benard, S.;
Neuville, L.; Zhu, J. Org. Lett. 2012, 14, 5980. (b) Bastug, G.; Eviolitte,
C.; Marko, I. E. Org. Lett. 2012, 14, 3502. (d) Pizzetti, M.; De Luca, E.;
Petricci, E.; Porcheddu, A.; Taddei, M. Adv. Synth. Catal. 2012, 354,
2453. (e) Cano, R.; Ramon, D. J.; Yus, M. J. Org. Chem. 2011, 76, 654.
(f) Matsushita, H.; Lee, S.; Joung, M.; Clapham, B.; Janda, K. D.
Tetrahedron Lett. 2004, 45, 313. (g) Brasche, G.; Buchwald, S. L. Angew.
Chem., Int. Ed. 2008, 47, 1932. (h) Nguyen, T. B.; Ermolenko, L.; Al-
Mourabit, A. Heterocycles 2012, 86, 555. (i) Huang, J.; He, Y.; Wang,
Y.; Zhu, Q. Chem.;Eur. J. 2012, 18, 13964. (j) Peng, J.; Ye, M.; Zong,
C.; Hu, F.; Feng, L.; Wang, X.; Wang, Y.; Chen, C. J. Org. Chem. 2011,
76, 716. (k) Lewis, J. C.; Berman, A. M.; Bergman, R. G.; Ellman, J. A.
J. Am. Chem. Soc. 2008, 130, 2493. (l) Shen, M.; Driver, T. G. Org. Lett.
2008, 10, 3367. (m) Hubbard, J. W.; Piegols, A. M.; Soederberg, B. C. G.
Tetrahedron 2007, 63, 7077. (n) Nguyen, T. B.; Ermolenko, L.; Dean,
W. A.; Al-Mourabit, A. Org. Lett. 2012, 14, 5948. (o) Nguyen, T. B.;
Ermolenko, L.; Al-Mourabit, A. Green Chem. 2013, 15, 2713.
(1) Pd/XantPhos: (a) Xie, Y.; Liu, S.; Liu, Y.; Wen, Y.; Deng, G. Org.
Lett. 2012, 14, 1692. Ru(acac)3/dppe: (b) Liu, Y.; Chen, W.; Feng, C.;
Deng, G. J. Chem.;Asian J. 2011, 6, 1142. Au: (c) Tang, C. H.; He, L.;
Liu, Y. M.; Cao, Y.; He, H. Y.; Fan, K. N. Chem.;Eur. J. 2011, 17,
7172. dppf: (d) Wang, H.; Cao, X.; Xiao, F.; Liu, S.; Deng, G. Org. Lett.
2013, 15, 4900. (e) Wu, M.; Hu, X.; Liu, J.; Liao, Y.; Deng, G. Org. Lett.
2012, 14, 2722. Ir/Pd complex: (f) Zanardi, A.; Mata, J. A.; Peris, E.
Chem.;Eur. J. 2010, 16, 10502.
(2) (a) Xiao, F.; Liu, Y.; Tang, C.; Deng, G. Org. Lett. 2012, 14, 984.
(3) Nguyen, T. B.; Ermolenko, L.; Al-Mourabit, A. J. Am. Chem.
Soc. 2013, 135, 118.
r
10.1021/ol403064z
XXXX American Chemical Society