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tives 101 (PG=SO2Py, 95%) and 102 (PG=Ts, 87%) in high
yields.
These products can be further derivatized into the corre-
sponding 1H-benzo[d]imidazol-2(3H)-ones 103 and 104 by
using triphosgene (Scheme 10). Subsequent deprotection of
the N-Ts protecting group afforded the unprotected heteroar-
ene 105 in 81% yield. Interestingly, heterocyclic product 103 is
well-suited for a subsequent nitration reaction under our Cu-
catalyzed methodology, occurring selectively at the para-posi-
tion with regard to the NH group, as illustrated in the prepara-
tion of product 106 (77% yield). Additionally, the PdII-catalyzed
cyclization through the cascade sulfonamidation–oxidation of
the glyoxalate-derived imine 107,[19] obtained in situ from con-
densation of aniline 101 with ethyl glyoxalate, led to the for-
mation of the benzimidazole derivative 108 in reasonable yield
(52% over two steps).
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[12] a) B. Urones, A. M. Martꢀnez, N. Rodrꢀguez, R. Gꢁmez Arrayꢂs, J. C. Carre-
tive CÀH amination of protected anilines, see: b) A. M. Martꢀnez, N. Ro-
drꢀguez, R. Gꢁmez Arrayꢂs, J. C. Carretero, Chem. Commun. 2014, 50,
2801.
[13] This selectivity was not improved by using other typical N-protected
groups. For further information, see the Supporting Information.
[14] The model reaction of p-toluidine derivative 3 with HNO3 (1.0 equiv)
under the optimized reaction conditions [10 mol% of Cu(NO3)2·xH2O]
can also be performed in a 1:1 mixture of MeCN/H2O, affording 6 in
92% yield after 1 h at 1008C.
In summary, we have developed a reliable Cu-catalyzed pro-
cedure for the selective nitration of para-substituted and
ortho-substituted aniline derivatives by using one equivalent of
HNO3, which produces water as the only stoichiometric by-
product. This protocol is compatible with a variety of N-pro-
tecting groups and features remarkable tolerance with regard
to the arene substitution, including highly electron-deficient
groups. This procedure can be extended to the preparation of
dinitrated aniline derivatives by using two equivalents of
HNO3. The method is amenable to scale-up and enables the
construction of relevant nitrogenated architectures, such as
benzo[d]imidazol-2(3H)-ones and benzimidazoles.
[15] Other copper salts, such as CuCl or Cu(OAc)2, were similarly applicable
in the model nitration of 3 to give 5 (see the Supporting Information
for details).
Acknowledgements
[16] For a review on decarboxylative coupling reactions, see: N. Rodrꢀguez,
L. J. Goossen, Chem. Soc. Rev. 2011, 40, 5030.
We thank the Ministerio de Economꢀa y Competitividad
(MINECO, CTQ2012-35790) and the Consejerꢀa de Educaciꢁn de
la Comunidad de Madrid (AVANCAT, S2009/PPQ-1634) for finan-
cial support. N.R. thanks the MICINN for a Ramꢁn y Cajal con-
tract and the Marie Curie Foundation (CIG: CHAAS-304085).
E.H. thanks the Gobierno Vasco for a predoctoral fellowship.
[17] For thermal decomposition of Cu(NO3)2·xH2O releasing nitrogen dioxide,
see: a) I. V. Morozov, K. O. Znamenkov, Y. M. Korenev, O. A. Shlyakhtin,
pounds in Ullmann’s Encyclopedia of Industrial Chemistry 2005, Wiley-
VCH, Weinheim. See also ref. [9]. The applicability of other Cu salts as
precatalysts, such as Cu(OAc)2 or CuCl (easily oxidable under O2), is fea-
sible with this hypothesis because anion exchange could occur with
HNO3, leading to the incorporation of nitrate ions into the CuII moiety.
[18] For a related mechanism in the Cu-catalyzed ortho-azidation of anilines,
on Cu-catalyzed CÀH functionalization by a single-electron transfer pro-
cess, see: b) C. Zhang, C. Tanga, N. Jiao, Chem. Soc. Rev. 2012, 41, 3464.
For reviews on Cu-catalyzed aerobic CÀH functionalization, see: c) A. E.
Wendlandt, A. M. Suess, S. S. Stahl, Angew. Chem. 2011, 123, 11256;
Angew. Chem. Int. Ed. 2011, 50, 11062; d) S. E. Allen, R. R. Walvoord, R.
recent Cu-catalyzed CÀH functionalization reactions, see: e) L. D. Tran, I.
Popov, O. Daugulis, J. Am. Chem. Soc. 2012, 134, 18237; f) M. Shang, S.-
ences therein.
Keywords: anilines · benzimidazoles · copper · nitration · nitric
acid
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Received: June 17, 2014
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