Dehydrogenative N-incorporation: A direct approach to quinoxaline N-oxides under mild conditions

Article abstract of DOI:10.1002/anie.201406479

An efficient method for the synthesis of quinoxaline N-oxides proceeds by the dehydrogenative N-incorporation of simple imines by C(sp²)-H and C(sp³)-H bond functionalization. The overall transformation involves the cleavage of three

Full text of DOI:10.1002/anie.201406479

Angewandte
Chemie
DOI: 10.1002/anie.201406479
À
C N Bond Formation
Dehydrogenative N-Incorporation: A Direct Approach to Quinoxaline
N-Oxides under Mild Conditions**
Feng Chen, Xiaoqiang Huang, Xinyao Li, Tao Shen, Miancheng Zou, and Ning Jiao*
À
Abstract: An efficient method for the synthesis of quinoxaline
incorporation by the functionalization of multiple C H
bonds in a substrate. Hence, the development of new methods
for the incorporation of nitrogen atoms into simple substrates
by concise and efficient routes is still attractive.
N-oxides proceeds by the dehydrogenative N-incorporation of
2
3
À
À
simple imines by C(sp ) H and C(sp ) H bond functionaliza-
tion. The overall transformation involves the cleavage of three
À
C H bonds. The reaction is easily handled and proceeds under
mild conditions. Simple and readily available tert-butyl nitrite
(TBN) was employed as the NO source.
N-heterocyclic N-oxides are ubiquitous structural motifs
in biologically active compounds[10] and chiral ligands.[11]
Various organic oxidants have been explored to synthesize
N-oxides from the corresponding nitrogen-containing hetero-
cycles.[12] However, these N-heterocycles need to be prepared
in advance, and other nitrogen atoms of the substrates would
be unselectively over-oxidized. Some transition-metal-cata-
N
itrogen-containing molecules, especially nitrogen-con-
taining heterocyclic compounds, are ubiquitous in natural
and bioactive products,[1] drugs,[2] and materials.[3] Accord-
À
À
ingly, the construction of C N bonds is an essential issue in
organic chemistry and has received much attention. Transi-
lyzed reactions for the synthesis of N-oxides through C H
bond functionalization have been disclosed, but the parent
N-oxide derivatives were employed as the substrates.[13] The
direct synthesis of N-oxides from simple substrates through
À
tion-metal-catalyzed C N bond-forming reactions have been
intensively investigated over the past decades; they have
become an efficient synthetic strategy[4,5] and include the
the cleavage of several C H bonds has not been reported.
Herein, we reported a novel and efficient intermolecular
dehydrogenative nitrogen atom incorporation through the
functionalization of C(sp ) H and C(sp ) H bonds for the
synthesis of quinoxaline N-oxides from imines, which are
readily available through the condensation of anilines with
ketones and commonly employed synthons for some useful
organic compounds [Eq. (1)]. Notably, the cleavage of one
À
À
palladium- and copper-catalyzed formation of C N bonds
from aryl halides and amines.[6–8]
2
3
À
À
À
Recently, the transition-metal-catalyzed direct C H bond
À
activation for the construction of C N bonds has been heavily
investigated.[5] For example, intermolecular and intramolec-
3
2
À
À
À
ular C(sp ) H and C(sp ) H aminations or C(sp) H amida-
[5,9]
À
tions for the formation of C N bonds have been disclosed.
2
3
À
À
Despite the significance of these methods, there are still some
challenging issues that remain to be addressed: 1) the control
of the chemo- and regioselectivity in intermolecular amina-
tion reactions, 2) the development of new and versatile
nitrogen sources to replace the traditionally required nitrogen
sources with strongly electron-withdrawing groups, and 3) the
implementation of one-pot methods for nitrogen atom
C(sp ) H bond and two C(sp ) H bonds is achieved for
multiple C N bond formation with simple and readily
available tert-butyl nitrite (TBN) as the nitrogen source
À
under mild conditions.
[*] F. Chen,[+] X. Huang,[+] X. Li,[+] T. Shen, M. Zou, Prof. Dr. N. Jiao
State Key Laboratory of Natural and Biomimetic Drugs
Peking University
Xue Yuan Rd. 38, Beijing 100191 (China)
E-mail: jiaoning@bjmu.edu.cn
Homepage: http://sklnbd.bjmu.edu.cn/nj
This nitrogen incorporation reaction was initially studied
with (E)-4-methoxy-N-(1-phenylethylidene)aniline[14] (1a)
and TBN[15] (2). The desired product 3a was isolated in
64% yield after heating the starting materials in MeNO2 at
608C for 60 minutes (entry 1, Table 1). The structure of 3a
was confirmed by X-ray single-crystal diffraction. When some
other solvents, such as DMF, alcohols, or acetone, were tested,
the desired product was not obtained (see the Supporting
Information). Copper and palladium catalysts could not
improve the efficiency of this transformation (Supporting
Information, Table S1). When tetrabutylammonium bromide
(TBAB, 10 mol%) was added to the reaction, the yield could
be improved to 76% (entry 2, Table 1), whereas the addition
of LiBr, NaBr, KBr, TBAI (tetrabutylammonium iodide), and
TBAC (tetrabutylammonium chloride) resulted in lower
Prof. Dr. N. Jiao
State Key Laboratory of Elemento-organic Chemistry
Nankai University
94 Weijin Road, Tianjin 300071 (China)
[+] These authors contributed equally to this work.
[**] Financial support from the National Natural Science Foundation of
China (21325206, 21172006), the National Young Top-notch Talent
Support Program, and the Ph.D. Programs Foundation of the
Ministry of Education of China (20120001110013) are greatly
appreciated. We thank the Sanzhong Luo group at ICCAS for help
with in situ IR experiments. We thank Yuepeng Yan in this group for
reproducing the synthesis of 3g and 3j.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201406479.
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Communications
Table 1: Screening of the reaction conditions.[a]
substituents at the para, meta, or ortho position and aceto-
phenone also performed well (3q–3u).
Furthermore, quinoxaline N-oxides with a substituent in
the 2-position could be obtained smoothly through the
nitrogen incorporation process of the corresponding imines
(3v–3x, Scheme 2). In particular, N-oxide 3x with a fused
heterocycle was directly afforded in 65% yield. Therefore,
substituted imines, which were easily synthesized from
various amines with different aromatic ketones, were suitable
substrates for direct N-oxide synthesis.
The practicability and applicability of this quinoxaline
N-oxide synthesis are remarkable. With this concise method,
an efficient one-pot synthesis of quinoxaline N-oxides from
amines and ketones was developed [Eq. (2)]. Aniline (4a)
Entry
TBAB [mol%]
Solvent
t [min]
Yield[b] [%]
1
2
3
4
–
10
10
5
5
–
MeNO2
MeNO2
MeNO2
MeCN
MeCN
MeCN
60
60
15
15
15
50
64
76
74
77
75
67
5[c]
6
[a] Reaction conditions: 1a (0.4 mmol), 2 (1.2 mmol), TBAB, and solvent
(3 mL) with stirring under air at 608C. [b] Yield of isolated product.
[c] Conducted on a 5 mmol scale (1.13 g).
and acetophenone (5a) underwent a condensation reaction in
the presence of 4 ꢀ molecular sieve (M.S.),[16] and the
subsequent nitrogen-incorporation process gave the desired
yields (Table S1). To our delight, the reaction finished within
15 minutes, producing the desired product in 74% yield
(entry 3). The reaction temperature was also
screened, and 608C was found to be optimal
(Table S1). A yield of 77% was obtained when
MeCN was used as the solvent instead of MeNO2
(entry 4). In contrast, the reaction in the absence
of TBAB took longer and proceeded with low
efficiency (67% yield, entry 6). A gram-scale
experiment was also conducted under the stan-
dard conditions; the desired product 3a was
obtained in 75% yield (entry 5).
With the optimized reaction conditions in
hand, the scope of this nitrogen incorporation
reaction was investigated (Scheme 1). The func-
tional-group compatibility of this transformation
is wide. Several substituted methyl imines, which
were easily prepared from 4-methoxyaniline and
various acetophenone derivatives, reacted
smoothly with TBN to generate the correspond-
ing quinoxaline N-oxides in moderate to good
yields under the standard conditions (3b–3j).
Electron-donating and electron-withdrawing
groups at the aryl ring of the acetophenone
moiety were compatible with this transformation.
Halide substituents, such as F, Cl, and Br, did not
affect the reactivity of the substrates (3 f–3h, 3m–
3o, and 3t). Imines 1i and 1j, which were
generated from heteroaryl methyl ketones with
4-methoxyaniline, could be converted into the
desired products 3i and 3j in 65% and 78% yield,
respectively. Some other substituted methyl
imines, which were synthesized from aniline
with different acetophenone derivatives, could
also be converted into the corresponding qui-
noxaline N-oxides in moderate to good yields
Scheme 1. Direct transformation of substituted imines into quinoxaline N-oxides.
Reaction conditions: 1 (0.4 mmol), 2 (1.2 mmol), TBAB (0.02 mmol), and MeCN
(3 mL) with stirring under air for 15 minutes.
(3k–3p). Meanwhile, some substrates that were
generated from various aromatic amines with
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product 3a was not obtained. The results exclude the
possibility that a-iminonitriles and quinoxalines are involved
as intermediates in this transformation. Hence, it is not
possible that amination and oxidation occur by a relay
mechanism. The NO moiety must therefore be introduced
into the molecule as one unit.
Moreover, the kinetic profile of the reaction was moni-
tored by in situ Fourier transform infrared (FT-IR) spectros-
copy in the presence or absence of TBAB. The results in
Figure S5 clearly suggest that TBAB accelerates the reaction.
Furthermore, the amount of the side products 6 and 9 could
be reduced by the addition of TBAB (see the Supporting
Information). Because of the results shown in Table 1
(entries 4 and 6), TBAB is not a catalyst of the reaction, but
functions as an additive. However, the mechanism by which
TBAB influences the outcome of this reaction is still not
completely clear.
When the reaction of 1a was monitored by EPR
spectroscopy under the standard conditions in the presence
of the free radical spin-trapping agent 5,5-dimethyl-1-pyrro-
line N-oxide (DMPO), a signal with six peaks, which
corresponds to the adduct of DMPO and the
carbon-centered radical,[20] was observed (g =
2.011, aN = 15.3 G, aHb = 22.4 G; Figure S1a).
The EPR results indicate that the carbon-
centered radical might be a key intermediate
in the present reaction. Furthermore, no EPR
signals could be recorded in the absence of TBN
or 1a (Figure S1b and S1c, respectively). These
results demonstrate that the carbon-centered
radical is formed by the reaction of 1a with
TBN.
Scheme 2. Synthesis of 2-substituted quinoxaline N-oxides.
quinoxaline N-oxide 3a in 56% yield [Eq. (2)]. However, the
reaction of aniline with acetone did not yield the correspond-
ing quinoxaline N-oxide.
Quinoxaline N-oxides are versatile intermediates in
organic synthesis and generally undergo further transforma-
tions with high reactivity and regioselectivity. For instance,
product 3a could be deoxidized into quinoxaline derivative 6
in 64% yield using TiCl4/NaI as the reducing agent
(Scheme 3).[17] Furthermore, quinoxaline N-oxides are suit-
To better understand the mechanism of this
transformation, the nitrogen incorporation
Scheme 3. Synthetic transformations of quinoxaline N-oxides. DBU=1,8-diazabicyclo-
[5.4.0]undec-7-ene, TMS=trimethylsilyl.
reaction of imine 1 and TBN, as a model
reaction, was studied by density functional
theory (DFT) calculations (Figure 1).[21] Ini-
able precursors to various quinoxaline derivatives through
tially, TBN decomposes into a NO radical and a tert-butoxy
C C and C N bond formation. Product 3a could be
converted into cyanoquinoxaline 7 in 70% yield in the
presence of TMSCN and DBU (Scheme 3).[18] N-(7-Methoxy-
3-phenylquinoxalin-2-yl)-N-methylacetamide (8) was also
radical,[15] which is an endergonic process by 22.4 kcalmolÀ1
.
À
À
The first step of the cascade reaction corresponds to the
abstraction of a hydrogen atom of imine 1 by the tert-butoxy
radical via transition state TS1 with an activation free energy
of 20.1 kcalmolÀ1 to afford methyl imine radical intermediate
INT1. The NO radical is a poor hydrogen-atom abstractor
(DG° = 48.2 kcalmolÀ1). Then, INT1 reacts with the NO
radical to form INT2, which is an exergonic process by
21.6 kcalmolÀ1. Further abstraction of a hydrogen atom in
INT2 by a tert-butoxy radical is facile, only requiring
15.5 kcalmolÀ1 in activation free energy. This process is
significantly exergonic by 61.7 kcalmolÀ1. The subsequent
electrocyclic reaction of INT3 readily proceeds through TS3
with an activation free energy of only 14.7 kcalmolÀ1 to
furnish cyclic intermediate INT4. Finally, the aromatization
process that involves the abstraction of a hydrogen atom in
INT4 by a tert-butoxy radical is once again significantly
exergonic by 137.1 kcalmolÀ1 and gives rise to the final
quinoxaline N-oxide 3. Reviewing the overall energy profile,
we found that the tert-butoxy and NO radicals are the active
species. Increasing the stability and concentration of these
easily prepared from 3a with N-methylacetamide through
[19]
À
C N bond formation (Scheme 3).
Some control experiments were conducted to gain insight
into the mechanism of this transformation. Considering that
a-iminonitrile 9 and quinoxaline 6 could be possible inter-
mediates, they were prepared and subjected to the optimized
reaction conditions [Eq. (3) and (4)]. However, the desired
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.
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tion to an oxime intermediate followed by an
electrocyclic reaction, could be ruled out because
of much higher energy barriers (Figure S6).
Furthermore, the fast reaction (less than
15 min) and the low efficiency in the presence
of TEMPO [see Eq. (S1)] also support the
hypothesis that the transformation proceeds
through a single electron transfer (SET) process.
On the basis of the above preliminary results,
a plausible mechanism for this synthesis of
quinoxaline N-oxides under transition-metal-
free conditions involves nitrogen atom incorpo-
2
3
À
À
ration through C(sp ) H and C(sp ) H bond
functionalization (Scheme 4). Initially, tert-butyl
nitrite could decompose into an NO radical and
a tert-butoxy radical.[15] Methyl imine radical
INT1a could be generated by the abstraction of
a hydrogen atom with the tert-butoxy radical.[15c]
Then, INT1a reacts with the NO radical to form
INT2a, which is further attacked by a tert-butoxy
radical to produce INT3a. The cyclic intermedi-
ate INT4a is then generated by the subsequent
electrocyclic reaction of INT3a. Finally, aroma-
tization of INT4a through the abstraction of
a hydrogen atom by a tert-butoxy radical leads to
the final product 3a (Scheme 4).
Figure 1. DFT energy profiles for the nitrogen incorporation reaction of imine 1 with
TBN.
In conclusion, we have developed a novel
transition-metal-free approach to quinoxaline
N-oxides that involves the functionalization of
2
3
À
À
radicals would enhance the rate of reaction. The first
abstraction of a hydrogen atom from imine 1 by a tert-
butoxy radical is the rate-determining step, and the subse-
quent electrocyclic reaction of the radical intermediate serves
as the key step, which is in good agreement with the
experimental observations. TBAB is likely to stabilize the
tert-butoxy and NO radicals and increase their concentrations
in the reaction mixture.
C(sp ) H and C(sp ) H bonds for nitrogen atom incorpo-
2
3
À
À
ration. One C(sp ) H bond and two C(sp ) H bonds are
À
cleaved to achieve multiple C N bond formation. The
method employs simple and readily available methyl imines
or even the corresponding parent aniline and acetophenone
derivatives in a one-pot reaction. Simple and commercially
available tert-butyl nitrite is employed as the NO source. All
of these features as well as its transition-metal-free conditions
make this method highly efficient and practical. EPR
measurements and DFT calculations suggest that the nitro-
gen-incorporation reaction involves multiple SET processes.
Although it is known that the nitrosyl exchange reaction
between tert-butyl nitrite and alcohols works well,[22] a nucle-
ophilic substitution reaction on tert-butyl nitrite with an
enamine nucleophile has not been reported. Furthermore,
through DFT calculations, the ionic pathway, which involves
nucleophilic attack of an enamine to TBN and tautomeriza-
Received: June 23, 2014
Revised: July 7, 2014
Published online: August 5, 2014
À
Keywords: C N bond formation · cyclization ·
dehydrogenative coupling · imines · nitrogen oxides
.
[1] a) R. Hili, A. K. Yudin, Nat. Chem. Biol. 2006, 6, 284; b) N. K.
Boaen, M. A. Hillmyer, Chem. Soc. Rev. 2005, 34, 267; c) S.
Banerjee, T. Hemraj-Benny, S. S. Wong, Adv. Mater. 2005, 17, 17;
d) T. Henkel, R. M. Brunne, H. Mꢁller, F. Reichel, Angew.
Chem. 1999, 111, 688; Angew. Chem. Int. Ed. 1999, 38, 643.
[2] a) G. Jones in Comprehensive Heterocyclic Chemistry II, Vol. 5
(Eds.: A. R. Katritzky, C. W. Rees, E. F. V. Scriven, A. McKil-
lop), Pergamon, Oxford, UK, 1996, p. 167; b) Pharmaceutical
Chemistry. Drug Synthesis, Vol. 1 (Eds.: H. J. Roth, A. Klee-
mann), Prentice Hall Europe, London, 1988, p. 407.
Scheme 4. Proposed pathway for the formation of quinoxaline N-
oxides.
[3] a) Electronic Materials: The Oligomer Approach (Eds.: K.
Mꢁllen, G. Wegner), Wiley-VCH, Weinheim, 1998; b) P.
10498 www.angewandte.org
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2014, 53, 10495 –10499

Angewandte
Chemie
Novꢂk, K. Mꢁller, K. S. V. Santhanam, O. Haas, Chem. Rev.
1997, 97, 207; c) P. A. Gale, Acc. Chem. Res. 2006, 39, 465.
[4] a) Metal-Catalyzed Cross-Coupling Reactions (Eds.: A. de Mei-
jere, F. Diederich), Wiley-VCH, Weinheim, 2004; b) K. Kunz, U.
Scholz, D. Ganzer, Synlett 2003, 2428; c) S. V. Ley, A. W.
Thomas, Angew. Chem. 2003, 115, 5558; Angew. Chem. Int. Ed.
2003, 42, 5400; d) R. Chinchilla, C. Nꢂjera, Chem. Rev. 2007, 107,
874; e) J.-P. Corbet, G. Mignani, Chem. Rev. 2006, 106, 2651;
f) M. Kienle, S. R. Dubakka, K. Brade, P. Knochel, Eur. J. Org.
Chem. 2007, 4166; g) E. M. Beccalli, G. Broggini, M. Martinelli,
S. Sottocornola, Chem. Rev. 2007, 107, 5318; h) R. Martin, S. L.
Buchwald, Acc. Chem. Res. 2008, 41, 1461; i) J. F. Hartwig, Acc.
Chem. Res. 2008, 41, 1534; j) F. Monnier, M. Taillefer, Angew.
Chem. 2008, 120, 3140; Angew. Chem. Int. Ed. 2008, 47, 3096;
k) S. Z. Zard, Chem. Soc. Rev. 2008, 37, 1603, and references
therein.
[5] a) F. Collet, R. H. Dodd, P. Dauban, Chem. Commun. 2009,
5061; b) S. H. Cho, J. Y. Kim, J. Kwak, S. Chang, Chem. Soc. Rev.
2011, 40, 5068; c) T. R. M. Rauws, B. U. W. Maes, Chem. Soc.
Rev. 2012, 41, 2463; d) I. P. Beletskaya, A. V. Cheprakov,
Organometallics 2012, 31, 7753; e) Z. Shi, C. Zhang, C. Tang,
N. Jiao, Chem. Soc. Rev. 2012, 41, 3381; f) C. Zhang, C. Tang, N.
Jiao, Chem. Soc. Rev. 2012, 41, 3464; g) G. Song, F. Wang, X. Li,
Chem. Soc. Rev. 2012, 41, 3651; h) J. Bariwal, E. Van der Eycken,
Chem. Soc. Rev. 2013, 42, 9283; i) D. N. Zalatan, J. Du Bois in
Topics in Current Chemistry, Vol. 292 (Eds.: J.-Q. Yu, Z. Shi),
Springer, Berlin, 2010, pp. 347 – 378.
Q. Yu, J. Am. Chem. Soc. 2011, 133, 7652; o) J. Y. Kim, S. H.
Park, J. Ryu, S. H. Cho, S. H. Kim, S. Chang, J. Am. Chem. Soc.
2012, 134, 9110; p) J. A. Souto, P. Becker, ꢃ. Iglesias, K. MuÇiz,
J. Am. Chem. Soc. 2012, 134, 15505; q) C. Tang, N. Jiao, J. Am.
Chem. Soc. 2012, 134, 18924; r) I. I. Strambeanu, M. C. White, J.
Am. Chem. Soc. 2013, 135, 12032; s) Q. Nguyen, K. Sun, T. G.
Driver, J. Am. Chem. Soc. 2012, 134, 7262; t) T. A. Ramirez, Q.
Wang, Y. Zhu, H. Zheng, X. Peng, R. G. Cornwall, Y. Shi, Org.
Lett. 2013, 15, 4210; u) J. A. Souto, D. Zian, K. MuÇiz, J. Am.
Chem. Soc. 2012, 134, 7242.
[10] a) G. OꢄDonnell, R. Poeschl, O. Zimhony, M. Gunaratnam,
J. B. C. Moreira, S. Neidle, D. Evangelopoulos, S. Bhakta, J. P.
Malkinson, H. I. Boshoff, A. Lenaerts, S. Gibbons, J. Nat. Prod.
2009, 72, 360; b) G. M. Nicholas, J. W. Blunt, M. H. G. Munro, J.
Nat. Prod. 2001, 64, 341.
[11] a) A. V. Malkov, P. Kocovsky, Eur. J. Org. Chem. 2007, 29; b) N.
Takenaka, R. S. Sarangthem, B. Captain, Angew. Chem. 2008,
120, 9854; Angew. Chem. Int. Ed. 2008, 47, 9708.
[12] a) J. A. Bull, J. J. Mousseau, G. Pelletier, A. B. Charette, Chem.
Rev. 2012, 112, 2642; b) A. Albini, S. Pietra, Heterocyclic N-
Oxides, CRC Press, Boca Raton, FL, 1991.
[13] a) H.-S. Yeom, S. Shin, Synlett 2008, 924; b) H.-S. Yeom, Y. Lee,
J.-E. Leeb, S. Shin, Org. Biomol. Chem. 2009, 7, 4744; c) A. J.
Maroulis, K. C. Domzaridou, C. P. Hadjiantoniou-Maroulis,
Synthesis 1998, 1769; d) R. Aggarwal, G. Sumran, A. Saini,
S. P. Singh, Tetrahedron Lett. 2006, 47, 4969; e) I. Nakamura, D.
Zhang, M. Terada, J. Am. Chem. Soc. 2010, 132, 7884; f) Z. Shi,
D. C. Koester, M. Boultadakis-Arapinis, F. Glorius, J. Am.
Chem. Soc. 2013, 135, 12204.
[14] For some recent reactions of simple methyl imines, see: a) Y.
Wei, I. Deb, N. Yoshikai, J. Am. Chem. Soc. 2012, 134, 9098; b) Y.
Liu, H. Du, J. Am. Chem. Soc. 2013, 135, 6810; c) F. Chen, X.
Huang, Y. Cui, N. Jiao, Chem. Eur. J. 2013, 19, 11199; d) Y. Lian,
J. R. Hummel, R. G. Bergman, J. A. Ellman, J. Am. Chem. Soc.
2013, 135, 12548.
[6] a) A. S. Guram, S. L. Buchwald, J. Am. Chem. Soc. 1994, 116,
7901; b) A. S. Guram, R. A. Rennels, S. L. Buchwald, Angew.
Chem. 1995, 107, 1456; Angew. Chem. Int. Ed. Engl. 1995, 34,
1348; c) J. P. Wolfe, S. Wagaw, S. L. Buchwald, J. Am. Chem. Soc.
1996, 118, 7215.
[7] a) F. Paul, J. Patt, J. F. Hartwig, J. Am. Chem. Soc. 1994, 116,
5969; b) J. Louie, J. F. Hartwig, Tetrahedron Lett. 1995, 36, 3609;
c) M. S. Driver, J. F. Hartwig, J. Am. Chem. Soc. 1996, 118, 7217.
À
[8] Copper catalysts are also used for C N bond formation; for
[15] For some recent reactions of TBN, see: a) T. Hirabayashi, S.
Sakaguchi, Y. Ishii, Angew. Chem. 2004, 116, 1140; Angew.
Chem. Int. Ed. 2004, 43, 1120; b) S. Prateeptongkum, I. Jovel, R.
Jackstell, N. Vogl, C. Weckbecker, M. Beller, Chem. Commun.
2009, 1990; c) Z. Shu, Y. Ye, Y. Deng, Y. Zhang, J. Wang, Angew.
Chem. 2013, 125, 10767; Angew. Chem. Int. Ed. 2013, 52, 10573;
d) T. Taniguchi, Y. Sugiura, T. Hatta, A. Yajima, H. Ishibashi,
Chem. Commun. 2013, 49, 2198; e) T. Shen, Y. Yuan, N. Jiao,
Chem. Commun. 2014, 50, 554.
[16] K. Taguchi, F. H. Westheimer, J. Org. Chem. 1971, 36, 1570.
[17] R. Balicki, Chem. Ber. 1990, 123, 647.
[18] A. Miyashita, T. Kawashima, C. Iijima, T. Higashino, Hetero-
cycles 1992, 33, 211.
[19] P. J. Manley, M. T. Bilodeau, Org. Lett. 2002, 4, 3127.
[20] a) K. Michail, A. Baghdasarian, M. Narwaley, N. Aljuhani, A. G.
Siraki, Chem. Res. Toxicol. 2013, 26, 1872; b) S. I. Dikalov, R. P.
Mason, Free Radical Biol. Med. 2001, 30, 187.
[21] All of the geometry optimizations and frequency calculations
were performed with the (U)B3LYP functional implemented in
Gaussian09. The 6-311 ++ G(d,p) basis set was used for all
atoms. All of the energies discussed in the paper are Gibbs free
energies with the CPCM solvation correction in MeCN based on
the structures in the gas phase determined with the same basis
set. Computational details and references are given in the
Supporting Information.
examples, see: a) M. Taillefer, H.-J. Cristau, P. P. Cellier, J.-F.
Spindler, Fr 2833947-WO 0353225 (Priority No. Fr 200116547),
2001; b) M. Taillefer, H.-J. Cristau, P. P. Cellier, J.-F. Spindler, A.
Ouali, Fr 2840303-WO 03101966 (Priority No. Fr 200206717),
2002; c) S. L. Buchwald, A. Klapars, J. C. Antilla, G. E. Job, M.
Wolter, F. Y. Kwong, G. Nordmann, E. J. Hennessy, WO02/
085838 (Priority No. US 2001 0286268), 2001; d) D. Ma, Y.
Zhang, J. Yao, S. Wu, S. Tao, J. Am. Chem. Soc. 1998, 120, 12459;
e) D. Ma, C. Xia, Org. Lett. 2001, 3, 2583.
[9] For some recent examples, see: a) T. Hamada, X. Ye, S. S. Stahl,
J. Am. Chem. Soc. 2008, 130, 833; b) K. MuÇiz, C. H. Hçvel-
mann, J. Streuff, J. Am. Chem. Soc. 2008, 130, 763; c) J. A.
Jordan-Hore, C. C. C. Johansson, M. Gulias, E. M. Beck, M. J.
Gaunt, J. Am. Chem. Soc. 2008, 130, 16184; d) T.-S. Mei, X.
Wang, J.-Q. Yu, J. Am. Chem. Soc. 2009, 131, 10806; e) J.
Neumann, S. Rakshit, T. Drçge, F. Glorius, Angew. Chem. 2009,
121, 7024; Angew. Chem. Int. Ed. 2009, 48, 6892; f) Y. Tan, J. F.
Hartwig, J. Am. Chem. Soc. 2010, 132, 3676; g) K.-H. Ng, A. S. C.
Chan, W.-Y. Yu, J. Am. Chem. Soc. 2010, 132, 12862; h) J. Y.
Kim, S. H. Cho, J. Joseph, S. Chang, Angew. Chem. 2010, 122,
10095; Angew. Chem. Int. Ed. 2010, 49, 9899; i) C. Qin, N. Jiao, J.
Am. Chem. Soc. 2010, 132, 15893; j) B. Xiao, T.-J. Gong, J. Xu,
Z.-J. Liu, L. Liu, J. Am. Chem. Soc. 2011, 133, 1466; k) K. Sun, Y.
Li, T. Xiong, J. Zhang, Q. Zhang, J. Am. Chem. Soc. 2011, 133,
1694; l) B. J. Stokes, S. Liu, T. G. Driver, J. Am. Chem. Soc. 2011,
133, 4702; m) S. H. Cho, J. Yoon, S. Chang, J. Am. Chem. Soc.
2011, 133, 5996; n) E. J. Yoo, S. Ma, T.-S. Mei, K. S. L. Chan, J.-
[22] M. P. Doyle, J. W. Terpstra, R. A. Pickering, D. M. LePoire, J.
Org. Chem. 1983, 48, 3379.
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