Copper-catalyzed aerobic oxidative inert C-C and C-N bond cleavage: A new strategy for the synthesis of tertiary amides

Article abstract of DOI:10.1002/chem.201403144

A copper-catalyzed aerobic oxidative amidation reaction of inert C-C bonds with tertiary amines has been developed for the synthesis of tertiary amides, which are significant units in many natural products, pharmaceuticals, and fine chemicals. This method combines C-C bond activation, C-N bond cleavage, and C-H bond oxygenation in a one-pot protocol, using molecular oxygen as the sole oxidant without any additional ligands.

Full text of DOI:10.1002/chem.201403144

DOI: 10.1002/chem.201403144
Full Paper
&
Tertiary Amide Synthesis
Copper-Catalyzed Aerobic Oxidative Inert CÀC and CÀN Bond
Cleavage: A New Strategy for the Synthesis of Tertiary Amides
Xiuling Chen, Tieqiao Chen, Qiang Li, Yongbo Zhou, Li-Biao Han, and Shuang-Feng Yin*[a]
Abstract: A copper-catalyzed aerobic oxidative amidation re-
action of inert CÀC bonds with tertiary amines has been de-
veloped for the synthesis of tertiary amides, which are signif-
icant units in many natural products, pharmaceuticals, and
fine chemicals. This method combines CÀC bond activation,
CÀN bond cleavage, and CÀH bond oxygenation in a one-
pot protocol, using molecular oxygen as the sole oxidant
without any additional ligands.
Introduction
The present protocol also provides a facile and efficient ap-
proach for the preparation of tertiary amides,[10] which have
wide applications in the synthesis of many natural products,
pharmaceuticals, and fine chemicals.[11]
Transition-metal-catalyzed selective unstrained CÀC bond
cleavage, which enables the possibility of direct utilization of
inert starting materials, has attracted much attention.[1,2] In
recent years, numerous efficient catalytic systems,[3,4] such as
arylation with halobenzenes,[5] amidation with formamide or
amines (primary and secondary amines),[6] esterification with al-
cohols,[7] and others,[8] have been developed for the functional-
ization of inert CÀC bonds, which have contributed greatly to
modern organic synthesis. The oxidative cleavage of CÀN
bonds represents an important biochemical reaction and offers
a major means for the detoxification of xenobiotics,[9] and is
also of significant synthetic interest since such bonds are
common in numerous molecules. Given that tertiary amines
contain three CÀN bonds and are easily prepared, efficient acti-
vation of these CÀN bonds and further application in organic
synthesis is very attractive. Herein, we disclose a novel copper-
catalyzed aerobic oxidative amidation reaction of inert CÀC
bonds with tertiary amines through selective CÀC/CÀN activa-
tion and CÀH oxygenation with dioxygen [Eq. (1)]. This
method accomplishes CÀC bond activation, CÀN bond cleav-
age, and CÀH bond oxygenation with dioxygen in one pot.
Results and Discussion
Initially, the reaction of 2-phenylacetonitrile (1a) with triethyl-
amine (2a) catalyzed by copper salts was selected as a model
reaction for optimization of the reaction conditions, and the
obtained results are compiled in Table 1 (for further details, see
the Supporting Information). Using CuCl2/pyridine as the cata-
lyst, the reaction of 2-phenylacetonitrile (1a) with triethylamine
(2a) proceeded smoothly under dioxygen atmosphere and the
corresponding product diethylbenzamide (3a) was produced
Table 1. Optimization of the reaction conditions.[a]
[Cu]
Ligand
Solvent
Yield[b]
[%]
1
2
3
4
5
6
7
8[c]
9[d]
10[e]
CuCl2
CuCl2
CuCl2
CuCl2
–
CuCl
CuCl2
CuCl2
CuCl2
CuCl2
pyridine
1,10-phenanthroline
2,2-bipyridine
–
–
–
–
–
–
–
toluene
toluene
toluene
toluene
toluene
toluene
DMF
toluene
toluene
toluene
84
72
28
92
–
80
9
18
–
[a] X. Chen,+ Dr. T. Chen,+ Q. Li, Dr. Y. Zhou, Prof. L.-B. Han, Prof. S.-F. Yin
State Key Laboratory of Chemo/Biosensing and Chemometrics
College of Chemistry and Chemical Engineering, Hunan University
Changsha 410081 (P. R. China)
Fax: (+86)731-88821171
E-mail: sf_yin@hnu.edu.cn
[+] These authors contributed equally to this work.
–
[a] Reaction conditions: 1a (0.2 mmol), 2a (0.24 mmol), catalyst
(0.01 mmol, 5 mol%), ligand (0.02 mmol, 10 mol%), O2 (1 atm) in a Schlenk
tube (25 mL) at 1108C, 48 h. [b] GC yields based on 1a using dodecane
as an internal standard. [c] Under air (1 atm). [d] 0.5 mmol H2O2 was em-
ployed as oxidant under N2 atmosphere (1 atm). [e] 0.5 mmol tert-butyl
hydroperoxide (TBHP) was used as oxidant under N2 atmosphere (1 atm).
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201403144.
Chem. Eur. J. 2014, 20, 12234 – 12238
12234
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
in 84% yield (Table 1, entry 1). It is worth noting that when
stronger bidentate ligands such as 1,10-phenanthroline or 2,2-
bipyridine were used instead, the catalyst showed low efficien-
cy (Table 1, entries 2 and 3). Thus, it was deduced that an ex-
ternal amine ligand was not necessary and the starting tertiary
amine perhaps had sufficient intrinsic ligating ability. Indeed,
the present catalytic system showed higher efficiency and di-
ethylbenzamide (3a) was obtained in 92% yield without the
addition of an external ligand under similar reaction conditions
(Table 1, entry 4). Among the copper salts investigated, CuCl2
exhibited the highest catalytic efficiency (Table 1, entries 4 and
6; Supporting Information). It should be noted that a copper
salt was essential for this CÀC/CÀN bond activation reaction,
since it did not proceed at all in the absence of a copper cata-
lyst (Table 1, entry 5). As regards the solvents investigated, tol-
uene proved to be the best choice (Table 1, entry 7; Support-
ing Information). This amidation reaction was also dependent
on the pressure of dioxygen; for example, when it was per-
formed under air atmosphere, 3a was obtained in only 18%
yield (Table 1, entry 8). Finally, the addition of external oxidants
such as H2O2 and TBHP under nitrogen atmosphere did not im-
prove the efficiency of this transformation (Table 1, entries 9
and 10).
Table 2. Cu-catalyzed aerobic oxidative amidation of 2-phenylacetonitrile
(1a) with tertiary amines 2.[a]
Amine 2a–2l
Product
Yield[b]
[%]
1
2
3
81
86
85
4
90
5
6
7
92
89
91
3e
The substrate scope of the present copper-catalyzed aerobic
oxidative amidation reaction through CÀC/CÀN bond cleavage
was further investigated under the optimal conditions de-
scribed above. As shown in Table 2, 2-phenylacetonitrile (1a)
reacted readily with both symmetrical and asymmetrical ali-
phatic tertiary amines through CÀC and CÀN bond activation,
giving the corresponding tertiary amides in high yields. For
symmetrical tertiary amines, only one of the three CÀN bonds
was cleaved to give the product, and the reactivity was inde-
pendent of the alkyl chain length (Table 2, entries 1–3 and 9).
For asymmetrical tertiary amines, high selectivity in the CÀN
bond cleavage was observed with the present catalytic system.
For example, under catalysis by 5 mol% CuCl2, N,N-dimethylcy-
clohexylamine (2d) underwent selective N-Me cleavage, and
the aerobic oxidative amidation with 2-phenylacetonitrile (1a)
yielded 3d highly efficiently (Table 2, entry 4). High selectivity
in the CÀN bond cleavage was also observed with cyclic
amines such as piperidine-derived tertiary amines (2e-1, 2e-2),
morpholine-derived tertiary amine 2 f, and 1-methylpyrrolidine
2g (Table 2, entries 5–8). Aromatic tertiary amines 2i and 2j
also served as efficient substrates under the current catalytic
reaction conditions and could be selectively converted to the
corresponding amides 3i and 3j in yields of 73% and 79%, re-
spectively (Table 3, entries 10 and 11). However, when N-meth-
ylpyrrole (2k) and N-methylpyrrolidone (2l) were used as sub-
strates, none of the expected products were detected. This
may have been due to the lone pair of electrons on the N
atom participating in the conjugating system and hindering
the CÀN bond activation (Table 2, entries 12 and 13). The pres-
ent copper-catalyzed aerobic oxidative amidation reaction
through selective CÀC/CÀN bond cleavage proved to be facile
and efficient for the synthesis of asymmetrical tertiary amides
compared with those involving asymmetrical secondary
amines, which are expensive and difficult to prepare.[10]
8
90
92
73
79
9[c]
10
11
12
–
–
–
–
13[d]
[a] Reaction conditions: 1a (0.2 mmol), tertiary amine (0.24 mmol), CuCl2
(0.01 mmol, 5 mol%), toluene (1 mL), O2 (1 atm) in a Schlenk tube (25 mL)
at 1108C, 48 h. [b] Isolated yield. [c] 24 h. [d] 2l (1 mL).
As compiled in Table 3, under the optimized conditions, 2-
phenylacetonitriles bearing both electron-rich and electron-de-
ficient groups underwent selective CÀC bond cleavage and
were amidated by the tertiary amines, giving the correspond-
ing amide products in high yields (Table 3, entries 1–7). For ex-
ample, the reactions of 2-(4-methylphenyl)acetonitrile (1b)
with triethylamine and tribenzylamine proceeded smoothly to
produce amides 3k and 3l in yields of 87% and 89%, respec-
Chem. Eur. J. 2014, 20, 12234 – 12238
www.chemeurj.org
12235
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Table 3. Cu-catalyzed aerobic oxidative amidation of 2-phenylacetonitrile
derivatives 1 with tertiary amines 2.[a]
Table 4. Cu-catalyzed aerobic oxidative amidation of substrate 1 with ter-
tiary amine 2.[a]
Yield[b]
[%]
Substrate 1g–1j
Amine
Product
Yield[b]
[%]
Substrate 1b–1 f
Amine
Product
1[c]
2a
3a
60
1
2a
2h
2a
2h
87
89
91
87
2[c]
3[c]
1g
1g
2h
2i
3h
3i
63
55
2[c]
1b
4
5
6
7
2a
2i
3a
3i
75
70
24
37
1h
1i
3
2a
2i
3a
3i
4[c]
1c
8
2a
–
–
5[c]
2h
2a
2h
85
90
89
[a] Reaction conditions: 1g–1j (0.2 mmol), tertiary amine (0.24 mmol),
CuCl2 (0.01 mmol, 5 mol%), toluene (1 mL), O2 (1 atm) in a Schlenk tube
(25 mL) at 1108C, 24 h. [b] GC yields based on 1 using dodecane as an in-
ternal standard. [c] 2 (0.5 mmol).
6
7[c]
ence of 5 mol% CuCl2, the CÀC s-bond of 1,3-diphenylpropan-
2-one (1g) was selectively cleaved, allowing smooth reaction
with tertiary amines 2a, 2h, and 2i to give the desired amide
products in moderate yields (Table 4, entries 1–3).[12] With the
current catalytic system, the CÀC s-bond of 2-phenylacetalde-
hyde (1h) was cleaved, allowing reactions with 2a and 2i to
proceed readily to provide amides 3a and 3i in yields of 75%
and 70%, respectively (Table 2, entries 4 and 5). Amides 3a
and 3i could also be obtained from the reactions of 2-phenyl-
acetic acid (1i) with 2a and 2i under the optimal reaction con-
ditions, albeit in relatively low yields (Table 2, entries 4 and 5).
This may have been due to the acidity of 2-phenylacetic acid
(1i) preventing coordination between the amine and copper
salt. However, when methyl 2-phenylacetate (1j) and 2a were
used as substrates, CÀC and CÀN bond activation was not ob-
served under the present reaction conditions (Table 4, entry 8).
It is worth noting that high selectivity for C-Me bond cleavage
was also observed for the reactions of toluene derivatives
bearing electron-withdrawing groups with N,N-dimethylaniline
(2i) (Table 4, entries 3, 5, and 7).
To gain some insight into the reaction mechanism, several
control experiments were carried out as shown above. In the
absence of amines, benzoyl cyanide (1k) was generated in
35% yield under the present reaction conditions [Eq. (2)]. The
resulting benzoyl cyanide (1k) reacted rapidly with tri-n-pro-
pylamine (2b) to afford a 90% yield of 3b in only 6 h under
similar conditions [Eq. (3)]. These results indicated that benzoyl
cyanide (1k) may have been an effective intermediate for this
transformation.[8a] The reaction of 1a and 2b in the presence
[a] Reaction conditions: substrate 1b–1 f (0.2 mmol), tertiary amine
(0.24 mmol), CuCl2 (0.01 mmol, 5 mol%), toluene (1 mL), O2 (1 atm) in
a
Schlenk tube (25 mL) at 1108C, 48 h. [b] Isolated yield. [c] CuCl2
(0.01 mmol, 5 mol%), 24 h.
tively (Table 3, entries 1 and 2). Excellent yields were observed
when the reactions of 2-(4-bromophenyl)acetonitrile (1c) with
triethylamine and tribenzylamine were carried out under the
present catalytic conditions (Table 3, entries 3 and 4). 2-(4-Ni-
trophenyl)acetonitrile (1d), a substrate bearing a strongly elec-
tron-deficient group, also reacted with 2h to provide the de-
sired product 3o in 85% yield (Table 3, entry 5). To our delight,
the heteroaryl-substituted amide 3p was obtained from the re-
action of 2-(thiophen-2-yl)acetonitrile with 2a using the pres-
ent copper-catalyzed aerobic oxidative amidation, indicating
that this method offers an efficient approach for introducing
an aromatic heterocycle into functional molecules (Table 3,
entry 6). 2-(Naphthalen-2-yl)acetonitrile (1 f) also served as an
efficient substrate and reacted with 2h to furnish the amide
3q in 89% yield through selective CÀC/CÀN activation cata-
lyzed by 5 mol% CuCl2 under dioxygen atmosphere (Table 3,
entry 7).
Besides acetonitriles substituted with aromatic groups, other
toluene derivatives bearing electron-withdrawing groups could
also be amidated by tertiary amines, giving the expected
amides through selective CÀC/CÀN bond activation under the
optimal reaction conditions, as shown in Table 4. In the pres-
Chem. Eur. J. 2014, 20, 12234 – 12238
www.chemeurj.org
12236
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
of 18O2 (1 atm) generated the 18O-labeled product [18O]-3ba in
80% yield [Eq. (4)], as determined by MS and HRMS (see the
Supporting Information). However, with the addition of
0.2 mmol H218O, only [16O]-3b was obtained in 82% yield and
no 18O-labeled product was detected under the optimal condi-
tions [Eq. (5)]. Thus, the oxygen atoms of the product amides
are derived from molecular dioxygen. Besides, the addition of
2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) did not result in
a decrease in the yield of 3b, ruling out the involvement of
a free radical process in the present reaction [Eq. (6)].
oxygen to form [LmCun+1] composed of the copper salt, amine
ligand, and molecular oxygen, and this is followed by autoxida-
tion of the amine ligand to give the iminium-type intermediate
I2a, which is then hydrolyzed and oxidized to the key inter-
mediate I2b by elimination of aldehyde.[13] I2b further reacts
with benzoyl compound I1a derived from the oxidation of
1 with oxygen in the presence of a copper catalyst to give the
corresponding amide 3 with regeneration of the copper cata-
lyst.[8a]
Conclusion
In conclusion, a novel and efficient copper-catalyzed aerobic
oxidative amidation through CÀC/CÀN bond cleavage has
been developed. This method successfully combines CÀC
bond activation, CÀN bond cleavage, and CÀH bond oxygena-
tion with dioxygen. This protocol also provides a practical,
neutral, and mild synthetic approach to tertiary amides, which
are important units in biologically active molecules.
Experimental Section
General procedure: A 25 mL Schlenk-type tube equipped with
a magnetic stir bar was charged with substrate amine 1 (1a–1k)
(0.2 mmol) and CuCl2 (0.0013 g, 5 mol%). The reaction tube was
evacuated and back-filled with O2. Tertiary amines 2 (2a–2l)
(0.24 mmol) and toluene (1 mL) were added at room temperature
under O2 atmosphere, and the reaction mixture was stirred at
110 8C for 24–36 h. The reaction was monitored by GC or GC-MS.
After completion of the reaction, the resulting solution was cooled
to room temperature and neutralized with a saturated aqueous so-
lution of NH4Cl. The product was extracted with EtOAc or CHCl3,
and the extracts were dried over anhydrous Na2SO4 and concen-
trated in vacuo. The crude product was purified by flash column
chromatography on silica gel to give the desired product.
According to relevant literature reports[8a,13] and the above
experimental results, a possible catalytic cycle for the copper-
catalyzed aerobic oxidative amidation of compounds 1 with
tertiary amines through CÀC/CÀN bond activation is proposed
as shown in Scheme 1. The copper catalyst is first oxidized by
Acknowledgements
This work was supported by the NSFC (U1162109, 21172062,
21373080), the Program for Changjiang Scholars and Innova-
tive Research Team in University (IRT1238), the Program for
New Century Excellent Talents in Universities (NCET-10–0371),
and the Fundamental Research Funds for the Central Universi-
ties (Hunan University).
Keywords: aerobic oxidation · amidation · amides · CÀC
activation · CÀN cleavage
[1] For reviews on CÀC bond activation, see: a) Y. J. Park, J. W. Park, C. H.
Jun, Acc. Chem. Res. 2008, 41, 222–234; b) M. Tobisu, N. Chatani, Chem.
Soc. Rev. 2008, 37, 300–307; c) M. Rubin, M. Rubina, V. Gevorgyan,
Chem. Rev. 2007, 107, 3117–3179; d) C. H. Jun, Chem. Soc. Rev. 2004, 33,
610–618; e) A. de Meijere, Chem. Rev. 2003, 103, 931–932.
[2] “Cleavage of Carbon-Carbon Single Bonds by Transition Metals”: M.
Murakami, Y. Ito, in Activation of Unreactive Bonds and Organic Synthe-
sis—Topics in Organometallic Chemistry Series, Vol. 3, (Ed.: S. Murai),
Springer, Berlin, New York, 1999, pp. 97–129.
[3] Traditional metal-catalyzed methods for CÀC bond cleavage: for the
Scheme 1. A possible mechanism for the amidation reaction.
use of Rh catalysts, see: a) H. Li, Y. Li, X. S. Zhang, K. Chen, X. Wang, Z.
Chem. Eur. J. 2014, 20, 12234 – 12238
www.chemeurj.org
12237
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Shi, J. Am. Chem. Soc. 2011, 133, 15244–15247; b) M. Tobisu, H. Kinuta,
Y. Kita, E. Rꢁmond, N. Chatani, J. Am. Chem. Soc. 2012, 134, 115–118;
c) Q. Shuai, L. Yang, X. Guo, O. Baslꢁ, C. J. Li, J. Am. Chem. Soc. 2010,
132, 12212–12213; for the use of Ru catalysts, see: d) J. Liu, Q. Liu, H.
Yi, C. Qin, R. Bai, X. Qi, Y. Lan, A. Lei, Angew. Chem. 2014, 126, 512–516;
Angew. Chem. Int. Ed. 2014, 53, 502–506; for the use of Pd catalysts,
see: e) P. Hu, M. Zhang, X. Jie, W. Su, Angew. Chem. 2012, 124, 231–235;
Angew. Chem. Int. Ed. 2012, 51, 227–231; f) Y. Hirata, A. Yada, E. Morita,
Y. Nakao, T. Hiyama, M. Ohashi, S. Ogoshi, J. Am. Chem. Soc. 2010, 132,
10070–10077; g) S. I. Murahashi, T. Naota, N. Nakajima, J. Org. Chem.
1986, 51, 898–901; for the use of Au catalysts, see: h) N. Asao, T.
Nogami, S. Lee, Y. Yamamoto, J. Am. Chem. Soc. 2003, 125, 10921–
10925; for the use of Ni catalysts, see: i) T. Patra, S. Agasti, A. Modak, D.
Maiti, Chem. Commun. 2013, 49, 8362–8364; j) T. Patra, S. Agasti,
Akanksha, D. Maiti, Chem. Commun. 2013, 49, 69–71; k) Y. Nakao, Y.
Hirata, T. Hiyama, J. Am. Chem. Soc. 2006, 128, 7420–7421; l) Y. Hirata, T.
Inui, Y. Nakao, T. Hiyama, J. Am. Chem. Soc. 2009, 131, 6624–6631; m) Y.
Nakao, A. Yada, S. Ebata, T. Hiyama, J. Am. Chem. Soc. 2007, 129, 2428–
2429; n) M. P. Watson, E. N. Jacobsen, J. Am. Chem. Soc. 2008, 130,
12594–12595; o) K. Nakai, T. Kurahashi, S. Matsubara, J. Am. Chem. Soc.
2011, 133, 11066–11068; for other methods, see: p) X. Zhang, M. Wang,
3289; Angew. Chem. Int. Ed. 2012, 51, 3231–3235; b) V. Prasad, R. R.
Kale, B. B. Mishra, D. Kumar, V. K. Tiwari, Org. Lett. 2012, 14, 2936–2939;
c) L. Colombeau, T. Traorꢁ, P. Compain, O. R. Martin, J. Org. Chem. 2008,
73, 8647–8650; d) S. C. Ghosh, J. S. Y. Ngiam, C. L. L. Chai, A. M. Seayad,
T. T. Dang, A. Q. Chen, Adv. Synth. Catal. 2012, 354, 1407–1412; e) S. C.
Ghosh, J. S. Y. Ngiam, A. M. Seayad, D. T. Tuan, C. L. L. Chai, A. Q. Chen, J.
Org. Chem. 2012, 77, 8007–8015; f) C. Zhang, Z. Xu, L. R. Zhang, N. Jiao,
Angew. Chem. 2011, 123, 11284–11288; Angew. Chem. Int. Ed. 2011, 50,
11088–11092; g) M. W. Zhu, K. Fujita, R. Yamaguchi, J. Org. Chem. 2012,
77, 9102–9109; h) R. Cadoni, A. Porcheddu, G. Giacomelli, L. D. Luca,
Org. Lett. 2012, 14, 5014; i) J. W. W. Chang, T. M. U. Ton, S. Tania, P. C.
Taylor, P. W. H. Chan, Chem. Commun. 2010, 46, 922–924; j) G.-L. Li,
K. K. Y. Kung, M. K. Wong, Chem. Commun. 2012, 48, 4112–4114; k) L.
Zhang, S. Wang, S. Zhou, G. Yang, E. Sheng, J. Org. Chem. 2006, 71,
3149–3153; l) S. Y. Seo, T. J. Marks, Org. Lett. 2008, 10, 317–319; m) J. Li,
F. Xu, Y. Zhang, Q. Shen, J. Org. Chem. 2009, 74, 2575; for examples of
transformations from alcohols to amides, see: n) K. Xu, Y. Hu, S. Zhang,
Z. Zha, Z. Wang, Chem. Eur. J. 2012, 18, 9793–9797; o) L. U. Nordstrøm,
H. Vogt, R. Madsen, J. Am. Chem. Soc. 2008, 130, 17672–17673; p) F.
Xiao, Y. Liu, C. Tang, G. Deng, Org. Lett. 2012, 14, 984–987; for examples
of transformations from alkyne to amide, see: q) W. K. Chan, C. M. Ho,
M. K. Wong, C. M. Che, J. Am. Chem. Soc. 2006, 128, 14796–14797; r) W.
Wei, X. Hu, X. Yan, Q. Zhang, M. Cheng, J. Ji, Chem. Commun. 2012, 48,
305–307; for an example of transformation from an a-bromo nitroal-
kane to an amide, see: s) B. Shen, D. M. Makley, J. N. Johnston, Nature
2010, 465, 1027–1032; for other methods furnishing amides, see:
t) R. J. Carroll, H. Leisch, E. Scocchera, T. Hudlicky, D. P. Cox, Adv. Synth.
Catal. 2008, 350, 2984–2992; u) C. Vila, M. Rueping, Green Chem. 2013,
15, 2056–2059; v) D. N. Sawant, Y. S. Wagh, K. D. Bhatte, B. M. Bhanage,
J. Org. Chem. 2011, 76, 5489–5494; w) C. Hu, X. Yan, X. Zhou, Z. Li, Org.
Biomol. Chem. 2013, 11, 8179–8182; x) W. Mai, G. Song, J. Yuan, L. Yang,
G. Sun, Y. Xiao, P. Mao, L. Qu, RSC Adv. 2013, 3, 3869–3872; y) Y. Li, L.
Ma, F. Jia, Z. Li, J. Org. Chem. 2013, 78, 5638; z) Y. Li, F. Jia, Z. Li, Chem.
Eur. J. 2013, 19, 82–86.
´
Y. Zhang, L. Wang, RSC Adv. 2013, 3, 1311–1316; q) J. Mecinovic, R. B.
Hamed, C. J. Schofield, Angew. Chem. 2009, 121, 2834–2838; Angew.
Chem. Int. Ed. 2009, 48, 2796–2800; r) H. Li, W. Li, W. Liu, Z. He, Z. Li,
Angew. Chem. 2011, 123, 3031–3034; Angew. Chem. Int. Ed. 2011, 50,
2975–2978; s) X. Kou, J. Fan, X. Tong, Z. Shen, Chin. J. Org. Chem. 2013,
33, 1407–1422 and references therein.
[4] For a review on aerobic copper-catalyzed CÀC bond cleavage, see: S. E.
Allen, R. R. Walvoord, R. Padilla-Salinas, M. C. Kozlowski, Chem. Rev.
2013, 113, 6234–6458.
[5] a) C. He, S. Guo, L. Huang, A. Lei, J. Am. Chem. Soc. 2010, 132, 8273–
8275; b) R. Shang, Y. Fu, J. B. Li, S. Zhang, Q. Guo, L. Liu, J. Am. Chem.
Soc. 2009, 131, 5738–5739.
[6] a) C. Zhang, Z. Xu, T. Shen, G. Wu, L. Zhang, N. Jiao, Org. Lett. 2012, 14,
2362–2365; b) Q. Zhao, H. Lia, L. Wang, Org. Biomol. Chem. 2013, 11,
6772–6779; c) X. Sun, M. Wang, P. Li, X. Zhang, L. Wang, Green Chem.
2013, 15, 3289–3294.
[7] C. Zhang, P. Feng, N. Jiao, J. Am. Chem. Soc. 2013, 135, 15257–15262.
[8] a) J. Jin, Q. Wen, P. Lu, Y. Wang, Chem. Commun. 2012, 48, 9933–9935;
b) Q. Song, Q. Feng, K. Yang, Org. Lett. 2014, 16, 624–627; c) E. J. Park,
S. Lee, S. Chang, J. Org. Chem. 2010, 75, 2760–2762.
[11] a) J. M. Humphrey, A. R. Chamberl, Chem. Rev. 1997, 97, 2243–2266;
b) C. L. Allen, J. M. J. Williams, Chem. Soc. Rev. 2011, 40, 3405–3415.
[12] It is noteworthy that N,N-diethyl-2-phenylacetamide was produced in
30% yield in this case, which demonstrates that the remaining 1,3-di-
phenylpropan-2-one underwent the coupling process with amine sub-
strate 2a to produce the corresponding amide.
[13] S. Guo, B. Qian, Y. Xie, C. Xia, H. Huang, Org. Lett. 2011, 13, 522–525.
[9] a) B. Meunier, S. P. de Visser, S. Shaik, Chem. Rev. 2004, 104, 3947–3980;
b) I. G. Denisov, T. M. Makris, S. G. Sligar, I. Schlichting, Chem. Rev. 2005,
105, 2253–2277.
Received: April 17, 2014
[10] For some selected examples of transformations from aldehyde to
amide, see: a) Z. Liu, J. Zhang, S. Chen, Angew. Chem. 2012, 124, 3285–
Revised: June 20, 2014
Published online on August 5, 2014
Chem. Eur. J. 2014, 20, 12234 – 12238
www.chemeurj.org
12238
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim