Copper-catalyzed aerobic oxidative coupling of aryl acetaldehydes with anilines leading to α-ketoamides

Article abstract of DOI:10.1002/anie.201105285

Efficient and practical: The title reaction provides an efficient route to α-ketoamides compounds, which are ubiquitous structural units in a number of biologically active compounds. N-substituted anilines are suitable substrates for this transformation.

Full text of DOI:10.1002/anie.201105285

Communications
DOI: 10.1002/anie.201105285
a-Ketoamides
Copper-Catalyzed Aerobic Oxidative Coupling of Aryl
Acetaldehydes with Anilines Leading to a-
Ketoamides**
Chun Zhang, Zejun Xu, Liangren Zhang, and Ning Jiao*
Angewandte
Chemie
11088
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 11088 –11092

a-Ketoamides are important units in biologically active
molecules, synthetic drugs, and drug candidates
(Scheme 1).[1] Furthermore, they serve as useful precursors
for a variety of functional group transformations.[2] Conse-
Scheme 2. Methods for the synthesis of a-ketoamides.
aryl acetaldehydes with anilines by a novel mechanistic
process to give a-ketoamides; this reaction is highly efficient
À
and has a broad substrate scope (Scheme 2, 4). Two Csp3 H,
À
À
one Csp2 H, and one N H bond cleavages are involved in this
novel chemistry.
Scheme 1. Biologically active molecules.
À
With regard to sustainable chemistry, oxidative C H bond
functionalization is one of the most attractive and powerful
strategies in organic synthesis.[9] For these transformations,
molecular oxygen is an ideal oxidant. Significantly, the use of
dioxygen activation for functionalization reactions represents
one of the most ideal processes in organic synthesis.[7]
Activation of dioxygen by copper enzymes has been observed
in some biological oxygenase systems, such as monooxyge-
quently, lots of effort has been made to construct a-
ketoamides.[3–8] Among these methods, amidation of a-keto
acids and a-keto acyl halides (Scheme 2, 1),[3] oxidation of a-
hydroxyamides and a-aminoamides,[4] transition-metal-cata-
lyzed double carbonylative amination of aryl halides,[5]
oxidative coupling,[6a] and other methods[6] (Scheme 2, 2)
have been widely used. Despite the numerous efforts toward
the synthesis of a-ketoamides, the development of mild,
efficient, and environmentally friendly methods is still
desired: 1) Precursors should be easily prepared or handled;
2) Instead of stoichiometric oxidants, such as metal salts or
peroxide, environmentally friendly molecular oxygen, as the
ideal oxidant, is desirable.[7] 3) The reduction of the amount of
environmentally unfriendly by-products should be given more
attention. Recently, Cu-catalyzed oxidative amidation/dike-
tonization of terminal alkynes leading to a-ketoamides was
reported (Scheme 2, 3).[8] However, some drawbacks of this
method may limit it applications. Firstly, the homocoupling of
terminal alkynes is difficult to control, hence an excess of
alkynes (5.0 equiv) must be employed. Secondly, the substrate
scope is limited beacuse anilines that contain electron-with-
drawing groups give only a trace amount of the desired
products. Thirdly, N-substituted anilines did not react. Herein,
we present a copper-catalyzed aerobic oxidative coupling of
nase tyrosinase and dopamine b-monooxygenase that effect
[10]
À
hydroxylation of C H bonds. Recently, copper-catalyzed
reactions that involve dioxygen activation and use rather
simple models to realize biomimetic syntheses have been
given considerable attention.[11] To the best of our knowledge,
À
the aerobic oxidative transformation of adjacent C H bonds
to form a-ketoamides by dioxygen activation has not been
reported.
Our study commenced with the reaction of 2-phenyl-
acetaldehyde (1a) and 4-aminobenzonitrile (2a) catalyzed by
copper salts. Interestingly, N-(4-cyanophenyl)-2-oxo-2-phe-
nylacetamide (3aa) was produced in 68% yield when CuBr
was used as the catalyst (Table 1, entry 1). The reaction in the
absence of a Cu catalyst was not very successful (Table 1,
entry 2). Other Cu catalysts including CuII salts gave lower
reaction efficiencies (see, Table 1, entries 1, 3, and 4, and the
Supporting Information). We then surveyed the effect of
different solvents; the reactions proceeded with low yields in
benzene, DMF, and other solvents (Table 1, entries 1, 5, and 6,
and the Supporting Information). Further studies indicated
that base can promote this transformation, and two equiv-
alents of pyridine is optimal. The reaction efficiency
decreased when using other bases, such as Na2CO3, and
triethylamine (Table 1, entries 1, 7–10, and the Supporting
Information). Both increasing and decreasing the temper-
ature resulted in lower yields (Table 1, entries 11 and 12).
Furthermore, various ligands were investigated, but the
results were unsatisfactory (see the Supporting Information).
Gratifyingly, the presence of molecular sieves (4 ꢀ) resulted
in an increase in the yield of 3aa to 82% (Table 1, entry 13).
Under these optimized conditions (Table 1, entry 13), the
scope of the substituted aldehydes (1) was investigated
[*] C. Zhang, Z. Xu, L. Zhang, Dr. N. Jiao
State Key Laboratory of Natural and Biomimetic Drugs
School of Pharmaceutical Sciences, Peking University
Xue Yuan Rd. 38, Beijing 100191 (China)
E-mail: jiaoning@bjmu.edu.cn
Dr. N. Jiao
State Key Laboratory of Organometallic Chemistry
Chinese Academy of Sciences, Shanghai 200032 (China)
[**] Financial support from Peking University, the National Science
Foundation of China (No. 20872003), and the National Basic
Research Program of China (973 Program 2009CB825300) are
greatly appreciated. We thank Prof. Jingfen Lu for helpful discussion.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201105285.
Angew. Chem. Int. Ed. 2011, 50, 11088 –11092
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 11089

Communications
Table 1: Cu-catalyzed aerobic oxidative coupling of 1a with 2a.[a]
Table 3: Copper-catalyzed aerobic oxidative coupling of 1a with a range
of anilines 2.[a]
entry
[Cu]
solvent
Additives (equiv)
Yield[%][b]
1
2
3
4
5
6
7
8
CuBr
none
CuCl
CuOAc
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
CuBr
toluene
toluene
toluene
toluene
benzene
DMF
toluene
toluene
toluene
toluene
toluene
toluene
toluene
pyridine (2.0)
pyridine (2.0)
pyridine (2.0)
pyridine (2.0)
pyridine (2.0)
pyridine (2.0)
Na2CO3 (2.0)
triethylamine (2.0)
pyridine (3.0)
pyridine (1.0)
pyridine (2.0)
pyridine (2.0)
4 ꢀ MS (200 mg)
pyridine (2.0)
68
5
Entry
R2
R3
3
Yield [%][b]
1
2
3
4
5
6
7
8
4-CNC6H4
3-CNC6H4
2-CNC6H4
4-COOEtC6H4
4-CF3C6H4
4-NO2C6H4
4-CF3OC6H4
3,5-(OMe)2C6H3
2,4,5-F3C6H2
2,5-F2C6H3
3,4,5-Cl3C6H2
4-Br-3-CF3C6H3
Ph
H
H
H
H
H
H
H
H
H
H
H
H
Me
Me
Me
Et
PhCH2
Ph
H
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
3aj
3ak
3al
3am
3an
3ao[c]
3ap
3aq
3ar
82
70
70
60
70
90
52
35
86
90
73
75
65
60
41[c]
40
56
36
0
55
43
61
29
trace
45
66
55
59
61
82
9
10
11[c]
12[d]
13
9
10
11
12
13
14
15
16
17
18
19
[a] Reaction conditions: 1a (0.5 mmol), 2a (0.25 mmol), cat.
4-ClC6H4
4-MeC6H4
Ph
Ph
Ph
(0.025 mmol), solvent (2.5 mL), O2 (1 atm), 908C, 12 h. [b] Yields of the
isolated product. [c] The reaction was carried out at 608C. [d] The
reaction was carried out at reflux. DMF=N,N’-dimethylformamide.
nC5H11
3as
[a] Standard reaction conditions: 1a (0.5 mmol), 2 (0.25 mmol), CuBr
(0.025 mmol), pyridine (0.5 mmol), toluene (2.5 mL), 908C, O2 (1 atm),
12 h. [b] Yields of the isolated products. [c] 1a (0.25 mmol), 2o
(0.5 mmol).
Table 2: Copper-catalyzed aerobic oxidative coupling of a range of
aldehydes 1 with 2a.[a]
The scope of the copper-catalyzed aerobic oxidative
coupling leading to a-ketoamides was further expanded to a
range of substituted anilines 2 (Table 3). These results
demonstrate that reactions of anilines with both electron-
donating and electron-withdrawing groups proceed well with
moderate to excellent yields. Notably, even when chloro- and
bromo-substituted anilines were employed as substrates, they
reacted with 1a to produce the desired a-ketoamides 3ak,
3al, and 3an in 73%, 75%, and 60% yield respectively. It is
noteworthy that N-substituted anilines such as N-methyl-, N-
ethyl-, N-benzyl-, and N-phenylaniline could be smoothly
transformed into the desired products in moderate yields
(Table 3, entries 13–18). However, an alkyl amine can not be
converted into the desired product (Table 3, entry 19). The
results show that anilines bearing electron-donating substitu-
tents gave lower yields than those bearing electron-with-
drawing substitutents. One important reason for this fact is
that an electron-rich amine could form a radical cation, which
could react to give an azo compound very easily,[12] thus
suggesting a different reaction pathway leads to the formation
of our target product in a low yield. At the same time,
electron-poor amines would be unable to transform into an
amine radical cation under our reaction conditions, so afford
the target products in higher yields.
Entry
1
R1
3
Yield [%][b]
1
2
3
4
5
6
7
8
9
10
1a
1b
1c
1d
1e
1 f
1g
1h
1i
Ph
3aa
3ba
3ca
3da
3ea
3 fa
3ga
3ha
3ia
82
83
77
71
73
84
78
75
75
0
4-OMeC6H4
4-MeC6H4
3-MeC6H4
2-MeC6H4
4-FC6H4
4-ClC6H4
4-BrC6H4
b-naphthyl
nC4H9
1j
3ja
[a] Standard reaction conditions: 1 (0.5 mmol), 2a (0.25 mmol), CuBr
(0.025 mmol), pyridine (0.5 mmol), toluene (2.5 mL), 908C, O2 (1 atm),
12 h. [b] Yields of the isolated products. M.S.=molecular sieves.
(Table 2). Both electron-rich and electron-deficient aryl
acetaldehydes could be smoothly transformed into the
desired products. Furthermore, substituents at different
positions on the arene group (para, meta, and ortho positions)
did not affect the reaction efficiency. It is noteworthy that
halo-substituted aryl acetaldehydes were tolerated well, thus
leading to halo-substituted products, which could be used for
further transformations (Table 2, entries 7 and 8). In addition,
the naphthyl-substituted acetaldehyde, 2-(naphthalen-2-yl)-
acetaldehyde (1i) was also tolerated in this transformation,
thus generating 3ia in 75% yield (Table 2, entry 9). However,
an alkyl aldehyde did not afford the desired product (Table 2,
entry 10).
As a-ketoamides are ubiquitous structural motifs that can
be found in many drugs and bioactive compounds,[1] the
present method provides a simple and easily practical
protocol for the construction of bioactive compounds from
simple and readily available starting materials. For example, I,
which is reported as an orexin receptor antagonist (Sche-
11090 www.angewandte.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 11088 –11092

Scheme 3. The synthesis of orexin receptor antagonist I. Reaction
conditions: 1a (0.25 mmol), 4 (0.375 mmol), CuBr (0.025 mmol),
pyridine (0.5 mmol), toluene (2.5 mL), 908C, O2 (1 atm), 12 h. Yields
are of the isolated products.
me 1),[1a] can be easily synthesized from the simple 2-phenyl-
acetaldehyde (1a) and 4 in 40% yield (Scheme 3).
The reaction of 1a and 2a in the presence of 18O2 (1 atm)
generated the 18O labelled product [18O]-3aa in 80% yield
[Eq. (1)], as determined by MS and HRMS (see the
Scheme 4. A proposed mechanism for the direct transformation.
oxidized by molecular oxygen to form the more-active CuII
salt under these reaction conditions; this active CuII species
can be detected by EPR (see the Supporting Informa-
tion).[11,14] Then, CuII could combine with 10 to form CuIII
complex 11.[15,16] Further intramolecular addition to the imine
À
and N Cu bond homolysis would form the radical inter-
Supporting Information). This result indicates that both the
oxygen atoms of the a-ketoamides originated from molecular
dioxygen. Furthermore, the reaction of 2-phenylacetic acid
(5) and 2a under the standard reaction conditions was
investigated. However, the desired product 3aa was not
obtained [Eq. (2)]. N-(4-Cyanophenyl)-2-phenylacetamide
mediate 12,[15] which could be oxidized by CuII or molecular
oxygen, thus resulting in intermediate 13.[17] Subsequent
fragmentation[18] of 13 would produce the desired a-keto-
amide 3.
In conclusion, we have demonstrated a novel Cu-cata-
lyzed aerobic oxidative coupling of aryl acetaldehydes with
anilines leading to a-ketoamides, which are ubiquitous
structural units in a number of biological active compounds;
this reaction is highly efficient and has a broad substrate
À
À
À
scope. Two Csp3 H, one Csp2 H, and one N H bond are
cleaved in this chemistry. It is noteworthy that N-substituted
anilines are suitable substrates for this transformation.
À
(6) under the standard reaction conditions could not be
converted into 3aa [Eq. (3)]. Meanwhile, 2-oxo-2-phenyl-
acetaldehyde (7) and 2-oxo-2-phenylacetic acid (8) were not
detected in the reaction of 1a under the standard reaction
conditions [Eq. (4)]. These results indicate that 5, 6, 7, and 8
are not intermediates of this copper-catalyzed aerobic oxida-
tive transformation.
Oxidative C H bond coupling and the use of molecular
oxygen (1 atm) as the oxidant make this transformation
sustainable and practical. A plausible mechanism is proposed
on the basis of mechanistic studies. Further studies to clearly
understand the reaction mechanism and the synthetic appli-
cations are ongoing in our laboratory.
Received: July 27, 2011
Published online: September 14, 2011
Keywords: amides · copper · cross-coupling · oxidation · oxygen
.
[1] a) H. Knust, M. Nettekoven, E. Pinard, O. Roche, M. Rogers-
Evans, PCT Int. Appl. WO 2009016087, 2009; b) C. A. Crowley,
N. G. J. Delaet, J. Ernst, C. G. Grove, B. Hepburn, B. King, C. J.
Larson, S. Miller, K. Pryor, L. J. Shuster, PCT Int. Appl. WO
2007146712, 2007; c) S. ꢁlvarez, R. ꢁlvarez, H. Khanwalkar, P.
Germain, G. Lemaire, F. Rodrꢂguez-Barrios, H. Gronemeyer,
A. R. de Lera, Bioorg. Med. Chem. 2009, 17, 4345; d) D. V. Patel,
R. D. J. Gless, H. Webb, K. Heather, S. K. Anandan, B. R.
Aavula, PCT Int. Appl. WO 2008073623, 2008.
On the basis of the above results and EPR studies (see the
Supporting Information), a plausible mechanism for the
copper-catalyzed aerobic oxidative coupling is illustrated in
Scheme 4. Aldehyde 1 and aniline 2 initially react to form
imine 9. Imine 9 could be oxidized to superoxide radical 10 by
a radical pathway under O2.[13] At the same time, the CuI salt is
[2] a) J. L. Jesuraj, J. Sivaguru, Chem. Commun. 2010, 46, 4791;
b) Z. Zhang, Q. Zhang, Z. Ni, Q. Liu, Chem. Commun. 2010, 46,
1269; c) K. K. S. Sai, P. M. Esteves, E. T. da Penha, D. A.
Klumpp, J. Org. Chem. 2008, 73, 6506; d) D. Tomita, K.
Angew. Chem. Int. Ed. 2011, 50, 11088 –11092
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org 11091

Communications
Yamatsugu, M. Kanai, M. Shibasaki, J. Am. Chem. Soc. 2009,
131, 6946; e) L. Yang, D.-X. Wang, Z.-T. Huang, M.-X. Wang, J.
Am. Chem. Soc. 2009, 131, 10390.
Chem. Int. Ed. 2011, 50, 5678; c) S. Chiba, L. Zhang, G. Y. Ang,
B. W.-Q. Hui, Org. Lett. 2010, 12, 2052; d) J. Wang, J. Wang, Y.
Zhu, P. Lu, Y. Wang, Chem, Chem. Commun. 2011, 47, 3275;
e) L. Zhang, G. Y. Ang, S. Chiba, Org. Lett. 2011, 13, 1622; f) A.
Hꢄusser, M. Trautmann, E. Roduner, Chem. Commun. 2011, 47,
6954; g) C. Wꢆrtele, O. Sander, V. Lutz, T. Waitz, F. Tuczek, S.
Schindler, J. Am. Chem. Soc. 2009, 131, 7544; h) H. R. Lucas, L.
Li, A. A. Narducci Sarjeant, M. A. Vance, E. I. Salomon, K. D.
Karlin, J. Am. Chem. Soc. 2009, 131, 3230; i) I. Garcia-Bosch, A.
Company, J. R. Frisch, M. Torrent-Sucarrat, M. Cardellach, I.
Gamba, M. Gꢆell, L. Casella, L. Que, Jr., X. Ribas, J. M. Luis, M.
Costas, Angew. Chem. 2010, 122, 2456; Angew. Chem. Int. Ed.
2010, 49, 2406; j) S. Palavicini, A. Granata, E. Monzani, L.
Casella, J. Am. Chem. Soc. 2005, 127, 18031; for mechanistic
studies, see: k) A. E. King, L. M. Huffman, A. Casitas, M.
Costas, X. Ribas, S. S. Stahl, J. Am. Chem. Soc. 2010, 132, 12068;
l) A. E. King, T. C. Brunold, S. S. Stahl, J. Am. Chem. Soc. 2009,
131, 5044; m) Y.-H. Zhang, J.-Q. Yu, J. Am. Chem. Soc. 2009,
131, 14654; n) N. Decharin, S. S. Stahl, J. Am. Chem. Soc. 2011,
133, 5732; o) A. N. Campbell, P. B. White, L. A. Guzei, S. S.
Stahl, J. Am. Chem. Soc. 2010, 132, 15116; p) Y. Wei, H. Zhao, J.
Kan, W. Su, M. Hong, J. Am. Chem. Soc. 2010, 132, 2522; q) E.
Boess, D. Sureshkumar, A. Sud, C. Wirtz, C. Fares, M.
Klussmann, J. Am. Chem. Soc. 2011, 133, 8106; r) P. Chen, E. I.
Solomon, J. Am. Chem. Soc. 2004, 126, 4991; s) M. P. Lanci, V. V.
Simirnov, C. J. Cramer, E. V. Gauchenova, J. Sundermeyer, J. P.
Roth, J. Am. Chem. Soc. 2007, 129, 14697; t) M. Rolff, J.
Schottenheim, G. Peters, F. Tuczek, Angew. Chem. 2010, 122,
6583; Angew. Chem. Int. Ed. 2010, 49, 6438; u) K. Schrçder, B.
Join, A. J. Amali, K. Junge, X. Ribas, M. Costas, M. Beller,
Angew. Chem. 2011, 123, 1461; Angew. Chem. Int. Ed. 2011, 50,
1425.
[3] a) A. Chiou, T. Markidis, V. C. Kokotou, R. Verger, G. Kokotus,
Org. Lett. 2000, 2, 347; b) G. M. Dubowchik, J. L. Ditta, J. J.
Herbst, S. Bollini, A. Vinitsky, Bioorg. Med. Chem. Lett. 2000,
10, 559; c) G. M. Dubowchik, V. M. Vrudhula, B. Dasgupta, J.
Ditta, T. Chen, S. Sheriff, K. Sipman, M. Witmer, J. Tredup,
D. M. Vyas, T. A. Verdoorn, S. Bollini, A. Vinitsky, Org. Lett.
2001, 3, 3987; d) R. P. Singh, J. M. Shreeve, J. Org. Chem. 2003,
68, 6063.
[4] a) J. E. Semple, T. D. Owens, K. Nguyen, O. E. Levy, Org. Lett.
2000, 2, 2769; b) L. Banfi, G. Guanti, R. Riva, Chem. Commun.
2000, 985; c) M. Nakamura, J. Inoue, T. Yamada, Bioorg. Med.
Chem. Lett. 2000, 10, 2807; d) A. Papanikos, J. Rademann, M.
Medal, J. Am. Chem. Soc. 2001, 123, 2176; e) J. Chen, X. Chen,
M. Bois-Choussy, J. Zhu, J. Am. Chem. Soc. 2006, 128, 87; f) L.
El Kaꢃm, R. Gamez-Montano, L. Grimaud, T. Ibarra-Rivera,
Chem. Commun. 2008, 1350.
[5] a) J. Liu, R. Zhang, S. Wang, W. Sun, C. Xia, Org. Lett. 2009, 11,
1321; b) E. R. Murphy, J. R. Martinelli, N. Zaborenko, S. L.
Buchwald, K. F. Jensen, Angew. Chem. 2007, 119, 1764; Angew.
Chem. Int. Ed. 2007, 46, 1734; c) T. Fukuyama, S. Nishitani, T.
Inouye, K. Morimoto, I. Ryu, Org. Lett. 2006, 8, 1383; d) M.
Iizuka, Y. Kondo, Chem. Commun. 2006, 1739.
[6] a) J.-M. Grassot, G. Masson, J. Zhu, Angew. Chem. 2008, 120,
961; Angew. Chem. Int. Ed. 2008, 47, 947; b) M. Bouma, G.
Masson, J. Zhu, J. Org. Chem. 2010, 75, 2748; c) D. Coffinier,
L. E. Kaim, L. Grimaud, Org. Lett. 2009, 11, 1825; d) R.
Mossetti, T. Pirali, G. C. Tron, J. Zhu, Org. Lett. 2010, 12, 820;
e) Q. Liu, S. Perreault, T. Rovis, J. Am. Chem. Soc. 2008, 130,
14066; f) Z. F. Al-Rashid, W. L. Johnson, R. P. Hsung, Y. Wei, P.-
Y. Yao, R. Liu, K. Zhao, J. Org. Chem. 2008, 73, 8780; g) B. Song,
S. Wang, C. Sun, H. Deng, B. Xu, Tetrahedron Lett. 2007, 48,
8982.
[12] C. Zhang, N. Jiao, Angew. Chem. 2010, 122, 6310; Angew. Chem.
Int. Ed. 2010, 49, 6174.
[13] a) A. Rieche, E. Hoeft, H. Schultze, Chem. Ber. 1964, 97, 195;
b) Science of Synthesis. Compounds with One Saturated Carbon-
Heteroatom Bond. Peroxides, Vol. 38 (Ed.: A. Berkessel),
Thieme, Stuttgart, 2009, pp. 9 – 141; c) A. G. Davies, R. V.
Foster, R. Nery, J. Chem. Soc. 1954, 2204; d) H. Yamamoto, M.
Akutagawa, H. Aoyama, Y. Omote, J. Chem. Soc. Perkin Trans. 1
1980, 2300; e) H. Nakamura, T. Goto, Bull. Chem. Soc. Jpn.
1988, 61, 3776.
[14] a) H. V. Obias, Y. Lin, N. N. Murthy, E. Pidcock, E. I. Solomon,
M. Ralle, N. J. Blackburn, Y.-M. Neuhold, A. D. Zuberbꢆhler,
K. D. Karlin, J. Am. Chem. Soc. 1998, 120, 12960; b) V.
Mahadevan, M. J. Henson, E. I. Solomon, T. D. P. Stack, J. Am.
Chem. Soc. 2000, 122, 10249; c) A. Kunishita, H. Ishimaru, S.
Nakashima, T. Ogura, S. Itoh, J. Am. Chem. Soc. 2008, 130, 4244;
d) M. Taki, S. Teramae, S. Nagatomo, Y. Tachi, T. Kitagawa, S.
Itoh, S. Fukuzumi, J. Am. Chem. Soc. 2002, 124, 6367; e) N. W.
Aboelella, B. F. Gherman, L. M. R. Hill, J. T. York, H. Holm,
V. G. Young, Jr, C. J. Cramer, W. B. Tolman, J. Am. Chem. Soc.
2006, 128, 3445.
[15] a) F. C. Sequeira, B. W. Turnpenny, S. R. Chemler, Angew.
Chem. 2010, 122, 6509; Angew. Chem. Int. Ed. 2010, 49, 6365;
b) W. Zeng, S. R. Chemler, J. Am. Chem. Soc. 2007, 129, 12948;
c) P. H. Fuller, J.-W. Kim, S. R. Chemler, J. Am. Chem. Soc. 2008,
130, 17638.
[16] a) P. Renaud, M. P. Sibi, Radicals in Organic Synthesis, Wiley-
VCH, Weinheim, 2001; b) D. J. Rawlinson, G. Sosnovsky, Syn-
thesis 1972, 1, and references therein.
[7] Dioxygen has been used as an ideal oxidant, for some reviews,
see: a) T. Punniyamurthy, S. Velusamy, J. Iqbal, Chem. Rev. 2005,
105, 2329; b) S. S. Stahl, Angew. Chem. 2004, 116, 3480; Angew.
Chem. Int. Ed. 2004, 43, 3400; c) M. S. Sigman, D. R. Jensen,
Acc. Chem. Res. 2006, 39, 221; d) J. Piera, J.-E. Bꢄckvall, Angew.
Chem. 2008, 120, 3558; Angew. Chem. Int. Ed. 2008, 47, 3506;
e) K. M. Gligorich, M. S. Sigman, Chem. Commun. 2009, 3854;
f) B. M. Stoltz, Chem. Lett. 2004, 33, 362.
[8] C. Zhang, N. Jiao, J. Am. Chem. Soc. 2010, 132, 28.
À
[9] For some reviews on C H bond activation in the last two years,
see: a) C.-L. Sun, B.-J. Li, Z.-J. Shi, Chem. Commun. 2010, 46,
677; b) G. E. Dobereiner, R. H. Crabtree, Chem. Rev. 2010, 110,
681; c) D. A. Colby, R. G. Bergman, J. A. Ellman, Chem. Rev.
2010, 110, 624; d) C. Copꢅret, Chem. Rev. 2010, 110, 656; e) T. W.
Lyons, M. S. Sanford, Chem. Rev. 2010, 110, 1147; f) I. A. I.
Mkhalid, J. H. Barnard, T. B. Marder, J. M. Murphy, J. F.
Hartwig, Chem. Rev. 2010, 110, 890; g) M. P. Doyle, R. Duffy,
M. Ratnikov, L. Zhou, Chem. Rev. 2010, 110, 704; h) A. Gunay,
K. H. Theopold, Chem. Rev. 2010, 110, 1060; i) D. Balcells, E.
Colt, O. Eisenstein, Chem. Rev. 2010, 110, 749; j) F. Bellina, R.
Rossi, Chem. Rev. 2010, 110, 1082; k) C.-L. Sun, B.-J. Li, Z.-J.
Shi, Chem. Rev. 2011, 111, 1293; l) C. S. Yeung, V. M. Dong,
Chem. Rev. 2011, 111, 1215; m) J. Le Bras, J. Muzart, Chem. Rev.
2011, 111, 1170; n) L. Ackermann, Chem. Rev. 2011, 111, 1315.
[10] For reviews, see: a) E. I. Solomon, P. Chen, M. Metz, S.-K. Lee,
A. E. Palmer, Angew. Chem. 2001, 113, 4702; Angew. Chem. Int.
Ed. 2001, 40, 4570; b) E. I. Solomon, U. M. Sundaram, T. E.
Machonkin, Chem. Rev. 1996, 96, 2563.
[17] a) Y.-X. Chen, L.-F. Qian, W. Zhang, B. Han, Angew. Chem.
2008, 120, 9470; Angew. Chem. Int. Ed. 2008, 47, 9330; b) G.
Speier, L. Pꢇrkꢇnyi, J. Org. Chem. 1986, 51, 218.
[18] a) L. Simꢇndi, T. M. Simꢇndi, Z. May, G. Besenyei, Coord.
Chem. Rev. 2003, 245, 85; b) K. Schank, H. Beck, F. Werner,
Helv. Chim. Acta 2000, 83, 1611.
[11] For some copper-catalyzed reactions involving dioxygen activa-
tion in recent years, see: a) S. Chiba, L. Zhang, J.-Y. Lee, J. Am.
Chem. Soc. 2010, 132, 7266; b) H. Wang, Y. Wang, D. Liang, L.
Liu, J. Zhang, Q. Zhu, Angew. Chem. 2011, 123, 5796; Angew.
11092 www.angewandte.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 11088 –11092