Copper-catalyzed selective oxidative acylation of secondary anilines with ethyl glyoxalate: Domino synthesis of indoline-2,3-diones

Article abstract of DOI:10.1002/adsc.201300044

A novel, easy and useful copper-catalyzed selective acylation of secondary anilines with ethyl glyoxalate has been developed, and the corresponding indoline-2,3-dione derivatives were prepared. The procedure comprises the sequential intermolecular copper-catalyzed selective oxidative ortho-site aromatic acylation of the NH group in secondary anilines and intramolecular nucleophilic attack of the NH group to the ester. The inexpensive, easy and efficient method should provide a new strategy for synthesis of dicarbonyl compounds. Copyright

Full text of DOI:10.1002/adsc.201300044

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DOI: 10.1002/adsc.201300044
Copper-Catalyzed Selective Oxidative Acylation of Secondary
Anilines with Ethyl Glyoxalate: Domino Synthesis of Indoline-
2,3-diones
Tao Liu,a Haijun Yang,a Yuyang Jiang,b and Hua Fua,b,*
a
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of
Chemistry, Tsinghua University, Beijing 100084, Peopleꢀs Republic of China
Fax : (+ 86)-10-6278-1695; e-mail: fuhua@mail.tsinghua.edu.cn
Key Laboratory of Chemical Biology (Guangdong Province), Graduate School of Shenzhen, Tsinghua University,
b
Shenzhen 518057, Peopleꢀs Republic of China
Received: January 17, 2013; Revised: March 6, 2013; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201300044.
Abstract: A novel, easy and useful copper-catalyzed lines and intramolecular nucleophilic attack of the
selective acylation of secondary anilines with ethyl NH group to the ester. The inexpensive, easy and ef-
glyoxalate has been developed, and the correspond- ficient method should provide a new strategy for syn-
ing indoline-2,3-dione derivatives were prepared. thesis of dicarbonyl compounds.
The procedure comprises the sequential intermolecu-
À
lar copper-catalyzed selective oxidative ortho-site ar- Keywords: acylation; C H functionalization; copper;
omatic acylation of the NH group in secondary ani- indoline-2,3-diones; selectivity
Introduction
tive substrates for various acylation reactions in the
transition metal-catalyzed C H activation. For exam-
À
Nitrogen-containing heterocycles are ubiquitous subu- ple, amines could efficiently be transformed into
nits of a variety of biologically active substances,[1] amides by using aldehydes as the partners
and they have been assigned as privileged structures (Scheme 1a).[9] Aromatic C H bond acylations per-
À
in drug development.[2] The indoline-2,3-dione deriva- formed well in the presence of ortho-site directing
tives found in natural products[3] show various biologi- groups. Recently, the acylation of 2-arylpyridines with
cal activities such as anticonvulsant,[4a] antimicro- aldehydes has been developed by using the pyridine
bial,[4b] antitumor,[4c] antiviral,[4d] anti-HIV,[4e] and anti- moiety as the directing group (Scheme 1b).[10] Aceta-
tubercular,[4f] and they are used as important inter- nilides are also common substrates for ortho-acylation
mediates in organic synthesis.[5] The traditional syn- of aromatic C H bonds (Scheme 1c). Recently, Li
[11]
À
thesis of indoline-2,3-diones usually uses coupling of and co-workers have developed an efficient copper-
anilines with oxalyl chloride in the presence of excess catalyzed oxidative intramolecular acylation of N-
AlCl3.[6] However, the method is environmentally un- alkyl-2-oxo-N-phenylacetamides leading to indoline-
friendly, and it does not meet the requirements of 2,3-diones (Scheme 1d).[12] However, to the best of
modern green chemistry. Therefore, it is highly desira- our knowledge, the direct ortho-site aromatic C H
ble to develop a convenient and practical approach to functionalization of anilines did not work in the ab-
À
this kind of compound.
sence of directing groups in the previous research
Recently, transition metal-catalyzed C H function- works.[13] Considering the low-cost and low toxicity of
alization has emerged as a sustainable and intriguing copper catalysts, the good functional tolerance of
protocol because it does not need one to preinstall copper-catalyzed reactions,[14] and the efficacy in the
functional groups which can minimize the requisite copper-catalyzed synthesis of N-heterocycles via the
À
[15,16]
À
reagents, separation processes, waste, energy, time C H functionalization strategy,
we investigated
and cost,[7] and some valuable products including N- the copper-catalyzed oxidative reactions of secondary
heterocycles[8] have been synthesized via this strategy. anilines with ethyl glyoxalate. Surprisingly, indoline-
However, it is still a challenge to develop an efficient 2,3-diones were obtained via sequential intermolecu-
À
and highly selective approach. Aldehydes are attrac- lar selective oxidative ortho-site aromatic C H acyla-
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Scheme 1. (a) Transition metal-catalyzed acylation of amines with aldehydes. (b–d) Transition metal-catalyzed ortho-acyla-
À
tion of aromatic C H bonds in the presence of directing groups. (e) No acylation of NH group in secondary anilines under
copper catalysis. (f) Copper-catalyzed selectively oxidative acylation and amidation of secondary anilines with ethyl glyoxa-
late leading to indoline-2,3-diones (our strategy).
tion of NH group and intramolecular formation of the Results and Discussion
amide bond (Scheme 1f). However, acylation prod-
ucts of the NH group in secondary anilines were not At first, diphenylamine was chosen as the partner of
observed (Scheme 1e). In addition, no decarbonyla- ethyl glyoxalate to optimize the reaction conditions
tion occurred in the copper-catalyzed oxidative acyla- including the catalysts, oxidants, solvents, ligands and
tion reactions. In fact, the decarbonylation had often temperature. As shown in Table 1, various copper
been observed in the previous transition metal-cata- salts were screened (entries 1–8) using 1.5 equivalents
À
lyzed acylation of aromatic C H bonds by using the of tert-butyl hydroperoxide (TBHP) in decane as the
dicarbonyl compounds as the acylating agents.[11b,17] oxidant, dichloroethane as the solvent at 1008C for
Herein, we report this novel copper-catalyzed selec- 24 h, and Cu
ACHTUNGRTEN(NUNG OAc)2 exhibited the highest activity
tive acylation of secondary anilines with ethyl glyoxa- (entry 4). No target product was observed in the ab-
late leading to indoline-2,3-diones.
sence of a copper catalyst (entry 9). Other solvents
were attempted (entries 10–13), and toluene provided
the highest yield (entry 10). Various ligands were
added to the reaction systems (entries 14–17), and the
yield was greatly increased in the presence of
0.2 equiv. of nicotinic acid (entry 16). The results
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Copper-Catalyzed Selective Oxidative Acylation of Secondary Anilines with Ethyl Glyoxalate
Table 1. Copper-catalyzed reaction of diphenylamine with
ethyl glyoxalate leading to 1-phenylindoline-2,3-dione (2n):
optimization of conditions.[a]
20 mol% nicotinic acid as the ligand, and toluene as
the solvent at 1008C.
With the optimum reaction conditions in hand, we
investigated the scope of substrates for the copper-
catalyzed oxidative acylation and amidation of secon-
dary anilines (1) with ethyl glyoxalate leading to indo-
line-2,3-dione derivatives (2). As shown in Table 2,
the tested substrates afforded moderate to good
yields. For substituted N-alkylanlines, the acylation
undisputably occurred on the aromatic ring (en-
tries 1–14). For the N-alkylanline with a meta-sub-
stituent, N-cyclohexyl-3-methylbenzenamine, two acy-
lation products (2k and 2k’) were obtained (entry 11).
When the substrates were diarylamines, the site of
acylation highly depended on the electronic effect of
the two aromatic rings, and the phenyl rings contain-
ing rich-electron groups were favored (entries 15–21).
The copper-catalyzed domino reactions could tolerate
Entry Cat.
Oxidant Solvent Ligand Yield [%][b]
1
2
3
4
5
6
7
8
CuI
CuBr
CuCl
TBHP DCE
TBHP DCE
TBHP DCE
30
23
24
33
27
29
26
21
0
Cu
Cu
Cu
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
CuCl2
CuO
–
TBHP DCE
TBHP DCE
TBHP DCE
9
10
11
12
13
14
15
16
17
18
19
20
21
22
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
Cu
N
44
39
0
À
some functional groups including C Cl bonds (en-
tries 4, 12, and 16-18), and CF3 groups (entries 19 and
20) in the substrates. Interestingly, the copper-cata-
lyzed acylation selectively occurred on the ortho-site
of the NH group in the secondary anilines, and the di-
carbonyl group was retained in the target products.
Therefore, the present method provides a novel and
useful strategy for synthesis of dicarbonyl compounds.
In order to explore the mechanism for copper-cata-
lyzed oxidative coupling of secondary anilines with
ethyl glyoxalate leading to indoline-2,3-diones, two
control experiments were performed under the stan-
dard conditions. Treatment of diphenylamine with di-
ethyl oxalate did not provided amidation product 3
(Scheme 2a), and the result showed that the domino
reactions of secondary anilines with ethyl glyoxalate
did not start from nucleophilic attack of NH to ester.
Treatment of 3 under the standard conditions did not
lead to 2o (Scheme 2b), and this result showed that
the formation of the target product (2) was not from
intermediate 3. Control experiments were performed
for the treatment of ethyl glyoxalate with tert-butyl
trace
34
65
44
12
trace
0
55d
58e
[a]
Reaction conditions: diphenylamine (1a) (0.25 mmol),
ethyl glyoxalate in toluene (50%, 0.5 mmol), catalyst
(0.025 mmol), TBHP in decane (5.5M, 0.375 mmol),
ligand (0.05 mmol), solvent (1 mL), reaction temperature
(1008C), reaction time (24 h).
[b]
[c]
[d]
[e]
Isolated yield.
TBHP in water (70%, 0.375 mmol).
Reaction temperature (908C).
Reaction temperature (1108C). Tf=CF3SO2À; TFA=
CF3COOÀ; TBHP=tert-butyl hydroperoxide; DCE=1,2-
dichloroethane; PA=picolinic acid; NA=nicotinic acid;
EN=ethyl nicotinate.
hydroperoxide under catalysis of CuACTHNURTGNENG(U OAc)2, and the
in situ ESR showed the corresponding free radical
signal (see the Supporting Information for the de-
tails). Therefore, a possible mechanism for the
showed that the electronic nature of the ligands (i.e., copper-catalyzed synthesis of indoline-2,3-dione deriv-
pKa) also was a key factor for the formation of the atives (2) is proposed as shown in Scheme 3. First, co-
target product. A similar result was found by Stoltzꢀs ordination of copper catalyst Cu(II) with ligand NH
group.[18] The reactivity obviously decreased upon in secondary aniline and two oxygens in ethyl glyoxa-
using aqueous TBHP as the oxidant (entry 18). late provides I, and reaction of I with tert-butyl hydro-
Oxygen (entry 19) and K2S2O8 (entry 20) were used as peroxide gives free radicals II[11b] and t-BuOC. ortho-
oxidants, and they gave poor results. We attempted Aromatic acylation of the NH group in II gives III
different temperature (entries 21 and 22), and 1008C freeing the copper catalyst and ligand, and dissocia-
was suitable (compare entries 16, 21 and 22). There- tion of the hydrogen free radical in III in the presence
fore, the optimum conditions for the copper-catalyzed of t-BuOC yields IV. Finally, intramolecular nucleophil-
protocol are as follows: 10 mol% CuACHTUNRGTNEUNG(OAc)2 as the ic attack of the NH group to the ester in IV affords
catalyst, 1.5 equiv. of TBHP in decane as the oxidant, the target product (2). The structure of complex II
makes acylation of the aryl group more favorable
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Scheme 2. Under the standard conditions: (a) Treatment of diphenylamine with diethyl oxalate. (b) Treatment of ethyl (di-
phenylcarbamoyl)formate.
Table 2. Copper-catalyzed synthesis of indoline-2,3-dione derivatives (2).[a]
Entry
1
Temp./Time
2
Yield [%][b]
36
1008C/24 h
2a
2b
2
3
4
1008C/24 h
1008C/24 h
1108C/48 h
55
58
45
2c
2d
5
6
1008C/24 h
1108C/24 h
2e
2f
46
51
7
8
1108C/48 h
1108C/24 h
2g
2h
54
53
9
1008C/24 h
2i
59
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Copper-Catalyzed Selective Oxidative Acylation of Secondary Anilines with Ethyl Glyoxalate
Table 2. (Continued)
Entry
Temp./Time
2
Yield [%][b]
10
1008C/24 h
2j
64
2k
2k’
11
1008C/24 h
52: 2k/2k’ (2:1)
12
13
14
1108C/48 h
1108C/48 h
1008C/24 h
2l
49
47
65
2m
2n
15
16
17
18
1008C/24 h
1008C/24 h
1108C/24 h
1008C/24 h
2o
2p
2q
2r
60
52
58
42
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Table 2. (Continued)
Entry
Temp./Time
2
Yield [%][b]
19
1108C/24 h
2s
2t
60
20
1008C/24 h
53
[a]
Reaction conditions: secondary aniline (1) (0.25 mmol), ethyl glyoxalate in toluene (50%, 0.5 mmol), CuACHTUNGTRENNUNG(OAc)2
(0.025 mmol), TBHP in decane (5.5M, 0.375 mmol), nicotinic acid (0.05 mmol), toluene (1 mL), reaction temperature
(100 or 1108C), reaction time (24 or 48 h).
Isolated yield.
[b]
Scheme 3. Possible mechanism for the copper-catalyzed oxidative synthesis of indoline-2,3-dione derivatives (2).
than acylation of the NH group. In addition, the de- the inexpensive, easy and efficient method for the
carbonylation of ethyl glyoxalate is suppressed be- synthesis of dicarbonyl compounds should attract
cause of efficient coordination of Cu(II) with the much attention in academic and industrial researches.
ethyl glyoxalate unit in I and II.
Investigations on further application of this reaction
are in progress.
Conclusions
Experimental Section
We have developed a novel and useful copper-cata-
lyzed method for the synthesis of indoline-2,3-dione
General Procedure for Synthesis of Compounds 2a–t
derivatives. The protocol uses inexpensive Cu
ACHTUNGERTN(NUNG OAc)2
as the catalyst, picolinic acid as the ligand, and tert-
A 25-mL Schlenk tube was charged with a magnetic stirrer
butyl hydroperoxide as the oxidant, readily available and toluene (1.0 mL). Secondary aniline (1) (0.25 mmol),
ethyl glyoxalate in toluene (50%, 100 mL, 0.5 mmol),
Cu(OAc)2 (0.025 mmol, 5 mg), TBHP in decane (5.5M,
secondary anilines and ethyl glyoxalate as the starting
materials, and the corresponding indoline-2,3-dione
derivatives were prepared in moderate to good yields.
The procedure involves intermolecular copper-cata-
lyzed selective oxidative ortho-site aromatic acylation
of the NH group in secondary anilines and intramo-
lecular nucleophilic attack of the NH group to the
ester. This is the first copper-catalyzed example for
the synthesis of dicarbonyl compounds using ethyl
AHCTUNGTRENNUNG
70 mL, 0.375 mmol) and nicotinic acid (0.05 mmol, 6 mg)
were added to the tube. The mixture was stirred at 100 or
1108C for 24 or 48 h (see Table 2 for details). The resulting
mixture was cooled to room temperature, the solvent was
removed on a rotary evaporator, and the residue was puri-
fied by column chromatography on silica gel using petrole-
um ether/ethyl acetate as eluent to give the desired target
product (2). Three representative examples are shown
glyoxalate as the dicarbonylating agent. Therefore, below.
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Copper-Catalyzed Selective Oxidative Acylation of Secondary Anilines with Ethyl Glyoxalate
1-Isopropyl-5-methylindoline-2,3-dione (2c): Eluent: pe-
troleum ether/ethyl acetate (10:1); yield: 29 mg (58%); red
solid; mp 84–868C. 1H NMR (CDCl3, 300 MHz): d=7.34–
7.41 (m, 2H), 6.91 (d, J=8.1 Hz, 1H), 4.52 (m, 1H), 2.32 (s,
3H), 1.51 (d, J=8.0 Hz, 3H), 1.48 (d, J=8.0 Hz, 3H);
13C NMR (CDCl3, 75 MHz): d=184.2, 158.0, 148.3, 138.6,
133.1, 126.0, 118.1, 111.3, 44.7, 20.6, 19.5; HR-MS (ESI):
m/z=226.0843, calcd. for (C12H13NO2 +Na)+: 226.0844.
5-Methyl-1-p-tolylindoline-2,3-dione (2o): Eluent: petrole-
um ether/ethyl acetate (10:1); yield: 38 mg (60%); red solid;
mp 157–1598C. 1H NMR (CDCl3, 300 MHz): d=7.33–7.35
(m, 3H), 7.26 (d, J=8.8 Hz, 3H), 7.72 (d, J=8.1 Hz, 1H),
2.42 (s, 3H), 2.34 (s, 3H); 13C NMR (CDCl3, 75 MHz): d=
183.4, 157.6, 149.8, 138.9, 138.8, 134.2, 130.6, 127.8, 125.8,
125.8, 117.6, 111.2, 21.3, 20.8; HR-MS (ESI): m/z=274.0845,
calcd. for (C16H13NO2 +Na)+: 274.0844.
Aboul-Fadl, F. A. S. Bin-Jubair, Int. J. Res. Pharm. Sci.
2010, 1, 113.
[5] G. S. Singh, Z. Y. Desta, Chem. Rev. 2012, 112, 6104,
and references cited therein.
[6] a) Z. Razavi1, F. McCapra, Luminescence 2000, 15,
239; b) Z. Razavi1, F. McCapra, Luminescence 2000,
15, 245; c) S. Lakatos, J. Fetter, F. Bertha, P. Huszthy,
T. Tꢂth, V. Farkas, G. Orosz, M. Hollꢂsi, Tetrahedron
2008, 64, 1012.
[7] a) S. S. Stahl, Angew. Chem. 2004, 116, 3480; Angew.
Chem. Int. Ed. 2004, 43, 3400; b) T. Punniyamurthy, S.
Velusamy, J. Iqbal, Chem. Rev. 2005, 105, 2329; c) L.
Ackermann, R. Vicente, A. R. Kapdi, Angew. Chem.
2009, 121, 9976; Angew. Chem. Int. Ed. 2009, 48, 9792;
d) X. Chen, K. M. Engle, D.-H. Wang, J.-Q. Yu, Angew.
Chem. 2009, 121, 5196; Angew. Chem. Int. Ed. 2009, 48,
5094; e) O. Daugulis, H.-Q. Do, D. Shabashov, Acc.
Chem. Res. 2009, 42, 1074; f) T. W. Lyons, M. S. San-
ford, Chem. Rev. 2010, 110, 1147; g) J. Wencel-Delord,
T. Drçge, F. Liu, F. Glorius, Chem. Soc. Rev. 2011, 40,
4740; h) C. S. Yeung, V. M. Dong, Chem. Rev. 2011,
111, 1215; i) L.-M. Xu, B.-J. Li, Z. Yang, Z.-J. Shi,
Chem. Soc. Rev. 2010, 39, 712; j) C. Liu, H. Zhang, W.
Shi, A. Lei, Chem. Rev. 2011, 111, 1780; k) C. Liu, H.
Zhang, W. Shi, A. Lei, Chem. Rev. 2011, 111, 1780;
l) A. N. Campbell, S. S. Stahl, Acc. Chem. Res. 2012, 45,
851; m) Z. Shi, C. Zhang, C. Tang, N. Jiao, Chem. Soc.
Rev. 2012, 41, 3381.
1-[3-(Trifluoromethyl)phenyl]-5-methylindoline-2,3-dione
(2s): Eluent: petroleum ether/ethyl acetate (10:1); yield:
1
46 mg (60%); red solid; mp 192–1948C. H NMR (CDCl3,
300 MHz): d=7.70–7.66 (m, 3H), 7.64–7.70 (m, 1H), 7.52 (s,
1H), 7.38 (d, J=8.1 Hz, 1H), 6.81 (d, J=8.1 Hz, 1H) 2.36
(s, 3H); 13C NMR (CDCl3, 75 MHz): d=182.4, 157.3, 148.7,
139.1, 134.9, 133.9, 132.3 (J=33.1 Hz), 130.7, 129.4, 126.2,
125.4 (J=4.1 Hz), 121.7 (J=290.0 Hz), 122.7 (J=4.1 Hz),
117.7, 111.0, 20.8; HR-MS (ESI): m/z=328.0558, calcd. for
(C16H10F3NO2 +Na)+: 328.0561.
[8] a) W. C. P. Tsang, N. Zheng, S. L. Buchwald, J. Am.
Chem. Soc. 2005, 127, 14560; b) J. A. Jordan-Hore,
C. C. C. Johansson, M. Gulias, E. M. Beck, M. J. Gaunt,
J. Am. Chem. Soc. 2008, 130, 16184; c) Q. Xiao, W.-H.
Wang, G. Liu, F.-K. Meng, J.-H. Chen, Z. Yang, Z.-J.
Shi, Chem. Eur. J. 2009, 15, 7292; d) K. Inamoto, T.
Saito, M. Katsuno, T. Sakamoto, K. Hiroya, Org. Lett.
2007, 9, 2931; e) T.-S. Mei, X. Wang, J.-Q. Yu, J. Am.
Chem. Soc. 2009, 131, 10806; f) J. J. Neumann, S. Rak-
shit, T. Drçge, F. Glorius, Angew. Chem. 2009, 121,
7024; Angew. Chem. Int. Ed. 2009, 48, 6892; g) M.
Wasa, J.-Q. Yu, J. Am. Chem. Soc. 2008, 130, 14058.
[9] a) C. L. Allen, S. Davulcu, J. M. J. Williams, Org. Lett.
2010, 12, 5096; b) S. Muthaiah, S. C. Ghosh, J.-E. Jee,
C. Chen, J. Zhang, S. H. Hong, J. Org. Chem. 2010, 75,
3002; c) W.-J. Yoo, C.-J. Li, J. Am. Chem. Soc. 2006,
128, 13064; d) S. Kegnæs, J. Mielby, U. V. Mentzel, T.
Jensen, P. Fristrup, A. Riisager, Chem. Commun. 2012,
48, 2427; e) H. Yao, K. Yamamoto, Chem. Asian J.
2012, 7, 1542; f) S. C. Ghosh, J. S. Y. Ngiam, C. L. L.
Chai, A. M. Seayad, T. T. Dang, A. Chen, Adv. Synth.
Catal. 2012, 354, 1407.
Acknowledgements
The authors wish to thank the National Natural Science
Foundation of China (Grant Nos. 21172128 and 21105054),
the Ministry of Science and Technology of China (Grant No.
2012CB722605) and the Doctoral Program of Higher Educa-
tion (No. 20090002110058) for financial support.
References
[1] R. W. DeSimone, K. S. Currie, S. A. Mitchell, J. W.
Darrow, D. A. Pippin, Comb. Chem. High Throughput
Screening 2004, 7, 473.
[2] P. D. Leeson, B. Springthorpe, Nat. Rev. Drug Discov-
ery 2007, 6, 881.
[3] a) J. Bergman, O. Lindstrom, U. Tilstam, Tetrahedron
1988, 44, 2879; b) J. F. M. da Silva, S. J. Garden, A. C. J.
Pinto, J. Braz. Chem. Soc. 2001, 12, 273, and references
cited therein.
[10] a) O. Basle, J. Bidange, Q. Shuai, C.-J. Li, Adv. Synth.
Catal. 2010, 352, 1145; b) X. Jia, S. Zhang, W. Wang, F.
Luo, J. Cheng, Org. Lett. 2009, 11, 3120.
[11] a) Y. Wu, B. Li, F. Mao, X. Li, F. Y. Kwong, Org. Lett.
2011, 13, 3258; b) S. Wang, Z. Yang, J. Liu, K. Xie, A.
Wang, X. Chen, Z. Tan, Chem. Commun. 2012, 48,
9924.
[12] B.-X. Tang, R.-J. Song, C.-Y. Wu, Y. Liu, M.-B. Zhou,
W.-T. Wei, G.-B. Deng, D.-L. Yin, J.-H. Li, J. Am.
Chem. Soc. 2010, 132, 8900.
[4] a) M. Verma, S. N. Pandeya, K. N. Singh, J. P. Stables,
Acta Pharm. 2004, 54, 49; b) A. Raj, R. Raghunathan,
M. R. Sridevikumaria, N. Raman, Bioorg. Med. Chem.
2003, 11, 407; c) R. Tripathy, A. Reiboldt, P. A. Messi-
na, M. Iqbal, J. Singh, E. R. Bacon, T. S. Angeles, S. X.
Yang, M. S. Albom, C. Robinson, H. Chang, B. A. Rug-
geri, J. P. Mallamo, Bioorg. Med. Chem. Lett. 2006, 16,
2158; d) T. Jiang, K. L. Kuhen, K. Wolff, H. Yin, K.
Bieza, J. Caldwell, B. Bursulaya, T. Tuntlad, K. Zhang,
D. Karanewsky, Y. He, Bioorg. Med. Chem. Lett. 2006,
16, 2109; e) B. T. Ratan, B. Anand, P. Yogeeswari, D.
Sriram, Bioorg. Med. Chem. Lett. 2005, 15, 4451; f) T.
[13] a) M. D. K. Boele, G. P. F. van Strijdonck, A. H. M.
de Vries, P. C. J. Kamer, J. G. de Vries, P. W. N. M. van
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
7
ÞÞ
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Tao Liu et al.
FULL PAPERS
Leeuwen, J. Am. Chem. Soc. 2002, 124, 1586; b) O.
Daugulis, V. G. Zaitsev, Angew. Chem. 2005, 117, 4114;
Angew. Chem. Int. Ed. 2005, 44, 4046; c) V. G. Zaitsev,
D. Shabashov, O. Daugulis, J. Am. Chem. Soc. 2005,
127, 13154; d) S. Yang, B. Li, X. Wan, Z. Shi, J. Am.
Chem. Soc. 2007, 129, 6066.
2008, 47, 6411; b) G. Brasche, S. L. Buchwald, Angew.
Chem. 2008, 120, 1958; Angew. Chem. Int. Ed. 2008, 47,
1932; c) S. Ueda, H. Nagasawa, J. Am. Chem. Soc.
2009, 131, 15080; d) P. Saha, T. Ramana, N. Purkait,
M. A. Ali, R. Paul, T. Punniyamurthy, J. Org. Chem.
2009, 74, 8719; e) H. Wang, Y. Wang, D. Liang, L. Liu,
J. Zhang, Q. Zhu, Angew. Chem. 2011, 123, 5796;
Angew. Chem. Int. Ed. 2011, 50, 5677; f) Y.-F. Wang, H.
Chen, X. Zhu, S. Chiba, J. Am. Chem. Soc. 2012, 134,
11980; g) T. Liu, H. Fu, Synthesis 2012, 44, 2805, and
references cited therein.
[14] For recent reviews on copper-catalyzed cross couplings,
see: a) S. V. Ley, A. W. Thomas, Angew. Chem. 2003,
115, 5558; Angew. Chem. Int. Ed. 2003, 42, 5400; b) K.
Kunz, U. Scholz, D. Ganzer, Synlett 2003, 2428; c) I. P.
Beletskaya, A. V. Cheprakov, Coord. Chem. Rev. 2004,
248, 2337; d) G. Evano, N. Blanchard, M. Toumi,
Chem. Rev. 2008, 108, 3054; e) D. Ma, Q. Cai, Acc.
Chem. Res. 2008, 41, 1450; f) F. Monnier, M. Taillefer,
Angew. Chem. 2009, 121, 7088; Angew. Chem. Int. Ed.
2009, 48, 6954; g) D. S. Surry, S. L. Buchwald, Chem.
Sci. 2010, 1, 13; h) H. Rao, H. Fu, Synlett 2011, 745,
and references cited therein.
[16] a) X. Wang, Y. Jin, Y. Zhao, L. Zhu, H. Fu, Org. Lett.
2012, 14, 452; b) H. Xu, H. Fu, Chem. Eur. J. 2012, 18,
1180.
[17] a) P. Fang, M. Li, H. Ge, J. Am. Chem. Soc. 2010, 132,
11898; b) M. Li, H. Ge, Org. Lett. 2010, 12, 3464; c) W.
Zhou, H. Li, L. Wang, Org. Lett. 2012, 14, 4594.
[18] E. M. Ferreira, B. M. Stoltz, J. Am. Chem. Soc. 2003,
125, 9578.
[15] For selected papers, see: a) S. Ueda, H. Nagasawa,
Angew. Chem. 2008, 120, 6511; Angew. Chem. Int. Ed.
8
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ÝÝ
These are not the final page numbers!

FULL PAPERS
Copper-Catalyzed Selective Oxidative Acylation of
Secondary Anilines with Ethyl Glyoxalate: Domino
Synthesis of Indoline-2,3-diones
9
Adv. Synth. Catal. 2013, 355, 1 – 9
Tao Liu, Haijun Yang, Yuyang Jiang, Hua Fu*
Adv. Synth. Catal. 0000, 000, 0 – 0
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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These are not the final page numbers!