Cobalt(III)-Catalyzed Intramolecular Cross-Dehydrogenative C?H/X?H Coupling: Efficient Synthesis of Indoles and Benzofurans

Article abstract of DOI:10.1002/chem.201604111

An efficient cobalt(III)-catalyzed intramolecular cross-dehydrogenative C?H/N?H coupling of ortho-alkenylanilines has been developed utilizing O₂as a terminal oxidant. The developed reaction tolerates various reactive functional groups and allo

Full text of DOI:10.1002/chem.201604111

A Journal of
Accepted Article
Title: Cobalt(III) Catalyzed Intramolecular Cross-Dehydrogenative C-H/X-H Coup-
ling: Efficient Synthesis of Indoles and Benzofurans
Authors: Jayanta Ghorai; Angula Chandra Shekar Reddy; Pazhamalai Anbarasan
This manuscript has been accepted after peer review and the authors have elected
to post their Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by using the Digital
Object Identifier (DOI) given below. The VoR will be published online in Early View as
soon as possible and may be different to this Accepted Article as a result of editing.
Readers should obtain the VoR from the journal website shown below when it is pu-
blished to ensure accuracy of information. The authors are responsible for the content
of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.201604111
Link to VoR: http://dx.doi.org/10.1002/chem.201604111
Supported by

Chemistry - A European Journal
10.1002/chem.201604111
COMMUNICATION
Cobalt(III) Catalyzed Intramolecular Cross-Dehydrogenative C-
H/X-H Coupling: Efficient Synthesis of Indoles and Benzofurans
Jayanta Ghorai, Angula Chandra Shekar Reddy and Pazhamalai Anbarasan*
Abstract: An efficient cobalt(III)-catalyzed intramolecular cross-
dehydrogenative C-H/N-H coupling of ortho-alkenylanilines has been
developed utilizing O2 as a terminal oxidant. The developed reaction
tolerates various reactive functional groups and allows the synthesis
of diverse indole derivatives in good to excellent yield. The method
was successfully extended to the synthesis of benzofuran via
intramolecular cross-dehydrogenative C-H/O-H coupling of ortho-
alkenylphenols.
O2/TEMPO[8] as oxidant. Very recently, a ruthenium based
photocatalyst promoted intramolecular C-H/N-H coupling of
ortho-alkenylanilines was documented by Zheng et. al.[9]
Besides these, metal free strategies were also realized for the
synthesis of indoles.[10] Instead, synthesis of benzofurans
through intramolecular C-H/O-H coupling of ortho-alkenylphenol
is limited to either palladium and copper co-catalyzed[11] or
substoichiometric copper[12] catalyzed transformation. However,
most of these methods suffer from use of precious metal catalyst,
the need of super stoichiometric amounts of oxidant, generation
of a large amount of waste, and low yield. Thus, development of
a general and efficient method for the intramolecular C-H/X-H
coupling of ortho-alkenylanilines/phenols employing non-
precious metal-based catalyst and O2 as the sole oxidant is
highly desirable.
Transition metal catalyzed cross-dehydrogenative coupling
(CDC) has emerged as an efficient synthetic transformation in
organic synthesis for the construction of C-C and C-heteroatom
bonds.[1] In addition, CDC generates significantly less volume of
waste and byproduct, uses readily accessible substrates without
pre-functionalization, and as a consequence, provides a high
atom and step economy. In this context, intramolecular
formation of C-N/O bonds[2] via CDC is of continuing interest in
pharmaceutical and medicinal chemistry for the synthesis of
therapeutically important N- and O-heterocycles. Representative
examples of bioactive molecules containing indole and
benzofuran are shown in Figure 1.
a) Previous synthesis of indole through CDC
X = NR, O
R2
R2
R3
TM
TM = Pd, Cu, Ru
R3 Oxidant = BQ, Cu(II),
MnO2, PhIO
R
R
Oxidant
H
XH
X
b) Co-catalyzed synthesis of indole/benzofuran through CDC: this work!
R2
• low catalyst loading
• catalytic additive
• O2 as sole oxidant
• broad substrates scope
• X-H and C-H activation
R2
R3
Co
R1
R3
R1
O
Cu(II)/O2
H
X
XH
N
N
I
N
O
H
F
HN
Scheme 1. Synthesis of indoles via intramolecular CDC.
OHC
OH
O
N
I
HO2C
H
Et2N
amiodarone
OH
OMe
fluvastatin (prevents
trigonoliimine C
The cobalt catalyzed functionalizations of C(sp2)-H bond have
seen exponential growth in transition metal catalysis.[13] Of
particular interest is the Cp*Co(III) based catalysis pioneered by
the group of Kanai,[14] Glorius,[15] Ackermann,[16] Ellman,[17]
Jiao,[18] Chang,[19] Cheng,[20] Sundararaju[21] and others[22]. Most
of the transformations are directed toward the construction of C-
C bond formation, but the coupling of C-heteroatom bonds is
scarcely studied.[23] Kanai et. al[24] disclosed the cobalt(III)
catalyzed C-H amidation using sulfonyl azides. On the other
hand, Chang et. al,[19a, 19c] Ackermann et. al,[16e] Jiao et. al[18a]
and Li et. al[25] utilized acetoxycarbamates, dioxazolones and
anthranils. Similarly, C-H halogenation was achieved by group of
Glorius[26] and Pawar[27]. However, construction of C-heteroatom
bonds through cross-dehydrogenative coupling of C-H/X-H bond
is unknown in Cp*Co(III) based catalysis (Scheme 1b). Inspired
by the recent development in cobalt(III) catalyzed C-H bond
functionalization and our continuing interest in the
functionalization of C-H bonds,[28] we herein disclose the
cobalt(III) catalyzed synthesis of indoles and benzofurans
(antiarrhythmic agent)
cardiovascular disease)
(anti-HIV agent)
Figure 1. Indole and benzofuran containing bioactive molecules.
Although numerous methods for the synthesis of indoles are
known in the literature,[3] transition-metal catalyzed synthesis of
indoles through intramolecular CDC of C-H/N-H bonds of ortho-
alkenylanilines is rather limited (Scheme 1a). For instance,
Hegedus et. al,[4] Stille et. al[5] and Buchwald et. al[6]
demonstrated the synthesis of indoles via CDC utilizing
palladium catalysts in the presence of stoichiometric oxidant.
Chemler and co-workers reported copper catalyzed C-N bond
[7]
formation for the synthesis of indoles employing MnO2 or
[a]
Mr. J. Ghorai, Mr. A. C. S. Reddy and Prof. Dr. P. Anbarasan
Department of Chemistry
Indian Institute of Technology Madras
Chennai - 600036
E-mail: anbarasansp@iitm.ac.in
through
intramolecular
C-H/X-H
coupling
of
ortho-
alkenylanilines/phenols.
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved

Chemistry - A European Journal
10.1002/chem.201604111
COMMUNICATION
At the beginning, electronically different aniline derivatives 1a-1d
were synthesized and employed in the cobalt catalyzed
intramolecular CDC of C-H/N-H bond. Initial reaction of ortho-
alkenylaniline 1a-d in the presence of 2 mol % of Cp*CoI2CO
and 5 mol % of NaOAc in toluene under O2 atmosphere at
100 °C revealed that moderately electron rich benzylated aniline
1b is the best substrate for the present reaction, where the
expected product 2b was isolated in 8% yield (Table 1, entries
1-4).
10 and 11). Finally, entry 9 was chosen as optimized conditions
for cobalt catalyzed intramolecular CDC.
Having successfully optimized the conditions for the
intramolecular C-H/N-H coupling, the scope and limitation of the
reaction was investigated (Schemes
2 and 3). Various
substituted ortho-alkenylanilines were examined under the
optimized conditions to afford corresponding indoles 2 in good
yield (Scheme 2). Importantly, electron rich methoxy and
benzyloxy substituted as well as electron deficient fluoro, p-
tosyloxy
and
ethoxycarbonyl
substituted
ortho-(α-
Table 1. Cobalt catalyzed synthesis of indoles 2.[a]
phenylethenyl)aniline derivatives underwent smooth reaction to
afford indoles 2h, 2i, 2m, 2n and 2o, respectively. Similarly,
highly reactive functional groups such as acetal, ester and
TBDMS ether were well tolerated and led to the synthesis of
indoles 2j, 2k and 2l in 80%, 76% and 61% yield, respectively.
Ph
Ph
Co(III)-cat. (mol %)
additives, O2
toluene, temp
12 h
1a: R = H
1b: R = Bn
1c: R = C(O)OEt
1d: R = C(O)Ph
N
R
NH
R
2a-d
entr
y
1
Co(III)-cat.
(mol %)
additives (mol %)
temp
(°C)
yield
Ph
Ph
(%)[b]
Cp*CoI2CO (2 mol %)
Cu(OAc)2·H2O (7.5 mol %)
R
R
O2, toluene, 100 °C
1
2
3
4
5
6
7
1a
1b
1c
1d
1b
1b
1b
Cp*CoI2CO (2)
Cp*CoI2CO (2)
Cp*CoI2CO (2)
Cp*CoI2CO (2)
Cp*CoI2CO (2)
[Cp*CoI2]2 (2)
NaOAc (5)
100
100
100
100
100
100
100
0
N
R1
NH
R1
12 h
1
2
NaOAc (5)
8
CH3
Ph
N
Ph
Ph
Ph
H3C
NaOAc (5)
0
NaOAc (5)
0
N
H3C
AcO
N
N
Bn
Bn
2b: 81%
p-MeC6H4
2e: 72%
CuI (7.5), NaOAc (5)
CuI (7.5), NaOAc (5)
CuI (7.5), NaOAc (5)
20
22
8
p-MeC6H4
2g: 72%
2f: 73%
Ph
Ph
Ph
Ph
BnO
O
O
[Cp*Co(MeCN)3]
(SbF6)2 (2)
N
N
O
N
N
Bn
Bn
Bn
p-MeC6H4
2k: 76%
2j: 80%
2h: 78%
Si
8
1b
Cp*CoI2CO (2)
Cu(OAc)2·H2O
NaOAc (5)
(7.5),
100
80
2i: 70%
Ph
Ph
OEt
Ph
Ph
F
TsO
9
1b
1b
1b
Cp*CoI2CO (2)
Cp*CoI2CO (2)
Cp*CoI2CO (2)
Cu(OAc)2·H2O (7.5)
Cu(OAc)2·H2O (7.5)
Cu(OAc)2·H2O (7.5)
100
90
81
66
71
O
O
N
N
10
11
N
Bn
N
p-MeC6H4
2m: 77%
p-MeC6H4
2n: 72%
2o: 70%
110
p-MeC6H4
2l: 61%
[a] Reaction conditions: ortho-alkenylaniline 1 (50 mg, 0.173 mmol), Co(III)-
cat. (mol %), additive (mol %), O2, toluene (2 mL), temp, 12 h. [b] All are
isolated yields.
Scheme 2. Co(III)-catalyzed cross-dehydrogenative C-N coupling of ortho-(α-
phenylethenyl)anilines 1.
Consequently, the generality of substituents at the nitrogen
and alkene moieties were studied. Changing the substitution at
nitrogen with functionalized benzyl group gave the indoles 2p-2s
in good yield (Scheme 3). Chelating cyano- substituted benzyl
and readily labile cinnamyl- containing ortho-alkenylanilines
underwent smooth reaction under the present conditions to
afford 2t and 2u in 62% and 68% yield. Similarly,
heteroarylmethyl substituted indoles 2v and 2w were also
achieved from corresponding ortho-alkenylaniline derivatives.
Introduction of sterically demanding acyclic and cyclic alkyl
substituents at nitrogen were also well tolerated to furnish the
products 2x-2ac in good to excellent yield. ortho-Alkenylanilines
derived from biologically important N-heterocycles such as
tetrahydroquinoline and dibenzazepine under the cobalt
catalyzed conditions afforded the fused indole 2ad and 2ae in
Next, to improve the yield of 2b, Co(III)-catalyst and the
influence of co-oxidant were examined. Changing the Co(III)
catalyst to [Cp*CoI2]2 and [Cp*Co(MeCN)3](SbF6)2 did not show
any significant improvement (Table 1, entries 6 and 7). Instead,
addition of 7.5 mol % of CuI as a co-oxidant increased the yield
of 2b to 20% (Table 1, entry 5). Keeping the Cp*CoI2CO as the
best catalyst, various co-oxidants were examined (see
Supporting Information). Among them, Cu(OAc)2·H2O gave the
product 2b in 80% yield (Table 1, entry 8). Interestingly, a similar
yield (81%) was observed with Cu(OAc)2·H2O, even in the
absence of NaOAc, which is possibly due to the dual role (base
and ligand) of acetate ion present in Cu(OAc)2·H2O (Table 1,
entry 9). Furthermore, variation of temperature from 100 °C to
90 or 110 °C afforded the product in lower yield (Table 1, entry
This article is protected by copyright. All rights reserved

Chemistry - A European Journal
10.1002/chem.201604111
COMMUNICATION
78% and 84% yield, respectively. The structure of 2ae was
R2
R2
Cp*CoI2CO (2 mol %)
unambiguously confirmed by single crystal X-ray analysis[29]
.
Cu(OAc)2·H2O (7.5 mol %)
O2, toluene, 100 °C
12 h
R
R
Furthermore, indoles having a substituted aryl moiety at the 3-
position (2af and 2ag) were also synthesized from the
corresponding ortho-alkenylanilines in good yield.
O
OH
4
3
Cl
R2
CH3
R2
O
4b: 67%
4a: 68%
Cp*CoI2CO (2 mol %)
Cu(OAc)2·H2O (7.5 mol %)
O2, toluene, 100 °C
12 h
O
O
4c: 63%
R
R
R
OMe
N
R1
NH
R1
S
N
2
1
R = Me; 4d: 71%
R = F; 4e: 78%
R = NMe2; 4f: 67%
O
R
R
4h: 81%
O
Ph
Ph
Ph
4g: 79%
Ph
O
N
N
N
N
Scheme 4. Co(III)-catalyzed cross-dehydrogenative C-O coupling of ortho-
alkenylphenols 3.
H3C
2p: R = H; 72%
2q: R = OMe; 70% 2s: R = OMe; 72%
H3CO
2r: R = H; 70%
NC
2t: 62%
2u: 68%
A preliminary mechanistic investigation was subsequently
performed to shine light on the role of catalyst and mechanism.
Treatment of 1b with equimolar amount of Cp*CoI2CO under a
N2 atmosphere gave the indole 2b in 36% yield. Interestingly,
addition of an equimolar amount of NaOAc improved the yield to
48%, suggesting that both Cp*CoI2CO and acetate is very
essential for the present reaction (Scheme 5a).
Ph
Ph
MeO
Ph
Ph
Ph
N
N
N
N
N
H3C
H3C
CH3
CH3
2y: 74%
2z: 76%
2x: 75%
S
O
2w: 65%
Ph
2v: 70%
MeO
Ph
Ph
a)
Ph
N
Cp*CoI2CO
(100 mol%)
toluene
n = 1; 2aa: 80%
n = 2; 2ab: 76%
n = 3; 2ac: 84%
N
Without NaOAc : 36%
N
Bn
With NaOAc
: 48%
NH
Bn
100 °C, 12 h
1b
2ae: 84%
tBu
2b
Ph
n
F
b)
Standard conditions
Ph
No reaction
MeO
NH
Bn
MeO
1ah
N
c)
O
O
N
R
2ag: 76%
N
R
Standard
conditions
R = p-MeC6H4
2ad: 78%
2af: 78%
HN
2ai: 50%
N
Bn
1ai
Ph
Scheme 3. Co(III)-catalyzed cross-dehydrogenative C-N coupling of ortho-
alkenylanilines 1.
69%
H(D)
H(D)
Bn
Ph
Ph
d)
Standard
conditions
5 h, D2O (2 equiv)
+
H(D)
O
OH
recovered
3a: 43%
OH
After the successful development of cobalt catalyzed
intramolecular C-H/N-H coupling, immediate extension of the
method to intramolecular C-H/O-H coupling of ortho-
alkenylphenols to benzofuran was readily envisioned.
Gratifyingly, reaction of ortho-(α-phenylethenyl)phenol 3a under
the cobalt catalyzed conditions, which was employed for the
synthesis of indoles, furnished the corresponding benzofuran 4a
in 68% yield via the successful intramolecular C-H/O-H coupling
(Scheme 4). Subsequently, various substituted ortho-
alkenylphenols were tested under the optimized conditions to
broaden the scope of the present method. As can be seen in
Scheme 4, all the electronically and sterically different ortho-
alkenylphenols afforded the corresponding benzofurans 4b-4f in
good yield. Most importantly, heteroaryl substituted benzofuran
4g and 4h were also achieved in 79% and 81% yields,
respectively, from the appropriate ortho-alkenylphenols.
50% conversion
4a: 40%
38%
70%
3a
Scheme 5. Co(III)-catalyzed cross-dehydrogenative C-O coupling of ortho-
alkenylphenols 3.
To determine whether the reaction goes through C-H bond
activation pathway or radical pathway, ortho-alkenylaniline 1ah
and 1ai was subjected to the standard conditions. The reaction
of 1ah led to no reaction[9] and all the starting materials were
recovered. Radical clock experiment of 1ai under the standard
conditions did not afford trapped product, only formation of
indole 2ai was observed. These results are not in favor of radical
pathway (Schemes 5b-c). Consequently, a deuterium exchange
experiment was performed with 3a in the presence of 2
equivalents of D2O under the standard conditions. At 50% of
This article is protected by copyright. All rights reserved

Chemistry - A European Journal
10.1002/chem.201604111
COMMUNICATION
[1]
[2]
a) S. A. Girard, T. Knauber, C.-J. Li, in From C-H to C-C Bonds: Cross-
Dehydrogenative-Coupling, The Royal Society of Chemistry, 2015, pp.
1-32; b) I. B. Krylov, V. A. Vil’, A. O. Terent’ev, Beilstein J. Org. Chem.
2015, 11, 92-146; c) M.-L. Louillat, F. W. Patureau, Chem. Soc. Rev.
2014, 43, 901-910; d) C.-J. Li, Acc. Chem. Res. 2009, 42, 335-344.
a) J. Jiao, K. Murakami, K. Itami, ACS Catal. 2016, 6, 610-633; b) P.
Subramanian, G. C. Rudolf, K. P. Kaliappan, Chem. Asian J. 2016, 11,
168-192; c) J. Yuan, C. Liu, A. Lei, Chem. Commun. 2015, 51, 1394-
1409; d) X.-X. Guo, D.-W. Gu, Z. Wu, W. Zhang, Chem. Rev. 2015, 115,
1622-1651; e) E. M. Beccalli, G. Broggini, M. Martinelli, S. Sottocornola,
Chem. Rev. 2007, 107, 5318-5365.
conversion, analysis of both 4a and recovered 3a showed a
significant amount of deuterium incorporation at C2 and alkene
carbon (Scheme 5d). This revealed that the present reaction
involves the initial Co-C bond formation via C-H bond activation
and it is reversible.
[Cp*CoI2CO]
R
2 HOAc + 1/2 O2
Cu(OAc)2
2 CuOAc
2 Cu(OAc)2
[Cp*Co]
[Cp*CoOAc]
H2O
A
[3]
[4]
a) M. Inman, C. J. Moody, Chem. Sci. 2013, 4, 29-41; b) D. F. Taber, P.
K. Tirunahari, Tetrahedron 2011, 67, 7195-7210; c) R. Vicente, Org.
Biomol. Chem. 2011, 9, 6469-6480; d) K. Krüger, A. Tillack, M. Beller,
Adv. Synth. Catal. 2008, 350, 2153-2167; e) G. R. Humphrey, J. T.
Kuethe, Chem. Rev. 2006, 106, 2875-2911; f) G. W. Gribble, J. Chem.
Soc., Perkin Trans. 1 2000, 1045-1075.
XH
1 or 3
D
R
R
O
H
R
X
[Co]
a) P. J. Harrington, L. S. Hegedus, K. F. McDaniel, J. Am. Chem. Soc.
1987, 109, 4335-4338; b) P. J. Harrington, L. S. Hegedus, J. Org.
Chem. 1984, 49, 2657-2662.
X
H
O
2 or 4
B
[Co]
X = NR1 or O
[Co] = Cp*Co
X
H
HOAc
[5]
[6]
M. E. Krolski, A. F. Renaldo, D. E. Rudisill, J. K. Stille, J. Org. Chem.
1988, 53, 1170-1176.
C
D. Tsvelikhovsky, S. L. Buchwald, J. Am. Chem. Soc. 2010, 132,
14048-14051.
Scheme 6. Co(III)-catalyzed cross-dehydrogenative C-O coupling of ortho-
alkenylphenols 3.
[7]
[8]
[9]
T. W. Liwosz, S. R. Chemler, Chem. –Eur. J. 2013, 19, 12771-12777.
T. W. Liwosz, S. R. Chemler, Synlett 2015, 26, 335-339.
S. Maity, N. Zheng, Angew. Chem., Int. Ed. 2012, 51, 9562-9566.
Based on the preliminary mechanistic investigation and
Co(III)-catalyzed functionalization of C-H bonds, plausible
mechanism was postulated for present CDC (Scheme 6). After
the initial formation of catalytically active cobalt species A,
acetate assisted C-H metalation of 1/3 would occur to form the
cobaltacycle C through the formation of complex B. C-N Bond
reductive elimination from C followed by deprotonation would
afford product 2/4 along with reduced cobalt species D.
Oxidation of D with copper acetate/O2 would regenerate the
cobalt species A to continue the catalytic cycle.
[10] a) L. Fra, A. Millán, J. A. Souto, K. Muñiz, Angew. Chem., Int. Ed. 2014,
53, 7349-7353; b) Y. H. Jang, S. W. Youn, Org. Lett. 2014, 16, 3720-
3723; c) S. Ortgies, A. Breder, Org. Lett. 2015, 17, 2748-2751; d) Y.-L.
Li, J. Li, A.-L. Ma, Y.-N. Huang, J. Deng, J. Org. Chem. 2015, 80, 3841-
3851.
[11] a) G. Casiraghi, G. Casnati, G. Puglia, G. Sartori, G. Terenghi,
Synthesis 1977, 122-124; b) M. S. C. Pedras, M. Hossain, Bioorg. Med.
Chem. 2007, 15, 5981-5996; c) S. Agasti, U. Sharma, T. Naveen, D.
Maiti, Chem. Commun. 2015, 51, 5375-5378.
[12] M. J. Moure, R. SanMartin, E. Dominguez, Angew. Chem., Int. Ed.
2012, 51, 3220-3224.
[13] a) L. Ackermann, J. Org. Chem. 2014, 79, 8948-8954; b) K. Gao, N.
Yoshikai, Acc. Chem. Res. 2014, 47, 1208-1219; c) M. Zhang, Y.
Zhang, X. Jie, H. Zhao, G. Li, W. Su, Org. Chem. Front. 2014, 1, 843;
d) M. Moselage, J. Li, L. Ackermann, ACS Catal. 2015, 498-525.
[14] a) T. Yoshino, H. Ikemoto, S. Matsunaga, M. Kanai, Angew. Chem., Int.
Ed. 2013, 52, 2207-2211; b) Y. Suzuki, B. Sun, K. Sakata, T. Yoshino,
S. Matsunaga, M. Kanai, Angew. Chem., Int. Ed. 2015, 54, 9944-9947;
c) B. Sun, T. Yoshino, M. Kanai, S. Matsunaga, Angew. Chem., Int. Ed.
2015, 54, 12968-12972; d) H. Ikemoto, T. Yoshino, K. Sakata, S.
Matsunaga, M. Kanai, J. Am. Chem. Soc. 2014, 136, 5424-5431.
[15] a) Q. Lu, S. Vásquez-Céspedes, T. Gensch, F. Glorius, ACS Catal.
2016, 2352-2356; b) A. Lerchen, S. Vásquez-Céspedes, F. Glorius,
Angew. Chem., Int. Ed. 2016, 55, 3208-3211; c) J. H. Kim, S. Greßies,
F. Glorius, Angew. Chem., Int. Ed. 2016; d) T. Gensch, S. Vásquez-
Céspedes, D.-G. Yu, F. Glorius, Org. Lett. 2015, 17, 3714-3717; e) D.
Zhao, J. H. Kim, L. Stegemann, C. A. Strassert, F. Glorius, Angew.
Chem., Int. Ed. 2015, 54, 4508-4511; f) X. Wang, A. Lerchen, F. Glorius,
Org. Lett. 2016, 18, 2090-2093.
In conclusion, an efficient cobalt(III)-catalyzed intramolecular
cross-dehydrogenative
C-H/N-H
coupling
of
ortho-
alkenylanilines has been developed utilizing O2 as terminal
oxidant along with a catalytic amount of co-oxidant, for the first
time. The developed reaction tolerates various reactive
functional groups and allows for the synthesis of diverse indole
derivatives in good to excellent yield. Successful extension of
the method was demonstrated through the synthesis of
benzofurans from ortho-alkenylphenols, which involves an
efficient intramolecular cross-dehydrogenative C-H/O-H coupling.
Furthermore, preliminary mechanistic investigation revealed the
initial formation of Co-C bond via C-H bond activation.
Acknowledgements
[16] a) H. Wang, M. Moselage, M. González, L. Ackermann, ACS Catal.
2016, 6, 2705-2709; b) H. Wang, J. Koeller, W. Liu, L. Ackermann,
Chem. –Eur. J. 2015, 21, 15525-15528; c) N. Sauermann, M. J.
González, L. Ackermann, Org. Lett. 2015, 17, 5316-5319; d) J. Li, L.
Ackermann, Angew. Chem., Int. Ed. 2015, 54, 8551-8554; e) R. Mei, J.
Loup, L. Ackermann, ACS Catal. 2016, 6, 793-797.
We thank the Department of Science and Technology (Project
No. SR/S1/OC-48/2012) for financial support. J.G. thanks
University Grants Commission (UGC) and A.C.R. thanks Council
of Scientific & Industrial Research (CSIR) for a fellowship.
[17] a) J. R. Hummel, J. A. Ellman, J. Am. Chem. Soc. 2015, 137, 490-498;
b) J. R. Hummel, J. A. Ellman, Org. Lett. 2015, 17, 2400-2403.
Keywords: cobalt • cross-dehydrogenative coupling • indole •
benzofuran • C-H activation
This article is protected by copyright. All rights reserved

Chemistry - A European Journal
10.1002/chem.201604111
COMMUNICATION
[18] a) Y. Liang, Y.-F. Liang, C. Tang, Y. Yuan, N. Jiao, Chem. –Eur. J.
2015, 21, 16395-16399; b) Y. Liang, N. Jiao, Angew. Chem., Int. Ed.
2016, 55, 4035-4039.
D.-H. Tan, C.-Y. Jiang, J.-Q. Wu, Q. Li, H. Wang, Adv. Synth. Catal.
2016, 358, 1705-1710.
[24] B. Sun, T. Yoshino, S. Matsunaga, M. Kanai, Adv. Synth. Catal. 2014,
356, 1491-1495.
[19] a) J. Park, S. Chang, Angew. Chem., Int. Ed. 2015, 54, 14103-14107;
b) A. B. Pawar, S. Chang, Org. Lett. 2015, 17, 660-663; c) P. Patel, S.
Chang, ACS Catal. 2015, 5, 853-858.
[25] a) F. Wang, H. Wang, Q. Wang, S. Yu, X. Li, Org. Lett. 2016, 18, 1306-
1309; b) L. Li, H. Wang, S. Yu, X. Yang, X. Li, Org. Lett. 2016, 18,
3662-3665.
[20] a) S. Prakash, K. Muralirajan, C.-H. Cheng, Angew. Chem., Int. Ed.
2016, 55, 1844-1848; b) P. Gandeepan, P. Rajamalli, C.-H. Cheng,
Angew. Chem., Int. Ed. 2016, 55, 4308-4311.
[26] D.-G. Yu, T. Gensch, F. de Azambuja, S. Vásquez-Céspedes, F.
Glorius, J. Am. Chem. Soc. 2014, 136, 17722-17725.
[21] a) M. Sen, D. Kalsi, B. Sundararaju, Chem. –Eur. J. 2015, 21, 15529-
15533; b) N. Barsu, M. Sen, J. R. Premkumar, B. Sundararaju, Chem.
Commun. 2016, 52, 1338-1341; c) M. Sen, B. Emayavaramban, N.
Barsu, J. R. Premkumar, B. Sundararaju, ACS Catal. 2016, 2792-2796.
[22] a) Z. Z. Zhang, B. Liu, J. W. Xu, S. Y. Yan, B. F. Shi, Org. Lett. 2016,
18, 1776-1779; b) L. Kong, S. Yu, X. Zhou, X. Li, Org. Lett. 2016, 18,
588-591; c) Z.-Z. Zhang, B. Liu, C.-Y. Wang, B.-F. Shi, Org. Lett. 2015,
17, 4094-4097; d) E. Ozkal, B. Cacherat, B. Morandi, ACS Catal. 2015,
6458-6462; e) X.-G. Liu, S.-S. Zhang, C.-Y. Jiang, J.-Q. Wu, Q. Li, H.
Wang, Org. Lett. 2015, 17, 5404-5407.
[27] A. B. Pawar, D. M. Lade, Org. Biomol. Chem. 2016, 14, 3275-3283.
[28] a) M. Chaitanya, D. Yadagiri, P. Anbarasan, Org. Lett. 2013, 15, 4960-
4963; b) M. Chaitanya, P. Anbarasan, J. Org. Chem. 2015, 80, 3695-
3700; c) M. Chaitanya, P. Anbarasan, Org. Lett. 2015, 17, 3766-3769;
d) P. Saravanan, P. Anbarasan, Org. Lett. 2014, 16, 848-851; e) D.
Yadagiri, P. Anbarasan, Org. Lett. 2014, 16, 2510-2513.
[29] CCDC 1439467 contains the supplementary crystallographic data for
the compound 1439462ae. The data can be obtained free of charge
from
The
Cambridge
Crystallographic
Data
Centre
via
http://www.ccdc.cam.ac.uk/data_request/cif.
[23] a) R. Mei, H. Wang, S. Warratz, S. A. Macgregor, L. Ackermann, Chem.
–Eur. J. 2016, 22, 6759-6763; b) S.-S. Zhang, X.-G. Liu, S.-Y. Chen,
This article is protected by copyright. All rights reserved

Chemistry - A European Journal
10.1002/chem.201604111
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
COMMUNICATION
Jayanta Ghorai, Angula Chandra Shekar
Reddy and Pazhamalai Anbarasan*
Page No. – Page No.
Cobalt(III) Catalyzed Intramolecular
Cross-Dehydrogenative C-H/X-H
Coupling: Efficient Synthesis of
Indoles and Benzofurans
Efficient and general cobalt(III)-catalyzed intramolecular cross-dehydrogenative C-
H/N-H coupling of ortho-alkenylanilines have been developed utilizing molecular
oxygen as terminal oxidant for the synthesis of diverse indole derivatives in good to
excellent yield. Successful extension of the method was demonstrated through
intramolecular cross-dehydrogenative C-H/O-H coupling of ortho-alkenylphenols for
the synthesis of benzofuran.
This article is protected by copyright. All rights reserved