Cobalt-Catalyzed Oxidative C?H/C?H Cross-Coupling between Two Heteroarenes

Article abstract of DOI:10.1002/anie.201604580

The first example of cobalt-catalyzed oxidative C?H/C?H cross-coupling between two heteroarenes is reported, which exhibits a broad substrate scope and a high tolerance level for sensitive functional groups. When the amount of Co(OAc)₂?4 H₂O is reduced from 6.0 to 0.5 mol %, an excellent yield is still obtained at an elevated temperature with a prolonged reaction time. The method can be extended to the reaction between an arene and a heteroarene. It is worth noting that the Ag₂CO₃oxidant is renewable. Preliminary mechanistic studies by radical trapping experiments, hydrogen/deuterium exchange experiments, kinetic isotope effect, electron paramagnetic resonance (EPR), and high resolution mass spectrometry (HRMS) suggest that a single electron transfer (SET) pathway is operative, which is distinctly different from the dual C?H bond activation pathway that the well-described oxidative C?H/C?H cross-coupling reactions between two heteroarenes typically undergo.

Full text of DOI:10.1002/anie.201604580

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International Edition: DOI: 10.1002/anie.201604580
German Edition: DOI: 10.1002/ange.201604580
À
C C Cross-Coupling
À
À
Cobalt-Catalyzed Oxidative C H/C H Cross-Coupling between Two
Heteroarenes
Guangying Tan, Shuang He, Xiaolei Huang, Xingrong Liao, Yangyang Cheng, and
Jingsong You*
Abstract: The first example of cobalt-catalyzed oxidative
Despite this seminal discovery by Murahashi, cobalt-
À
À
À
C H/C H cross-coupling between two heteroarenes is
reported, which exhibits a broad substrate scope and a high
tolerance level for sensitive functional groups. When the
amount of Co(OAc)2·4H2O is reduced from 6.0 to
0.5 mol%, an excellent yield is still obtained at an elevated
temperature with a prolonged reaction time. The method can
be extended to the reaction between an arene and a heteroarene.
It is worth noting that the Ag2CO3 oxidant is renewable.
Preliminary mechanistic studies by radical trapping experi-
ments, hydrogen/deuterium exchange experiments, kinetic
isotope effect, electron paramagnetic resonance (EPR), and
high resolution mass spectrometry (HRMS) suggest that
a single electron transfer (SET) pathway is operative, which
catalyzed C H functionalization only started to attract
attention around 2010.[6,7] Among these transformations, the
À
cobalt-catalyzed C H arylation of (hetero)arenes, with (het-
ero)arylation reagents such as (hetero)aryl halides/pseudo-
À
À
halides or organometallic reagents (C H/C X-type), has
become an area of intense research (Scheme 1a).[8] For
À
is distinctly different from the dual C H bond activation
À
À
pathway that the well-described oxidative C H/C H cross-
coupling reactions between two heteroarenes typically
undergo.
B
i(hetero)aryls are highly important structural motifs
distributed in natural products, pharmaceuticals, biologically
active molecules, and functional materials.[1] From the view-
point of step and atom economy, transition-metal-catalyzed
À
Scheme 1. Evolution of cobalt-catalyzed C H (hetero)arylation of
(hetero)arene. X=Cl, Br, I, MgBr, OR (R=alkyl substituent);
Q=8-quinolinyl.
À
À
oxidative C H/C H cross-coupling reactions between two
(hetero)arenes offer the most straightforward approach to
bi(hetero)aryls, which do not require pre-activated substrates
such as (hetero)aryl halides/surrogates and (hetero)aryl
organometallic reagents.[2] Despite tremendous efforts over
the last decade, such reactions are often performed with
expensive and rare second row transition-metal catalysts such
as palladium, rhodium, and ruthenium complexes.[3] First row
transition metals (iron, cobalt, nickel, and copper) are
typically inexpensive and earth-abundant; the replacement
of second row transition metals as catalysts with first row
transition metals would be revolutionary. Pioneering work in
this field has demonstrated that copper enables the oxidative
À
example, cobalt catalysts enable the C H arylation of
simple arenes with aryl halides by radical pathways.[8a–c] The
À
C H arylation of (hetero)arenes with aryl Grignard reagents,
aryl chlorides, sulfamates, carbamates, and carboxylates have
been established through the cobalt-catalyzed chelation-
assisted strategy.[8d–f] However, the cobalt-catalyzed oxidative
C H/C H cross-coupling between two (hetero)arenes (C H/
C H-type) is challenging and remains unsolved so far, which
is exemplified by recent reports on the cobalt-promoted
dimerization of aminoquinoline benzamides and aminoqui-
noline thiophenecarboxylic acid amides.[9] Herein, we wish to
address a solution for this significant challenge (Scheme 1b).
Over the last decade, N,N-bidentate directing groups have
shown a powerful efficacy in palladium, ruthenium, nickel,
À
À
À
À
À
À
C H/C H cross-coupling reaction between two (hetero)ar-
enes.[4]
À
Cobalt-mediated C H functionalization dates back to
2
3
À
À
1955, in which a cobalt-carbonyl-catalyzed ortho-carbonyla-
copper, and iron-catalyzed C(sp ) H and C(sp ) H bond
tion of azobenzene gave an isoindolinone derivative.[5]
functionalization reactions.[4d,10] Very recently, cobalt catalysis
À
assisted by bidentate directing groups was applied in C H
bond activation.[11] Thus, we envisaged that the N,N-biden-
tate-assisted strategy could enable cobalt-catalyzed oxidative
[*] G. Tan, S. He, X. Huang, X. Liao, Y. Cheng, Prof. Dr. J. You
Key Laboratory of Green Chemistry and Technology of Ministry of
Education, College of Chemistry, Sichuan University
29 Wangjiang Road, Chengdu 610064 (P.R. China)
E-mail: jsyou@scu.edu.cn
À
À
C H/C H cross-coupling between two (hetero)arenes. Our
investigation commenced with the reaction between
N-(quinolin-8-yl)thiophene-2-carboxamide 1a and benz-
oxazole 2a (for optimization details see the Supporting
Information, Tables S1–S6). As shown in Table S1
Supporting information for this article can be found under:
http://dx.doi.org/10.1002/anie.201604580.
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Table 1: The scope of (hetero)aromatic acid derivatives.[a,b]
(Supporting Information), oxidants play a crucial role in the
chemoselectivity of cross-coupling over homocoupling. Silver
salts are beneficial to the cross-coupling reaction. Using
Ag2CO3 as the oxidant, the cross-coupled product 3a was
obtained in a 64% yield along with 11% of 3aa resulting from
the homocoupling of 1a.[12] Replacing silver salts with other
oxidants (for example, Mn(OAc)3·2H2O, K2S2O8, PhI(OAc)2,
NaClO3, Oxone, DTBP, O2) only gave the homocoupled
product 3aa. Solvents also significantly affect the chemo-
selectivity (Supporting Information, Table S2). For example,
dioxane gave 3aa in a 46% yield and 3a was obtained in only
a 7% yield. Other cobalt salts, such as Co(acac)2, CoCl2, and
Cp*Co(CO)I2, are less effective than Co(OAc)2·4H2O
(Supporting Information, Table S3). The addition of
1.0 equiv of pivalic acid (PivOH), which acts as both
a proton donor and a ligand in the catalytic process, improved
the yield to 74% (Supporting Information, Table S4). Finally,
the cross-coupled product 3a was obtained in an 85% yield
with only a 4% yield of homocoupled 3aa under the optimal
catalytic system (Co(OAc)2·4H2O (6 mol%), Ag2CO3
(1.5 equiv) and PivOH (1.0 equiv) in toluene at 1208C for
6 h), and no homocoupling of benzoxazole 2a was observed
(Supporting Information, Table S5, entry 3). When the
amount of Co(OAc)2·4H2O was reduced to 0.5 mol%, an
excellent yield of 90% was obtained at 1408C for 24 h
(Supporting Information, Table S5, entry 11). Interestingly, in
the absence of benzoxazole 1a underwent dimerization to
give homocoupled 3aa in an 84% yield (Supporting Infor-
mation, Table S6, entry 1), which suggests that the rate of the
cross-coupling path is much faster than that of homocoupling
of 1a under our optimized reaction conditions. Moreover, the
other directing groups investigated did not lead to any of the
desired products (see unreactive substrates 5–9, Part III in the
Supporting Information), revealing the significant role of the
8-aminoquinoline-containing secondary amide group.
[a] 1 (0.2 mmol), 2a (0.3 mmol, 1.5 equiv) and Co(OAc)2·4H2O
(6.0 mol%) in toluene (0.5 mL) at 1208C for 6 h. [b] Isolated yields.
[c] Co(OAc)2·4H2O (0.5 mol%) and 2a (3.0 equiv) at 1508C for 24 h.
[d] 1408C for 12 h. [e] Cp*Co(CO)I2 instead of Co(OAc)2·4H2O.
With the optimized conditions in hand, we explored the
scope of heteroaromatic acids. As summarized in Table 1,
a range of representative heteroarenes, such as thiophene,
furan, indole, pyrrole, imidazole, thiazole, and pyridine,
underwent smooth coupling with benzoxazole (2a), deliver-
ing the corresponding biheteroaryls (3a–3m). The substrates
with two potentially reactive sites gave rise to the bi-
heteroarylated products (3m and 3n). The method could be
extended to benzoic acids, affording the aryl–heteroaryl
skeletons (3n–3s). For the substrate 1, the degree of
homocoupling is dependent on the reactivity of the substrate
itself. In the lower yielding examples, only trace amounts of
homocoupled products were observed.
Subsequently, the scope of azoles was examined (Table 2).
Benzoxazoles with both electron-withdrawing and electron-
donating groups engaged in this reaction with excellent yields
(4a–4g). Benzothiazoles and thiazoles were also compatible
with this method (4h–4y). Especially sensitive functional
groups, such as chloro, bromo, formyl, ester, cyano, vinyl,
acetyl, nitro, acetoxyl, and even hydroxyl, were well-tolerated
under the optimized conditions. Using 4,7-bis(4-nonylthiazol-
5-yl)benzo[c][1,2,5]thiadiazole 2z as the coupling partner, the
bis-heteroarylated product was obtained in a 66% yield (4y).
Other azoles, such as imidazoles, purines, caffeine, oxazoles,
and 1,3,4-oxadiazoles, reacted with 1a to give the desired
products in moderate yields (4z-4ae). Furthermore,
2-(p-tolyl)-[1,2,4]triazolo[1,5-a]pyrimidine underwent aryla-
tion at the C7 position to provide 4af in a 78% yield.[12]
À
Notably, for the acidic C H azole partner 2, no homocoupling
was observed.
Consultation of Table 2 reveals that the cross-coupling
À
reactions occur at the relatively acidic C H position of
azoles.[13] Benzoxazole (pKa = 24.8) exhibits an excellent
reactivity. Thiazoles (pKa ꢀ 28) are also compatible with
this method. The less acidic N-methylbenzimidazole (pKa =
32.5) requires an elevated temperature to deliver the desired
À
product. The acidic C H bonds of the aforementioned azoles
possess pKa values ranging from approximately 24 to 32.
However, pKa value does not exclusively determine reactivity
and does not enable prediction of coupling for other
(hetero)arenes. For example, polyfluoroarenes failed to give
any desired product.
Considering the synthetic usefulness of the coupling
method, we further illustrated the scalability of the reaction.
Under the standard conditions, the reaction of 1a (1.02 g)
with 2a was performed and the desired 3a was obtained in an
84% yield, which represents a gram-scale preparation
[Eq. (1)].
2
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Table 2: The scope of azoles.[a,b]
For the sake of reducing cost and waste, we sought to
recycle oxidant Ag2CO3. To our delight, silver residue could
be recycled by simple treatment with HNO3 and Na2CO3 in
sequence [Eq. (3)].
The regenerated Ag2CO3 promoted the coupling reaction,
affording 3a in an 81% yield [Eq. (4)]. It is worth noting that
Ag2CO3 barely lost activity after a fifth recovery round
(Supporting Information, Table S7).
To gain some insight into the reaction mechanism,
hydrogen/deuterium exchange experiments were performed
(Supporting Information, Equations (S7)–(S11)). When
N-(quinolin-8-yl)benzamide 1n reacted with D2O (20 equiv)
in both the presence and absence of benzoxazole 2a under the
standard conditions for 2 h, deuterated [Dn]-1n was not
obtained (Supporting Information, Equations (S7) and
[a] 1a (0.2 mmol) and 2 (0.3 mmol, 1.5 equiv) in toluene (0.5 mL) at
1208C for 6 h. [b] Isolated yields. [c] Co(OAc)2·4H2O (0.5 mol%) and 2a
(3.0 equiv) at 1508C for 24 h. [d] 1a (0.3 mmol) and 2z (0.1 mmol).
[e] 1408C. [f] 1508C.
À
(S11)), suggesting that the cleavage of the C H bond of
N-(quinolin-8-yl)benzamide is an irreversible process. While
2a reacted with D2O only in the presence of Ag2CO3 and
PivOH (Supporting Information, Equation (S10)), the H/D
exchange ratio of 2a was 63%. Under the same conditions,
Co(OAc)2·4H2O gave only 9% of deuterated [D]-2a
(Supporting Information, Equation (S9)). In the presence of
cobalt and silver, the H/D exchange ratio of 2a was 92%
(Supporting Information, Equation (S8)). These results imply
À
that silver salt may serve a key role in the cleavage of the C H
bond of azole[14] and explain the significance of a silver
oxidant with respect to product selectivity. However, at the
present stage we require clearer evidence to certify the
formation of an azole–silver species. Subsequently, kinetic
isotope effects (KIE) for both coupling partners were
investigated. Two parallel competition reactions between 2a
or [D]-2a with 1n did not give a significant kinetic isotope
effect (KIE) value (kH/kD = 1.0; Supporting Information,
Equation (S12)). A primary KIE of 1.0 was observed for 1n
Notably, using only 0.5 mol% of Co(OAc)2·4H2O, the desired
3a product could also be obtained in a 61% yield [Eq. (S3)].
Furthermore, the directing group could be removed from the
coupled product 4h [Eq. (2)].[4d]
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and [D5]-1n with 2a (Supporting Information, Eq. (S13)). The
coordinated CoII species was oxidized into the CoIII inter-
mediate IM4 in the presence of Ag2CO3.[11a,f] In Path b, CoIII
species reacts with 1a to generate IM3 via an intermolecular
SET process.[11f] The coordination of IM3 to CoIII species
generates IM4. However, in the absence of Ag2CO3 neither
catalytic nor stoichiometric amounts of Cp*Co(CO)I2
afforded any cross- and homocoupled products, except for
the recovery of 1a and 2a (Supporting Information, Equa-
tions (S14)–(S16)), implying that Path b is less favorable than
Path a. Subsequently, an irreversible intermolecular SET
process between IM4 and CoIII afforded IM5 with the loss
of a proton.[11f,15a] IM5 reacts with a heteroarene to form the
key heterocoupling intermediate IM6 with the aid of
Ag2CO3,[14] followed by reductive elimination to release the
coupled product. The generated CoI species is re-oxidized
into the CoIII species by Ag+ to complete the catalytic cycle.
In summary, we have developed a unique cobalt-catalyzed
À
low KIE value implies that the C H bond cleavage of arenes
is not involved in the rate-determining step.[8a,b,11f] The above
observations suggest that the reaction mechanism is distinct
À
À
from those of the well-described C H/C H cross-coupling
reactions between two (hetero)arenes, in which significant
isotope effects are generally observed.[3e,f,4b,d,f]
Subsequently, we found that radical scavengers, such as
2,2,6,6-tetramethylpiperidine (TEMPO), 2,6-di-tert-butyl-4-
methylphenol (BHT), and ascorbic acid, significantly inhib-
ited the reaction, suggesting the possibility of a radical
pathway (Supporting Information, Table S8). To further
clarify this hypothesis, a series of EPR experiments were
carried out with the addition of free-radical spin-trapping
agent DMPO (5,5-dimethyl-1-pyrroline N-oxide). To our
delight, EPR signals were observed when DMPO was added
to the reaction system (Supporting Information, Figure S3).
HRMS analysis revealed formation of an adduct of 1a with
DMPO (m/z 366.1276), suggesting that the generated radical
was trapped by DMPO to form a relatively stable radical
species (Supporting Information, Figure S6). A mixture of
CoIII [Cp*Co(CO)I2] and 1a in toluene showed an EPR signal
(Supporting Information, Figure S4), whereas CoII did not
give rise to any significant information, indicating that the
radical might be triggered by CoIII. The CoIII species involved
in the catalytic cycle is generated by oxidation of CoII with
Ag2CO3. Indeed, the product (3a) was obtained in a 90%
yield using Cp*Co(CO)I2 instead of Co(OAc)2·4H2O. More-
over, a mixture of Cp*Co(CO)I2 and 2a in toluene did not
lead to any significant EPR signal (Supporting Information,
Figure S5).
À
À
oxidative C H/C H cross-coupling reaction between two
(hetero)aromatics, which delivers wide array of bi-
a
(hetero)aryls. A broad range of functional groups, especially
for sensitive functional groups such as chloro, bromo, formyl,
ester, cyano, vinyl, acetyl, nitro, acetoxyl, and even hydroxyl,
are tolerated well. A preliminary mechanistic study suggests
a SET pathway. Further investigation to extend the applica-
tion of this method is in progress.
Acknowledgements
This work was supported by grants from the National NSF of
China (Nos. 21432005, 21272160 and 21321061).
Based on the above observations and known cobalt-
À
À
À
catalyzed C H bond functionalizations, two plausible
Keywords: bi(hetero)aryls · cobalt catalysis · oxidative C H/C
H cross-coupling · SET pathway
mechanistic pathways are proposed (Scheme 2).[8a,b,11,15] In
Path a, the coordination of amide 1a to a CoIII species
(generated from the oxidation of Co(OAc)2·4H2O) forms the
intermediate IM1,[11a] followed by an intramolecular SET
process from the thiophene ring to the coordinated CoIII, to
form the cation–radical intermediate IM2.[15c] The resulting
[1] a) A. R. Murphy, J. M. J. Frꢀchet, Chem. Rev. 2007, 107, 1066;
b) I. S. Young, P. D. Thornton, A. Thompson, Nat. Prod. Rep.
2010, 27, 1801; c) C. Wang, H. Dong, W. Hu, Y. Liu, D. Zhu,
Chem. Rev. 2012, 112, 2208.
[2] a) C. Liu, H. Zhang, W. Shi, A. Lei, Chem. Rev. 2011, 111, 1780;
b) S. H. Cho, J. Y. Kim, J. Kwak, S. Chang, Chem. Soc. Rev. 2011,
40, 5068; c) D. Zhao, J. You, C. Hu, Chem. Eur. J. 2011, 17, 5466.
À
À
[3] For selected oxidative C H/C H cross-coupling between two
heteroarenes with Pd, Rh, and Ru, see: a) P. Xi, F. Yang, S. Qin,
D. Zhao, J. Lan, G. Gao, C. Hu, J. You, J. Am. Chem. Soc. 2010,
132, 1822; b) C.-Y. He, S. Fan, X. Zhang, J. Am. Chem. Soc. 2010,
132, 12850; c) Z. Wang, K. Li, D. Zhao, J. Lan, J. You, Angew.
Chem. Int. Ed. 2011, 50, 5365; Angew. Chem. 2011, 123, 5477;
d) N. Kuhl, M. N. Hopkinson, F. Glorius, Angew. Chem. Int. Ed.
2012, 51, 8230; Angew. Chem. 2012, 124, 8354; e) X. Qin, H. Liu,
D. Qin, Q. Wu, J. You, D. Zhao, Q. Guo, X. Huang, J. Lan, Chem.
Sci. 2013, 4, 1964; f) C.-Y. He, Z. Wang, C.-Z. Wu, F.-L. Qing, X.
Zhang, Chem. Sci. 2013, 4, 3508; g) X. Qin, X. Li, Q. Huang, H.
Liu, D. Wu, Q. Guo, J. Lan, R. Wang, J. You, Angew. Chem. Int.
Ed. 2015, 54, 7167; Angew. Chem. 2015, 127, 7273.
[4] a) M. Kitahara, N. Umeda, K. Hirano, T. Satoh, M. Miura, J. Am.
Chem. Soc. 2011, 133, 2160; b) M. Nishino, K. Hirano, T. Satoh,
M. Miura, Angew. Chem. Int. Ed. 2012, 51, 6993; Angew. Chem.
2012, 124, 7099; c) X. Qin, B. Feng, J. Dong, X. Li, Y. Xue, J. Lan,
Scheme 2. Plausible mechanistic pathway.
4
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Angewandte
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Chemie
J. You, J. Org. Chem. 2012, 77, 7677; d) M. Nishino, K. Hirano, T.
Satoh, M. Miura, Angew. Chem. Int. Ed. 2013, 52, 4457; Angew.
Chem. 2013, 125, 4553; e) R. Odani, K. Hirano, T. Satoh, M.
Miura, Angew. Chem. Int. Ed. 2014, 53, 10784; Angew. Chem.
2014, 126, 10960; f) S. Zhao, J. Yuan, Y.-C. Li, B.-F. Shi, Chem.
Commun. 2015, 51, 12823.
[9] a) T. Truong, J. Alvarado, L. D. Tran, O. Daugulis, Org. Lett.
2010, 12, 1200; b) L. Grigorjeva, O. Daugulis, Org. Lett. 2015, 17,
1204.
[10] a) V. G. Zaitsev, D. Shabashov, O. Daugulis, J. Am. Chem. Soc.
2005, 127, 13154; b) Y. Aihara, N. Chatani, J. Am. Chem. Soc.
2014, 136, 898; c) S. Asako, L. Ilies, E. Nakamura, J. Am. Chem.
Soc. 2013, 135, 17755; d) G. Rouquet, N. Chatani, Chem. Sci.
2013, 4, 2201; e) R. Shang, L. Ilies, E. Nakamura, J. Am. Chem.
Soc. 2015, 137, 7660.
[5] S. Murahashi, S. Horite, J. Am. Chem. Soc. 1955, 77, 6403.
[6] a) K. Gao, N. Yoshikai, Acc. Chem. Res. 2014, 47, 1208; b) L.
Ackermann, J. Org. Chem. 2014, 79, 8948; c) N. Yoshikai, Bull.
Chem. Soc. Jpn. 2014, 87, 843; d) D. Tilly, G. Dayaker, P. Bachu,
Catal. Sci. Technol. 2014, 4, 2756.
[7] a) K. Gao, P.-S. Lee, T. Fujita, N. Yoshikai, J. Am. Chem. Soc.
2010, 132, 12249; b) L. Ilies, Q. Chen, X. Zeng, E. Nakamura, J.
Am. Chem. Soc. 2011, 133, 5221; c) T. Yoshino, H. Ikemoto, S.
Matsunaga, M. Kanai, Chem. Eur. J. 2013, 19, 9142; d) T.
Yoshino, H. Ikemoto, S. Matsunaga, M. Kanai, Angew. Chem.
Int. Ed. 2013, 52, 2207; Angew. Chem. 2013, 125, 2263; e) B. Sun,
T. Yoshino, S. Matsunaga, M. Kanai, Adv. Synth. Catal. 2014,
356, 1491; f) D.-G. Yu, T. Gensch, F. de Azambuja, S. Vꢁsquez-
Cꢀspedes, F. Glorius, J. Am. Chem. Soc. 2014, 136, 17722; g) J. Li,
L. Ackermann, Angew. Chem. Int. Ed. 2015, 54, 8551; Angew.
Chem. 2015, 127, 8671; h) J. R. Hummel, J. A. Ellman, J. Am.
Chem. Soc. 2015, 137, 490.
[8] a) W. Liu, H. Cao, J. Xin, L. Jin, A. Lei, Chem. Eur. J. 2011, 17,
3588; b) H. Li, C.-L. Sun, M. Yu, D.-G. Yu, B.-J. Li, Z.-J. Shi,
Chem. Eur. J. 2011, 17, 3593; c) C. T. To, T. L. Chan, B. Z. Li,
Y. Y. Hui, T. Y. Kwok, S. Y. Lam, K. S. Chan, Tetrahedron Lett.
2011, 52, 1023; d) B. Li, Z.-H. Wu, Y.-F. Gu, C.-L. Sun, B.-Q.
Wang, Z.-J. Shi, Angew. Chem. Int. Ed. 2011, 50, 1109; Angew.
Chem. 2011, 123, 1141; e) W. Song, L. Ackermann, Angew.
Chem. Int. Ed. 2012, 51, 8251; Angew. Chem. 2012, 124, 8376;
f) K. Gao, P.-S. Lee, C. Long, N. Yoshikai, Org. Lett. 2012, 14,
4234.
[11] a) L. Grigorjeva, O. Daugulis, Angew. Chem. Int. Ed. 2014, 53,
10209; Angew. Chem. 2014, 126, 10373; b) L. Grigorjeva, O.
Daugulis, Org. Lett. 2014, 16, 4684; c) L. Grigorjeva, O.
Daugulis, Org. Lett. 2014, 16, 4688; d) X. Wu, K. Yang, Y.
Zhao, H. Sun, G. Li, H. Ge, Nat. Commun. 2015, 6, 6462; e) L.-B.
Zhang, X.-Q. Hao, Z.-J. Liu, X.-X. Zheng, S.-K. Zhang, J.-F.
Gong, J.-L. Niu, M.-P. Song, Angew. Chem. Int. Ed. 2015, 54, 272;
Angew. Chem. 2015, 127, 274; f) X.-K. Guo, L.-B. Zhang, D. Wei,
J.-L. Niu, Chem. Sci. 2015, 6, 7059; g) J. Zhang, H. Chen, C. Lin,
Z. Liu, C. Wang, Y. Zhang, J. Am. Chem. Soc. 2015, 137, 12990.
[12] CCDC 1433074 (3a) and 1442502 (4af) contain the supplemen-
tary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
[13] For calculated pKa values in DMSO, see: K. Shen, Y. Fu, J.-N. Li,
L. Liu, Q.-X. Guo, Tetrahedron 2007, 63, 1568.
[14] W. Han, P. Mayer, A. R. Ofial, Angew. Chem. Int. Ed. 2011, 50,
2178; Angew. Chem. 2011, 123, 2226.
[15] a) J. K. Kochi, R. T. Tang, T. Bernath, J. Am. Chem. Soc. 1973,
95, 7114; b) J. Iqbal, B. Bhatia, N. K. Nayyar, Chem. Rev. 1994,
94, 519; c) X. Chen, X.-S. Hao, C. E. Goodhue, J.-Q. Yu, J. Am.
Chem. Soc. 2006, 128, 6790.
Received: May 11, 2016
Published online: && &&, &&&&
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!

Angewandte
Communications
Chemie
Communications
À
C C Cross-Coupling
G. Tan, S. He, X. Huang, X. Liao, Y. Cheng,
J. You*
&&&& — &&&&
À
À
Cobalt-Catalyzed Oxidative C H/C H
Cross-Coupling between Two
Heteroarenes
A bidentate 8-quinolinyl ligand assists the
cobalt-catalyzed title reaction between
two (hetero)arenes exhibiting a broad
substrate scope and a high tolerance level
for sensitive functional groups. The pre-
liminary mechanistic study suggests that
a single electron transfer pathway is
operative.
6
www.angewandte.org
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
These are not the final page numbers!