Palladium-Catalyzed Regioselective C-2 Arylation of Benzofurans with N′-Acyl Arylhydrazines

Article abstract of DOI:10.1002/ejoc.201800374

A novel ligand-free palladium-catalyzed C-2 arylation of benzofurans has been developed using N′-acyl arylhydrazines as the coupling partners and TEMPO as an oxidant. This protocol features a wide functional-group tolerance and highly regioselective products with good to excellent yields.

Full text of DOI:10.1002/ejoc.201800374

A Journal of
Accepted Article
Title: Palladium-Catalyzed Regioselective C-2 Arylation of Benzofurans
with N'-Acyl Arylhydrazines
Authors: Jun Cao, Zi-Li Chen, Shu-Min Li, Gao-Feng Zhu, Yuan-Yong
Yang, Cong Wang, Wen-Zhang Chen, Jian-Ta Wang, Ji-Quan
Zhang, and Lei Tang
This manuscript has been accepted after peer review and appears as an
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 published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800374
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800374
Supported by

10.1002/ejoc.201800374
European Journal of Organic Chemistry
COMMUNICATION
Palladium-Catalyzed Regioselective C-2 Arylation of Benzofurans
with N'-Acyl Arylhydrazines
[c]
Jun Cao,[a,c],‡ Zi-Li Chen,[b],‡ Shu-Min Li,[c] Gao-Feng Zhu,[c] Yuan-Yong Yang, Cong Wang,[c] Wen-
Zhang Chen,[d] Jian-Ta Wang,[c] Ji-Quan Zhang,[a,c,d]* and Lei Tang[a,d]
*
Abstract: A novel ligand-free palladium-catalyzed C-2 arylation of
benzofurans has been developed using N'-acyl arylhydrazines as
the coupling partners and TEMPO as an oxidant. This protocol
features a wide functional group tolerance and highly regioselective
products with good to excellent yields.
Introduction
Benzofurans are versatile synthetic building blocks and
important structural motifs in both natural products and potential
drug molecules.1 Among these benzofuran scaffolds, 2-aryl
benzofurans have attracted considerable amounts of attention
due to their diverse biological profiles, exhibiting antioxidant,2
antitumor,3 anti-AD (Alzheimer's disease),4 antibacterial,1a
antitubercular5 and hypoglycemic activities (Figure 1).6
Scheme 1. Pd-catalyzed C-2 arylation of benzofurans.
much more attention. Since then, diverse electrophiles have
been demonstrated as efficient aryl coupling partners, including
arenes,10 aryl halides,7f arylboronic acids,11 diaryliodonium
salts,7g benzenesulfonyl chlorides12 and aryldiazonium salts.7a
(Scheme 1). In general, these C-2 arylation reactions are
palladium-catalyzed processes. Other transition-metal catalysts,
such as copper salts,13 rhodium salts14 and manganese salts15
have also proved to be efficient, giving arylated products in
moderate yields. It should be noted that some metal-free
reaction systems have also been successfully developed for this
transformation. For example, Daugulis and co-workers have
performed pioneering work using sterically hindered TMPLi as a
non-nucleophilic base and pentane/THF as the solvent system,
providing the desired products in good yields.16 Due to the low
reactivity of the C-H bond at the C-2 position of benzofuran,
these procedures frequently suffered from variable conversions
and yields, limited substrate scope and required costly ligands to
assist the reaction. Therefore, the development of a novel
practical protocol for the direct C-2 regioselective arylation of
benzofuran, especially using a readily available catalyst under
ligand-free conditions, is still highly desirable.
Due to the stability and high dissociation energy of their C-N
bond, arylhydrazines have recently become a hot topic as
potential aryl donors in cross-coupling reactions. They have
been successfully utilized as arylating agents for the direct
arylation of olefins,17 indoles,18 glycals,19 ketone,20 alcohols,21
naphthoquinones22 and pyridines,23 revealing excellent reactive
efficiencies and broad substrate scope. To the best of our
knowledge, there is no report on the arylation of benzofurans
using arylhydrazines as the aryl source. Our previous work
demonstrated that N'-acyl arylhydrazine is an efficient coupling
partner for the arylation of arylhydrazines24 and olefins.25 As we
continued exploring the reaction profiles of N'-acyl
arylhydrazines, we envisioned that the direct arylation of
Figure 1. Structures of bioactive C-2 aryl benzofurans.
Considering their broad range of applications, the
development of new methods for the readily scalable
preparation of 2-aryl benzofurans has been a continuous area of
research interest during the past few decades.7 The traditional
procedures used for the synthesis of 2-aryl benzofurans mainly
involve a palladium-catalyzed tandem cross-coupling/cyclization
process starting from o-halophenols and alkylenes.8 Although
they offer desireable functional group tolerance and improved
yields for the target compounds, the scope of o-halophenols was
limited and the aryl alkylenes need to be pre-functionalized in
most cases. Therefore, a straightforward arylation to access 2-
aryl benzofuran motifs via C-H activation under transition-metal
catalyzed/mediated conditions is much more efficient,
convenient and readily scalable. In 1990, Ohta and co-workers
reported the first direct arylation of benzofuran via C-H activation
of benzofuran using Pd(PPh3)4 as the catalyst.9 Although low
yielding (≤ 25%), this convenient transformation has attracted
[a] State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou
Medical University, Guiyang, 550014, PR China. E-mail: zjqgmc@163.com (J.-Q.
Zhang); tlei1974@hotmail.com (L. Tang);.
[b] Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, PR China
[c] College of Pharmacy, Guizhou Medical University, Guiyang, 550025, PR China
[d] Guizhou Provincial Engineering Technology Research Center for Chemical Drug
R&D, Guizhou Medical University, Guiyang, 550004, PR China
benzofurans
via
C-H
functionalization using
N'-acyl
arylhydrazines can be performed regioselectively under
transition-metal catalyzed conditions. Herein, we present our
‡ Equal contribution to the paper
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.

10.1002/ejoc.201800374
European Journal of Organic Chemistry
COMMUNICATION
recent findings on the preparation of 2-aryl benzofurans using a
palladium-catalyzed reaction system (Scheme 1).
dipole was more compatible with this catalytic system.
Considering the redox process of palladium catalyzed reactions,
diverse oxidants were then investigated (entries 7-11). It was
found that NMO (2.0 equiv.) could significantly promote the
arylation of benzofuran giving the desired arylated product in 63%
yield (entry 9), while 1,4-benzoquinone and PhI(OAc)2 showed a
remarkable inhibitory effect on the catalytic reaction (entries 7
and 8). To our delight, the reaction could be further improved
using TEMPO (2.0 equiv.) as the oxidant and a desirable yield of
76% was obtained (entry 10). When pure O2 was employed as
the oxidant, a moderate yield of 3a (47%, entry 11) was obtained.
Our previous work demonstrated that an organic acid can
efficiently activate the N'-acyl arylhydrazines used in the
arylation of olefins.25 Therefore, various organic acids, including
TFA, AcOH and TsOH, were also evaluated (entries 12-14).
Unexpectedly, TFA and TsOH showed no obvious influence on
the Pd-catalyzed cross-coupling reaction, while AcOH exhibited
a significant negative effect on the arylation reaction. To assess
the solvent effect, different types of solvents, including inert,
dipolar aprotic and protonic solvents, were screened (entries 15-
19). Unfortunately, all of them showed disappointing results.
Further detailed investigations on the ratio of catalyst and
oxidant indicated that 15 mol% of PdCl2(MeCN)2 and 3.0 equiv
of TEMPO were optimal for this C-2 arylation reaction (entries
20-23). Additionally, the reaction could also work under an argon
atmosphere albeit with a much lower yield (entry 24); a similar
result was presented in our previous work and the reaction may
occur via a different mechanism in the absence of oxygen.24,25
Results and Discussion
During our initial studies, benzofuran (1a) and N'-acetyl
phenylhydrazine (2a) were selected as the substrates in our
model reaction. Various conditions were screened and the
results are summarized in Table 1. The desired arylation product
3a was obtained in only 10% yield in the presence of 10 mol%
PdCl2 in DMSO at 100 ℃ (Table 1, entry 1). To improve the
reaction efficiency, various palladium catalysts were investigated
(entries 2-5), and it was found that PdCl2(MeCN)2 exhibited a
better catalytic capability resulting in a 20% yield of the desired
arylated product (entry 2). Encouragingly, the yield of 3a was
significantly improved when dioxane was used as the reaction
solvent (from 20% to 52%, entry 6), which indicated that solvent
Table 1. Optimization of the reaction conditionsa
Entry
1
[Pd]
Oxidant
none
Solvent
DMSO
DMSO
DMSO
DMSO
DMSO
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
toluene
THF
Yieldb (%)
10
PdCl2
2
PdCl2(MeCN)2
PdCl2[(PPh3)2]
Pd2(dba)3
none
20
3
none
14
Table 2. Substrate scope of N'-acyl arylhydrazines.a,b,c
4
none
trace
trace
52
5
Pd(OAc)2
none
6
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
PdCl2(MeCN)2
none
7
1,4-benzoquinone
PhI(OAc)2
NMO
trace
trace
63
8
3a, 85%
9
2l (PhNHNHTs),
3b, 82%
3c, 86%
3f, 89%
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
TEMPO
O2
76
24%
47
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO
TEMPO (3.0 equiv.)
TEMPO (3.0 equiv.)
none
60.3c
traced
64e
3e, 90%
2m (R2 = CF3), 39%
3d, 91%
43
trace
trace
37
MeCN
3g, 58%
2n (R2 = t-BuO),
35%
MeOH
3h, 84%
3i, 74%
EtOH
45
53f
2o (R2 = CF3), 84%
dioxane
dioxane
dioxane
dioxane
dioxane
75g
85g
86h
11i
3j, 57%
3k, 76%
a 1a (0.30 mmol), 2a (0.45 mmol), oxidant (2 equiv.), [Pd] (10 mol%), DMSO
(2.0 mL, dried over 4Å MS), 100 ℃, 24 h. b Isolated yields. c TFA (2.0 equiv.)
a
Reaction conditions: 1a (0.30 mmol), 2 (0.45 mmol), PdCl2(MeCN)2, (15
mol%), TEMPO (3.0 equiv.), dioxane (2.0 mL), air, 100 ℃, 24 h. b 2a-k, R2: Me
substituted. c Isolated yields.
f
was added. d AcOH (2.0 equiv.) was added. e TsOH (2.0 equiv.) was added.
5 mol% Pd(CN)2Cl2 was added; g 15 mol% Pd(CN)2Cl2 was added; h 20 mol%
Pd(CN)2Cl2 was added; i Proceed under Ar.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800374
European Journal of Organic Chemistry
COMMUNICATION
Under the optimized reaction conditions, a wide range of N'-
acyl arylhydrazines were evaluated to establish the scope of the
Pd-catalyzed C-2 arylation reaction (Table 2). Various N'-acetyl
arylhydrazines with both electron-donating and electron-
withdrawing substituents on the aromatic ring were all good
coupling partners in this transformation, affording the desired
products in good to excellent yields. Generally, various halide
substituents on the aryl ring were well tolerated (3b-d, 3i-j) and
electron-donating groups such as OMe and Me substituents
revealed higher reaction efficiencies than those with electron-
withdrawing substituent (3e, 3h, 3g, 3k). Notably, even with a
reaction partner bearing an electron-withdrawing CF3 group (2f)
on the aryl ring, a 89% yield of the C-2 arylated product 3f was
obtained under the optimal reaction conditions. Functional
groups on the meta position such as 3h and 3i, were also well
tolerated, while a substituent on the ortho position gave only a
moderate yield of coupling product 3j, which was attributed to
the effect of steric hindrance on the catalytic process. To
evaluate the reaction profiles of diverse acyl groups on the N'
position of the arylhydrazines, N'-CF3 substituted substrates 2m
and 2o were selected as coupling partners for 1a, respectively. It
was found that a substrate bearing an electron-donating OMe
group on the aryl ring (2m) gave 3e in only 39% yield, while a
substrate bearing an electron-withdrawing substituent (2o)
exhibited a higher reaction activity than 2a, yielding 3g in 84%
yield. Other acyl substituted partners, such as 2l and 2n,
displayed undesirable results.
more bulky substrate, 5-phenyl benzofuran (2i), was also
compatible with the optimal conditions although requiring a
longer reaction time (3s). A similar steric hindrance effect was
also noticed when ortho-Me substituted benzofuran was
employed as the reaction partner and a moderate yield of
coupling product 3t was obtained. We also evaluated the
compatility of furan and 2,3-dihydrobenzofuran (3u and 3v), but
no corresponding products were isolated from the reaction
systems. To our delight, benzothiophene and thiophene were
also tolerated in this Pd-catalyzed C-2 arylation reaction, giving
3w and 3x in 73% and 36% yield, respectively, and this may be
extremely favourable for the preparation of related structural
motifs containing bioactive molecules.
Moreover, this coupling reaction can also be performed on a
gram scale under the optimized conditions with only a slight drop
in yield (Scheme 2). In addition, we have also carried out two
examples to assess the potential utility of this practical direct Pd-
catalyzed arylation reaction (Scheme 3). Using readily
accessible 6-methoxyl benzofuran (1e) as the starting material,
the potential antibacterial agent 4 was obtained in a 61% yield
via demethylation and the subsequent Pd-catalyzed C-2
arylation reaction (Scheme 3a). Similarly, the potent mTOR
inhibitor 5 can be conveniently prepared using 1d and 2a as
coupling partners followed by demethylation and C-4 alkylation
to give the target compound in 59% yield (Scheme 3b).
The reaction scope was further expanded to diverse
functionalized benzofurans. As shown in Table 3, most of
benzofurans bearing substituents at C-5, C-6 and C-7 positions
showed good functional group tolerance, giving their
corresponding products in good to excellent yield (3l-r). The
Scheme 2. Gram scale synthesis of 3a.
Table 3. Substrate scope of benzofurans.a,b
Scheme 3. Preparation of bioactive candidates.
3a, 85%
3n, 91%
3q, 82%
3l, 85%
3o, 90%
3r, 93%
3m, 81%
3p, 86%
3s, 75%[c]
3v, trace
To further explore the mechanism of this Pd-catalyzed
arylation reaction, we carried out several control experiments
(Scheme 4). Firstly, we took 2-methyl benzofuran (1p) as the
substrate coupled with 2a under the standard conditions and no
desired product 6 was observed in the reaction mixture (Scheme
4b). As a free radical scavenger BHT (2.0 equiv.) was
introduced to the reaction system and no inhibitory effect was
noticed, which indicated the arylation reaction underwent a non-
radical process (Scheme 4c). Besides, arylating agent 2a could
be rapidly converted to diazene intermediate 7 using TEMPO at
room temperature (confirmed by GC-MS, 7 was not stable under
these conditions), which could be further coupled with 1a under
the standard conditions to afford product 3a in 89% yield
(Scheme 4e-f).
3t, 57%
3u, trace
3x, 36%
3w, 73%
a
Reaction conditions: 1 (0.30 mmol), 2a (0.45 mmol), PdCl2(MeCN)2, (15
b
mol%), TEMPO (3.0 equiv.), dioxane (2.0 mL), air, 100 ℃, 24 h. Isolated
yields. c Reacted at 100 ℃ for 36 h.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800374
European Journal of Organic Chemistry
COMMUNICATION
yields. This approach is a valuable strategy to develop new
arylating agents for the quick preparation of C-2-arylbenzofurans.
Experimental Section
General procedure for the Pd-catalyzed C-2 arylation of benzofurans
A mixture of benzofuran 1 (0.30 mmol), N’-acyl arylhydrazine 2 (0.45
mmol), PdCl2(MeCN)2 (0.045 mmol), and TEMPO (0.90 mmol) in dioxane
(2.0 mL) was stirred at 100 ℃ for 24 h. After completion of the reaction
(indicated by TLC), the mixture was quenched with saturated NaCl
solution and extracted with EtOAc, followed by washing with H2O and
saturated NaCl solution, and finally dried over Na2SO4. The crude
product was purified by flash column chromatography to provide the
corresponding product 3.
Acknowledgements
This work was financially supported by the National Natural
Science Fundation of China (No. 81703356, 81660348,
81560559), the National Science Grand Fundation of Guizhou
Province (No. JZ[2015]2001), the Guizhou High-School
Engineering Research Center for Medicinal Chemistry (KY2014-
219), the Social Development of Technical Supporting Fundation
of Guizhou Province (No. [2016]2819, [2017]2839), the National
Science Fundation of Health and Family planning Commission
of Guizhou Province (gzwjkj2016-1-051) and the Science
Funcation of Guiyang ([20161001]016, [2017]30-28)
Scheme 4. Control experiments.
Based on these experiments and the literature,7a,11a,12,24,25 we
proposed a possible mechanism for the Pd-catalyzed arylation
reaction (Figure 2). N'-Acyl aryhydrazine (A) was oxidized by the
Pd(II) species to give diazene intermediate B. The reductive
Pd(0) coordinated with B to form azo-palladium(II) complex C,
which further coordinated with benzofuran (D) to afford
intermediate E. The migration of the aryl group to the α-carbon
atom of benzofuran gave F. Degeneration of the
organopalladium intermediate F afforded the coupling product G
and regenerated the Pd(0) species, which may be reoxidized to
the Pd(II) species in the presence of TEMPO.
Keywords: Arylation • Palladium • Benzofuran • Arylhydrazines
• Regioselective
[1] a) H. Khanam, Shamsuzzaman, Eur. J. Med. Chem. 2015, 97, 483-504; b)
R. Naik, D. S. Harmalkar, X. Xu, K. Jang, K. Lee, Eur. J. Med. Chem.
2015, 90, 379-393; c) A. Radadiya, A. Shah, Eur. J. Med. Chem. 2015, 97,
356-376.
[2] K. Chand, Rajeshwari, A. Hiremathad, M. Singh, M. A. Santos, R. S. Keri,
Pharmacol. Rep. 2017, 69, 281-295.
[3] C. Salome, V. Narbonne, N. Ribeiro, F. Thuaud, M. Serova, A. de
Gramont, S. Faivre, E. Raymond, L. Desaubry, Eur. J. Med. Chem. 2014,
74, 41-49.
[4] Y. Cheng, M. Ono, H. Kimura, S. Kagawa, R. Nishii, H. Saji, Bioorg. Med.
Chem. Lett. 2010, 20, 6141-6144.
[5] A. Aggarwal, M. K. Parai, N. Shetty, D. Wallis, L. Woolhiser, C. Hastings,
N. K. Dutta, S. Galaviz, R. C. Dhakal, R. Shrestha, S. Wakabayashi, C.
Walpole, D. Matthews, D. Floyd, P. Scullion, J. Riley, O. Epemolu, S.
Norval, T. Snavely, G. T. Robertson, E. J. Rubin, T. R. Ioerger, F. A. Sirgel,
R. van der Merwe, P. D. van Helden, P. Keller, E. C. Bottger, P. C.
Karakousis, A. J. Lenaerts, J. C. Sacchettini, Cell 2017, 170, 249-259.e25.
[6] M. Dixit, B. K. Tripathi, A. K. Tamrakar, A. K. Srivastava, B. Kumar, A. Goel,
Bioorg. Med. Chem. 2007, 15, 727-734.
[7] Selected references: a) H. P. L. Gemoets, I. Kalvet, A. V. Nyuchev, N.
Erdmann, V. Hessel, F. Schoenebeck, T. Noel, Chem. Sci. 2017, 8, 1046-
1055; b) A. Bruneau, K. P. J. Gustafson, N. Yuan, C.-W. Tai, I. Persson, X.
Zou, J.-E. Baeckvall, Chem. - Eur. J. 2017, 23, 12886-12891; c) M. J.
Bosiak, ACS Catal. 2016, 6, 2429-2434; d) H. Fang, L. Guo, Y. Zhang, W.
Yao, Z. Huang, Org. Lett. 2016, 18, 5624-5627; e) D. Yang, Y. Zhu, N.
Yang, Q. Jiang, R. Liu, Adv. Synth. Catal. 2016, 358, 1731-1735; f) S.-C.
Yin, Q. Zhou, X.-Y. Zhao, L.-X. Shao, J. Org. Chem. 2015, 80, 8916-8921;
g) D.-T. D. Tang, K. D. Collins, J. B. Ernst, F. Glorius, Angew. Chem. Int.
Ed. 2014, 53, 1809-1813;
Figure 2. Proposed mechanism.
Conclusions
[8] Selected references: a) A. Zanardi, J. A. Mata, E. Peris, Organometallics
2009, 28, 4335-4339; b) S.-H. Wang, P.-H. Li, L. Yu, L. Wang, Org. Lett.
2011, 13, 5968-5971.
[9] A. Ohta, Y. Akita, T. Ohkuwa, M. Chiba, R. Fukunaga, A. Miyafuji, T.
Nakata, N. Tani, Y. Aoyagi, Heterocycles 1990, 31, 1951-1958.
[10] T. A. Dwight, N. R. Rue, D. Charyk, R. Josselyn, B. DeBoef, Org. Lett.
2007, 9, 3137-3139.
[11] a) S.-D. Yang, C.-L. Sun, Z. Fang, B.-J. Li, Y.-Z. Li, Z.-J. Shi, Angew.
Chem. Int. Ed. 2008, 47, 1473-1476; b) R. Cano, J. M. Perez, D. J.
Ramon, G. P. McGlacken, Tetrahedron 2016, 72, 1043-1050.
[12] L. Loukotova, K. Yuan, H. Doucet, ChemCatChem 2014, 6, 1303-1309.
In summary, we have developed a novel Pd-catalyzed
direct C-2 arylation reaction of benzofurans using N'-acyl
arylhydrazines as the aryl donor. The procedure, using TEMPO
as the oxidant, is quite simple and highly regioselective, and can
be applied to a broad scope of substrates in good to excellent
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800374
European Journal of Organic Chemistry
COMMUNICATION
[13] H.-Q. Do, R. M. K. Khan, O. Daugulis, J. Am. Chem. Soc. 2008, 130,
15185-15192.
[14] J. Wencel-Delord, C. Nimphius, H. Wang, F. Glorius, Angew. Chem. Int.
Ed. 2012, 51, 13001-13005.
[15] S. K. Guchhait, M. Kashyap, S. Saraf, Synthesis 2010, 1166-1170.
[16] T. Truong, O. Daugulis, J. Am. Chem. Soc. 2011, 133, 4243-4245.
[17] M.-K. Zhu, J.-F. Zhao, T.-P. Loh, Org. Lett. 2011, 13, 6308-6311.
[18] Y. Chen, S. Guo, K. Li, J. Qu, H. Yuan, Q. Hua, B. Chen, Adv. Synth.
Catal. 2013, 355, 711-715.
[19] Y. Bai, L. M. H. Kim, H. Liao, X.-W. Liu, J. Org. Chem. 2013, 78, 8821-
8825.
[20] Y. Su, X. Sun, G. Wu, N. Jiao, Angew. Chem. Int. Ed. 2013, 52, 9808-
9812.
[21] T. Taniguchi, H. Zaimoku, H. Ishibashi, Chem. - Eur. J. 2011, 17, 4307-
4312, S4307/4301-S4307/4370.
[22] P. Patil, A. Nimonkar, K. G. Akamanchi, J. Org. Chem. 2014, 79, 2331-
2336.
[23] Y. Li, W. Liu, C. Kuang, Chem. Commun. 2014, 50, 7124-7127.
[24] J.-Q. Zhang, G.-B. Huang, J. Weng, G. Lu, A. S. C. Chan, Org. Biomol.
Chem. 2015, 13, 2055-2063.
[25] J.-Q. Zhang, J. Cao, W. Li, S.-M. Li, Y.-K. Li, J.-T. Wang, L. Tang, New J.
Chem. 2017, 41, 437-441.
[26] C. Salomé, N. Ribeiro, T. Chavagnan, F. Thuaud, M. Serova, A. de
Gramont, S. Faivre, E. Raymond, L. Désaubry, Eur. J. Med. Chem. 2014,
81, 181-191.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800374
European Journal of Organic Chemistry
COMMUNICATION
Key Topic
Arylhydrazines, arylation
Table of Contents Graphic:
An efficient and ligand-free palladium-catalyzed arylation
of benzofurans has been developed with N’-acyl
arylhydrazines as the coupling partners. This protocol
features a wide functional group tolerance and highly
regioselective
products.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800374
European Journal of Organic Chemistry
COMMUNICATION
This article is protected by copyright. All rights reserved.