Copper-Catalyzed Aerobic Annulation of Hydrazones: Direct Access to Cinnolines

Article abstract of DOI:10.1002/adsc.201700669

A novel method was developed for the construction of biologically active poly-substituted cinnolines from easily accessible hydrazones in good to excellent yields. A simple copper catalyst could efficiently promote C?N bond formation through selective C?H functionalization and dehydrogenative amination. Furthermore, the inert C?Heteroatom (O/F/N) bonds are susceptible to cleavage in high selectivity in the newly developed aerobic annulation, in preference to the alternative C?H bond, which is left intact. (Figure presented.).

Full text of DOI:10.1002/adsc.201700669

Title: Copper-Catalyzed Aerobic Annulation of Hydrazones: Direct
Access to Cinnolines
Authors: Chunling Lan, Zhuang Tian, Xuchun Liang, Mingchun Gao,
Wenting Liu, Yu An, Wencheng Fu, Guanming Jiao, Junjie
Xiao, and Bin Xu
This manuscript has been accepted after peer review and appears as an
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201700669
Link to VoR: http://dx.doi.org/10.1002/adsc.201700669

10.1002/adsc.201700669
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Copper-Catalyzed Aerobic Annulation of Hydrazones: Direct
Access to Cinnolines
Chunling Lan,†a Zhuang Tian,†a Xuchun Liang,c Mingchun Gao,a Wenting Liu,a Yu
An,a Wencheng Fu,c Guanming Jiao,c Junjie Xiao*,c and Bin Xu*,a,b
a
Department of Chemistry, Innovative Drug Research Center, Qianweichang College, Shanghai University, Shanghai
200444, China.
Fax: (+86)-21-6613-2830; phone: (+86)-21-6613-2830; e-mail: xubin@shu.edu.cn
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
b
Sciences, Shanghai 200032, China
Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai 200444, China.
c
Fax: (+86)-21-6613-8131; phone: (+86)-21-6613-8131; e-mail: junjiexiao@live.cn
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
intramolecular dehydrogenative cyclization of
hydrazones.[6c]
Abstract. A novel method was developed for the
construction of biologically active poly-substituted
cinnolines from easily accessible hydrazones in good to
Hydrazones are important and commonly used
building blocks in organic synthesis. Among them, N-
tosylhydrazones have rapidly become versatile
precursors in transition metal-catalyzed cross-
coupling reactions.[7] N-Phosphorylhydrazones were
also explored as ideal reactants in the synthesis of
isoquinolines,[8a] indazoles[8b] and pyrazoles.[8c] In the
context of our research aiming at efficient
construction of nitrogen-containing heterocycles
through C−H functionalization,[9] we herein describe
a copper-catalyzed intramolecular aerobic cyclization
reaction, whereby a sequential N−P bond cleavage,
C−N bond formation and dehydrogenative
aromatization was involved from easily accessible
aromatic hydrazones (Scheme 1). To the best of our
knowledge, this reaction represents the first example
for the synthesis of cinnolines via a copper-catalyzed
aerobic annulation reaction of N-phosphoryl-
hydrazones. It is noteworthy that the unusual
cleavage of inert C−Heteroatom bonds occurs
selectively in the presence of C−H bond, when the
substrates containing alkoxy, fluoro and dialkyl
amino groups are subjected to the catalytic reaction.
excellent yields.
A simple copper catalyst could
efficiently promote C−N bond formation through
selective C–H functionalization and dehydrogenative
amination. Furthermore, the inert C−heteroatom (O/F/N)
bonds are susceptible to cleavage in high selectivity in
the newly developed aerobic annulation, in preference to
the alternative C–H bond, which is left intact.
Keywords: annulation; cinnolines; copper; hydrazones;
C−H functionalization; nitrogen heterocycles.
Synthetic approach to biological active nitrogen-
containing heterocycles from C−N bond formation
via selective C–H functionalization is of considerable
interest.[1] In the past decades, particular attention has
been paid to inexpensive transition metals such as
copper, iron, and nickel in order to achieve high
practicability in industrial applications.[2] As one of
the most direct strategies for C–N bond formation in
the presence of non-noble metals, copper-catalyzed
aerobic C−H amination has recently been well
documented.[3]
Cinnoline derivatives represent an important class
of nitrogen-containing heterocycles with a wide range
of unique biological and pharmacological activities.
These effects include antibacterial, anticancer,
antifungal, antihypertensive, anti-inflammatory, and
anti-parasitic activity,[4] which have led to the
development of various synthetic methods. The first
synthesis of cinnoline was reported by von Richter in
1883 from o-aminophenylpropiolic acid.[5] Other
improved methods to build this useful scaffold
include rhodium- or copper-catalyzed intermolecular
annulation of either azo compounds[6a] or
dibromides,[6b] and through the copper-catalyzed
Scheme 1. Metal-catalyzed synthesis of cinnolines.
Initially, we started our investigation by exploring
the reaction of 1-(diethoxyphosphoryl)-2-(benzyl-
phenylmethylidene) hydrazine (1a) in the presence of
CuSO4·5H2O in toluene under an air atmosphere at
1
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10.1002/adsc.201700669
Advanced Synthesis & Catalysis
110 oC. Intriguingly, 3-phenylcinnoline (2a) could be
obtained in 16% yield (Table 1, entry 1),[10] while no
products were obtained using CuCl2·2H2O, CuBr2,
Cu(TFA)2 or CuI as the copper source (entries 2−5).
When Cu(OPiv)2, Cu(OAc)2 or Cu(OAc)2·H2O was
used as the catalyst, the yield was increased
dramatically and the cinnoline product could be
isolated in up to 94% yield (entries 6−8). An
extensive screening of solvents (entries 9−13),
temperature (entry 14), copper loading (entry 15) and
atmosphere (entries 16 and 17) revealed that the use
of Cu(OAc)2·H2O (30 mol %) as a catalyst in toluene
at 110 oC under an air atmosphere turned out to be the
best reaction conditions (entry 8). Furthermore,
hydrazone substrates with different substitutions
(=N−NHR) were also investigated. When the
P(O)(OEt)2 group was replaced by P(O)(OMe)2 or
P(O)(Oi-Pr)2, the yield of 2a decreased (entries 18–
19). No desired product or reduced efficiency was
observed for non-phosphate leaving groups (entries
20–24), indicating that the phosphoryl group was
essential for such a transformation. The reason may
be due to the unique steric and electronic properties
of the phosphoryl group as a leaving group.
Table 2. Substrates with various aryl substituents
gave the corresponding cinnolines smoothly (2a–i),
regardless of their different steric and electronic
properties, and the halo atoms could be preserved for
further transformations (2b−e, 2h). The newly
established protocol was not limited to the simple
benzene-containing aromatics, substrates with
naphthyl (2j), furanyl (2k) and thienyl (2l) groups
were all compatible with the reaction and gave the
desired products in good yields. In addition, 3-alkyl
substituted cinnolines could be synthesized smoothly
through this approach (2m and 2n). Notably, this
reaction tended to occur at the less sterically hindered
position. For example, the unsymmetrical ketone-
derived hydrazone 1n, which has two potential
reaction sites, will afford the cinnoline product 2n
exclusively in 84% yield. Tetracyclic fused cinnoline
(2o) could also be achieved from corresponding
dihydronaphthalenone hydrazone 1o through the
sequential cyclization and aromatization steps.
However, the thiophene fused substrate failed to give
the corresponding cinnoline (2p) under the standard
conditions.
Table 2. Substrate scope of hydrazones.[a,b]
With the optimized reaction conditions in hand,
various hydrazones were examined as shown in
Table 1. Optimization of reaction conditions.[a]
time
(h)
24
24
24
24
24
11
11
11
13
14
12
13
10
16
18
10
10
24
24
24
24
24
24
24
Yield[b]
(%)
16
N.R.
N.R.
N.R.
N.R.
87
91
94
76
82
entry
Cu source
solvent
R
1
2
3
4
5
6
7
8
9
CuSO4·5H2O
CuCl2·2H2O
CuBr2
Cu(TFA)2
CuI
Cu(OPiv)2
Cu(OAc)2
Cu(OAc)2·H2O
Cu(OAc)2·H2O
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DMSO
DMF
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
P(O)(OMe)2
P(O)(Oi-Pr)2
H
10 Cu(OAc)2·H2O
11 Cu(OAc)2·H2O
12 Cu(OAc)2·H2O
dioxane
PhOMe
79
83
87
13 Cu(OAc)2·H2O t-AmylOH
14 Cu(OAc)2·H2O
15 Cu(OAc)2·H2O
16 Cu(OAc)2·H2O
17 Cu(OAc)2·H2O
18 Cu(OAc)2·H2O
19 Cu(OAc)2·H2O
20 Cu(OAc)2·H2O
21 Cu(OAc)2·H2O
22 Cu(OAc)2·H2O
23 Cu(OAc)2·H2O
24 Cu(OAc)2·H2O
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
72[c]
82[d]
N.R.[e]
86[f]
77
82
N.R.
N.R.
N.R.
57
Ts
PhC(O)
Ac
Ph
N.R.
[a]
Reaction conditions: 1a (0.3 mmol), copper source (30
mol %) in solvent (1.5 mL), at 110 °C under air. t-
AmylOH = tert-amyl alcohol. N.R. = No Reaction.
[b] Isolated yield.
[c] At 100 oC.
[a]
Reaction conditions: 1 (0.3 mmol), Cu(OAc)2·H2O (0.3
[d] Copper species (0.2 equiv) was used.
[e] Under nitrogen atmosphere.
[f] Under oxygen atmosphere.
equiv), toluene (0.5-1.5 mL), at 110 °C under air.
[b] Isolated yield.
2
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10.1002/adsc.201700669
Advanced Synthesis & Catalysis
Various substituents on the cinnoline skeleton were
lower propensity of the methoxy residue to act as a
leaving group.[11] The fact that the C−O bond
cleavage is prior to C–H activation provides an
efficient pathway for the annulation through C−O
bond activation. When hydrazone 5c bearing both
fluoro and methoxy substitutions was applied to the
reaction, the cyclization product 6a was isolated as
the major product with the present C–O bond intact
(entry 3). Furthermore, the mono-fluoro substituted
substrate 5d could afford 2a in 97% yield with only a
trace amount of fluoro-containing product 6c
observed (entry 4), implying the C–F bond is more
reactive than C−H bond in this reaction.[12] However,
the cinnoline 6c could be easily produced in 73%
yield through de-fluorination/cyclization reaction
from di-fluoro substrate 5e (entry 5). To our delight,
even the cleavage of C−N bond could be realized in
this new catalytic reaction, affording 2a in good yield
(entry 6).[13]
also investigated (Table 3). Substrates bearing either
electron-donating (4a–b, 4h and 4l) or electron-
withdrawing groups (4e–g) underwent annulation
successfully and gave target products in good yields.
The C−N bond formation prefers to occur at the less
sterically hindered positions for meta-substituted
substrates, with the 6-methyl and 6-chloro substituted
cinnolines (4h-A and 4i) obtained as the major
product. However, for substrates with halo atoms (Br,
Cl) in the ortho-position, the reaction afforded the
corresponding products smoothly with different
regioselectivity (4j and 4k), which may be due to the
different dissociation energy of C–Br, C−Cl and C–H
bonds.
Table 3. Hydrazone scope with aryl substitution.[a,b]
Table 4. C−Heteroatom bond activation for cinnolines.[a,b]
[a]
Reaction conditions: 1 (0.3 mmol), Cu(OAc)2·H2O (0.3
[a]
equiv), toluene (0.5-1.5 mL), at 110 °C under air.
Reaction conditions: 5a–f (0.3 mmol), Cu(OAc)2·H2O
(0.3 equiv), toluene (0.5 mL), at 110 °C under air.
[b] Isolated yield.
[b] Isolated yield.
Unexpectedly, for those substrates with alkoxy-
substitutions (5a–b), the cleavage of C–O(alkyl) bond
was observed to afford cinnoline 2a predominately
(Table 4, entries 1 and 2). Generally, the activation
energy for cleaving C–OMe bond is significantly
higher, which is probably due to the reluctance of the
C–OMe bond towards oxidative addition and the
To gain insight into the pathway of this reaction, a
preliminary mechanistic investigation was carried out
as shown in Scheme 2. Under the standard conditions,
the addition of 2,2,6,6-tetramethyl-piperidine-1-oxy
(TEMPO) or 2,6-di-tert-butyl-4-methylphenol (BHT)
decreased the product yields significantly from
3
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10.1002/adsc.201700669
Advanced Synthesis & Catalysis
substrate 1a via C–H bond activation, while no
obvious effects could be observed for other substrates
(5a, 5d and 5f) involving the cleavage of C−O bond,
C−F bond and C−N bond (Eq. 1). These results imply
that the dehydrogenative cyclization from 1a may
experience a single electron transfer (SET) pathway,
while the other routes undergo an ionic process. The
formation of diethyl phosphorofluoridate 7 could be
detected by 19F and 31P NMR spectra,[14] which
illustrates the possible intermediate during the
reaction (Eq. 2). Furthermore, N-tosyl hydrazone 5g
bearing a –NMe2 substitution failed to produce 2a
(Eq. 3), which is in accordance with the previous
result (Table 1, entry 21), and indicates that the
cleavage of N−P bond is crucial regardless of the
reaction pathway.
fluoro-substitution, the concomitant tetraethyl
diphosphate could be captured by fluorine anion to
give compound 7.[17]
Scheme 3. Plausible mechanism for the synthesis of 2a.
In summary, a novel and efficient copper-catalyzed
aerobic annulation involving the dehydrogenative
amination has been developed to afford
pharmacologically interesting cinnolines in good to
excellent yields. The newly established approach
selectively realizes the unusual cleavages of inert
C−Heteroatom(O/F/N) bonds, leaving the present
C−H bond intact. The characteristics of wide
substrate scope, good functionality tolerance and
operational simplicity will make the described
reaction a broad utility in organic synthesis. Further
insights into the biological applications of cinnoline
derivatives are under investigation in our lab.
Scheme 2. Preliminary mechanistic studies.
Although a detailed reaction pathway remains to be
clarified, a plausible mechanism for this reaction was
proposed (Scheme 3). Initially, hydrazone 1a reacted
with Cu(OAc)2 to give intermediate A through a SET
pathway (Path A).[3c,15] Radical B was formed after
the deprotonation, which was then transferred into a
cyclohexadienyl type radical C via intramolecular
attack of the nitrogen cation radical on the phenyl
ring. This was then followed by the formation of
intermediate D with the assistance of Cu(OAc)2.
Cinnoline 2a could be finally achieved through
successive deprotonation, hydrolysis and oxidative
aromatization from intermediate D, together with the
generation of diethyl phosphate, which could be
further dehydrated to give tetraethyl diphosphate.
Meanwhile, the Cu(I) species was oxidized to
Cu(OAc)2 in the presence of HOAc under an air
atmosphere to complete the catalytic circle. When
substrates bearing –OMe, −F or −NMe2 substitution
at the ortho position were subjected to the reaction,
the catalytic process underwent an alternative
pathway (Path B). Complex G was initially produced
through nucleophilic attack of hydrazone 5 by
Cu(OAc)2. The key intermediate E, formed through a
three-membered intermediate H by copper-assisted
nucleophilic substitution,[16] afforded the final
product 2a after undergoing the hydrolysis and
oxidative aromatization steps. For the substrate with
Experimental Section
General procedure for the synthesis of cinnolines from
hydrazones: To a test tube, diethyl (2-(1,2-diphenyl-
ethylidene)hydrazinyl)phosphonate 1a (103.9 mg, 0.3
mmol) and Cu(OAc)2·H2O (18.0 mg, 0.09 mmol) in
toluene (1.5 mL) was added. The mixture was stirred at
o
110 C under an air atmosphere. Upon completion, the
reaction was quenched with H2O (30 mL) and extracted
with EtOAc (310 mL). The combined organic layer
was washed with brine, dried over Na2SO4 and
concentrated in vacuo. The given residue was purified
by column chromatography on silica gel (petroleum
ether/EtOAc = 6/1) to give 2a (58.2 mg, 94%) as a pale
yellow solid.
Author Contributions
† These authors contributed equally.
4
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10.1002/adsc.201700669
Advanced Synthesis & Catalysis
Acknowledgements
1103. For selected examples, see: e) H. Wang, Y. Yu,
X. Hong, B. Xu, Chem. Commun. 2014, 50, 13485; f)
T. Fang, Q. Tan, Z. Ding, B. Liu, B. Xu, Org. Lett.
2014, 16, 2342; g) J. Sun, Q. Tan, W. Yang, B. Liu, B.
Xu, Adv. Synth. Catal. 2014, 356, 388; h) M. Gao, Y.
Li, Y. Gan, B. Xu, Angew. Chem. 2015, 127, 8919;
Angew. Chem., Int. Ed. 2015, 54, 8795; i) H. Mao, M.
Gao, B. Liu, B. Xu, Org. Chem. Front. 2016, 3, 516;
j) Y. Li, M. Gao, B. Liu, B. Xu. Org. Chem. Front.
2017, 4, 445; k) X. Hong, Q. Tan, B. Liu, B. Xu,
Angew. Chem. 2017, 129, 4019; Angew. Chem., Int.
Ed. 2017, 56, 3961.
We thank the National Natural Science Foundation of China (No.
21672136) for financial support. The authors thank Prof. Qitao
Tan and Prof. Bingxin Liu for their helpful discussion and Prof.
Hongmei Deng (Laboratory for Microstructures, SHU) for NMR
spectroscopic measurements.
References
[1] For selected reviews of C−N bond formation, see: a)
D. A. Colby, R. G. Bergman, J. A. Ellman, Chem.
Rev. 2010, 110, 624; b) T. W. Lyons, M. S. Sanford,
Chem. Rev. 2010, 110, 1147; c) A. Corma, A. Leyva-
Perez, M. J. Sabater, Chem. Rev. 2011, 111, 1657; d)
R. I. McDonald, G. Liu, S. S. Stahl, Chem. Rev. 2011,
111, 2981; e) J. D. Weaver, A. A. Recio, J. Grenning,
J. A. Tunge, Chem. Rev. 2011, 111, 1846; f) G. Song,
F. Wang, X. Li, Chem. Soc. Rev. 2012, 41, 3651; g) L.
Huang, M. Arndt, K. Gooßen, H. Heydt, L. J. Gooßen,
Chem. Rev. 2015, 115, 2596.
[2] For selected reviews, see: a) C. Sun, B. Li, Z.-J. Shi,
Chem. Rev. 2011, 111, 1293; b) B. M. Rosen, K. W.
Quasdorf, D. A. Wilson, N. Zhang, A. Resmerita, N.
K. Garg, V. Percec, Chem. Rev. 2011, 111, 1346.
[3] For selected reviews, see: a) G. Evano, N. Blanchard,
M. Toumi, Chem. Rev. 2008, 108, 3054; b) S. E.
Allen, R. R. Walvoord, R. Padilla-Salinas, M. C.
Kozlowski, Chem. Rev. 2013, 113, 6234; c) X. Guo,
D. Gu, Z. Wu, W. Zhang, Chem. Rev. 2015, 115,
1622.
[4] For selected reviews on cinnoline derivatives with
biological activity, see: a) A. L. Ruchelman, S. K.
Singh, A. Ray, X. Wu, J.-M. Yang, N. Zhou, A. Liu,
L. F. Liu, E. J. LaVoiea, Bioorg. Med. Chem. 2004,
12, 795; b) W. Lewgowd, A. Stanczak, Arch. Pharm.
Chem. Life Sci. 2007, 340, 65; c) N. Gautam, O. P.
Chourasia, Indian J. Chem. 2010, 49B, 830; d) H.
Tsuji, Y. Yokoi, Y. Sato, H. Tanaka, E. Nakamura,
Chem. Asian J. 2011, 6, 2005.
[10] CCDC 1043006 (2a) contains the supplementary
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.
[11] For reviews on transition-metal catalyzed C−O bond
cleavage, see: a) D. Yu, B. Li, Z.-J. Shi, Acc. Chem.
Res. 2010, 43, 1486; b) J. Cornella, C. Zarate, R.
Martin, Chem. Soc. Rev. 2014, 43, 8081.
[12] For reviews on transition-metal catalyzed C−F bond
cleavage, see: a) E. Clot, O. Eisenstein, N. Jasim, S.
A. MacGregor, J. E. McGrady, R. N. Perutz, Acc.
Chem. Res. 2011, 44, 333; b) M. Klahn, U. Rosenthal,
Organometallics 2012, 31, 1235.
[13] For reviews on transition-metal catalyzed C−N bond
cleavage, see: a) K. Ouyang, W. Hao, W. Zhang, Z.
Xi, Chem. Rev. 2015, 115, 12045; b) Q. Wang, Y. Su,
L. Li, H. Huang, Chem. Soc. Rev. 2016, 45, 1257.
[14] a) T. Sierakowski, J. J. Kiddle, Tetrahedron Lett.
2005, 46, 2215; b) A. K. Gupta, J. Acharya, D. K.
Dubey, M. P. Kaushik, J. Fluorine Chem. 2008, 129,
226.
[15] a) A. Casitas, X. Ribas, Chem. Sci. 2013, 4, 2301; b)
Y. Bao, Y. Yan, K. Xu, J. Su, Z. Zha, Z. Wang, J.
Org. Chem. 2015, 80, 4736.
[16] B. M. Choudary, C. Sridhar, M. L. Kantam, G. T.
Venkanna, B. Sreedhar, J. Am. Chem. Soc. 2005, 127,
9948.
[17] A. Hood, W. Lange, J. Am. Chem. Soc. 1950, 72,
4956.
[5] V. von Richter, Chem. Ber. 1883, 16, 677.
[6] a) D. Zhao, Q. Wu, X. Huang, F. Song, T. Lv, J. You,
Chem. Eur. J. 2013, 19, 6239; b) C. J. Ball, J.
Gilmore, M. C. Willis, Angew. Chem. 2012, 124,
5816; Angew. Chem., Int. Ed. 2012, 51, 5718; c) G.
Zhang, J. Miao, Y. Zhao, H. Ge, Angew. Chem. 2012,
124, 8443; Angew. Chem., Int. Ed. 2012, 51, 8318.
[7] For selected reviews, see: a) J. Barluenga, C. Valdés,
Angew. Chem., Int. Ed. 2011, 50, 7486; b) Y. Zhang,
J. Wang in Stereoselective Alkene Synthesis, Springer,
Berlin, 2012, pp. 239-269; b) Z. Shao, H. Zhang,
Chem. Soc. Rev. 2012, 41, 560; d) Q. Xiao Y. Zhang,
J. Wang, Acc. Chem. Res. 2013, 46, 236.
[8] a) W. Liu, X. Hong, B. Xu, Synthesis 2013, 45, 2137;
b) Z. Ding, Q. Tan, B. Liu, K. Zhang, B. Xu, Acta
Chim. Sinica. 2015, 73, 1302; c) Z. Ding, Q. Tan, M.
Gao, B. Xu, Org. Biomol. Chem. 2015, 13, 4642.
[9] For selected reviews, see: a) H. Wang, B. Xu, Chin. J.
Org. Chem. 2015, 35, 588; b) M. Gao, B. Xu, Chem.
Rec. 2016, 16, 1701; c) Q. Tan, B. Xu, in Studies in
Natural Products Chemistry, Elsevier, 2016, pp. 299-
340; d) B. Song, B. Xu, Chem. Soc. Rev. 2017, 46,
5
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10.1002/adsc.201700669
Advanced Synthesis & Catalysis
COMMUNICATION
Copper-Catalyzed Aerobic Annulation of
Hydrazones: Direct Access to Cinnolines
Adv. Synth. Catal. 2017, 359, Page – Page
Chunling Lan, Zhuang Tian, Xuchun Liang,
Mingchun Gao, Wenting Liu, Yu An, Wencheng
Fu, Guanming Jiao, Junjie Xiao* and Bin Xu*
6
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