Nickel-Catalyzed Annulation of o-Haloarylamidines with Aryl Acetylenes: Synthesis of Isoquinolone and 1-Aminoisoquinoline Derivatives

Article abstract of DOI:10.1002/adsc.201801635

An efficient method for the synthesis of substituted 1(2H)-isoquinolone derivatives via nickel-catalyzed annulation of substituted 2-halobenzamidines with aryl alkynes in the presence of water is described. Benzo[4,5]imidazo[2,1-a]isoquinolines were formed as the dominated products when dry dimethyl sulfoxide was used as the solvent. Furthermore, when benzyl substituted amidines were used as the substrates, debenzylation reaction occured to provide various 1-aminoisoquinoline products. (Figure presented.).

Full text of DOI:10.1002/adsc.201801635

Title: Nickel-Catalyzed Annulation of o-Haloarylamidines with Aryl
Acetylenes: Synthesis of Isoquinolone and 1-Aminoisoquinoline
Derivatives
Authors: Hao Xie, Qiaoyan Xing, Zhifei Shan, Fuhong Xiao, and
Guojun Deng
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: Adv. Synth. Catal. 10.1002/adsc.201801635
Link to VoR: http://dx.doi.org/10.1002/adsc.201801635

10.1002/adsc.201801635
Advanced Synthesis & Catalysis
UPDATE
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Nickel-Catalyzed Annulation of o-Haloarylamidines with Aryl
Acetylenes: Synthesis of Isoquinolone and 1-Aminoisoquinoline
Derivatives
Hao Xie,a Qiaoyan Xing,a Zhifei Shan,a Fuhong Xiao,a* and Guo-Jun Deng a*
a
Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally
Friendly Chemistry and Application of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan
411105, China. E-mail: gjdeng@xtu.edu.cn; fhxiao@xtu.edu.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))
annulation of benzamides with alkynes with or
Abstract. An efficient method for the synthesis of
substituted 1(2H)-isoquinolone derivatives via nickel- without external oxidant.[14] Subsequently, other
transition metals such as Ru,[15] Pd[16] and Ni were
catalyzed annulation of substituted 2-halobenzamidines
with aryl alkynes in the presence of water is described.
Benzo[4,5]imidazo[2,1-a]isoquinolines were formed as the
dominated products when dry dimethyl sulfoxide was used
as the solvent. Furthermore, when benzyl substituted
amidines were used as the substrates, debenzylation
reaction occured to provide various 1-aminoisoquinoline
products.
also successfully employed for this kind of
transformation.[17] In 2014, Manna and Antonchick
described a new isoquinolone synthesis through the
dehydrogenative condensation of alkynes with
benzamides in the absence of metal catalyst.[18] In the
same year, Zhu and Zheng reported that hypervalent
iodine could be used as the promoter for the similar
condensation reaction.[19] Although the transition-
Keywords: Nickel catalysis; debenzylation; regioselective;
isoquinolones; 1-aminoisoquinolines
metal-catalyzed
annulations
of
substituted
benzamides with alkynes have proved to be the most
powerful and direct methods for the construction of
substituted isoquinolones, however, internal alkynes
(especially symmetrical internal alkynes) were often
used as the reactants to provide the corresponding
3,4-disubstituted isoquinolones as the major products.
As an important class of nitrogen-containing
heterocycles, isoquinolones represent a privileged
structure motif that have been found in many natural
products as well as biologically active molecules.[1]
Moreover, the isoquinolone derivatives are widely
used as key intermediates in various organic
transformations.[2] Accordingly, the development of
efficient methods for the construction of isoquinolone
derivatives has attracted considerable interest. There
are a number of approaches for the synthesis of
isoquinolone derivatives through conventional
reactions such as intramolecular cyclizations of
benzamide derivatives[3] or oxidation from the
corresponding isoquinoline derivatives.[4] They also
can be obtained effectively by the intermolecular
cyclization of 2-halobenzamides with alkynes,[5] β-
ketoesters,[6] ketones,[7] and 1,3-indandiones[8]
promoted by copper or zinc catalysts.
In addition to these classic methods, transition-
metal-catalyzed C-H bond activation and annulation
of benzamide derivatives with alkynes afford
straightforward methods for the facile construction of
substituted isoquinolones.[9] The research groups of
Guimond/Fagnou,[10] Rovis,[11] Miura[12] and Li[13]
independently developed the Cp*Rh-catalyzed
Scheme 1. Nickel-catalyzed annulation of 2-
halobenzamides with alkynes.
Unlike the widely utilized internal alkynes,
terminal alkynes which will leave a free position in
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801635
Advanced Synthesis & Catalysis
C3 or C4 position in isoquinolones are rarely used as
the condensation partners. In 2007, the Pal group
[e] Under Ar.
developed
a
Pd/Cu-catalyzed
intermolecular
annulation of 2-iodobenzoyl azides with terminal
alkynes to synthesize 3-substituted isoquinolones.[20]
In 2014, the same group reported a Pd-free process
using 2-iodobenzamides and terminal alkynes as the
starting materials and copper as the catalyst.[21] Very
recently, Zhai and co-workers disclosed a cobalt-
catalyzed Csp2-H alkenylation/annulation process
assisted by 2-(1-methylhydrazinyl)pyridine directing
group using Mn(OAc)3 as the oxidant.[22] Besides
terminal alkynes, other reactive reagents such as
sulfoxonium ylides (with N-methoxybenzamides),[23]
We initiated our investigation by choosing 2-
chloro-N-phenylbenzimidamide (1a) with
ethynylbenzene (2a) and H2O as model substrates to
obtain the optimized reaction conditions, and the
selected results are summarized in Table 1. No
desired product 2,3-diphenylisoquinolin-1(2H)-one
(3aa) was observed when the reaction was carried out
in the absence of nickel catalyst (entry 1). When the
reaction was performed using NiCl2 as the catalyst at
o
140 C in DMSO for 24 h, the desired annulation
product (3aa) was obtained in 21% yield (entry 2). A
variety of other nickel catalysts including Ni(OAc)2,
Ni(PPh3)2Br2, Ni(dppe)Cl2 and Ni(dppp)Cl2 was
examined (entries 3-6), Among the catalysts screened,
Ni(dppp)Cl2 showed the best efficiency to give the
corresponding product 3aa in 90% yield (entry 6).
Solvent screening showed that DMSO is the best
reaction medium for this kind of reaction (entries 7-
10). In addition, decreasing the reaction temperature
or without H2O both sharply decreased the reaction
yields (entries 11-12). A similar yield was obtained
when the reaction was run under argon (entry 13). A
very limited level of reaction was observed in the
absence of zinc powder (entry 14).
α-bromo
ketones
(with
N-(quinolin-
8yl)benzamides),[24] and even aromatic ketones (with
2-bromobenzonitriles)[25] were also used as
alternative substrates to prepare various 3-substituted
isoquinolones in the presence of Rh, Pd and Cu
catalyst, respectively. Although a few other methods
are also available,[26] 4-unsubstituted or 3,4-
unsubstituted isoquinoline synthesis from readily
available terminal alkynes without the use of precious
transition-metal catalysts under simple reaction
conditions is highly desirable. As our continuing
efforts on the heterocycle formation using low-cost
metal catalyst or under transition-metal-free
conditions,[27] herein we describe a nickel-catalyzed
3-substituted isoquinolone formation from o-
haloarylamidines and alkynes (Scheme 1). When
benzyl substituted amidines were used as the
substrates, debenzylation reaction occured to provide
various 1-aminoisoquinoline products which could be
used as versatile synthons for further transformation.
Table 2. Scope of o-haloarylamidines.[a]
Table 1. Optimization of reaction conditions.[a]
Entry Catalyst
1
Additive Solvent Yield (%)[b]
Zn
Zn
Zn
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
N.D.
21
26
19
82
2
NiCl2
3
Ni(OAc)2
4
5
6
7
8
9
10
11[c]
12[d]
13[e]
Ni(PPh3)2Br2 Zn
Ni(dppe)Cl2 Zn
Ni(dppp)Cl2 Zn
Ni(dppp)Cl2 Zn
Ni(dppp)Cl2 Zn
Ni(dppp)Cl2 Zn
Ni(dppp)Cl2 Zn
Ni(dppp)Cl2 Zn
Ni(dppp)Cl2 Zn
Ni(dppp)Cl2 Zn
Ni(dppp)Cl2
90
78
NMP
86
PhMe
35
PhCl
13
DMSO
DMSO
DMSO
DMSO
57
41
81
trace
14
[a]
Reaction conditions: 1a (0.2 mmol), 2a (0.3 mmol), Zn
[a]
Reaction conditions: 1 (0.2 mmol), 2a (0.3 mmol), Zn
(3.0 equiv), H2O (10 equiv), solvent (1.0 mL), under air
(3.0 equiv), H2O (10 equiv), DMSO (1.0 mL), under air at
at 140 oC for 24 h.
[b] GC Yield.
140 oC for 24 h. Isolated yield.
[c] 130 oC.
[d] In the absence of H2O.
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801635
Advanced Synthesis & Catalysis
yield was achieved when the methyl substituent was
far away from the chloro or amidine group (3ta). In
addition, halogen substituents such as fluoro and CF3
were all compatible (3ua and 3wa). Other N-
substituents of o-haloarylamidines, however, were
found to be less efficient in this kind of
transformation (3xa-3za).
Table 3. Scope of alkynes.[a]
Next, we probed the scope of viable alkynes 2
(Table 3). First, various terminal alkynes were tested
using 2-chloro-N-phenylbenzimidamide 1a as the
reaction partner. Substituted phenylacetylenes with
electron-donating groups and halogen functional
groups at the para position of the benzene ring
worked smoothly to produce the corresponding
isoquinolones 3ab-3ag in good to excellent yields
(67-92%). There seems to be little effect of the
substituent meta-position of the benzene ring on the
reaction yield, such as m-methphenylacetylene gave
similar yields of isoquinolones (3ab vs 3ah, 84% vs
79%). But the reaction yields decreased dramatically
when o-chlorophenylacetylenes were used as the
substrates, probably because of its steric hindrance
(3ae vs 3ai, 92% vs 62%). Pyridine-derived terminal
alkynes could also frequently undergo this
transformation to provide isoquinolones 3aj in 84%
yield. The reaction yield decreased dramatically when
dec-5-yne (2k) was used as the substrate. Upon using
diphenyl acetylene (2l), 3al was obtained in 82%
yield. Fortunately, the unsymmetric alkynes, such as
ethyl 3-phenylpropiolate (2m) and prop-1-yn-1-
ylbenzene (2n) were surveyed with 1a in excellent
yields with high regioselectivities.
[a]
Reaction conditions: 1a (0.2 mmol), 2 (0.3 mmol), Zn
(3.0 equiv), H2O (10 equiv), DMSO (1.0 mL), under air at
140 oC for 24 h. Isolated yield.
With the optimized reaction conditions established,
we next probed the scope and generality of this
reaction by changing the substituents on the N-phenyl
ring (Table 2). In general, substrates 1 bearing
electron-donating groups at the para position could
smoothly react with ethynylbenzene (2a) to give the
corresponding products in good to high yields (3ba-
3ha). In particular, when ethoxy groups were
presented, the corresponding products 3fa were
obtained in 97% yield. Substrates with aromatic
substituents on the phenyl ring such as phenyl and 2-
naphthyl was also able to couple with ethynylbenzene
(2a) to give the corresponding products 3ga and 3ha
in 71% and 80% yields, respectively. Halogen
functional groups such as fluoro, chloro and bromo
were compatible under the standard reaction
conditions (3ia-3ka). In addition, the substituents on
the meta-position of phenyl ring slightly affected the
reaction yields (3la and 3ma). However, the ortho-
halogen substituents sharply decreased the reaction
yield (3na and 3oa), which could probably be
attributed to the formation of adduct 5a via a
intramolecular coupling reaction. It is worth noting
that multi-substituted substrates could also smoothly
react with ethynylbenzene (2a) to give the
corresponding products in moderate to good yields
(3pa-3ra). Furthermore, various amidines derived
from substituted 2-chlorobenzonitriles were also
tested. Unexpectedly, the desired product 3sa was
obtained only in 19% yield when 2-chloro-6-methyl-
N-phenylbenzimidamide (1s) was employed.
Moderate yield was obtained when 2-chloro-3-
methyl-N-phenylbenzimidamide (1v) was used. Good
Scheme 2. Effect of different halogen leaving-groups.
Furthermore, the optimized conditions were
successfully applied to other o-halo amidines
(Scheme 2). Halogens such as F, Cl and Br were all
good leaving groups to provide the same product 3aa,
and bromo is the best leaving group to give the
desired product in 88% yield.
We next investigated the reaction of N-benzyl-2-
chlorobenzimidamide
with
ethynylbenzenes.
Surprisingly, 3-phenylisoquinolin-1-amine (4a-H)
was obtained in 50% yield under non-aqueous
reaction conditions with the extrusion of the benzyl
group. Inspired by this discovery, the generality of
this transformation was examined, and the results are
summarized in Table 4. It was noteworthy that the
fluoro group on the the para-position of N-benzyl
substrate proved to be more amenable than methyl
group (4a-Me vs 4a-F, 54% vs 66%), perhaps due to
the electronic effect. Various terminal aromatic
alkynes bearing methyl, trifluoromethyl and halogen
functional groups on the para position of the benzene
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801635
Advanced Synthesis & Catalysis
ring could be successfully used as the coupling
partners to provide various 1-aminoisoquinolines (4b-
4f). Internal alkyne such as 1,2-diphenylethyne was
also effective substrates although a lower yield was
observed for 4g.
obvious that the fluoro group on the the ortho-
position of N-phenyl substrate proved to be more
agreeable than chloro group (5a-F vs 5a-Cl, 66% vs
45%), perhaps due to the steric hindrance and the
electronic effect. Here, the cost-effective nickel
catalyst proved effective in the annulation of alkynes
2, fully accepting valuable methyl, methoxy, and
halogen functional groups. Internal alkyne such as
1,2-diphenylethyne fell short in providing
comparable results.
Table 4. Reaction of N-benzyl-2-chlorobenzimidamides
with alkynes.[a]
To understand the mechanism of the reaction, we
performed some control experiments under modified
conditions (Scheme 3). No desired product was
observed when 2-chloro-N-phenylbenzamide (1a’)
was treated with ethynylbenzene (2a) under the
standard conditions. Similarly, no desired product
was discovered when 1a’ reacted with 2a in the
presence of aqueous ammonia. Furthermore, adduct
5a was detected when 1o was treated with 2a under
standard conditions. These results indicate that 1a’
may not be the intermediate, which is different from
previous literature reports.[5], [16] The incorporation of
oxygen was further confirmed through labeling
experiments by performing the reaction with 18O-
labeled H2O, where GC−MS analysis showed 18O
atom incorporated into the product (Scheme 3, c).
[a]
Reaction conditions: 1 (0.2 mmol), 2 (0.3 mmol), Zn
(3.0 equiv), molecular sieve (50 mg), DMSO (1.0 mL),
under air at 140 oC for 24 h. Isolated yield.
Table 5. Synthesis of benzoimidazoisoquinoline
derivatives.[a]
Scheme 3. Control experiments.
On the basis of the above experiment and previous
literature reports,5,16 a plausible mechanism is
proposed to account for the present nickel-catalyzed
annulations reaction (Scheme 4). The reaction starts
with the reduction of Ni(II) to Ni(0) by zinc powder.
The
oxidative
addition
of
2-chloro-N-
phenylbenzimidamide 1 to Ni(0) leads to the
formation of a five-membered ring nickelacycle A.
Coordinative insertion of ethynylbenzene 2a into the
Ni-C band to give seven-membered ring nickelacycle
intermediates C from B.[28] The regioselectivity
comes from the steric effect of the terminal
acetylenes whereby the less hindered substituent H is
favored to sit next to the more hindered aromatic ring
rather than the amide side.[29] Reductive elimination
of C affords intermediate D, which undergoes
hydrolysis to give the desired isoquinolinone 3aa,
and the catalytically active Ni(0) catalyst for the next
catalytic cycle. The reaction pathway of 3aa and 4a
are very similar, since a trace amount of N-benzylated
[a]
Reaction conditions: 1 (0.2 mmol), 2 (0.3 mmol), Zn
o
(3.0 equiv), DMSO (1.0 mL), under air at 140 C for 24 h.
Isolated yield.
To our surprise, as we mentioned previously,
benzo[4,5]imidazo[2,1-a]isoquinoline
5a
was
obtained as the major product when 2-chloro-N-(2-
fluorophenyl)benzimidamide 1n and 2-chloro-N-(2-
chlorophenyl)benzimidamide 1o were used as the
substrates in the absence of H2O (Table 5).It was
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801635
Advanced Synthesis & Catalysis
References
isoquinolones was obtained in presence of H2O. This
result indicates that the protonation instead of
[1] a) K. W. Bentley, Nat. Prod. Rep. 2006, 23, 444; b) Z.
Jin, Nat. Prod. Rep. 2013, 30, 849; c) G. R. Pettit, S.
Ducki, S. A. Eastham and N. J. Melody, Nat. Prod.
2009, 72, 1279; d) K. W. Bentley in Isoquinoline
Alkaloids, Hardwood Academy, Amsterdam, 1998, vol.
1.
hydrolysis of intermediate
D
to afford the
intermediate E, which undergoes debenzylation to
give the desired 4a.
[2] For selected examples, see: a) S. Lee, S. Mah, S. Hong,
Org. Lett. 2015, 17, 3864; b) Y. Moon, D. Kwon, S.
Hong, Angew. Chem. Int. Ed. 2012, 51, 11333; c) M. P.
Huestis, J. Org. Chem. 2016, 81, 12545; d) D. Das, R.
Samanta, Adv. Synth. Catal. 2018, 360, 379.
[3] a) T. Yao, R. C. Larock, J. Org. Chem. 2005, 70, 1432;
b) H. Gao, J. Zhang, Adv. Synth. Catal. 2009, 351, 85;
c) E. R. Walker, S. Y. Leung, A. G. M. Barrett,
Tetrahedron Lett. 2005, 46, 6537; d) H. Sashid, A.
Kawamukai, Synthesis 1999, 1999, 1145.
[4] a) J. J. Youte, D. Barbier, A. Al-Mourabit, D. Gnecco,
C. Marazano, J. Org. Chem. 2004, 69, 2737; b) I. M.
Khalil, D. Barker, B. R. Copp, J. Org. Chem. 2016, 81,
282; c) T. Ishi-i, R. Hirashima, N. Tsutsumi, S.
Amemori, S. Matsuki, Y. Teshima, R. Kuwahara, S.
Mataka, J. Org. Chem. 2010, 75, 6858; d) T. Fan-
Chiang, H. Wang, J. Hsieh, Tetrahedron 2016, 72,
Scheme 4. Proposed mechanism.
5640; For
a recent visible-light-mediated clean
oxidation procedure, see: e) Y. H. Jin, L. Y. Ou, H. J.
Yang, H. Fu, J. Am. Chem. Soc. 2017, 139, 14237.
In summary, we have demonstrated an efficient
and convenient nickel-catalyzed annulation of
substituted 2-halobenzamides with alkynes to give
the corresponding isoquinolinone in excellent results.
Meanwhile, we have successfully developed a novel
approach for the synthesis of benzo[4,5]imidazo[2,1-
a]isoquinolines. Further applications of this
methodology in natural product synthesis are in
progress.
[5] C. Liu, K. Parthasarathy, C. Cheng, Org. Lett. 2010,
12, 3518.
[6] F. Wang, H. Liu, H. Fu, Y. Jiang, Y. Zhao, Org. Lett.
2009, 11, 2469.
[7] Y. Shi, X. Zhu, H. Mao, H. Hu, C. Zhu, Y. Cheng,
Chem. -Eur. J. 2013, 19, 11553.
[8] C. Huang, V. Kavala, C. Kuo, A. Konala, T. Yang, C.
J. Yao, J. Org. Chem. 2017, 82, 1961.
Experimental Section
[9] For a selected review, see: G. Y. Song, F. Wang, X. W.
General Procedure for the Synthesis of 3-substituted
isoquinolones
Li, Chem. Soc. Rev. 2012, 41, 3651.
[10] N. Guimond, C. Gouliaras, K. Fagnou, J. Am. Chem.
Soc. 2010, 132, 6908.
A
10 mL reaction vessel was charged with o-
haloarylamidines (0.2 mmol), acetylenes (0.3 mmol), 1,3-
bis(diphenylphosphino)propane]nickel(II) chloride (10
mol%), zinc powder (3.0 equiv.), H2O (10 equiv.) and
DMSO (1.0 mL) under air. The reaction vessel was stirred
[11] T. K. Hyster, T. Rovis, J. Am. Chem. Soc. 2010, 132,
10565.
[12] S. Mochida, N. Umeda, K. Hirano, T. Satoh, M.
o
at 140 C for 24 h. After cooling to room temperature, the
Miura, Chem. Lett. 2010, 2010, 744.
volatiles were removed under reduced pressure. The
residue was purified by column chromatography using
ethyl acetate and petroleum ether as eluent to yield the
desired product 3.
[13] G. Song, D. Chen, C.-L. Pan, R. H. Crabtree, X. Li, J.
Org. Chem. 2010, 75, 7487.
[14] For other Rh-catalyzed isoquinolone synthesis, see: a)
N. Guimond, S. I. Gorelsky, K. Fagnou, J. Am. Chem.
Soc. 2011, 133, 6449; b) X. Xu, Y. Liu, C.-M. Park,
Angew. Chem. Int. Ed. 2012, 51, 9372; c) H. Wang, C.
Grohmann, C. Nimphius, F. Glorius, J. Am. Chem.
Soc. 2012, 134, 19592; d) J. R. Huckins, E. A. Bercot,
O. R. Thiel, T. L. Hwang, M. M. Bio, J. Am. Chem.
Soc. 2013, 135, 14492; e) D. G. Yu, F. de Azambuja,
F. Glorius, Angew. Chem. Int. Ed. 2014, 53, 2754; f)
N. S. Upadhyay, V. H. Thorat, R. Sato, P. Annamalai,
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (21572194, 21502160, and
21871226). The Collaborative Innovation Center of New
Chemical Technologies for Environmental Benignity and
Efficient Resource Utilization, the Hunan Provincial
Innovative Foundation for Postgraduate (CX2017B301).
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801635
Advanced Synthesis & Catalysis
S. Chuang, C. H. Cheng, Green Chem. 2017, 19,
[21] R. G. Chary, G. Dhananjaya, K. V. Prasad, S.
Vaishaly, Y. S. S. Ganesh, B. Dulla, K. S. Kumar, M.
Pal, Chem. Commun. 2014, 50, 6979.
3219; g) N. Quiñones, A. Seoane, R. García-Fandiño,
J. L. Mascareñas, M. Gulías, Chem. Sci. 2013, 4,
2874; h) B. Yu, Y. Chen, M. Hong, P. Guan, S. F.
Gan, H. Chao, Z. J. Zhao, J. Zhao, Chem. Commun.
2015, 51, 14365; i) D. Y. Li, H. J. Chen, P. N. Liu,
Org. Lett. 2014, 16, 6176.
[22] S. X. Zhai, S. X. Qiu, X. M. Chen, J. Wu, H. Zhao, C.
Tao, Y. Li, B. Cheng, H. F. Wang, H. B. Zhai, Chem.
Commun. 2018, 54, 98.
[23] Y. W. Xu, G. F. Zheng, X. F. Yang, X. W. Li, Chem.
Commun. 2018, 54, 670.
[15] For Ru-catalyzed isoquinolone syntheses, see: a) L.
Ackermann, A. V. Lygin, N. Hofmann, Angew. Chem.
Int. Ed. 2011, 50, 6379; b) B. Li, H. Feng, S. Xu, B.
Wang, Chem. -Eur. J. 2011, 17, 12573; c) L.
Ackermann, S. Fenner, Org. Lett. 2011, 13, 6548; d) J.
Ghesquire, N. Gauthie, J. D. Winter, P. Gerbaux, C.
Moucheron, E. Defrancq, A. K. D. Mesmaeker, Chem.
-Eur. J. 2012, 18, 355; e) B. Li, H. Feng, N. Wang, J.
Ma, H. Song, S. Xu, B. Wang, Chem. -Eur. J. 2012,
18, 12873; f) M. Deponti, S. I. Kozhushkov, D. S.
Yufit, L. Ackermann, Org. Biomol. Chem. 2013, 11,
142; g) C. Kornhaaß, C. Kuper, L. Ackermann, Adv.
Synth. Catal. 2014, 356, 1619; h) K. Gollapelli, S.
Kallepu, N. Govindappa, J. Nanubolu, R. Chegondi,
Chem. Sci. 2016, 7, 4748; i) X. G. Li, M. Sun, K. Liu,
P. N. Liu, Adv. Synth. Catal. 2015, 357, 395.
[24] C. X. Xie, Z. Dai, Y. D. Niu, C. Ma, J. Org. Chem.,
2018, 83, 2317.
[25] M. S. Maya, X. Q. Xu, X. J. Feng, Y. Yamamoto, M.
Bao, J. Org. Chem. 2015, 80, 3998.
[26]a) N. J. Webb, S. P. Marsden, S. A. Raw, Org. Lett.
2014, 16, 4718; b) W. K. Luo, X. Shi, W. Zhou, L.
Yang, Org. Lett. 2016, 18, 2036; c) P. C. Too, S.
Chiba, Chem. Commun. 2012, 48, 7634; d) D. Wang,
R. X. Zhang, R. H. Deng, S. Lin, S. M. Guo, Z. H.
Yan, J. Org. Chem. 2016, 81, 11162; e) A.
Dieudonńe-Vatran, M. Azoulay, J. C. Florent, Org.
Biomol. Chem. 2012, 10, 2683; f) M. L. Zhang, H. J.
Zhang, W. Q. Ruan, T. B. Wen, Eur. J. Org. Chem.
2015, 2015, 5914; g) X. Wei, M. Zhao, Z. Du, X. Li,
Org. Lett. 2011, 13, 4636; h) P. P. Kaishap, G. Duarah,
D. Chetia, S. Gogoi, Org. Biomol. Chem. 2017, 15,
3491; i) K. Muralirajan, R. Kuppusamy, S. Prakash, C.
H. Cheng, Adv. Synth. Catal. 2016, 358, 774.
[16] For Ni- & Pd-catalyzed isoquinolone syntheses, see:
a) H. Shiota, Y. Ano, Y. Aihara, Y. Fukumoto, N.
Chatani, J. Am. Chem. Soc. 2011, 133, 14952; b) B.
Ye, N. Cramer, Angew. Chem. Int. Ed. 2014, 53,
7896; c) H. Zhong, D. Yang, S. Wang, J. Huang,
Chem. Commun. 2012, 48, 3236; d) Y. Kajita, S.
Matsubara, T. Kurahashi, J. Am. Chem. Soc. 2008,
130, 6058; e) T. Miura, M. Yamauchi, M. Murakami,
Org. Lett. 2008, 10, 3085; f) A. Obata, Y. Ano, N.
Chatani, Chem. Sci. 2017, 8, 6650; g) Z. Q. He, Y.
Huang, ACS Catal. 2016, 6, 7814; h) W. -Z. Wang, J.
Xie, B. Zhang, Org. Biomol. Chem. 2018, 16, 3983.
[27] a) H. W. Huang, J. H. Cai, X. C. Ji, F. H. Xiao, Y.
Chen, G. J. Deng, Angew. Chem. Int. Ed. 2016, 55,
307; b) H. Xie, J. Cai, Z. Wang, H. Huang, G. J. Deng,
Org. Lett. 2016, 18, 2196; c) B. Li, P. Ni, H. Huang, F.
Xiao, G. J. Deng, Adv. Synth. Catal. 2017, 359, 4300;
d) S. P. Chen, Y. X. Li, P. H. Ni, B. C. Yang, H. W.
Huang, G. J. Deng, J. Org. Chem. 2017, 82, 2935.
[17] For
other
selected
transition-metal-catalyzed
[28] N. Wang, S. C. Zheng, L. L. Zhang, Z. Guo, X. Y.
isoquinolone synthesis, see: a) G. Cera, T. Haven, L.
Ackermann, Chem. Commun. 2017, 53, 6460; b) G.
Sivakumar, A. Vijeta, M. Jeganmohan, Chem. -Eur. J.
2016, 22, 5899; c) M. Sen, R. Mandal, A. Das, D.
Kalsi, B. Sundaraju, Chem. -Eur. J. 2017, 23, 17454.
Liu, ACS Catal. 2016, 6, 3496.
[29] N. Zhang, B. Li, H. Zhong, J. Huang, Org. Biomol.
Chem. 2012, 10, 9429.
[18] a) S. Manna, A. P. Antonchick, Angew. Chem. Int. Ed.
2014, 53, 7324; b) R. W. Jin, F. W. Patureau,
ChemCatChem 2015, 7, 223.
[19] Z. W. Chen, Y. Z. Zhu, J. W. Ou, Y. P. Wang, J. Y.
Zheng, J. Org. Chem. 2014, 79, 10988.
[20] V. R. Batchu, D. K. Barange, D. Kumar, B. R.
Sreekanth, K. Vyas, E. A. Reddy, M. Pal, Chem.
Commun. 2007, 2007, 1966.
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801635
Advanced Synthesis & Catalysis
UPDATE
Nickel-Catalyzed
Annulation
of
o-
Haloarylamidines with Aryl Acetylenes: Synthesis
of
Isoquinolone
and
1-Aminoisoquinoline
Derivatives
Adv. Synth. Catal. Year, Volume, Page – Page
Hao Xie, Qiaoyan Xing, Zhifei Shan, Fuhong
Xiao,* and Guo-Jun Deng *
7
This article is protected by copyright. All rights reserved.