Synthesis of Dichlorocyanomethyl-Functionalized Oxindoles by Cascade Reactions Initiated by Copper(I)-Catalytically Generated Dichlorocyanomethyl Radical

Article abstract of DOI:10.1002/adsc.202000600

An efficient and convenient protocol for synthesis of dichlorocyanomethyl-functionalized oxindoles through the cascade reactions of dichlorocyanomethyl radical with N-arylacrylamides is reported. The electrophilic dichlorocyanomethyl radical, which is gen

Full text of DOI:10.1002/adsc.202000600

Title: Synthesis of Dichlorocyanomethyl-Functionalized Oxindoles by
Cascade Reactions Initiated by Copper(I)-Catalytically Generated
Dichlorocyanomethyl Radical
Authors: Fengrui Che, Jiangbin Zhong, Linhan Yu, Chaopeng Ma,
Chunzheng Yu, Maorong Wang, Zhichen Hou, and Yuexia
Zhang
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.202000600
Link to VoR: https://doi.org/10.1002/adsc.202000600

10.1002/adsc.202000600
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: ((will be filled in by the editorial staff))
Synthesis of Dichlorocyanomethyl-Functionalized Oxindoles by
Cascade Reactions Initiated by Copper(I)-Catalytically Generated
Dichlorocyanomethyl Radical
Fengrui Che,a Jiangbin Zhong,‡a Linhan Yu,‡a Chaopeng Ma,a Chunzheng Yu,a Maorong
Wang,b Zhichen Hou,a and Yuexia Zhanga,*
a College of Chemistry and Chemical Engineering, Qingdao University, 308 Ningxia Road, Qingdao 266071, P. R. of
China
E-mail: zhangyx@qdu.edu.cn
b State Key Laboratory of Bio-Fibers and Eco-Textiles, Qingdao University, 308 Ningxia Road, Qingdao 266071, P. R. of
China
‡
J.Z. and L.Y. contributed equally.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http:// ((Please delete if not appropriate))
(AIBN) and other reagents, have also been
established.[8] Very recently, Juliá and Leonori
disclosed that α-aminoalkyl radicals could serve as
halogen-atom transfer agents.[9]
Abstract: An efficient and convenient protocol for
synthesis of dichlorocyanomethyl-functionalized
oxindoles through the cascade reactions of
dichlorocyanomethyl radical with N-arylacrylamides is
reported. The electrophilic dichlorocyanomethyl
radical, which is generated from readily available
trichloroacetonitrile via a copper-catalyzed single-
electron transfer (SET) process, undergoes radical
addition with the electron-deficient C=C bonds of N-
arylacrylamides,
cyclization, to
followed
provide
by
intramolecular
dichlorocyanomethyl-
functionalized oxindoles. No external oxidant is needed
in this transformation.
Keywords: trichloroacetonitrile; oxindoles; single-
electron transfer; N-arylacrylamides; radical
Organic halides are very important and versatile
building blocks in synthetic organic chemistry.[1] For
instance, they are widely used to construct C-C bonds
under transition-metal catalysis, such as in Heck
reaction,[2] Suzuki cross-coupling,[3] Nozaki-Hiyama-
Kishi reaction[4] and Stille cross-coupling.[5] Organic
halides are routinely considered as carbon radical
sources for radical reactions which enable rapid
access to molecules of relevance to pharmaceuticals,
agrochemicals and materials.[6] In general, homolytic
carbon-halogen cleavage via halogen-atom transfer
(XAT) has proven to be highly reliable in generating
carbon radicals from organic halides (Scheme 1A). In
this area, transition metal-catalyzed halogen-atom
transfer radical reactions (Kharasch reactions) have
been well developed.[7] Methods for carbon radicals
formation from organic halides by abstracting
halogen atom using radical initiators, such as
organotin reagents (e.g., nBu3SnH), silicon reagents,
trialkylborane-O2 systems, azobis(isobutyronitrile)
Scheme 1. (A) Generation of carbon radicals from organic
halides via XAT; (B) Reported tandem radical
addition/cyclization reactions of N-arylacrylamides with
diverse radicals; (C) This work: Copper-catalyzed
generation of electrophilic dichlorocyanomethyl radical
from trichloroacetonitrile via single-electron transfer and
its cascade reactions with N-arylacrylamides.
Trichloroacetonitrile (Cl3CCN), a special organic
halide bearing both chloro and cyano functional
groups, has been utilized as radical donor for
difunctionalization of electron-rich olefins in
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000600
Advanced Synthesis & Catalysis
Kharasch
reactions.[10]
The
addition
of
on a 0.4 mmol scale of 1 in 0.27 M concentration in
dichlorocyanomethyl radical derived from Cl3CCN to
DCE at 90 °C for 48 h) on hand, the scope of this
electron-deficient C=C bonds (like N-arylacrylamides) radical cascade reaction was evaluated (Table 2). N-
remains challenging due to the highly electrophilic
nature of dichlorocyanomethyl radical.[10b] N-
Arylacrylamides have been proved to be elegant
radical acceptors, which readily undergo radical
addition and cyclization sequence to afford diverse
functionalized oxindoles, the core of a wide variety of
bioactive natural products and pharmaceutically
Table 1. Optimization of the Reaction Conditionsa
active
molecules.[11]
The
radical
cascade
functionalization/cyclization of N-arylacrylamides
with diverse radicals has recently flourished (Scheme
1B). It has been reported that many kinds of radicals
could smoothly proceed radical addition/cyclization
reactions with N-arylacrylamides. They are
trifluoromethyl radical,[12] polyhalocarbon radicals,[13]
cyanomethyl radical,[14,15] silyl radicals,[16] acetonyl
radicals,[17] acyl radicals,[18] halo radicals,[19] aryl
radicals[20] and various alkyl radicals.[21] To the best
our knowledge, however, the cascade reaction of
dichlorocyanomethyl radical with N-arylacrylamides
Catalyst
(mol%)
Solvent
(mL)
Toluene
(2.0)
Toluene
(2.0)
Toluene
(2.0)
Toluene
(2.0)
Toluene
(2.0)
Toluene
(2.0)
Toluene
(2.0)
Yield
(%)b
Entry
1
Base
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
DBU
CuCl (20)
CuBr (20)
CuI (20)
75
64
51
46
61
40
25
77
53
40
80
84
77
90
77
72
2
3
4
Cu2O (20)
CuCl (20)
CuCl (20)
CuCl (20)
CuCl (20)
CuCl (20)
CuCl (20)
CuCl (20)
CuCl (20)
CuCl (20)
CuCl (20)
CuCl (10)
CuCl (5)
to
construct
dichlorocyanomethyl-substituted
5
oxindoles has never been reported. Here we report a
dichlorocyanomethylarylation of electron-deficient
alkenes with electrophilic dichlorocyanomethyl
radical which is generated from Cl3CCN via a
copper-catalyzed single-electron transfer (SET)[22]
process (Scheme 1C). This approach relies on the
Giese-type radical addition[23] of an electrophilic
radical onto an electron-deficient olefin, as opposed
to previous reports, where the dichlorocyanomethyl
radical added across unactivated double bonds.[10]
We initiated our present study by using N-methyl-
N-phenylmethacrylamide 1a as a model substrate to
search for suitable reaction conditions (Table 1). The
screening of copper catalysts indicated that CuCl was
an effective catalyst for this radical cascade reaction,
6
7
DIPEA
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
K3PO4
Toluene
(2.0)
8
9
PhCl (2.0)
CH3CN
(2.0)
10
11
12c
13c
14c,d
15c,d
DCE (2.0)
DCE (1.5)
DCE (1.0)
DCE (1.5)
DCE (1.5)
DCE (1.5)
providing
the
desired
dichlorocyanomethyl-
substituted oxindole 3a in satisfactory yield (Table 1,
entry 1). The structure of 3a was further confirmed by
single crystal X-ray diffraction analysis.[24] The use of
other catalysts, such as CuBr, CuI and Cu2O, instead
of CuCl led to lower yields (entries 2-4). We next
chose CuCl as an optimal catalyst for further
optimization. A switch of the base Cs2CO3 to K2CO3
resulted in a slightly lower yield (entry 5). Employing
organic bases such as DBU and DIPEA as base failed
to afford better results (entries 6-7). K3PO4 was found
to be a better base than Cs2CO3 (entry 8). Among the
different solvents tested, 1,2-dichloroethane (DCE)
gave the best result (entries 9-11). It was finally
found that product 3a could be obtained in 84% yield
(entry 12) when the reaction was carried out in 1.5
mL DCE at 90 °C. Further decreasing the
concentration led to a drop in product yield (entry 13).
A significant excellent yield (90%) was achieved
(entry 14) when the reaction time was prolonged to
48 h. Furthermore, lower catalyst loadings led to
lower yields (entries 15-16).
16c,d
a
Conditions: 1a (0.4 mmol), trichloroacetonitrile 2 (3.5
equiv), catalyst (5–20 mol%), base (2.0 equiv), solvent
(1.0–2.0 mL) at 110 °C for 24 h. b Isolated yields. cAt 90 °C.
d
Reaction
time
=
48
h.
DBU,
1,8-
diazabicyclo[5.4.0]undec-7-ene; DCE, 1,2-dichloroethane;
DIPEA, N,N-diisopropylethylamine.
phenylmethacrylamides with different N substituents,
such as methyl, ethyl, isopropyl and benzyl, could
react exceptionally well, providing products 3a-d
with good yields. Various N-arylacrylamides bearing
methyl, ethyl, isopropyl, trifluoromethoxyl and
benzyloxyl groups at the para position of the
aromatic ring were also excellent substrates, leading
With the optimized reaction conditions (20 mol%
CuCl, 2.0 equiv of K3PO4 and 3.5 equiv of Cl3CCN
to
products
3e-i
in
75-84%
yields.
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000600
Advanced Synthesis & Catalysis
Dichlorocyanomethyl-functionalized oxindoles 3j-l
bearing different substituents at the ortho position of
aromatic ring, could be prepared in good yields by
arylacrylamides smoothly proceeded through the
tandem radical addition/cyclization reactions to yield
the corresponding oxindoles 3q-r in satisfactory
yields. The formation of a small amount of 3,4-
dihydroquinolin-2-one product 3s2 was observed
when N-methyl-N,2-diphenylacrylamide was used as
a substrate. It might be attributed to the steric factors.
However, N-arylacrylamides without α-substituents
or the C=C bond bearing bulky groups or a sensitive
functionality, were found to be incompatible with this
transformation, leading to messy mixtures. We also
tried other similar radical precursors, such as 1,1,1-
trichloroacetone, methyl trichloroacetate, ethyl
trichloroacetate and 1,1,1-trichlorotrifluoroethane.
Unfortunately, these radical precursors couldn't give
any desired product due to the more negative Ep/2
values than trichloroacetonitrile except 1,1,1-
trichloroacetone (see supporting information table
S2).
Table 2. Substrate Scopea
Scheme 2. Scale-up reaction and transformations of
product.
To further confirm the synthetic practicality and
utility of this novel methodology, gram-scale
synthesis of 3a was performed under our optimal
conditions (Scheme 2a). When 6.0 mmol scale of N-
methyl-N-phenylmethacrylamide 1a was involved,
the desired oxindole 3a was isolated in 81% yield,
which can be further transformed into oxindole 4
under reduction condition (Scheme 2b). Moreover,
alkenes 5a and 5b were obtained under reflux in
EtOH in the presence of NaOH at 80 °C (Scheme 2c).
Control experiments and free radical trapping
experiments (Scheme 3) were also performed to
develop the picture of a mechanism. Reducing the
loading of K3PO4 to one equivalent led to a big drop
in yield. No desired product 3a was formed in the
absence of K3PO4 (Scheme 3A). These results
indicated that a deprotonation step might be involved
in reaction pathway. The formation of 3a was
inhibited by adding free radicals, such as 2,2,6,6-
tetramethylpiperidinooxy (TEMPO) or 4-OMe-
TEMPO, into the reaction system. The trapping
a The reactions were carried out with N-arylacrylamide 1
(0.4 mmol), trichloroacetonitrile 2 (3.5 equiv), CuCl (20
mol%), K3PO4 (2.0 equiv) in DCE (1.5 mL) at 90 °C for 48
b
h. Isolated yields are shown. The regioisomeric ratios
refer to the isolated products. c Combined yields are given.
this transformation. For substrates with substituents at
the meta position of the aromatic ring, the formation
of regioisomers was observed, with moderate
selectivity
(3m-p).
Multisubstituted
N-
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000600
Advanced Synthesis & Catalysis
product of dichlorocyanomethyl radical by 4-OMe-
TEMPO was detected by HRMS (Scheme 3B).
Scheme 4. Proposed mechanism.
Experimental Section
General
Procedure
for
Synthesis
of
Dichlorocyanomethyl-Functionalized Oxindoles
To a 15 mL sealed tube containing a magnetic stir bar were
added CuCl (7.9 mg, 0.08 mmol, 20 mol%), K3PO4 (170
mg, 2.0 equiv), and N-arylacrylamide 1 (0.4 mmol). 1,2-
Dichloroethane (1.5 mL) and trichloroacetonitrile 2 (141
µL, 3.5 equiv) were then added. After stirred for 48 h at
90 °C, the mixture was concentrated under reduced
pressure and purified by silica gel column chromatography
(eluent: petroleum ether/ethyl acetate (v/v) = 2:1 ~ 10:1) to
afford dichlorocyanomethyl-functionalized oxindole 3.
Scheme 3. Mechanistic experiments.
The proposed reaction pathway is illustrated in
Scheme 4. Trichloroacetonitrile 2 (Ep/2 = –1.028 V vs.
Ag/AgCl) undergoes a reductive SET process with
catalyst CuCl (Ep/2 [Cu(I)/Cu(II)] = –0.239 V vs.
Ag/AgCl) followed by cleavage C-Cl bond to furnish
the key carbon-centered dichlorocyanomethyl radical
I. This species reacts with electron-deficient C=C
bond of N-arylacrylamide 1 to provide a new carbon-
centered radical intermediate II, which undergoes
intramolecular cyclization with the aromatic ring to
form cyclohexadienyl radical III. Finally, SET
between radical intermediate III and CuCl2 formed in
the first SET oxidation, followed by deprotonation
with K3PO4, generates the oxindole product 3 along
with the regeneration of CuCl.
Acknowledgements
We are grateful to professor Lingbing Kong at Shandong
University and Dr. Longjiang Huang at Qingdao University of
Science & Technology for assistance with X-ray and HRMS,
respectively. We acknowledge financial support by the National
Natural Science Foundation of China (21801149), Shandong
Province Natural Science Foundation of China (ZR2018BB025)
and Qingdao University.
References
The present results demonstrate a novel and
convenient preparation of dichlorocyanomethyl-
[1] a) F. Alonso, I. P. Beletskaya, M. Yus, Chem. Rev. 2002, 102,
4009-4091; b) M. B. Smith, J. March in March’s Advanced
Organic Chemistry: Reactions, Mechanisms, and Structure,
5th ed.; Wiley-Interscience: New York, 2001.
[2] For selected reviews on Heck reaction, see: a) R. F. Heck, Org.
React. 1982, 27, 345-390; b) S. Braese, A. de Meijere, Metal-
Catalyzed Cross-Coupling Reactions (2nd Edition) 2004, 1,
217-315.
[3] For selected papers on Suzuki cross-coupling, see: a) A.
Suzuki, Pure Appl. Chem. 1991, 63, 419-422; b) J. H.
Kirchhoff, C. Dai, G. C. Fu, Angew. Chem. Int. Ed. 2002, 41,
1945-1947.
[4] For selected papers on Nozaki-Hiyama-Kishi reaction, see: a)
Y. Okude, S. Hirano, T. Hiyama, H. Nozaki, J. Am. Chem.
Soc. 1977, 99, 3179-3181; b) M. Durandetti, J.-Y. Nedelec, J.
Perichon, Org. Lett. 2001, 3, 2073-2076.
functionalized
oxindoles
by
addition
of
dichlorocyanomethyl radical, generated from readily
available trichloroacetonitrile via CuCl-catalyzed
SET process, to the electron-deficient C=C bonds of
N-arylacrylamides, followed by intramolecular
cyclization. The reactions proceeded under mild
conditions. No any external oxidant is needed in this
transformation. The application of this radical for
other useful transformations is ongoing in our
laboratory.
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000600
Advanced Synthesis & Catalysis
[5] For selected reviews on Stille cross-coupling see: a) T.-Y. Luh,
Klussmann, Synlett 2015, 26, 1973-1976; c) X.-F. Xia, S.-L.
Zhu, M. Zeng, Z. Gu, H. Wang, W. Li, Tetrahedron 2015,
71, 6099-6103; d) Y. Zhao, N. Sharma, U. K. Sharma, Z. Li,
G. Song, E. V. Van der Eycken, Chem. Eur. J. 2016, 22,
5878-5882.
Rev. on Heteroa. Chem. 1996, 15, 61-82; b) P. Espinet, A. M.
Echavarren, Angew. Chem. Int. Ed. 2004, 43, 4704-4734.
[6] For recent reviews on radical reactions, see: a) A. Studer,
Chem.-Eur. J. 2001, 7, 1159-1164; b) A. Studer, D. P.
Curran, Angew. Chem. Int. Ed. 2016, 55, 58-102; c) M. Yan,
J. C. Lo, J. T. Edwards, P. S. Baran, J. Am. Chem. Soc. 2016,
138, 12692-12714; d) J. Xuan, A. Studer, Chem. Soc. Rev.
2017, 46, 4329-4346; e) J. Xuan, X.-K. He, W.-J. Xiao,
Chem. Soc. Rev. 2020, 49, 2546-2556.
[7] For review on Kharasch reaction, see: J. M. Munoz-Molina, T.
R. Belderrain, Science of Synthesis, C-1 Building Blocks in
Organic Synthesis 2014, 2, 459-473.
[8] a) W. P. Neumann, Synthesis 1987, 665-683; b) A. Krief, A.-
M. Laval, Chem. Rev. 1999, 99, 745-777; c) P. Renaud, M. P.
Sibi, Radicals in Organic Synthesis, ed. Wiley-VCH,
Weinheim, 1st edn, 2001; d) C. Chatgilialoglu, C. Ferreri, Y.
Landais, V. I. Timokhin, Chem. Rev. 2018, 118, 6516-6572.
[9] T. Constantin, M. Zanini, A. Regni, N. S. Sheikh, F. Julia, D.
Leonori, Science 2020, 367, 1021-1026.
[10] a) L. Forti, F. Ghelfi, E. Libertini, U. M. Pagnoni, E. Soragni,
Tetrahedron 1997, 53, 17761-17768; b) S. Kamijo, S.
Yokosaka, M. Inoue, Tetrahedron 2012, 68, 5290–5296.
[11] For selected reviews, see: a) B. S. Jensen, CNS Drug Rev.
2002, 8, 353-360; b) C. V. Galliford, K. A. Scheidt, Angew.
Chem. Int. Ed. 2007, 46, 8748-8758; c) G. S. Singh, Z. Y.
Desta, Chem. Rev. 2012, 112, 6104-6155.
[12] For selected papers, see: a) X. Mu, T. Wu, H. Wang, Y. Guo,
G. Liu, J. Am. Chem. Soc. 2012, 134, 878-881; b) L. Li, M.
Deng, S.-C. Zheng, Y.-P. Xiong, B. Tan, X.-Y. Liu, Org.
Lett. 2014, 16, 504-507; c) L. Zhang, Z. Li, Z.-Q. Liu, Org.
Lett. 2014, 16, 3688-3691; d) F. Yang, P. Klumphu, Y.-M.
Liang, B. H. Lipshutz, Chem. Commun. 2014, 50, 936-938;
e) L. Shi, X. Yang, Y. Wang, H. Yang, H. Fu, Adv. Synth.
Catal. 2014, 356, 1021-1028; f) J.-Y. Guo, R.-X. Wu, J.-K.
Jin, S.-K. Tian, Org. Lett. 2016, 18, 3850-3853; g) Z. Zhang,
L. Zhang, Y. Cao, F. Li, G. Bai, G. Liu, Y. Yang, F. Mo,
Org. Lett. 2019, 21, 762-766.
[13] For selected papers, see: a) Y. Liu, J.-L. Zhang, R.-J. Song, J.-
H. Li, Org. Chem. Front. 2014, 1, 1289-1294; b) M.-Z. Lu,
T.-P. Loh, Org. Lett. 2014, 16, 4698-4701; c) Y. Tian, Z.-Q.
Liu, RSC Adv. 2014, 4, 64855-64859; d) C.-W. Chan, P.-Y.
Lee, W.-Y. Yu, Tetrahedron Lett. 2015, 56, 2559-2563; e) Y.
An, Y. Li, J. Wu, Org. Chem. Front. 2016, 3, 570-573; f) F.
Chen, Y. Wang, S. Zhao, W. Jiang, C. Huo, Org. Biomol.
Chem. 2017, 15, 7710-7714; g) Z. Ruan, Z. Huang, Z. Xu, G.
Mo, X. Tian, X.-Y. Yu, L. Ackermann, Org. Lett. 2019, 21,
1237-1240.
[18] a) W. Fu, F. Xu, Y. Fu, M. Zhu, J. Yu, C. Xu, D. Zou, J. Org.
Chem. 2013, 78, 12202-12206; b) H. Wang, L.-N. Guo, X.-
H. Duan, Adv. Synth. Catal. 2013, 355, 2222-2226; c) F. Jia,
K. Liu, H. Xi, S. Lu, Z. Li, Tetrahedron Lett. 2013, 54, 6337-
6340; d) L. Zheng, H. Huang, C. Yang, W. Xia, Org. Lett.
2015, 17, 1034-1037; e) M.-Z. Zhang, P.-Y. Ji, Y.-F. Liu, C.-
C. Guo, J. Org. Chem. 2015, 80, 10777-10786; f) X. Fan, T.
Lei, B. Chen, C.-H. Tung, L.-Z. Wu, Org. Lett. 2019, 21,
4153-4158.
[19] a) M.-Z. Zhang, W.-B. Sheng, Q. Jiang, M. Tian, Y. Yin, C.-
C. Guo, J. Org. Chem. 2014, 79, 10829-10836; b) M.-Z.
Zhang, X. Wang, M.-Y. Gong, L. Chen, W.-B. Shi, S.-H. He,
Y. Jiang, T. Chen, Org. Biomol. Chem. 2018, 16, 5197-5202;
c) Y. Su, L. Cao, Y. Shi, Y. Feng, W. Xue, G. Cao, K.-H.
Wang, D. Huang, C. Huo, Y. Hu, Synthesis 2019, 51, 2331-
2338.
[20] a) B. Zhou, W. Hou, Y. Yang, H. Feng, Y. Li, Org. Lett.
2014, 16, 1322-1325; b) L. Shi, Y. Wang, H. Yang, H. Fu,
Org. Biomol. Chem. 2014, 12, 4070-4073; c) S. Tang, D.
Zhou, Y.-C. Wang, Eur. J. Org. Chem. 2014, 3656-3661; d)
Y. Yang, J. Han, X. Wu, S. Mao, J. Yu, L. Wang, Synlett
2014, 25, 1419-1424; e) Z. Ni, S. Wang, X. Huang, J. Wang,
Y. Pan, Tetrahedron Lett. 2015, 56, 2512-2516; f) Y. Yu, P.
Zheng, Y. Wu, X. Ye, Org. Biomol. Chem. 2018, 16, 8917-
8921.
[21] For selected papers, see: a) W.-T. Wei, M.-B. Zhou, J.-H.
Fan, W. Liu, R.-J. Song, Y. Liu, M. Hu, P. Xie, J.-H. Li,
Angew. Chem. Int. Ed. 2013, 52, 3638-3641; b) J. Xie, P. Xu,
H. Li, Q. Xue, H. Jin, Y. Cheng, C. Zhu, Chem. Commun.
2013, 49, 5672-5674; c) Z. Li, Y. Zhang, L. Zhang, Z.-Q.
Liu, Org. Lett. 2014, 16, 382-385; d) Z. Xu, C. Yan, Z.-Q.
Liu, Org. Lett. 2014, 16, 5670-5673; e) P. Biswas, S. Paul, J.
Guin, Angew. Chem. Int. Ed. 2016, 55, 7756-7760; f) Z. Li,
X. Cui, L. Niu, Y. Ren, M. Bian, X. Yang, B. Yang, Q. Yan,
J. Zhao, Adv. Syn. Catal. 2017, 359, 246-249; g) C. Pan, Y.
Fu, Q. Ni, J.-T. Yu, J. Org. Chem. 2017, 82, 5005−5010; h)
A. Ling, L. Zhang, R. X. Tan, Z.-Q. Liu, J. Org. Chem. 2018,
83, 14489-14497.
[22] For our recent work on copper-catalyzed SET reaction see: X.
Yi, S. Lei, W. Liu, F. Che, C. Yu, X. Liu, Z. Wang, X. Zhou,
Y. Zhang, Org. Lett. 2020, 22, 4583-4587.
[23] G. S. C. Srikanth, S. L. Castle, Tetrahedron 2005, 61, 10377-
10441.
[14] a) J. Li, Z. Wang, N. Wu, G. Gao, J. You, Chem. Commun.
2014, 50, 15049-15051; b) J.-L. Zhang, Y. Liu, R.-J. Song,
G.-F. Jiang, J.-H. Li, Synlett 2014, 25, 1031-1035; c) Z. Ni,
X.; Huang, J. Wang, Y. Pan, RSC Adv. 2016, 6, 522-526.
[15] For our recent work on cyanomethylation, see: F. Che, M.
Wang, C. Yu, X. Sun, D. Xie, Z. Wang, Y. Zhang, Org.
Chem. Front. 2020, 7, 868-872.
[24] CCDC 1980948 (3a) 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.
[25] H. G. Roth, N. A. Romero, D. A. Nicewicz, Synlett 2016, 27,
714-723.
[16] L. Zhang, D. Liu, Z.-Q. Liu, Org. Lett. 2015, 17, 2534-2537.
[17] a) H. Wang, L.-N. Guo, X.-H. Duan, Chem. Commun. 2013,
49, 10370-10372; b) E. Boess, S. Karanestora, A.-E.
Bosnidou, B. Schweitzer-Chaput, M. Hasenbeck, M.
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.202000600
Advanced Synthesis & Catalysis
COMMUNICATION
Synthesis of Dichlorocyanomethyl-Functionalized
Oxindoles by Cascade Reactions Initiated by
Copper(I)-Catalytically
Generated
Dichlorocyanomethyl Radical
Adv. Synth. Catal. Year, Volume, Page – Page
Fengrui Che,a Jiangbin Zhong,‡a Linhan Yu,‡a
Chaopeng Ma,a Chunzheng Yu,a Maorong Wang,b
Zhichen Hou,a and Yuexia Zhanga,*
6
This article is protected by copyright. All rights reserved.