Full text of DOI:10.1016/j.tet.2018.01.050

Tetrahedron xxx (2018) 1e9
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Tetrahedron
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Synthesis of 2-(2-oxoindolin-3-ylidene)-2-arylacetonitriles through
transition metal-free C(sp2)eCN bond construction
Demeng Xie, Zheng Li*
College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, Gansu, 730070, PR China
a r t i c l e i n f o
a b s t r a c t
An efficient method for the construction of C(sp2)eCN bonds directly from C(sp2-H) cyanation of 3-
arylideneindolin-2-ones with benzoyl cyanide under transition metal-free condition is described.
Various 2-(2-oxoindolin-3-ylidene)-2-arylacetonitriles were efficiently synthesized using air as an
oxidant under mild conditions. This protocol has excellent functional group tolerance and can be easily
scaled up with good efficiency. This reaction successfully offers an alternative to structurally diverse
alkenyl nitriles.
Article history:
Received 22 December 2017
Received in revised form
23 January 2018
Accepted 29 January 2018
Available online xxx
© 2018 Elsevier Ltd. All rights reserved.
Keywords:
3-Arylideneindolin-2-one
Benzoyl cyanide
Transition metal-free condition
2-(2-oxoindolin-3-ylidene)-2-
arylacetonitrile
Alkenyl nitrile
1. Introduction
internal olefins using benzoyl cyanide as a cyanating agent and air
as an oxidant under transition metal-free condition.
Alkenyl nitriles1 have been widely used as pharmaceuticals
and agrochemicals because of their biological activities,2 such as
the Parkinson's disease drug entacapone, the anticancer agent
trilostane and the herbicides 2-cyano-3-(substituted)acrylates
(Fig. 1).3
Moreover, the nitrile group could serve as a useful synthetic
precursor for further transformation into desired functionalities,
such as amine, carbonyl, amide, and carboxylic acid.4 The reported
synthetic methods for alkenyl nitriles include the carbocyanation of
alkynes,5 the cyanation of alkenyl halides,6 C(sp3)ꢀH functionali-
zation of allylarenes or alkenes with trimethylsilyl azide,7 the
dehydrogenative coupling of primary alcohols with nitriles,8 and
the reaction of aldehydes and simple or substituted acetonitriles9
(Scheme 1). However, these methodologies suffer from the use of
expensive transition-metal catalysts and halide substrates. There-
fore, more general, economical and greener methods still need to
be developed.
2. Results and discussion
Initially, (E)-3-(4-methylbenzylidene)indolin-2-one (1a) was
selected as a model substrate to react with benzoyl cyanide in
acetonitrile using potassium carbonate as a base under open air
condition (Scheme 2). The possible reaction approach for this re-
action might include Michael addition to afford 2-(2-oxoindolin-3-
yl)-2-(4-tolyl)acetonitrile (2a) as a final product. However, none of
the expected product was detected. To our delight, (Z)-2-(2-
oxoindolin-3-ylidene)-2-(4-tolyl)acetonitrile (3a) was isolated
with high stereoselectivity, which was confirmed by comparison 1H
NMR and 13C NMR spectra with literature.10 This result implied that
the C(sp2)eCN bond was efficiently formed by C(sp2)eH cyanation
of 1a under transition metal-free condition.
In order to optimize the reaction conditions, the different bases
and solvents were examined for the reaction (Table 1). Some tested
inorganic bases, such as K2CO3, Cs2CO3, KOH and NaHCO3 showed a
certain effect on the reaction to afford 3a in low yield (Table 1,
entries 1e4). In contrast, organic bases, such as Et2NH, piperidine,
DBU and DABCO could not promote the reaction (Table 1, entries
5e8). In the later research, it was found that the base combination
could produce different effects (Table 1, entries 9e13). Amongst
In this work, we reported an efficient method for the con-
struction of C(sp2)eCN bonds through C(sp2)eH cyanation of
* Corresponding author.
E-mail address: lizheng@nwnu.edu.cn (Z. Li).
https://doi.org/10.1016/j.tet.2018.01.050
0040-4020/© 2018 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Xie D, Li Z, Synthesis of 2-(2-oxoindolin-3-ylidene)-2-arylacetonitriles through transition metal-free C(sp2)
eCN bond construction, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.01.050

2
D. Xie, Z. Li / Tetrahedron xxx (2018) 1e9
Fig. 1. Representative examples containing alkenyl nitrile structures.
Scheme 1. Preparation of alkenyl nitriles.
them, the combination of K2CO3 and KOH could largely improve the
yield of 3a (Table 1, entry 13).
In addition, the solvent effect on the reaction was studied. A
higher yield of 3a was observed when the reaction was performed
in MeCN (Table 1, entry 13). A lower yield of 3a was obtained in THF,
1,4-dioxane, MeOH and EtOH (Table 1, entries 14e17). Other sol-
vents such as toluene, dichloromethane, and DMSO were ineffec-
tive for the reaction (Table 1, entries 18e20).
Please cite this article in press as: Xie D, Li Z, Synthesis of 2-(2-oxoindolin-3-ylidene)-2-arylacetonitriles through transition metal-free C(sp2)
eCN bond construction, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.01.050

D. Xie, Z. Li / Tetrahedron xxx (2018) 1e9
3
high yield. Furthermore, the substituents at ortho-, meta- and para-
positions of aromatic rings did not exhibit significant effect on the
yield. Substrate containing fused ring (naphthyl) could also proceed
smoothly to produce the corresponding product in high yield (3t).
Meanwhile, substrate including heteroaromatic ring (thienyl) fur-
nished the desired product in moderate yield (3s). In addition,
substrates bearing disubstituted aromatic rings also allowed for the
easy synthesis of the corresponding products in high yield
(3uꢀ3w). However, the attempt for the substrate including
aliphatic chain, such as (E)-3-(2-methylpropylidene)indolin-2-one
and (E)-3-(2,2-dimethylpropylidene)indolin-2-one, was not suc-
cessful, and none of the expected products were observed under
the standard conditions.
The method could also be applied to the substrates bearing
substituents on 2-oxoindoline rings using standard conditions. The
corresponding products 4 could be isolated in good yield. The re-
sults are summarized in Table 3.
With the success over generality of the protocol, the reaction of
1a with benzoyl cyanide was also performed on gram scale. The
reaction of 1.18 g of 1a with 0.79 g of benzoyl cyanide in the pres-
ence of 0.70 g of K2CO3, 0.28 g of KOH and 0.18 g of H2O in MeCN
(10 mL) was performed under the optimized condition to give
0.99 g of 3a in 76% isolated yield. This success of gram scale reaction
further showed the potency of optimized condition for the bulk
processes (Scheme 3).
Scheme 2. The reaction of 1a with benzoyl cyanide.
Table 1
Optimization of the reaction conditions.a
Some control experiments were carried out using 1a as a model
substrate (Scheme 4). The reaction of 1a with benzoyl cyanide using
the similar condition under N2 atmosphere only gave Michael
addition product 2a (65%) as a product, and 3a was not detected.
The further reaction of 2a using the standard condition under air
atmosphere afforded 3a in 99% yield within 1 h. This result implied
that 2a might be the intermediate of the reaction and air was an
indispensable condition for the formation of 3a.
A plausible mechanism is proposed for the synthesis of 3a
(Scheme 5). Benzoyl cyanide is first attacked by water in the
presence of potassium carbonate to produce cyanide ion in situ,
which reacts with 1a by Michael addition to form intermediate 2a.
2a could be isolated and characterized in the experiment. Then
CeH hydroxylation of 2a is promoted by potassium hydroxide us-
ing atmospheric air as an oxidant to afford intermediate A. The
similar reactions were also reported by Gnanaprakasam and co-
workers.11 Finally, intermediate A undergoes dehydration to give 3a
as a final product.
Entry
Base
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
K2CO3
Cs2CO3
KOH
NaHCO3
Et2NH
Piperidine
DBU
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
THF
43
13
14
Trace
NR
NR
Trace
Trace
48
DABCO
9
K2CO3-Cs2CO3
K2CO3- NaHCO3
K2CO3- Et2NH
K2CO3- DBU
K2CO3-KOH
K2CO3-KOH
K2CO3-KOH
K2CO3-KOH
K2CO3-KOH
K2CO3-KOH
K2CO3-KOH
K2CO3-KOH
10
11
12
13
14
15
16
17
18
19
20
21
Trace
Trace
97
20
Trace
56
21
NR
NR
NR
1,4-Dioxane
MeOH
EtOH
PhMe
DCM
3. Conclusions
In conclusion, we have developed a transition metal-free direct
C(sp2-H) cyanation of internal olefins to construct C(sp2)eCN bond.
This method provides an efficient and high yield way to syntheti-
cally construct useful alkenyl nitriles. The new methods are char-
acterized by high efficiency, shorter reaction time, high yield and
excellent functional group tolerance, providing a practical and
versatile approach to a wide range of alkenyl nitriles. A gram-scale
reaction has been attempted to illustrate the potency of reported
procedure towards the bulk synthesis. This protocol not only ex-
tends the application of benzoyl cyanide in synthetic organic
DMSO
a
Reaction conditions: 1a (0.5 mmol), benzoyl cyanide (0.6 mmol), base
(0.5 mmol, for base combination, 0.5 mmol for each base used) and H2O (1 mmol) in
solvent (5 mL) at 80 ꢁC for 3 h under air condition.
b
Isolated yields.
With the optimal conditions in hand, we turned our focus to
unearth the generality of the method by reactions of various (E)-3-
arylideneindolin-2-ones with benzoyl cyanide to access various
(Z)-2-(2-oxoindolin-3-ylidene)-2-arylacetonitriles in acetonitrile
using K2CO3 and KOH as bases under air condition, and the results
are summarized in Table 2. The reactions could tolerate a wide
range of functional groups, and produce the corresponding prod-
ucts in satisfactory yield. Substrates bearing both electron-donating
(Me, MeO and OH) and electron withdrawing (F, Cl, Br and CF3)
groups on aromatic rings could give the corresponding products in
chemistry but also offers a novel method for the preparation of a-
cyano substituted internal olefins, which are important structural
units in a number of biological active compounds.
4. Experimental
4.1. General information
1H NMR and 13C NMR spectra were recorded on a Mercury-
Please cite this article in press as: Xie D, Li Z, Synthesis of 2-(2-oxoindolin-3-ylidene)-2-arylacetonitriles through transition metal-free C(sp2)
eCN bond construction, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.01.050

4
D. Xie, Z. Li / Tetrahedron xxx (2018) 1e9
Table 2
Scope of aromatic rings of 1 for the synthesis of 3.a
600 MB or 400 MB instrument using CDCl3 and DMSO‑d6 as sol-
vents and Me4Si as internal standard. Elemental analyses were
performed on a Vario El Elemental Analysis instrument. Melting
points were observed in an electrothermal melting point apparatus.
3-Arylideneindolin-2-ones (1) were synthesized according to
literature method.12
4.2. Typical procedure for the synthesis of 3a-w and 4a-e
The mixture of (E)-3-arylideneindolin-2-ones (0.5 mmol), ben-
zoyl cyanide (0.6 mmol), potassium carbonate (0.5 mmol), potas-
sium hydroxide (0.5 mmol) and water (1.0 mmol) in acetonitrile
(5 mL) was stirred at 80 ꢁC for 3 h. The reaction was monitored by
Please cite this article in press as: Xie D, Li Z, Synthesis of 2-(2-oxoindolin-3-ylidene)-2-arylacetonitriles through transition metal-free C(sp2)
eCN bond construction, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.01.050

D. Xie, Z. Li / Tetrahedron xxx (2018) 1e9
5
Table 3
Scope of 2-oxoindoline rings of 1 for the synthesis of 4.a
Scheme 3. Gram-scale experiment for 3a.
Scheme 4. Control experiments.
TLC. After the completion of the reaction, the mixture was extracted
with ethyl acetate (3 ꢂ 10 mL), and the resulting solution was
washed with saturated brine (3 ꢂ 10 mL), dried over anhydrous
sodium sulfate, and concentrated under reduced pressure. The
residue was isolated by column chromatography using petroleum
ether and ethyl acetate (v/v 3:1) as eluent to give pure product. The
analytical data for products are given below.
4.2.1. (Z)-2-(2-oxoindolin-3-ylidene)-2-(p-tolyl)acetonitrile (3a)10
Orange red solid; mp 196e198 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
10.92 (s, 1H), 7.48 (d, J ¼ 8.1 Hz, 2H), 7.38 (d, J ¼ 8.0 Hz, 2H), 7.25
d
(td, J ¼ 7.6, 1.4 Hz, 1H), 6.83 (d, J ¼ 7.8 Hz, 1H), 6.72e6.64 (m, 2H),
2.38 (s, 3H). 13C NMR (150 MHz, DMSO‑d6)
d 165.87, 144.13, 141.10,
138.45, 133.58, 130.55, 130.35, 128.95, 124.56, 121.93, 120.49, 117.77,
115.17, 111.08, 21.47. Anal. Calcd. For C17H12N2O: C, 78.44; H, 4.65; N,
10.76. Found: C, 78.40; H, 4.66; N, 10.72.
Please cite this article in press as: Xie D, Li Z, Synthesis of 2-(2-oxoindolin-3-ylidene)-2-arylacetonitriles through transition metal-free C(sp2)
eCN bond construction, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.01.050

6
D. Xie, Z. Li / Tetrahedron xxx (2018) 1e9
Scheme 5. Proposed mechanism for 3a.
4.2.2. (Z)-2-(2-oxoindolin-3-ylidene)-2-(o-tolyl)acetonitrile (3b)
Orange red solid; mp 59e61 ꢁC; 1H NMR (400 MHz, CDCl3)
4.2.6. (Z)-2-(3-methoxphenyl)-2-(2-oxoindolin-3-ylidene)
acetonitrile (3f)
d
8.94 (s, 1H), 7.46 (td, J ¼ 7.3, 1.8 Hz, 1H), 7.41e7.30 (m, 3H),
Orange red solid; mp 189e191 ꢁC; 1H NMR (400 MHz, DMSO‑d6)
7.28e7.23 (m, 1H), 6.96 (d, J ¼ 7.8 Hz, 1H), 6.70 (td, J ¼ 7.7, 1.0 Hz,
d
10.95 (s, 1H), 7.50 (t, J ¼ 7.9 Hz, 1H), 7.26 (t, J ¼ 7.7 Hz, 1H),
1H), 6.24 (d, J ¼ 7.7 Hz, 1H), 2.36 (s, 3H). 13C NMR (150 MHz, CDCl3)
7.18e7.12 (m, 3H), 6.83 (d, J ¼ 7.8 Hz,1H), 6.71 (t, J ¼ 7.7 Hz,1H), 6.57
d
166.14,142.28,138.89,136.17,133.05,131.91,131.33,130.43,128.32,
(d, J ¼ 7.8 Hz, 1H), 3.77 (s, 3H). 13C NMR (150 MHz, DMSO‑d6)
127.17, 125.13, 122.63, 120.66, 116.15, 115.79, 110.87, 19.41. Anal.
Calcd. For C17H12N2O: C, 78.44; H, 4.65; N, 10.76. Found: C, 78.52; H,
4.64; N, 10.71.
d 165.81, 160.35, 144.23, 139.07, 134.45, 133.72, 131.39, 124.90,
122.01, 120.83, 120.43, 117.55, 116.77, 114.64, 114.03, 111.11, 55.89.
Anal. Calcd. For C17H12N2O2: C, 73.90; H, 4.38; N, 10.14. Found: C,
74.00; H, 4.35; N, 10.10.
4.2.3. (Z)-2-(2-oxoindolin-3-ylidene)-2-(m-tolyl)acetonitrile (3c)10
Orange red solid; mp 187e189 ꢁC; 1H NMR (400 MHz, CDCl3)
4.2.7. (Z)-2-(4-methoxyphenyl)-2-(2-oxoindolin-3-ylidene)
acetonitrile (3g)10
d
9.51 (s, 1H), 7.45e7.33 (m, 4H), 7.30e7.24 (m, 1H), 7.05 (d,
J ¼ 7.8 Hz, 1H), 6.87 (d, J ¼ 7.8 Hz, 1H), 6.73 (td, J ¼ 7.7, 1.1 Hz, 1H),
2.43 (s, 3H). 13C NMR (100 MHz, CDCl3)
166.77, 142.56, 139.45,
Orange red solid; mp 163e165 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
d
10.90 (s, 1H), 7.56 (d, J ¼ 8.7 Hz, 2H), 7.26 (td, J ¼ 7.6, 1.3 Hz, 1H),
d
7.12 (d, J ¼ 8.8 Hz, 2H), 6.83 (d, J ¼ 7.8 Hz, 1H), 6.79 (d, J ¼ 6.5 Hz,
137.86, 133.09, 132.65, 131.49, 129.24, 129.14, 125.79, 124.74, 122.17,
120.40, 117.21, 116.73, 111.30, 21.32. Anal. Calcd. For C17H12N2O: C,
78.44; H, 4.65; N, 10.76. Found: C, 78.37; H, 4.67; N, 10.79.
1H), 6.73 (td, J ¼ 7.7, 1.1 Hz, 1H), 3.84 (s, 3H). 13C NMR (150 MHz,
DMSO‑d6)
d 165.98, 161.46, 144.00, 137.74, 133.42, 130.92, 125.16,
124.39, 121.94, 120.64, 117.90, 115.39, 115.16, 111.03, 55.92. Anal.
Calcd. For C17H12N2O2: C, 73.90; H, 4.38; N,10.14. Found: C, 73.97; H,
4.37; N, 10.11.
4.2.4. (Z)-2-(2-oxoindolin-3-ylidene)-2-phenylacetonitrile (3d)10
Orange red solid; mp 195e197 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
d
10.95 (s, 1H), 7.62e7.56 (m, 5H), 7.26 (td, J ¼ 7.8, 1.3 Hz, 1H), 6.83
(d, J ¼ 7.8 Hz, 1H), 6.68 (td, J ¼ 7.7, 1.0 Hz, 1H), 6.52 (d, J ¼ 7.9 Hz, 1H).
13C NMR (150 MHz, DMSO‑d6)
165.80, 144.23, 139.00, 133.72,
4.2.8. (Z)-2-(2-hydroxyphenyl)-2-(2-oxoindolin-3-ylidene)
acetonitrile (3h)
Orange red solid; mp 169e171 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
d
133.26, 131.07, 130.08, 128.92, 124.67, 121.97, 120.43, 117.68, 114.91,
111.13. Anal. Calcd. For C16H10N2O: C, 78.03; H, 4.09; N,11.38. Found:
C, 77.94; H, 4.11; N, 11.42.
d
10.89 (s, 1H), 10.22 (s, 1H), 7.41e7.37 (m, 1H), 7.33 (dd, J ¼ 7.7,
1.7 Hz, 1H), 7.25 (td, J ¼ 7.7, 1.2 Hz, 1H), 7.03 (d, J ¼ 8.2 Hz, 1H), 6.96
(td, J ¼ 7.5, 1.1 Hz, 1H), 6.83 (d, J ¼ 7.8 Hz, 1H), 6.71 (t, J ¼ 7.7 Hz, 1H),
6.43 (d, J ¼ 7.8 Hz, 1H). 13C NMR (150 MHz, DMSO‑d6)
d 165.77,
155.27, 143.88, 139.14, 133.33, 132.42, 130.20, 124.96, 122.05, 120.91,
120.36, 119.69, 117.14, 117.05, 112.51, 110.87. Anal. Calcd. For
4.2.5. (Z)- 2-(2-methoxphenyl)-2-(2-oxoindolin-3-ylidene)
acetonitrile (3e)
Orange red solid; mp 159e161 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
C16H10N2O2: C, 73.27; H, 3.84; N, 10.68. Found: C, 73.35; H, 3.82; N,
10.63.
d
10.93 (s, 1H), 7.58 (ddd, J ¼ 8.9, 7.6, 1.7 Hz, 1H), 7.43 (dd, J ¼ 7.6,
1.7 Hz, 1H), 7.28e7.23 (m, 2H), 7.13 (t, J ¼ 7.5 Hz, 1H), 6.83 (d,
J ¼ 7.8 Hz, 1H), 6.69 (t, J ¼ 7.7 Hz, 1H), 6.30 (d, J ¼ 7.9 Hz, 1H), 3.78 (s,
4.2.9. (Z)-2-(2-fluorophenyl)-2-(2-oxoindolin-3-ylidene)
acetonitrile (3i)
3H). 13C NMR (150 MHz, DMSO‑d6)
d 165.64, 156.78, 144.00, 139.49,
133.56, 132.82, 130.28, 124.72, 122.12, 121.88, 121.19, 120.70, 116.93,
112.95, 111.93, 111.03, 56.37. Anal. Calcd. For C17H12N2O2: C, 73.90;
H, 4.38; N, 10.14. Found: C, 73.83; H, 4.41; N, 10.19.
Orange red solid; mp 143e145 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
d
11.02 (s, 1H), 7.70e7.65 (m, 2H), 7.48 (t, J ¼ 9.5 Hz, 1H), 7.43 (t,
J ¼ 8.1 Hz, 1H), 7.29 (t, J ¼ 7.8 Hz, 1H), 6.85 (d, J ¼ 7.8 Hz, 1H), 6.73 (t,
Please cite this article in press as: Xie D, Li Z, Synthesis of 2-(2-oxoindolin-3-ylidene)-2-arylacetonitriles through transition metal-free C(sp2)
eCN bond construction, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.01.050

D. Xie, Z. Li / Tetrahedron xxx (2018) 1e9
7
J ¼ 7.7 Hz, 1H), 6.37 (d, J ¼ 7.8 Hz, 1H). 13C NMR (150 MHz, DMSO‑d6)
4.2.15. (Z)-2-(2-bromophenyl)-2-(2-oxoindolin-3-ylidene)
acetonitrile (3o)
d
165.35, 159.07 (d, J ¼ 247.6 Hz), 144.51, 141.01, 134.28, 133.74 (d,
J ¼ 8.3 Hz), 131.23, 126.35 (d, J ¼ 3.3 Hz), 124.65, 122.34, 120.49 (d,
J ¼ 15.0 Hz), 120.21, 117.26 (d, J ¼ 20.5 Hz), 116.64, 111.30, 107.64.
Anal. Calcd. For C16H9FN2O: C, 72.72; H, 3.43; N, 10.60. Found: C,
72.67; H, 3.44; N, 10.65.
Orange red solid; mp 171e173 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
11.03 (s, 1H), 7.90 (dd, J ¼ 8.1, 1.2 Hz, 1H), 7.65 (dd, J ¼ 7.6, 1.8 Hz,
d
1H), 7.61 (td, J ¼ 7.5, 1.2 Hz, 1H), 7.54 (td, J ¼ 7.7, 1.7 Hz, 1H), 7.28 (td,
J ¼ 7.7,1.2 Hz,1H), 6.85 (d, J ¼ 7.9 Hz,1H), 6.69 (td, J ¼ 7.7,1.0 Hz,1H),
5.99 (d, J ¼ 7.6 Hz, 1H). 13C NMR (150 MHz, DMSO‑d6)
d 165.40,
144.40, 140.51, 134.18, 134.12, 133.43, 132.84, 130.97, 129.79, 124.89,
122.43, 121.80, 120.26, 116.13, 113.01, 111.31. Anal. Calcd. For
4.2.10. (Z)-2-(3-fluorophenyl)-2-(2-oxoindolin-3-ylidene)
acetonitrile (3j)
C16H9BrN2O: C, 59.10; H, 2.79; N, 8.62. Found: C, 59.16; H, 2.80; N,
Orange red solid; mp 226e228 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
8.58.
d
10.97 (s, 1H), 7.67e7.62 (m, 1H), 7.53 (dt, J ¼ 9.4, 2.1 Hz, 1H),
7.48e7.41 (m, 2H), 7.28 (td, J ¼ 7.8, 1.2 Hz, 1H), 6.84 (d, J ¼ 7.8 Hz,
4.2.16. (Z)-2-(3-bromophenyl)-2-(2-oxoindolin-3-ylidene)
acetonitrile (3p)
1H), 6.73 (t, J ¼ 7.7 Hz, 1H), 6.48 (d, J ¼ 8.1 Hz, 1H). 13C NMR
(150 MHz, DMSO‑d6)
d
165.67, 162.86 (d, J ¼ 245.0 Hz), 144.39,
Orange red solid; mp 209e211 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
139.70, 135.30 (d, J ¼ 8.1 Hz), 133.97, 132.46 (d, J ¼ 8.5 Hz), 125.22 (d,
J ¼ 2.9 Hz), 124.86, 122.14, 120.26, 118.01 (d, J ¼ 20.7 Hz), 117.31,
116.02 (d, J ¼ 22.8 Hz), 113.18 (d, J ¼ 2.3 Hz), 111.21. Anal. Calcd. For
d
10.97 (s, 1H), 7.86 (t, J ¼ 1.8 Hz, 1H), 7.79 (ddd, J ¼ 8.0, 2.1, 1.0 Hz,
1H), 7.63 (dt, J ¼ 7.8, 1.3 Hz, 1H), 7.54 (t, J ¼ 7.9 Hz, 1H), 7.28 (td,
J ¼ 7.7,1.2 Hz,1H), 6.84 (d, J ¼ 7.8 Hz,1H), 6.73 (td, J ¼ 7.7,1.0 Hz,1H),
C
16H9FN2O: C, 72.72; H, 3.43; N, 10.60. Found: C, 72.80; H, 3.40; N,
6.48 (d, J ¼ 7.8 Hz, 1H). 13C NMR (150 MHz, DMSO‑d6)
d 165.65,
10.57.
144.44, 139.76, 135.41, 134.00, 133.85, 132.27, 131.48, 128.13, 124.78,
123.00, 122.13, 120.29, 117.35, 113.00, 111.25. Anal. Calcd. For
C
8.65.
16H9BrN2O: C, 59.10; H, 2.79; N, 8.62. Found: C, 59.01; H, 2.81; N,
4.2.11. (Z)-2-(4-fluorophenyl)-2-(2-oxoindolin-3-ylidene)
acetonitrile (3k)
Orange red solid; mp 259e261 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
4.2.17. (Z)-2-(4-bromophenyl)-2-(2-oxoindolin-3-ylidene)
acetonitrile (3q)
d
10.95 (s, 1H), 7.69 (dd, J ¼ 8.6, 5.4 Hz, 2H), 7.43 (t, J ¼ 8.8 Hz, 2H),
7.27 (t, J ¼ 8.4 Hz, 1H), 6.84 (d, J ¼ 7.8 Hz, 1H), 6.73 (t, J ¼ 7.7 Hz, 1H),
Orange red solid; mp 267e269 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
10.95 (s, 1H), 7.80 (dd, J ¼ 8.4, 2.1 Hz, 2H), 7.59 (dd, J ¼ 8.5, 2.1 Hz,
6.55 (d, J ¼ 7.8 Hz, 1H). 13C NMR (150 MHz, DMSO‑d6)
d 165.75,
d
163.54 (d, J ¼ 247.2 Hz), 144.26, 139.25, 133.79, 131.64 (d, J ¼ 8.7 Hz),
129.57 (d, J ¼ 3.0 Hz), 124.74, 122.10, 120.39, 117.62, 117.27 (d,
J ¼ 22.2 Hz), 113.85, 111.15. Anal. Calcd. For C16H9FN2O: C, 72.72; H,
3.43; N, 10.60. Found: C, 72.68; H, 3.45; N, 10.56.
2H), 7.29 (t, J ¼ 7.8 Hz, 1H), 6.85 (d, J ¼ 7.8 Hz, 1H), 6.75 (t, J ¼ 7.6 Hz,
1H), 6.59 (d, J ¼ 7.9 Hz, 1H). 13C NMR (150 MHz, DMSO‑d6)
d 165.72,
144.34, 139.30, 133.94, 133.16, 132.47, 131.22, 124.81, 124.62, 122.18,
120.30, 117.40, 113.62, 111.21. Anal. Calcd. For C16H9BrN2O: C, 59.10;
H, 2.79; N, 8.62. Found: C, 59.15; H, 2.77; N, 8.66.
4.2.12. (Z)-2-(2-chlorophenyl)-2-(2-oxoindolin-3-ylidene)
acetonitrile (3l)
4.2.18. (Z)-2-(2-oxoindolin-3-ylidene)-2-(4-(trifluoromethyl)
phenyl)acetonitrile (3r)10
Orange red solid; mp 191e193 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
Orange red solid; mp 237e239 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
11.00 (s, 1H), 7.97 (d, J ¼ 8.1 Hz, 2H), 7.88 (d, J ¼ 8.5 Hz, 2H), 7.29
d
11.03 (s, 1H), 7.74 (d, J ¼ 8.1 Hz, 1H), 7.69e7.62 (m, 2H), 7.57 (td,
J ¼ 7.5,1.2 Hz,1H), 7.28 (t, J ¼ 7.7 Hz,1H), 6.85 (d, J ¼ 7.8 Hz,1H), 6.70
d
(t, J ¼ 7.7 Hz, 1H), 6.04 (d, J ¼ 8.1 Hz, 1H). 13C NMR (150 MHz,
(td, J ¼ 7.7, 1.2 Hz, 1H), 6.85 (d, J ¼ 7.8 Hz, 1H), 6.73 (td, J ¼ 7.7, 1.0 Hz,
1H), 6.48 (d, J ¼ 7.7 Hz, 1H). 13C NMR (150 MHz, DMSO‑d6)
d
165.63,
DMSO‑d6)
d 165.36, 144.46, 140.81, 134.23, 132.82, 132.05, 131.43,
131.04, 130.98, 129.27, 124.81, 122.42, 120.23, 116.21, 111.31, 111.15.
Anal. Calcd. For C16H9ClN2O: C, 68.46; H, 3.23; N, 9.98. Found: C,
68.55; H, 3.21; N, 9.95.
144.51, 139.95, 137.39, 134.17, 131.19, 130.98, 130.17, 127.10 (q,
J ¼ 3.7 Hz), 125.15, 124.87, 123.34, 122.23, 120.13, 117.33, 113.08,
111.28. Anal. Calcd. For C17H9F3N2O: C, 64.97; H, 2.89; N, 8.91.
Found: C, 65.09; H, 2.87; N, 8.87.
4.2.13. (Z)-2-(3-chlorophenyl)-2-(2-oxoindolin-3-ylidene)
acetonitrile (3m)
4.2.19. (Z)-2-(2-oxoindolin-3-ylidene)-2-(thiophen-3-yl)
acetonitrile (3s)10
Orange red solid; mp 196e198 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
Reddish brown solid; mp 179e181 ꢁC; 1H NMR (600 MHz,
d
10.97 (s, 1H), 7.74 (s, 1H), 7.66 (d, J ¼ 7.9 Hz,1H), 7.63e7.57 (m, 2H),
DMSO‑d6)
d
10.95 (s, 1H), 7.97 (dd, J ¼ 5.1, 1.2 Hz, 1H), 7.60 (dd,
7.28 (t, J ¼ 7.6 Hz, 1H), 6.84 (d, J ¼ 7.8 Hz, 1H), 6.73 (t, J ¼ 7.7 Hz, 1H),
J ¼ 3.6, 1.2 Hz, 1H), 7.31 (td, J ¼ 7.7, 1.2 Hz, 1H), 7.27 (dd, J ¼ 5.1,
3.6 Hz, 1H), 7.08 (d, J ¼ 8.0 Hz, 1H), 6.85 (d, J ¼ 7.8 Hz, 1H), 6.80 (td,
6.47 (d, J ¼ 7.7 Hz, 1H). 13C NMR (150 MHz, DMSO‑d6)
d 165.65,
144.43, 139.77, 135.20, 134.63, 134.00, 132.09, 130.96, 128.71, 127.76,
124.80, 122.14, 120.28, 117.33, 113.06, 111.25. Anal. Calcd. For
J ¼ 7.7, 1.1 Hz, 1H). 13C NMR (150 MHz, DMSO‑d6)
d 165.74, 144.31,
138.93, 134.17, 133.94, 131.97, 131.83, 128.98, 124.52, 122.09, 120.32,
117.20, 111.19, 108.07. Anal. Calcd. For C14H8N2OS: C, 66.65; H, 3.20;
N, 11.10. Found: C, 66.69; H, 3.19; N, 11.05.
C
16H9ClN2O: C, 68.46; H, 3.23; N, 9.98. Found: C, 68.38; H, 3.25; N,
10.02.
4.2.14. (Z)-2-(4-chlorophenyl)-2-(2-oxoindolin-3-ylidene)
acetonitrile (3n)
4.2.20. (Z)-2-(naphthalen-2-yl)-2-(2-oxoindolin-3-ylidene)
acetonitrile (3t)
Orange red solid; mp 256e258 ꢁC; 1H NMR (600 MHz, CDCl3)
Orange red solid; mp 210e212 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
d
7.84 (s, 1H), 7.56 (d, J ¼ 8.6 Hz, 2H), 7.53 (d, J ¼ 8.5 Hz, 2H), 7.29 (t,
d
11.01 (s, 1H), 8.17 (d, J ¼ 8.3 Hz, 1H), 8.09 (d, J ¼ 8.2 Hz, 1H), 7.87 (d,
J ¼ 7.7 Hz, 1H), 6.89 (d, J ¼ 7.9 Hz, 1H), 6.87 (d, J ¼ 7.9 Hz, 1H), 6.78 (t,
J ¼ 8.4 Hz, 1H), 7.74 (dd, J ¼ 7.1, 1.2 Hz, 1H), 7.68 (dd, J ¼ 8.2, 7.1 Hz,
1H), 7.62 (ddd, J ¼ 8.0, 6.7, 1.2 Hz, 1H), 7.56 (ddd, J ¼ 8.2, 6.8, 1.3 Hz,
1H), 7.17 (td, J ¼ 7.7, 1.2 Hz, 1H), 6.82 (d, J ¼ 7.7 Hz, 1H), 6.45 (td,
J ¼ 7.7, 1.0 Hz, 1H), 5.74 (d, J ¼ 6.7 Hz, 1H). 13C NMR (150 MHz,
J ¼ 7.7 Hz, 1H). 13C NMR (150 MHz, DMSO‑d6)
d 165.71, 144.33,
139.37, 135.85, 133.92, 132.08, 131.04, 130.25, 124.82, 122.17, 120.30,
117.47, 113.56, 111.19. Anal. Calcd. For C16H9ClN2O: C, 68.46; H, 3.23;
N, 9.98. Found: C, 68.50; H, 3.21; N, 9.99.
DMSO‑d6)
d 165.59, 144.45, 141.11, 133.88, 133.70, 131.13, 130.19,
Please cite this article in press as: Xie D, Li Z, Synthesis of 2-(2-oxoindolin-3-ylidene)-2-arylacetonitriles through transition metal-free C(sp2)
eCN bond construction, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.01.050

8
D. Xie, Z. Li / Tetrahedron xxx (2018) 1e9
129.59, 129.41, 128.25, 127.56, 127.53, 126.59, 125.08, 124.27, 121.99,
120.47, 117.39, 112.50, 111.08. Anal. Calcd. For C20H12N2O: C, 81.07;
H, 4.08; N, 9.45. Found: C, 81.16; H, 4.07; N, 9.40.
d 165.99,149.56,142.10,137.70,136.55,131.28,131.10,130.40,129.54,
120.66,119.82,116.87,116.51,111.31. Anal. Calcd. For C16H8ClN3O3: C,
59.00; H, 2.48; N, 12.90. Found: C, 58.90; H, 2.50; N, 12.96.
4.2.21. (Z)-2-(2,5-dimethoxyphenyl)-2-(2-oxoindolin-3-ylidene)
acetonitrile (3u)
4.2.27. (Z)-2-(4-methoxyphenyl)-2-(2-oxo-1-phenylindolin-3-
ylidene)acetonitrile (4d)
Orange red solid; mp 202e204 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
Orange red solid; mp 207e209 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
d
10.93 (s, 1H), 7.26 (td, J ¼ 7.7, 1.2 Hz, 1H), 7.19 (d, J ¼ 9.1 Hz, 1H),
d
7.68 (d, J ¼ 8.8 Hz, 2H), 7.64 (t, J ¼ 7.8 Hz, 2H), 7.55e7.50 (m, 3H),
7.13 (dd, J ¼ 9.1, 3.1 Hz,1H), 7.05 (d, J ¼ 3.1 Hz,1H), 6.83 (d, J ¼ 7.8 Hz,
7.35 (td, J ¼ 7.8, 1.4 Hz, 1H), 7.22 (d, J ¼ 8.7 Hz, 2H), 6.98 (d,
1H), 6.73 (td, J ¼ 7.7, 1.0 Hz, 1H), 6.37 (d, J ¼ 7.8 Hz, 1H), 3.72 (s, 3H),
J ¼ 8.0 Hz, 1H), 6.92 (t, J ¼ 7.7 Hz, 1H), 6.77 (d, J ¼ 7.9 Hz, 1H), 3.91 (s,
3.70 (s, 3H). 13C NMR (150 MHz, DMSO‑d6)
d 165.65, 154.07, 150.70,
3H). 13C NMR (150 MHz, DMSO‑d6)
d 164.12, 161.68, 144.80, 136.48,
144.02, 139.59, 133.58, 124.85, 122.18, 121.74, 120.69, 117.76, 116.90,
115.28, 114.23, 111.59, 111.02, 56.74, 56.20. Anal. Calcd. For
133.96, 133.40, 130.99, 130.18, 128.93, 127.37, 126.92, 124.42, 123.11,
120.21, 117.80, 116.42, 115.55, 110.21, 55.98. Anal. Calcd. For
C
18H14N2O3: C, 70.58; H, 4.61; N, 9.15. Found: C, 70.47; H, 4.63; N,
C23H16N2O2: C, 78.39; H, 4.58; N, 7.95. Found: C, 78.46; H, 4.57; N,
9.19.
7.92.
4.2.22. (Z)-2-(2-hydroxy-3-methoxyphenyl)-2-(2-oxoindolin-3-
ylidene)acetonitrile (3v)
4.2.28. (Z)-2-(4-bromophenyl)-2-(2-oxo-1-phenylindolin-3-
ylidene)acetonitrile (4e)
Orange red solid; mp 232e234 ꢁC; 1H NMR (400 MHz, CDCl3)
Orange red solid; mp 169e171 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
d
9.03 (s, 1H), 7.23 (td, J ¼ 7.7, 1.5 Hz, 1H), 7.03e6.97 (m, 3H), 6.91 (d,
J ¼ 7.9 Hz, 1H), 6.76e6.65 (m, 2H), 3.97 (s, 3H), 3.89 (s, 1H). 13C NMR
d
7.84 (d, J ¼ 8.5 Hz, 2H), 7.64 (d, J ¼ 8.5 Hz, 2H), 7.59 (t, J ¼ 7.8 Hz,
2H), 7.52e7.44 (m, 3H), 7.32 (t, J ¼ 8.3 Hz,1H), 6.88 (t, J ¼ 7.7 Hz,1H),
(150 MHz, CHCl3)
d 166.36, 147.30, 143.78, 142.27, 138.67, 132.79,
6.72 (d, J ¼ 8.5 Hz, 2H). 13C NMR (150 MHz, DMSO‑d6)
d 163.88,
125.29, 122.29, 121.47, 120.83, 120.72, 118.56, 116.41, 112.49, 112.22,
110.72, 56.28. Anal. Calcd. For C17H12N2O3: C, 69.86; H, 4.14; N, 9.58.
Found: C, 69.78; H, 4.15; N, 9.62.
145.12, 138.13, 133.90, 133.81, 133.31, 132.33, 131.20, 130.22, 129.01,
127.31, 124.89, 124.87, 123.33, 119.86, 117.32, 114.78, 110.36. Anal.
Calcd. For C22H13BrN2O: C, 65.85; H, 3.27; N, 6.98. Found: C, 65.77;
H, 3.28; N, 7.02.
4.2.23. (Z)-2-(5-chloro-2-hydroxyphenyl)-2-(2-oxoindolin-3-
ylidene)acetonitrile (3w)
Orange red solid; mp 181e183 ꢁC; 1H NMR (400 MHz, DMSO‑d6)
4.3. The isolation of 2a from the reaction system
d
10.95 (s, 1H), 10.58 (s, 1H), 7.50e7.41 (m, 2H), 7.28 (td, J ¼ 7.7,
1.2 Hz, 1H), 7.05 (d, J ¼ 8.8 Hz, 1H), 6.85 (d, J ¼ 7.8 Hz, 1H), 6.77 (td,
The mixture of 1a (0.5 mmol), benzoyl cyanide (0.6 mmol), po-
tassium carbonate (0.5 mmol), potassium hydroxide (0.5 mmol)
and water (1.0 mmol) in acetonitrile (5 mL) was stirred at 80 ꢁC for
3 h under nitrogen atmosphere. The reaction was monitored by
TLC. After the completion of the reaction, the mixture was extracted
with ethyl acetate (3 ꢂ 10 mL), and the resulting solution was
washed with saturated brine (3 ꢂ 10 mL), dried over anhydrous
sodium sulfate, and concentrated under reduced pressure. The
residue was isolated by column chromatography using petroleum
ether and ethyl acetate (v/v 3:1) as eluent to give 2a (the mixture of
diastereoisomers in 1:1 ratio). The analytical data for products are
given below.
J ¼ 7.7, 1.1 Hz, 1H), 6.44 (d, J ¼ 7.9 Hz, 1H). 13C NMR (150 MHz,
DMSO‑d6)
d 165.63, 154.34, 144.09, 139.85, 133.66, 132.06, 129.56,
124.95, 123.62, 122.24, 121.22, 120.70, 118.78, 116.85, 111.03, 110.65.
Anal. Calcd. For C16H9ClN2O2: C, 64.77; H, 3.06; N, 9.44. Found: C,
64.85; H, 3.04; N, 9.40.
4.2.24. (Z)-2-(6-chloro-2-oxoindolin-3-ylidene)-2-
phenylacetonitrile (4a)
Orange red solid; mp 188e190 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
d
11.11 (s, 1H), 7.59e7.58 (m, 5H), 6.85 (d, J ¼ 1.9 Hz, 1H), 6.77 (dd,
J ¼ 8.5, 2.0 Hz, 1H), 6.52 (d, J ¼ 8.4 Hz, 1H). 13C NMR (150 MHz,
DMSO‑d6)
d 165.78, 145.41, 137.85, 137.80, 132.98, 131.27, 130.14,
128.93, 125.82, 121.90, 119.36, 117.53, 115.51, 111.10. Anal. Calcd. For
16H9ClN2O: C, 68.46; H, 3.23; N, 9.98. Found: C, 68.37; H, 3.25; N,
10.01.
4.3.1. (R/S)-2-(2-oxoindolin-3-yl)-2-(p-tolyl)acetonitrile (2a)
C
Light yellow liquid; 1H NMR (600 MHz, CDCl3)
d 8.23 (s, 1H), 7.79
(s, 1H), 7.69 (d, J ¼ 7.5 Hz, 1H), 7.32 (d, J ¼ 8.0 Hz, 2H), 7.27e7.19 (m,
5H), 7.09 (td, J ¼ 7.6, 1.1 Hz, 1H), 6.99 (d, J ¼ 8.1 Hz, 2H), 6.96e6.88
(m, 4H), 6.69 (d, J ¼ 7.8 Hz, 1H), 6.53 (d, J ¼ 7.5 Hz, 1H), 4.76 (d,
J ¼ 4.0 Hz, 1H), 4.61 (d, J ¼ 4.2 Hz, 1H), 4.02 (d, J ¼ 4.1 Hz, 1H), 3.86
(d, J ¼ 4.1 Hz, 1H), 2.40 (s, 3H), 2.22 (s, 3H). 13C NMR (150 MHz,
4.2.25. (Z)-2-(5-bromo-2-oxoindolin-3-ylidene)-2-
phenylacetonitrile (4b)10
Orange red solid; mp 267e269 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
d
11.09 (s, 1H), 7.62e7.60 (m, 5H), 7.43 (dd, J ¼ 8.4, 2.0 Hz, 1H), 6.80
CDCl3) d 175.54, 174.91, 141.71, 141.34, 138.67, 138.51, 129.86, 129.37,
(d, J ¼ 8.4 Hz, 1H), 6.52 (d, J ¼ 2.0 Hz, 1H). 13C NMR (150 MHz,
129.20, 129.14, 128.42, 127.70, 127.24, 125.40, 125.36, 124.32, 124.26,
122.79, 122.53, 119.74, 117.08, 110.25, 109.90, 50.13, 49.04, 38.46,
36.95, 21.12, 21.02.
DMSO‑d6)
d 165.39, 143.32, 138.13, 135.79, 132.85, 131.43, 130.17,
128.87, 126.91, 122.51, 117.29, 116.46, 113.30, 113.04. Anal. Calcd. For
16H9BrN2O: C, 59.10; H, 2.79; N, 8.62. Found: C, 59.22; H, 2.78; N,
C
8.58.
Acknowledgements
4.2.26. (Z)-2-(4-chlorophenyl)-2-(5-nitro-2-oxoindolin-3-ylidene)
acetonitrile (4c)
The authors thank the National Natural Science Foundation of
China (21462038) and Key Laboratory of Eco-Environment-Related
Polymer Materials of Ministry of Education for the financial support
of this work.
Orange red solid; mp 289e291 ꢁC; 1H NMR (600 MHz, DMSO‑d6)
d
11.69 (s, 1H), 8.20 (dd, J ¼ 8.8, 2.3 Hz, 1H), 7.73 (s, 4H), 7.40 (d,
J ¼ 2.2 Hz,1H), 7.03 (d, J ¼ 8.7 Hz,1H). 13C NMR (150 MHz, DMSO‑d6)
Please cite this article in press as: Xie D, Li Z, Synthesis of 2-(2-oxoindolin-3-ylidene)-2-arylacetonitriles through transition metal-free C(sp2)
eCN bond construction, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.01.050

D. Xie, Z. Li / Tetrahedron xxx (2018) 1e9
Group Preparations. Weinheim: VCH; 1989.
9
Appendix A. Supplementary data
5. Nakao Y, Yada A, Ebata S, Hiyama TJ. J Am Chem Soc. 2007;129:2428e2429.
6. (a) Powell KJ, Han LC, Sharma P, Moses JE. Org Lett. 2014;16:2158e2161;
(b) Zhang J, Xu CY, Wu W, Cao S. Chem Eur J. 2016;22:9902e9908.
7. Qin C, Jiao N. J Am Chem Soc. 2010;132:15893e15895.
8. Chakraborty S, Das UK, Ben-David Y, Milstein D. J Am Chem Soc. 2017;139:
11710e11713.
Supplementary data related to this article can be found at
https://doi.org/10.1016/j.tet.2018.01.050.
References
9. (a) Lanari D, Alonzi M, Ferlin F, Santoro S, Vaccaro L. Org Lett. 2016;18:
2680e2683;
1. (a) Smith MB, March J. March's Advanced Organic Chemistry. sixth ed. NJ: John
Wiley & Sons; 2007;
(b) Tomioka T, Takahashi Y, Vaughan TG, Yanase T. Org Lett. 2010;12:
2171e2173.
(b) Anbarasan P, Schareina T, Beller M. Chem Soc Rev. 2011;40:5049e5067.
2. (a) An M, Sarker AK, Jung DC, Hong JD. Bull Kor Chem Soc. 2011;32:2083e2086;
(b) Fleming FF. Nat Prod Rep. 1999;16:596e606.
3. Fleming FF, Yao L, Ravikumar PC, Funk L, Shook BC. J Med Chem. 2010;53:
7902e7917.
10. Miura T, Toyoshima T, Kozawa O, Murakami M. Chem Lett. 2010;39:
1132e1133.
11. Chaudhari MB, Sutar Y, Malpathak S, Hazra A, Gnanaprakasam B. Org Lett.
2017;19:3628e3631.
12. Barakat A, Al-Majid AM, Islam MS, Ali M, Soliman SM, Siddiqui MRH,
Ghabbour HA, Fun HK. J Chem Sci. 2015;127:1547e1556.
4. (a) Rappoport Z. The Chemistry of the Cyano Group. London: Interscience Pub-
lishers; 1970;
(b) Larock RC. Comprehensive Organic Transformations: A Guide to Functional
Please cite this article in press as: Xie D, Li Z, Synthesis of 2-(2-oxoindolin-3-ylidene)-2-arylacetonitriles through transition metal-free C(sp2)
eCN bond construction, Tetrahedron (2018), https://doi.org/10.1016/j.tet.2018.01.050