Visible-Light-Induced Decarboxylative Cyclization of 2-Alkenylarylisocyanides with α-Oxocarboxylic Acids: Access to 2-Acylindoles

Article abstract of DOI:10.1021/acs.joc.0c00039

An efficient and practical protocol for visible-light-induced decarboxylative cyclization of 2-alkenylarylisocyanides with α-oxocarboxylic acids has been developed, which afforded a broad range of 2-acylindoles in moderate to good yields. The reaction proceeds through a cascade of acyl radical addition/cyclization reactions under irradiation of an Ir3+ photoredox catalyst without external oxidants and features simple operation, scalability, a broad substrate scope, and good functional group tolerance.

Full text of DOI:10.1021/acs.joc.0c00039

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Article
Visible-light-induced decarboxylative
cyclization of 2-alkenylarylisocyanides with #-
oxocarboxylic acids: direct access to 2-acylindoles
Xiaofei ZHANG, Peiyuan ZHU, Ruihong ZHANG, Xiang Li, and Tuanli Yao
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00039 • Publication Date (Web): 29 Jun 2020
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Visible-light-induced
decarboxylative
cyclization
of
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2-alkenylarylisocyanides with α-oxocarboxylic acids: direct access to
2-acylindoles
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Xiaofei Zhang,*a,b Peiyuan Zhu,a Ruihong Zhang,a Xiang Li,*a,b Tuanli Yao*a,b
a College of Chemistry and Chemical Engineering, Shaanxi University of Science and
Technology, Xi’an, Shaanxi 710021, China
Email: zhangxiaofei@sust.edu.cn; lix@sust.edu.cn; yaotuanli@sust.edu.cn
b Shaanxi Key Laboratory of Chemical Additives for Industry, Shaanxi University of
Science and Technology, Xi’an 710021, China
ABSTRACT: An efficient and practical protocol for visible-light-induced
decarboxylative cyclization of 2-alkenylarylisocyanides with α-oxocarboxylic acids
has been developed, which afforded a broad range of 2-acylindoles in moderate to
good yields. The reaction proceeds through a cascade of acyl radical
addition/cyclization under irradiation of Ir3+ photoredox catalyst without external
oxidants, and features with simple operation, scalability, broad substrate scope and
good functional group tolerance.
R1
R1
[Ir(dF(CF3)ppy)2(dtb-bpy)]PF6
K2HPO4
O
O
OH
R
+
Ar
R
DMF, 12h, rt
20 W Blue LEDs
N
Ar
O
H
NC
yield up to 65%
30 examples
Simple operation and mild conditions
Scable
Broad substrate scope
Good functional group tolerance
INTRODUCTION
Functionalized indoles are widely found in pharmaceuticals and nature products.1 In
the past decades, considerable efforts have been devoted to the development of
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efficient methods for the synthesis of functionalized indoles.2 Traditionally, the indole
scaffolds are constructed by cyclization reactions such as Hemetsberger or
Cadogan−Sundberg indole synthesis, intramolecular Ullmann or Heck coupling
reactions.3 Although these cyclization reactions are effective, preparation of required
starting materials through multistep reactions dramatically limits their application.
Recently, transition-metal-catalyzed site-selective C-H bond activation of indoles has
become one of the most powerful and straightforward methods for the synthesis of
functionalized indoles,4 C2, C3 or C7-substituted indoles were synthesized by
arylation,5 cyanation,6 alkylation7 and alkenylation reactions.8 Among various
functionalized indoles, 2-acylindoles are extremely important structural components
that present in many natural products, pharmaceuticals, and biological active
compounds (Figure 1).9 Therefore, the development of mild and practical protocols
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for the synthesis of 2-acylindoles is of great value.
OH
O
N
O
OH
N
H
O
N
O
N
O
H
H
Calothrixin B
Uvarindole C
anticancer D-64131
Figure 1. Representative compounds containing 2-acylindole scaffolds
Generally, 2-acylindoles are synthesized through nucleophilic addition of
2-lithioindoles,10 palladium-catalyzed cross-couplings11 or cyclization reactions.12
Transition-metal-catalyzed, ligand directed C2-H acylation of indoles has been
reported in the past decades.13 However, these methods suffered from requirement of
prefunctionalization, harsh reaction conditions and excess oxidants. Aryl isocyanides
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have been widely applied for the construction of N-containing heterocycles involving
a radical cyclization process.14 In the cases of 2-alkenylarylisocyanides, Fukuyama
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and
coworkers
reported
AIBN/Bu3SnH-mediated
cyclization
of
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2-alkenylarylisocyanides to synthesize 2-stannyl-3-substituted indole compounds
(Scheme 1a).15a Chatani et al. developed a method for the synthesis of
2-boryl-3-substituted indoles via the copper(I)-catalyzed borylative cyclization of
2-alkenylphenyl isocyanides using diboronates (Scheme 1b).15c Jamison and
co-workers developed a copper-catalyzed method to prepare 2-aryl-3-substituted
indole derivatives using arylboronic acids (Scheme 1c).15d
Visible-light-induced photocatalysts have emerged as a powerful tool for the radical
transformations.16 The application of this strategy to the cyclization of
2-alkenylarylisocyanides with P-radicals was demonstrated by Yang and coworkers
recently, a variety of 2-phosphinoylindoles was obtained in good yields (Scheme
1d).17 On the other hand, α-oxocarboxylic acids have been recognized as a good acyl
radical precursor that could undergo decarboxylation under photocatalyst to generate
the acyl radicals.18 Inspired by these previous works, we envisioned that reaction of
acyl radicals generated form α-oxocarboxylic acids with 2-alkenylarylisocyanides
would be a versatile process for the synthesis of 2-acylindoles. Herein, we report
synthesis of 2-acylindoles through visible-light-induced decarboxylative cyclization
of 2-alkenylarylisocyanides with α-oxocarboxylic acids under mild conditions.
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Fukuyama's work:
COOR
COOR
R1
COOR
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7
8
HSnBu3, AIBN
Pd
R1-X
SnBu3
(a)
N
H
N
NC
H
9
Chatani's work:
COOR
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COOR
R1
COOR
B(Pin)
Cu(I)/PPh3
B2(Pin)2
Pd
R1-X
(b)
N
H
N
H
NC
Jamison's work
COOR
COOR
Ar
CuCl2, , KOt-Bu, 
Ar-B(OH)2
+
(c)
(d)
N
H
NC
Yang's work
Ar
Ar
O
O
Ru(II)
H
P
R2
R1
P
R1
+
R2
5W blue LED
N
H
NC
This work:
R
R
O
O
Photocatalyst
Visible light
OH
+
Ar
(e)
N
H
Ar
NC
O
Scheme 1 Cyclization of 2-alkenylarylisocyanides
RESULTS AND DISCUSSION
Initially, the reaction of 2-alkenylarylisocyanide 1a and 2-oxo-2-phenylacetic acid 2a
was first examined under 20 W blue LEDs. The desired product 3a was isolated in a
12% yield in the presence of PC-A ([Ir(dF(CF3)ppy)2(dtb-bpy)]PF6) and K2CO3 in
CH3CN (Table 1, entry 1). Encouraged by this result, we next screened different
solvents including DMA, DMF, DMSO, THF, DCM (Table 1, entries 2-7) and DMF
was proved to be the best solvent which provided the desired product 3a in a 55%
yield(Table 1, entry 4). Then bases (K3PO4, K2HPO4, Cs2CO3, KOAc, NaOAc,
DIPEA, Et3N) were screened (Table 1, entries 8-14). When K2HPO4 was used, the
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yield was improved to 61% (Table 1, entry 9). Photocatalysts were also essential to
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this
decarboxylative
cyclization.
PC-B
([Ir(dtb-bpy)(ppy)2]PF6),
PC-C
8
9
([Ir(dF(CF3)ppy)2(1,10-Phen)]PF6), PC-D Ir(ppy)3, PC-E (Ru(bpy)3Cl2) and PC-F
(Eosin Y) did not give better results, and the reaction did not take place in the absence
of photocatalyst (Table 1, entries 15-20). When the reaction was performed in dark,
the reaction did not take place (Table 1, entry 21). When the reaction was performed
in the absence of base, the yield decreased dramatically, which indicated that base
was also essential to this reaction (Table 1, entry 22).
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Table 1 Optimization of Reaction Conditionsa
CN
O
Photocatalyst
CN
O
OH
Base
+
Solvent, 12 h, r.t.
20 W Blue LED
N
NC
1a
O
H
2a
3a
Entry
Photocatalyst
PC-A
Base
Solvent
CH3CN
DMA
DMSO
DMF
Yieldb (%)
1
2
3
4
5
6
7
8
9
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K3PO4
12
50
49
55
32
41
NR
48
61
PC-A
PC-A
PC-A
PC-A
DCM
THF
PC-A
PC-A
MeOH
DMF
PC-A
PC-A
K2HPO4
DMF
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21c
22
PC-A
Cs2CO3
KOAc
DMF
44
16
PC-A
PC-A
PC-A
PC-A
PC-B
PC-C
PC-D
PC-E
PC-F
-
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
NaOAc
DIPEA
Et3N
21
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32
41
K2HPO4
K2HPO4
K2HPO4
K2HPO4
K2HPO4
K2HPO4
K2HPO4
-
17
41
20
NR
NR
NR
NR
21
PC-A
PC-A
a
Reaction conditions: 1a (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), catalyst (2.0 mol%)
and base (0.4 mmol, 2 equiv.) in solvent (2 mL), irradiated with 20 W blue LEDs for 12 h at room
temperature. b Isolated yields. NR = no reaction. c Reaction was conducted in dark.
With the optimized conditions in hand, we next evaluated the substrate scope with
respect to 2-alkenylarylisocyanides, and the results was summarized in Table 2. It was
found that the electronic effect had no obvious influence on this transformation. Both
electron-donating and electron–withdrawing groups on 2-alkenylarylisocyanide were
tolerated, affording the corresponding product 3b-3o in moderate to good yields.
Halogenes such as F, Cl, CF3 were also compatible. Unfortunately,
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dichloro-substituted isocyanide only gave product 3k in a low 27% yield. Notably,
2-alkenylarylisocyanide bearing synthetic valuable -CN could be smoothly converted
into the corresponding product 3n in 47% yield. The functional groups on the alkenyl
were finally checked. Both COOEt and CONMe2 were tolerated and afforded the
desired products 3o and 3p in 51%, 37% yields, respectively. The structure of 3o was
confirmed by X-ray crystallography (CCDC, No. 1977763).
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Table 2 Scope of 2-alkenylarylisocyanides
R2
R2
+
O
[Ir(dF(CF3)ppy)2(dtb-bpy)]PF6
K2HPO4
O
R1
OH
R1
DMF, 12 h, r.t.
20 W Blue LEDs
NC
N
O
H
2a
3
1
NC
NC
NC
NC
O
O
O
O
N
H
N
N
N
H
H
H
3e
, 48%
NC
3c
3d
, 65%
, 54%
3b
, 50%
NC
NC
NC
F
t-Bu
Cl
O
O
O
O
N
N
N
N
O
H
H
H
H
3g
, 51%
3f
, 52%
3h
, 44%
3i
, 47%
NC
NC
NC
NC
Cl
O
F3C
O
O
O
N
N
N
Cl
N
H
H
F3C
O
H
H
Cl
3k
, 27%
3j
, 49%
3m
, 46%
3l
, 43%
NC
EtO2C
N
NC
O
O
O
N
N
N
H
H
H
3n
3p
, 37%
, 47%
3o
, 51%
Reaction conditions: 1a (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), K2HPO4 (0.4mmol, 2.0
equiv.) and [Ir(dF(CF3)ppy)2(dtb-bpy)]PF6 (2.0 mol%) in DMF (2 mL) with 20W blue LEDs for
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12 h.
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The scope of α-oxocarboxylic acids was next explored. As shown in Table 3, various
acids bearing the electron-donating groups (e.g., CH3, C2H5, OCH3 and NMe2) could
successfully be converted to the corresponding products 4a-4i in 40-65% yields.
Furthermore, substituents at meta or para position of 2-oxo-2-phenylacetic acid did
not affect the efficiency of reactions. Acids with a fluorine also reacted with
isocyanide 1a to generate the corresponding products 4j and 4k. However,
ortho-fluoro-substituted acid gave the desired product 4j in a low yield. Pleasingly,
heterocyclic α-oxocarboxylic acid afforded the cyclization product 4l in a 38%
yield. Unfortunately, NO2-substituted 2-oxo-2-phenylacetic acid, alkyl substituted
(e.g., CH3 and t-Bu) α-oxocarboxylic acids, pivalic acid and benzoic acid failed to
give the desired product 4m-4q.
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Table 3 Scope of α-oxocarboxylic acids
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NC
[Ir(dF(CF3)ppy)2(dtb-bpy)]PF6
O
K2HPO4
O
CN
OH
+
R3
DMF, 12 h, r.t
20 W Blue LEDs
N
O
NC
1a
H
2
4
R3
O
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NC
NC
NC
NC
O
O
O
N
N
N
N
H
H
H
H
4a
4b,
4c
4d
, 61%
, 65%
55%
, 65%
NC
NC
NC
NC
O
O
O
O
N
N
H
N
H
N
H
H
O
N
O
4e
4f
4g
4h
, 40%
, 52%
, 51%
, 43%
NC
NC
NC
NC
O
O
O
O
F
N
N
N
H
N
H
H
H
S
F
4i
4j
4k
4I
, 41%
, 28%
, 53%
, 38%
Unsuccessful results
NC
NC
NC
NC
O
O
R
N
H
N
N
N
H
H
H
NO2
4n
4o
R = Me
4q
, 0%
4m
4p
, 0%
, 0%
t-Bu
Reaction condition: 1a (0.2 mmol, 1.0 equiv.), 2a (0.4 mmol, 2.0 equiv.), K2HPO4 (0.4 mmol, 2.0
equiv.) and [Ir(dF(CF3)ppy)2(dtb-bpy)]PF6 (2.0 mol%) in DMF (2 mL) with 20W blue LEDs for 12 h.
To highlight the synthetic utility of this reaction, a gram-scale experiment was
performed and product 3a was obtained in a 51% yield (Scheme 2a). Product 3a was
then subjected to the reduction reaction, and the corresponding product 5 was isolated
in a 75% yield (Scheme 2b). Moreover, the product 5o can be easily hydrolyzed and
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N-methylated in the presence of (MeO)2SO2 and NaOH, and the desired product 6
6
7
was obtained in 92% yield.[19]
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CN
CN
[Ir(dF(CF3)ppy)2(dtb-bpy)]PF6
K2HPO4
O
O
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11
12
13
14
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OH
+
N
(a)
DMF, 72 h, r.t.
20 W Blue LEDs
O
H
NC
(6.5 mmol, 1.00g)
1a
2a
3a
(0.86g, 51%)
(13.0 mmol, 1.95 g)
CN
O
CN
OH
NaBH4
N
EtOH, r.t., 15 min
N
H
(b)
H
3a
5,
75%
CO2Et
O
COOH
(MeO)2SO2
NaOH
O
N
H
N
acetone, reflux, 1 h
(c)
3o
6,
92%
Scheme 2 Scale-up experiment and transformations of product 3a, 3o
To gain insight of the reaction mechanism, the radical trapping experiments were
performed by adding TEMPO or BHT as the radical scavenger. When 2.0 equivalents
of TEMPO or BHT were added, the reaction did not take place, which suggested a
radical process might involve in this reaction. Furthermore, when using D2O as the
cosolvent, deuterated product 3a was obtained in a 45% yield, and 33% of deuteration
was detected at benzyl position. When DMF-d7 was used as the solvent, the
deuterated product [D]-3a was not detected. These results indicate that the proton of
benzyl position might come from the water existed in DMF (Scheme 3). The reaction
of potassium 2-oxo-2-phenylacetate 2a’ and 1a also works with a competitive yield of
54%, which demonstrates that the base could facilitate the elimination of CO2.
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CN
CN
+
O
[Ir(dF(CF3)ppy)2(dtb-bpy)]PF6
K2HPO4, 20W Blue LEDs
O
OH
N
DMF, 12 h, r.t.
TEMPO (2 equiv)
or
O
H
NC
1a
2a
3a
0%
BHT (2 equiv)
33%
D
CN
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CN
+
O
[Ir(dF(CF3)ppy)2(dtb-bpy)]PF6
K2HPO4, 20W Blue LEDs
O
OH
N
DMF, 12 h, r.t.
D2O (0.2 mL)
O
H
NC
1a
2a
3a-d
45%
0 %
D
CN
CN
+
O
[Ir(dF(CF3)ppy)2(dtb-bpy)]PF6
K2HPO4, 20W Blue LEDs
O
OH
N
d7-DMF, 12 h, r.t.
O
H
NC
1a
2a
3a
50%
CN
CN
+
O
O
[Ir(dF(CF3)ppy)2(dtb-bpy)]PF6
20W Blue LEDs, r.t.
K
O
N
H
O
NC
1a
2a'
3a
54%
Scheme 3 Mechanistic Studies
On the basis of our own studies and the previous reports, a plausible catalytic cycle
was proposed in Scheme 4. First, the irritation of the photocatalyst Ir3+ with visible
light affords the excited-state Ir3+*. The potassium 2-oxo-2-phenylacetate 2a’
generated from phenylglyoxylic acid 2a was oxidized by excited-state Ir3+* affords
benzoyl radical I, along with the formation of Ir2+. Then the benzoyl radical I was
trapped by 2-alkenylarylisocyanide (1a) to produce A, which was followed by
5-exo-trig cyclization to afford benzyl radical B. The reduction of benzyl radical B
with Ir2+ specie through a SET pathway produces benzyl anion C and Ir3+ specie was
formed at the same time to fulfill1g the catalytic cycle. Finally, benzyl anion C
underwent protonation and isomerization to yield the desired product 3a.
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*Ir3+
O
CN
O
COO
K
K2HPO4
2a
N
Ph
2a'
H
3a
CO2
Ir3+
+H+
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O
tautomerization
CN
O
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Ir2+
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Ph
C
CN
CN
O
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N
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N
C
A
B
Ph
Scheme 4 Proposed Mechanism
CONCLUSION
In summary, we have developed a mild approach for the synthesis of 2-acylindoles
via visible-light-induced decarboxylative cyclization of 2-alkenylarylisocyanides with
α-oxocarboxylic acids. This reaction is performed under air at room temperature,
which features simple operation, scalability, broad substrate scope and good
functional group tolerance. The primary mechanism investigations suggested a radical
process in this reaction.
EXPERIMENTAL SECTION
General Information. All reagents and all solvents were used directly as obtained
1
13
commercially unless otherwise noted. H and C NMR spectra were recorded on a
Bruker AM 400 spectrometer (operating at 400 and 101 MHz, respectively) in CDCl3
(with tetramethylsilane as internal standard, δ = 7.26 ppm for 1H NMR; 77.16 ppm for
13C NMR), DMSO-d6 (with tetramethylsilane as internal standard, δ = 2.50 ppm for
1H
NMR;
39.52
ppm
for
13C
NMR).
HPLC/MS analysis was carried out with gradient elution (5% CH3CN to 100% CH3C
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N) on an Agilent 1200 RRLC with a photodiode array UV detector and an Agilent 62
24 TOF mass spectrometer (also used to produce high resolution mass spectra). The
infrared (IR) spectra were acquired as thin films using a universal ATR sampling
accessory on a Bruker Vertex 80 FT-IR spectrometer and the absorption frequencies
are reported in cm-1 using KBr plates. Melting points were determined on a Stanford
Research Systems OptiMelt apparatus. 20W blue LEDs (LDL04-20W,  = 455 nm)
were purchased from Qianfang Lighting Technology Co., Ltd. The material of the
irradiation vessel is borosilicate glass and the distance between the light source to the
irradiation vessel is about 3 cm. α-keto acids[20], arylisocyanides 1b-1p[21], and
photocatalyst A-C[22] were synthesized according the reported literature. The
arylisocyanides 1a[23], 1o[24], 1p[23], 6[19] and all the α-keto acids[25] are compounds
known.
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General Procedure for the Synthesis of Arylisocyanides. Aniline (2.5 mmol, 1.0
equiv), palladium acetate (10 mol%), tri-orthotolyl phosphine (20 mol%) were added
to a screw-cap pressure vial containing a stir bar. The vial was equipped with a rubber
septum and the vessel was evacuated and back-filled with argon three times. DMF
(degassed, 5mL), triethylamine (3.0 equiv) and alkenyl coupling partner (1.2 equiv)
were added through a needle. The pressure vial was sealed and stirred at 130 ºC for 8
hours. After cooling to room temperature, the mixture was quenched with saturated
aqueous solution of NaCl (30 mL) and extracted with ethyl acetate (3×30 mL), the
combined organic layer was dried over Na2SO4. The filtrate was concentrated in
vacuo and the resulting mixture was purified by flash column chromatography on
silica gel to afford the corresponding 2-alkenylarylaniline.
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Acetic anhydride (1.5 equiv) and formic acid (1.6 equiv) were stirred at 50 ºC in
a sealed tube for 1.5 hours. The resulting anhydride was cooled to room temperature
and was added dropwise over 10 min to a stirred solution of 2-alkenyl aniline (2.0
mmol, 1.0 equiv) in THF (8mL) at 0 ºC. The solution was warmed to room
temperature and stirred for 1 hour. A saturated aqueous solution of sodium
bicarbonate (30 mL) was added slowly to the mixture and then the organic layer was
extracted with ethyl acetate (3×30 mL). The combined organic layer was dried over
Na2SO4, filtered and concentrated in vacuo. The crude product was used directly in
the next step without further purification.
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A solution (12 mL) of the crude formamide (2.0 mmol, 1.0 equiv) and
triethylamine (3.0 equiv) in THF was cooled to 0 ºC and phosphoryl chloride (1.5
equiv) was added dropwise while maintaining the reaction temperature at 0 ºC. After
reacted for an additional 1 hour at 0 ºC, the mixture was warmed to room temperature
and quenched with saturated aqueous solution of sodium bicarbonate (30 mL). The
mixture was extracted with ethyl acetate (3×30 mL) and the combined organic layer
was dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was
purified via flash column chromatography on silica gel to afford the corresponding
arylisocyanides.
General Procedure for the Synthesis of Indole Products. To a 10 mL vial equipped
with a magnetic stirrer bar, arylisocyanides 1 (0.2 mmol), α-keto acids 2 (0.4 mmol),
[Ir(dF(CF3)ppy)2(dtb-bpy)]PF6 (2 mol%), K2HPO4 (0.4 mmol) and DMF (2 mL) were
added in sequence. Two 20W blue LEDs was placed at a distance of about 3cm from
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the reaction vessel. After the reaction was complete (as monitored by TLC), the
mixture was quenched with H2O (10 mL) and extracted with ethyl acetate (3×10 mL),
the combined organic layer was dried over Na2SO4, filtered and concentrated in
vacuo. The crude residue was purified via flash column chromatography on silica gel
to afford the corresponding indole products.
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General Procedure for Gram-scale Experiment. To a 250 mL round bottom flask
equipped with a magnetic stirrer bar, arylisocyanides 1a (6.5 mmol, 1.00 g), α-keto
acids 2a (13.00 mmol, 1.95 g), [Ir(dF(CF3)ppy)2(dtb-bpy)]PF6 (0.065 mmol, 75 mg),
K2HPO4 (13.00 mmol, 2.26 g) and DMF (65 mL) were added in sequence. Two 20W
blue LEDs was placed at a distance of about 3cm from the reaction vessel. After the
reaction was complete (as monitored by TLC, 3 days), the mixture was quenched with
H2O (100 mL) and extracted with ethyl acetate (3×150 mL), the combined organic
layer was dried over Na2SO4, filtered and concentrated in vacuo. The crude residue
was purified via flash column chromatography on silica gel to afford the
corresponding indole products (0.86 g, 51%).
3-(2-Isocyano-5-methylphenyl)acrylonitrile (1b). This product was obtained as a
yellow solid (238 mg, 71% yield). Eluent: petroleum ether/ethyl acetate 6:1 (v/v).
m.p.: 138-139℃; 1H NMR (400 MHz, DMSO-d6) δ 7.78 (s, 1H), 7.68 (d, J = 16.6 Hz,
1H), 7.57 (d, J = 8.1 Hz, 1H), 7.41 (d, J = 8.1 Hz, 1H), 6.66 (d, J = 16.6 Hz, 1H), 2.37
(s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 168.1, 143.6, 140.5, 132.7, 129.3,
127.5, 127.0, 122.3, 118.1, 101.3, 20.8. IR (neat): 2216, 2117, 1619, 1482 cm-1;
HRMS (ESI) calculated for C11H8N2 [M+H]+: 169.0760, found: 169.0762.
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3-(2-Isocyano-4-methylphenyl)acrylonitrile (1c). This product was obtained as a
yellow solid (229 mg, 68% yield). Eluent: petroleum ether/ethyl acetate 6:1 (v/v).
m.p.: 137-138℃; 1H NMR (400 MHz, DMSO-d6) δ 7.82 (d, J = 8.1 Hz, 1H), 7.63 (d,
J = 16.6 Hz, 1H), 7.50 (s, 1H), 7.40 (d, J = 8.1 Hz, 1H), 6.62 (d, J = 16.6 Hz, 1H),
2.35 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 168.3, 143.3, 143.0, 131.1,
127.8, 126.8, 126.6, 124.5, 118.2, 100.4, 20.5. IR (neat): 2210, 2113, 1604, 1496
cm-1; HRMS (ESI) calculated for C11H8N2 [M+H]+: 169.0760, found: 169.0763.
3-(2-Isocyano-3-methylphenyl)acrylonitrile (1d). This product was obtained as a
yellow solid (161 mg, 48% yield). Eluent: petroleum ether/ethyl acetate 6:1 (v/v).
m.p.: 118-119℃; 1H NMR (400 MHz, DMSO-d6) δ 7.75 (d, J = 7.7 Hz, 1H), 7.69 (d,
J = 16.6 Hz, 1H), 7.53 – 7.45 (m, 2H), 6.65 (d, J = 16.6 Hz, 1H), 2.38 (s, 3H).
13C{1H} NMR (101 MHz, DMSO-d6) δ 170.9, 143.9, 135.7, 132.9, 129.6, 129.6,
124.6, 124.2, 118.1, 101.4, 18.4. IR (neat): 2217, 2113, 1619, 1447 cm-1; HRMS
(ESI) calculated for C11H8N2 [M+H]+: 169.0760, found: 169.0762.
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3-(2-Isocyano-3,5-dimethylphenyl)acrylonitrile (1e). This product was obtained as
a white solid (273 mg, 75% yield). Eluent: petroleum ether/ethyl acetate 6:1 (v/v).
m.p.: 134-135℃; 1H NMR (400 MHz, DMSO-d6) δ 7.64 – 7.57 (m, 2H), 7.33 (s, 1H),
6.60 (d, J = 16.4 Hz, 1H), 2.32 (s, 6H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 170.3,
144.0, 139.6, 135.4, 133.6, 129.3, 124.5, 122.4, 118.2, 101.1, 20.7, 18.3. IR (neat):
2216, 2109, 1610, 1461 cm-1; HRMS (ESI) calculated for C12H10N2 [M+H]+:
183.0917, found: 183.0913.
3-(2-Isocyano-4-methoxyphenyl)acrylonitrile (1f). This product was obtained as a
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yellow solid (250 mg, 68% yield). Eluent: petroleum ether/ethyl acetate 6:1 (v/v).
m.p.: 131-132℃; 1H NMR (400 MHz, DMSO-d6) δ 7.89 (d, J = 8.9 Hz, 1H), 7.60 (d,
J = 16.6 Hz, 1H), 7.31 (s, 1H), 7.17 (d, J = 8.8 Hz, 1H), 6.54 (d, J = 16.6 Hz, 1H),
3.85 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 168.5, 161.8, 143.0, 128.1,
126.0, 122.0, 118.5, 117.3, 112.3, 98.5, 56.2. IR (neat): 2210, 2121, 1602, 1453 cm-1;
HRMS (ESI) calculated for C11H8N2O [M+H]+: 185.0709, found: 185.0706.
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3-(5-(Tert-butyl)-2-isocyanophenyl)acrylonitrile (1g). This product was obtained as
a green solid (294 mg, 70% yield). Eluent: petroleum ether/ethyl acetate 6:1 (v/v).
1
m.p.: 94-95℃; H NMR (400 MHz, DMSO-d6) δ 7.89 (s, 1H), 7.67 (d, J = 16.6 Hz,
13
1H), 7.59 (s, 2H), 6.80 (d, J = 16.6 Hz, 1H), 1.29 (s, 9H). C{1H} NMR (101 MHz,
DMSO-d6) δ 168.2, 153.3, 143.7, 129.2, 129.1, 127.3, 123.7, 122.3, 118.2, 101.5,
35.0, 30.6. IR (neat): 2218, 2117, 1612, 1478 cm-1; HRMS (ESI) calculated for
C14H14N2 [M+H]+: 211.1230, found: 211.1229.
3-(5-Fluoro-2-isocyanophenyl)acrylonitrile (1h). This product was obtained as a
yellow solid (210 mg, 61% yield). Eluent: petroleum ether/ethyl acetate 6:1 (v/v).
1
m.p.: 128-129℃; H NMR (400 MHz, DMSO-d6) δ 7.89 (d, J = 9.5 Hz, 1H), 7.84 –
7.74 (m, 1H), 7.69 (d, J = 16.5 Hz, 1H), 7.54 – 7.44 (m, 1H), 6.76 (d, J = 16.5 Hz,
1H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 168.8, 161.8 (d, J = 250.5 Hz), 142.6 (d,
J = 2.0 Hz), 132.2 (d, J = 9.1 Hz), 130.3 (d, J = 9.1 Hz), 121.2, 119.3 (d, J = 24.2 Hz),
117.7, 113.6 (d, J = 26.3 Hz), 103.1. 19F NMR (377 MHz, CDCl3) δ -106.8. IR (neat):
2225, 2121, 1609, 1480 cm-1; HRMS (ESI) calculated for C10H5FN2 [M+Na]+:
195.0329, found: 195.0328.
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3-(5-Chloro-2-isocyanophenyl)acrylonitrile (1i). This product was obtained as a
yellow solid (244 mg, 65% yield). Eluent: petroleum ether/ethyl acetate 6:1 (v/v).
m.p.: 132-133℃; 1H NMR (400 MHz, DMSO-d6) δ 8.09 (s, 1H), 7.75 (d, J = 8.5 Hz,
1H), 7.72 – 7.63 (m, 2H), 6.80 (d, J = 16.5 Hz, 1H). 13C{1H} NMR (101 MHz,
DMSO-d6) δ 169.8, 142.4, 135.0, 131.8, 131.5, 129.5, 126.7, 123.4, 117.8, 103.2. IR
(neat): 2219, 2117, 1622, 1472 cm-1; HRMS (ESI) calculated for C10H5ClN2 [M+H]+:
189.0214, found: 189.0226.
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3-(4-Chloro-2-isocyanophenyl)acrylonitrile (1j). This product was obtained as a
yellow solid (263 mg, 70% yield). Eluent: petroleum ether/ethyl acetate 6:1 (v/v).
1
m.p.: 161-162℃; H NMR (400 MHz, DMSO-d6) δ 7.99 – 7.84 (m, 2H), 7.69 – 7.63
13
(m, 2H), 6.71 (d, J = 16.6 Hz, 1H). C{1H} NMR (101 MHz, DMSO-d6) δ 170.0,
142.5, 136.1, 130.6, 128.6, 128.3, 127.5, 125.5, 117.9, 102.2. IR (neat): 2215, 2120,
1622, 1478 cm-1; HRMS (ESI) calculated for C10H5ClN2 [M+H]+: 189.0214, found:
189.0222.
3-(3,5-Dichloro-2-isocyanophenyl)acrylonitrile (1k). This product was obtained as
a green solid (320 mg, 72% yield). Eluent: petroleum ether/ethyl acetate 6:1 (v/v).
m.p.: 135-136℃; 1H NMR (400 MHz, DMSO-d6) δ 8.10 – 8.02 (m, 2H), 7.67 (d, J =
16.4 Hz, 1H), 6.82 (d, J = 16.5 Hz, 1H). 13C{1H} NMR (101 MHz, DMSO-d6) δ
174.6, 142.1, 135.2, 133.1, 131.8, 131.3, 125.6, 122.3, 117.5, 104.4. IR (neat): 2222,
2113, 1622, 1461 cm-1; HRMS (ESI) calculated for C10H4Cl2N2 [M+H]+: 222.9824,
found: 222.9827.
3-(2-Isocyano-5-(trifluoromethyl)phenyl)acrylonitrile (1l). This product was
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obtained as a yellow solid (222 mg, 50% yield). Eluent: petroleum ether/ethyl acetate
6
7
1
6:1 (v/v). m.p.: 118-119℃; H NMR (400 MHz, DMSO-d6) δ 8.34 (s, 1H), 7.97 –
8
9
13
7.90 (m, 2H), 7.73 (d, J = 16.6 Hz, 1H), 6.92 (d, J = 16.6 Hz, 1H). C{1H} NMR
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(101 MHz, DMSO-d6) δ 171.2, 142.3, 130.8, 130.4 (q, J = 33.3 Hz), 129.0, 128.6 (q,
J = 4.0 Hz), 127.5, 124.2 (q, J = 4.0 Hz), 123.1 (q, J = 273.7 Hz), 117.7, 103.8. 19F
NMR (377 MHz, CDCl3) δ -63.1. IR (neat): 2219, 2119, 1612, 1482 cm-1; HRMS
(ESI) calculated for C11H5F3N2 [M+Na]+: 245.0297, found: 245.0305.
3-(2-Isocyano-4-(trifluoromethyl)phenyl)acrylonitrile (1m). This product was
obtained as a yellow solid (235 mg, 53% yield). Eluent: petroleum ether/ethyl acetate
6:1 (v/v). m.p.: 118-119℃; 1H NMR (400 MHz, DMSO-d6) δ 8.20 (s, 1H), 8.14 (d, J
= 8.3 Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 16.6 Hz, 1H), 6.84 (d, J = 16.6
13
Hz, 1H). C{1H} NMR (101 MHz, DMSO-d6) δ 170.4, 142.4, 133.5, 131.8 (q, J =
33.3 Hz), 128.2, 126.9 (q, J = 4.0 Hz), 125.0 (q, J = 4.0 Hz), 122.9 (q, J = 273.7 Hz),
19
117.6, 104.4 (one carbon missing due to overlap). F NMR (377 MHz, CDCl3) δ
-63.3. IR (neat): 2221, 2120, 1620 cm-1; HRMS (ESI) calculated for C11H5F3N2
[M+Na]+: 245.0297, found: 245.0296.
3-(2-Cyanovinyl)-4-isocyanobenzonitrile (1n). This product was obtained as a
yellow solid (100 mg, 28% yield). Eluent: petroleum ether/ethyl acetate 4:1 (v/v).
m.p.: 147-148℃; 1H NMR (400 MHz, DMSO-d6) δ 8.51 (s, 1H), 8.09 (d, J = 8.3 Hz,
1H), 7.92 (d, J = 8.3 Hz, 1H), 7.73 (d, J = 16.5 Hz, 1H), 6.82 (d, J = 16.5 Hz, 1H).
13C{1H} NMR (101 MHz, DMSO-d6) δ 172.0, 142.1, 135.2, 131.3, 130.9, 128.9,
127.6, 117.6, 117.2, 113.1, 103.7. IR (neat): 2233, 2222, 2123, 1484 cm-1; HRMS
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(ESI) calculated for C11H5N3 [M+H]+: 180.0556, found: 180.0559.
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2-(2-Benzoyl-1H-indol-3-yl)acetonitrile (3a). This product was obtained as a yellow
solid (31.7 mg, 61% yield). Eluent: petroleum ether/ethyl acetate 3:1 (v/v). m.p.:
154-155℃; 1H NMR (400 MHz, DMSO-d6) δ 11.90 (s, 1H), 7.87 (d, J = 8.1 Hz, 1H),
7.83 (d, J = 7.7 Hz, 2H), 7.77 – 7.69 (m, 1H), 7.66 – 7.58 (m, 2H), 7.52 (d, J = 8.3 Hz,
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1H), 7.37 (t, J = 7.6 Hz, 1H), 7.21 (t, J = 7.5 Hz, 1H), 4.21 (s, 2H). C{1H} NMR
(101 MHz, DMSO-d6) δ 188.0, 138.1, 136.5, 132.8, 131.4, 129.1, 128.8, 126.3, 125.8,
120.8, 120.2, 118.6, 113.2, 111.2, 13.5. IR (neat): 3325, 2253, 1633, 1534, 1442 cm-1;
HRMS (ESI) calculated for C17H12N2O [M+H]+: 261.1022, found: 261.1023.
2-(2-Benzoyl-5-methyl-1H-indol-3-yl)acetonitrile (3b). This product was obtained
as a yellow solid (27.4 mg, 50% yield). Eluent: petroleum ether/ethyl acetate 3:1 (v/v).
m.p.: 159-160℃; 1H NMR (400 MHz, DMSO-d6) δ 11.77 (s, 1H), 7.81 (d, J = 7.6 Hz,
2H), 7.74 – 7.79 (m, 1H), 7.66 – 7.56 (m, 3H), 7.41 (d, J = 8.4 Hz, 1H), 7.21 (d, J =
8.5 Hz, 1H), 4.16 (s, 2H), 2.43 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 187.9,
138.2, 135.0, 132.7, 131.4, 129.6, 129.1, 128.8, 127.9, 126.6, 119.1, 118.6, 113.0,
110.7, 21.3, 13.4. IR (neat): 3323, 2251, 1632, 1534 cm-1; HRMS (ESI) calculated for
C18H14N2O [M+H]+: 275.1179, found: 275.1175.
2-(2-Benzoyl-6-methyl-1H-indol-3-yl)acetonitrile (3c). This product was obtained
as a yellow solid (35.6 mg, 65%). Eluent: petroleum ether/ethyl acetate 3:1 (v/v). m.p.:
121-122℃; 1H NMR (400 MHz, DMSO-d6) δ 11.74 (s, 1H), 7.81 (d, J = 7.8 Hz, 2H),
7.78 – 7.69 (m, 2H), 7.64 – 7.59 (m, 2H), 7.29 (s, 1H), 7.05 (d, J = 8.3 Hz, 1H), 4.16
(s, 2H), 2.44 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 187.8, 138.3, 137.0,
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135.7, 132.6, 131.0, 129.1, 128.8, 124.4, 122.9, 119.9, 118.6, 112.5, 111.4, 21.7, 13.6;
IR (neat): 3325, 2252, 1630, 1532 cm-1; HRMS (ESI) calculated for C18H14N2O
[M+H]+: 275.1179, found: 275.1177.
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2-(2-Benzoyl-7-methyl-1H-indol-3-yl)acetonitrile (3d). This product was obtained
as a white solid (29.6 mg, 54% yield). Eluent: petroleum ether/ethyl acetate 3:1 (v/v).
m.p.: 202-203℃; 1H NMR (400 MHz, DMSO-d6) δ 11.77 (s, 1H), 7.85 (d, J = 7.7 Hz,
2H), 7.76 – 7.70 (m, 1H), 7.67 (d, J = 7.8 Hz, 1H), 7.64 – 7.58 (m, 2H), 7.20 – 7.08
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(m, 2H), 4.08 (s, 2H), 2.52 (s, 3H); C{1H} NMR (101 MHz, DMSO-d6) δ 188.0,
138.2, 136.1, 133.0, 132.1, 129.4, 128.8, 126.2, 126.0, 122.7, 121.0, 118.6, 117.6,
111.3, 17.0, 13.6. IR (neat): 3317, 2250, 1626, 1535 cm-1; HRMS (ESI) calculated for
C18H14N2O [M+H]+: 275.1179, found: 275.1176.
2-(2-Benzoyl-5,7-dimethyl-1H-indol-3-yl)acetonitrile (3e). This product was
obtained as a yellow solid (27.6 mg, 48% yield). Eluent: petroleum ether/ethyl acetate
3:1 (v/v). m.p.: 175-176℃; 1H NMR (400 MHz, DMSO-d6) δ 11.66 (s, 1H), 7.83 (d, J
= 7.4 Hz, 2H), 7.76 – 7.68 (m, 1H), 7.65 – 7.57 (m, 2H), 7.43 (s, 1H), 7.01 (s, 1H),
4.04 (s, 2H), 2.48 (s, 3H), 2.40 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 188.0,
138.3, 134.7, 132.9, 132.1, 129.8, 129.4, 128.8, 128.2, 126.5, 122.4, 118.6, 116.6,
110.8, 21.2, 16.9, 13.5. IR (neat): 3309, 2251, 1627, 1536 cm-1; HRMS (ESI)
calculated for C19H16N2O [M+H]+: 289.1335, found: 289.1336.
2-(2-Benzoyl-6-methoxy-1H-indol-3-yl)acetonitrile (3f). This product was obtained
as a yellow solid (30.2 mg, 52% yield). Eluent: petroleum ether/ethyl acetate 3:1
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(v/v). m.p.: 121-122℃; H NMR (400 MHz, DMSO-d6) δ 11.70 (s, 1H), 7.83 – 7.73
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(m, 3H), 7.73 – 7.67 (m, 1H), 7.65 – 7.57 (m, 2H), 6.94 (s, 1H), 6.87 (d, J = 8.9 Hz,
1H), 4.17 (s, 2H), 3.81 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 187.2, 158.9,
138.5, 137.9, 132.4, 130.5, 128.9, 128.8, 121.2, 120.9, 118.6, 112.8, 112.2, 94.2, 55.2,
13.6. IR (neat): 3325, 2252, 1627, 1529 cm-1; HRMS (ESI) calculated for C18H14N2O2
[M+H]+: 291.1128, found: 291.1129.
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2-(2-Benzoyl-5-(tert-butyl)-1H-indol-3-yl)acetonitrile (3g). This product was
obtained as a yellow solid (32.2 mg, 51% yield). Eluent: petroleum ether/ethyl acetate
3:1 (v/v). m.p.: 55-56℃; 1H NMR (400 MHz, DMSO-d6) δ 11.77 (s, 1H), 7.85 – 7.79
(m, 3H), 7.74 – 7.68 (m, 1H), 7.65 – 7.58 (m, 2H), 7.51 – 7.44 (m, 2H), 4.23 (s, 2H),
1.37 (s, 9H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 187.9, 143.3, 138.3, 134.9,
132.6, 131.5, 129.1, 128.8, 126.1, 124.7, 118.7, 115.2, 112.9, 111.4, 34.6, 31.5, 13.5.
IR (neat): 3328, 2253, 1633, 1535 cm-1; HRMS (ESI) calculated for C21H20N2O
[M+H]+: 317.1648, found: 317.1648.
2-(2-Benzoyl-5-fluoro-1H-indol-3-yl)acetonitrile (3h). This product was obtained as
a yellow solid (24.5 mg, 44% yield). Eluent: petroleum ether/ethyl acetate 3:1 (v/v).
m.p.: 176-178℃; 1H NMR (400 MHz, DMSO-d6) δ 12.00 (s, 1H), 7.83 (d, J = 7.5 Hz,
2H), 7.77 – 7.59 (m, 4H), 7.57 – 7.49 (m, 1H), 7.29 – 7.20 (m, 1H), 4.20 (s, 2H).
13C{1H} NMR (101 MHz, DMSO-d6) δ 187.8, 157.5 (d, J = 236.3 Hz), 137.9, 133.1,
132.9, 129.2, 128.9, 126.5 (d, J = 10.1 Hz), 118.5, 114.9 (d, J = 26.3 Hz), 114.8 (d, J
= 10.1 Hz), 111.2 (d, J = 6.1 Hz), 104.4 (d, J = 24.2 Hz), 13.5 (one carbon missing
due to overlap). 19F NMR (377 MHz, DMSO-d6) δ -20.6. IR (neat): 3317, 2253, 1636,
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1533 cm-1; HRMS (ESI) calculated for C17H11FN2O [M+Na]+: 301.0748, found:
301.0749.
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2-(2-Benzoyl-5-chloro-1H-indol-3-yl)acetonitrile (3i). This product was obtained as
a white solid (27.6 mg, 47% yield). Eluent: petroleum ether/ethyl acetate 3:1 (v/v).
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m.p.: 181-182℃; H NMR (400 MHz, DMSO-d6) δ 12.09 (s, 1H), 7.99 (s, 1H), 7.83
(d, J = 7.4 Hz, 2H), 7.78 – 7.70 (m, 1H), 7.66 – 7.59 (m, 2H), 7.53 (d, J = 8.8 Hz, 1H),
7.37 (d, J = 8.8 Hz, 1H), 4.21 (s, 2H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 187.9,
137.8, 134.8, 133.0, 132.7, 129.2, 128.9, 127.3, 125.9, 125.3, 119.4, 118.5, 115.0,
110.7, 13.4. IR (neat): 3317, 2253, 1637, 1532 cm-1; HRMS (ESI) calculated for
C17H11ClN2O [M+H]+: 295.0633, found: 295.0633.
2-(2-Benzoyl-6-chloro-1H-indol-3-yl)acetonitrile (3j). This product was obtained as
a yellow solid (28.8 mg, 49% yield). Eluent: petroleum ether/ethyl acetate 3:1 (v/v).
m.p.: 198-199℃; 1H NMR (400 MHz, DMSO-d6) δ 12.03 (s, 1H), 7.91 (d, J = 8.7 Hz,
1H), 7.86 – 7.80 (m, 2H), 7.77 – 7.70 (m, 1H), 7.66 – 7.59 (m, 2H), 7.54 (s, 1H), 7.24
(d, J = 8.7 Hz, 1H), 4.21 (s, 2H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 187.8, 137.9,
136.6, 132.9, 132.3, 130.4, 129.2, 128.9, 125.1, 121.9, 121.4, 118.4, 112.6, 111.4,
13.5. IR (neat): 3317, 2253, 1634, 1531 cm-1; HRMS (ESI) calculated for
C17H11ClN2O [M+H]+: 295.0633, found: 295.0629.
2-(2-Benzoyl-5,7-dichloro-1H-indol-3-yl)acetonitrile (3k). This product was
obtained as a yellow solid (17.7 mg, 27% yield). Eluent: petroleum ether/ethyl acetate
3:1 (v/v). m.p.: 70-71℃; 1H NMR (400 MHz, DMSO-d6) δ 12.49 (s, 1H), 8.00 (s, 1H),
7.87 – 7.81 (m, 2H), 7.78 – 7.70 (m, 1H), 7.65 – 7.55 (m, 3H), 4.14 (s, 2H). 13C{1H}
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NMR (101 MHz, DMSO-d6) δ 187.9, 137.5, 134.8, 133.6, 132.0, 129.7, 128.9, 128.4,
125.2, 124.6, 118.6, 118.3, 111.0, 13.3 (one carbon missing due to overlap). IR (neat):
3278, 2204, 1644, 1568 cm-1; HRMS (ESI) calculated for C17H10Cl2N2O [M+H]+:
329.0243, found: 329.0244.
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2-(2-Benzoyl-5-(trifluoromethyl)-1H-indol-3-yl)acetonitrile (3l). This product was
obtained as a yellow solid (28.2 mg, 43% yield). Eluent: petroleum ether/ethyl acetate
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3:1 (v/v). m.p.: 149-150℃; H NMR (400 MHz, CDCl3) δ 9.30 (s, 1H), 8.11 (s, 1H),
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7.83 – 7.77 (m, 2H), 7.69 – 7.52 (m, 5H), 3.94 (s, 2H). C{1H} NMR (101 MHz,
CDCl3) δ 188.2, 138.0, 137.3, 133.6, 133.1, 129.4, 129.0, 126.4, 124.7 (q, J = 272.7
Hz), 124.4 (q, J = 33.3 Hz), 123.6 (q, J = 3.0 Hz), 118.6 (q, J = 4.0 Hz), 117.1, 113.3,
112.2, 14.5. 19F NMR (377 MHz, CDCl3) δ -60.9. IR (neat): 3312, 2256, 1640, 1541
cm-1; HRMS (ESI) calculated for C18H11F3N2O [M+Na]+: 351.0716, found: 351.0725.
2-(2-Benzoyl-6-(trifluoromethyl)-1H-indol-3-yl)acetonitrile (3m). This product
was obtained as a white solid (30.1 mg, 46% yield). Eluent: petroleum ether/ethyl
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acetate 3:1 (v/v). m.p.: 146-147℃; H NMR (400 MHz, CDCl3) δ 9.27 (s, 1H), 7.94
(d, J = 8.5 Hz, 1H), 7.84 – 7.78 (m, 2H), 7.75 (s, 1H), 7.71 – 7.64 (m, 1H), 7.61 –
7.54 (m, 2H), 7.48 (d, J = 8.5 Hz, 1H), 3.96 (s, 2H). 13C{1H} NMR (101 MHz, CDCl3)
δ 188.2, 138.0, 135.1, 133.6, 129.5, 129.2, 129.1, 129.0 (q, J = 31.3 Hz), 124.6 (q, J =
272.7 Hz), 121.6, 118.4 (q, J = 3.0 Hz), 117.2, 111.3, 110.4 (q, J = 4.0 Hz), 14.5 (one
carbon missing due to overlap). 19F NMR (377 MHz, CDCl3) δ -61.6. IR (neat): 3313,
2255, 1640, 1513 cm-1; HRMS (ESI) calculated for C18H11F3N2O [M+Na]+: 351.0716,
found: 351.0722.
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2-Benzoyl-3-(cyanomethyl)-1H-indole-5-carbonitrile (3n). This product was
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1:1 (v/v). m.p.: 226-227℃; H NMR (400 MHz, DMSO-d6) δ 12.45 (s, 1H), 8.53 (s,
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1H), 7.87 – 7.81 (m, 2H), 7.79 – 7.72 (m, 1H), 7.72 – 7.60 (m, 4H), 4.24 (s, 2H).
13C{1H} NMR (101 MHz, DMSO-d6) δ 187.8, 137.6, 137.5, 133.6, 133.3, 129.3,
129.0, 127.5, 126.7, 126.0, 120.0, 118.3, 114.6, 111.8, 102.9, 13.4. IR (neat): 3299,
2223, 1645, 1538 cm-1; HRMS (ESI) calculated for C18H11N3O [M+H]+: 286.0975,
found: 286.0977.
Ethyl 2-(2-benzoyl-1H-indol-3-yl)acetate (3o). This product was obtained as a
yellow solid (31.3 mg, 51% yield). Eluent: petroleum ether/ethyl acetate 6:1 (v/v).
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m.p.: 138-139℃; H NMR (400 MHz, CDCl3) δ 8.97 (s, 1H), 7.82 – 7.74 (m, 2H),
7.64 (d, J = 8.2 Hz, 1H), 7.62 – 7.54 (m, 1H), 7.52 – 7.44 (m, 2H), 7.42 – 7.30 (m,
2H), 7.19 – 7.13 (m, 1H), 4.09 (q, J = 7.1 Hz, 2H), 3.81 (s, 2H), 1.20 (t, J = 7.1 Hz,
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3H). C{1H} NMR (101 MHz, CDCl3) δ 189.0, 171.1, 139.2, 136.6, 132.5, 132.3,
129.0, 128.8, 128.5, 126.7, 121.3, 121.1, 116.5, 112.3, 61.1, 31.5, 14.4. IR (neat):
3345, 1728, 1631, 1534, 1443 cm-1; HRMS (ESI) calculated for C19H17NO3 [M+H]+:
308.1281, found 308.1290.
2-(2-Benzoyl-1H-indol-3-yl)-N,N-dimethylacetamide (3p). This product was
obtained as a yellow solid (22.6 mg, 37% yield). Eluent: petroleum ether/ethyl acetate
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6:1 (v/v). m.p.: 159-160℃; H NMR (400 MHz, CDCl3) δ 9.01 (s, 1H), 7.79 – 7.70
(m, 3H), 7.62 – 7.54 (m, 1H), 7.52 – 7.43 (m, 2H), 7.36 – 7.27 (m, 2H), 7.17 – 7.09
(m, 1H), 3.86 (s, 2H), 2.90 (s, 3H), 2.83 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
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189.0, 170.4, 139.6, 136.8, 132.2, 131.8, 129.0, 128.9, 128.7, 126.6, 122.0, 121.0,
118.5, 112.2, 37.4, 35.9, 31.3. IR (neat): 3256, 1634, 1530, 1444 cm-1; HRMS (ESI)
calculated for C19H18N2O2 [M+H]+: 307.1441, found 307.1445.
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2-(2-(4-Methylbenzoyl)-1H-indol-3-yl)acetonitrile (4a). This product was obtained
as a yellow solid (35.6 mg, 65% yield). Eluent: petroleum ether/ethyl acetate 3:1 (v/v).
m.p.: 175-176℃; 1H NMR (400 MHz, CDCl3) δ 9.08 (s, 1H), 7.82 (d, J = 8.2 Hz, 1H),
7.74 – 7.68 (m, 2H), 7.46 – 7.35 (m, 2H), 7.34 (d, J = 7.9 Hz, 2H), 7.28 – 7.20 (m,
1H), 3.93 (s, 2H), 2.45 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 188.2, 144.1,
136.2, 135.8, 131.8, 129.9, 129.2, 127.2, 127.0, 121.8, 120.6, 117.6, 112.6, 111.1,
21.9, 14.6. IR (neat): 3325, 2252, 1633, 1534 cm-1; HRMS (ESI) calculated for
C18H14N2O [M+H]+: 275.1179, found: 275.1177.
2-(2-(4-Ethylbenzoyl)-1H-indol-3-yl)acetonitrile (4b). This product was obtained as
a yellow solid (31.7 mg, 55% yield). Eluent: petroleum ether/ethyl acetate 3:1 (v/v).
m.p.: 126-127℃; 1H NMR (400 MHz, CDCl3) δ 8.99 (s, 1H), 7.83 (d, J = 8.2 Hz, 1H),
7.77 – 7.71 (m, 2H), 7.46 – 7.35 (m, 4H), 7.27 – 7.23 (m, 1H), 3.96 (s, 2H), 2.75 (q, J
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= 7.6 Hz, 2H), 1.29 (t, J = 7.6 Hz, 3H). C{1H} NMR (101 MHz, CDCl3) δ 188.2,
150.3, 136.2, 136.0, 131.8, 129.3, 128.8, 127.2, 127.0, 121.8, 120.7, 117.7, 112.6,
111.2, 29.2, 15.4, 14.6. IR (neat): 3323, 2252, 1632, 1534 cm-1; HRMS (ESI)
calculated for C19H16N2O [M+H]+: 289.1335, found: 289.1337.
2-(2-(4-Isopropylbenzoyl)-1H-indol-3-yl)acetonitrile (4c). This product was
obtained as a yellow solid (39.3 mg, 65% yield). Eluent: petroleum ether/ethyl acetate
3:1 (v/v). m.p.: 105-106℃; 1H NMR (400 MHz, DMSO-d6) δ 11.85 (s, 1H), 7.86 (d, J
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= 8.1 Hz, 1H), 7.81 – 7.75 (m, 2H), 7.55 – 7.45 (m, 3H), 7.36 (t, J = 7.6 Hz, 1H), 7.24
– 7.17 (m, 1H), 4.23 (s, 2H), 3.03 (dt, J = 13.6, 6.8 Hz, 1H), 1.32 – 1.20 (m, 6H).
13C{1H} NMR (101 MHz, DMSO-d6) δ 187.5, 153.7, 136.4, 135.8, 131.6, 129.5,
126.8, 126.2, 125.6, 120.7, 120.0, 118.6, 113.2, 110.9, 33.6, 23.5, 13.4. IR (neat):
3325, 2253, 1633, 1534 cm-1; HRMS (ESI) calculated for C20H18N2O [M+H]+:
303.1492, found: 303.1491.
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2-(2-(3,5-Dimethylbenzoyl)-1H-indol-3-yl)acetonitrile (4d). This product was
obtained as a white solid (35.2 mg, 61% yield). Eluent: petroleum ether/ethyl acetate
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3:1 (v/v). m.p.: 161-162℃; H NMR (400 MHz, CDCl3) δ 9.10 (s, 1H), 7.85 (d, J =
8.2 Hz, 1H), 7.50 – 7.42 (m, 4H), 7.32 – 7.27 (m, 2H), 3.90 (s, 2H), 2.44 (s, 6H).
13C{1H} NMR (101 MHz, CDCl3) δ 188.8, 139.2, 138.7, 136.3, 134.9, 132.0, 127.4,
127.1, 126.6, 121.9, 120.7, 117.6, 112.6, 111.2, 21.4, 14.7. IR (neat): 3322, 2252,
1633, 1534 cm-1; HRMS (ESI) calculated for C19H16N2O [M+H]+: 289.1335, found:
289.1337.
2-(2-(3-Methoxybenzoyl)-1H-indol-3-yl)acetonitrile (4e). This product was
obtained as a yellow solid (30.2 mg, 52% yield). Eluent: petroleum ether/ethyl acetate
3:1 (v/v). m.p.: 152-153℃; 1H NMR (400 MHz, DMSO-d6) δ 11.89 (s, 1H), 7.86 (d, J
= 8.1 Hz, 1H), 7.57 – 7.48 (m, 2H), 7.41 – 7.26 (m, 4H), 7.24 – 7.17 (m, 1H), 4.19 (s,
2H), 3.85 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 187.7, 159.3, 139.5, 136.5,
131.3, 130.1, 126.3, 125.9, 121.4, 120.8, 120.2, 118.9, 118.6, 113.5, 113.2, 111.3,
55.4, 13.5. IR (neat): 3326, 2252, 1634, 1586, 1533 cm-1; HRMS (ESI) calculated for
C18H14N2O2 [M+H]+: 291.1128, found: 291.1127.
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2-(2-(4-Methoxybenzoyl)-1H-indol-3-yl)acetonitrile (4f). This product was
obtained as a yellow solid (29.7 mg, 51% yield). Eluent: petroleum ether/ethyl acetate
3:1 (v/v). m.p.: 171-172℃;1H NMR (400 MHz, DMSO-d6) δ 11.86 (s, 1H), 7.89 –
7.80 (m, 3H), 7.54 – 7.49 (m, 1H), 7.36 (t, J = 7.6 Hz, 1H), 7.20 (t, J = 7.5 Hz, 1H),
7.16 (d, J = 8.1 Hz, 2H), 4.20 (s, 2H), 3.89 (s, 3H). 13C{1H} NMR (101 MHz,
DMSO-d6) δ 186.5, 163.1, 136.2, 131.8, 131.7, 130.5, 126.2, 125.4, 120.6, 119.9,
118.6, 114.1, 113.0, 110.2, 55.6, 13.4. IR (neat): 3346, 1719, 1597, 1540, 1439, 1266
cm-1; HRMS (ESI) calculated for C18H14N2O2 [M+H]+: 291.1128, found: 291.1127.
2-(2-(4-(Dimethylamino)benzoyl)-1H-indol-3-yl)acetonitrile (4g). This product was
obtained as a yellow solid (26.1 mg, 43% yield). Eluent: petroleum ether/ethyl acetate
3:1 (v/v). m.p.: 228-229℃; 1H NMR (400 MHz, DMSO-d6) δ 11.79 (s, 1H), 7.81 (d, J
= 8.1 Hz, 1H), 7.74 (d, J = 8.3 Hz, 2H), 7.52 – 7.46 (m, 1H), 7.32 (t, J = 7.6 Hz, 1H),
7.18 (t, J = 7.5 Hz, 1H), 6.83 (d, J = 8.3 Hz, 2H), 4.16 (s, 2H), 3.07 (s, 6H). 13C{1H}
NMR (101 MHz, DMSO-d6) δ 185.5, 153.4, 135.9, 132.8, 131.8, 126.3, 124.8, 124.7,
120.3, 119.7, 118.8, 112.9, 111.0, 108.7, 39.7, 13.4. IR (neat): 3299, 1676, 1586,
1533 cm-1; HRMS (ESI) calculated for C19H17N3O [M+H]+: 304.1444, found:
304.1446.
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2-(2-([1,1'-Biphenyl]-4-carbonyl)-1H-indol-3-yl)acetonitrile (4h). This product was
obtained as a yellow solid (26.9 mg, 40% yield). Eluent: petroleum ether/ethyl acetate
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3:1 (v/v). m.p.: 178-179℃; H NMR (400 MHz, DMSO-d6) δ 11.94 (s, 1H), 7.97 –
7.87 (m, 5H), 7.84 – 7.77 (m, 2H), 7.58 – 7.49 (m, 3H), 7.49 – 7.42 (m, 1H), 7.38 (t, J
= 7.6 Hz, 1H), 7.22 (t, J = 7.5 Hz, 1H), 4.26 (s, 2H). 13C{1H} NMR (101 MHz,
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The Journal of Organic Chemistry
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DMSO-d6) δ 187.5, 144.2, 138.9, 136.9, 136.5, 131.5, 130.0, 129.2, 128.5, 127.0,
126.9, 126.3, 125.8, 120.8, 120.2, 118.7, 113.2, 111.2, 13.5. IR (neat): 3317, 2252,
1632, 1609, 1534 cm-1; HRMS (ESI) calculated for C23H16N2O [M+H]+: 337.1335,
found: 337.1334.
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2-(2-(2-Naphthoyl)-1H-indol-3-yl)acetonitrile (4i). This product was obtained as a
yellow solid (25.5 mg, 41% yield). Eluent: petroleum ether/ethyl acetate 3:1 (v/v).
m.p.: 197-198℃; 1H NMR (400 MHz, DMSO-d6) δ 11.99 (s, 1H), 8.46 (s, 1H), 8.19 –
8.10 (m, 2H), 8.11 – 8.05 (m, 1H), 7.95 – 7.87 (m, 2H), 7.77 – 7.61 (m, 2H), 7.57 –
7.50 (m, 1H), 7.39 (t, J = 7.6 Hz, 1H), 7.23 (t, J = 7.5 Hz, 1H), 4.26 (s, 2H). 13C{1H}
NMR (101 MHz, DMSO-d6) δ 188.0, 136.5, 135.3, 134.9, 132.0, 131.6, 131.0, 129.7,
128.7, 128.6, 127.7, 127.1, 126.4, 125.8, 124.9, 120.8, 120.2, 118.6, 113.2, 111.1,
13.6. IR (neat): 3314, 2251, 1626, 1533 cm-1; HRMS (ESI) calculated for C21H14N2O
[M+H]+: 311.1179, found: 311.1171.
2-(2-(2-Fluorobenzoyl)-1H-indol-3-yl)acetonitrile (4j). This product was obtained
as a yellow solid (15.6 mg, 28% yield). Eluent: petroleum ether/ethyl acetate 3:1 (v/v).
m.p.: 157-158℃; 1H NMR (400 MHz, CDCl3) δ 8.99 (s, 1H), 7.82 (d, J = 8.2 Hz, 1H),
7.64 – 7.55 (m, 2H), 7.45 – 7.39 (m, 2H), 7.37 – 7.30 (m, 1H), 7.27 – 7.22 (m, 2H),
3.92 (s, 2H). 13C{1H} NMR (101 MHz, CDCl3) δ 184.2, 159.6 (d, J = 253.5 Hz),
136.5, 134.0 (d, J = 8.1 Hz), 131.7, 130.2 (d, J = 2.0 Hz), 127.8, 127.2, 127.1, 125.3
(d, J = 4.0 Hz), 122.0, 121.0, 117.2 (d, J = 9.1 Hz), 116.9, 112.7, 112.3, 14.1. 19F
NMR (377 MHz, CDCl3) δ -12.4. IR (neat): 3326, 2253, 1639, 1533 cm-1; HRMS
(ESI) calculated for C17H11FN2O [M+Na]+: 301.0748, found: 301.0752.
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