Metal-Free Dehydrogenative Double C-H Sulfuration to Access Thieno[2,3- b]indoles Using Elemental Sulfur

Article abstract of DOI:10.1021/acs.joc.9b01586

We report a base-promoted metal-free approach for the synthesis of thieno[2,3-b]indole derivatives. This method combined four C-H σ-bond cleavage reactions of two different kinds of C-H bonds and two C-S σ-bond formation processes. A series of thieno[2,3-

Full text of DOI:10.1021/acs.joc.9b01586

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Article
Metal-Free Dehydrogenative Double C-H Sulfuration to
Access Thieno[2,3-b]indoles Using Elemental Sulfur
Jianming Liu, Yanyan Zhang, Yuanyuan Yue, Zhixian Wang,
Huibin Shao, Kelei Zhuo, Qing-Zhang Lv, and Zhiguo Zhang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01586 • Publication Date (Web): 07 Aug 2019
Downloaded from pubs.acs.org on August 7, 2019
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Metal-Free
Dehydrogenative
Double
C-H
Sulfuration
to
Access
Thieno[2,3-b]indoles Using Elemental Sulfur
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Jianming Liu*, Yanyan Zhang, Yuanyuan Yue, Zhixian Wang, Huibin Shao, Kelei
Zhuo, Qingzhang Lv* and Zhiguo Zhang*
Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key
Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and
Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, P. R. China.
E-mail address: jmliu@htu.cn, lvqz@htu.cn and zhangzg@htu.edu.cn.
Abstract: We reported a base-promoted metal-free approach for the synthesis of
thieno[2,3-b]indole derivatives. This method combined four C-H σ-bonds cleavage
reaction of two different kinds of C-H bonds and two C-S σ-bond formation process.
Series of thieno[2,3-b]indoles were obtained starting from 3-benzyl indole derivatives
with good yields and high regioselectivity with the elemental sulfur serving as the
cheap and readily available sulfur source. Good efficiency could be kept even the
reaction was performed on a gram scale. A plausible mechanism was proposed on the
basis of mechanistic studies.
Keywords: C-H functionalization, cyclization, C-S bond formation, thienoindole
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derivatives, elemental sulfur.
INTRODUCTION
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Thieno[2,3-b]indole is one kind of important backbones, which is widely existed in a
variety of natural products, biologically active agent and pharmaceutical molecules.1-5
Hence, seeking efficient methodologies for facile access to the thieno[2,3-b]indoles
has attracted a lot of attention in synthetic organic chemistry during the past
decades.6-10 It has been recognized as a powerful strategy to construct S-containing
compounds by harnessing elemental sulfur as the sulfur source. It is common for
numerous and mild oxidation states of elemental sulfur to select as a promising
oxidant.11-14 Meanwhile, elemental sulfur could incorporate ring systems to arrange
functional components in the construction of heterocycles.15-36 Recently, Li and Deng
have developed an efficient approach for the construction of thienoindole derivatives
starting from indole, ketone and sulfur powder.37,38 Then, Deng et al. demonstrated
the formation of the thieno[2,3-b]indoles by the reaction of indoles, alkenes or
3
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alkynes, and sulfur powder via a cascade reaction. In above transformation, DMF
played a vital role to convert the alkenes or alkynes into thioamides. Meanwhile, a
tandem approach to substituted thienoindoles from indoles, α, β-unsaturated
carboxylic acids, and elemental sulfur was also furnished by Fu and coworkers.40
Despite these advances had been established, the incoprporation of elemental sulfur
into substrate process hardly provided the thieno[2,3-b]indoles containing carbonyl
groups. However, several challenges remained in choosing an efficient approach for
the preparation of thieno[2,3-b]indoles contained containing carbonyl group. First, it
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is a concern what materials could be chosen as the suitable substrates. Second, the
scope of the transformation and the attractive and valuable route represents another
difficulty.
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Indole has proven to be ubiquitous scaffolds for enantioselective preparation of
natural products, pharmaceuticals and agrochemicals.41-43 Here, we discovered that
β-indolylketone derivatives could serve as an effective and easily available substrates
for making thieno[2,3-b]indoles contained carbonyl groups via a double C-S bond
formation process. β-Indolylketone derivatives were easily obtained by the
Friedel-Crafts alkylation of the available indoles with α, β-unsaturated ketones with
4
4
the aid of Lewis acid. The sulfur atom derived from elemental sulfur connect two
different C-H bonds of substrate. Firstly, in the presence of base, the deprotonation of
β-indolylketone gave the carbanion, followed by the electrophilic attack of elemental
sulfur to form a β-indolylketone-sulfur species. After the elimination of elemental
sulfur (Sn-1), the intermolecular nucleophilic cyclization occurred regiospecifically at
the 2-position of the indole ring due to the indole C-H bond activity. Finally, the
desired thienoindoles was released by the oxidative aromatization (Scheme 1). In
above process, double C-S bond formation was achieved through cleavage four C-H
σ-bonds in the presence of elemental sulfur and base. Herein, we reported a facile
2
method for the construction of thienoindoles via the selective cleavage of C(sp )-H
3
bonds and C(sp )-H bonds from easily available β-indolylketone, elemental sulfur,
and base.
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Scheme 1. Dual C-S Bond Formation via the Selective Cleavage of C(sp )-H Bonds
3
and C(sp )-H Bonds.
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RESULTS AND DISCUSSION
To test our hypothesis, 3-(1H-indol-3-yl)-3-phenyl-1-(o-tolyl)propan-1-one (1a)
was chosen as the model substrate to establish the optimized conditions of the dual
C-S bond formation reaction. Firstly, a detailed survey of solvents revealed that other
solvents afford the bad results in the similar condition. DMSO was the most suitable
solvent, affording the desired product (2a) in 97% yield (Table 1, entries 1-6). Then
t
we turned our investigation to explore the role of the base. It was noting that KO Bu,
t
LiO Bu, Na
2
CO
3
, K
2
CO
3
, and K
3
PO provided positive results, and afforded moderate
4
to good yields (Table 1, entries 7-11). Meanwhile, organic base, such as DBU and
DABCO, provided the final product in trace and 90% yield, respectively (Table 1,
entries 12 and 13). The amount of elemental sulfur did not affect the oxidative
cyclization obviously. Both increasing and decreasing the mount of elemental sulfur
generated the desired product 2a in excellent yield (Table 1, entries 14-16). Neither at
a lower temperature nor at a higher temperature influenced the yield of the final
product (Table 1, entries 17-19). The optimized condition was shown as follow: 1a
t
o
(0.30 mmol), S
8
(0.20 mmol), NaO Bu (1.0 equiv), DMSO (2.0 mL), 120 C, 24 h in
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N atmosphere.
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Table1. Optimization of Reaction Conditions.a
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yield (%)b
entry
S
8
base
solvent
tem. ( C)
t
1
2
S
8
S
8
S
8
S
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S
8
S
8
S
8
S
8
S
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S
8
S
8
S
8
S
8
S
8
S
8
S
8
S
8
S
8
S
8
(0.20 mmol)
(0.20 mmol)
(0.20 mmol)
(0.20 mmol)
(0.20 mmol)
(0.20 mmol)
(0.20 mmol)
(0.20 mmol)
(0.20 mmol)
(0.20 mmol)
(0.20 mmol)
(0.20 mmol)
(0.20 mmol)
(0.10 mmol)
(0.30 mmol)
(0.10 mmol)
(0.20 mmol)
(0.20 mmol)
(0.20 mmol)
Na OBu
DMSO
1,4-dioxane
Toluene
Xylene
DMF
120
120
120
120
120
120
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10
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52
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95
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trace
83
94
91
87
94
86
t
Na OBu
t
3
Na OBu
t
4
Na OBu
t
5
Na OBu
t
6
Na OBu
DMAc
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
t
7
K OBu
t
8
Li OBu
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Na
2
CO
CO
PO
3
10
11
12
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14
15
16
17
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19
K
K
2
3
3
4
DABCO
DABCO
t
Na OBu
t
Na OBu
t
Na OBu
t
Na OBu
t
Na OBu
t
Na OBu
DMSO
a
t
Standard condition: 1a (0.3 mmol), S
8
(0.20 mmol), NaO Bu (1.0 equiv), DMSO (2.0 mL), N
2
,
o
120 C, 24 h.
b
Isolated yield.
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With the optimized double C-H sulfuration conditions in hand, we next examined
the substrate scope of the β-indolylketones (Scheme 2). To our delight,
3
-(1H-indol-3-yl)-1,3-diphenylpropan-1-one (1b) was well tolerated, and provided the
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desired product 2b in 89% yield. The structure of 2b was unambiguously confirmed
by a single-crystal X-ray diffraction analysis.42 The electron-donating group and
electron-withdrawing group at the para-position of the aromatic ring could influence
the yield of corresponding products dramatically (2c and 2d). Notably, functionalized
substrates bearing a bromide atom at the meta-position of the aromatic ring was
compatible with the reaction conditions, affording the desired product in 90% yield
(2e). Furthermore, β-indolylketones with different substituents such as methyl,
methoxy and chloride groups at another aromatic ring converted to the corresponding
products in good yields (2f-2h). In addition, a variety of functional groups at
para-position of another aromatic ring, such as methyl, chloride, nitrile, and phenyl
groups, were confirmed suitable to provide the final products from 74% to 92% yields
(
2i-2l). More importantly, the reaction of substrates containing naphthyl group also
proceeded smoothly to deliver the desired thienoindoles from moderate to good yields
2m-2o). Finally, we further applied this approach to deliver the thienoindoles
(
contained furan, thiophene and benzothiophene groups in 64-87% yields (2p-2r).
Unfortunately, the reaction of substrates containing alky and pyridyl group was not
compatible with the reaction (2s-2t). The desired products were not observed. The
structures of 2o and 2q were unambiguously confirmed by a single-crystal X-ray
diffraction analysis.45
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Scheme 2. Extension of the Reaction Scope.a, b
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Reaction conditions: 1 (0.30 mmol), S
8
(0.20 mmol), NaO Bu (1.0 equiv), DMSO (2.0 mL), N
2
,
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Isolated yield.
c
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d
o
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Next, we sought to examine the substituents of indole ring (Scheme 3). The
substrates bearing methyl, phenyl and benzyl group at the α-position of the indole ring
were well tolerated, furnishing the dual C-S bond formation in good yields (4a-4c).
Meanwhile, β-indolylketones bearing the methyl and methoxy at the 4- and
5
-positions of the indole were compatible with the optimized conditions, and the
thienoindoles were achieved in high yields (4d-4g). As well, electron-withdrawing
group at the 5-position of the indole ring smoothly reacted with the elemental sulfur,
and afforded the corresponding products from 62% to 90% yields (4h-4k).
Furthermore, the electron-donating groups and electron-withdrawing groups at the 6-
and 7-position of the indole ring were also suitable substrates to generate the final
products in excellent yields (4l-4q). In addition, indole bearing benzyl oxygen groups
was conducted to undergo the transformation in 81% yield (4r). Notably, the substrate
contained phenyl group at 2-position of indole ring could undergo the selective dual
C-S bond formation reaction to generate the unexpected product 4s in moderate yield.
In the reaction system, the substrate 3s underwent the cleavage of C-C bond to afford
the byproduct 2a in 40% yield. The structure of 4s was unambiguously confirmed by
a single-crystal X-ray diffraction analysis.45
Scheme 3. Scope of Dual C-S Bond Formation.a
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8
(0.20 mmol), NaO Bu (1.0 equiv), DMSO (2.0 mL), N
2
,
o
1
20 C, 24 h.
b
Isolated yield.
To demonstrate the practical of our method, the dual C-S bond formation was
conducted in large scale synthesis (7.0 mmol). As a result, the desired product 2b was
isolated in 64% yield in 1.58 g (Scheme 4).
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Scheme 4. Gram-Scale Experiment.
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To gain some insight of the dual C-S bond formation, several control experiments
were explored in different conditions. In the absence of base, only a trace of product
was obtained in standard condition (Scheme 5a). This result demonstrated that base
played a decisive role and captured the hydrogen at the α-position of the carbonyl
group. Hence, radical trapping experiments were conducted under the optimized
conditions to probe whether a radical process was involved or not (Scheme 5b and 5c).
The dual C-S bond formations were not completely suppressed by TEMPO and BHT.
These results showed that the radical process maybe involved in the dual C-S bond
formation reaction. In addition, the intramolecular kinetic isotope effect was applied
to conduct under the optimized conditions on a 0.3 mmol scale with 88% D content
starting material 5a. The result exhibited that the cleavage of C-H bond at the
α-position of the carbonyl group was not the rate-limiting step (Scheme 5d).
Subsequently, another intramolecular kinetic isotope effect carried out with a 0.30
mmol starting material was also investigated under the optimized conditions. The
observed isotopic effect (k
H
D
/k = 1.14) demonstrated that the cleavage of C-H bond at
the 2-position of the indole ring was not the rate-limiting step (Scheme 5e).
Scheme 5. Mechanistic Experiments
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Based on the results and some previous reports,11, 20, 23, 32 we proposed the
mechanism of the dual C-S bond formations (Scheme 6). The substrate 1a converted
to intermediate I and its proper tautomeric equilibrium I’, followed by the lose
hydrogen proton with the help of base. Subsequently, an intermediate II was formed
by an electrophilic attack of the elemental sulfur at the α-position of the carbonyl
group. The intramolecular nucleophilic cyclization of the intermediate II provided an
intermediate III by elimination of the elemental sulfur (Sn-1). Finally, the desired
thienoindole was released by the oxidative aromatization of elemental sulfur.12,13
Scheme 6. Proposed Reaction Mechanism for the Formation of 2a.
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CONCLUSION
In summary, we have achieved a novel process of elemental sulfur promoted the
dual C-S bond formation that proceeded smoothly to afford poly-substituted
thienoindoles. This approach could be extended to explore the dual C-S bond
formation of broad range of β-indolylketones. Importantly, the approach is suitable for
larger scale synthesis without decreasing the yield of the desired product. In this
transformation, the dual C-S bonds are prepared by the selective cleavage of the
2
3
C(sp )-H bond and C(sp )-H bonds with the aid of base. Furthermore, the dual C-S
bond formation underwent the electrophilic attack of elemental sulfur and
intramolecular nucleophilic cyclization to form the corresponding product.
EXPERIMENTAL SECTION
General Information. All the solvents and other reagents were purchased from
commercial suppliers without the purification. All reactions were performed in N
2
atmosphere unless otherwise. The 1 and 3 were prepared by the reported literatures.44
1
13
1
1
H and C{ H} NMR spectra were recorded on Bruker Avance/600 ( H: 600 MHz,
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C{ H}: 150 MHz at 25 ºC) or Bruker Avance/400 ( H: 400 MHz, C{ H}: 100
1
19
MHz at 25 ºC) and TMS as internal standard. H and F NMR multiplicities are
reported as follows: singlet (s), doublet (d), doublet of doublets (dd), quartet (q),
multiplet (m), and broad resonance (br). All high-resolution mass spectra (HRMS)
were measured on a mass spectrometer by using electrospray ionization (ESI-oa-TOF).
Melting points were measured on a melting point apparatus equipped with a
thermometer and were uncorrected. All reactions were monitored by thin-layer
chromatography (TLC) through GF254 silica gel-coated plates. Flash chromatography
was conducted on neutral aluminum oxide (200-300 mesh, purchased from
Sinopharm Chemical Reagent Co., Ltd).
1
1
1
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General procedure for the synthesis of β-indolylketones (1 and 3): In a 25 mL
flame-dried Schlenk tube equipped with a stir bar, indole (0.50 mmol, 58.6 mg),
chalcone (0.55 mmol, 114.5 mg) and TsOH·H
and the tube was then sealed. The Schlenk tube was purged three times with N
CH CN (2.5 mL) was injected into the Schlenk tube with a syringe under N
2
O (5.0 mol%, 4.8 mg) were combined
2
. Then,
3
2
o
atmosphere. The Schlenk tube contents were then allowed to stir at 50 C by heating
mantle for 24 h. After cooling to room temperature, the residue was concentrated in
vacuum. The residue was neutralized by NaHCO
extracted by ethyl acetate (5×25 mL). The combined organic phases were dried over
Na SO , and concentrated in vacuum. The residue was purified by column
chromatography on silica gel to afford the desired starting materials 1 and 3
-(1H-indol-3-yl)-3-phenyl-1-(o-tolyl)propan-1-one (1a).44 The title compound
3
and then the aqueous phase was
2
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3
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was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the white solid,
o
1
1
52.7 mg, 90% yield; m.p. 110-113 C. H NMR (400 MHz, CDCl
7.51 (d, J = 8.0 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.33-7.25 (m, 5H), 7.23-7.10 (m,
H), 7.01-6.92 (m, 1H), 4.95 (t, J = 8.0 Hz, 1H), 3.73-3.59 (m, 2H), 2.20 (s, 3H).
3
) δ 7.99 (br, 1H),
0
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3-(1H-indol-3-yl)-1,3-diphenylpropan-1-one (1b).44 The title compound was
prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the white solid,
o
1
149.7 mg, 92% yield; m.p. 115-118 C. H NMR (400 MHz, DMSO-d
6
) δ 10.79 (br,
1
H), 7.90 (d, J = 8.0 Hz, 2H), 7.46 (td, J = 8.0, 4.0 Hz, 1H), 7.38-7.30 (m, 5H), 7.25
(dd, J = 8.0, 4.0 Hz, 2H), 7.11 (t, J = 6.0 Hz, 2H), 7.00-6.91 (m, 2H), 6.80 (t, J = 8.0
Hz, 1H), 4.83 (t, J = 6.0 Hz, 1H), 3.83 (q, J = 8.0 Hz, 1H), 3.71 (q, J = 8.0 Hz, 1H).
(1c).44
1
-(4-Chlorophenyl)-3-(1H-indol-3-yl)-3-phenylpropan-1-one
The title
compound was prepared according to the general procedure and purified by flash
column chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the pink
o
1
solid, 161.9 mg, 90% yield; m.p. 144-147 C. H NMR (400 MHz, DMSO-d
6
) δ 10.80
(br, 1H), 7.88 (d, J = 8.0 Hz, 2H), 7.40-7.25 (m, 7H), 7.09 (t, J = 8.0 Hz, 2H),
6
.99-6.92 (m, 2H), 6.80 (t, J = 8.0 Hz, 1H), 4.82 (t, J = 8.0 Hz, 1H), 3.82 (q, J = 8.0
Hz, 1H), 3.69 (q, J = 8.0 Hz, 1H).
-(1H-indol-3-yl)-1-(4-methoxyphenyl)-3-phenylpropan-1-one (1d).44 The title
3
compound was prepared according to the general procedure and purified by flash
column chromatography (petroleum ether/ethyl acetate = 20:1, v/v) to give the pink
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solid, 159.9 mg, 90% yield; m.p. 162-169 C. H NMR (400 MHz, DMSO-d
6
) δ 10.87
(
br, 1H), 8.00 (d, J = 8.0 Hz, 2H), 7.42 (td, J = 10.0, 4.0 Hz, 3H), 7.33 (d, J = 8.0 Hz,
2
H), 7.21 (t, J = 8.0 Hz, 2H), 7.10-6.99 (m, 4H), 6.90 (t, J = 8.0 Hz, 1H), 4.90 (t, J =
1
1
1
1
1
1
1
1
1
1
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2
2
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2
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2
2
2
3
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3
3
3
3
3
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5
5
5
5
5
6
0
1
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0
8.0 Hz, 1H), 3.85 (q, J = 8.0 Hz, 1H), 3.79 (s, 3H), 3.73 (q, J = 8.0 Hz, 1H).
-(3-Bromophenyl)-3-(1H-indol-3-yl)-3-phenylpropan-1-one (1e). The
1
title
compound was prepared according to the general procedure and purified by flash
column chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the white
o
1
solid, 194.1 mg, 96% yield; m.p. 128-131 C. H NMR (400 MHz, DMSO-d
(br, 1H), 8.17 (d, J = 4.0 Hz, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H),
.49-7.35 (m, 6H), 7.22 (t, J = 6.0 Hz, 2H), 7.11-7.03 (m, 2H), 6.92 (t, J = 8.0 Hz,
1H), 4.92 (t, J = 8.0 Hz, 1H), 3.98 (q, J = 8.0 Hz, 1H), 3.85 (q, J = 8.0 Hz, 1H);
6
) δ 10.91
7
1
3
1
C{ H} NMR (151 MHz, DMSO-d ) δ 197.8, 145.7, 139.4, 136.9, 136.2, 131.3,
6
1
31.1, 128.6, 128.3, 127.5, 126.9, 126.3, 126.8, 122.5, 121.5, 119.3, 118.8, 118.5,
+
111.9, 44.9, 38.1. HRMS (ESI-TOF) m/z: [M+Na] Calcd for C23
H18BrNONa
+
(
M+Na ): 426.0464; Found 426.0464.
4
4
3-(1H-indol-3-yl)-1-phenyl-3-(o-tolyl)propan-1-one (1f). The title compound was
prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the yellow solid,
o
1
166.3 mg, 98% yield; m.p. 92-96 C. H NMR (400 MHz, DMSO-d
.09 (d, J = 8.0 Hz, 2H), 7.60-7.45 (m, 6H), 7.30-7.02 (m, 6H), 5.33 (t, J = 8.0 Hz,
1H), 4.05-3.81 (m, 2H), 2.58 (s, 3H).
-(1H-indol-3-yl)-3-(3-methoxyphenyl)-1-phenylpropan-1-one (1g).47 The title
6
) δ 11.02 (br, 1H),
8
3
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compound was prepared according to the general procedure and purified by flash
column chromatography (petroleum ether/ethyl acetate = 20:1, v/v) to give the yellow
o
1
solid, 168.8 mg, 95% yield; m.p. 121-124 C. H NMR (400 MHz, DMSO-d ) δ 10.92
6
0
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(br, 1H), 8.02 (d, J = 8.0 Hz, 2H), 7.53 (d, J = 8.0 Hz, 2H), 7.45-7.37 (m, 4H), 7.14 (t,
J = 6.0 Hz, 1H), 7.08-7.02 (m, 3H), 6.94 (t, J = 8.0 Hz, 1H), 6.67 (d, J = 8.0 Hz, 1H),
4.97 (t, J = 8.0 Hz, 1H), 3.96 (q, J = 8.0 Hz, 1H), 3.83 (q, J = 8.0 Hz, 1H), 3.63 (s,
3
H).
(1h).49
3
-(3-Fluorophenyl)-3-(1H-indol-3-yl)-1-phenylpropan-1-one
The title
compound was prepared according to the general procedure and purified by flash
column chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the pink
o
1
solid, 168.3 mg, 98% yield; m.p. 123-125 C. H NMR (400 MHz, CDCl
H), 7.92 (d, J = 8.0 Hz, 2H), 7.53 (td, J = 6.0, 4.0 Hz, 1H), 7.44-7.40 (m, 3H), 7.30
d, J = 8.0 Hz, 1H), 7.21-7.13 (m, 3H), 7.04-7.00 (m, 2H), 6.97 (d, J = 4.0 Hz, 1H),
6.84 (td, J = 8.0, 4.0 Hz, 1H), 5.07 (t, J = 6.0 Hz, 1H), 3.80 (q, J = 6.7 Hz, 1H), 3.70
q, J = 9.3 Hz, 1H).
3
) δ 8.02 (br,
1
(
(
3-(1H-indol-3-yl)-1-phenyl-3-(p-tolyl)propan-1-one (1i).44 The title compound was
prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the pink solid,
o
1
156.1 mg, 92% yield; m.p. 118-122 C. H NMR (600 MHz, DMSO-d
H), 8.00 (d, J = 6.0 Hz, 2H), 7.62 (td, J = 9.0, 6.0 Hz, 1H), 7.51 (t, J = 9.0 Hz, 2H),
7.39 (d, J = 12.0 Hz, 1H), 7.31-7.25 (m, 4H), 7.01 (td, J = 9.0, 6.0 Hz, 3H), 6.88 (td, J
9.0, 6.0 Hz, 1H), 4.82 (t, J = 6.0 Hz, 1H), 3.87 (q, J = 8.0 Hz, 1H), 3.78 (q, J = 8.0
6
) δ 10.82 (br,
1
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Hz, 1H), 2.19 (s, 3H).
-(4-Chlorophenyl)-3-(1H-indol-3-yl)-1-phenylpropan-1-one (1j).44 The title
3
compound was prepared according to the general procedure and purified by flash
column chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the pink
1
1
1
1
1
1
1
1
1
1
2
2
2
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2
2
2
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0
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8
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0
o
1
solid, 152.9 mg, 85% yield; m.p. 116-119 C. H NMR (400 MHz, DMSO-d
6
) δ 10.90
(br, 1H), 8.02 (dd, J = 8.0, 4.0 Hz, 2H), 7.62 (td, J = 8.0, 4.0 Hz, 1H), 7.51 (td, J = 8.0,
4
.0 Hz, 2H), 7.44-7.41 (m, 3H), 7.37 (d, J = 8.0 Hz, 1H), 7.32 (d, J = 8.0 Hz, 1H),
.27 (dd, J = 8.0, 4.0 Hz, 2H), 7.03 (t, J = 8.0 Hz, 1H), 6.90 (t, J = 8.0 Hz, 1H), 4.88 (t,
7
J = 8.0 Hz, 1H), 3.93 (q, J = 8.0 Hz, 1H), 3.83 (q, J = 8.0 Hz, 1H).
-(1-(1H-indol-3-yl)-3-oxo-3-phenylpropyl)benzonitrile (1k).47 The title compound
4
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 15:1, v/v) to give the white solid,
o
1
1
62.9 mg, 93% yield; m.p. 116-119 C. H NMR (400 MHz, DMSO-d
1H), 8.03 (d, J = 8.0 Hz, 2H), 7.69 (dd, J = 8.0, 4.0 Hz, 2H), 7.65-7.60 (m, 3H),
.53-7.43 (m, 4H), 7.34 (d, J = 8.0 Hz, 1H), 7.05 (t, J = 8.0 Hz, 1H), 6.92 (t, J = 8.0
Hz, 1H), 4.98 (t, J = 8.0 Hz, 1H), 4.06-3.90 (m, 2H).
-([1,1'-Biphenyl]-4-yl)-3-(1H-indol-3-yl)-1-phenylpropan-1-one (1l).47 The title
6
) δ 10.97 (br,
7
3
compound was prepared according to the general procedure and purified by flash
column chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the light
o
1
pink solid, 58.2 mg, 29% yield; m.p. 219-223 C. H NMR (400 MHz, DMSO-d ) δ
6
10.90 (br, 1H), 8.05 (d, J = 8.0 Hz, 2H), 7.65-7.58 (m, 3H), 7.54-7.49 (m, 7H), 7.41 (t,
J = 8.0 Hz, 3H), 7.34-7.29 (m, 2H), 7.05 (t, J = 6.0 Hz, 1H), 6.92 (t, J = 8.0 Hz, 1H),
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4.95 (t, J = 8.0 Hz, 1H), 4.01-3.86 (m, 2H).
-(1H-indol-3-yl)-3-(naphthalen-1-yl)-1-phenylpropan-1-one (1m).48 The title
3
compound was prepared according to the general procedure and purified by flash
column chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the white
0
1
2
3
4
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0
1
2
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o
1
solid, 176.5 mg, 94% yield; m.p. 73-79 C. H NMR (400 MHz, DMSO-d
6
) δ 10.88
(br, 1H), 8.40 (d, J = 8.0 Hz, 1H), 8.01 (d, J = 8.0 Hz, 2H), 7.90 (d, J = 8.0 Hz, 1H),
7
1
.74 (d, J = 8.0 Hz, 1H),7.61-7.45 (m, 6H), 7.40-7.32 (m, 3H), 7.24 (d, J = 4.0 Hz,
H), 7.02 (t, J = 8.0 Hz, 1H), 6.85 (t, J = 8.0 Hz, 1H), 5.80 (td, J = 8.0, 4.0 Hz, 1H),
4.09 (q, J = 8.0 Hz, 1H), 3.89 (q, J = 8.0 Hz, 1H).
-(1H-indol-3-yl)-3-(naphthalen-2-yl)-1-phenylpropan-1-one (1n).49 The title
3
compound was prepared according to the general procedure and purified by flash
column chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the pink
o
1
solid, 178.3 mg, 95% yield; m.p. 155-158 C. H NMR (400 MHz, DMSO-d
(br, 1H), 8.03 (dd, J = 8.0, 4.0 Hz, 2H), 7.96 (d, J = 4.0 Hz, 1H), 7.83-7.75 (m, 3H),
.61-7.56 (m, 2H), 7.50-7.34 (m, 7H), 7.04 (t, J = 6.0 Hz, 1H), 6.89 (t, J = 8.0 Hz,
1H), 5.11 (t, J = 8.0 Hz, 1H), 4.05 (q, J = 8.0 Hz, 1H), 3.95 (q, J = 8.0 Hz, 1H).
-(1H-indol-3-yl)-1-(naphthalen-2-yl)-3-phenylpropan-1-one (1o).47 The title
6
) δ 10.95
7
3
compound was prepared according to the general procedure and purified by flash
column chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the white
o
1
solid, 180.2 mg, 96% yield; m.p. 151-155 C. H NMR (400 MHz, DMSO-d
(br, 1H), 8.80 (s, 1H), 8.13 (d, J = 8.0 Hz, 1H), 8.00-7.95 (m, 3H), 7.68-7.60 (m, 2H),
.45 (d, J = 8.0 Hz, 3H), 7.38 (s, 1H), 7.32 (dd, J = 8.0, 4.0 Hz, 1H), 7.23 (dd, J = 6.0,
6
) δ 10.87
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4.0 Hz, 2H), 7.10 (td, J = 6.0, 4.0 Hz, 1H), 7.03 (t, J = 8.0 Hz, 1H), 6.90 (t, J = 8.0 Hz,
1
H), 4.95 (t, J = 8.0 Hz, 1H), 4.10 (q, J = 8.0 Hz, 1H), 3.93 (q, J = 8.0 Hz, 1H).
-(Furan-2-yl)-3-(1H-indol-3-yl)-3-phenylpropan-1-one (1p). 44 The title compound
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8
9
0
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the green solid,
o
1
140.2 mg, 89% yield; m.p. 117-121 C. H NMR (400 MHz, DMSO-d
6
) δ 10.88 (br,
1
H), 7.95 (s, 1H), 7.60 (d, J = 4.0 Hz, 1H), 7.44-7.39 (m, 3H), 7.33 (dd, J = 8.0, 4.0
Hz, 2H), 7.23 (t, J = 8.0 Hz, 2H), 7.11 (t, J = 8.0 Hz, 1H), 7.04 (t, J = 8.0 Hz, 1H),
6.91 (t, J = 6.0 Hz, 1H), 6.89 (d, J = 4.0 Hz, 1H), 4.87 (t, J = 8.0 Hz, 1H), 3.73 (q, J =
8
.0 Hz, 1H), 3.58 (q, J = 6.7 Hz, 1H).
3-(1H-indol-3-yl)-3-phenyl-1-(thiophen-2-yl)propan-1-one
(1q).44
The
title
compound was prepared according to the general procedure and purified by flash
column chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the purple
o
1
solid, 140.9 mg, 85% yield; m.p. 116-119 C. H NMR (400 MHz, DMSO-d
6
) δ 10.86
(br, 1H), 8.13 (d, J = 4.0 Hz, 1H), 7.95 (dd, J = 8.0, 4.0 Hz, 1H), 7.41 (t, J = 8.0 Hz,
3H), 7.34 (s, 1H), 7.30 (d, J = 8.0 Hz, 1H), 7.24-7.20 (m, 3H), 7.10 (td, J = 8.0, 4.0
Hz, 1H), 7.02 (dd, J = 8.0, 4.0 Hz, 1H), 6.89 (td, J = 8.0, 4.0 Hz, 1H), 4.86 (t, J = 8.0
Hz, 1H), 3.86 (q, J = 8.0 Hz, 1H), 3.70 (q, J = 8.0 Hz, 1H).
1-(Benzo[b]thiophen-2-yl)-3-(1H-indol-3-yl)-3-phenylpropan-1-one (1r). The title
compound was prepared according to the general procedure and purified by flash
column chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the red
o
1
solid, 177.4 mg, 93% yield; m.p. 187-191 C. H NMR (400 MHz, CDCl ) δ 7.97 (br,
3
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1H), 7,89 (s, 1H), 7.82 (d, J = 8.0 Hz, 2H), 7.43 (dd, J = 8.0, 4.0 Hz, 2H), 7.39-7.35
(m, 3H), 7.30-7.23 (m, 4H), 7.17-7.12 (m, 2H), 7.01 (td, J = 8.0, 4.0 Hz, 2H), 5.09 (t,
13
1
J = 6.0 Hz, 1H), 3.85 (q, J = 8.0 Hz, 1H), 3.72 (q, J = 6.7 Hz, 1H); C{ H} NMR
(151 MHz, CDCl ) δ 193.0, 143.9, 143.9, 142.6, 139.1, 136.7, 129.0, 128.5, 127.8,
27.4, 126.6, 126.5, 126.0, 125.0, 123.0, 122.2, 121.5, 119.6, 119.5, 119.0, 111.2, 45.8,
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1
+
+
38.7. HRMS (ESI-TOF) m/z: [M+Na] Calcd for C25
H19NOSNa (M+Na ): 404.1080;
Found 404.1080.
3
-(1-Methyl-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3a).44 The title compound
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the white solid,
o
1
161.2 mg, 95% yield; m.p. 168-174 C. H NMR (400 MHz, DMSO-d
6
) δ 8.00 (d, J =
.0 Hz, 2H), 7.62 (t, J = 6.0 Hz, 1H), 7.50 (t, J = 8.0 Hz, 2H), 7.45 (d, J = 8.0 Hz, 1H),
.40 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.22 (t, J = 6.0 Hz, 2H), 7.09 (t, J =
8
7
8.0 Hz, 2H), 6.93 (t, J = 8.0 Hz, 1H), 4.87 (t, J = 8.0 Hz, 1H), 3.92-3.80 (m, 2H), 3.71
s, 3H).
(
1,3-Diphenyl-3-(1-phenyl-1H-indol-3-yl)propan-1-one (3b).48 The title compound
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give orange oil, 170.6
o
1
mg, 85% yield; m.p. 101-104 C. H NMR (400 MHz, CDCl
H), 7.51-7.43 (m, 3H), 7.41-7.38 (m, 6H), 7.33 (td, J = 8.0, 4.0 Hz, 2H), 7.23 (td, J =
8.0, 4.0 Hz, 3H), 7.15-7.09 (m, 3H), 7.04 (t, J = 6.0 Hz, 1H), 5.12 (td, J = 8.0, 4.0 Hz,
H), 3.84-3.71 (m, 2H).
3
) δ 7.89 (d, J = 8.0 Hz,
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3-(1-Benzyl-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3c).50 The title compound
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the pink solid,
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o
1
162.1 mg, 78% yield; m.p. 139-141 C. H NMR (400 MHz, CDCl
.0, 4.0 Hz, 2H), 7.52 (td, J = 8.0, 4.0 Hz, 1H), 7.46-7.35 (m, 5H), 7.29-7.23 (m, 5H),
7.21-7.09 (m, 3H), 7.05-6.98 (m, 3H), 6.94 (s,1H), 5.25 (s, 2H), 5.08 (t, J =8.0 Hz,
3
) δ 7.90 (dd, J =
8
1
H), 3.83-3.69 (m, 2H).
3
-(4-Methyl-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3d).51 The title compound
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the yellow solid,
o
1
146.0 mg, 86% yield; m.p. 134-136 C. H NMR (400 MHz, CDCl
3
) δ 7.99 (br, 1H),
.91 (dd, J = 8.0, 4.0 Hz, 2H), 7.52 (td, J = 8.0, 4.0 Hz, 1H), 7.41 (t, J = 6.0 Hz, 2H),
.23-7.19 (m, 4H), 7.15-7.10 (m, 2H), 7.00 (t, J = 8.0 Hz, 1H), 6.92 (d, J = 4.0 Hz,
7
7
1H), 6.74 (dd, J = 8.0, 4.0 Hz, 1H), 5.40 (t, J = 8.0 Hz, 1H), 3.73 (q, J = 8.0 Hz, 1H),
.60 (q, J = 8.0 Hz, 1H), 2.50 (s, 3H).
3
5
2
3-(4-Methoxy-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3e). The title compound
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 20:1, v/v) to give the yellow solid,
o
1
172.4 mg, 97% yield; m.p. 139-142 C. H NMR (400 MHz, CDCl
3
) δ 7.95-7.91 (m,
3
H), 7.52 (td, J = 8.0, 4.0 Hz, 1H), 7.41 (td, J = 8.0, 4.0 Hz, 2H), 7.35 (dd, J = 8.0, 4.0
Hz, 2H), 7.23 (dd, J = 8.0, 4.0 Hz, 2H), 7.14 (td, J = 8.0, 4.0 Hz, 1H), 7.06 (t, J = 8.0
Hz, 1H), 6.91 (d, J = 8.0 Hz, 1H), 6.66 (d, J = 4.0 Hz, 1H), 6.44 (d, J = 8.0 Hz, 1H),
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5.39 (q, J = 4.0 Hz, 1H), 3.88 (q, J = 8.0 Hz, 1H), 3.77 (s, 3H), 3.70 (q, J = 8.0 Hz,
1
H).
3
-(5-Methyl-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3f).47 The title compound
0
1
2
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0
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0
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0
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9
0
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the brown solid,
o
1
149.4 mg, 88% yield; m.p. 170-171 C. H NMR (400 MHz, DMSO-d
6
) δ 10.70 (br,
1
H), 8.00 (dd, J = 8.0, 4.0 Hz, 2H), 7.62 (td, J = 8.0, 4.0 Hz, 1H), 7.51 (td, J = 8.0, 4.0
Hz, 2H), 7.39 (dd, J = 8.0, 4.0 Hz, 2H), 7.27 (d, J = 4.0 Hz, 1H), 7.24-7.17 (m, 4H),
7.10 (td, J = 8.0, 4.0 Hz, 1H), 6.84 (d, J = 8.0 Hz, 1H), 4.83 (t, J = 8.0 Hz, 1H), 3.88
(q, J = 8.0 Hz, 1H), 3.78 (q, J = 8.0 Hz, 1H), 2.30 (s, 3H).
4
4
3-(5-Methoxy-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3g). The title compound
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 20:1, v/v) to give the brown solid,
o
1
145.7 mg, 82% yield; m.p. 138-141 C. H NMR (600 MHz, DMSO-d
H), 8.02 (d, J = 6.0 Hz, 2H), 7.63 (td, J = 9.0, 6.0 Hz, 1H), 7.52 (td, J = 9.0, 6.0 Hz,
2H), 7.42 (dd, J = 12.0, 6.0 Hz, 2H), 7.29 (s, 1H), 7.24-7.19 (m, 3H), 7.11 (td, J = 9.0,
6
) δ 10.70 (br,
1
6
.0 Hz, 1H), 6.87 (s, 1H), 6.68 (dd, J = 12.0, 6.0 Hz, 1H), 4.83 (t, J = 6.0 Hz, 1H),
.91 (q, J = 8.0 Hz, 1H), 3.81 (q, J = 8.0 Hz, 1H), 3.68 (s, 3H).
3
3-(5-Chloro-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3h).47 The title compound
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the pink solid,
o
1
1
70.9 mg, 95% yield; m.p. 148-150 C. H NMR (400 MHz, CDCl ) δ 8.07 (br, 1H),
3
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7.91 (d, J = 8.0 Hz, 2H), 7.53 (t, J = 8.0 Hz, 1H), 7.42 (t, J = 8.0 Hz, 2H), 7.37 (d, J =
4
.0 Hz, 1H), 7.31 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 7.17 (td, J = 6.0, 4.0
Hz, 2H), 7.06 (dd, J = 8.0, 4.0 Hz, 1H), 6.97 (d, J = 8.0 Hz, 1H), 4.99 (t, J = 6.0 Hz,
1H), 3.76 (q, J = 8.0 Hz, 1H), 3.68 (q, J = 8.0 Hz, 1H).
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3
-(5-Fluoro-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3i).47 The title compound
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the white solid,
o
1
1
64.8 mg, 96% yield; m.p. 149-152 C. H NMR (400 MHz, DMSO-d
1H), 8.02 (dd, J = 8.0, 4.0 Hz, 2H), 7.61 (t, J = 8.0 Hz, 1H), 7.50 (t, J = 8.0 Hz, 2H),
.44 (td, J = 8.0, 4.0 Hz, 3H), 7.31 (q, J = 5.3 Hz, 1H), 7.23 (t, J = 8.0 Hz, 2H), 7.17
(dd, J = 10.0, 4.0 Hz, 1H), 7.11 (t, J = 8.0 Hz, 1H), 6.88 (td, J = 10.0, 4.0 Hz, 1H),
6
) δ 10.99 (br,
7
4
.85 (t, J = 8.0 Hz, 1H), 3.94 (q, J = 8.0 Hz, 1H), 3.82 (q, J = 8.0 Hz, 1H).
3
-(3-Oxo-1,3-diphenylpropyl)-1H-indole-5-carbonitrile (3j).51 The title compound
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 15:1, v/v) to give the white solid,
o
1
119.1 mg, 68% yield; m.p. 164-167 C. H NMR (400 MHz, CDCl
3
) δ 8.51 (br, 1H),
.93 (dd, J = 8.0, 4.0 Hz, 2H), 7.72 (s, 1H), 7.56 (td, J = 8.0, 4.0 Hz, 1H), 7.44 (td, J =
.0, 4.0 Hz, 2H), 7.33-7.27 (m, 6H), 7.21-7.17 (m, 1H), 7.14 (dd, J = 4.0, 4.0 Hz, 1H),
7
8
5.03 (t, J = 8.0 Hz, 1H), 3.80 (q, J = 8.0 Hz, 1H), 3.69 (q, J = 8.0 Hz, 1H).
Methyl 3-(3-oxo-1,3-diphenylpropyl)-1H-indole-5-carboxylate (3k). The title
compound was prepared according to the general procedure and purified by flash
column chromatography (petroleum ether/ethyl acetate = 20:1, v/v) to give the pink
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o
1
solid, 153.4 mg, 80% yield; m.p. 228-230 C. H NMR (400 MHz, DMSO-d
6
) δ 11.32
(
br, 1H), 8.12 (d, J = 4.0 Hz, 1H), 8.01 (td, J = 8.0, 4.0 Hz, 2H), 7.69 (dd, J = 8.0, 4.0
Hz, 1H), 7.62 (td, J = 8.0, 4.0 Hz, 1H), 7.51 (td, J = 8.0, 4.0 Hz, 3H), 7.41 (dd, J = 8.0,
4.0 Hz, 3H), 7.25 (t, J = 6.0 Hz, 2H), 7.12 (td, J = 8.0, 4.0 Hz, 1H), 4.93 (t, J = 8.0 Hz,
0
1
2
3
4
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8
9
0
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2
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0
1
3
1
1
H), 3.96 (q, J = 9.3 Hz, 1H), 3.81 (s, 3H), 3.80 (q, J = 8.0 Hz, 1H); C{ H} NMR
(151 MHz, DMSO-d ) δ 198.7, 167.7, 145.4, 139.4, 137.3, 133.6, 129.2, 128.7, 128.5,
28.2, 126.5, 126.5, 124.4, 122.6, 121.6, 120.3, 120.0, 111.8, 52.1, 45.1, 37.8. HRMS
6
1
+
+
(
ESI-TOF) m/z: [M+Na] Calcd for C25
406.1414.
-(6-Methyl-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3l).52 The title compound
H21NO
3
Na (M+Na ): 406.1414; Found
3
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the yellow solid,
o
1
1
52.7 mg, 90% yield; m.p. 161-163 C. H NMR (400 MHz, CDCl
8.0, 4.0 Hz, 2H), 7.82 (br, 1H), 7.53 (td, J = 8.0, 4.0 Hz, 1H), 7.42 (td, J = 8.0, 4.0 Hz,
H), 7.34 (dd, J = 8.0, 4.0 Hz, 2H), 7.29 (d, J = 12.0 Hz, 1H), 7.25-7.22 (m, 2H), 7.15
(td, J = 8.0, 4.0 Hz, 1H), 7.11 (d, J = 4.0 Hz, 1H), 6.92 (d, J = 4.0 Hz, 1H), 6.84 (d, J
8.0 Hz, 1H), 5.04 (t, J = 6.0 Hz, 1H), 3.80 (q, J = 8.0 Hz, 1H), 3.71 (q, J = 8.0 Hz,
H), 2.40 (s, 3H).
3
) δ 7.92 (dd, J =
2
=
1
3-(6-Chloro-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3m).44 The title compound
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the brown solid,
o
1
1
42.1 mg, 79% yield; m.p. 156-158 C. H NMR (400 MHz, DMSO-d ) δ 11.02 (br,
6
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1H), 8.01 (dd, J = 8.0, 4.0 Hz, 2H), 7.61 (td, J = 8.0, 4.0 Hz, 1H), 7.50 (t, J = 8.0 Hz,
2
2
H), 7.41 (td, J = 8.0, 4.0 Hz, 4H), 7.36 (d, J = 4.0 Hz, 1H), 7.22 (td, J = 8.0, 4.0 Hz,
H), 7.10 (td, J = 6.0, 4.0 Hz, 1H), 6.91 (d, J = 8.0, 1H), 4.86 (t, J = 8.0 Hz, 1H), 3.92
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4
4
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5
5
5
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5
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0
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(q, J = 8.0 Hz, 1H), 3.81 (q, J = 8.0 Hz, 1H).
-(6-Fluoro-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3n). The title compound was
3
prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the white solid,
o
1
1
28.8 mg, 75% yield; m.p. 122-124 C. H NMR (400 MHz, CDCl
7.91 (d, J = 8.0 Hz, 2H), 7.52 (td, J = 8.0, 4.0 Hz, 1H), 7.41 (t, J = 8.0 Hz, 2H), 7.31
td, J = 8.0, 4.0 Hz, 2H), 7.28-7.22 (m, 3H), 7.15 (td, J = 8.0, 4.0 Hz, 1H), 6.93 (dd, J
= 10.0, 4.0 Hz, 2H), 6.75 (td, J = 10.0, 4.0 Hz, 1H), 5.01 (t, J = 8.0 Hz, 1H), 3.76 (q, J
3
) δ 8.01 (br, 1H),
(
1
3
1
=
8.0 Hz, 1H), 3.66 (q, J = 8.0 Hz, 1H); C{ H} NMR (151 MHz, CDCl
3
) δ 198.7,
1
60.0 (J = 241 Hz), 144.2, 137.1, 136.6 (J = 13.6 Hz), 133.2, 128.6 (J = 16.6 Hz),
128.1, 127.8, 126.5, 123.3, 121.6 (J = 3.0 Hz), 120.3 (J = 10.6 Hz), 119.3 (J = 3.0 Hz),
+
1
08.3, 108.1, 97.6, 97.4, 45.3, 38.2. HRMS (ESI-TOF) m/z: [M+ Na] Calcd for
+
C
23
H
18FNONa (M+Na ): 366.1265; Found 366.1266.
4
8
3
-(7-Methoxy-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3o). The title compound
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 20:1, v/v) to give the brown solid,
o
1
1
63.5 mg, 92% yield; m.p. 132-135 C. H NMR (400 MHz, CDCl
7.92 (dd, J = 8.0, 4.0 Hz, 2H), 7.52 (td, J = 8.0, 4.0 Hz, 1H), 7.42 (td J = 8.0, 4.0 Hz,
H), 7.34 (dd, J = 8.0, 4.0 Hz, 2H), 7.23 (dd, J = 8.0, 4.0 Hz, 2H), 7.15 (td, J = 8.0,
3
) δ 8.17 (br, 1H),
2
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4.0 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 6.96 (dd, J = 4.0, 4.0 Hz, 1H), 6.93 (t, J = 8.0
Hz, 1H), 6.59 (d, J = 8.0 Hz, 1H), 5.04 (t, J = 8.0 Hz, 1H), 3.91 (s, 3H), 3.80 (q, J =
8
.0 Hz, 1H), 3.72 (q, J = 8.0 Hz, 1H).
0
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8
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3-(7-Bromo-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3p). The title compound was
prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the yellow solid,
o
1
1
96.1 mg, 97% yield; m.p. 117-120 C. H NMR (400 MHz, DMSO-d
6
) δ 11.12 (br,
1
H), 8.02 (d, J = 8.0 Hz, 2H), 7.61 (t, J = 8.0 Hz, 1H), 7.51 (d, J = 8.0 Hz, 2H),
7.48-7.46 (m, 2H), 7.42 (d, J = 8.0 Hz, 2H), 7.22 (t, J = 8.0 Hz, 3H), 7.10 (td, J = 8.0,
.0 Hz, 1H), 6.86 (t, J = 8.0 Hz, 1H), 4.89 (t, J = 6.0 Hz, 1H), 3.97 (q, J = 8.0 Hz, 1H),
4
1
3
1
3.84 (q, J = 8.0 Hz, 1H); C{ H} NMR (151 MHz, DMSO-d
6
) δ 198.7, 145.4, 137.3,
1
1
35.0, 133.6, 129.1, 128.6, 128.5, 128.2, 126.4, 124.0, 123.8, 120.3, 120.0, 118.8,
+
04.6, 44.6, 38.1. HRMS (ESI-TOF) m/z: [M+Na] Calcd for C23
H18BrNONa
+
(M+Na ): 426.0464; Found 426.0464.
3
-(7-Chloro-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3q). The title compound was
prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 30:1, v/v) to give the white solid,
o
1
1
70.9 mg, 95% yield; m.p. 99-100 C. H NMR (400 MHz, CDCl
7.92 (dd, J = 8.0, 4.0 Hz, 2H), 7.54 (td, J = 8.0, 4.0 Hz, 1H), 7.42 (td, J = 8.0, 4.0 Hz,
H), 7.32 (td, J = 8.0, 4.0 Hz, 3H), 7.26 (dd, J = 8.0, 4.0 Hz, 1H), 7.24 (d, J = 4.0 Hz,
1H), 7.17 (dd, J = 8.0, 4.0 Hz, 1H), 7.14 (dd, J = 10.0, 4.0 Hz, 1H), 7.06 (dd, J = 4.0,
.0 Hz, 1H), 6.93 (t, J = 8.0 Hz, 1H), 5.05 (t, J = 6.0 Hz, 1H), 3.80 (q, J = 8.0 Hz, 1H),
3
) δ 8.19 (br, 1H),
2
4
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3
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3.70 (q, J = 8.0 Hz, 1H); C{ H} NMR (151 MHz, CDCl
3
) δ 198.3, 143.9, 137.1,
1
33.9, 133.1, 128.6, 128.5, 128.1, 127.8, 126.5, 121.9, 121.6, 120.5, 120.3, 118.3,
+
1
16.6, 45.1, 38.2. HRMS (ESI-TOF) m/z: [M+Na] Calcd for C23H18ClNONa
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
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0
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0
+
(M+Na ): 382.0969; Found 382.0969.
3
-(7-(Benzyloxy)-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3r). The title compound
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 20:1, v/v) to give the pink solid,
o
1
1
61.8 mg, 75% yield; m.p. 139-142 C. H NMR (400 MHz, DMSO-d
1H), 8.01 (dd, J = 8.0, 4.0 Hz, 2H), 7.61 (td, J = 8.0, 4.0 Hz, 1H), 7.51 (q, J = 8.0 Hz,
H), 7.41-7.37 (m, 4H), 7.32 (td, J = 8.0, 4.0 Hz, 1H), 7.27 (d, J = 4.0 Hz, 1H), 7.21
(td, J = 8.0, 4.0 Hz, 2H), 7.09 (td, J = 8.0, 4.0 Hz, 1H), 7.02 (d, J = 8.0 Hz, 1H), 6.79
6
) δ 10.96 (br,
4
(
t, J = 8.0 Hz, 1H), 6.67 (d, J = 8.0 Hz, 1H), 5.21 (s, 2H), 4.84 (t, J = 6.0 Hz, 1H),
.91 (q, J = 8.0 Hz, 1H), 3.81 (q, J = 9.3 Hz, 1H); 13C{ H} NMR (151 MHz,
) δ 198.9, 145.8, 145.5, 137.9, 137.3, 133.6, 129.1, 128.9, 128.6, 128.5,
28.2, 128.2, 128.0, 127.0, 126.2, 122.2, 119.2, 119.1, 112.3, 103.4, 69.6, 44.7, 38.2.
1
3
DMSO-d
6
1
+
+
HRMS (ESI-TOF) m/z: [M+Na] Calcd for C23
Found 382.0969.
H18ClNONa (M+Na ): 382.0969;
1
,3-Diphenyl-3-(2-phenyl-1H-indol-3-yl)propan-1-one (3s).53 The title compound
was prepared according to the general procedure and purified by flash column
chromatography (petroleum ether/ethyl acetate = 20:1, v/v) to give the white solid,
o
1
174.7 mg, 87% yield; m.p. 114-116 C H NMR (400 MHz, CDCl
3
) δ 8.08 (br, 1H),
7
.70 (d, J = 8.0 Hz, 2H), 7.57-7.52 (m, 1H), 7.32 (t, J = 8.0 Hz, 5H), 7.20-7.13 (m,
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8H), 7.07-6.99 (m, 3H), 5.28 (t, J = 6.0 Hz, 1H), 3.88-3.78 (m, 2H).
The general procedure for the synthesis of 2 and 4 (2a as example): In a 25 mL
Schlenk
equipped
with
a
magnetic
stirrer,
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3-(1H-indol-3-yl)-3-phenyl-1-(o-tolyl)propan-1-one (1a) (0.30 mmol, 101.8 mg),
t
elemental sulfur (S
8
) (0.20 mmol, 51.3 mg) and NaO Bu (0.30 mmol, 28.8 mg) was
combined and the Schenk tube was sealed. Then anhydrous dimethyl sulfoxide
(
DMSO) (2.0 mL) was injected in tube under N atmosphere. After this, the Schlenk
2
o
tube was conducted at 120 C by heating mantle for 24 h. After cooling to room
temperature, water (30 mL) was added and the aqueous phase was extracted by
EtOAc (5×30 mL). The combined organic phases were dried over Na
2
SO , and
4
concentrated in vacuum. The residue was purified by chromatography (petroleum
ether/ethyl acetate = 7:1, v/v) on neutral aluminum oxide to afford the desired product
2
a in 97% yield.
The general procedure for the gram scale synthesis of 2b. In a 100 mL Schlenk
equipped with a magnetic stirrer, 3-(1H-indol-3-yl)-1,3-diphenylpropan-1-one (1b)
t
(7.0 mmol, 2.28 g), elemental sulfur (S
8
) (4.7 mmol, 1.21 g) and NaO Bu (14 mmol,
1
.35 g) was combined and the Schenk tube was sealed. Then anhydrous dimethyl
sulfoxide (DMSO) (40 mL) was injected in tube under N atmosphere. After this, the
2
o
Schlenk tube was conducted at 100 C by heating mantle for 48 h. After cooling to
room temperature, water (100 mL) was added and the aqueous phase was extracted by
EtOAc (5×100 mL). The combined organic phases were dried over Na
2
SO
4
, and
concentrated in vacuum. The residue was purified by chromatography (petroleum
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ether/ethyl acetate = 7:1, v/v) on neutral aluminum oxide to afford the desired product
2
b in 64% yield.
t
The dual C-S bond formation of 1a in the absence of NaO Bu. In a 25 mL Schlenk
1
1
1
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1
1
1
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1
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equipped with a magnetic stirrer, 3-(1H-indol-3-yl)-3-phenyl-1-(o-tolyl)propan-1-one
(1a) (0.30 mmol, 101.8 mg) and elemental sulfur (S
8
) (0.20 mmol, 51.3 mg) was
combined and the Schenk tube was sealed. Then anhydrous dimethyl sulfoxide
(
DMSO) (2.0 mL) was injected in tube under N atmosphere. After this, the Schlenk
2
o
tube was conducted at 120 C by heating mantle for 24 h. After cooling to room
temperature, water (30 mL) was added and the aqueous phase was extracted by
EtOAc (5×30 mL). The combined organic phases were dried over Na
2
SO , and
4
concentrated in vacuum. Only a trace of product was observed in residue.
The dual C-S bond formation of 1a in the presence of TEMPO. In a 25 mL
Schlenk equipped with magnetic stirrer,
a
3-(1H-indol-3-yl)-3-phenyl-1-(o-tolyl)propan-1-one (1a) (0.30 mmol, 101.8 mg),
t
elemental sulfur (S
8
) (0.20 mmol, 51.3 mg), NaO Bu (0.30 mmol, 28.8 mg) and
TEMPO (0.60 mmol, 93.8 mg) was combined and the Schenk tube was sealed. Then
anhydrous dimethyl sulfoxide (DMSO) (2.0 mL) was injected in tube under N
2
o
atmosphere. After this, the Schlenk tube was conducted at 120 C by heating mantle
for 24 h. After cooling to room temperature, water (30 mL) was added and the
aqueous phase was extracted by EtOAc (5×30 mL). The combined organic phases
were dried over Na
2
SO
4
, and concentrated in vacuum. The residue was purified by
chromatography (petroleum ether/ethyl acetate = 7:1, v/v) on neutral aluminum oxide
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