Decarboxylative/decarbonylative C3-acylation of indoles: Via photocatalysis: A simple and efficient route to 3-acylindoles

Article abstract of DOI:10.1039/c6gc00516k

A simple and efficient strategy for the preparation of 3-acylindoles via visible-light promoted C3-acylation of free (NH)- and N-substituted indoles with α-oxocarboxylic acids was developed. The reaction tolerates a wide range of functional groups, and the corresponding 3-acylindoles were obtained in high yields under mild conditions.

Full text of DOI:10.1039/c6gc00516k

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ARTICLE
Decarboxylative/Decarbonylative C3-acylation of indoles via
photocatalysis: a simple and efficient route to 3-acylindoles
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
a,b
Qing Shi, Pinhua Li,* Xianjin Zhu, and Lei Wang*
DOI: 10.1039/x0xx00000x
A simple and efficient strategy for the preparation of 3-acylindoles via visible-light promoted C3-acylation of free (NH)- and
N-substituted indoles with a-oxocarboxylic acids was developed. The reaction tolerates a wide range of functional groups,
and the corresponding 3-acylindoles were obtained in high yields under mild conditions.
www.rsc.org/
Zhou developed a visible-light photoredox synthesis of 3-acylindoles
Introduction
through an intramolecular oxidative cyclization of o-alkynylated
1
4
N,N-dialkylamines, and Li reported a simple and efficient visible-
Acylated indoles are ubiquitous in biologically active natural
products and pharmaceutical compounds, and are also versatile
precursors for the synthesis of alkaloids and other related
1
5
light-promoted method for the C3-thiocyanation of indoles. As a
continuation of our interest in visible-light photochemistry and
16
inspired by the reported results, we hypothesized that benzoyl
radical generated from a-oxocarboxylic acids could react with
indoles to form 3-acylindoles. We wish to report herein a novel and
mild protocol to 3-acylindoles through a visible-light irradiated C3-
acylation of free (NH)-indoles and N-substituted indoles with a-
heterocycles, such as anti-diabetic, anti-cancer, and inhibitor of
1
HIV-1 integrase.
Additionally, 3-acylindoles are valuable
2
intermediates in a variety of functional group transformations. The
most classic methods for the preparation of 3-acylindoles are
3
4
Friedel-Crafts reaction, Vilsmeier–Haack reaction, and the
5
oxocarboxylic acids in the presence of rose bengal as a
reaction of indole with acyl chlorides. Recently, the synthesis of 3-
17
photocatalyst at ambient conditions (Scheme 1).
acylindoles has got considerable attention, and some significant
approaches have been achieved, such as Ru- and Fe-catalyzed
6
acylation of indoles using anilines as carbonyl sources, Pd-
7
catalyzed acylation of indoles via nitriles as acylating agents, Cu-
8
and Pd-promoted acylation of indoles by α-oxocarboxylic acids,
and Pd-catalyzed carbonylation of indoles with CO and arylboronic
9
acids. Moreover, there are a few efficient methods for the
Scheme 1 Visible-light irradiated C3-acylation of indoles
synthesis of 3-acylindoles through tandem reactions based on
3
10
C(sp )–H bond activation. However, most of the existing methods
are often harmful to the environment. To develop new routes to
them from readily available precursors under mild and
environmentally friendly conditions is highly desirable.
Initially, a model reaction of indole (1a) with phenylglyoxylic
acid (2a) was chosen to optimize the reaction conditions. When
eosin Y (2.0 mol%) was used as a photoredox catalyst, and the
reaction was conducted in ethanol under the irradiation of 3 W
green LED in air for 10 h, it was pleasing to find that the reaction
does indeed proceed and afforded the desired acylation product 3a
Visible light is an environmentally benign and infinitely
available energy source for activating chemical transformations.
11
Although first proposed by Ciamician a century ago, there was no
much attention in this field until 2008 when MacMillan disclosed
the visible light photoredox catalysis as a powerful tool in organic
1
13
in 31% yield. The structure of 3a was characterized by H and
C
18
NMR, and further confirmed by X-ray single crystal analysis. An
improved yield (51%) of 3a was obtained when 4Å molecular sieve
was added (Table 1, entry 1). A slightly improved yield of 3a was
achieved when an oxygen balloon was used instead of air
atmosphere. However, the desired acylation product 3a was also
obtained in 14% yield when the reaction was performed under
nitrogen atmosphere (Table 1, entry 2). In the absence of visible-
light irradiation, no desired product was formed, and only a trace
amount of 3a was detected without photocatalyst (Table 1, entries
3 and 4). Subsequently, a number of photocatalysts, including Ru-
and Ir-complexes and organic dyes (eosin Y, Mes-Acr-Me,
fluorescein, methylene blue, acridine red, neutral red), solvents,
12
synthesis. In the past few years, the visible-light promoted
chemical reactions have received considerable attention, and
1
3
emerged as a hot research topic in organic chemistry. In 2014,
a.
Department of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000, P.
R. China; E-mail: pphuali@126.com, leiwang@chnu.edu.cn.
Tel.: +86-561-380-2069; fax: +86-561-309-0518
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
b.
Chemistry, Chinese Academy of Sciences, Shanghai 200032, P. R. China
Footnotes relating to the title and/or authors should appear here.
†
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
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Journal Name
O
O
O
O
and molar ratio of substrates were examined to improve the
reaction efficiency. It should be noted that the colour of light
emitting diode (LED) was used to match the absorption wavelength
of photocatalyst. Among the photocatalysts examined, rose bengal
H CO
H C
3
3
N
N
H
N
H
3a, 79%
3b, 55%
3e, 81%
3h, 81%
H
3c, 73%
O
O
O
O
F
Cl
Br
a
Table 1 Optimization of the reaction conditions
N
H
N
H
N
H
3d, 85%
3f, 76%
O
O
O
NC
F
Cl
N
N
H
N
H
b
H
3g, 47%
3i, 85%
3l, 59%
Entry
Photocatalyst Light source
Solvent
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
MeCN
Toluene
Yield (%)
O
c
1
2
3
4
5
6
7
8
9
Eosin Y
Eosin Y
－
Green LED
Green LED
Green LED
－
31 , 51
d
e
53 , 14
N
H
N
H
N
H
H3C
F
Cl
3j, 67%
3k, 62%
f
n.r.
O
O
O
O
O
H3C
Eosin Y
trace
trace
trace
Ru(bpy)
2
Cl
2
Blue LED
Green LED
Green LED
Blue LED
CH3
CH3
N
H
N
H
N
H
Br
3m, 63%
3n, 72%
3o, 70%
fac-Ir(ppy)
3
O
g
Mes-Acr-Me
Fluorescein
36
Ph
CH3
15
40
45
49
71
41
30
43
40
n.r.
n.r.
N
N
N
H
CH3 3r, 70%
3p, 88%
CH3 3q, 72%
Methylene blue Visible light
a
Reaction conditions: 1 (0.30 mmol), 2a (0.60 mmol), rose bengal (1.0
mol%), 4Å molecular sieve (80 mg), ethanol (2.0 mL), 3W green LED, air, r.t.,
0 h. Isolated yield.
1
1
1
1
1
1
1
1
1
1
2
2
0
1
2
3
4
5
6
7
8
9
0
1
Acridine red
Neutral red
Rose bengal
Rose bengal
Rose bengal
Rose bengal
Rose bengal
Rose bengal
Rose bengal
Rose bengal
Rose bengal
Rose bengal
Visible light
Green LED
Green LED
Green LED
Green LED
Green LED
Green LED
Green LED
Green LED
Green LED
Green LED
Green LED
b
1
showed the highest reactivity, which was used widely in visible light
1
9
promoted organic transformation. Unfortunately, Ru(bpy)
fac-Ir(ppy) were no longer the effective catalysts in this reaction
Table 1, entries 5−11). A series of solvents were screened, and
ethanol was the most effective medium for the reaction, affording
product 3a in 71% yield (Table 1, entries 12−18). The loading of
photocatalyst, the ratio of 1a to 2a, as well as the reaction time
were optimized, which are also summarized in Table 1 (Table 1,
entries 19−21).
To explore the generality of this direct acylation reaction,
different substituted indoles reacted with phenylglyoxylic acid (2a)
under the optimized conditions. The results are listed in Table 2. A
variety of free (NH)-indoles and N-substituted indoles underwent
the direct acylation with 2a smoothly to afford the desired products
in good to excellent yields. It should be noted that indoles with an
electron-poor group on the phenyl rings gave the higher yields of
the corresponding products, while indoles with an electron-rich
group on the phenyl rings generated the low yields of the desired
2 2
Cl and
3
(
CHCl
ClCH CH
DMF
3
2
2
Cl
DMSO
EtOH
EtOH
EtOH
h
i
j
35 , 73, 64
k
l
58 , 79
m
n
51 , 80
a
Reaction conditions: 1a (0.30 mmol), 2a (0.45 mmol), photocatalyst (2.0
mol%), solvent (2.0 mL), 4Å molecular sieve (80 mg), r.t., air, 3W LED for
b
c
d
1
0 h. Isolated yield. In the absence of 4Å molecular sieve. Oxygen
e f g
balloon instead of air. Nitrogen atmosphere. n.r. = no reaction. Mes-Acr-
Me = 10-methyl-9-(2,4,6-trimethylphenyl)acridinium perchlorate. Rose
bengal (0.5 mol%) was used. Rose bengal (1.0 mol%) was added. Rose
h
i
j
3
products in the most of cases. For example, indoles attached CH O
k
l
bengal (3.0 mol%) was used. 2a (0.30 mmol) was added. 2a (0.60 mmol)
was used. 6 h. 15 h.
and CH3 on their 5-positions reacted with 2a to generate the
corresponding products 3b and 3c in 55% and 73% yields,
respectively. On the other hand, the reactions of indoles having F,
Cl and Br on their 5-positions or 6-positions with 2a to afford the
desired products (3d−f, 3h and 3i) in 76−85% yields. However, 5-
cyanoindole reacted with 2a to give the product 3g in 47% yield.
m
n
a
Table 2 The generality of indoles
3
The indoles with both an electron-donating group (CH ) and an
electron-withdrawing group (F, Cl and Br) on their 7-positions
showed a comparable reactivity in the reactions with 2a, providing
the 3-acylated indoles (3j−m) in
a range of 59−67% yields.
2
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Moreover, 2,6-dimethyl-1H-indole, 2-methyl-1H-indole, 2-phenyl- electron-deficient groups including p-F, p-Cl, p-Br, p-I, p-CF
3
, and p-
1
H-indole, N-methylindole and 2-methyl-N-methylindole could also NO exhibited good reactivity and gave high yields of the
2
be involved in the acylation reactions, and high yields (70−88%) of corresponding products (4e–j). ortho- and meta-Substituted
the desired products (3n−r) were obtained. It should be noted that phenylglyoxylic acids reacted with indole 1a to provide the
when 3-methylindole and 3-cyanoindole were subjected to the corresponding products (4k–n) in moderate to good yields. 2-
reaction under the optimized reaction conditions, no reaction was Naphthyl-2-oxo-acetic acid also gave the anticipated product 4o in
occurred and the starting materials were recovered. To our 52% yield. It is worth noting that aliphatic α-oxocarboxylic acids,
disappointed, when other electron enriched heterocycles, including such as 2-oxopropanoic acid, 2-oxobutanoic acid and 2-cyclopropyl-
pyrrole, N-methyl pyrrole, furan, benzofuran, thiophene, 2-oxoacetic acid, were also compatible in this reaction, giving fair
thianaphthene, imidazole, benzimidazole, thiazole, benzothiazole yields of the desired products (4p–r).
and benzoxazole were involved in the reaction, none of the desired
To understand this transformation, a numbers of control
products was obtained. In addition, the electron enriched aromatics, experiments and analytical survey were conducted. In the presence
such as phenol and N,N-dimethylaniline were also failed in this of rose bengal and 3W green LED irradiation, benzoyl radical
transformation.
derived from 2a was in situ trapped by TEMPO (2,2,6,6-tetramethyl-
-piperidinyloxy), affording the corresponding adduct 5 in 52% yield
(ESI for detail). In addition, a simultaneous decarboxylation process
release of CO ) and decarbonylation process (release of CO) was
confirmed by FT-IR analysis of the resulting gas during the reaction.
The ratio of CO /CO was found to be 30.1/1 from the result of FT-IR
1
a
Table 3 The scope of α-oxocarboxylic acids
(
2
2
analysis (ESI, Figure S3 and S4), indicating the decarboxylation
process in majority. Further, it is established that the photoexcited
rose bengal (RB*) could react with molecular oxygen to generate
O
O
O
O
O
tBu
1
20
CH3
OCH3
Br
Et
2
singlet oxygen ( O ). In order to determine the active species of
oxygen
involved
in
the
present
reaction,
2,2,6,6-
N
H
N
N
H
H
tetramethylpiperidine (TEMP) and 5,5-dimethyl-pyrroline-N-oxide
4
a, 71%
d, 47%
4b, 64%
4e, 71%
4h, 79%
4c, 50%
4f, 67%
1
2•−
(
2
DMPO) were employed to capture O and O , respectively.
O
O
O
O
F
Cl
Irradiation of the ethanol solution of TEMP and rose bengal (RB) in
air by green LED resulted in the formation of a strong characteristic
N
H
N
N
1
H
H
signal of O adduct with TEMP, and this signal decreased obviously
4
2
as addition of phenylglyoxylic acid (2a) into the solution (ESI for
O
1
I
CF3
detail). It is indicated that 2a reacted with
O
2
2
efficiently to
•−
consume it rapidly. However, there is no signal of O adduct with
N
H
N
H
N
2•−
H
DMPO, excluding the formation of O in the reaction system.
4
g, 75%
4i, 90%
On the basis of our observation and literature report, a plausible
pathway for the reaction was proposed with indole (1a) and
phenylglyoxylic acid (2a), as shown in Scheme 2. At first, RB was
excited to its excited state RB* under green LED irradiation. Then,
the formed RB* was interacted with molecular oxygen to generate
O
O
NO2
CH3
4k, 50%
Cl
N
H
N
H
N
4j, 80%
Cl
H
4
l, 86%
1
20
singlet oxygen
2
O via the energy transfer, along with the
O
O
O
generation of RB to its ground state. Subsequently, the obtained
1
O
2
reacted with 2a and followed by a decarboxylation, leading to
hydroperoxyl radical (I) and benzoyl radical (II) along with the
release of CO . The reaction of benzoyl radical (II) occurred through
Cl
m, 65%
Cl
N
H
N
H
N
H
4
4n, 60%
4o, 51%
4r, 49%
2
O
O
O
the different transformation pathway simultaneously. In path A,
benzoyl radical (II) added to the carbon-carbon double bond of
indole (1a) at C3-position to afford intermediate radical (III) and
N
H
N
N
H
4p, 69%
H
4q, 52%
a
Reaction conditions: 1a (0.30 mmol), 2 (0.60 mmol), rose bengal (1.0 followed by a one-electron oxidation in the presence of the formed
mol%), 4Å molecular sieve (80 mg), ethanol (2.0 mL), 3W green LED, air, r.t.,
hydroperoxyl radical (I) to generate intermediate IV, which was
b
1
0 h. Isolated yield.
deprotonated (aromatization process) to give the final product 3-
benzoylindole (3a). On the other hand (path B), in the presence of
the obtained I, the free indole (1a) was oxidized to indolinium
radical cation (V) via a singlet electron transfer (SET) process, as the
Subsequently, the scope of α-oxocarboxylic acids was also
investigated under the optimized reaction conditions. As shown in
Table 3, a series of functional groups on the phenyl rings in 2-oxo-2-
arylacetic acids were tolerated, leading to the desired products in
21
related papers. Subsequently, the generated benzoyl radical (II)
added to the carbon-carbon double bond of indolinium radical
cation (V) at C3-position to afford an intermediate VI, which was
underwent an aromatization process to generate 3-benzoylindole
good to excellent yields. It was found that electron- sufficient
t
groups such as p-CH
3
, p-C
2
H
5
, p- C
4
H
9
, and p-CH
3
O showed lower
reactivity, providing the products 4a−d in 47–71% yields, while
(
3a) as the final product. It should be noted that the benzoyl radical
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(II) could undergoes a decarbonylative process to form phenyl free All chemical shifts are given as δ value (ppm) with reference to
radical and CO (CO
2
/CO = 30.1/1).
tetramethylsilane (TMS) as an internal standard. The peak patterns
are indicated as follows: s, singlet; d, doublet; t, triplet; m,
multiplet; q, quartet. The coupling constants, J, are reported in
Hertz (Hz). High resolution mass spectroscopy data of the product
were collected on an Agilent Technologies 6540 UHD Accurate-
Mass Q-TOF LC/MS (ESI). Indoles were purchased from Energy
Chemical. α-Oxocarboxylic acids were prepared according to the
O2
RB*
RB
Detected by
ESR
hv
O
1O2
OH
Ph
22
2a
O
reported methods. All the solvents and commercially available
reagents were purchased from commercial suppliers. Products
were purified by flash chromatography on 200–300 mesh silica gels,
O
O
O
OOH
I
Ph
Ph
TEMPO
5
O
2
SiO .
Trapped by
TEMPO
Major
Ph
Typical procedure for C3-acylation of indole with phenylglyoxylic
acid
O
Detected by CO2
FT-IR
Detected by
FT-IR
Minor
CO
Ph
II
Indole (1a, 0.30 mmol), phenylglyoxylic acid (2a, 0.6 mmol), rose
bengal (0.0030 mmol, 1.0 mol%), 4Å molecular sieve (80 mg) and
ethanol (2.0 mL) was added to an oven-dried reaction vessel
equipped with magnetic stirring bar, and the reaction vessel was
irradiated using 3 W green LED at room temperature under air
atmosphere for 10 h. After the reaction was completed, the
reaction solution was concentrated under reduced pressure to yield
crude product, which was purified by flash chromatography (silica
gel, petroleum ether/ethyl acetate = 3:1) to give the desired
product 3a in 79% yield as a pale yellow solid.
Path B
Ph
Path A
+
N
H
N
H
1
a
V
O
SET
O
Ph
HOO
OOH
H
I
N
N
N
H
H
H
VI
III
OOH
1a
I
HOO
O
Ph
H2O2
O
Ph
N
H
N
H
IV
Characterization data for all products
3
a
8a
1
HOO
(1H-Indol-3-yl)(phenyl)methanone (3a): Pale yellow solid. H NMR
400 MHz, DMSO-d ) δ: 12.07 (s, 1H), 8.27 (d, J = 6.4 Hz, 1H), 7.93 (s,
H), 7.79 (d, J = 7.2 Hz, 2H), 7.62−7.59 (m, 1H), 7.56−7.52 (m, 3H),
H2O2
(
6
1
7
1
1
1
3
Scheme 2 The proposed mechanism
6
.29−7.22 (m, 2H); C NMR (100 MHz, DMSO-d ) δ: 189.94, 140.53,
36.69, 135.69, 130.98, 128.34, 128.32, 126.22, 123.09, 121.86,
21.44, 115.00, 112.20.
Conclusions
2
3
In summary, we have developed a convenient and efficient (5-Methoxy-1H-indol-3-yl)(phenyl)methanone (3b): Pale yellow
1
method for the preparation of 3-acylindoles through visible-light- solid. H NMR (400 MHz, DMSO-d ) δ: 11.96 (s, 1H), 7.87 (d, J = 2.8
6
promoted C3-acylation of free (NH)- and N-substituted indoles with Hz, 1H), 7.81 (d, J = 2.4 Hz, 1H), 7.78 (d, J = 6.8 Hz, 2H), 7.61−7.57
a-oxocarboxylic acids under mild reaction conditions. Comparing (m, 1H), 7.55−7.51 (m, 2H), 7.43 (d, J = 8.8 Hz, 1H), 6.91 (dd, J = 2.4
1
1
3
with the existing procedures for the synthesis of 3-acylindoles, this Hz, J = 8.4 Hz, 1H), 3.81 (s, 3H); C NMR (100 MHz, DMSO-d ) δ:
2
6
protocol has several advantages, such as the use of an inexpensive, 189.90, 155.57, 140.65, 135.84, 131.56, 130.88, 128.34, 128.24,
commercial available, and easily degradable organic-dye (rose 127.06, 114.86, 113.00, 112.95, 103.27, 55.29.
bengal) as photocatalyst, ethanol as a low toxicity solvent, ambient
2
4
(
5-Methyl-1H-indol-3-yl)(phenyl)methanone (3c): Pale yellow
conditions (room temperature and air atmosphere) and green LED
irradiation, and high regioselectivity and good functional group
compatibility. Moreover, a plausible reaction mechanism has been
proposed on the basis of the control experiments and ESR
investigations. An in-depth mechanistic study and further attempts
to other visible-light promoted organic transformations through the
energy transfer pathway are currently underway in our laboratory.
1
solid. H NMR (400 MHz, DMSO-d
.86 (s, 1H), 7.77 (d, J = 7.2 Hz, 2H), 7.61−7.58 (m, 1H), 7.55−7.51
m, 2H), 7.41 (d, J = 8.0 Hz, 1H), 7.09 (d, J = 8.0 Hz, 1H), 2.43 (s, 3H);
6
) δ: 11.96 (s, 1H), 8.09 (s, 1H),
7
(
1
3
6
C NMR (100 MHz, DMSO-d ) δ: 189.93, 140.66, 135.70, 135.03,
1
1
30.91, 130.73, 128.33, 128.29, 126.52, 124.59, 121.20, 114.66,
11.85, 21.33.
6
(
5-Fluoro-1H-indol-3-yl)(phenyl)methanone (3d): Pale yellow
1
Experimental section
General remarks
6
solid. H NMR (400 MHz, DMSO-d ) δ: 12.19 (s, 1H), 8.03 (s, 1H),
7
7
d
1
.97 (dd, J
.62−7.52 (m, 4H), 7.15−7.10 (m, 1H); C NMR (100 MHz, DMSO-
) δ: 189.78, 158.71 (d, J = 233.2 Hz), 140.21, 137.11, 133.32,
1 2
= 10.0 Hz, J =2.4 Hz, 1H), 7.80 (d, J = 7.2 Hz, 2H),
1
3
1
13
The H NMR and C NMR spectra were recorded on a 400 MHz
Bruker FT-NMR spectrometers (400 MHz or 100 MHz, respectively).
6
31.12, 128.39, 128.32, 126.91 (d, J = 11.0 Hz), 115.07 (d, J = 4.5
4
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+
Hz), 113.48 (d, J = 9.8 Hz), 111.29 (d, J = 25.9 Hz), 106.31 (d, J = 24.5 115.80 (d, J = 1.8 Hz), 108.13 (d, J = 15.6 Hz). HRMS (ESI) ([M+H] )
Hz).
Calcd. For C15H10FNO: 240.0819, Found: 240.0819.
6
(
5-Chloro-1H-indol-3-yl)(phenyl)methanone (3e): Pale yellow (7-Chloro-1H-indol-3-yl)(phenyl)methanone (3l): Pale yellow solid.
1
1
solid. H NMR (400 MHz, DMSO-d
6
) δ: 12.25 (s, 1H), 8.26 (d, J = 1.6
6
H NMR (400 MHz, DMSO-d ) δ: 12.49 (s, 1H), 8.23 (d, J = 7.6 Hz,
Hz, 1H), 8.03 (s, 1H), 7.80 (d, J = 7.2 Hz, 2H), 7.63−7.59 (m, 1H), 1H), 7.93 (s, 1H), 7.81 (d, J = 6.8 Hz, 2H), 7.64−7.60 (m, 1H),
1
3
13
7
.57−7.52 (m, 3H), 7.30−7.27 (m, 1H); C NMR (100 MHz, DMSO- 7.57−7.53 (m, 2H), 7.36 (d, J = 7.6 Hz, 1H) 7.27−7.23 (m, 1H);
) δ: 189.83, 140.09, 136.93, 135.22, 131.25, 128.44, 128.37, NMR (100 MHz, DMSO-d ) δ: 189.90, 140.02, 136.06, 133.59,
27.46, 126.68, 123.18, 120.60, 114.59, 113.89. 131.34, 128.44, 128.41, 128.16, 123.00, 122.74, 120.42, 116.53,
C
d
6
6
1
+
1
15.91. HRMS (ESI) ([M+H] ) Calcd. For C15
H10ClNO: 256.0524,
2
4
(
5-Bromo-1H-indol-3-yl)(phenyl)methanone (3f):
Pale yellow
Found: 256.0527.
1
solid. H NMR (400 MHz, DMSO-d
6
) δ: 12.25 (s, 1H), 8.41 (s, 1H),
8
.01 (d, J = 2.8 Hz, 1H), 7.80 (d, J = 7.2 Hz, 2H), 7.63−7.60 (m, 1H), (7-Bromo-1H-indol-3-yl)(phenyl)methanone (3m): Pale yellow
1
3
1
7.56−7.50 (m, 3H), 7.42−7.39 (m, 1H); C NMR (100 MHz, DMSO- solid. H NMR (400 MHz, DMSO-d
6
) δ: 12.34 (s, 1H), 8.27 (d, J = 7.6
d
6
) δ: 189.79, 140.04, 136.76, 135.45, 131.25, 128.43, 128.35, Hz, 1H), 7.89 (s, 1H), 7.81 (d, J = 6.8 Hz, 2H), 7.64−7.60 (m, 1H),
1
3
128.04, 125.72, 123.61, 114.69, 114.44, 114.31.
7.57−7.49 (m, 3H), 7.22−7.18 (m, 1H); C NMR (100 MHz, DMSO-
d
6
) δ: 189.93, 140.00, 136.00, 135.09, 131.33, 128.44, 128.38,
6
1
3
-Benzoyl-1H-indole-5-carbonitrile (3g): Pale yellow solid. H NMR
1
27.92, 125.82, 123.36, 120.88, 115.93, 104.66. HRMS (ESI)
+
(400 MHz, DMSO-d
6
) δ: 12.54 (s, 1H), 8.62 (s, 1H), 8.18 (s, 1H), 7.82
(
[M+H] ) Calcd. For C15H10BrNO: 300.0019, Found: 300.0023.
(
d, J = 7.2 Hz, 2H), 7.71 (d, J = 8.4 Hz, 1H), 7.65−7.61 (m, 2H),
1
3
7
1
1
.57−7.54 (m, 2H); C NMR (100 MHz, DMSO-d
38.57, 137.80, 131.53, 128.51, 128.45, 126.51, 126.09, 126.03, solid. H NMR (400 MHz, DMSO-d
20.12, 115.11, 113.76, 104.16. 3H), 7.51−7.48 (m, 2H), 7.27 (d, J = 8.0 Hz, 1H), 7.22 (s, 1H), 6.94 (d,
6
) δ: 189.79, 139.69, (2,5-Dimethyl-1H-indol-3-yl)(phenyl)methanone (3n): Pale yellow
1
6
) δ: 11.81 (s, 1H), 7.61−7.56 (m,
1
3
J = 7.6 Hz, 1H), 2.33 (s, 3H), 2.27 (s, 3H); C NMR (100 MHz, DMSO-
(
6-Fluoro-1H-indol-3-yl)(phenyl)methanone (3h): Pale yellow solid.
d
6
) δ: 191.66, 144.27, 141.78, 133.29, 130.85, 129.54, 128.25,
27.93, 127.59, 123.20, 119.95, 112.22, 110.82, 21.31, 14.20. HRMS
1
H NMR (400 MHz, DMSO-d
6
) δ: 12.12 (s, 1H), 8.27−8.24 (m, 1H),
1
+
7
.95 (s, 1H), 7.80 (d, J = 7.2 Hz, 2H), 7.62−7.52 (m, 3H), 7.33−7.31
(
ESI) ([M+H] ) Calcd. For C17H15NO: 250.1226, Found: 250.1232.
13
(m, 1H), 7.13−7.08 (m, 1H); C NMR (100 MHz, DMSO-d
6
) δ:
2
4
1
89.82, 159.40(d, J = 235.7 HZ), 158.23, 140.21, 136.79 (d, J = 12.5 (2-Methyl-1H-indol-3-yl)(phenyl)methanone (3o): Pale yellow
1
Hz), 136.31 (d, J = 2.4 Hz), 131.11, 128.36, 128.32, 122.91 (d, J = 0.9 solid. H NMR (400 MHz, DMSO-d ) δ: 11.95 (s, 1H), 7.62−7.56 (m,
6
Hz), 122.62 (d, J = 9.9 Hz), 114.95, 110.17 (d, J = 23.6 Hz), 98.43 (d, J 3H), 7.52−7.48 (m, 2H), 7.39 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.0 Hz,
+
13
=
25.6 Hz). HRMS (ESI) ([M+H] ) Calcd. For C15
H
10FNO: 240.0825, 1H), 7.14−7.10 (m, 1H), 7.03−6.99 (m, 1H), 2.39 (s, 3H); C NMR
Found: 240.0826.
(100 MHz, DMSO-d
6
) δ: 191.71, 144.40, 141.68, 134.97, 130.97,
28.31, 127.98, 127.28, 121.79, 120.91, 120.00, 112.49, 111.22,
4.15.
1
1
(
6-Chloro-1H-indol-3-yl)(phenyl)methanone (3i): Pale yellow solid.
1
H NMR (400 MHz, DMSO-d
6
) δ: 12.16 (s, 1H), 8.24 (d, J = 8.4 Hz,
2
5
1
1
7
1
1
2
H), 7.99 (s, 1H), 7.80 (d, J = 7.2 Hz, 2H), 7.63−7.52 (m, 4H), Phenyl(2-phenyl-1H-indol-3-yl)methanone (3p): White solid.
.28−7.25 (m, 1H); C NMR (100 MHz, DMSO-d
37.17, 136.54, 131.19, 128.39, 128.34, 127.62, 125.02, 122.75, 7.54−7.52 (m, 3H), 7.40−7.34 (m, 3H), 7.26−7.14 (m, 7H); C NMR
22.15, 114.93, 111.94. HRMS (ESI) ([M+H] ) Calcd. For C15
56.0524, Found: 256.0524.
H
1
3
6 6
) δ: 189.81, 140.11, NMR (400 MHz, DMSO-d ) δ: 12.20 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H),
13
+
H
10ClNO: (100 MHz, DMSO-d
131.30, 129.50, 129.02, 128.42, 128.17, 127.99, 127.74, 122.82,
21.36, 120.56, 112.17, 111.83.
6
) δ: 192.13, 144.02, 139.82, 135.83, 131.57,
1
2
3
1
(7-Methyl-1H-indol-3-yl)(phenyl)methanone (3j): White solid. H
8
a
1
NMR (400 MHz, DMSO-d
6
) δ: 12.08 (s, 1H), 8.09 (d, J = 7.6 Hz, 1H), (1-Methyl-1H-indol-3-yl)(phenyl)methanone (3q): Yellow solid. H
) δ: 8.28 (d, J = 7.6 Hz, 1H), 8.00 (s, 1H), 7.79
.56−7.52 (m, 2H), 7.16−7.13 (m, 1H), 7.06 (d, J = 7.2 Hz, 1H), 2.53 (d, J = 7.2 Hz, 2H), 7.63−7.53 (m, 4H), 7.36−7.27 (m, 2H), 3.88 (s,
7
.87 (d, J = 2.0 Hz, 1H), 7.79 (d, J = 7.2 Hz, 2H), 7.62−7.59 (m, 1H), NMR (400 MHz, CDCl
3
7
1
3
13
(
s, 3H); C NMR (100 MHz, DMSO-d
6
) δ: 190.01, 140.58, 136.14, 3H); C NMR (100 MHz, CDCl
35.19, 130.99, 128.36, 128.34, 126.04, 123.69, 122.08, 121.50, 130.97, 128.35, 128.28, 126.65, 123.15, 122.22, 121.58, 113.82,
19.01, 115.40, 16.66. 110.61, 33.08.
3
) δ: 189.42, 140.50, 139.39, 137.33,
1
1
8
a
(
7-Fluoro-1H-indol-3-yl)(phenyl)methanone (3k): Pale yellow solid. (1,2-Dimethyl-1H-indol-3-yl)(phenyl)methanone (3r): White solid.
1
1
H NMR (400 MHz, DMSO-d
6
) δ: 12.64 (s, 1H), 8.08 (d, J = 8.0 Hz,
3
H NMR (400 MHz, CDCl ) δ: 7.75 (d, J = 7.2 Hz, 2H), 7.56−7.52 (m,
1
7
H), 7.97 (s, 1H), 7.81 (d, J = 7.2 Hz, 2H), 7.63−7.59 (m, 1H), 1H), 7.46−7.42 (m, 2H), 7.32−7.29 (m, 2H), 7.22−7.18 (m, 1H),
1
3
13
.56−7.52 (m, 2H), 7.24−7.19 (m, 1H), 7.14−7.09 (m, 1H); C NMR 7.08−7.04 (m, 1H), 3.37 (s, 3H), 2.58 (s, 3H); C NMR (100 MHz,
) δ: 189.93 (d, J = 1.4 Hz), 150.32, 147.89, CDCl ) δ: 192.82, 144.64, 141.48, 136.55, 131.37, 129.00, 128.18,
(100 MHz, DMSO-d
6
3
1
40.14, 136.09, 131.28, 129.96 (d, J = 4.7 Hz), 128.42 (d, J = 0.8 Hz), 127.07, 122.00, 121.39, 120.95, 113.62, 109.09, 29.63, 12.47.
24.55 (d, J = 13.2 Hz), 122.48 (d, J = 6.1 Hz), 117.60 (d, J = 3.5 Hz),
1
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ARTICLE
Journal Name
7
b
1
13
(
1H-Indol-3-yl)(p-tolyl)methanone (4a): Yellow solid. H NMR 1H), 7.29−7.22 (m, 2H); C NMR (100 MHz, DMSO-d
6
) δ: 188.96,
(
400 MHz, DMSO-d ) δ: 12.04 (s, 1H), 8.27−8.25 (m, 1H), 7.94 (d, J = 139.76, 137.20, 136.69, 135.86, 130.26, 126.11, 123.16, 121.95,
.8 Hz, 1H), 7.71 (d, J = 8.0 Hz, 2H), 7.54−7.52 (m, 1H), 7.33 (d, J = 121.38, 114.74, 112.22, 98.49. HRMS (ESI) ([M+H] ) Calcd. For
13
6
+
2
8
.0 Hz, 2H), 7.28−7.22 (m, 2H), 2.40 (s, 3H); C NMR (100 MHz,
) δ: 189.65, 140.96, 137.81, 136.65, 135.27, 128.86,
28.50, 126.30, 122.99, 121.73, 121.44, 115.08, 112.15, 20.98.
C
15
H
10INO: 347.9880, Found: 347.9890.
DMSO-d
6
1
(1H-Indol-3-yl)(4-(trifluoromethyl)phenyl)methanone (4i): Pale
1
yellow solid. H NMR (400 MHz, DMSO-d
6
) δ: 12.21 (s, 1H),
1
(4-Ethylphenyl)(1H-indol-3-yl)methanone (4b): Yellow solid.
H
8
7
d
1
7
1
C
.30−8.28 (m, 1H), 7.99−7.96 (m, 3H), 7.89 (d, J = 8.0 Hz, 2H),
1
3
NMR (400 MHz, DMSO-d ) δ: 12.05 (s, 1H), 8.28−8.26 (m, 1H), 7.95
6
.56−7.54 (m, 1H), 7.31−7.25 (m, 2H); C NMR (100 MHz, DMSO-
) δ: 188.70, 144.08 (q, J = 2.72 Hz, J = 1.36 Hz), 136.81, 136.51,
30.74 (q, J = 63.3 Hz, J = 31.6 Hz), 128.99, 126.05, 125.32 (q, J
.5 Hz, J = 3.7 Hz), 124.00 (q, J = 541.5 Hz, J = 270.8 Hz), 123.33,
22.15, 121.42, 114.82, 112.31. HRMS (ESI) ([M+H] ) Calcd. For
NO: 290.0787, Found: 290.0791.
(s, 1H), 7.74 (d, J = 8.0 Hz, 2H), 7.54−7.52 (m, 1H), 7.36 (d, J = 8.0 Hz,
6
1
2
2
H), 7.28−7.22 (m, 2H), 2.69 (q, J
1
= 15.2 Hz, J
2
= 7.6 Hz, 2H), 1.23 (t,
) δ: 189.64, 147.09,
38.06, 136.65, 135.32, 128.58, 127.68, 126.31, 122.99, 121.73,
1
2
1
=
1
3
J = 7.6 Hz, 3H); C NMR (100 MHz, DMSO-d
6
2
1
2
+
1
1
+
21.45, 115.06, 112.14, 28.06, 15.25. HRMS (ESI) ([M+H] ) Calcd.
15NO: 250.1226, Found: 250.1226.
16 10 3
H F
For C17
H
2
4
(
1
1H-Indol-3-yl)(4-nitrophenyl)methanone (4j): Pale yellow solid.
(
4-(tert-Butyl)phenyl)(1H-indol-3-yl)methanone (4c): Yellow solid.
6
H NMR (400 MHz, DMSO-d ) δ: 12.25 (s, 1H), 8.35 (d, J = 8.8 Hz,
1
H NMR (400 MHz, DMSO-d
6
) δ: 12.03 (s, 1H), 8.28−8.26 (m, 1H),
2
7
1
1
H), 8.29−8.27 (m, 1H), 8.01−7.98 (m, 3H), 7.56−7.54 (m, 1H),
.31−7.25 (m, 2H); C NMR (100 MHz, DMSO-d ) δ: 188.14, 148.63,
6
7
7
1
1
.96 (d, J = 2.4 Hz, 1H), 7.75 (d, J = 8.4 Hz, 2H), 7.56−7.51 (m, 3H),
.28−7.21 (m, 2H), 1.34 (s, 9H); C NMR (100 MHz, DMSO-d ) δ:
6
13
1
3
45.94, 136.83, 136.77, 129.50, 125.95, 123.57, 123.47, 122.30,
89.58, 153.83, 137.80, 136.64, 135.41, 128.34, 126.29, 125.10,
21.42, 114.84, 112.38.
23.00, 121.74, 121.45, 115.02, 112.13, 34.60, 30.94. HRMS (ESI)
+
([M+H] ) Calcd. For C19
H
19NO: 278.1539, Found: 278.1532.
7b
1
(
1H-Indol-3-yl)(m-tolyl)methanone (4k): Pale yellow solid.
H
NMR (400 MHz, DMSO-d ) δ: 12.03 (s, 1H), 8.27−8.25 (m, 1H), 7.93
6
2
3
(
1H-Indol-3-yl)(4-methoxyphenyl)methanone (4d): Yellow solid.
(
d, J = 2.8 Hz, 1H), 7.59−7.57 (m, 2H), 7.54−7.52 (m, 1H), 7.44−7.41
m, 2H), 7.28−7.22 (m, 2H), 2.41 (s, 3H); C NMR (100 MHz, DMSO-
1
H NMR (400 MHz, DMSO-d
6
) δ: 12.01 (s, 1H), 8.24 (d, J = 7.2 Hz,
13
(
1
7
H), 7.95 (s, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.52 (d, J = 7.2 Hz, 1H),
d
1
2
6
) δ: 190.09, 140.59, 137.67, 136.69, 135.63, 131.59, 128.76,
1
3
.27−7.20 (m, 2H), 7.07 (d, J = 8.4 Hz, 2H), 3.85 (s, 3H); C NMR
) δ: 188.74, 161.69, 136.60, 134.78, 132.95,
28.19, 126.24, 125.55, 123.06, 121.82, 121.45, 115.09, 112.19,
0.95.
(100 MHz, DMSO-d
6
1
30.56, 126.41, 122.92, 121.62, 121.44, 115.06, 113.62, 112.12,
5.35.
5
(
1
3-Chlorophenyl)(1H-indol-3-yl)methanone (4l): Pale yellow solid.
H NMR (400 MHz, DMSO-d
6
) δ: 12.14 (s, 1H), 8.27−8.25 (m, 1H),
7
b
1
(
4-Fluorophenyl)(1H-indol-3-yl)methanone (4e): White solid. H
7
2
1
1
.99 (s, 1H), 7.77−7.74 (m, 2H), 7.67−7.65 (m, 1H), 7.58−7.54 (m,
H), 7.30−7.24 (m, 2H); C NMR (100 MHz, DMSO-d ) δ: 188.21,
6
13
6
NMR (400 MHz, DMSO-d ) δ: 12.07 (s, 1H), 8.26 (d, J = 6.8 Hz, 1H),
7
.95 (s, 1H), 7.89−7.86 (m, 2H), 7.54 (d, J = 7.2 Hz, 1H), 7.37−7.32
m, 2H), 7.29−7.22 (m, 2H); C NMR (100 MHz, DMSO-d
42.43, 136.76, 136.19, 133.23, 130.72, 130.30, 127.84, 126.97,
13
(
6
) δ:
26.10, 123.24, 122.04, 121.39, 114.71, 112.28. HRMS (ESI)
+
1
1
1
88.48, 163.75 (d, J = 247.0 Hz), 137.00 (d, J = 3.0 Hz), 136.70,
(
[M+H] ) Calcd. For C15
H
15ClNO: 256.0524, Found: 256.0525.
35.64, 130.96 (d, J = 8.8 Hz), 126.23, 123.12, 121.88, 121.41,
15.25 (d, J = 21.4 Hz), 114.87, 112.21.
(2,5-Dichlorophenyl)(1H-indol-3-yl)methanone (4m): Pale yellow
1
solid. H NMR (400 MHz, DMSO-d
6
) δ: 12.21 (s, 1H), 8.19−8.17 (m,
2
3
1
(
4-Chlorophenyl)(1H-indol-3-yl)methanone (4f): White solid. H
1H), 7.77 (s, 1H), 7.63−7.60 (m, 3H), 7.54−7.52 (m, 1H), 7.30−7.25
1
3
NMR (400 MHz, DMSO-d
6
6
) δ: 12.15 (s, 1H), 8.30−8.28 (m, 1H), 7.98 (m, 2H); C NMR (100 MHz, DMSO-d ) δ: 186.39, 141.76, 137.39,
(
s, 1H), 7.81 (d, J = 8.0 Hz, 2H), 7.58−7.54 (m, 3H), 7.30−7.24 (m, 137.06, 131.80, 131.41, 130.43, 128.40, 128.22, 125.30, 123.42,
H); C NMR (100 MHz, DMSO-d ) δ: 188.62, 139.15, 136.76, 122.36, 121.11, 115.64, 112.51. HRMS (ESI) ([M+H] ) Calcd. For
6
1
3
+
2
1
1
35.88, 135.83, 130.21, 128.42, 126.20, 123.21, 122.00, 121.46,
14.87, 112.26.
C
15
H
9
2
CI NO: 290.0134, Found: 290.0135.
(
2-Chlorophenyl)(1H-indol-3-yl)methanone (4n): Pale yellow solid.
1
2
4
1
H NMR (400 MHz, DMSO-d ) δ: 12.13 (s, 1H), 8.18−8.16 (m, 1H),
6
(
4-Bromophenyl)(1H-indol-3-yl)methanone (4g): Yellow solid. H
13
7
.65 (d, J = 3.2 Hz, 1H), 7.58−7.44 (m, 5H), 7.30−7.24 (m, 2H);
C
NMR (400 MHz, DMSO-d ) δ: 12.14 (s, 1H), 8.27−8.25 (m, 1H), 7.98
6
13
6
NMR (100 MHz, DMSO-d ) δ: 188.20, 140.28, 137.01, 136.83,
(
s, 1H), 7.73 (s, 4H), 7.53 (d, J = 7.2 Hz, 1H), 7.29−7.23 (m, 2H);
NMR (100 MHz, DMSO-d ) δ: 188.70, 139.47, 136.72, 135.91,
31.35, 130.39, 126.14, 124.67, 123.19, 121.98, 121.40, 114.78,
12.24.
C
1
1
2
30.65, 129.72, 129.61, 128.66, 127.02, 125.40, 123.32, 122.25,
6
+
21.14, 116.05, 112.49. HRMS (ESI) ([M+H] ) Calcd. For C15
56.0524, Found: 256.0525.
H15ClNO:
1
1
1
(
1H-Indol-3-yl)(naphthalen-2-yl)methanone (4o): Pale yellow solid.
(
1H-Indol-3-yl)(4-iodophenyl)methanone (4h): Pale yellow solid. H
NMR (400 MHz, DMSO-d ) δ: 12.12 (s, 1H), 8.26−8.24 (m, 1H), 7.97
s, 1H), 7.91 (d, J = 8.0 Hz, 2H), 7.57 (d, J = 8.0 Hz, 2H), 7.53−7.51 (m,
1
H NMR (400 MHz, DMSO-d
6
) δ: 12.10 (s, 1H), 8.42 (s, 1H),
6
8
.33−8.31 (m, 1H), 8.12 (d, J = 7.6 Hz, 1H), 8.07−8.01 (m, 3H), 7.90
(
6
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Journal Name
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DOI: 10.1039/C6GC00516K
ARTICLE
1
3
(
d, J = 8.0 Hz, 1H), 7.66−7.55 (m, 3H), 7.31−7.25 (m, 2H); C NMR
100 MHz, DMSO-d ) δ: 189.86, 137.75, 136.74, 135.90, 134.12,
32.16, 129.15, 128.86, 128.01, 127.55, 126.60, 126.31, 125.24,
W. M. Stalick, Synthesis, 2004, 2277.
) R. J. Sundberg, The Chemistry of Indoles, Academic Press,
New York, 1970; ( ) J. C. Powers, J. Org. Chem., 1965, 30, 2534;
(c) F. Seemann, E. Wiskott, P. Niklaus and F. Troxler, Helv. Chim.
Acta, 1971, 54, 2411.
(
(
4)
5)
(a
(
6
b
1
1
+
23.10, 121.87, 121.47, 115.22, 112.21. HRMS (ESI) ([M+H] ) Calcd.
13NO: 272.1070, Found: 272.1071.
For C19
H
(
(b
a
) J. Bergman and L. Venemaim, Tetradadron, 1990, 46, 6061;
) J. E. Taylor, M. D. Jones, J. M. J. Williams and S. D. Bull, Org.
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b
1
1
-(1H-Indol-3-yl)ethanone (4p): Yellow solid. H NMR (400 MHz,
DMSO-d ) δ: 11.92 (s, 1H), 8.30−8.30 (m, 1H), 8.21 (d, J = 7.2 Hz,
H), 7.48 (d, J = 7.6 Hz, 1H), 7.23−7.16 (m, 2H), 2.46 (s, 3H);
NMR (100 MHz, DMSO-d ) δ: 192.61, 136.65, 134.25, 125.29,
22.68, 121.61, 121.31, 116.81, 112.04, 27.21.
c
6
d
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C
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(
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-(1H-Indol-3-yl)propan-1-one (4q): Yellow solid. H NMR (400
) δ:11.89 (s, 1H), 8.30 (s, 1H), 8.21 (d, J = 7.2 Hz, 1H),
.47 (d, J = 7.6 Hz, 1H), 7.22−7.15 (m, 2H), 2.87 (q, J = 7.2 Hz, J
4.4 Hz, 2H), 1.12 (t, J = 7.6 Hz, 3H); C NMR (100 MHz, DMSO-d
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MHz, DMSO-d
6
7
1
1
2
=
1
3
6
)
δ:195.82, 136.60, 133.39, 125.41, 122.58, 121.52, 121.52, 116.00,
+
(
(
a
) X.-F. Xia, L.-L. Zhang, X.-R. Song, Y.-N.Niu, X.-Y. Liu and Y.-M.
) A. Gogoi, S. Guin, S.
) A. Gogoi,
1
11.99, 31.84, 9.06. HRMS (ESI) ([M+H] ) Calcd. For C11
74.0913, Found: 256.0914.
H11NO:
b
1
c
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A. Modi, S. Guin, S. K. Rout, D. Das and B. K. Patel, Chem.
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photoredox catalysis, see: (a) K. Zeitler, Angew. Chem., Int.
Ed., 2009, 48, 9785; (b) T. P. Yoon, M. A. Ischay and J. Du,
Cyclopropyl(1H-indol-3-yl)methanone (4r): Yellow solid. H NMR
(400 MHz, DMSO-d
6
) δ: 11.96 (s, 1H), 8.50 (d, J = 2.0 Hz, 1H), 8.22
(
(
(
(
d, J = 7.2 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.23−7.15 (m, 2H),
.74−2.68 (m, 1H), 0.98 (s, 2H), 0.87−0.85 (m, 2H); C NMR (100
1
3
2
MHz, DMSO-d
21.40, 117.12, 111.97, 17.11, 9.05. HRMS (ESI) ([M+H] ) Calcd. For
11NO: 186.0913, Found: 186.0914.
6
) δ: 194.19, 136.60, 133.66, 125.24, 122.68, 121.54,
+
1
12
C H
Nat. Chem., 2010,
Stephenson, Chem. Soc. Rev., 2011, 40, 102; (d) A. E. Allen
and D. W. C. MacMillan, Chem. Sci., 2012, , 633; (e) L. Shi
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Acknowledgements
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and W. Xia, Chem. Soc. Rev., 2012, 41, 7687; (f ) J. W. Tucker
and C. R. J. Stephenson, J. Org. Chem., 2012, 77, 1617; (g) J.
Xuan and W.-J. Xiao, Angew. Chem., Int. Ed., 2012, 51, 6828;
We gratefully acknowledge the National Natural Science
Foundation of China (Nos. 21572078, 21372095) and the Key
Project of Science and Technology of Anhui Educational Bureau (No.
KJ2015ZD34) for financial support of this work.
(
4
h) D. P. Hari and B. Koenig, Angew. Chem., Int. Ed., 2013, 52
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734; (i) G. Deng, Z. Wang, J. Xia, P. Qian, R. Song, M. Hu, L.
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Notes and reference
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c
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d
(
(
17) During the preparation of our manuscript, Gu and co-
workers reported a similar reaction under more complicated
conditions, see: L. Gu, C. Jin, J. Liu, H. Zhang, M. Yuan and G.
Li, Green Chem., 2016, 18, 1201.
2
e
f
18) X-ray single crystal structure of 3a (CCDC: 1449407).
6
g
This journal is © The Royal Society of Chemistry 20xx
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ARTICLE
Journal Name
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Supporting Information
Decarboxylative/Decarbonylative C3-acylation of indoles via photocatalysis:
a simple and efficient route to 3-acylindoles
a
a
a
a,b
Qing Shi, Pinhua Li,* Xianjin Zhu, and Lei Wang*
a
Department of Chemistry, Huaibei Normal University, Huaibei, Anhui 235000, P. R. China, Tel:
86ꢀ561ꢀ3802ꢀ069 Fax: +86ꢀ561ꢀ3090ꢀ518 Eꢀmail: leiwang@chnu.edu.cn
+
b
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, Shanghai 200032, P. R. Chin
a
Table of Contents for Supporting Information
1
2
. Reaction mechanism study...….………………………………………………………2
1
13
. H and C NMR spectra of the products.....................................................................7
1

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1
1
. Reaction mechanism study
.1 Determination of singlet oxygen
In order to determine the active species of oxygen involved in the present reaction,
,2,6,6ꢀtetramethylpiperidine (TEMP) and 5,5ꢀdimethylꢀpyrrolineꢀNꢀoxide (DMPO) were
2
1
2•−
employed to capture O and O , respectively. Irradiation of the ethanol solution of TEMP
2
and rose bengal (RB) in air by green LED resulted in the formation of a strong characteristic
1
signal of O adduct with TEMP (Figure S1b vs S1a), and this signal decreased obviously as
2
addition of phenylglyoxylic acid (2a) into the solution (Figure S1c). It is indicated that 2a
1
2•−
reacted with O efficiently to consume it rapidly. However, there is no signal of O adduct
2
2
•−
with DMPO, excluding the formation of O in the reaction system.
Figure S1. Electron spin resonance (ESR) spectra: (a) a solution of TEMP (0.12 mol/L), rose bengal
(
1.0 mol%) in airꢀsaturated C H OH without green LED irradiation; (b) a solution of TEMP (0.12 M), rose
2 5
bengal (1.0 mol%) in airꢀsaturated C H OH with green LED irradiation for 30 s; (c) a solution of TEMP
2
5
(
0.12 mol/L), rose bengal (1.0 mol%) in airꢀsaturated C H OH with green LED irradiation for 30 s, then with
2 5
−
2
addition of 2a (1.5×10 mol/L).
2

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1
.2 Benzoyl radical-trapping experiment
Phenylglyoxylic acid (2a, 0.30 mmol), 2,2,6,6ꢀtetramethylꢀ1ꢀoxylpiperidine (TEMPO, 1.0
mmol), rose bengal (RB, 0.003 mmol), 4Å molecular sieve (80 mg) were dissolved in ethanol
2.0 mL) in an ovenꢀdried reaction vessel equipped with magnetic stirring bar, and the reaction
(
vessel was irradiated using green LED at room temperature under air atmosphere for 10 h.
After the reaction was carried out, concentrated under reduced pressure to yield the crude
product, which was purified by flash chromatography (silica gel, petroleum ether/ethyl acetate
=
20:1 to 10:1), affording the adduct 5 as a colorless solid in 52% yield.
2
,2,6,6ꢀTetramethylpiperidinꢀ1ꢀyl benzoate (5) (See: H. Tan, H. Li, W. Ji, L. Wang, Angew.
1
Chem., Int. Ed., 2015, 54, 8374): White solid. H NMR (400 MHz, CDCl ) δ: 8.08 (d, J = 7.6
3
Hz, 2H), 7.58−7.55 (m, 1H), 7.47−7.44 (m, 2H), 1.81−1.75 (m, 2H), 1.70−1.67 (m, 1H),
1
3
1
.63−1.57 (m, 2H), 1.47−1.44 (m, 1H), 1.28 (s, 6H), 1.13 (s, 6H); C NMR (100 MHz, CDCl )
3
δ: 166.15, 132.64, 129.61, 129.36, 128.26, 60.21, 38.92, 31.80, 20.68, 16.84. HRMS (ESI)
+
(
[M+H] ) Calcd. For C H NO : 262.1802, Found: 262.1805. The following Figure S2 is the
1
6
24
2
HRMS analysis of reaction mixture.
Figure S2. Analysis of reaction mixture by HRMS
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.3 Determination of CO and CO during the reaction by FT-IR
2
An Schlenk tube equipped with a magnetic stirrer bar was charged with indole (1a, 0.30
mmol), phenylglyoxylic acid (2a, 0.6 mmol), rose bengal (1.0 mol%), 4Å molecular sieve (80
mg) and ethanol (2.0 mL). The reaction vessel was exposed to green LED at room temperature
for 10 h. After completion of the reaction, the resulting gas from the reaction system was
directly determined by a Bruker Tensor 27 FTꢀIR, and the concentration of CO and CO was
2
found to be 2839.70, and 94.27 ppm (Figure S3 and Figure S4), respectively.
Sample
Background
0
0
0
.6
.3
.0
2
220 2240 2260 2280 2300 2320 2340 2360 2380 2400
ꢀ1
Wavenumber (cm )
Figure S3. FTꢀIR analysis of the formation of CO in the reaction
2
5

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0
0
0
0
0
.0
.8
.6
.4
.2
.0
Sample
Background
2
060 2080 2100 2120 2140 2160 2180 2200 2220 2240
ꢀ1
Wavenumber (cm )
Figure S4. FTꢀIR analysis of the formation of CO in the reaction
6

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13
2
. H and C NMR spectra of the products
7

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