Na 2 CO 3-Catalyzed N-Acylation of Indoles with Alkenyl Carboxylates

Article abstract of DOI:10.1055/s-0037-1609937

The N-acylation of indoles has been accomplished via inorganic base catalysis. It provided an efficient and simple catalysis system for the preparation of N-acylindoles with alkenyl carboxylates as acylating agents. A broad variety of indoles undergo the smooth N-acylation using Na ₂ CO ₃ as catalyst in MeCN at 120? °C to give the corresponding N-acylindoles in good to excellent yields.

Full text of DOI:10.1055/s-0037-1609937

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–F
paper
A
en
X.-Y. Zhou, X. Chen
Paper
Synthesis
Na2CO3-Catalyzed N-Acylation of Indoles with Alkenyl Carboxylates
Xiao-Yu Zhou*
Xia Chen*
R
R
R'
Na2CO3 (20 mol%)
O
R'
N
+
N
O
R''
MeCN, 120 °C
H
R''
School of Chemistry and Materials Engineering, Liupanshui
Normal University, Liupanshui, 553004, China
zhouxiaoyu20062006@126.com
O
♣ Selective N-Acylation of Indoles
♦ Inorganic Base as Catalyst
♠ Simple Reaction Conditions
♥ 20 Examples
R'' = alkyl or phenyl
Up to >99% Yield
Received: 07.06.2018
Accepted after revision: 04.08.2018
Published online: 04.09.2018
of aromatic compounds14 and indoles15 with nitrile as acy-
lating agents. Unfortunately, N-acylation of indoles under
mild reaction conditions are limited. The NBoc indoles were
prepared by 4-(N,N-dimethylamino)pyridine (DMAP)-cata-
lyzed acylation of indoles in the presence of di-tert-butyl
dicarbonate (Boc2O) with high selectivity. But this method
is not suitable for the synthesis of other N-acylindoles.2c In
1998, Ottoni and his colleagues disclosed the methods of N-
benzenesulfonylation, N-acetylation, N-methylation, and N-
benzylation of indoles under strong basic conditions
(NaOH, KOH, and Et3N).16 More specifically, 3-acylindoles
are normal by-products in the synthesis of N-acylindoles
and a highly regioselective method is necessary to be devel-
oped.
Recently, DBU-catalyzed N-acylation of indoles with
carbonylimidazoles,17 DMAP-catalyzed N-acylation of in-
doles with carboxylic acids and Boc2O,18 and N-heterocyclic
carbene (NHC)-catalyzed N-acylation of indoles with aro-
matic and conjugated aldehydes19 have been reported. In
these methods, moderate to excellent yields have been
achieved for the synthesis of N-acylindoles with high selec-
tivity. In addition, transesterification and amination of es-
ters is a direct strategy for the synthesis of esters and am-
ides. With this in mind, we envisioned that this strategy
could be applied to N-acylation of indoles, which would
lead to a new method for late stage synthesis of N-acylin-
doles or N-acylindolines (Scheme 1).
DOI: 10.1055/s-0037-1609937; Art ID: ss-2018-h380-op
Abstract The N-acylation of indoles has been accomplished via inor-
ganic base catalysis. It provided an efficient and simple catalysis system
for the preparation of N-acylindoles with alkenyl carboxylates as acylat-
ing agents. A broad variety of indoles undergo the smooth N-acylation
using Na2CO3 as catalyst in MeCN at 120 °C to give the corresponding
N-acylindoles in good to excellent yields.
Key words inorganic base, catalysis, acylation, indole, alkenyl carbox-
ylates
A wide range of natural products, pharmaceuticals, and
fine chemicals contain indole moieties.1 In order to utilize
the indole skeletons in organic synthesis effectively, the
transformation and functionalization of indole and its de-
rivatives have attracted much attention. Oxidation,2 reduc-
tion,3 nucleophilic addition,4 Friedel–Crafts reactions,5 cat-
alyzed oxidative cross-coupling reactions,6 and C–H bond
activation7 have been reported widely. Besides, the acyla-
tion process has been recognized as a powerful strategy for
the N-protection of indoles. Therefore, a series of acylating
agents and catalysis systems have been sought for acylation
of indoles.
The acylation in 2- or 3-position of indoles is a tradi-
tional method for the functionalization of indoles. 3-
Acylindoles are obtained in many cases, such as in the dial-
kylaluminum chloride promoted 3-acylation of NH indoles
in the presence of acyl chlorides,8 anhydrides, nitriles or
amino acid derivatives,9 1,5-diazabicyclo[4.3.0]non-5-ene
(DBN)-10 and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)-
promoted11 Friedel–Crafts acylation of indoles, copper-cat-
alyzed intramolecular C–H oxidation/acylation of formyl-N-
arylformamides,12 Ru- and Fe-catalyzed C3-selective acyla-
tion of indoles with anilines,13 and directed meta-acylation
To develop a method for the synthesis of N-acylindo-
lines, a palladium-catalyzed N-acylation-transfer hydroge-
nation of indoles was carried out using indole (1a) and vi-
nyl acetate (2a) as model starting materials, Pd/C (10 wt%)
as catalyst, and sodium formate (HCO2Na·2H2O, 200 mol%)
as reductive base in acetonitrile at 100 °C. In this reaction,
1-(1H-indol-1-yl)ethanone (3aa) was isolated in 65% yield
(Table 1, entry 1) and 31% starting material 1a was recov-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

B
X.-Y. Zhou, X. Chen
Paper
Synthesis
Table 1 Conditions for the Optimization for Base-Catalyzed N-Acyla-
O
anhydrides, nitriles or
carbonyl halides as agents
R'
tion of Indolesa
Previous Work
base or Lewis acid catalysis system
N
O
cat. (y mol%)
Acylation
R
N
+
N
solvent, 100 °C
N
R
O
Me
H
Me
O
3aa
carbonylimidazoles, carboxylic acids
or aldehydes as agents
1a
2a (x equiv)
N
DBU, DMAP or NHC catalysis system
Entry 2a x
Catalyst
Solvent
Yield
(%)b
R'
O
(equiv) (y, mol%)
This work
1
2
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1.0
3.0
4.0
4.0
4.0
4.0
4.0
4.0
4.0
Pd/C (10 wt%) HCO2Na·2H2O (200) MeCN
65
67
59
21
70
39
73
79
80
85
81
R
R
+
R'
Na2CO3 (20 mol%)
MeCN, 120 °C
O
HCO2Na·2H2O (200)
Et3N (200)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
R'
N
N
H
3
O
R''
R''
O
Inorganic base catalysis system!
4
NaOAc (200)
K2CO3 (200)
MgO (200)
Na2CO3 (200)
Na2CO3 (100)
Na2CO3 (50)
Na2CO3 (20)
Na2CO3 (10)
–
5
Scheme 1 Selective acylation of indoles for the synthesis of acylin-
doles
6
7
ered without the formation of the corresponding N-acylin-
doline and 3-acylindole. Therefore, we focused on the re-
search about the selective N-acylation of indoles using vinyl
esters as acylating agent. Then the catalyst, the amount of
acylating agent, solvent, and temperature were evaluated to
improve the yield of the product 3aa, respectively. The re-
sults are shown in Table 1.
8
9
10
11
12
13
14
15
16
17
18
19
20c
21d
trace
Na2CO3 (20)
Na2CO3 (20)
Na2CO3 (20)
Na2CO3 (20)
Na2CO3 (20)
Na2CO3 (20)
Na2CO3 (20)
Na2CO3 (20)
Na2CO3 (20)
74
87
92
11
First, sodium formate as base was tested in MeCN at
100 °C without the Pd/C and 67% of 3aa was isolated (Table
1, entry 2). It indicated that the metal catalyst was not nec-
essary for the N-acylation of indoles. Then, the reactivity of
other bases was tested, including Et3N, NaOAc, K2CO3, MgO,
and Na2CO3 (entries 3–7). Pleasingly, replacing
HCO2Na·2H2O with Na2CO3 increased the yield to 73% (entry
7). To improve the yield further, the amount of base was op-
timized (entries 7–12) and 20 mol% Na2CO3 was found to be
the optimized dosage (85% yield, entry 10). However, the N-
acylation of indole cannot proceed smoothly without a base
(entry 12). The dosage of acylating agent was optimized
(entries 13–15) and the best result was obtained (92% yield,
entry 15) when 4.0 equivalent 2a was added. At last, other
solvents and temperature were separately evaluated to im-
prove the yield of the product 3aa. The choice of solvent
significantly influenced the yield (entries 15–19), with
MeCN proving to be the optimal reaction medium, presum-
ably due to solubility of Na2CO3. Especially, only trace
amounts of the desired product 3aa were observed when
ethanol was used as the solvent (EtOH, entry 18). It is pre-
sumed that a transesterification had occurred between vi-
nyl acetate and EtOH. To our delight, the reaction efficiency
was further increased to 97% by elevating temperature to
120 °C (entry 21).
toluene
1,4-dioxane 40
EtOH
THF
trace
35
42
97
MeCN
MeCN
a Unless other stated, all reactions are carried out with 1a (59 mg, 0.50
mmol), 2a (x equiv), cat. (y mol%), solvent (3.0 mL), Temp (°C), 24 h.
b Isolated yield.
c Carried out at 80 °C.
d Carried out at 120 °C.
nyl carboxylates 2a–f and the moderate to excellent isolated
yields (56–99%) of products 3 were obtained, respectively.
While ethyl acetate was used as acylating agent to form 3aa,
no product was detected and the starting materials were re-
covered (Table 2, entry 7). It is important to note that the
alkyl carboxylates are not suitable for the N-acylation of in-
dole and it is considered to be due to the stability of alkyl
carboxylates.
Subsequently, the substrate scope of indole for this N-
acylation under the optimal reaction conditions was stud-
ied, as shown in Table 3. No target products were detected
when indoles 1b–d were utilized as the starting materials,
respectively (Table 3, entries 1–3). We envision that the ste-
ric effect of Me, Ph, and CO2Me at 2-position of indole inhib-
With optimized conditions in hand, we next sought to
define the scope of carboxylates 2. As shown in Table 2, the
N-acylation of indole 1a could proceed smoothly with alke-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

C
X.-Y. Zhou, X. Chen
Paper
Synthesis
Table 2 Screen on the Scope of Substrate 2a
Table 3 Screen on the Scope of Substrate 1a
R
N
R
Na2CO3 (20 mol%)
MeCN, 120 °C
O
R'
Na2CO3 (20 mol%)
O
R'
N
+
+
N
N
MeCN, 120 oC
O
R''
O
Me
H
R''
H
Me
O
O
1a
2
3
1
2a
3
Entry Substrate 2
Product 3
Yield (%)b
97
Entry Substrate 1
Product 3
Yield (%)b
NR
O
1
N
O
N
H
1
2
N
Ac
2a
3aa
Ac
1b
1b
1c
O
2
3aa
95
75
O
Ph
Ph
NR
NR
N
N
H
2b
Ac
3ca
O
N
3
CO2Me
CO2Me
Et
Pr
O
2c
3
N
N
H
Et
Pr
3ac
O
Ac
1d
3da
O
O
O
4
5
N
56
77
O
2d
3ad
4
82
O
N
N
H
Ac
1e
3ea
O
N
O
2e
O
5
6
>99
98
N
N
3ae
H
Ac
1f
3fa
O
MeO
MeO
BnO
Ph
O
6
7
N
>99
NR
2f
3af
Ph
N
N
H
O
Ac
1g
1h
3ga
O
BnO
AcO
NC
3aa
O
2g
7
61
N
H
N
a Unless otherwise stated, all reactions are carried out with 1a (59 mg, 0.50
mmol), 2 (2.0 mmol, 4.0 equiv), Na2CO3 (10.6 mg, 0.10 mmol, 20 mol%) in
MeCN (3.0 mL) at 120 °C for 24 h.
3ha
3ia
Ac
HO
NC
Br
b Isolated yield. NR: No reaction.
8
9
91
91
89
78
N
H
N
Ac
1h
ited the N-acylation process. As expected, 3-substituent
and 5-substituent on indole were tolerated well under this
procedure (61–99%, entries 4–10). 1H-Pyrrolo[2,3-b]pyri-
dine (1l) and 2,3,4,9-tetrahydro-1H-carbazole (1m) were
tested and the corresponding products were isolated in
good yields (78% and 79%, entries 11 and 12). And substrate
1n failed to give the corresponding product (entry 13), pre-
sumably due to steric effect.
N
H
N
Ac
1j
3ja
Br
10
11
N
N
H
Ac
1k
3ka
N
N
N
N
H
Ac
1l
3la
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

D
X.-Y. Zhou, X. Chen
Paper
Synthesis
Table 3 (continued)
Na2CO3-Catalyzed N-Acylation of Indoles; General Procedure
A mixture of indole 1 (0.50 mmol), Na2CO3 (10.6 mg, 0.10 mmol, 20
mol%), and alkenyl carboxylate 2 (2.0 mmol, 4.0 equiv) in MeCN (3
mL) was added into a Schlenk flask (25 mL) and stirred at 120 °C until
completion of the reaction. Then the solvent was evaporated under
reduced pressure and the residue was purified by column chromatog-
raphy (petroleum ether/EtOAc 20:1 to 5:1) to afford the desired
acylindoles 3 (Tables 2 and 3).
Entry Substrate 1
Product 3
Yield (%)b
O
O
12
79
N
N
H
Ac
1m
3ma
1-(1H-Indol-1-yl)ethanone (3aa)16
Yield: 76.8 mg (97%); colorless oil; Rf = 0.67 (hexane/EtOAc 10:1).
13
NR
1H NMR (500 MHz, CDCl3): δ = 8.48 (d, J = 7.4 Hz, 1 H), 7.58 (d, J = 7.6
Hz, 1 H), 7.37–7.36 (m, 2 H), 7.31–7.28 (m, 1 H), 6.63 (d, J = 3.8 Hz, 1
H), 2.59 (s, 3 H).
N
N
H
Ac
1n
3na
a Unless otherwise stated, all reactions are carried out with 1 (0.50 mmol),
2a (172 mg, 2.0 mmol, 4.0 equiv), Na2CO3 (10.6 mg, 0.10 mmol, 20 mol%)
in MeCN (3.0 mL) at 120 °C for 24 h.
13C NMR (126 MHz, CDCl3): δ = 168.5, 135.3, 130.3, 125.1, 124.9,
123.5, 120.7, 116.4, 108.9, 23.7.
b Isolated yield. NR: No reaction.
1-(1H-Indol-1-yl)propan-1-one (3ac)
Yield: 64.6 mg (75%); colorless oil; Rf = 0.66 (hexane/EtOAc 10:1).
Based on the above results, the N-acylation of indoles
can be achieved using alkenyl cayboxylates as acylation
agents but not by using alkyl carboxylates. We predict that
acetaldehyde (5), which was formed by the isomerization of
ethenol 4, was the driving force in the N-acylation of in-
doles and alkenyl cayboxylates, as shown in Scheme 2.
While, EtOH was produced when alkyl carboxylates were
utilized as agents and the reversed reaction inhibited the
formation of N-acylindoles.
IR (KBr): 2988, 2915, 1720, 1611, 1589, 1469, 1380, 1352, 1246, 1153,
1065, 982, 758 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.47 (d, J = 8.2 Hz, 1 H), 7.56 (d, J = 7.8
Hz, 1 H), 7.46 (d, J = 3.8 Hz, 1 H), 7.38–7.33 (m, 1 H), 7.28–7.25 (m, 1
H), 6.63 (d, J = 3.8 Hz, 1 H), 2.94 (t, J = 7.3 Hz, 2 H), 1.34 (t, J = 7.3 Hz, 3
H).
13C NMR (126 MHz, CDCl3): δ = 172.1, 135.5, 130.2, 125.0, 124.4,
123.5, 120.7, 116.5, 108.9, 29.1, 8.7.
HRMS: m/z [M + Na]+ calcd for C11H11NONa: 196.0738; found:
196.0741.
Na2CO3 (20 mol%)
MeCN, 120 °C
O
1-(1H-Indol-1-yl)butan-1-one (3ad)
N
+
N
Yield: 51.9 mg (56%); colorless oil; Rf = 0.68 (hexane/EtOAc 10:1).
O
H
O
IR (KBr): 2965, 2922, 1710, 1600, 1585, 1470, 1376, 1352, 1258, 1150,
1a
2a
3aa
1065, 980, 910, 752 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.48 (d, J = 8.2 Hz, 1 H), 7.56 (d, J = 7.7
Hz, 1 H), 7.46 (d, J = 3.7 Hz, 1 H), 7.35 (t, J = 7.7 Hz, 1 H), 7.28–7.25 (m,
1 H), 6.63 (d, J = 3.7 Hz, 1 H), 2.89 (t, J = 7.4 Hz, 2 H), 1.88 (m, 2 H),
1.08 (t, J = 7.4 Hz, 3 H).
O
OH
H
4
5
Scheme 2 The speculated reason for N-acylation of indoles
13C NMR (126 MHz, CDCl3): δ = 171.4, 135.5, 130.2, 125.0, 124.6,
123.5, 120.7, 116.6, 108.9, 37.7, 18.1, 13.7.
HRMS: m/z [M + Na]+ calcd for C12H13NONa: 210.0895; found:
210.0896.
In summary, using alkenyl carboxylates as acylating
agents, the Na2CO3-catalyzed N-acylation of indoles was
successfully achieved in up to >99% yield. Equally import-
ant, it will play an important role in protecting group
chemistry, especially in terms of N-protection of indoles.
1-(1H-Indol-1-yl)hexan-1-one (3ae)
Yield: 82.6 mg (77%); colorless oil; Rf = 0.68 (hexane/EtOAc 10:1).
IR (KBr): 2978, 2933, 1700, 1605, 1580, 1473, 1379, 1346, 1250, 1151,
1070, 980, 910, 843, 752 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.47 (d, J = 8.2 Hz, 1 H), 7.54 (d, J = 7.7
Hz, 1 H), 7.41 (d, J = 3.8 Hz, 1 H), 7.35–7.30 (m, 1 H), 7.26–7.23 (m, 1
H), 6.60 (d, J = 3.8 Hz, 1 H), 2.85 (t, J = 7.5 Hz, 2 H), 1.84–1.78 (m, 2 H),
1.42–1.35 (m, 4 H), 0.92 (t, J = 7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 171.6, 135.6, 130.3, 125.0, 124.6,
123.5, 120.7, 116.6, 108.9, 35.8, 31.3, 24.3, 22.4, 13.9.
Commercially available reagents were used throughout without fur-
ther purification. The chemical shifts for 1H NMR were recorded in
ppm downfield from TMS with the solvent resonance as the internal
standard. The chemical shifts for 13C NMR were recorded in ppm
downfield using the central peak of CDCl3 (77.23 ppm) as the internal
standard. Coupling constants (J) are reported in Hz and refer to appar-
ent peak multiplications. Flash column chromatography was per-
formed on silica gel (200–300 mesh). TLC analysis was performed us-
ing glass-backed plates coated with 0.2 mm silica gel.
HRMS: m/z [M + Na]+ calcd for C14H17NONa: 238.1208; found:
238.1210.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

E
X.-Y. Zhou, X. Chen
Paper
Synthesis
(1H-Indol-1-yl)(phenyl)methanone (3af)
13C NMR (126 MHz, CDCl3): δ = 168.3, 155.6, 137.1, 128.6, 127.9,
127.5, 125.9, 117.3, 114.3, 109.0, 104.9, 70.5, 23.7.
HRMS: m/z [M + Na]+ calcd for C17H15NO2Na: 288.1000; found:
Yield: 110.0 mg (>99%); white solid; mp 55–57 °C; Rf = 0.70 (hex-
ane/EtOAc 10:1).
288.1004.
IR (neat): 2960, 2921, 1710, 1610, 1584, 1477, 1375, 1350, 1255,
1157, 1062, 980, 910, 836, 752 cm–1
.
1-Acetyl-1H-indol-5-yl Acetate (3ia)
1H NMR (500 MHz, CDCl3): δ = 8.41 (d, J = 8.2 Hz, 1 H), 7.76–7.70 (m, 2
H), 7.61–7.58 (m, 2 H), 7.53–7.50 (m, 2 H), 7.40–7.24 (m, 3 H), 6.61 (d,
J = 3.7 Hz, 1 H).
Yield: 99.2 mg (91%); white solid; mp 133–135 °C; Rf = 0.58 (hex-
ane/EtOAc 10:1).
13C NMR (126 MHz, CDCl3): δ = 168.7, 136.0, 134.5, 131.8, 130.7,
129.5, 129.1, 128.5, 128.3, 127.6, 124.9, 123.9, 120.8, 116.3, 108.5.
IR (neat): 2960, 2920, 1705, 1611, 1587, 1480, 1379, 1353, 1250,
1160, 1061, 983, 912, 840, 748 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.44 (d, J = 8.7 Hz, 1 H), 7.44 (d, J = 3.7
Hz, 1 H), 7.28 (d, J = 2.2 Hz, 1 H), 7.06 (dd, J = 8.7, 2.2 Hz, 1 H), 6.61 (d,
J = 3.7 Hz, 1 H), 2.62 (s, 3 H), 2.32 (s, 3 H).
HRMS: m/z [M + Na]+ calcd for C15H11NONa: 244.0738; found:
244.0738.
1,1′-(1H-Indole-1,3-diyl)diethanone (3ea)16
13C NMR (126 MHz, CDCl3): δ = 169.9, 168.4, 146.9, 133.2, 131.1,
126.3, 118.7, 117.2, 113.3, 109.0, 23.8, 21.1.
Yield: 82.5 mg (82%); white solid; mp 150–152 °C; Rf = 0.34 (hex-
HRMS: m/z [M + Na]+ calcd for C12H11NO3Na: 240.0637; found:
ane/EtOAc 5:1).
1H NMR (500 MHz, CDCl3): δ = 8.37–8.32 (m, 2 H), 8.01 (s, 1 H), 7.42–
240.0641.
7.37 (m, 2 H), 2.71 (s, 3 H), 2.57 (s, 3 H).
1-Acetyl-1H-indole-5-carbonitrile (3ja)
13C NMR (126 MHz, CDCl3): δ = 193.7, 168.6, 135.9, 131.1, 127.2,
Yield: 84.0 mg (91%); white solid; mp 138–140 °C; Rf = 0.41 (hex-
126.2, 125.1, 122.4, 121.8, 116.1, 27.9, 24.0.
ane/EtOAc 10:1).
1-(5-Methyl-1H-indol-1-yl)ethanone (3fa)
IR (neat): 2961, 2926, 2251, 1714, 1606, 1580, 1470, 1375, 1350,
1255, 1157, 1062, 981, 914, 832, 754 cm–1
.
Yield: 8.7 mg (>99%); white solid; mp 63–65 °C; Rf = 0.65 (hex-
1H NMR (500 MHz, CDCl3): δ = 8.55 (d, J = 8.6 Hz, 1 H), 7.90 (s, 1 H),
7.61–7.55 (m, 2 H), 6.71 (d, J = 3.8 Hz, 1 H), 2.68 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 168.7, 137.3, 130.3, 128.2, 127.3,
ane/EtOAc 10:1).
IR (neat): 2980, 2930, 1716, 1608, 1586, 1469, 1376, 1287, 1250,
1156, 1064, 987, 910, 836, 790, 763 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.29 (br s, 1 H), 7.33 (s, 2 H), 7.15 (d,
J = 8.1 Hz, 1 H), 6.54 (d, J = 3.2 Hz, 1 H), 2.59 (s, 3 H), 2.43 (s, 3 H).
125.6, 119.5, 117.4, 108.7, 107.1, 23.9.
HRMS: m/z [M + Na]+ calcd for C11H8N2ONa: 207.0534; found:
13C NMR (126 MHz, CDCl3): δ = 168.4, 133.1, 130.6, 126.3, 125.2,
207.0533.
120.7, 116.1, 108.9, 23.8, 21.3.
1-(5-Bromo-1H-indol-1-yl)ethanone (3ka)
HRMS: m/z [M + Na]+ calcd for C11H11NONa: 196.0738; found:
Yield: 106.0 mg (89%); white solid; mp 111–113 °C; Rf = 0.60 (hex-
196.0736.
ane/EtOAc 10:1).
1-(5-Methoxy-1H-indol-1-yl)ethanone (3ga)
IR (neat): 2962, 2920, 1700, 1603, 1580, 1475, 1378, 1261, 1145,
1068, 976, 841, 760, 643 cm–1
.
Yield: 92.8 mg (98%); white solid; mp 82–84 °C; Rf = 0.66 (hex-
1H NMR (500 MHz, CDCl3): δ = 8.32 (d, J = 8.5 Hz, 1 H), 7.68 (s, 1 H),
7.44–7.41 (m, 2 H), 6.57 (d, J = 3.3 Hz, 1 H), 2.63 (s, 3 H).
13C NMR (126 MHz, CDCl3): δ = 168.5, 134.2, 127.9, 126.3, 123.5,
ane/EtOAc 10:1).
IR (neat): 2961, 2915, 1706, 1614, 1580, 1475, 1377, 1350, 1261,
1155, 1060, 985, 913, 841, 750 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.33 (d, J = 6.2 Hz, 1 H), 7.37 (s, 1 H),
7.02 (d, J = 2.4 Hz, 1 H), 6.95 (dd, J = 9.0, 2.4 Hz, 1 H), 6.56 (d, J = 3.7
Hz, 1 H), 3.85 (s, 3 H), 2.60 (s, 3 H).
117.94, 116.9, 108.3, 23.8.
HRMS: m/z [M + Na]+ calcd for C10H8BrNONa: 259.9687; found:
259.9690.
13C NMR (126 MHz, CDCl3): δ = 168.3, 156.4, 131.3, 130.2, 125.8,
117.2, 113.4, 109.0, 103.5, 55.6, 23.6.
1-(1H-Pyrrolo[2,3-b]pyridin-1-yl)ethanone (3la)
HRMS: m/z [M + Na]+ calcd for C11H11NO2Na: 212.0687; found:
Yield: 62.3 mg (78%); white solid; mp 165–167 °C; Rf = 0.31 (hex-
ane/EtOAc 5:1).
212.0688.
IR (neat): 2979, 2922, 1730, 1621, 1592, 1460, 1368, 1343, 1257,
1-[5-(Benzyloxy)-1H-indol-1-yl]ethanone (3ha)
1152, 1059, 984, 843, 740 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 8.37 (dd, J = 4.8, 1.4 Hz, 1 H), 7.99 (d,
J = 4.1 Hz, 1 H), 7.88 (dd, J = 7.8, 1.4 Hz, 1 H), 7.20 (dd, J = 7.8, 4.8 Hz, 1
H), 6.59 (d, J = 4.1 Hz, 1 H), 3.06 (s, 3 H).
Yield: 81.1 mg (61%); white solid; mp 127–129 °C; Rf = 0.61 (hex-
ane/EtOAc 10:1).
IR (neat): 2960, 2925, 1700, 1605, 1581, 1482, 1380, 1355, 1260,
1150, 1062, 980, 908, 833 cm–1
.
13C NMR (126 MHz, CDCl3): δ = 169.1, 147.8, 143.8, 129.3, 125.4,
1H NMR (500 MHz, CDCl3): δ = 8.34 (d, J = 7.1 Hz, 1 H), 7.48–7.45 (m, 2
H), 7.40–7.38 (m, 3 H), 7.34–7.31 (m, 1 H), 7.10 (d, J = 2.2 Hz, 1 H),
7.04 (dd, J = 9.0, 2.2 Hz, 1 H), 6.56 (d, J = 3.7 Hz, 1 H), 5.11 (s, 2 H), 2.61
(s, 3 H).
123.7, 118.7, 105.7, 25.8.
HRMS: m/z [M + Na]+ calcd for C9H8N2ONa: 183.0534; found:
183.0531.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

F
X.-Y. Zhou, X. Chen
Paper
Synthesis
9-Acetyl-2,3-dihydro-1H-carbazol-4(9H)-one (3ma)
(3) (a) Kuwano, R.; Sato, K.; Kurokawa, T.; Karube, D.; Ito, Y. J. Am.
Chem. Soc. 2000, 122, 7614. (b) Wang, D.-S.; Chen, Q.-A.; Li, W.;
Yu, C.-B.; Zhou, Y.-G.; Zhang, X. J. Am. Chem. Soc. 2010, 132,
8909. (c) Duan, Y.; Li, L.; Chen, M.-W.; Yu, C.-B.; Fan, H.-J.; Zhou,
Y.-G. J. Am. Chem. Soc. 2014, 136, 7688.
Yield: 90.0 mg (79%); yellow solid; mp 136–138 °C; Rf = 0.33 (hex-
ane/EtOAc 5:1).
IR (neat): 2972, 2930, 1773, 1750, 1609, 1589, 1501, 1366, 1343,
1250, 1153, 1060, 981, 912, 847, 743 cm–1
.
(4) (a) Cacchi, S.; Fabrizi, G. Chem. Rev. 2005, 105, 2873. (b) Shiri, M.
Chem. Rev. 2012, 112, 3508. (c) Boyarskiy, V. P.; Ryabukhin, D.
S.; Bokach, N. A.; Vasilyev, A. V. Chem. Rev. 2016, 116, 5894.
(5) (a) Bur, S. K.; Padwa, A. Chem. Rev. 2004, 104, 2401. (b) Mąkosza,
M.; Wojciechowski, K. Chem. Rev. 2004, 104, 2631. (c) Busto, E.;
Gotor-Fernández, V.; Gotor, V. Chem. Rev. 2011, 111, 3998.
(d) Zhang, H.; Hu, R.-B.; Liu, N.; Li, S.-X.; Yang, S.-D. Org. Lett.
2016, 18, 28. (e) Morimoto, N.; Morioku, K.; Suzuki, H.;
Takeuchi, Y.; Nishina, Y. Org. Lett. 2016, 18, 2020. (f) Petrone, D.
A.; Kondo, M.; Zeidan, N.; Lautens, M. Chem. Eur. J. 2016, 22,
5684.
(6) (a) Bras, J. L.; Muzart, J. Chem. Rev. 2011, 111, 1170. (b) Liu, C.;
Yuan, J.; Gao, M.; Tang, S.; Li, W.; Shi, R.; Lei, A. Chem. Rev. 2015,
115, 12138. (c) Yang, Y.; Lan, J.; You, J. Chem. Rev. 2017, 117,
8787.
(7) (a) Colby, D. A.; Bergman, R. G.; Ellman, J. A. Chem. Rev. 2010,
110, 624. (b) Hummel, J. R.; Boerth, J. A.; Ellman, J. A. Chem. Rev.
2017, 117, 9163.
1H NMR (500 MHz, CDCl3): δ = 8.38–8.29 (m, 1 H), 7.89–7.81 (m, 1 H),
7.38–7.33 (m, 2 H), 3.30 (t, J = 6.1 Hz, 2 H), 2.81 (s, 3 H), 2.61–2.57 (m,
2 H), 2.26–2.24 (m, 2 H).
13C NMR (126 MHz, CDCl3): δ = 222.7, 195.7, 170.4, 125.0, 124.7,
122.1, 114.3, 37.8, 27.5, 26.4, 23.5.
HRMS: m/z [M + Na]+ calcd for C14H13NO2Na: 250.0844; found:
250.0845.
Funding Information
The work was supported by the Youth Science and Technology Talent
Development Project in Education Department of Guizhou Province
(Grant No. qianjiaohe KY zi [2017] number 261) and Innovation Team
of Liupanshui Normal University (Grant No. LPSSYKJTD201601).
)(
(8) Okauchi, T.; Itonaga, M.; Minami, T.; Owa, T.; Kitoh, K.; Yoshino,
H. Org. Lett. 2000, 2, 1485.
Supporting Information
(9) Ottoni, O.; Neder, A. V. F.; Dias, A. K. B.; Cruz, R. P. A.; Aquino, L.
B. Org. Lett. 2001, 3, 1005.
(10) Taylor, J. E.; Jones, M. D.; Williams, J. M. J.; Bull, S. D. Org. Lett.
2010, 12, 5740.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1609937.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
(11) Johansson, H.; Urruticoechea, A.; Larsen, I.; Pedersen, D. S.
J. Org. Chem. 2015, 80, 471.
References
(1) (a) Kochanowska-Karamyan, A. J.; Hamann, M. T. Chem. Rev.
2010, 110, 4489. (b) Lancianesi, S.; Palmieri, A.; Petrini, M.
Chem. Rev. 2014, 114, 7108.
(12) Tang, B.-X.; Song, R.-J.; Wu, C.-Y.; Liu, Y.; Zhou, M.-B.; Wei, W.-
T.; Deng, G.-B.; Yin, D.-L.; Li, J.-H. J. Am. Chem. Soc. 2010, 132,
8900.
(2) (a) Guchhait, S. K.; Chaudhary, V.; Rana, V. A.; Priyadarshani, G.;
Kandekar, S.; Kashyap, M. Org. Lett. 2016, 18, 1534. (b) Kong, L.;
Wang, M.; Zhang, F.; Xu, M.; Li, Y. Org. Lett. 2016, 18, 6124.
(c) Zhou, X.-Y.; Chen, X.; Wang, L.-G. Synlett 2016, 27, 2742.
(d) Yarlagadda, S.; Ramesh, B.; Reddy, C.; Srinivas, R. L.; Sridhar,
B.; Reddy, B. V. S. Org. Lett. 2017, 19, 170. (e) Zhou, X.-Y.; Chen,
X.; Wang, L.-G. Synthesis 2017, 49, 3662. (f) Zhou, X.-Y.; Chen,
X.; Wang, L.-G.; Yang, D.; Li, J.-H. Synlett 2018, 29, 835.
(13) Wu, W.; Su, W. J. Am. Chem. Soc. 2011, 133, 11924.
(14) Akai, S.; Peat, A. J.; Buchwald, S. L. J. Am. Chem. Soc. 1998, 120,
9119.
(15) Jiang, T.-S.; Wang, G.-W. Org. Lett. 2013, 15, 788.
(16) Ottoni, O.; Cruz, R.; Alves, R. Tetrahedron 1998, 54, 13915.
(17) Heller, S. T.; Schultz, E. E.; Sarpong, R. Angew. Chem. Int. Ed.
2012, 51, 8304.
(18) Umehara, A.; Ueda, H.; Tokuyama, H. J. Org. Chem. 2016, 81,
11444.
(19) Ta, L.; Sundén, H. Chem. Commun. 2018, 54, 531.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F