Base-promoted domino reaction for the synthesis of 2,3-disubstituted indoles from 2-aminobenzaldehyde/2-amino aryl ketones, tosylhydrazine, and aromatic aldehydes

Article abstract of DOI:10.1016/j.tet.2016.06.046

A base-promoted domino reaction to synthesize the 2,3-disubstituted indoles from 2-aminobenzaldehyde/2-amino aryl ketones, tosylhydrazine, and aromatic aldehydes has been developed. This strategy provides a simple and beneficial way for the construction of 2,3-disubstituted indole compounds from readily available starting materials under mild conditions.

Full text of DOI:10.1016/j.tet.2016.06.046

Accepted Manuscript
Base-promoted domino reaction for the synthesis of 2,3-disubstituted indoles from 2-
aminobenzaldehyde/2-amino aryl ketones, tosylhydrazine, and aromatic aldehydes
Yan-Dong Wu, Jun-Rui Ma, Wen-Ming Shu, Kai-Lu Zheng, An-Xin Wu
PII:
S0040-4020(16)30568-3
10.1016/j.tet.2016.06.046
TET 27860
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 12 April 2016
Revised Date: 16 June 2016
Accepted Date: 20 June 2016
Please cite this article as: Wu Y-D, Ma J-R, Shu W-M, Zheng K-L, Wu A-X, Base-promoted domino
reaction for the synthesis of 2,3-disubstituted indoles from 2-aminobenzaldehyde/2-amino aryl ketones,
tosylhydrazine, and aromatic aldehydes, Tetrahedron (2016), doi: 10.1016/j.tet.2016.06.046.
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Base-Promoted Domino Reaction for the
Synthesis of 2,3-Disubstituted Indoles from 2-
Aminobenzaldehyde/2-Amino Aryl ketones,
Tosylhydrazine, and Aromatic Aldehydes
Leave this area blank for abstract info.
Yan-Dong Wu*, Jun-Rui Ma, Wen-Ming Shu, Kai-Lu Zheng, An-Xin Wu*
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China
Normal University, Wuhan 430079, P. R. China.

1
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Tetrahedron
journal homepage: www.elsevier.com
Base-Promoted Domino Reaction for the Synthesis of 2,3-Disubstituted Indoles from
2-Aminobenzaldehyde/2-Amino Aryl ketones, Tosylhydrazine, and Aromatic
Aldehydes
Yan-Dong Wu*, Jun-Rui Ma, Wen-Ming Shu, Kai-Lu Zheng, An-Xin Wu*
aKey Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, P. R. China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A base-promoted domino reaction to synthesize the 2,3-disubstituted indoles from 2-
aminobenzaldehyde/2-amino aryl ketones, tosylhydrazine, and aromatic aldehydes has been
developed. This strategy provides a simple and beneficial way for the construction of 2,3-
disubstituted indole compounds from readily available starting materials under mild conditions.
Available online
Keywords:
2,3-disubstituted indoles
base-promoted domino reaction
2-aminobenzaldehyde/2-amino aryl ketones
tosylhydrazine
aromatic aldehydes
1. Introduction
aminobenzaldehyde/2-amino aryl ketones, tosylhydrazine , and
aromatic aldehydes (Scheme 1d).
The 2,3-disubstituted indole skeleton is widely existed in
natural products (e.g., Cephalandole B, Cephalandole C) and
biologically active compounds possessing a wide spectrum of
properties such as antimycobacterial, antibacterial, and anticancer.
5-HT6 and GPRC6A have been used as several G protein-coupled
receptors (Scheme 1).1-3 In addition, 2,3-disubstituted indole
scaffolds also serves as an important intermediate in synthetic
organic chemistry.4 Consequently, the development of efficient
synthetic approaches to 2,3-disubstituted indoles has attracted
much attention from chemists.
Scheme 1. Natural products and pharmacological biological
active compounds containing 2,3-disubstituted indole core.
To date, several methods have been established for the
synthesis of 2,3-disubstituted indole derivatives.5 Among these,
the most general method is probably the Fischer indole synthesis,
in which 2,3-disubstituted indoles are prepared from
phenylhydrazines and ketones or aldehydes in the presence of
protic acid or Lewis acid catalyst (Scheme 1a).6-8 In addition,
Hupperts and co-workers reported the first titanium catalyzed
carbonyl coupling reactions for the preparation of 2,3-
disubstituted indoles (Scheme 1b).9 In recent years, transition-
metal-catalyzed cyclization has been developed to synthesize the
2,3-disubstituted indoles from arylamines and alkynes (Scheme
1c).10-12 Despite these achievements, there is still a need to
develop more powerful and straightforward procedures to
synthesize 2,3-disubstituted indole and its related derivatives in
mild conditions. Herein, we developed a base-promoted domino
reaction to synthesize the 2,3-disubstituted indoles from 2-
Scheme 2. Typical protocols for the synthesis of indoles. TM
= transition metal.

2
Tetrahedron
ACCEPTED MANUSCRIPT
2. Results and Discussion
moderate to good yields (3aa-3ac; 53–55%; 3aj-3ak; 62-68%).
Moderate yields were obtained for halo-substituted substrates
(3ad-3ai; 53–65%). Furthermore, 2-naphthaldehyde also
provided the expected products 3al in 50% yield. Fortunately, the
structure of 3aa was further confirmed by X-ray crystallographic
analysis (see Supporting Information (SI)).
To test the feasibility of the proposed strategy, we commenced
our study by choosing 1-(2-aminophenyl)ethanone (1a), 4-
methylbenzaldehyde (2b) and tosylhydrazine as model
substrates, as shown in Table 1. Initially, 1-(2-aminophenyl)
ethanone (1a) and tosylhydrazine were conducted in 1,4-dioxane
at 110 oC.13e Following, 4-methylbenzaldehyde was added to
optimize the reaction conditions. The reaction occurred with 1.0
Table 2. Scope of aromatic aldehydes a,b
o
equiv of Cs2CO3 in 1,4-dioxane at 110 C for 24 hours to afford
3-methyl-2-(p-tolyl)-1H-indole (3ab) in 10% yield (Table 1,
entry 1). When the dosage of Cs2CO3 was increased to 4.0
equivalents, the yield increased to 55% (Table 1, entry 3).
However, further increase in the amount of Cs2CO3 did not lead
to significant difference in the yield (Table 1, entry 4).
Subsequently, screening a variety of solvents revealed that the
solvent had great influence on the reaction (entries 5-11), which
suggested that 1,4-dioxane was the most effective solvent so far
for the formation of 3ab. Later, different bases were also tested,
including K2CO3, Na2CO3, NaOH, KOH, t-BuOK, NaOEt,
DABCO, DBU, and NEt3 (entries 12-20), and Cs2CO3 was
proven to be the optimal base.
a Reaction conditions: 1-(2-aminophenyl)ethanone 1a (1.0 mmol, 1.0 equiv),
tosylhydrazine (1.0 mmol, 1.0 equiv) and aromatic aldehydes 2 (1.2 mmol,
1.2 equiv) and Cs2CO3 (4.0 mmol, 4.0 equiv) was stirred in 1,4-dioxane (10
mL) at 110 oC for 24 hours. b Isolated yields.
Table 1. Optimization of the reaction conditionsa
i) TsNHNH2
dioxane, 110 o
O
The scope of this reaction was further extended to different
substituted 2-aminobenzaldehydes/2-amino aryl ketones 1 (Table
3). Pleasingly, 2-aminobenzaldehyde 1b was well tolerated in the
reaction, leading to desired product 3ba in 70% yield. When R2 =
Me, and R1 were a bromo or iodo substituent, the reaction
delivered the corresponding products 3ca and 3da in 67% and
71% yields respectively. Moreover, moderate yields were gained
with aryl substituents in the R1 position (3ea-3ga; 64%–68%).
C
Me
CHO
N
H
NH2
Me
2b
conditions
3ab
1a
ii)
Base
(equiv)
Temp
(oC)
110
Yieldb
(%)
10
20
55
50
0
Entry
Solvent
1
2
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
toluene
Cs2CO3 (1.0)
Cs2CO3 (3.0)
Cs2CO3 (4.0)
Cs2CO3 (5.0)
Cs2CO3 (4.0)
Cs2CO3 (4.0)
Cs2CO3 (4.0)
Cs2CO3 (4.0)
Cs2CO3 (4.0)
Cs2CO3 (4.0)
Cs2CO3 (4.0)
K2CO3 (4.0)
Na2CO3 (4.0)
NaOH (4.0)
KOH (4.0)
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
Table 3. Scope of 2-aminobenzaldehyde/2-amino aryl ketones a,b
3
i) TsNHNH2
dioxane, 110 o
O
4
R2
R1
C
R1
R2
NH2
5
O
N
H
ii)
Ph
H
6
DCE
0
2a
3
1
Cs2CO3, dioxane, 110 o
C
7
DMSO
0
Br
I
8
DMF
0
N
H
N
H
N
9
H2O
5
H
3ba, 70%
3ca, 67%
3da, 71%
10
11
12
13
14
15
16
17
18
19
20
glycol
10
0
Br
pyrrolidone
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
Ph
N
H
35
40
10
30
0
N
H
N
H
3ea, 68%
3fa, 64%
3ga, 65%
a Reaction conditions: 1 (1.0 mmol, 1.0 equiv), tosylhydrazine (1.0 mmol, 1.0
equiv) and benzaldehyde 2a (1.2 mmol, 1.2 equiv) and Cs2CO3 (4.0 mmol,
b
4.0 equiv) was stirred in 1,4-dioxane (10 mL) at 110 oC for 24 hours.
t-BuOK (4.0)
NaOEt (4.0)
Isolated yields.
20
22
0
Next, our attention turned to the exploration of a more
efficient approach to synthesize 2,3-disubstituted indoles from
commercial available starting materials. A one-pot two-step
protocol was trialed for the synthesis of aromatic-3-methyl-1H-
indoles 3 using 2-aminobenzaldehydes/2-amino aryl ketones 1,
tosylhydrazine, and aromatic aldehydes 2 in 1,4-dioxane with
Cs2CO3 at 110 oC for 25 hours. Various substituted 2-
aminobenzaldehydes/2-amino aryl ketones 1, tosylhydrazine and
aromatic aldehydes 2 were found compatible with the reaction, as
shown in Scheme 3.
1,4-dioxane DABCO (4.0)
1,4-dioxane
1,4-dioxane
DBU (4.0)
NEt3 (4.0)
50
a Reaction conditions: 1a (0.1 mmol, 1.0 equiv), tosylhydrazine (1.0 mmol,
1.0 equiv), 2b (0.12 mmol, 1.2 equiv), base (0.4 mmol, 4.0 equiv), and
solvent (3 mL) in a sealed vessel for 24 hours. b Isolated yields.
With the optimized conditions in hand, the generality and
scope of the aromatic aldehydes was next investigated. To our
delight, the reaction demonstrated wide scope for the structure of
aromatic aldehydes which proceeded smoothly to afford the
corresponding products in moderate to good yields (50-68%;
Table 2), regardless of their electronic or steric properties. Aryl
aldehydes bearing electron-neutral (H), electron-donating (4-Me,
4-OMe) and electron-withdrawing (4-NO2, 3-NO2) substituents
could be transformed into the corresponding products in

3
relative to tetramethylsilane. 13C spectra were recorded in
ACCEPTED MANUSCRIPT
CDCl3 or DMSO-d6 on 100/150 MHz NMR spectrometers and
resonances (δ) are given in ppm. HRMS were obtained on an
apex-Ultra MS equipped with APCI. MS was recorded using
ESI. Melting points were determined using an electrothermal
capillary melting point apparatus and not corrected. The
structures of 3aa and 4a were confirmed by X-ray diffraction.
aReaction conditions: (i) 2-aminobenzaldehyde/2-amino aryl ketones 1 (1.0
mmol, 1.0 equiv), tosylhydrazine (1.0 mmol, 1.0 equiv) was stirred in 1,4-
4.2. General procedure for synthesis of 3 (3aa as an example)
o
dioxane (10 mL) at 110 C for 5 h. (ii) aromatic aldehydes 2 (1.2 mmol, 1.2
equiv) and Cs2CO3 (4.0 mmol, 4.0 equiv) was stirred in 1,4-dioxane at 110 oC
for 20 hours. bIsolated yields.
2-amino aryl ketone 1a (135.1 mg, 1.0 mmol) with
tosylhydrazine (186.0 mg, 1.0 mmol) was stirred in 1,4-dioxane
(15 mL) at 110 oC for 5 h till almost completed conversion of the
substrates by TLC analysis. Then benzaldehyde 2a (127.2 mg,
1.2 mmol) and Cs2CO3 (1.3 g, 4.0 mmol) were also stirred in 1,4-
dioxane (15 mL) at 110oC for 24 hours almost completed
conversion of the substrates by TLC analysis. The mixture was
extracted with EtOAc three times (3 × 50 mL), and the combined
organic extracts were then washed with brine. After drying over
Na2SO4 and evaporation, The crude product was purified by
column chromatography on silica gel (eluent: petroleum
ether/EtOAc = 25/1) to afford the product 3aa.
Scheme 3. The synthesis of aromatic-3-methyl-1H-indoles in
one pota,b
On the basis of the aforementioned results, a plausible
mechanism was proposed as outlined in Scheme 4 (3aa as
example).
Initially,
the
condensation
of
1-(2-
aminophenyl)ethanone 1a and tosylhydrazine afforded the
corresponding tosylhydrazone intermediate 4a,13 which
subsequently generated diazo intermediate A13a,c (determined by
MS : see the SI) in situ in the presence of Cs2CO3. The
nucleophilic carbon of its resonance structure A’ in turn attached
the electrophilic carbonyl carbon of 2a providing the
intermediate B,14 which formed intermediate C through an
4.3. Characterization data
4.3.1 3-methyl-2-phenyl-1H-indole (3aa). Yield 53%, 109.8 mg;
o
elimination process. Then intermediate
C
underwent
white solid; mp 103-104 C; IR (KBr): 3418, 1639, 1602, 1485,
1458, 1425, 1384, 1331, 1304, 1183, 1151, 1119, 1043, 1014,
816, 757, 745, 720, 699, 580, 528, 495, 468, 433 cm-1; 1H NMR
(400 MHz, CDCl3): δ (ppm) 8.01 (s, 1H), 7.67-7.61 (m, 2H), 7.59
(s, 1H), 7.52-7.48 (m, 2H), 7.40-7.37 (m, 2H), 7.25-7.17 (m, 2H),
2.50 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 136.5, 134.7,
134.0, 130.7, 129.5, 128.4, 128.0, 123.0, 120.2, 119.6, 111.3,
109.3, 10.4; HRMS (ESI): m/z [M+H]+ calcd for C15H14N:
208.1121; found: 208.1118.
intramolecular cyclization via dehydration to furnish intermediate
D. Finally, intermediate D was converted into the desired product
3aa via tautomerization.
4.3.2 3-methyl-2-(p-tolyl)-1H-indole (3ab). Yield 55%, 121.6
o
mg; white solid; mp 110-111 C; IR (KBr): 3377, 1640, 1509,
1486, 1317, 1302, 1186, 1151, 997, 845, 825, 757, 743, 727, 688,
1
746, 525, 514 cm–1; H NMR (600 MHz, CDCl3): δ (ppm) 7.98
(s, 1H), 7.62 (d, J = 7.8 Hz, 1H), 7.49 (d, J = 7.8 Hz, 2H), 7.37
(d, J = 8.4 Hz, 1H), 7.31 (d, J = 7.8 Hz, 2H), 7.22 (t, J = 7.8 Hz,
1H), 7.17 (t, J = 7.8 Hz, 1H), 2.47 (s, 3H), 2.44 (s, 3H); 13C
NMR (150 MHz, CDCl3) δ (ppm) 137.1, 135.6, 134.1, 130.4,
130.0, 129.5, 127.6, 122.1, 119.4, 118.8, 110.5, 108.2, 21.2, 9.6;
HRMS (ESI): m/z [M+Na]+ calcd for C16H15NNa: 244.1097;
found: 244.1100.
Scheme 4. A plausible mechanism
3. Conclusion
In summary, we have established a base-promoted domino
reaction strategy to directly synthesize 2,3-disubstituted indoles
from
2-aminobenzaldehyde/2-amino
aryl
ketones,
tosylhydrazine, and aromatic aldehydes. This is a directly
beneficial strategy for constructing 2,3-disubstituted indole
compounds from readily available starting materials under mild
conditions, which operates via sequential condensation,
nucleophilic addition, elimination, and intramolecular
cyclization. Further investigations into the mechanism and
applications of this reaction are currently ongoing.
4.3.3 2-(4-methoxyphenyl)-3-methyl-1H-indole (3ac). Yield 54%,
128.0 mg; white solid; mp 95-96 oC; IR (KBr): 3422, 1668, 1644,
1606, 1587, 1510, 1453, 1385, 1314, 1156, 1188, 1114, 1028,
1
847, 762, 686, 640, 524 cm–1; H NMR (600 MHz, CDCl3): δ
(ppm) 9.45 (s, 1H), 8.21 (d, J = 7.8 Hz, 2H), 7.51 (d, J = 7.8 Hz,
1H), 7.40 (d, J = 7.2 Hz, 1H), 7.34 (t, J = 7.8 Hz, 1H), 7.18 (t, J
= 7.8 Hz, 1H), 6.93 (d, J = 8.4 Hz, 2H), 3.85 (s, 3H), 1.62 (s,
3H); 13C NMR (150 MHz, CDCl3) δ (ppm) 176.9, 162.2, 138.3,
130.2, 130.0, 126.0, 124.2, 124.1, 121.7, 120.6, 114.1, 94.6, 55.6,
21.9; HRMS (ESI): m/z [M] calcd for C16H15NO: 237.1148;
found: 237.1133.
4. Experimental
4.1. General
All substrates and reagents were commercially available and
used without further purification. TLC analysis was performed
using pre-coated glass plates. Flash column chromatography was
performed on silica gel (200–300 mesh). IR spectra were
4.3.4 2-(2-chlorophenyl)-3-methyl-1H-indole (3ad). Yield 64%,
154.3 mg; white solid; mp 132-133 C; IR (KBr): 3387, 1478,
o
1454, 1432, 1383, 1362, 1322, 810, 770, 748, 736, 717, 682, 579,
1
533, 521, 492, 467, 439 cm–1; H NMR (600 MHz, CDCl3): δ
1
recorded as KBr pellets with absorption in cm–1. H spectra were
(ppm) 8.09 (s, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.59-7.58 (m, 1H),
7.52-7.51 (m, 1H), 7.42-7.38 (m, 3H), 7.30 (t, J = 7.8 Hz, 1H),
recorded in CDCl3 or DMSO-d6 on 400/600 MHz NMR
spectrometers and resonances (δ) are given in parts per million

4
Tetrahedron
7.24 (t, J = 7.8 Hz, 1H), 2.38 (s, 3H); 13C NMR (150 MHz,
115.8, 115.7, 110.6, 108.6, 9.5; HRMS (ESI): m/z [M+H]+ calcd
ACCEPTED MANUSCRIPT
CDCl3) δ (ppm) 136.3, 134.2, 133.1, 132.4, 132.1, 130.8, 130.0,
129.4, 127.3, 123.1, 120.0, 119.7, 111.4, 1112, 10.2; HRMS
(ESI): m/z [M+H]+ calcd for C15H13ClN: 242.0731; found:
242.0737.
for C15H13FN: 226.1027; found: 226.1032.
4.3.10 3-methyl-2-(4-nitrophenyl)-1H-indole (3aj). Yield 68%,
171.4 mg; white solid; mp 180-181 C; IR (KBr): 3433, 1592,
o
1549, 1506, 1450, 1385, 1338, 1287, 1252, 1187, 1153, 1109,
1
4.3.5 2-(4-chlorophenyl)-3-methyl-1H-indole (3ae). Yield 60%,
144.6 mg; white solid; mp 126-127 C; IR (KBr): 3418, 1648,
1043, 1014, 863, 757, 747, 724, 697 cm–1; H NMR (600 MHz,
o
CDCl3): δ (ppm) 8.32 (d, J = 7.8 Hz, 2H), 8.16 (s, 1H), 7.73 (d, J
= 7.8 Hz, 2H), 7.65 (d, J = 7.8 Hz, 1H), 7.41 (d, J = 7.8 Hz, 1H),
1591, 1405, 1385, 1220, 1185, 1151, 1130, 1095, 1043, 1015,
996, 848, 751, 688, 573, 513 cm–1; H NMR (600 MHz, CDCl3):
7.29 (t, J = 7.2 Hz, 1H), 7.19 (t, J = 7.2 Hz, 1H), 2.53 (s, 3H); 13
C
1
δ (ppm) 8.02 (s, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.50 (d, J = 8.4 Hz,
2H), 7.44 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 7.8 Hz, 1H), 7.22 (t, J
= 7.2 Hz, 1H), 7.16 (t, J = 7.2 Hz, 1H), 2.45 (s, 3H); 13C NMR
(150 MHz, CDCl3) δ (ppm) 135.9, 132.2, 131.9, 131.8, 130.0,
129.1, 122.6, 121.3, 119.7, 119.0, 110.7, 109.3, 9.7; HRMS (ESI):
m/z [M] calcd for C15H12ClN: 241.0653; found: 241.0653.
NMR (150 MHz, CDCl3) δ (ppm) 146.9, 140.3, 137.2, 132.1,
130.5, 128.3, 124.9, 124.5, 120.8, 120.2, 112.9, 111.7, 10.8;
HRMS (ESI): m/z [M+H]+ calcd for C15H13N2O2: 253.0972;
found: 253.0972.
4.3.11 3-methyl-2-(3-nitrophenyl)-1H-indole (3ak). Yield 68%,
o
171.4 mg; white solid; mp 158-159 C; IR (KBr): 3379, 1615,
4.3.6 2-(2,4-dichlorophenyl)-3-methyl-1H-indole (3af). Yield
58%, 159.5 mg; white solid; oil; IR (KBr): 3414, 1639, 1585,
1523, 1452, 1384, 1306, 1184, 1151, 1130, 1043, 1015, 958, 867,
821, 774, 688 cm–1; 1H NMR (600 MHz, CDCl3): δ (ppm) 8.10 (s,
1H), 7.63 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 1.8 Hz, 1H), 7.40 (d, J
=7.8 Hz, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.36-7.34 (m, 1H), 7.26
(t, J = 7.8 Hz, 1H), 7.18 (t, J = 7.8 Hz, 1H), 2.30 (s, 3H); 13C
NMR (150 MHz, CDCl3) δ (ppm) 135.7, 134.5, 134.3, 133.1,
130.4, 130.2, 130.0, 128.7, 127.1, 122.7, 119.5, 119.1, 111.0,
110.8, 9.5; HRMS (ESI): m/z [M+H]+ calcd for C15H12Cl2N:
276.0341; found: 276.0327.
1575, 1551, 1520, 1347, 897, 881, 844, 800, 751, 741, 725, 717,
1
686, 666, 652, 586, 560, 529 cm–1; H NMR (600 MHz, CDCl3):
δ (ppm) 8.43 (s, 1H), 8.19 (d, J = 8.4 Hz, 1H), 8.14 (s, 1H), 7.91
(d, J = 7.8 Hz, 1H), 7.67 - 7.63 (m, 2H), 7.41 (d, J = 7.8 Hz, 1H),
7.28 (d, J = 7.8 Hz, 1H), 7.19 (t, J = 7.2 Hz, 1H), 2.51 (s, 3H);
13C NMR (150 MHz, CDCl3) δ (ppm) 148.6, 136.2, 134.9, 133.3,
131.3, 129.8, 129.7, 123.3, 122.0, 121.7, 120.0, 119.4, 111.0,
110.8, 9.8; HRMS (ESI): m/z [M+Na]+ calcd for C15H12N2NaO2:
275.0791; found: 275.0786.
4.3.12 3-methyl-2-(naphthalen-2-yl)-1H-indole (3al). Yield 50%,
o
128.6 mg; white solid; mp 137-138 C; IR (KBr): 3395, 1628,
4.3.7 2-(2-bromophenyl)-3-methyl-1H-indole (3ag). Yield 64%,
182.4 mg; white solid; mp 126-127 C; IR (KBr): 3383, 1479,
1600, 1488, 1456, 1424, 1385, 1330, 1303, 1239, 1219, 1184,
1151, 1130, 1043, 1014, 894, 857, 818, 750, 688, 577, 478 cm–1;
1H NMR (600 MHz, CDCl3): δ (ppm) 8.15 (s, 1H), 8.02 (s, 1H),
7.94 (d, J = 8.4 Hz, 1H), 7.91-7.88 (m, 2H), 7.74 (d, J = 8.4 Hz,
1H), 7.64 (d, J = 7.8 Hz, 1H), 7.55-7.50 (m, 2H), 7.41 (d, J = 8.4
Hz, 1H), 7.23 (d, J = 8.4 Hz, 1H), 7.18 (t, J = 7.2 Hz, 1H), 2.55 (s,
3H); 13C NMR (150 MHz, CDCl3) δ (ppm) 136.0, 134.0, 133.5,
132.4, 130.7, 130.0, 128.4, 128.0, 127.8, 126.5, 126.4, 126.2,
125.7, 122.4, 120.0, 119.0, 110.7, 109.2, 9.8; HRMS (ESI): m/z
[M+H]+ calcd for C19H16N: 258.1277; found: 258.1256.
o
1454, 1428, 1383, 1328, 1307, 1234, 1185, 1151, 814, 769, 949,
1
748, 733, 712, 681, 580, 521; H NMR (600 MHz, CDCl3): δ
(ppm) 7.98 (s, 1H), 7.69 (d, J = 7.8 Hz, 1H), 7.61 (d, J = 7.8 Hz,
1H), 7.41 (d, J =7.2 Hz, 1H), 7.37 (t, J = 7.8 Hz, 1H), 7.33 (d, J
= 8.4 Hz, 1H), 7.25(7)-7.23 (m, 1H), 7.21 (d, J = 8.4 Hz, 1H),
7.15 (t, J = 7.8 Hz, 1H), 2.27 (s, 3H); 13C NMR (150 MHz,
CDCl3) δ (ppm) 136.1, 134.6, 133.9, 133.6, 133.4, 130.3, 129.4,
127.9, 124.5, 123.1, 120.1, 119.8, 111.4, 111.0, 10.2; HRMS
(ESI): m/z [M+H]+ calcd for C15H13BrN: 286.0226; found:
286.0222.
4.3.13 2-phenyl-1H-indole (3ba). Yield 70%, 135.2 mg; white
o
solid; mp 185-186 C; IR (KBr): 3425, 1638, 1618, 1457, 1447,
4.3.8 2-(4-bromophenyl)-3-methyl-1H-indole (3ah). Yield 65%,
185.3 mg; white solid; mp 142-144 C; IR (KBr): 3418, 1639,
1403, 1300, 1186, 1151, 1130, 1043, 1016, 798, 763, 744, 689,
620, 507 cm–1; 1H NMR (600 MHz, CDCl3): δ (ppm) 8.35 (s, 1H),
7.68 (d, J = 7.8 Hz, 2H), 7.65 (d, J = 7.8 Hz, 1H), 7.46 (t, J = 7.8
Hz, 2H), 7.41 (d, J = 8.4 Hz, 1H), 7.34 (t, J = 7.2 Hz, 1H), 7.21 (t,
J = 7.2 Hz, 1H), 7.14 (t, J = 7.2 Hz, 1H), 6.85 (s, 1H); 13C NMR
(150 MHz, CDCl3) δ (ppm) 137.8, 136.7, 132.3, 129.2, 129.0,
127.7, 125.1, 122.3, 120.6, 120.2, 110.9, 99.9; HRMS (ESI): m/z
[M+H]+ calcd for C14H12N: 194.0964; found: 194.0966.
o
1546, 1484, 1460, 1436, 1330, 1308, 1184, 1152, 1120, 1070,
1
1043, 1014, 1002, 827, 756, 745, 500, 464 cm–1; H NMR (600
MHz, CDCl3): δ (ppm) 8.00 (s, 1H), 7.61-7.59 (m, 3H), 7.44 (d, J
= 8.4 Hz, 2H), 7.36 (d, J = 7.8 Hz, 1H), 7.22 (t, J = 7.2 Hz, 1H),
7.16 (t, J = 7.2 Hz, 1H), 2.44 (s, 3H); 13C NMR (150 MHz,
CDCl3) δ (ppm) 135.9, 132.2, 131.9, 131.8, 129.9, 129.1, 122.6,
121.3, 119.7, 119.0, 110.7, 109.3, 9.7; HRMS (ESI): m/z [M+H]+
calcd for C15H13BrN: 286.0226; found: 286.0223.
4.3.14 5-bromo-3-methyl-2-phenyl-1H-indole (3ca). Yield 67%,
o
190.9 mg; white solid; mp 133-134 C; IR (KBr): 3408, 1639,
4.3.9 2-(4-fluorophenyl)-3-methyl-1H-indole (3ai). Yield 53%,
119.3 mg; white solid; mp 135-136 C; IR (KBr): 3423, 1639,
1527, 1497, 1465, 1449, 1426, 1385, 1319, 1307, 1227, 1221,
1183, 1152, 1129, 1075, 1045, 1015, 817, 791, 768, 744, 700,
o
1
1602, 1505, 1459, 1437, 1384, 1306, 1218, 1186, 1154, 1130,
585, 575, 504, 479 cm–1; H NMR (600 MHz, CDCl3): δ (ppm)
1
1014, 947, 838, 814, 786, 747, 688, 578, 523, 512, 468 cm–1; H
8.04 (s, 1H), 7.71 (s, 1H), 7.54 (d, J = 7.2 Hz, 2H), 7.48 (t, J =
7.8 Hz, 2H), 7.37 (t, J = 7.2 Hz, 1H), 7.28-7.25 (m, 1H), 7.21 (d,
J = 8.4 Hz, 1H), 2.40 (s, 3H); 13C NMR (150 MHz, CDCl3) δ
(ppm) 135.2, 134.3, 132.7, 131.8, 128.9, 127.7 (0), 127.6(7),
124.9, 121.6, 112.6, 112.1, 108.2, 9.5; HRMS (ESI): m/z [M+H]+
calcd for C15H13BrN: 286.0226; found: 286.0210.
NMR (600 MHz, CDCl3): δ (ppm) 7.91 (s, 1H), 7.58 (d, J = 7.8
Hz, 1H), 7.51-7.49 (m, 2H), 7.33 (d, J = 8.4 Hz, 1H), 7.22-7.19
(m, 1H), 7.16 (d, J = 3.0 Hz, 1H), 7.14 (d, J = 9.0 Hz, 2H), 2.41
(s, 3H); 13C NMR (150 MHz, CDCl3) δ (ppm) 162.9, 161.2,
135.7, 133.1, 129.8, 129.4(1), 129.3(6), 122.3, 119.6, 118.9,

5
4.3.15 5-iodo-3-methyl-2-phenyl-1H-indole (3da). Yield 71%,
Supplementary data
ACCEPTED MANUSCRIPT
236.4 mg; white solid; mp 82-83 oC; IR (KBr): 3417, 1655, 1604,
1575, 1510, 1494, 1445, 1422, 1385, 1354, 1320, 1223, 1185,
1151, 1130, 1097, 1056, 1044, 1015, 958, 892, 819, 796, 777,
Supplementary data related to this article can be found online at
doi:
1
760, 701, 622, 564, 504 cm–1; H NMR (600 MHz, CDCl3): δ
(ppm) 8.04 (s, 1H), 7.93 (s, 1H), 7.55 (d, J = 7.8 Hz, 2H), 7.49 (t,
J = 7.8 Hz, 2H), 7.45 (d, J = 8.4 Hz, 1H), 7.38 (t, J = 7.8 Hz, 1H),
7.14 (d, J = 8.4 Hz, 1H), 2.41 (s, 3H); 13C NMR (150 MHz,
CDCl3) δ (ppm) 135.5, 135.4(5), 133.3, 133.2(6), 131.1, 129.6,
128.6, 128.4, 128.3(5), 113.3, 108.6, 83.5, 10.2; HRMS (ESI):
m/z [M+H]+ calcd for C15H13IN: 334.0087; found: 334.0080.
References and notes
1
For selected examples, see: (a) Edwankar, R. V.; Edwankar, C. R.;
Namjoshi, O. A.; Deschamps, J. R.; Cook, J. M. J. Nat. Prod. 2012, 75,
181-188. (b) Bandini, M.; Eichholzer, A. Angew. Chem. 2009, 121, 9786-
9824. (c) Bandini, M.; Eichholzer, A. Angew. Chem. Int. Ed. Engl. 2009,
48, 9608-9644. (d) Richter, J. M.; Ishihara, Y.; Masuda, T.; Whitefield, B.
W.; Llamas, T.; Pohjakallio, A.; Baran, P. S. J. Am. Chem. Soc. 2008, 130,
17938-17954. (e) Wu, P.-L.; Hsu, Y.-L.; Jao, C.-W. J. Nat. Prod. 2006,
69, 1467-1470. (f) Kawasaki, T.; Higuchi, K. Nat. Prod. Rep. 2005, 22,
761-793. (g) Toyota, M.; Ihara, M. Nat. Prod. Rep. 1998, 15, 327-340. (h)
Saxton, J. E. Nat. Prod. Rep. 1997, 14, 559-590. (i) Yang, L.-M.; Chen,
C.-F.; Lee, K.-H. Bioorg. Med. Chem. Lett. 1995, 5, 465-468.
4.3.16 3-methyl-2,5-diphenyl-1H-indole (3ea). Yield 68%, 192.5
o
mg; white solid; mp 197-198 C; IR (KBr): 3384, 1641, 1602,
1470, 1453, 1426, 1385, 1322, 1301, 1183, 1152, 1130, 1043,
1015, 949, 877, 815, 761, 750, 697, 576, 515 cm–1; 1H NMR (400
MHz, CDCl3): δ (ppm) 8.05 (s, 1H), 7.81 (s, 1H), 7.70 (d, J = 2.4
Hz, 1H), 7.68 (d, J = 1.8 Hz, 1H), 7.62 (d, J = 2.4 Hz, 1H), 7.60
(d, J = 1.8 Hz, 1H), 7.51 (d, J = 10.4 Hz, 2H), 7.48 (d, J = 6.6 Hz,
2H), 7.46 (s, 1H), 7.44 (s, 1H), 7.39 (t, J = 10.8 Hz, 1H), 7.33 (t,
J = 10.8 Hz, 1H), 2.53 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
(ppm) 142.5, 135.2, 134.6, 133.7, 133.1, 133.0, 130.4, 128.7,
128.5, 127.6, 127.3, 127.2, 126.1, 122.0, 117.4, 110.8, 9.9;
HRMS (ESI): m/z [M+H]+ calcd for C21H18N: 284.1434; found:
284.1428.
2
(a) Aksenov, A. V.; Smirnov, A. N.; Magedov, I. V.; Reisenauer, M. R.;
Aksenov, N. A.; Aksenova, I. V.; Pendleton, A. L.; Nguyen, G.; Johnston,
R. K.; Rubin, M.; De Carvalho, A.; Kiss, R.; Mathieu, V.; Lefranc, F.;
Correa, J.; Cavazos, D. A.; Brenner, A. J.; Bryan, B. A.; Rogelj, S.;
Kornienko, A.; Frolova, L. V. J. Med. Chem. 2015, 58, 2206-2220. (b)
Kumar, D.; Maruthi Kumar, N.; Tantak, M. P.; Ogura, M.; Kusaka, E.; Ito,
T. Bioorg. Med. Chem. Lett. 2014, 24, 5170-5174. (c) Ž. Hodnik, L.
Peterlin Mašič, T. Tomašić, D. Smodiš, C. D’Amore, S. Fiorucci and D.
Kikelj, J. Med. Chem. 2014, 57, 4819-4833. (d) Arisawa, M.; Kasaya, Y.;
Obata, T.; Sasaki, T.; Nakamura, T.; Araki, T.; Yamamoto, K.; Sasaki, A.;
Yamano, A.; Ito, M.; Abe, H.; Ito, Y.; Shuto, S. J. Med. Chem. 2012, 55,
8152-8163. (e) M. Pojarová, D. Kaufmann, R. Gastpar, T. Nishino, P.
Reszka, P. J. Bednarski and E. von Angerer, Biorg. Med. Chem. 2007, 15,
7368-7379. (f) Kaufmann, D.; Pojarová, M.; Vogel, S.; Liebl, R.; Gastpar,
R.; Gross, D.; Nishino, T.; Pfaller, T.; von Angerer, E. Biorg. Med. Chem.
2007, 15, 5122-5136. (g) Linnepe, P.; Schmidt, A. M.; Eilbracht, P. Org.
Biomol. Chem. 2006, 4, 302-313. (h) Weinstein, D. S.; Liu, W.; Gu, Z.;
Langevine, C.; Ngu, K.; Fadnis, L.; Combs, D. W.; Sitkoff, D.; Ahmad, S.;
Zhuang, S.; Chen, X.; Wang, F. L.; Loughney, D. A.; Atwal, K. S.; Zahler,
R.; Macor, J. E.; Madsen, C. S.; Murugesan, N. Bioorg. Med. Chem. Lett.
2005, 15, 1435-1440. (i) Golob, T.; Liebl, R.; von Angerer, E. Biorg. Med.
Chem. 2002, 10, 3941-3953. (j) Cooper, L. C.; Chicchi, G. G.; Dinnell, K.;
Elliott, J. M.; Hollingworth, G. J.; Kurtz, M. M.; Locker, K. L.; Morrison,
D.; Shaw, D. E.; Tsao, K.-L.; Watt, A. P.; Williams, A. R.; Swain, C. J.
Bioorg. Med. Chem. Lett. 2001, 11, 1233-1236. (k) Glennon, R. A.; Lee,
M.; Rangisetty, J. B.; Dukat, M.; Roth, B. L.; Savage, J. E.; McBride, A.;
Rauser, L.; Hufeisen, S.; Lee, D. K. H. J. Med. Chem. 2000, 43, 1011-
1018.
4.3.17 3-methyl-5-(naphthalen-2-yl)-2-phenyl-1H-indole (3fa).
o
Yield 64%, 213.2 mg; white solid; mp 150-151 C; IR (KBr):
3380, 1634, 1600, 1557, 1505, 1482, 1451, 1426, 1384, 12196,
1184, 1151, 1129, 1015, 950, 807, 770, 742, 703, 688, 615, 477
cm–1; 1H NMR (400 MHz, CDCl3): δ (ppm) 8.13 (s, 1H), 8.06 (s,
1H), 7.96-7.93 (m, 3H), 7.89 (d, J = 12.6 Hz, 2H), 7.64-7.60 (m,
3H), 7.54-7.49 (m, 3H), 7.47 (d, J = 12.0 Hz, 2H), 7.39 (t, J =
10.8 Hz, 1H), 2.58 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm)
139.8, 135.2, 134.6, 133.7, 133.0, 132.8, 132.0, 130.5, 128.7,
128.0, 127.9, 127.6, 127.5, 127.3, 126.1, 125.9, 125.3(3),
125.2(7), 122.2, 117.6, 110.9, 109.0, 9.9; HRMS (ESI): m/z
[M+H]+ calcd for C25H20N: 334.1590; found: 334.1582.
4.3.18 5-(4-bromophenyl)-3-methyl-2-phenyl-1H-indole (3ga).
Yield 65%, 234.7 mg; white solid; mp 226-227 oC; IR (KBr):
3378, 1468, 1450, 1394, 1320, 1308, 1293, 1183, 1152, 1130,
1076, 1043, 1007, 835, 824, 804, 769, 702, 515 cm–1; 1H NMR
(600 MHz, CDCl3): δ (ppm) 12.71 (s, 1H), 9.07 (d, J = 8.4 Hz,
1H), 8.10 (s, 1H), 8.09 (d, J = 7.2 Hz, 2H), 7.82 (dd, J1,2 =1.8, J1,3
=8.4 Hz, 1H), 7.61 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 6.6 Hz, 1H),
7.54 (t, J = 7.8 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 2.79 (s, 3H);
13C NMR (150 MHz, DMSO-d6) δ (ppm) 141.1, 135.8, 134.8,
132.9, 131.6, 130.0, 129.7, 128.8, 128.7, 127.5, 127.2, 120.8,
119.5, 116.6, 111.6, 107.5, 9.9; HRMS (ESI): m/z [M+H]+ calcd
for C21H17BrN: 362.0538; found: 362.0533.
3
(a) Naik, M.; Ghorpade, S.; Jena, L. K.; Gorai, G.; Narayan, A.; Guptha,
S.; Sharma, S.; Dinesh, N.; Kaur, P.; Nandishaiah, R.; Bhat, J.;
Balakrishnan, G.; Humnabadkar, V.; Ramachandran, V.; Naviri, L. K.;
Khadtare, P.; Panda, M.; Iyer, P. S.; Chatterji, M. ACS Med. Chem. Lett.
2014, 5, 1005-1009. (b) Gloriam, D. E.; Wellendorph, P.; Johansen, L. D.;
Thomsen, A. R.; Phonekeo, K.; Pedersen, D. S. Chem. Biol. 2011, 18,
1489-1498. (c) P Sharma, P.; Kumar, A.; Sahu, V.; Upadhyay, S.; Singh,
J. Med. Chem. Res. 2008, 18, 383-395. (d) Willoughby, C. A.; Hutchins, S.
M.; Rosauer, K. G.; Dhar, M. J.; Chapman, K. T.; Chicchi, G. G.;
Sadowski, S.; Weinberg, D. H.; Patel, S.; Malkowitz, L.; Di Salvo, J.;
Pacholok, S. G.; Cheng, K. Bioorg. Med. Chem. Lett. 2002, 12, 93-96. (e)
Wacker, D. A.; Kasireddy, P. Tetrahedron Lett. 2002, 43, 5189-5191. (f)
Gastpar, R.; Goldbrunner, M.; Marko, D.; von Angerer, E. J. Med. Chem.
1998, 41, 4965-4972.
For selected examples, see: (a) Johansson, H.; Urruticoechea, A.; Larsen,
I.; Sejer Pedersen, D. J. Org. Chem. 2015, 80, 471-481. (b) Yeung, C. S.;
Ziegler, R. E.; Porco, J. A.; Jacobsen, E. N. J. Am. Chem. Soc. 2014, 136,
13614-13617. (c) Showalter, H. D. H. J. Nat. Prod. 2013, 76, 455-467. (d)
Righi, M.; Topi, F.; Bartolucci, S.; Bedini, A.; Piersanti, G.; Spadoni, G.
J. Org. Chem. 2012, 77, 6351-6357. (e) Gribble, G. W. Pure Appl. Chem.
2003, 75, 1417-1432.
For selected examples, see: (a) Deng, G.-B.; Zhang, J.-L.; Liu, Y.-Y.; Liu,
B.; Yang, X.-H.; Li, J.-H. Chem. Commun. 2015, 51, 1886-1888. (b)
Zhang, Y. C.; Zhao, J. J.; Jiang, F.; Sun, S. B.; Shi, F. Angew. Chem. Int.
Ed. Engl. 2014, 53, 13912-13915. (c) Xin, D.; Burgess, K. Org. Lett. 2014,
16, 2108-2110. (d) Li, B.; Ma, J.; Xie, W.; Song, H.; Xu, S.; Wang, B. J.
Org. Chem. 2013, 78, 9345-9353. (e) Nguyen, Q.; Nguyen, T.; Driver, T.
G. J. Am. Chem. Soc. 2013, 135, 620-623. (f) Arcadi, A.; Cacchi, S.;
Fabrizi, G.; Goggiamani, A.; Iazzetti, A.; Marinelli, F. Org. Biomol.
Chem. 2013, 11, 545-548. (g) Tobisu, M.; Fujihara, H.; Koh, K.; Chatani,
4
5
Acknowledgments
We are grateful to the National Natural Science Foundation of
China (Grant Nos. 21272085 and 21472056) and the Excellent
Doctorial Dissertation Cultivation Grant from Central China Normal
University (2015YBYB053) for financial support. We would also
like to thank Dr. Chuanqi Zhou, Hebei University, for analytical
support and Xiang-Gao Meng for the supporting in X-ray diffraction
analysis.

6
Tetrahedron
N. J. Org. Chem. 2010, 75, 4841-4847. (h) Jana, S.; Clements, M. D.;
ACCEPTED MANUSCRIPT
Sharp, B. K.; Zheng, N. Org. Lett. 2010, 12, 3736-3739. (i) Zhou, L.;
Doyle, M. P. J. Org. Chem. 2009, 74, 9222-9224. (g) Shen, M.; Leslie, B.
E.; Driver, T. G. Angew. Chem. Int. Ed. Engl. 2008, 47, 5056-5059. (k)
Leogane, O.; Lebel, H. Angew. Chem. 2008, 120, 356-358. (l) Cui, S.-L.;
Wang, J.; Wang, Y.-G. J. Am. Chem. Soc. 2008, 130, 13526-13527. (m)
Banerjee, S.; Barnea, E.; Odom, A. L. Organometallics 2008, 27, 1005-
10014. (n) Bartoli, G.; Palmieri, G.; Petrini, M. Tetrahedron 1990, 46,
1379-1384. (o) Baccolini, G.; Dalpozzo, R.; Errani, E. Tetrahedron 1987,
43, 2755-2760.
6
7
(a) Fischer, E.; Hess, O. Ber. Dtsch. Chem. Ges. 1884, 17, 559-568. (b)
Fischer, E.; Jourdan, F. Ber. Dtsch. Chem. Ges. 1883, 16, 2241-2245.
(a) Inman, M.; Moody, C. J. Chem. Commun. 2011, 47, 788-790. (b)
Desroses, M.; Wieckowski, K.; Stevens, M.; Odell, L. R. Tetrahedron
Lett. 2011, 52, 4417-4420. (c) Liu, K. G.; Robichaud, A. J.; Lo, J. R.;
Mattes, J. F.; Cai, Y. Org. Lett. 2006, 8, 5769-5771. (d) Barluenga, J.;
Trincado, M.; Rubio, E.; González, J. M. Angew. Chem. Int. Ed. 2003, 42,
2406-2409.
8
9
(a) Jia, Z.; Nagano, T.; Li, X.; Chan, A. S. C. Eur. J. Org. Chem. 2013,
2013, 858-861. (b) He, Z.; Li, H.; Li, Z. J. Org. Chem. 2010, 75, 4636-
4639. (c) Minakata, S.; Kasano, Y.; Ota, H.; Oderaotoshi, Y.; Komatsu, M.
Org. Lett. 2006, 8, 3693-3695. (d) Smith, A. L.; Stevenson, G. I.; Swain,
C. J.; Castro, J. Tetrahedron Lett. 1998, 39, 8317-8320.
Fuerstner, A.; Hupperts, A. J. Am. Chem. Soc. 1995, 117, 4468-4475.
10 For some examples of Pd-catalyzed, see: (a) Yao, B.; Wang, Q. Chem.
Eur. J. 2014, 20, 12255-12261. (b) Phetrak, N.; Rukkijakan, T.;
Sirijaraensre, J.; Prabpai, S.; Kongsaeree, P.; Klinchan, C.; Chuawong, P.
J. Org. Chem. 2013, 78, 12703-12709. (c) Srinivas, K.; Saiprathima, P.;
Balaswamy, K.; Rao, M. M. J. Organomet. Chem. 2013, 741–742, 162-
167. (d) Nanjo, T.; Yamamoto, S.; Tsukano, C.; Takemoto, Y. Org. Lett.
2013, 15, 3754-3757. (e) Lu, B. Z.; Wei, H. X.; Zhang, Y.; Zhao, W.;
Dufour, M.; Li, G.; Farina, V.; Senanayake, C. H. J. Org. Chem. 2013, 78,
4558-4562. (f) Shi, Z.; Zhang, C.; Li, S.; Pan, D.; Ding, S.; Cui, Y.; Jiao,
N. Angew. Chem. Int. Ed. 2009, 48, 4572-4576. (g) Yu, W.; Du, Y.; Zhao,
K. Org. Lett. 2009, 11, 2417-2420. (h) Djakovitch, L.; Dufaud, V.; Zaidi,
R. Adv. Synth. Catal. 2006, 348, 715-724. (i) Ackermann, L.; Kaspar, L.
T.; Gschrei, C. J. Chem. Commun. 2004, 2824-2825. (j) Shen, M.; Li, G.;
Lu, B. Z.; Hossain, A.; Roschangar, F.; Farina, V.; Senanayake, C. H.
Org. Lett. 2004, 6, 4129-4132. (k) Takeda, A.; Kamijo, S.; Yamamoto, Y.
J. Am. Chem. Soc. 2000, 122, 5662-5663.
11 For some examples of Rh-catalyzed, see: (a) Fan, Z.; Song, S.; Li, W.;
Geng, K.; Xu, Y.; Miao, Z. H.; Zhang, A. Org. Lett. 2015, 17, 310-313.
(b) Zheng, L.; Hua, R. Chem. Eur. J. 2014, 20, 2352-2356. (c) Zhang, G.;
Yu, H.; Qin, G.; Huang, H. Chem. Commun. 2014, 50, 4331-4334. (d)
Muralirajan, K.; Cheng, C.-H. Adv. Synth. Catal. 2014, 356, 1571-1576.
(e) Zhao, D.; Shi, Z.; Glorius, F. Angew. Chem. Int. Ed. Engl. 2013, 52,
12426-12429. (f) Wang, C.; Huang, Y. Org. Lett. 2013, 15, 5294-5297.
(g) Muralirajan, K.; Cheng, C. H. Chem. 2013, 19, 6198-6202. (h) Stuart,
D. R.; Bertrand-Laperle, M. g.; Burgess, K. M. N.; Fagnou, K. J. Am.
Chem. Soc. 2008, 130, 16474-16475.
12 For some examples of other transition mental-catalyzed, see: (a) Huang,
F.; Wu, P.; Wang, L.; Chen, J.; Sun, C.; Yu, Z. J. Org. Chem. 2014, 79,
10553-10560. (b) Song, W.; Ackermann, L. Chem. Commun. 2013, 49,
6638-6640. (c) Lu, B.; Luo, Y.; Liu, L.; Ye, L.; Wang, Y.; Zhang, L.
Angew. Chem. Int. Ed. 2011, 50, 8358-8362. (d) Cacchi, S.; Fabrizi, G.;
Goggiamani, A. Org. Biomol. Chem. 2011, 9, 641-652. (e) Stuart, D. R.;
Alsabeh, P.; Kuhn, M.; Fagnou, K. J. Am. Chem. Soc. 2010, 132, 18326-
18339. (f) Kramer, S.; Dooleweerdt, K.; Lindhardt, A. T.; Rottländer, M.;
Skrydstrup, T. Org. Lett. 2009, 11, 4208-4211. (g) Kumar, M. P.; Liu, R.-
S. J. Org. Chem. 2006, 71, 4951-4955.
13 (a) Allwood, D. M.; Blakemore, D. C.; Ley, S. V. Org. Lett. 2014, 16,
3064-3067. (b) Allwood, D. M.; Blakemore, D. C.; Brown, A. D.; Ley, S.
V. J. Org. Chem. 2014, 79, 328-338. (c) Yadav, A. K.; Srivastava, V. P.;
Yadav, L. D. Chem. Commun. 2013, 49, 2154-2156. (d) Florentino, L.;
Aznar, F.; Valdés, C. Chem. Eur. J. 2013, 19, 10506-10510. (e) Huang, Z.;
Yang, Y.; Xiao, Q.; Zhang, Y.; Wang, J. Eur. J. Org. Chem. 2012, 2012,
6586-6593. (f) Nun, P.; Martin, C.; Martinez, J.; Lamaty, F. Tetrahedron
2011, 67, 8187-8194.
14 Reddy, B. V. S.; Reddy, M. R.; Rao, Y. G.; Yadav, J. S.; Sridhar, B. Org.
Lett. 2013, 15, 464-467.