Copper(ii)-catalyzed synthesis of multisubstituted indoles through sequential Chan-Lam and cross-dehydrogenative coupling reactions

Article abstract of DOI:10.1039/d0ra04592f

Starting from arylboronic acids and ester (Z)-3-aminoacrylates, one-pot syntheses of diverse indole-3-carboxylic esters have been described through copper(ii)-catalyzed sequential Chan-Lam N-arylation and cross-dehydrogenative coupling (CDC) reactions. The initial Chan-Lam arylation can proceed in DMF at 100 °C for 24 h to give ester (Z)-3-(arylamino)acrylate intermediates in the presence of Cu(OAc)2/tri-tert-butylphosphine tetrafluoroborate, a catalytic amount of myristic acid as the additive, KMnO4 and KHCO3. Sequentially, these in situ arylated intermediates can undergo an intramolecular oxidative cross-dehydrogenative coupling process in mixed solvents (DMF/DMSO = 2 : 1) at 130 °C to give C3-functionalized multi-substituted indole derivatives. This journal is

Full text of DOI:10.1039/d0ra04592f

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PAPER
Copper(II)-catalyzed synthesis of multisubstituted
indoles through sequential Chan–Lam and cross-
dehydrogenative coupling reactions†
ab
Cite this: RSC Adv., 2020, 10, 24830
Xin Chen,ab Yunyun Bian,a Baichuan Mo,ab Peng Sun,ab Chunxia Chen
*
a
*
and Jinsong Peng
Starting from arylboronic acids and ester (Z)-3-aminoacrylates, one-pot syntheses of diverse indole-3-
carboxylic esters have been described through copper(II)-catalyzed sequential Chan–Lam N-arylation
and cross-dehydrogenative coupling (CDC) reactions. The initial Chan–Lam arylation can proceed in
DMF at 100 ꢀC for 24 h to give ester (Z)-3-(arylamino)acrylate intermediates in the presence of
Cu(OAc)2/tri-tert-butylphosphine tetrafluoroborate, a catalytic amount of myristic acid as the additive,
KMnO4 and KHCO3. Sequentially, these in situ arylated intermediates can undergo an intramolecular
oxidative cross-dehydrogenative coupling process in mixed solvents (DMF/DMSO ¼ 2 : 1) at 130 ꢀC to
give C3-functionalized multi-substituted indole derivatives.
Received 24th May 2020
Accepted 22nd June 2020
DOI: 10.1039/d0ra04592f
rsc.li/rsc-advances
enamine or imine intermediates have emerged in recent years
(Scheme 1). In 2008, Glorius group8a reported the rst Pd-
1. Introduction
catalyzed oxidative cyclization of N-aryl enaminones/esters for
indole syntheses with Cu(OAc)2 as the oxidant. Shortly aer-
ward, Cacchi9 demonstrated a copper-catalyzed aerobic version
for the synthesis of indoles from N-aryl enaminones in DMF.
Subsequent to these original works, different catalytic system
(Pd,10 Cu,11 Fe,12 PIDA,13 I2,14 visible light,15 photoredox/metal,16
and electricity17) have been widely investigated to enlarge the
substrate scope. Using simple and easily available substrates,
domino one-pot processes combining the in situ formation of N-
arylated enamines or imines with subsequent cyclization have
also been developed for the synthesis of indoles. For instance,
Jiao group18 pioneered studies to construct an indole backbone
through an efficient Pd-catalyzed aerobic oxidative C–H func-
tionalization approach from simple anilines and activated
The indole unit is not only one of the most abundant structural
motifs in natural products,1 but is also ubiquitous among
agrochemicals,2 marketed medicines (such as dolasetron, tro-
pisetron, indomethacin, proglumetacin, and ondansetron),3
and progressive functional materials.4 In particular, substituted
indoles have been utilized as “privileged scaffolds” for drug
discovery of anti-inammatory, antihypertensive, anti-tumor,
anti-HIV, and antimigraine agents.5 Considering the impor-
tance of indole scaffolds for pharmaceutical research, the
development of practical syntheses of indole derivatives is of
immense interest to synthetic chemists.
Over the past century, a variety of approaches for indole
preparation have been well established.6 While numerous
classical procedures based on condensation and cyclization
have been developed,6b there is still a great demand to explore
new strategies and methodologies for the modular synthesis of
functionalized indoles from easily available starting materials.
Over the past decades, transition metal-mediated inter- and
intramolecular C–C and C–N bond forming reactions have
emerged as one of the most powerful and popular tools for
indole syntheses.7 Following this tendency, an attractive C–H
activation/cyclization strategy relying on the use of N-arylated
aCollege of Chemistry, Chemical Engineering and Resource Utilization, Northeast
Forestry University, No. 26 Hexing Road, Harbin, 150040, P. R. China
bMaterial Science and Engineering College, Northeast Forestry University, No. 26
Hexing Road, Harbin, 150040, P. R. China. E-mail: ccx1759@163.com;
jspeng1998@nefu.edu.cn
Scheme 1 Metal-catalyzed indole syntheses based on the N-arylated
enamines and imines.
† Electronic supplementary information (ESI) available: Copies of 1H, 13C NMR,
HRMS and IR spectra for new compounds. See DOI: 10.1039/d0ra04592f
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reaction of anilines and methyl peruoroalk-2-ynoates with
oxygen as the sole oxidant. Yoshikai group20 developed a Pd-
catalyzed method for the synthesis of indoles from N-aryl
imines directly derived from simple and obtainable anilines
and ketones. In addition, using simple anilines21 or aniline
derivatives with directing groups,22–27 various transitional metal-
catalyzed (such as Rh,22 Ru,23 Pd,24 Au,25 Ni,26 and Co27) protocols
have been well established through group-directed oxidative
C–H annulation of alkynes.
We have been devoting our efforts to develop metal-catalyzed
sequential one-pot processes containing a direct C–H func-
tionalization step for the construction of heterocyclic frame-
works.28 Over the past decades, oxidative cross-dehydrogenative
coupling (CDC) reactions have emerged as one of the most
powerful routes for C–C bond formations in organic synthesis.29
Scheme 2 Prospected sequence for the synthesis of indoles.
alkynes. Recently, Zhang and Cao19 reported a one-pot synthesis
of 2-(peruoroalkyl)indoles through sequential Michael-type
addition and Pd(II)-catalyzed cross-dehydrogenative coupling
Table 1 Condition optimization for the copper-catalyzed synthesis of indole 3aaa
Entry
Cu/ligand
Base
Solvent
Oxidant
Yieldb [%]
1
2
3
4
5
6
7
8
CuI/L1
CuBr/L1
CuCl/L1
Cu2O/L1
Cu(OTf)2/L1
CuCl2/L1
CuBr2/L1
CuSO4$5H2O/L1
Cu(OAc)2/L1
Cu(acac)2/L1
CuO/L1
Cu(OAc)2/L2-L17
Cu(OAc)2
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
Cu(OAc)2/L12
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
K2CO3
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMSO
THF
1,4-Dioxane
DMA
tert-Pentyl alcohol
DMF/DMSO
DMF/DMSO
DMF/DMSO
DMF/DMSO
DMF/DMSO
DMF/DMSO
DMF/DMSO
DMF/DMSO
DMF/DMSO
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
—
Air
Air
Air
Air
Air
Air
Air
Air
Air
Air
10/6c/7d
Trace
Trace
Trace
5
8
7
10
20
14
0
0–25
0
0
15
0
0
20
9
10
11
12e
13
14f
15
16
17
18
19
20
21
22
23
24
25
26
27g
28g
29g
30g
31g
32g
33g
34g
NaOH
Li2CO3
K3PO4
NaHCO3
NaOAc
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
KHCO3
17
18
10
15
Trace
19
Air
Air
20
33 (37)g
48
KMnO4
K2S2O8
TBHP
MnO2
KMnO4
KMnO4
KMnO4
KMnO4
21
20
30
55h
47i
48j
45k
a
Reaction conditions unless otherwise stated: 1a (0.5 mmol), 2a (0.2 mmol), base (0.6 mmol), catalyst (20 mol%), ligand (30 mol%), solvent (1.0
b
c
d
e
mL), air or oxidant, 70 ꢀC, 24 h, air. Isolated yield. 1.5 equiv. of 1a. 2.0 equiv. of 1a. The effect of various ligands was investigated, see
f
g
h
i
Scheme 1. N2. DMF (1.0 mL), 100 ꢀC, 24 h; then DMSO (0.5 mL), 130 ꢀC, 24 h. 20 mol% of myristic acid was added. 20 mol% of palmitic
acid was added. j 20 mol% of stearic acid was added. k 20 mol% of trimethylacetic acid was added.
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coupling reaction from simple anilines and ester arylpropio-
lates.31 Subsequent to our previous works, we became interested
in developing a new entry to multi-substituted indoles from
arylboronic acids and enamines through sequential copper(II)-
catalyzed Chan–Lam oxidative N-arylation and cross-
dehydrogenative coupling reaction (Scheme 2). Several poten-
tial issues need to be addressed: (1) the Chan–Lam arylation has
been extended to numerous nucleophilic partners for carbon–
heteroatom bonds formation,32 but not to enamines. (2) The
Chan–Lam N-arylation involving arylboronic acids is known to
occur in the presence of Cu(II) catalyst, while the Cu(I) catalyst
has usually been employed in the C–H functionalization step.9,30
Merging fundamentally different copper catalysis into one-pot
reaction is still challenging.
Scheme 3 Effect of ligands on the copper-catalyzed annulations
reaction. a Reaction conditions: 20 mol% Cu(OAc)2, KHCO3, DMF, air,
70 ꢀC, 24 h; isolated yields. b PCy3 was directly used.
2. Results and discussion
Ethyl (Z)-3-amino-3-phenylacrylate (2a) was selected as the
substrate to react with phenylboronic acid (1a) in the presence
of different combinations of copper catalysts, ligands, bases,
solvents and oxidants (Table 1). The blank experiment (without
For indole syntheses, we recently developed a Cu(I)-catalyzed 2-
fold arylation process through a tandem Ullmann-type C–N and
cross-dehydrogenative coupling sequence from enamines and
aryl iodides.30 More recently, a one-pot synthesis of 2-aryl
indole-3-carboxylate derivatives has also been established by
our group through stoichiometric copper salt-mediated
ꢀ
copper catalyst and ligand) was examined in DMF at 70 C for
24 h using KHCO3 as the base, and no desired product 3aa was
obtained. A survey of copper catalysts showed that Cu(OAc)2
provided better results (20% yield) than CuI, CuBr, CuCl, Cu2O,
Cu(OTf)2, CuCl2, CuBr2, CuSO4$5H2O, Cu(acac)2 and CuO (0–
sequential
hydroamination
and
cross-dehydrogenative
Table 2 The substrate scope of arylboronic acidsa
Entry
1
S-1
P-3
Yieldb
55
Entry
6
S-1
P-3
Yieldb
44
2
3
4
54
51
47
7
8
9
50
49
50
5
46
10c
52 (2 : 1)
a
Reaction conditions: 2 (0.2 mmol), arylboronic acids 1 (0.5 mmol), Cu(OAc)2 (20 mol%), tBu3P$HBF4 (30 mol%), myristic acid (0.04 mmol), KHCO3
(0.6 mmol), KMnO4 (0.1 mmol), DMF (1 mL), 100 ꢀC, 24 h; then DMSO (0.5 mL), 130 ꢀC, 24 h, air. b Yield of the isolated product. c The ratio of the
regioisomers was determined by NMR analysis.
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14% yields) with 2,20-bipyridine (L1) as the ligand and air as the provided a better result with 25% isolated yield. A survey of
oxidant (entries 1–11). To increase the yield of 3aa, we then reaction media showed that the use of DMF provided better
investigated the effect of various ligands (nitrogen-containing results than those obtained in DMSO, THF, 1,4-dioxane, DMA,
ligands L2–L6,33 N-heterocarbene ligand L7, mono- and tert-pentyl alcohol (entries 21–25). The binary mixed solvent
phosphorous ligands L8–L12, and Buchwald-type bulky biaryl composed of DMF and DMSO (DMF/DMSO, 2 : 1) gave the nal
phosphine ligands L13–L17, Scheme 3) on the reaction using product 3aa in 33% yield at 70 ꢀC (entry 26). With increased
Cu(OAc)2 as the catalyst (entry 7, Table 1). It turned out that reaction temperature and time, the yield of 3aa can been
tBu3P$HBF4 (L12) performed best, and the yield was improved improved from 33% to 37% (entry 26). Among the range of
to 25% with KHCO3 as the base under air atmosphere (Scheme oxidants (KMnO4, K2S2O8, TBHP, MnO2, and O2, entries 26–30)
3). It is worth noting that ligand and oxidant are essential to this that were surveyed, KMnO4 appeared to be optimal and gave 3aa
transformation and 3aa was not produced in the absence of with an enhanced yield (48%, entry 27). Attempts have been
ligand (entry 13) or oxidant (entry 14). The effect of other bases made under higher air or O2 pressure (3 atm), however, the
such as K2CO3, NaOH, Li2CO3, K3PO4, NaHCO3, and NaOAc on yields cannot obviously be improved. In 2001, Buchwald and co-
the reaction was next examined (entries 15–20), KHCO3 workers demonstrated that aliphatic acid can increase the
Table 3 Variation of the enamine unita
Entry
1
S-1
P-3
Yieldb
47
Entry
9
S-1
P-3
Yieldb
49
2
3
4
5
6
7
42
46
49
53
51
52
10
11
12
13
14
15
47
46
49
49
48
51
8
46
a
Reaction conditions: 2 (0.2 mmol), arylboronic acids 1 (0.5 mmol), Cu(OAc)2 (20 mol%), tBu3P$HBF4 (30 mol%), myristic acid (0.04 mmol), KHCO3
b
(0.6 mmol), KMnO4 (0.1 mmol), DMF (1 mL), 100 ꢀC, 24 h; then DMSO (0.5 mL), 130 ꢀC, 24 h, air. Yield of the isolated product.
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copper-catalyzed coupling reaction rate of arylboronic acids and
amines through the coordination of aliphatic acid to the copper
center to improve solubility of the copper catalyst in organic
solvents.34 Given the importance of aliphatic acids in achieving
a homogeneous catalyst system, various carboxylic acids such as
myristic acid, palmitic acid, stearic acid, and trimethylacetic
acid were explored as the additive. It was found that the addi-
tion of 1 equiv of myristic acid relative to Cu(OAc)2 improved the
yield of 3aa to 55% (entry 31), while other carboxylic acids had
little effect on the reaction (entries 32–34). In general, in the
t
presence of combinations of Cu(OAc)2, Bu3P$HBF4, KHCO3,
myristic acid and KMnO4, the synthesis of indoles 3 was con-
ducted in a one-pot fashion using DMF/DMSO as mixed
solvents.
Fig. 1 Unsuccessful enamine substrates.
Having established the feasibility of indole synthesis via
copper(II)-catalyzed sequential oxidative Chan–Lam arylation/
CDC process, we then explored the generality of arylboronic
acids using methyl or ethyl (Z)-3-amino-3-phenylacrylate as the
coupling partner (Table 2). As shown in Table 2, diverse
substituents (such as Me, OMe, F, Cl, ester, and methylthio) on
the aromatic moiety of boronic acids were applicable, and the
corresponding indole products 3aa–3ja can be obtained in 44–
55% yields. Arylboronic acids containing electron-donating
groups at the para (1b, 1c, and 1g), or meta (1j) position were
generally more reactive than those bearing electron-
withdrawing substituents (1d–1f) and provided higher yields
(entries 2–7, and 10, Table 2). However, the incorporation of
substituents in the ortho position of arylboronic acid seriously
hampered copper-catalyzed oxidative annulation process, and
the corresponding indoles cannot be obtained. In addition, a-
or b-naphthyl boronic acids 1h and 1i can also be smoothly
transformed into the corresponding products 3ha and 3ia in
49% and 50% yields, respectively (entries 8 and 9). For b-
naphthyl boronic acid 1i, there are two possible C–H activation
sites (a- and b-position), the CDC process occurred only at the a-
site to give a single regioisomer 3ia (entry 9). The specicity of
site selectivity (a/b) implies that the aromatic C–H alkenylation
is probably an outcome of electrophilic aromatic substitutions.
However, regioselectivity issues surfaced for meta-substituted
arylboronic acid (1j), and a mixture of two regioisomers (3ja and
3j0a) was obtained in a nearly 2 : 1 ratio, indicating intra-
molecular CDC reaction occurred at the most sterically acces-
sible site (entry 10).
repulsion of the ortho substituent. In addition, when the scope
of substrates was extended to aliphatic and carbocyclic
enamines [for example, ethyl (Z)-3-aminobut-2-enoate 2s and 3-
aminocyclohex-2-en-1-one 2u, Fig. 1], the reaction did not
happen to give the corresponding products. Enamine substrates
with an amide (2t), aromatic ketone (2v) or nitro group (2w) were
also examined under the standard conditions; however, no
product can be obtained. These unsuccessful results indicated
that the electron density of olen moiety was highly essential
for CDC process.
To gain insight into the mechanism of the reaction, some
designed control experiments were conducted. When the reac-
tion of 1a and 2a was conducted in DMF for 24 h, the Chan–Lam
N-arylated intermediate 9 and 3aa can be isolated in 68% and
10% yields, respectively. Then, the intermediate 9 was carried
out under the optimized reaction conditions, 65% of the
desired product 3aa was obtained. Based on the above results
and previous literature reports from our group30,31 and others,35
a reaction mechanism for the copper(II)-catalyzed oxidative
annulation of enamines with arylboronic acids was proposed.
The Scheme 4 showed a simplied sequence of events begin-
ning with the Cu(OAc)2. First, a soluble active cupric tetrade-
canoate species was formed through the anion exchange
reaction of Cu(OAc)2 and myristic acid in the presence of base.34
The coordination of (Z)-enamine 2 to the Cu(II) center to form 4,
which then reacted with a base to form a Cu–N bond and
afforded an intermediate complex 5. Engagement of arylboronic
acid 1 led to transmetalation via 4-membered transition state35a
and delivered aryl-Cu(II) species 6. The intermediate 6 was then
oxidized by Cu(II) to form an Cu(III) species 8, and the subse-
quent reductive elimination gave N-arylated intermediate 9 and
a Cu(I)OAc species 7. Completion of the catalytic cycle was
achieved via oxidation to Cu(II) in the presence of KMnO4
(Chan–Lam C–N coupling process). The coordination of N-ary-
lated intermediate 9 to Cu(II) gave a six-membered chelate ring
complex 10. A new C–Cu(II) complex 12 was then formed
through sequential a base-promoted deprotonation of N–H,
dissociation of acetate anion and complexation of the resulting
cationic Cu(II) species at a-carbon of 11. A deprotonation/re-
protonation process of alkyl-Cu(II) complex 12 afforded an
alkenyl copper 13 under basic conditions. Ortho-cupration of
The scope and limitation of ester (Z)-3-aminoacrylate
substrates were nally investigated in this one-pot sequential
oxidative process. As shown in Table 3, several functional
t
groups (such as Me, OMe, OEt, Bu, F, Cl, Br and CF3) are
tolerated under the standard conditions. For ester (Z)-3-amino-
3-arylpropiolates, the electronic nature of the aromatic motifs
did not seem to affect the efficiency: both electron-donating
t
(Me, MeO, EtO, and Bu) and electron-withdrawing substitu-
ents (F, Cl, Br, and CF3) can be incorporated at the para (2b–2j,
entries 1–9) and meta (2k–2o, entries 10–14) position, providing
indole derivatives 3ab–3ao in 42–53% yields. However, ester (Z)-
3-amino-3-arylpropiolates (2p–2r, Fig. 1) with substituents in
the ortho position of aromatic ring cannot proceed to give the
corresponding products, probably because of the strong steric
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Scheme 4 Proposed catalytic pathway for the formation of indole 3.
phenyl ring of 13 provided a six-membered copper-cycle inter- thin-layer chromatography (TLC). All reactions were conducted
mediate 14,9 which was then transformed into the product 3 in dried glassware. Purication of reaction products was done
and Cu(0) species 15 through reductive elimination process. by ash chromatography with 230–400 mesh silica gel. Ester (Z)-
Finally, Cu(0) was oxidized to the active Cu(II) catalyst by KMnO4 3-aryl-3-aminoacrylate substrates were prepared according to
for the next Chan–Lam arylation reaction.
the literature methods.36 Melting points were determined on
a melting point apparatus in open capillaries and are uncor-
rected. Infrared spectra of samples were recorded from 4000 to
500 cmꢁ1 in ATR (attenuated total reectance) mode using an
3. Conclusions
1
FT-IR instrument. H NMR spectra were recorded on a 400 or
In summary, we have developed a new one-pot approach to
diverse multi-substituted indoles through copper-catalyzed
oxidative annulations of enamines with readily accessible aryl-
boronic acids. The accomplished reaction comprises an inter-
molecular Chan–Lam arylation followed by an intramolecular
cross-dehydrogenative coupling reaction promoted by the
same copper catalyst. The success of the reaction heavily relies
on the careful selection of proper additive and oxidant. The
combination of myristic acid and KMnO4 was found to be
essential for the formation of C3-functionalized multi-
substituted indoles. Considering a broad substrate scope and
considerable valance of the products for medicinal science, this
novel synthetic method could be of utility for the discovery of
drugs.
500 MHz spectrometer, and 13C NMR spectra were recorded at
100, 125 or 150 MHz. Unless otherwise stated, deuterochloro-
form (CDCl3) was used as a solvent. Chemical shis (d) are given
in parts per million downeld relative to tetramethylsilane
(TMS). Chemical shis for carbon resonances are reported in
parts per million and are referenced to the carbon resonance of
the solvent CHCl3 (d ¼ 77.16 ppm). The splitting patterns are
reported as s (singlet), d (doublet), dd (double doublet), td
(triplet of doublet), t (triplet), q (quartet), br (broad), and m
(multiplet). Coupling constants are given in hertz. High-
resolution mass spectra were recorded on a BIO TOF Q mass
spectrometer equipped with an electrospray ion source (ESI),
operated in the positive mode.
4. Experimental section
4.1. General information
4.2. General procedure for synthesis of indole-3-carboxylate
derivatives
Chemicals were all purchased from commercial supplies and A 10 mL Schlenk tube or standard vial equipped with a magnetic
used without further purication unless otherwise stated. stirring bar was charged with ester (Z)-3-aryl-3-aminoacrylates
Solvents were dried and puried according to the standard (0.2 mmol, 1.0 equiv.), aryl boronic acid (0.5 mmol, 2.5
procedures before use. Reactions were monitored by analytical equiv.), KMnO4 (0.1 mmol, 15.8 mg), and KHCO3 (60 mg,
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0.6 mmol, 3.0 equiv.), and then Cu(OAc)2 (0.04 mmol, 8.0 mg), 790; 1H NMR (400 MHz, CDCl3) d 8.41 (s, 1H), 8.04 (s, 1H), 7.57
tBu3P$HBF4 (0.06 mmol, 17.4 mg) and myristic acid (0.04 mmol, (d, J ¼ 8.0 Hz, 2H), 7.29–7.27 (m, 3H), 7.11 (d, J ¼ 8.2 Hz, 1H),
9.1 mg) were added. Finally, DMF (1.0 mL) was added to the 4.34 (q, J ¼ 7.1 Hz, 2H), 2.53 (s, 3H), 2.43 (s, 3H), 1.35 (t, J ¼
mixture via syringe at room temperature under air. The vial was 7.1 Hz, 3H). 13C NMR (151 MHz, CDCl3) d 165.5, 144.7, 139.2,
sealed and put into a preheated oil bath at 100 ꢀC for 24 h. The 133.4, 131.5, 129.5, 129.2, 128.8, 128.0, 124.6, 121.8, 110.6,
mixture was cooled to room temperature, dimethyl sulfoxide 104.1, 59.6, 21.8, 21.4, 14.4. HRMS-ESI (m/z) calcd for
(0.5 mL) was then added via syringe, and the reaction mixture
was heated to 130 ꢀC for another 24 h. Finally, the mixture was
C
19H20NO2+ (M + H)+ 294.14886, found 294.14856.
Methyl 2-(4-methoxyphenyl)-5-methyl-1H-indole-3-
cooled to room temperature, quenched with water (3 mL), and carboxylate (3af). Yield, 53% (31.3 mg); white solid, mp 156–
diluted with ethyl acetate (5 mL). The layers were separated, and 158 ꢀC; IR (KBr, cmꢁ1): 3247, 1668, 1643, 1501, 1454, 1282, 1134,
the aqueous layer was extracted with 3 ꢂ 5 mL of ethyl acetate. 832, 801, 792; 1H NMR (400 MHz, CDCl3) d 8.47 (s, 1H), 7.97 (s,
The combined organic extracts were dried over anhydrous 1H), 7.56 (d, J ¼ 8.6 Hz, 2H), 7.23–7.21 (m, 1H), 7.06 (d, J ¼
sodium sulfate, ltered, and concentrated under vacuum. The 8.8 Hz, 1H), 6.92 (d, J ¼ 8.6 Hz, 2H), 3.83 (s, 3H), 3.81 (s, 3H),
crude product was then puried by a chromatography silica gel 2.49 (s, 3H). 13C NMR (151 MHz, CDCl3) d 165.1, 159.2, 143.8,
(H), eluting with ethyl acetate/petroleum ether (10–15%).
132.3, 130.4, 129.79, 126.8, 123.5, 123.2, 120.6, 112.6, 109.6,
Ethyl 2-phenyl-1H-indole-3-carboxylate (3aa).37 Yield, 55% 102.4, 54.3, 49.8, 20.7. HRMS-ESI (m/z) calcd for C18H18NO3+ (M
(29.2 mg); white solid, mp 155–158 ꢀC; IR (KBr, cmꢁ1): 3254, + H)+ 296.12812, found 296.12836.
1662, 1450, 1430, 1270, 1212, 1129, 1047, 744, 690; 1H NMR (400
Methyl
5-methoxy-2-(4-methoxyphenyl)-1H-indole-3-
MHz, CDCl3) d 8.76 (br, 1H), 8.22–8.20 (d, J ¼ 7.2 Hz, 1H), 7.61– carboxylate (3ag). Yield, 51% (31.8 mg); yellow solid, mp 158–
7.59 (m, 2H), 7.37–7.35 (m, 3H), 7.33–7.31 (m, 1H), 7.27–7.21 159 ꢀC; IR (KBr, cmꢁ1): 3226, 1664, 1499, 1488, 1454, 1252, 1209,
(m, 2H), 4.26 (q, J ¼ 7.1 Hz, 2H), 1.28 (t, J ¼ 7.1 Hz, 3H). 13C NMR 1172, 1137, 842, 825, 811, 788; 1H NMR (400 MHz, CDCl3) d 8.38
(151 MHz, CDCl3) d 164.5, 143.6, 134.2, 131.0, 128.6, 128.1, (s, 1H), 7.70 (d, J ¼ 2 Hz, 1H), 7.58 (d, J ¼ 8.6 Hz, 2H), 7.24 (s,
127.0, 126.5, 122.1, 121.0, 120.9, 110.1, 103.4, 58.7, 13.3.
1H), 6.97 (d, J ¼ 8.6 Hz, 2H), 6.90 (dd, J ¼ 8.6, 2.2 Hz, 1H), 3.91
Methyl 5-chloro-2-(4-chlorophenyl)-1H-indole-3-carboxylꢀate (s, 3H), 3.85 (s, 3H), 3.83 (s, 3H). 13C NMR (151 MHz, CDCl3)
(3ab). Yield, 47% (30.0 mg); light yellow solid, mp 163–165 C; d 165.0, 159.3, 154.7, 144.0, 129.8, 129.0, 127.5, 123.3, 112.6,
IR (KBr, cmꢁ1): 3249, 1677, 1666, 1485, 1444, 1296, 1210, 1135, 112.1, 110.6, 102.7, 54.8, 54.3, 49.8. HRMS-ESI (m/z) calcd for
1091, 786, 800, 823; H NMR (400 MHz, CDCl3) d 8.59 (s, 1H),
8.17–8.16 (d, J ¼ 1.6 Hz, 1H), 7.58–7.56 (d, J ¼ 8.5 Hz, 2H), 7.42–
C
18H18NO4+ (M + H)+ 312.12303, found 312.12314.
1
Methyl
2-[4-(tert-butyl)
phenyl]-5-methyl-1H-indole-3-
7.40 (d, J ¼ 8.5 Hz, 2H), 7.30–7.28 (m, 1H), 7.25–7.22 (m, 1H), carboxylate (3ah). Yield, 52% (33.4 mg); white solid, mp 189–
3.85 (s, 3H). 13C NMR (151 MHz, CDCl3) d 164.3, 143.3, 134.7, 190 ꢀC; IR (KBr, cmꢁ1): 3267, 1674, 1443, 1201, 1284, 1158, 1119,
132.5, 129.8, 128.7, 127.5, 127.4, 127.1, 122.9, 120.8, 111.1, 861, 789, 780; 1H NMR (400 MHz, CDCl3) d 8.39 (s, 1H), 8.00 (s,
+
103.5, 50.2. HRMS-ESI (m/z) calcd for C16H12Cl2NO2 (M + H)+ 1H), 7.61 (d, J ¼ 8.5 Hz, 2H), 7.48 (d, J ¼ 8.5 Hz, 2H), 7.28 (s, 1H),
320.02396, found 320.02390.
7.09 (d, J ¼ 8.3 Hz, 2H), 3.86 (s, 3H), 2.51 (s, 3H), 1.36 (s, 9H). 13
C
Ethyl
5-chloro-2-(4-uorophenyl)-1H-indole-3-carboxylate NMR (151 MHz, CDCl3) d 165.0, 151.3, 143.8, 132.3, 130.5, 128.1,
ꢀ
(3ac). Yield, 42% (26.7 mg); light yellow solid, mp 149–151 C; 128.0, 126.8, 124.2, 123.6, 120.7, 109.6, 102.7, 49.9, 33.8, 30.2,
IR (KBr, cmꢁ1): 3416, 1673, 1497, 1447, 1212, 1130, 840, 804, 20.7. HRMS-ESI (m/z) calcd for C21H24NO2+ (M + H)+ 322.18016,
786; 1H NMR (400 MHz, CDCl3) d 8.58 (s, 1H), 8.19–8.18 (d, J ¼ found 322.18030.
1.2 Hz, 1H), 7.64–7.60 (dd, J ¼ 8.5, 5.4 Hz, 2H), 7.30–7.27 (m,
Methyl 2-(4-ethoxyphenyl)-5-methyl-1H-indole-3-carboxylate
1H), 7.24–7.21 (m, 1H), 7.13 (t, J ¼ 8.6 Hz, 2H), 4.32 (q, J ¼ (3ai). Yield, 46% (28.4 mg); white solid, mp 195–197 ꢀC; IR
7.1 Hz, 2H), 1.33 (t, J ¼ 7.1 Hz, 3H). 13C NMR (151 MHz, CDCl3) (KBr, cmꢁ1): 3257, 1652, 1612, 1457, 1450, 1260, 1250, 1181,
1
1
d 164.9, 163.4 (164.2, 162.6, d, JC–F ¼ 249 Hz), 144.5, 133.4, 1142, 1048, 848, 799, 790; H NMR (500 MHz, CDCl3) d 8.40 (s,
3
131.5 (131.6, 131.5, d, JC–F ¼ 8 Hz), 128.6, 128.0, 127.6 (127.6, 1H), 7.98 (s, 1H), 7.58 (d, J ¼ 8.8 Hz, 2H), 7.24 (s, 1H), 7.07 (d, J ¼
127.5, d, 4JC–F ¼ 3 Hz), 123.8, 121.8, 115.3 (115.4, 115.3, d, 2JC–F 9.0 Hz, 2H), 6.94 (d, J ¼ 8.8 Hz, 2H), 4.06 (q, J ¼ 7.0 Hz, 2H), 3.85
¼ 21 Hz), 112.1, 104.6, 60.0, 14.4. HRMS-ESI (m/z) calcd for (s, 3H), 2.50 (s, 3H), 1.44 (t, J ¼ 7.0 Hz, 3H). 13C NMR (126 MHz,
+
C
17H14ClFNO2 (M + H)+ 318.06916, found 318.06912.
CDCl3) d 165.0, 158.7, 143.7, 132.3, 130.5, 129.8, 126.9, 123.5,
Methyl 2-(4-bromophenyl)-5-methyl-1H-indole-3-carboxylate 123.1, 120.7, 113.1, 109.5, 102.4, 62.5, 49.8, 20.7, 13.8. HRMS-
+
(3ad). Yield, 46% (31.7 mg); orange solid, mp 160–162 ꢀC; IR ESI (m/z) calcd for C19H20NO3 (M + H)+ 310.14377, found
(KBr, cmꢁ1): 3307, 1672, 1444, 1124, 830, 790; 1H NMR (400 310.14368.
MHz, CDCl3) d 8.44 (s, 1H), 7.98 (s, 1H), 7.57–7.49 (q, J ¼ 7.6 Hz,
Methyl 5-methyl-2-(4-(triuoromethyl) phenyl)-1H-indole-3-
4H), 7.27 (d, J ¼ 8.1 Hz, 1H), 7.11 (d, J ¼ 8.1 Hz, 1H), 3.84 (s, 3H), carboxylate (3aj). Yield, 49% (32.6 mg); white solid, mp 165–
2.50 (s, 3H). 13C NMR (151 MHz, CDCl3) d 165.8, 143.1, 133.5, 167 ꢀC; IR (KBr, cmꢁ1): 3288, 1665, 1446, 1325, 1221, 1166, 1134,
131.9, 131.4, 131.1, 131.0, 127.7, 125.2, 123.6, 121.8, 110.7, 1068, 849, 802, 693, 622; 1H NMR (500 MHz, CDCl3) d 8.66–8.56
+
104.4, 51.0, 21.7. HRMS-ESI (m/z) calcd for C17H15BrNO2 (M + (br, 1H), 8.00 (s, 1H), 7.77–7.69 (m, 4H), 7.31–7.29 (m, 1H), 7.13
H)+ 344.02807, found 344.02802.
(d, J ¼ 8.2 Hz, 1H), 3.85 (s, 3H), 2.51 (s, 3H). 13C NMR (126 MHz,
Ethyl 5-methyl-2-(p-tolyl)-1H-indole-3-carboxylate (3ae). CDCl3) d 164.7, 141.5, 134.6, 132.6, 131.0, 129.9 (130.2, 123.0,
Yield, 49% (27.4 mg); white solid, mp 157–159 ꢀC; IR 129.7, 129.5, q, 2JC–F ¼ 33 Hz), 128.8, 126.4, 125.2 (128.7, 126.5,
(KBr, cmꢁ1): 3280, 1656, 1440, 1267, 1217, 1158, 1143, 1048, 800, 124.0, 121.8, q, JC–F ¼ 276 Hz), 124.4, 124.0 (124.07, 124.04,
1
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3
124.01, 123.98, q, JC–F ¼ 4 Hz), 120.8, 109.8, 103.8, 50.0, 20.7. 3300, 1667, 1486, 1447, 1421, 1282, 1214, 1132, 792, 765, 740,
HRMS-ESI (m/z) calcd for C18H15F3NO2 (M + H)+ 334.10494, 697; 1H NMR (500 MHz, CDCl3) d 8.47 (s, 1H), 8.23–8.21 (m, 1H),
+
found 334.10495.
7.69–7.67 (m, 2H), 7.48–7.47 (m, 3H), 7.42–7.40 (m, 1H), 7.30–
Methyl 2-(3-uorophenyl)-5-methyl-1H-indole-3-carboxylate 7.28 (m, 2H), 3.85 (s, 3H). 13C NMR (126 MHz, CDCl3) d 164.7,
(3ak). Yield, 47% (26.6 mg); orange solid, mp 121–122 ꢀC; IR 143.5, 134.0, 130.9, 128.5, 128.3, 127.2, 126.5, 122.3, 121.2,
(KBr, cmꢁ1): 3267, 1674, 1443, 1201, 1158, 1119, 861, 789, 680; 121.1, 109.9, 103.6, 49.9.
1H NMR (400 MHz, CDCl3) d 8.55 (s, 1H), 7.98 (s, 1H), 7.38–7.33,
Methyl 5-methyl-2-phenyl-1H-indole-3-carboxylate (3ba).13,38
(m, 3H), 7.24 (s, 1H), 7.09 (d, J ¼ 7.7 Hz, 2H), 3.83 (s, 3H), 2.49 (s, Yield, 54% (28.6 mg); white solid, mp 154–156 ꢀC; IR
3H). 13C NMR (151 MHz, CDCl3) d 165.8, 162.3 (163.1, 161.5, d, (KBr, cmꢁ1): 3287, 2949, 1673, 1452, 1129, 800, 759, 696; 1H
1JC–F ¼ 246 Hz), 142.8, 134.1 (134.1, 134.0, d, JC–F ¼ 8 Hz), NMR (400 MHz, CDCl3) d 8.60 (br, 1H), 7.99 (s, 1H), 7.62–7.60
3
3
133.5, 131.8, 129.7 (129.7, 129.6, d, JC–F ¼ 8 Hz), 127.6, 125.2 (m, 2H), 7.40 (br, 3H), 7.23 (d, J ¼ 8.1 Hz, 1H), 7.07 (d, J ¼ 8.1 Hz,
(125.23, 125.21, d, JC–F ¼ 3 Hz), 125.1, 121.8, 116.7 (116.8, 1H), 3.81 (s, 3H), 2.49 (s, 3H). 13C NMR (151 MHz, CDCl3)
4
2
2
116.6, d, JC–F ¼ 23 Hz), 116.1 (116.1, 116.0, d, JC–F ¼ 21 Hz), d 164.9, 143.6, 132.4, 131.1, 130.5, 128.5, 128.5, 128.0, 127.1,
+
110.8, 104.4, 51.0, 21.7. HRMS-ESI (m/z) calcd for C17H15FNO2
126.7, 123.7, 120.7, 109.7, 49.8, 20.7.
(M + H)+ 284.10813, found 284.10825.
Methyl 5-methoxy-2-phenyl-1H-indole-3-carboxylate (3ca).38
Methyl 2-(3-chlorophenyl)-5-methyl-1H-indole-3-carboxylꢀate Yield, 49% (27.5 mg); white solid, mp 157–159 ꢀC; IR
(3al). Yield, 46% (27.5 mg); light yellow solid, mp 152–153 C; (KBr, cmꢁ1): 3294, 2950, 1678, 1485, 1462, 1268, 1206, 1167,
IR (KBr, cmꢁ1): 3266, 1673, 1478, 1443, 1139, 782; 1H NMR (400 1129, 1047, 1035, 804, 696; 1H NMR (400 MHz, CDCl3) d 8.70 (br,
MHz, CDCl3) d 8.53 (br, 1H), 7.98 (s, 1H), 7.60 (s, 1H), 7.51 (d, J ¼ 1H), 7.71 (d, J ¼ 3 Hz, 1H), 7.61–7.59 (m, 2H), 7.41–7.39 (m, 3H),
7.2 Hz, 1H), 7.37–7.31 (m, 2H), 7.24 (d, J ¼ 5.4 Hz, 1H), 7.09 (d, J 7.23 (d, J ¼ 8.8 Hz, 1H), 6.90 (dd, J ¼ 8.8, 2.5 Hz, 1H), 3.90 (s,
¼ 7.1 Hz, 1H), 3.83 (s, 3H), 2.49 (s, 3H). 13C NMR (151 MHz, 3H), 3.79 (s, 3H). 13C NMR (151 MHz, CDCl3) d 165.0, 154.7,
CDCl3) d 164.7, 141.6, 133.0, 132.7, 132.5, 130.8, 128.4, 128.3, 143.9, 131.0, 129.2, 128.4, 128.0, 127.4, 127.1, 112.4, 110.9,
128.1, 126.9, 126.6, 124.1, 120.8, 109.7, 103.5, 50.0, 20.7. HRMS- 103.0, 102.6, 54.8, 49.8.
+
ESI (m/z) calcd for C17H15ClNO2 (M + H)+ 300.07858, found
300.07837.
Methyl 5-uoro-2-phenyl-1H-indole-3-carboxylate (3da).
Yield, 47% (25.3 mg); white solid, mp 156–158 ꢀC; IR
Methyl 5-methyl-2-(m-tolyl)-1H-indole-3-carboxylate (3am). (KBr, cmꢁ1): 3282, 1667, 1487, 1464, 1454, 1270, 1213, 1138,
Yield, 49% (27.4 mg); light yellow solid, mp 136–138 ꢀC; IR 1047, 859, 701, 629; 1H NMR (400 MHz, CDCl3) d 8.58 (br, 1H),
(KBr, cmꢁ1): 3289, 1668, 1447, 1161, 1124, 1049, 786, 731, 698; 7.86 (dd, J ¼ 10.0, 2.4 Hz, 1H), 7.64–7.63 (m, 2H), 7.46–7.44 (m,
1H NMR (500 MHz, CDCl3) d 8.52 (br, 1H), 7.92 (s, 1H), 7.36–7.34 3H), 7.31–7.27 (m, 1H), 7.02 (td, J ¼ 9, 2.4 Hz, 1H), 3.83 (s, 3H).
(m, 2H), 7.24–7.21 (m, 1H), 7.17–7.13 (m, 2H), 7.01–6.99 (d, J ¼ 13C NMR (151 MHz, CDCl3) d 165.5, 159.3 (160.0, 158.5, d, 1JC–F
7.9 Hz, 1H), 3.74 (s, 3H), 2.42 (s, 3H), 2.30 (s, 3H). 13C NMR (126 ¼ 236 Hz), 146.1, 131.6 (131.59, 131.55, d, 3JC–F ¼ 6 Hz), 129.5,
MHz, CDCl3) d 164.8, 143.7, 136.8, 132.4, 131.0, 130.5, 128.9, 129.4, 128.4, 128.3, 111.8, 111.7, 111.6, 107.5 (107.6, 107.5, d,
4
128.8, 127.0, 126.8, 125.8, 123.7, 120.7, 109.5, 102.9, 49.8, 20.7, 2JC–F ¼ 26 Hz), 104.7 (104.72, 104.69, d, JC–F ¼ 4 Hz), 51.0.
+
20.4. HRMS-ESI (m/z) calcd for C18H18NO2+ (M + H)+ 280.13321, HRMS-ESI (m/z) calcd for C16H13FNO2 (M + H)+ 270.09248,
found 280.13309.
found 270.09256.
Ethyl 5-chloro-2-(p-tolyl)-1H-indole-3-carboxylate
Methyl 5-methoxy-2-(m-tolyl)-1H-indole-3-carboxylate (3an).
(3ea).
Yield, 49% (29.0 mg); light yellow solid, mp 138–140 ꢀC; IR Yield, 46% (28.8 mg); white solid, mp 190–192 ꢀC; IR
(KBr, cmꢁ1): 3395, 1667, 1451, 1213, 1195, 1164, 1124, 1050, (KBr, cmꢁ1): 3429, 3270, 1671, 1431, 1210, 1128, 824, 786; H
1
1029, 796; 1H NMR (400 MHz, CDCl3) d 8.71 (s, 1H), 7.68 (s, 1H), NMR (400 MHz, CDCl3) d 8.60 (br, 1H), 8.17 (d, J ¼ 1.6 Hz, 1H),
7.39–7.36 (m, 2H), 7.26–7.24 (m, 1H), 7.20–7.16 (m, 2H), 6.87 (d, 7.50 (d, J ¼ 8.0 Hz, 2H), 7.35–7.05 (m, 5H), 4.30 (q, J ¼ 7.1 Hz,
J ¼ 9.0 Hz, 1H), 3.87 (s, 3H), 3.77 (s, 3H), 2.32 (s, 3H). 13C NMR 2H), 2.37 (s, 3H), 1.33 (t, J ¼ 7.1 Hz, 3H). 13C NMR (151 MHz,
(151 MHz, CDCl3) d 165.1, 154.6, 144.2, 136.7, 130.9, 129.2, CDCl3) d 165.1, 146.0, 139.6, 133.4, 129.4, 128.9, 128.8, 128.5,
128.8, 128.7, 127.4, 126.9, 125.7, 112.2, 110.9, 102.8, 102.5, 54.7, 127.7, 123.4, 121.7, 112.0, 104.1, 59.9, 21.4, 14.4. HRMS-ESI (m/
+
49.8, 20.3. HRMS-ESI (m/z) calcd for C18H18NO3 (M + H)+ z) calcd for C18H17ClNO2+ (M + H)+ 314.09423, found 314.09406.
296.12812, found 296.12802.
Dimethyl 2-phenyl-1H-indole-3,5-dicarboxylate (3fa). Yield,
Methyl
2-(3-methoxyphenyl)-5-methyl-1H-indole-3- 44% (27.2 mg); white solid, mp 202–204 ꢀC; IR (KBr, cmꢁ1):
carboxylate (3ao). Yield, 48% (28.3 mg); yellow solid, mp 130– 3328, 1693, 1674, 1452, 1437, 1288, 1105, 762, 696; 1H NMR (400
132 ꢀC; IR (KBr, cmꢁ1): 3354, 1686, 1466, 1440, 1286, 1123, 878, MHz, CDCl3) d 8.93 (s, 1H), 8.68 (s, 1H), 8.00 (dd, J ¼ 8.6, 1.3 Hz,
804, 787; 1H NMR (400 MHz, CDCl3) d 8.81 (br, 1H), 8.01 (s, 1H), 1H), 7.69–7.67 (m, 2H), 7.48–7.41 (m, 4H), 3.96 (s, 3H), 3.88 (s,
7.28–7.26 (m, 1H), 7.22–7.17 (m, 3H), 7.08 (d, J ¼ 8.2 Hz, 1H), 3H). 13C NMR (151 MHz, CDCl3) d 166.9, 164.2, 144.8, 136.6,
6.91 (d, J ¼ 7.5 Hz, 1H), 3.82 (s, 3H), 3.78 (s, 3H), 2.51 (s, 3H). 13
C
130.3, 128.6, 128.5, 127.3, 126.1, 124.0, 123.7, 123.1, 109.8,
NMR (151 MHz, CDCl3) d 165.0, 158.0, 143.3, 132.4, 132.2, 130.4, 104.5, 51.0, 50.2. HRMS-ESI (m/z) calcd for C18H16NO4+ (M + H)+
128.5, 128.0, 126.7, 123.7, 120.8, 120.5, 114.1, 113.6, 109.8, 310.10738, found 310.10748.
102.7, 54.2, 49.8. HRMS-ESI (m/z) calcd for C18H18NO3+ (M + H)+
296.12812, found 296.12848.
Methyl
5-(methylthio)-2-phenyl-1H-indole-3-carboxylate
(3ga). Yield, 50% (29.7 mg); white solid, mp 131–133 ꢀC; IR
Methyl 2-phenyl-1H-indole-3-carboxylate (3ap).8b,30 Yield, (KBr, cmꢁ1): 3286, 1665, 1439, 1215, 1131, 1077, 766, 697; H
51% (25.6 mg); yellow solid, mp 137–139 ꢀC; IR (KBr, cmꢁ1): NMR (500 MHz, CDCl3) d 8.59 (s, 1H), 8.18 (s, 1H), 7.64–7.63 (m,
1
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2H), 7.45–7.44 (m, 3H), 7.31–7.25 (m, 2H), 3.83 (s, 3H), 2.57 (s,
3H). 13C NMR (126 MHz, CDCl3) d 164.6, 144.0, 132.6, 130.7,
130.1, 128.4, 128.3, 127.3, 127.2, 123.4, 120.5, 110.5, 102.9, 50.0,
17.0. HRMS-ESI (m/z) calcd for C17H16NO2S+ (M + H)+ 298.08963,
found 298.08957.
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Org. Chem., 2018, 7, 1467.
Methyl 2-phenyl-1H-benzo[g]indole-3-carboxylate (3ha).
Yield, 49% (29.5 mg); white solid, mp 185–187 ꢀC; IR
(KBr, cmꢁ1): 3219, 1668, 1472, 1436, 1199, 1128, 811, 746, 684;
1H NMR (400 MHz, CDCl3) d 9.16 (s, 1H), 8.31 (d, J ¼ 8.8 Hz, 1H),
8.02 (d, J ¼ 8.1 Hz, 1H), 7.97 (d, J ¼ 8.1 Hz, 1H), 7.73–7.70 (m,
3H), 7.56 (t, J ¼ 7.6 Hz, 1H), 7.51–7.45 (m, 4H), 3.88 (s, 3H). 13
C
NMR (151 MHz, CDCl3) d 164.8, 141.3, 131.1, 129.7, 129.0, 128.6,
128.0, 127.9, 127.2, 124.9, 123.6, 123.0, 121.8, 120.3, 120.0,
+
118.3, 105.2, 50.0. HRMS-ESI (m/z) calcd for C20H16NO2 (M +
H)+ 302.11756, found 302.11707.
Methyl
2-phenyl-3H-benzo[e]indole-1-carboxylate
(3ia).
Yield, 50% (30.0 mg); white solid, mp 192–193 ꢀC; IR
(KBr, cmꢁ1): 3310, 1666, 1460, 1442, 1195, 1145, 806, 698; H
1
NMR (400 MHz, CDCl3) d 8.91 (d, J ¼ 8.5 Hz, 1H), 8.71 (s, 1H),
7.91 (d, J ¼ 7.9 Hz, 1H), 7.67 (d, J ¼ 8.7 Hz, 1H), 7.60–7.54 (m,
3H), 7.49–7.42 (m, 5H), 3.82 (s, 3H). 13C NMR (151 MHz, CDCl3)
d 166.9, 138.7, 131.5, 131.4, 129.4, 127.8, 127.6, 127.5, 127.4,
127.0, 125.1, 124.3, 123.8, 123.0, 120.0, 111.1, 107.3, 50.6.
+
HRMS-ESI (m/z) calcd for C20H16NO2 (M + H)+ 302.11756,
¨
¨
found 302.11691.
8 (a) S. Wurtz, S. Rakshit, J. J. Neumann, T. Droge and
Mixture
of
methyl
6-methyl-2-phenyl-1H-indole-3-
F. Glorius, Angew. Chem., Int. Ed., 2008, 47, 7230; (b)
¨
¨
carboxylate (3ja) and methyl 4-methyl-2-phenyl-1H-indole-3-
carboxylate (3j0a).30,39 Yield, 52% (27.6 mg); yellow solid, the
ratio (3ja : 3j0a ¼ 2 : 1) is determined by NMR; IR (KBr, cmꢁ1):
3297, 2949, 1682, 1452, 1214, 1127, 1048, 813, 768, 696; 1H NMR
J. J. Neumann, S. Rakshit, T. Droge, S. Wurtz and
F. Glorius, Chem. - Eur. J., 2011, 17, 7298.
9 R. Bernini, G. Fabrizi, A. Sferrazza and S. Cacchi, Angew.
Chem., Int. Ed., 2009, 48, 8078.
(400 MHz, CDCl3) d 8.50 (br, 1.5Hoverlap), 8.07 (d, J ¼ 8.2 Hz, 10 (a) X.-L. Lian, Z.-H. Ren, Y.-Y. Wang and Z.-H. Guan, Org.
0
1H3ja), 7.65–7.63 (m, 2H3ja), 7.55–7.51 (m, 1H3j a), 7.45–7.40 (m,
Lett., 2014, 16, 3360; (b) A. Mishra and I. Deb, Adv. Synth.
Catal., 2016, 358, 2267.
0
4.50Hoverlap), 7.22 (d, J ¼ 8.0 Hz, 0.55H3j a), 7.17–7.10 (m,
0
2.54Hoverlap), 7.01 (d, J ¼ 7.1 Hz, 0.53H3j a), 3.83 (s, 3H3ja), 3.76 11 (a) F. Huang, P. Wu, L. Wang, J. Chen, C. Sun and Z. Yu, J.
0
0
(s, 1.56H3j a), 2.65 (s, 1.50H3j a), 2.47 (s, 3H3ja).
Org. Chem., 2014, 79, 10553; (b) P. Drouhin and
R. J. K. Taylor, Eur. J. Org. Chem., 2015, 2333; (c) J. Liu,
W. Wei, T. Zhao, X. Liu, J. Wu, W. Yu and J. Chang, J. Org.
Chem., 2016, 81, 9326; (d) F.-Z. Hu, S.-H. Zhao, H. Chen,
S.-W. Yu, X.-Y. Xu, W.-C. Yuan and X.-M. Zhang,
ChemistrySelect, 2017, 2, 1409.
Conflicts of interest
There are no conicts to declare.
12 Z.-H. Guan, Z.-Y. Yan, Z.-H. Ren, X.-Y. Liu and Y.-M. Liang,
Chem. Commun., 2010, 2823.
Acknowledgements
We are grateful for nancial support from Special Project for 13 W. Yu, Y. Du and K. Zhao, Org. Lett., 2009, 11, 2417.
Double First-Class-Cultivation of Innovative Talents (201815), 14 (a) Z. He, W. Liu and Z. Li, Chem.–Asian J., 2011, 6, 1340; (b)
the Fundamental Research Funds for the Central Universities
(2572017DB07), and Natural Science Foundation of Hei-
longjiang Province (B2017002, LC2018003).
Z. Jia, T. Nagano, X. Li and A. S. C. Chan, Eur. J. Org. Chem.,
2013, 858.
15 (a) C.-J. Wu, Q.-Y. Meng, T. Lei, J.-J. Zhong, W.-Q. Liu,
L.-M. Zhao, Z.-J. Li, B. Chen, C.-H. Tung and L.-Z. Wu, ACS
Catal., 2016, 6, 4635; (b) W.-Q. Liu, T. Lei, Z.-Q. Song,
X.-L. Yang, C.-J. Wu, X. Jiang, B. Chen, C.-H. Tung and
L.-Z. Wu, Org. Lett., 2017, 19, 3251.
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Chem., Int. Ed., 2014, 53, 13264.
17 S. Tang, X. Gao and A. Lei, Chem. Commun., 2017, 53, 3354.
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