Palladium-Catalyzed Sequential Vinylic C-H Arylation/Amination of 2-Vinylanilines with Aryl boronic Acids: Access to 2-Arylindoles

Article abstract of DOI:10.1021/acs.joc.7b02728

A palladium-catalyzed selective and successive vinylic C-H arylation/amination of 2-vinylanilines with arylboronic acids to generate indoles has been developed. This procedure represents a straightforward and practical approach to valuable multifunctionalized indoles.

Full text of DOI:10.1021/acs.joc.7b02728

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Article
Palladium-Catalyzed Sequential Vinylic C-H Arylation/Amination of
2-Vinylanilines with Aryl boronic Acids: Access to 2-Arylindoles
Ruixia Yu, Dejun Li, and Fanlong Zeng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02728 • Publication Date (Web): 30 Nov 2017
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Palladium‐Catalyzed Sequential Vinylic C‐H Arylation/Amination of 2‐Vinylanilines
with Aryl boronic Acids: Access to 2‐Arylindoles
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Ruixia Yu, Dejun Li and Fanlong Zeng*
Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of
Education, College of Chemistry & Materials Science, Northwest University, 1 Xuefu
Road, Xi’an Shaanxi, P. R. China, 710127
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Abstract:
Palladium‐catalyzed selective and successive vinylic C‐H arylation/amination of 2‐
vinylanilines with arylboronic acids to generate indoles has been developed. This
procedure represents a straightforward and practical approach to valuable multi‐
functionalized indoles.
Intruduction
Indoles represent one of the most important class of heterocyclic motifs, which are
ubiquitously observed in naturally occurring bioactive alkaloids and pharmaceuticals.1
Consequently, many efforts have been made on exploring efficient approaches to
indole skeletons. Nowadays, numerous elegant protocols are available to fulfill this
purpose.2 Among them, oxidative heteroannulation of 2‐vinylanilines is an appealing
alternative from both atom‐ and step‐economic points of view. The pioneer work of
Hegedus et al.3 have been followed by numerous modified procedures to achieve the
C‐N bond formation. Palladium‐catalyzed oxidative amination reactions have proven
to be efficient and powerful, and many of them have been successfully applied in
synthetic organic chemistry.4 Recently, a new class of alternative approaches based on
nitrogen‐centered radicals or cations addition to the vinyl to build the C‐N bond have
been developed by the research groups of Zheng,5 Chemler,6 Youn,7 and Deng,8
independently. Very recently, the intramolecular amination of 2‐vinylanilines
mediated by electrophilic cation of main group elements, such as iodine and selenium,
is described by Mu
̃
niz,9 Deng,10 Breder,11 and Zhao.12 Despite the remarkable advances
in the catalytic oxidative heteroannulation, the construction of C2‐selectively
functionalized indoles via sequential 1,1‐difunctionalization of the terminal vinyl on 2‐
vinylanlines has not been reported.
Given the advantages of C‐H bond activation,13 our group is interested in exploring
new efficient procedures to convert 2‐vinylanilines to potentially useful nitrogen‐
containing heterocycles through palladium‐catalyzed oxidative heteroannulation
reactions.14 Importantly, during the investigation, we found that the vinylic C(sp2)‐H
bond activation is via nucleophilic attack of the conjugated alkene on the electrophilic
palladium(II) followed by a base‐assisted deprotonation process (Scheme 1),14 which
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offers the possibility to sequentially difunctionalize the terminal vinyl group of 2‐
vinylanilines. Arylboronic acids have been successfully employed in oxidative Heck
reactions,15 and C(sp2)‐H bond arylation,16 we envisage arylboronic acids are suitable
arylation reagent for the step‐wise difuctionalization of the terminal vinyl group on 2‐
vinylanilines under oxidative conditions. We herein disclose a novel sequential vinylic
C‐H arylation/amination of 2‐vinylanilines with arylboronic acids to generate 2‐
arylindoles.
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Scheme 1. Pd‐Catalyzed Vinylic C‐H Bond Activation of 2‐Vinylanilnes
Results and Discussion
Initially, the reaction of Ts‐protected aniline 1a with 4‐methoxyphenyl boronic acid
(2a) was chosen as the model reaction to explore the feasibility and efficiency of the
domino protocol (Table 1). The nature of solvent had a significant impact on the
reaction efficiency and selectivity. Dioxane and THF offered excellent conversions, but
poor selectivities, furnishing mixtures of three products 3aa, 3aa’ and 3aa” (Table 1,
entries 1 and 2). Toluene and dichloroethane selectively delivered product 3aa’, yet in
poor yields (Table 1, entries 3 and 4). DMF and CH3CN eliminated the formation of the
direct amination product 3aa”, and DMF gave a better yield of vinylic C‐H arylation
product 3aa’ (Table 1, entries 5 and 6). The configuration of the C‐C double bond in
3aa’ is Z, determined by X‐ray crystallographic analysis (see the Supporting
Information). Next, we chose DMF as the solvent to examine oxidants. The utilization
of organic oxidants, such as PhI(OAc)2 and DDQ, was prone to result in the direct
amination product 3aa”, without engaging boronic acid 2a, which is consistent with
the results reported by Youn’s group7b (Table 1, entries 7 and 9). Employing silver salts
as oxidant, e.g. Ag2CO3, AgOAc, and Ag2O, selectively produced the anticipated
product 3aa, and the best performer Ag2CO3 furnished indole 3aa in 80% yield (Table
1, entries 10, 11, and 12). Utilizing PdCl2 or Pd(OTf)2 as the catalyst precursor, rather
than Pd(OAc)2, depressed the yields (Table 1, entries 13 and 14). It is noteworthy that
the protecting group Ts also played a key role in this transformation. Using Ms (1b) or
Ac (1c) as the protecting group instead of Ts gave inferior results. Interestingly, the free
amine 1d was also successfully converted to indole 3da, albeit in a poor yield.
Table 1. Optimization of Reaction Conditionsa
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yield(%)b
3/3’/3’’
entry
1
oxidant
solvent
1
2
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
Cu(OAc)2∙H2O
Cu(OAc)2∙H2O
Cu(OAc)2∙H2O
Cu(OAc)2∙H2O
Cu(OAc)2∙H2O
Cu(OAc)2∙H2O
PhI(OAc)2
BQ
DDQ
Ag2CO3
AgOAc
Ag2O
dioxane
THF
PhMe
DCE
18/ 50/20
20/55/18
‐‐/18/trace
‐‐/20/trace
10/69/trace
10/50/trace
‐‐/‐‐/10
trace/35/20
trace/‐‐/56
80/‐‐/trace
40/‐‐/trace
46/‐‐/trace
67/‐‐/3
3
4c
5
CH3CN
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
6
7
8
9
10
11
12
13d
14e
15
16
17
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
51/‐‐/trace
75/‐‐/10
10/21/‐‐
Ag2CO3
22/‐‐/‐‐
aAll reactions were carried out with 0.3 mmol 1, 0.6 mmol of
2a, 10 mol% of Pd(OAc)2, 5.0 equiv of [Cu2+], [Ag+], PhI(OAc)2,
o
b
BQ, or DDQ, 5 mL of solvent, sealed flask, 120 C, 12 h.
Isolated yield. c DCE = dichloroethane, d PdCl2, e Pd(OTf)2.
With the optimized reaction conditions established, the scope and limitations were
investigated by the reaction of 4‐methoxyphenyl boronic acid with various 2‐
vinylanilinic substrates, and the results are summarized in Table 2. Both electron‐
donating and ‐withdrawing groups, such as methyl (3e), methoxy (3f), and chloro (3g),
para to the nitrogen were well tolerated. Strongly electron‐withdrawing substituent
NO2 para to the nitrogen hampered the reaction efficiency and the para‐nitro product
3ha was obtained in 51% yields. Steric hindrance from the methyl group ortho to the
nitrogen (1i) markedly affects the outcome of this process, and the yield of 3ia
decreased to 30%. When R2 were 4‐MeO‐phenyl, 3‐MeO‐phenyl, 4‐Me‐phenyl, and 4‐
Cl‐phenyl, the corresponding products 3ja‐3ma were isolated in good to excellent
yields, revealing that the substituents on the phenyl group have no major impact on
this transformation. The substrates were smoothly converted to the desired products
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when R1 was a substituent rather than an H atom and R2 was a functionalized phenyl
group (3n, 3o and 3p). Utilizing a methyl or i‐propyl instead of an aromatic group
depressed the reaction efficiency (3qa, 3ra and 3sa). It is worth mentioning that, when
R2 was an H atom, the reaction efficiency dropped significantly, giving the desired
product in 14% yield. Gratifyingly, this procedure is also applicable to the 2‐
vinylnaphthalen‐1‐amine derivatives. The substrates 1t and 1u furnished the
corresponding products in moderate yields (58% and 52%).
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Table 2. The Scope of 2‐Vinylanilinesa
entry 1
R1
H
R2
Ph
Ph
3
yield
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8
1a
3aa 80
3ea 66
3fa 94
3ga 65 (9)c
3ha 51
3ia 30
1e 4‐Me
1f 4‐MeO Ph
1g 4‐Cl Ph
1h 4‐NO2 Ph
1i 2‐Me Ph
1j
1k
1l
H
H
H
4‐MeO‐Ph 3ja 90
3‐MeO‐Ph 3ka 68
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4‐Me‐Ph
4‐Cl‐Ph
2‐Cl‐Ph
4‐Me‐Ph
4‐Cl‐Ph
iPr
3la 64
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16
1m H
3ma 75 (8)c
3na 82
1n 4‐Cl
1o 4‐Me
1p 4‐Me
3oa 75
3pa 61
1q
H
3qa 52
1r 4‐Me
1s 4‐Cl
Me
Me
3ra 42(10)c
3sa 54
17
1t
3ta 58
18
1u
3ua 52
aAll reactions were carried out with 0.3 mmol 1,
0.6 mmol of 2a, 10 mol% of Pd(OAc)2, 2.5 equiv
of Ag2CO3, 5 mL of DMF, sealed flask, 120 oC, 12
h. b Isolated yield. c The yield of direct amination
product 3”.
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The generality of aryl boronic acids was next examined by the reaction of Ts‐
protected aniline 1a with a range of aryl boronic acids (Table 3). The results show that
the electronic properties of the substituents have a significant effect on the efficiency
of this reaction. Three different phenyl boronic acids with strongly electron‐donating
methoxy group(s) gave good yields, regardless of the effect of steric hindrance from
the MeO group(s) (Table 3, entries 1‐3). Phenyl boronic acids with weakly electron‐
donating methyl group(s) offered moderate yields (Table 3, entries 4‐6). The
unfunctionalized phenyl boronic acid produced the desired product 3ag in a poor yield
(37%) at 120 oC, while elevating the reaction temperature to 150 oC increased the yield
of 3ag to 79%. At the elevated temperature, the phenyl boronic acids with electron‐
deficient groups, e.g., 4‐Ph (2h), 4‐Cl (2i), 4‐CN (2j), 4‐CF3 (2l) and 4‐MeCO (2m),
furnished the anticipated products in good yields. Limitations encountered with 4‐
methoxycarbonylphenylboronic acid to result in the indole product 3ak in a poor yield.
1‐Naphthyl boronic acid was also a suitable coupling partner, giving the anticipated
product 3an in 68% yield. It is noteworthy that this procedure is not applicable to
heteroaryl boronic acids, such as 2‐furanboronic acid, 2‐Pyridineboronic acid, and 4‐
pyridineboronic acid.
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Table 3. The Scope of Aryl Boronic Acidsa
entry
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2
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4
5
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7
8
2
R3
3
yieldb
80
71
83
63
2a
2b
2c
2d
2e
2f
2g
2h
2i
4‐MeO
2‐MeO
2,6‐di‐MeO
4‐Me
2‐Me
3,5‐di‐Me
H
3aa
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
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61
79c
65c
66
4‐Ph
4‐Cl
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2k
2l
2m
2n
4‐CN
4‐CO2Me
4‐CF3
4‐MeCO
benzo[b]
3aj
3ak
3al
3am
3an
61
35
57c
62c
68c
aAll reactions were carried out with 0.3 mmol 1a,
0.6 mmol of 2, 10 mol% of Pd(OAc)2, 2.5 equiv of
o
b
Ag2CO3, 5 mL of DMF, sealed flask, 120 C, 12 h.
Isolated yield. c T = 150oC.
To gain mechanistic insight for the reaction, the following control experiments were
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conducted (Scheme 2). Decreasing reaction temperature to 90 oC led to the formation
of 3aa’ in 40% with trace amount of 3aa (Scheme 2, eq 1). Subjecting 3aa’ to the
optimized conditions gave the product 3aa in 94% (Scheme 2, eq 2), which manifests
the intermediacy of the vinylic C‐H arylation product 3aa’ in this transformation.
Employing Ag2CO3 or catalytic amount of Pd(OAc)2 with oxidant Cu(OAc)2 achieved the
intramolecular amination to generate indole 3aa, albeit with worse performance than
that of under optimized conditions (Scheme 2, eq 3 and 5), which indicates silver and
palladium with oxidant can promote the amination step, independently. The Ag2CO3‐
promoted intramolecular amination was slightly affected by TEMPO (2,2,6,6‐
tetramethylpiperidine‐N‐oxyl), but deterred by BHT (3,5‐di‐tert‐butyl‐4‐
hydroxytoluene), which is consistent with the observation of Youn’s group7a and shows
the reaction possibly involves a free‐radical process (Scheme 2, eq 4). Performing the
reaction of 1a and 2a under the optimized condition but without the presence of
Pd(OAc)2 resulted in indole 3aa” (77%), revealing the catalyst precursor Pd(OAc)2 is
requisite for vinylic C‐H arylation (Scheme 2, eq 7).
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Scheme 2. Control Experiments
yield (%)
additive
3aa
TEMPO (3.0 equiv)
BHT (3.0 equiv)
77
trace
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On the basis of the above observations, a possible mechanism for this
transformation is outlined in Scheme 3, with 1a and 2g as the model substrates.
Initially, the nitrogen atom of aniline 1a adds to Pd(II) species 4 with elimination of
acetic acid, and then followed by the formation of palladacycle complex 5 via vinylic
C‐H bond activation.14 The Pd(II) species 5 transmetalates with boronic acid 2g to give
the palladium species 6. Reductive elimination of 6 affords the intermediate product
3ag’ and releases the palladium(0) species, which is reoxidized to active Pd(II) species
by Ag2CO3. There are two pathways to form the desired product 3ag. In path a,
Intramolecular nucleophilic attack of the conjugated alkene on the electrophilic
palladium(II), and then followed by a base‐assisted deprotonation, results in the key
palladacycle complex 8. Reductive elimination of 8 engenders product 3ag, along with
palladium(0) species, which then is reoxidized by Ag2CO3 to the palladium(II) species
4. In pathway b, the intermediate product 3ag’ is oxidized by Ag2CO3 to the nitrogen
radical cation 9, the electronphilicity of which triggers intramolecular annulation to
afford the benzylic radical 10, with the loss of a proton. Hereafter, Ag2CO3 oxidizes
radical 10 to the benzylic carbocation 11, followed the constitution of the desired
product 3ag by deprotonation.
Scheme 3. Proposed Catalytic Cycle.
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In conclusion, a novel access to highly valuable indoles has been developed based
on palladium catalyzed sequential vinylic C‐H arylation/amination of 2‐vinylanilines
with aryl boronic acids. This procedure, tolerating a wide range of typical organic
functional groups, represents a straightforward and practical approach to multi‐
functionalized indoles. To our knowledge, it is the first example of selective and
successive 1,1‐difunctionalization of the terminal vinyl on 2‐vinylanlines to construct
indoles, and we thereupon believe it provides a basis for exploring new
transformations of 2‐vinylanilines or their analogues to valuable nitrogen‐containing
heterocycles.
EXPERIMENTAL SECTION
General information.
Unless otherwise noted, all the materials were purchased from commercial
suppliers and used as received. Solvents were freshly distilled by standard procedures
1
13
prior to use. All H and C{1H} NMR spectra were recorded on a Bruker 400 MHz
spectrometer. The NMR chemical shift values refer to CDCl3 (δ (1H), 7.26 ppm; δ (13C),
77.16 ppm). Mass spectra were obtained on a micrOTOF‐Q II mass spectrometer.
Crystals were collected on a Bruker SMART APEX II CCD (Mo‐ Kα radiation, λ = 0.71073
Å). The corresponding of 2‐vinylanilines to prepare 1a‐1i,17 1o,17 1p,17 1t,17 1u,17 1j‐
1m,18 1r,18 and 1s18 were synthesized by known literature methods.
General procedure for the preparation of new 2‐vinyl‐N‐tosylanilines.
The corresponding 2‐vinylaniline (5.00 mmol) was dissolved in dry pyridine (25 mL),
and the solution was treated with 4‐toluenesulfonyl chloride (5.50 mmol) at 0 °C. The
mixture was stirred at room temperature for 2 h, then poured into water and extracted
with CH2Cl2. The combined organic phase were dried over Mg2SO4, filtered, and
concentrated in vacuum. The reaction mixture was purified directly by flash
chromatography, using a mixture of petroleum ether and ethyl acetate (v/v = 15:1) as
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eluent.
2‐(1‐(4‐Methoxyphenyl)vinyl)‐N‐tosylbenzenamine (1j). White solid (1.25 g, 66%),
m.p. = 85‐86 Ԩ. 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.0 Hz, 1H), 7.44 (d, J = 8.0 Hz,
2H), 7.31 (t, J = 8.0 Hz, 1H), 7.10 (t, J = 8.0 Hz, 3H), 7.06 (d, J = 8.0 Hz, 1H), 6.94 (d, J =
8.0 Hz, 2H), 6.73 (d, J = 8.0 Hz, 2H), 6.57 (s, 1H), 5.57 (s, 1H), 4.76 (s, 1H), 3.81 (s, 3H),
2.37 (s, 3H). 13C NMR (101MHz, CDCl3) δ 160.0, 144.4, 143.8, 136.1, 134.3, 133.5, 131.2,
130.5, 129.5, 128.9, 127.8, 127.3, 124.8, 121.2, 115.2, 114.2, 55.4, 21.7. HRMS (ESI‐
TOF) m/z: [M + Na]+ Calcd for C22H21NO3SNa 402.1140; Found 402.1142.
2‐(1‐(3‐Methoxyphenyl)vinyl)‐N‐tosylbenzenamine (1k). White solid (0.7 g, 37%),
m.p. = 96‐97 Ԩ. 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.0 Hz 1H), 7.47 (d, J = 8.0 Hz,
2H), 7.36 (t, J = 8.0 Hz, 1H), 7.21 (t, J = 8.0 Hz, 1H), 7.15 (d, J = 8.0 Hz, 4H), 6.89 (d, J =
8.0 Hz, 1H), 6.69 (d, J = 8.0 Hz, 1H), 6.57 (d, J = 8.0 Hz, 2H), 5.71 (s, 1H), 4.93 (s, 1H),
3.75 (s, 3H), 2.40 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 159.9, 144.9, 143.8, 140.2, 135.9,
134.2, 133.2, 130.6, 129.9, 129.5, 129.0, 127.3, 124.9, 121.3, 118.9, 117.5, 113.9,
112.2, 55.2, 21.6. HRMS (ESI‐TOF) m/z: [M+H]+ Calcd for C22H22NO3S 380.1320; found
380.1313.
2‐(1‐p‐Tolylvinyl)‐N‐tosylbenzenamine (1l). White solid (1.11 g, 61%), m.p. = 73‐
74 Ԩ. 1H NMR (400 MHz, CDCl3) δ 7.79 (d, J = 8.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 2H), 7.37
(t, J = 8.0 Hz, 1H), 7.16 (d, J = 8.0 Hz, 4H), 7.08 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz,
2H), 6.62 (s, 1H), 5.69 (s, 1H), 4.87 (s, 1H), 2.42 (s, 3H), 2.40 (s, 3H).13C NMR (101 MHz,
CDCl3) δ 144.8, 143.7, 138.5, 136.0, 135.8, 134.2, 133.4, 130.5, 129.5, 129.4, 128.8,
127.2, 126.2, 124.8, 121.2, 116.2, 21.5, 21.2. HRMS (ESI‐TOF) m/z: [M+H]+ Calcd for
C22H22NO2S 364.1371; Found 364.1366.
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2‐(1‐(4‐Chlorophenyl)vinyl)‐N‐tosylbenzenamine (1m). White solid (0.57 g, 30%),
m.p. = 65‐66 Ԩ. 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 8.0 Hz, 1H), 7.41 (d, J = 8.0 Hz,
2H), 7.33 (t, J = 8.0 Hz, 1H), 7.10 (t, J = 8.0 Hz, 5H), 7.03 (d, J = 8.0 Hz, 1H), 6.90 (d, J =
13
8.0 Hz, 2H), 6.54 (s, 1H), 5.74 (s, 1H), 4.98 (s, 1H), 2.38 (s, 3H). C NMR (101 MHz,
CDCl3) δ 144.0, 143.9, 137.2, 136.1, 134.5, 134.3, 132.5, 130.5, 129.6, 129.2, 128.9,
127.6, 127.1, 124.9, 121.1, 117.7, 21.6. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for
C21H18ClNO2SNa 406.0644; Found 406.0621.
General procedure for palladium‐catalyzed reaction of 2‐vinylanilines with aryl
boronic acids
A mixture of Pd(OAc)2 (0.03 mmol), Ag2CO3 (0.75 mmol), 1 (0.3 mmol), 2 (0.6 mmol),
and DMF (5 mL) was added sequentially to a heavy glass flask. The reaction mixture
was stirred and heated at 120°C for 12 h. After the reaction cooled to rt, the solvent
was removed under reduced pressure. The residue was purified by chromatography
on silica gel to afford the desired product 3
2‐((Z)‐2‐(4‐Methoxyphenyl)‐1‐phenylvinyl)‐N‐tosylbenzenamine (3aa'). White
solid (94 mg, 69%), m.p. = 167‐168 Ԩ. 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 8.0 Hz,
1H), 7.36 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 1H), 7.25‐7.18 (m, 3H), 7.07 (t, J = 8.0
Hz, 5H), 6.98 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 6.70 (br s, 1H), 6.61 (d, J = 8.0
13
Hz, 2H), 3.75 (s, 3H), 2.30 (s, 3H). C NMR (101 MHz, CDCl3) δ 159.3, 143.6, 141.1,
136.2, 134.6, 134.2, 131.3, 130.6, 130.4, 130.1, 129.6, 129.1, 128.7, 128.5, 127.8,
127.3, 126.5, 124.8, 119.2, 113.9, 55.3, 21.6. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for
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C28H25NO3SNa 478.1453; Found 478.1465
2‐(4‐Methoxyphenyl)‐3‐phenyl‐1‐mesyl‐1H‐indole (3ba). White solid (91 mg, 75%),
m.p. = 156‐157 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.20 (d, J = 8.0 Hz, 1H), 7.60 (d, J = 8.0
Hz, 1H), 7.41 (t, J = 8.0 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.0 Hz, 4H), 7.23 (t,
J = 8.0 Hz, 3H), 6.84 (d, J = 8.0 Hz, 2H), 3.80 (s, 3H), 2.85 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 160.0, 137.0, 133.2, 132.8, 130.4, 130.0, 128.5, 127.2, 125.4, 124.5, 124,3,
122.8, 120.3, 115.8, 113.3, 55.3, 40.6. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for
C22H19NO3S Na 400.0983; Found 400.0966.
N‐(2‐((Z)‐2‐(4‐Methoxyphenyl)‐1‐phenylvinyl)phenyl)acetamide (3ca'). White
solid (22 mg, 21%), m.p. = 189‐190 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 8.0 Hz,
1H), 7.15‐7.38 (m, 1H), 7.36‐7.28 (m, 5H), 7.22 (br s, 1H), 7.15 (d, J = 4.0 Hz, 3H), 6.98
(d, J = 8.0 Hz, 2H), 6.70 (d, J = 8.0 Hz, 2H), 3.74 (s, 3H), 1.79 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 168.3, 159.3, 142.0, 135.6, 135.2, 130.8, 130.4, 129.9, 129.8, 128.9, 128.8,
127.9, 126.7, 124.7, 121.4, 114.0, 55.3, 24.6. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for
C23H21NO2Na 366.1470; Found 366.1459.
2‐(4‐Methoxyphenyl)‐3‐phenyl‐5‐methyl‐1‐tosyl‐1H‐indole (3ea). White solid (93
mg, 66%), m.p. = 172‐173 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 8.0 Hz, 1H), 7.29
(d, J = 8.0 Hz, 2H), 7.25‐7.16 (m, 5H), 7.14 (d, J = 8.0 Hz, 2H), 7.09‐7.05 (m, 3H), 7.03 (s,
1H), 6.78 (d, J = 8.0 Hz, 2H) , 3.80 (s, 3H), 2.37 (s, 3H), 2.28 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 159.7, 144.5, 137.1, 135.6, 135.4, 140.0, 133.4, 133.1, 130.9, 130.0, 129.3,
128.3, 127.0, 126.9, 126.5, 124.4, 123.2, 119.8, 116.2, 112.9, 55.3, 21.7, 21.4. HRMS
(ESI‐TOF) m/z: [M+H]+ Calcd for C29H26NO3S 468.1633; Found 468.1616.
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2‐(4‐Methoxyphenyl)‐3‐phenyl‐5‐methoxy‐1‐tosyl‐1H‐indole (3fa). White solid
(136 mg, 94%), m.p. = 187‐188 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 12.0 Hz, 1H),
7.25 (d, J = 8.0 Hz, 2H), 7.20‐7.16 (m, 3H), 7.11 ( d, J = 8.0 Hz, 2H), 7.05‐6.99 (m, 4H),
6.95 (d, J = 8.0 Hz, 1H), 6.84 (s, 1H), 6.76 (d, J = 8.0 Hz, 2H), 3.77 (s, 3H), 3.73 (s, 3H),
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2.25 (s, 3H). C NMR (101 MHz, CDCl3) δ 159.8, 157.2, 144.5, 137.9, 135.1, 133.4,
133.0, 131.9, 129.8, 129.3, 128.4, 127.0 127.0, 124.7, 123.1, 117.5, 113.7 112.9, 102.4
55.7, 55.3, 21.7. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for C29H25NO4SNa 506.1402;
Found 506.1383.
2‐(4‐Methoxyphenyl)‐3‐phenyl‐5‐chloro‐1‐tosyl‐1H‐indole (3ga). White solid (95
mg, 65%), m.p. = 186‐187 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.24 (d, J = 8.0 Hz, 1H), 7.34
(s, 1H), 7.26 (d, J = 8.0 Hz, 1H), 7.20 (d, J = 8.0 Hz, 2H), 7.16‐7.10 (m, 3H), 7.06 (d, J =
8.0 Hz, 2H), 6.99 (t, J = 8.0 Hz, 4H), 6.72 (d, J = 8.0 Hz, 2H), 3.74 (s, 3H), 2.23 (s, 3H). 13C
NMR (101 MHz, CDCl3) δ 160.0, 144.9, 138.3, 135.6, 135.1, 133.5, 132.3, 131.9, 130.1,
129.8, 129.5, 128.5, 127.2, 127.0, 125.2, 123.8, 122.5, 119.5, 117.5, 113.0, 55.3, 21.7.
HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for C28H22ClNO3SNa 510.0907; Found 510.0907.
2‐(4‐Methoxyphenyl)‐3‐phenyl‐5‐nitro‐1‐tosyl‐1H‐indole (3ha). White solid (76 mg,
51%), m.p. = 205‐206 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 8.0 Hz, 1H), 8.38 (s,
1H), 8.28 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 8.0 Hz, 2H), 7.27 (d, J = 8.0 Hz, 3H), 7.15‐7.10
(m. 6H), 6.81 (d, J = 8.0 Hz, 2H), 3.84 (s, 3H), 2.34 (s, 3H). 13C NMR (101 MHz, CDCl3) δ
160.3, 145.6, 144.9, 140.2, 139.7, 135.3, 133.6, 131.5, 130.3, 129.8, 129.7, 128.7 127.7,
127.2, 124.3, 121.8, 120.1, 116.4, 116.3, 113.1, 55.4, 21.8. HRMS (ESI‐TOF) m/z:
[M+Na]+ Calcd for C28H22N2O5SNa 521.1147; Found 521.1165.
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2‐(4‐Methoxyphenyl)‐3‐phenyl‐7‐methyl‐1‐tosyl‐1H‐indole (3ia). White solid (41
mg, 30%), m.p. = 179‐180 Ԩ. 1H NMR (400 MHz, CDCl3) δ 7.24‐7.19 (m, 4H), 7.15 (t, J
= 8.0 Hz, 1H), 7.09 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.0 Hz, 3H), 6.90 (d, J = 8.0 Hz, 2H),
6.82 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.0 Hz, 2H), 3.78 (s, 3H), 2.85 (s, 3H), 2.30 (s, 3H).
13C NMR (101 MHz, CDCl3) δ 159.6, 144.3, 140.3, 140.2, 135.9, 133.2, 132.8, 132.4,
131.3, 129.3, 128.8, 128.6, 128.4, 127.9, 127.4, 127.2, 125.9, 123.9, 117.5, 113.0, 55.3,
21.7, 21.6. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for C29H25NO3SNa 490.1453; Found
490.1440.
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2‐(4‐Methoxyphenyl)‐3‐(3‐methoxyphenyl)‐1‐tosyl‐1H‐indole (3ka). White solid
(99 mg, 68%), m.p. = 160‐161 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 8.0 Hz, 1H),
7.53 (d, J = 8.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.0 Hz, 2H), 7.29 (t, J = 8.0
Hz, 1H), 7.19‐7.14 (m, 3H), 7.08 (d, J = 8.0 Hz, 2H), 6.83 (d, J = 8.0 Hz, 2H), 6.74 (t, J =
13
8.0 Hz, 2H), 6.64 (s, 1H), 3.84 (s, 3H), 3.63 (s, 3H), 2.32 (s, 3H). C NMR (101 MHz,
CDCl3) δ 159.9, 159.4, 144.6, 137.3, 136.9, 135.5, 134.3, 133.5, 130.4, 129.4, 129.3,
127.0, 125.1, 124.3, 123.3, 122.4, 120.0, 116.4, 115.3, 112.9, 112.8, 55.3, 55.1, 21.7.
HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for C29H25NO4SNa 506.1402; Found 506.1391.
2‐(4‐Methoxyphenyl)‐3‐p‐tolyl‐1‐tosyl‐1H‐indole (3la). White solid (90 mg, 64%),
m.p. = 167‐168 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.0 Hz, 1H), 7.44 (d, J = 8.0
Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.23 (t, J = 8.0 Hz, 1H), 7.14 (d,
J = 8.0 Hz, 2H), 7.05‐6.99 (m, 4H), 6.96 (d, J = 8.0 Hz, 2H), 6.78 (d, J = 8.0 Hz, 2H), 3.79
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(s, 3H), 2.25 (s, 6H). C NMR (101 MHz, CDCl3) δ 159.7, 144.6, 137.3, 136.7, 136.6,
135.5, 133.5, 130.7, 129.8, 129.8, 129.3, 129.1, 127.0, 125.0, 124.4, 124.2, 123.2,
112.0, 116.4, 112.9, 55.2, 21.6, 21.3. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for
C29H25NO3SNa 490.1453; Found 490.1447.
2‐(4‐Methoxyphenyl)‐3‐(2‐chlorophenyl)‐5‐chloro‐1‐tosyl‐1H‐indole (3na). White
solid (129 mg, 82%), m.p. = 206‐207 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.26 (d, J = 8.0 Hz,
1H), 7.35 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H), 7.22 (d, J = 8.0 Hz, 2H), 7.18 (d, J =
8.0 Hz, 1H), 7.08 (d, J = 8.0 Hz, 1H), 7.06‐7.02 (m, 3H), 6.87 (d, J = 8.0 Hz, 1H), 6.74 (d,
J = 8.0 Hz, 2H), 3.76 (s, 3H), 2.29 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 160.0, 144.9,
140.0, 135.8, 134.9, 134.7, 132.7, 132.4, 132.3, 131.6, 130.3, 129.6, 129.4, 126.9,
125.2, 122.7, 122.5, 119.7, 118.0, 112.9, 55.2, 21.7. HRMS (ESI‐TOF) m/z: [M+Na]+
Calcd for C28H21Cl2NO3SNa 544.0517; Found 544.0509.
2‐(4‐Methoxyphenyl)‐3‐p‐tolyl‐5‐methyl‐1‐tosyl‐1H‐indole (3oa). White solid (108
mg, 75%), m.p. = 185‐186 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 8.0 Hz, 1H), 7.28
(d, J = 8.0 Hz, 2H), 7.20 (s, 1H), 7.18‐7.11 (m, 3H), 7.03‐6.91 (m, 6H), 6.77 (d, J = 8.0 Hz,
2H), 3.77 (s, 3H), 2.34 (s, 3H), 2.24 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 159.7, 144.4,
136.8, 136.5, 135.5, 135.3, 133.9, 133.4, 131.0, 130.0, 129.8, 129.3, 129.0, 127.0,
126.4, 124.4, 123.3, 119.8, 116.1, 112.8, 55.2, 21.6, 21.4, 21.3. HRMS (ESI‐TOF) m/z:
[M+Na]+ Calcd for C30H27NO3SNa 504.1609; Found 504.1627.
2‐(4‐Methoxyphenyl)‐3‐(4‐chlorophenyl)‐5‐methyl‐1‐tosyl‐1H‐indole (3pa). White
solid (92 mg, 61%), m.p. = 191‐192 Ԩ. 1H NMR 400 MHz, CDCl3) δ 8.27 (d, J = 8.0 Hz,
1H), 7.31 (d, J = 8.0 Hz, 2H), 7.24‐7.19 (m, 4H), 7.12 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 8.0
Hz, 2H), 7.01 (d, J = 8.0 Hz, 2H), 6.82 (d, J = 8.0 Hz, 2H), 3.85 (s, 3H), 2.41 (s, 3H), 2.32
(s, 3H). 13C NMR (101 MHz, CDCl3) δ 159.0, 144.6, 137.3, 135.5, 134.1, 133.4, 132.8,
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131.7, 131.2, 130.4, 129.4, 128.6, 127.0, 126.6, 123.1, 122.9, 119.5, 116.2, 113.0, 55.3,
21.7, 21.5. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for C29H24ClNO3SNa 524.1063; Found
524.1091.
2‐(4‐Methoxyphenyl)‐3‐isopropyl‐1‐tosyl‐1H‐indole (3qa). White solid (65 mg,
52%), m.p. = 156‐157 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 8.0 Hz, 1H), 7.64 (d, J
= 8.0 Hz, 1H), 7.33 (d, J = 8.0 Hz, 1H), 7.28 (d, J = 8.0Hz, 2H), 7.23 (d, J = 8.0 Hz, 1H),
7.13 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 6.91 (d, J = 8.0 Hz, 2H), 3.86 (s, 3H), 2.29
(s, 3H), 1.20 (s, 3H), 1.19 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 159.9, 144.4, 137.6, 135.9,
135.3, 132.9, 129.4, 129.3, 128.7, 126.9, 124.4, 123.9, 123.9, 123.4, 120.7, 116.2,
113.0, 55.4, 26.1, 22.2, 21.6. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for C25H25NO3SNa
442.1453; Found 442.1453.
2‐(4‐Methoxyphenyl)‐3,5‐dimethyl‐1‐tosyl‐1H‐indole (3ra). White solid (51mg,
42%), m.p. = 171‐172 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 8.0 Hz, 1H), 7.28‐7.23
(m, 4H), 7.17 (d, J = 8.0 Hz, 2H), 7.03 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.0 Hz, 2H), 3.88 (s,
3H), 2.44 (s, 3H), 2.28 (s, 3H), 1.99 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 159.7, 144.3,
136.8, 135.4, 135.3, 133.6, 132.8, 132.2, 129.3, 126.9, 126.2, 123.9, 119.4, 119.0,
116.1, 113.0, 55.4, 21.7, 21.5, 9.6. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for
C24H23NO3SNa 428.1296; Found 428.1287.
2‐(4‐Methoxyphenyl)‐3‐methyl‐6‐chloro‐1‐tosyl‐1H‐indole (3sa). White solid (69
mg, 54%), m.p. = 156‐157 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.35 (s, 1H), 7.31 (d, J = 8.0
Hz, 1H), 7.27 (d, J = 8.0 Hz, 3H), 7.21 (d, J = 12.0 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 6.96
(d, J = 8.0 Hz, 2H), 3.89 (s, 3H), 2.32 (s, 3H), 1.99 (s, 3H). 13C NMR (101 MHz, CDCl3) δ
159.9, 144.8, 137.5, 137.3, 135.2, 132.9, 130.7, 130.3, 129.5, 127.0, 124.5, 123.2,
119.7, 118.9, 116.4, 113.1, 55.4, 21.7, 9.5. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for
C23H20ClNO3SNa 448.0750; Found 448.0743.
2‐(4‐Methoxyphenyl)‐3‐phenyl‐1‐tosyl‐1H‐benzo[g]indole (3ta). White solid (88
mg, 58%), m.p. = 180‐181 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.88 (d, J = 8.0 Hz, 1H), 7.82
(d, J = 8.0 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.58 (t, J = 8.0 Hz, 1H), 7.43 (t, J = 8.0 Hz, 1H),
7.22‐7.15, (m, 4H), 7.12 (d, J = 8.0 Hz, 2H), 6.87‐6.89 (m, 4H), 6.73 (d, J = 8.0 Hz, 4H),
3.75 (s, 3H), 2.22 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 159.7, 144.5, 140.7, 136.1, 133.1,
132.7, 132.7, 132.2, 129.5, 128.7, 128.4, 128.3, 128.3, 127.6, 127.3, 127.3, 126.7,
126.6, 126.0, 125.3, 124.0, 118.2, 113.0, 55.3, 21.7. HRMS (ESI‐TOF) m/z: [M+Na]+
Calcd for C32H25NO3SNa 526.1453; Found 526.1442.
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2‐(4‐Methoxyphenyl)‐3‐(4‐chlorophenyl)‐1‐tosyl‐1H‐benzo[g]indole (3ua). White
solid (84 mg, 52%), m.p. = 165‐166 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.99 (d, J = 8.0 Hz,
1H), 7.96 (d, J = 8.0 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.72 (t, J = 8.0 Hz, 1H), 7.58 (t, J =
8.0 Hz, 1H), 7.34‐7.28 (m, 3H), 7.22 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 6.90 (d,
J = 8.0 Hz, 3H), 6.87‐6.83 (m, 3H), 3.91 (s, 3H), 2.36 (s, 3H). 13C NMR (101 MHz, CDCl3)
δ 159.9, 144.6, 141.0, 136.1, 133.3, 132.8, 132.7, 132.4, 132.1, 131.7, 130.8, 130.0,
129.0, 128.4, 128.3, 127.7, 127.3, 126.9, 126.6, 126.1, 125.4, 123.6, 117.8, 113.2, 55.4,
21.7. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for C32H24ClNO3SNa 560.1063; Found
560.1041.
2‐(2‐Methoxyphenyl)‐3‐phenyl‐1‐tosyl‐1H‐indole (3ab). White solid (97 mg, 71%),
m.p. = 182‐183 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.27 (d, J = 8.0 Hz, 1H), 7.48 (d, J = 8.0
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Hz, 1H), 7.38 (d, J = 8.0 Hz, 2H), 7.31‐7.26 (m, 2H), 7.23‐7.07 (m, 6H), 7.03 (d, J = 8.0
Hz, 2H), 6.89 (d, J = 8.0 Hz, 1H), 6.79 (d, J = 8.0 Hz, 1H), 6.75 (d, J = 8.0 Hz, 1H), 3.56 (s,
3H), 2.25 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 159.3, 144.4, 136.9, 136.2, 133.5, 133.3,
133.2, 130.7, 130.1, 129.5, 129.4, 128.2, 127.1, 126.9, 124.8, 124.0, 123.6, 120.5,
120.0, 119.7, 115.5, 110.5, 55.3, 21.6. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for
C28H23NO3SNa 476.1296; Found 476.1278.
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2‐(2,6‐Dimethoxyphenyl)‐3‐phenyl‐1‐tosyl‐1H‐indole (3ac). White solid (120 mg,
83%), m.p. = 256‐257 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.28 (d, J = 8.0 Hz, 1H), 7.57 (d, J
= 8.0 Hz, 1H), 7.53 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H),
7.27 (d, J = 4.0 Hz, 1H), 7.22‐7.18 (m, 5H), 7.11 (d, J = 8.0 Hz, 2H), 6.46 (d, J = 8.0 Hz,
2H), 3.49 (s, 6H), 2.32 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 159.9, 144.0, 137.0, 136.9,
133.8, 131.1, 130.1, 129.7, 129.2, 129.1, 128.0, 127.4, 126.8, 124.3, 123.8, 123.2,
119.8, 115.0, 109.5, 103.5, 55.5, 21.6. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for
C29H25NO4SNa 506.1402; Found 506.1412
2‐o‐Tolyl‐3‐phenyl‐1‐tosyl‐1H‐indole (3ae). White solid (83 mg, 63%), m.p. = 147‐
149 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.46 (J = 8.0 Hz, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.45
(d, J = 8.0 Hz, 1H), 7.41 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.0 Hz,
1H), 7.24‐7.15 (m, 4H), 7.15‐7.09 (m, 5H), 7.03 (d, J = 8.0 Hz, 1H), 2.35 (s, 3H), 1.96 (s,
3H). 13C NMR (101 MHz, CDCl3) δ 144.8, 139.8, 137.0, 136.2, 135.7, 132.9, 132.6, 130.6,
129.9, 129.6, 129.5, 129.5, 129.2, 128.3, 127.3, 127.0, 125.1, 124.7, 123.9, 123.9,
120.1, 115.7, 21.7, 20.3. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for C28H23NO2SNa
460.1347; Found 460.1347.
2‐(3,5‐Dimethylphenyl)‐3‐phenyl‐1‐tosyl‐1H‐indole (3af). White solid (83 mg, 61%),
m.p. = 158‐159 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 8.0
Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 1H), 7.25‐
7.20 (m, 3H), 7.11 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 6.95 (s, 1H), 6.79 (s, 2H),
2.32 (s, 2H), 2.23 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 144.6, 137.4, 137.3, 136.6, 135.8,
133.0, 130.7, 130.5, 130.3, 130.0, 130.0, 129.3, 128.2, 127.2, 127.0, 125.1, 124.3,
124.1, 120.1, 116.3, 21.7, 21.4. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for C29H25NO2SNa
474.1504; Found 474.1514.
2‐([1,1'‐Biphenyl]‐4‐yl)‐3‐phenyl‐1‐tosyl‐1H‐indole (3ah). White solid (97 mg, 65%),
m.p. = 131‐132 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.34 (d, J = 8..0 Hz, 1H), 7.57 (d, J = 8.0
Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.42‐7.31 (m, 4H), 7.28 (d, J = 8.0 Hz, 3H), 7.24 (d, J =
8.0 Hz, 2H), 7.20 (d, J = 8.0 Hz, 1H), 7.16‐7.12 (m, 3H), 7.04 (d, J = 8.0 Hz, 2H), 6.99 (d,
J = 8.0 Hz, 2H), 2.23 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 144.7, 140.9, 140.4, 137.5,
136.7, 135.2, 132.7, 132.5, 130.7, 129.9, 129.4, 128.9, 128.4, 127.6, 127.1, 127.0,
125.9, 125.3, 125.1, 124.4, 120.1, 116.4, 101.4, 21.6. HRMS (ESI‐TOF) m/z: [M]+ Calcd
for C33H25NO2S 499.1606; Found, 499.1611.
4‐(3‐Phenyl‐1‐tosyl‐1H‐indol‐2‐yl)benzonitrile (3aj). White solid (89 mg, 61%), m.p.
= 228‐229 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.0 Hz, 1H), 7.55 (d, J = 8.0 Hz,
2H), 7.42 (d, J = 8.0 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.31‐7.26 (m, 3H), 7.24‐7.22 (m,
3H), 7.08 (d, J = 8.0 Hz, 2H), 7.02‐6.99 (m, 2H), 2.30 (s, 3H). 13C NMR (101 MHz, CDCl3)
δ 145.2, 137.7, 136.1, 134.7, 132.6, 131.9, 131.2, 130.1, 129.8, 129.6, 128.7, 127.7,
126.9, 126.9, 126.1, 124.8, 120.5, 118.8, 116.6, 112.1, 21.7. HRMS (ESI‐TOF) m/z:
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[M+Na]+ Calcd for C28H20N2O2SNa 471.1143; Found 471.1146.
Methyl 4‐(3‐phenyl‐1‐tosyl‐1H‐indol‐2‐yl)benzoate (3ak). White solid (51 mg, 35%),
m.p. = 173‐174 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 8.0 Hz, 1H), 7.88 (d, J = 8.0
Hz, 2H), 7.39 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.27 (d, J = 8.0 Hz, 2H), 7.24‐
7.20 (m, 3H), 7.13 (d, J = 8.0 Hz, 3H), 7.01 (d, J = 8.0 Hz, 2H), 6.97 (d, J = 8.0 Hz, 2H),
3.85 (s, 3H), 2.24 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 167.0, 145.0, 137.6, 135.9, 135.7,
135.0, 132.2, 132.1, 130.6, 129.9, 129.9, 129.5, 128.6, 128.5, 127.4, 126.9, 126.0,
125.7, 124.6, 120.3, 116.5, 52.3, 21.7. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for
C29H23NO4SNa 504.1245; Found 504.1251.
1‐(4‐(3‐Phenyl‐1‐tosyl‐1H‐indol‐2‐yl)phenyl)ethanone (3am). White solid (87 mg,
62%), m.p. = 212‐213 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.35 (d, J = 8.0 Hz, 1H), 7.84 (d, J
= 8.0 Hz, 2H), 7.39 (t, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.0 Hz, 3H),
7.25 (d, J = 8.0 Hz, 1H), 7.21‐7.17 (m, 3H), 7.04 (d, J = 8.0 Hz, 2H), 7.00 (d, J = 8.0 Hz,
2H), 2.58 (s, 3H), 2.27 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 197.9, 145.0, 137.6, 136.6,
136.1, 135.7, 134.9, 133.4, 132.2, 130.7, 129.9, 129.5, 129.5, 128.5, 127.4, 127.4,
126.9, 125.8, 124.6, 120.4, 116.5, 26.8, 21.7. HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for
C29H23NO3SNa 488.1296; Found 488.1289.
2‐(Naphthalene‐1‐yl)‐3‐phenyl‐1‐tosyl‐1H‐indole (3an). White solid (97 mg, 68%),
m.p. = 206‐207 Ԩ. 1H NMR (400 MHz, CDCl3) δ 8.56 (d, J = 8.0 Hz, 1H), 7.93 (d, J = 8.0
Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.54 (t, J = 8.0 Hz, 2H), 7.49‐
7.44 (m, 2H), 7.41(d, J = 8.0 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 7.34‐7.28 (m, 3H), 7.14 (s,
5H), 7.00 (d, J = 8.0 Hz, 2H), 2.32 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 144.7, 137.2,
135.7, 134.4, 134.1, 130.0, 132.7, 130.9, 129.9, 129.7, 129.4, 129.3, 128.6, 128.2,
128.1, 127.1, 127.0, 126.3, 126.2, 125.7, 125.3, 125.2, 124.5, 124.0, 120.2, 115.8, 21.6.
HRMS (ESI‐TOF) m/z: [M+Na]+ Calcd for C31H23NO2SNa 496.1347; Found 496.1334.
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ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge via the Internet at
http://pubs.acs.org.
Characterization data of new compounds, including X‐ray crystal structures of 3aa’,
1H and 13C NMR spectra, and HRMS (PDF)
X‐ray crystallographic analysis, compound 3aa’ (CIF), CCDC number for 3aa’ is
1579545.
AUTHOR INFORMATION
Corresponding Author
*E‐mail: fzeng@nwu.edu.cn
ACKNOWLEDGMENT
We gratefully acknowledge Dr. Jamie Ferguson (Department of Chemistry, Emory &
Henry College) for constructive discussion, and the National Science Foundation of
China (No. 21302152) and Northwest University for financial support
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REFERENCES
(1) (a) Sundberg R. J. Indoles, Academic Press, San Diego, CA, 1996. (b) Kawasaki T.;
Higuchi, K. Nat. Prod. Rep., 2005, 22, 761‐793. (c) Bandini, M.; Eichholzer, A. Angew.
Chem., Int. Ed. 2009, 48, 9608‐9644. (d) Kochanowska‐Karamyan, A. J.; Hamann, M. T.
Chem. Rev. 2010, 110, 4489‐4497.
5
6
7
8
9
(2) For selected reviews, see: (a) Cacchi, S.; Fabrizi, G. Chem. Rev. 2011, 111, PR215‐
PR283, and references cited therein. (b) Shiri, M. Chem. Rev. 2012, 112, 3508‐3549. (c)
Platon, M.; Amardeil, R.; Djakovitch, L.; Hierso, J.‐C. Chem. Soc. Rev. 2012, 41, 3929‐
3968. (d) Inman, M.; Moody, C. J. Chem. Sci. 2013, 4, 29‐41.
(3) (a) Hegedus, L. S.; Allen, G. F.; Bozell, J. J.; Waterman, E. L. J. Am. Chem. Soc. 1978,
100, 5800‐5807. (b) Harrington, P. J.; Hegedus, L. S.; McDaniel, K. F. J. Am. Chem. Soc.
1987, 109, 4335‐4338.
(4) (a) Krolski, M. E.; Renaldo, A. F.; Rudisill, D. E.; Stille, J. K. J. Org. Chem. 1988, 53,
1170‐1176. (b) Larock, R. C.; Hightower, T. R.; Hasvold, L. A.; Peterson, K. P. J. Org. Chem.
1996, 61, 3584‐3585. (c) Tsvelikhovsky, D.; Buchwald, S. L. J. Am. Chem. Soc. 2010, 132,
14048‐14051. (d) Youn, S. W.; Bihn, J. H.; Kim, B. S. Org. Lett. 2011, 13, 3738‐3741. (e)
Youn, S. W.; Ko, T. Y.; Jang, Y. H. Angew. Chem., Int. Ed. 2017, 56, 6636‐6640.
(5) Maity, S.; Zheng, N. Angew. Chem., Int. Ed. 2012, 51, 9562‐9566.
(6) Liwosz, T. W.; Chemler, S. R. Chem.–Eur. J. 2013, 19, 12771‐12777.
(7) (a) Youn, S. W.; Ko, T. Y.; Jang, M. J.; Jang, S. S. Adv. Synth. Catal. 2015, 357, 227‐
234. (b) Jang, Y. H.; Youn, S. W. Org. Lett. 2014, 16, 3720‐3723.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(8) Ma, A.‐L.; Li, Y.‐L.; Li, J.; Deng, J. RSC Adv. 2016, 6, 35764‐35770.
(9) (a) Fra, L.; Millan, A.; Souto, J. A.; Mu
7353. (b) Fra, L.; Muniz, K. Chem. –Eur. J. 2016, 22, 4351‐4354.
̃
niz, K. Angew. Chem., Int. Ed. 2014, 53, 7349‐
̃
(10) Li, Y.‐L.; Li, J.; Ma, A.‐L.; Huang, Y.‐N.; Deng, J. J. Org. Chem. 2015, 80, 3841‐3851.
(11) Ortgies, S.; Breder, A. Org. Lett. 2015, 17, 2748‐2751.
(12) Zhang, X.; Guo, R. Zhao, X. Org. Chem. Front. 2015, 2, 1334‐1337.
(13) For selected recent reviews, see: (a) Yang, L.; Huang, H. Chem. Rev. 2015, 115,
3468‐3517. (b) Gensch, T.; Hopkinson, M. N.; Glorius, F.; Wencel‐Delord, J. Chem. Soc.
Rev. 2016, 45, 2900‐2936. (c) Zhu, R.‐Y.; Farmer, M. E.; Chen, Y.‐Q.; Yu, J.‐Q. Angew.
Chem., Int. Ed. 2016, 55, 10578‐10599. (d) Dong, Z.; Ren, Z.; Thompson, S. J.; Xu, Y.;
Dong, G. Chem. Rev. 2017, 117, 9333‐9403. (e) Hummel, J. R.; Boerth, J. A.; Ellman, J.
A. Chem. Rev. 2017, 117, 9163‐9227.
(14) (a) Wang, L.; Ferguson, J.; Zeng, F. Org. Biomol. Chem. 2015, 13, 11486‐11491.
(b) Wu, L.; Meng, Y.; Ferguson, J.; Wang, L.; Zeng, F. J. Org. Chem. 2017, 82, 4121‐4128.
(15) (a) Wang, D.; Weinstein, A. B.; White, P. B.; Stahl, S. S. Chem. Rev.
DOI:10.1021/acs.chemrev.7b00334. (b) He, Z.; Kirchberg, S.; Fröhlich, R.; Studer, A.
Angew. Chem., Int. Ed. 2012, 51, 3699‐3702. (c) Yoo, K. S.; Yoon, C. H.; Jung, K. W.; J.
Am. Chem. Soc. 2006, 128, 16384‐16393. (d) Andappan, M. M. S.; Nilsson, P.; Larhed,
M. Chem. Commun. 2004, 218‐219. (e) Jung, Y. C.; Mishra, R. K.; Yoon, C. H.; Jung, K.
W. Org. Lett. 2003, 5, 2231‐2234 (f) Yoon, C. H.; Yoo, K. S.; Yi, S. W.; Mishra, R. K.; Jung,
K. W. Org. Lett. 2004, 6, 4037‐4039.
(16) A selected review on C−H arylaꢁon with organometallics: Giri, R.; Thapa, S.;
Kafle, A. Adv. Synth. Catal. 2014, 356, 1395‐1411.
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(17) Arienti, A.; Bigi, F.; Maggi, R.; Marzi, E.; Moggi, P.; Rastelli, M.; Sartori, G.;
Tarantola, F. Tetrahedron 1997, 53, 3795‐3804.
6
7
(18) Yanai, H.; Mimura, H.; Kawada, K.; Taguchi, T. Tetrahedron 2007, 63, 2153‐2160.
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