Palladium-Catalyzed Direct C2-Biarylation of Indoles

Article abstract of DOI:10.1021/acs.joc.1c01123

Biaryl and indole units are important structural motifs in several bioactive molecules and functional materials. We have accomplished straightforward access to C2-biarylated indole derivatives through palladium-catalyzed C-H activation strategy with a bro

Full text of DOI:10.1021/acs.joc.1c01123

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Palladium-Catalyzed Direct C2-Biarylation of Indoles
Tamilarasu Murugesan, Chinraj Sivarajan, Chithra Mohan Jayakumari, Rajat Kumar Singh,
Sivaranjana Reddy Vennapusa, and Alagiri Kaliyamoorthy*
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Supporting Information
ACCESS
ABSTRACT: Biaryl and indole units are important structural
motifs in several bioactive molecules and functional materials. We
have accomplished straightforward access to C2-biarylated indole
derivatives through palladium-catalyzed C−H activation strategy
with a broad range of substrate scope in yields of 24 to 92%.
Besides, the UV/visible absorption and fluorescence properties of
the ensuing products were explored. The calculated higher dihedral
angle and rotational barrier values for the selected C2-biarylated indoles show that these compounds may display atropisomerism at
room temperature.
Scheme 1. Palladium-Catalyzed C2-Monoarylation and
-Biarylation of Indoles
iaryl compounds are one of the privileged molecules in
Bdrug discovery, and 4.3% of known drugs contain a
biphenyl framework. Besides, the presence of aromatic
substituents in a drug molecule enhances its binding to
proteins and influences the interaction between the aromatic
and hydrophobic residues. Furthermore, biaryl units are the
essential linchpin in ligands for asymmetric catalysis, precursor
for organic light-emitting compounds, organic electrolumines-
cent materials, and liquid crystals.1 Arylated indole and its
congeners are a central skeleton in many bioactive molecules.
In general, cross-coupling reactions have been historically used
to synthesize such skeletons from prefunctionalized indoles.2
In 2006, C2-arylation of electron-rich heteroarenes using
diaryliodonium salts as the arylating reagents in the presence of
Pd(II)-catalyst was reported by the Sanford group (Scheme
1a).3a Later, Fagnou and co-workers delineated their discovery
of palladium-catalyzed oxidative C2-arylation of indoles with
arenes in a highly regioselective manner (Scheme 1b).3b In
2008, Gaunt et al. demonstrated Cu(II)-catalyzed site-selective
C−H arylation of indoles at either C3 or C2-position
employing diaryliodonium salts as the arylating source.3c In
the same year, Larrosa and co-workers described the direct C2-
arylation of indoles with iodoarenes using Pd(OAc)2 as the
catalyst (Scheme 1c).3d A few other reports have been
documented for C2-arylation of indoles using aryl boronic
acids and aryldiazonium salts as the arylating agents.4
which often demands electron-rich indoles. To the best of our
knowledge, the synthetic route to C2-biarylation of indoles
Most of the strategies documented for the synthesis of C2-
arylated indoles use indoles without C3-substituent. Only
limited examples of indoles with C3-substituents,3a,5 and
tryptophan derivatives were evaluated for C2-arylation
reaction.6 The introduction of an aryl group into the C2-
position of an N-protected-C3-substituted indole is an arduous
task, owing to the steric congestion exerted by the substituents
present at C3- and N1-positions.5 Besides, the crucial step in
the aforementioned reports are electrophilic palladation step,
Received: May 13, 2021
Published: July 22, 2021
https://doi.org/10.1021/acs.joc.1c01123
J. Org. Chem. 2021, 86, 10838−10851
© 2021 American Chemical Society
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Table 1. Optimization of Reaction Conditions
substrate no.
Pd(OAc)2 (x mol %)
additive (y equiv)
PhI (equiv)
solvent
temp (°C)
time (h)
3aa (%)
4aa (%)
a
1
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.15
0.1
0.05
0.2
Ag2O (1)
AgTFA (1)
2
2
2
10
10
10
10
10
8
DCE
DCE
DCE
TFE
110
110
110
110
110
110
110
70
70
70
70
70
70
70
110
110
110
48
48
48
72
24
24
24
24
24
24
24
24
24
24
24
24
17
16
35
51
64
65
10
88
83
79
33
84
80
9
trace
nd
trace
10
trace
trace
nd
trace
nd
44
nd
nd
nd
nd
nd
nd
nd
trace
nd
trace
2
3
4
5
6
7
Ag2CO3 (1)
Ag2CO3 (2.5)
Ag2CO3 (2.5)
Ag2O (2.5)
AgOTf (2.5)
Ag2CO3(2.5)
Ag2CO3 (2.5)
Ag2CO3 (2.5)
Ag2CO3 (2.5)
Ag2CO3 (2.5)
Ag2CO3 (2.5)
Ag2CO3 (2.5)
HFIP
HFIP
HFIP
HFIP
HFIP
HFlP
HFIP
HFIP
HFIP
HFIP
HFIP
HFIP
b
8
9
10
11
12
13
14
15
16
17
7
5
10
10
10
10
10
10
c
d
Ag2CO3 (2.5)
Ag2CO3 (2.5)
e
0.2
HFIP
24
a
b
c
d
e
TFA (1 mL) and DBU (1 equiv) were used. Average isolated yield of four reactions. No Ag2CO3. No Pd(OAc)2. No TFA, nd = not detected.
with electron-withdrawing substituents at C3-position has not
been documented yet.
biarylated indole (3aa, 17%) along with monoarylated indole
(4aa, 10%) (Table 1, entry 1). The structures of both 3aa and
4aa were unequivocally elucidated by NMR and X-ray analysis.
The use of AgTFA as an additive produced in 3aa and 4aa in
16% and trace, respectively (entry 2). However, an additive
such as Ag2CO3 (1 equiv) rendered 3aa in 35% yield with a
trace amount of 4aa (entry 3). We screened several catalysts,
ligands, additives, and solvents, but none of the combinations
could increase the yield of 3aa (see Supporting Information).
Lately, HFIP has been commonly expended as the solvent for
C−H functionalization reactions, and it is regarded that the
coordinative interaction between HFIP and the metal adds to
the electrophilic metalation step.13 On this basis, the use of
TFE and HFIP as the solvent with 10 equiv of 2a delivered 3aa
in 51% and 64% yields, respectively, along with a trace amount
of biphenyl byproduct (entries 4 and 5). Comparable reactivity
was observed when Ag2CO3 was replaced with Ag2O (entry 6),
whereas, AgOTf diminished the yield of 3aa to 10% along with
44% of 4aa (entry 7). Gratifyingly, the high yield of 3aa was
obtained when the reaction was performed at 70 °C (entry 8),
and no biphenyl byproduct formation was observed under this
optimal reaction conditions. Furthermore, limiting the amount
of PhI from 10 to 8, 7, and 5 equiv decreased the yield of 3aa
to 83%, 79%, and 33% respectively (entries 9 to 11).
Additionally, reducing the catalytic loading of Pd(OAc)2 to
15 mol % and 10 mol % resulted in slight erosion in the yield
of 3aa, and further, reducing the catalyst loading to 5 mol %
significantly reduced the yield to 9% (entries 12 to 14).
Our substrate choice for C−H arylation of indole contains
an electron-withdrawing group such as sulfonyl group at C3-
position because the existence of sulfonyl moiety in a molecule
can improve bioactivity.7a Due to the weak coordination ability
of sulfone with the transition metal-catalysts, the use of sulfone
as the directing group in C−H functionalization reactions has
been less-explored in comparison with other sulfur-containing
compounds such as sulfides and sulfoxides.7b,f In the course of
our attempt toward the development of palladium-catalyzed
C4-arylation of 3-sulfonylindoles (wherein, the sulfonyl group
at the 3-position of indole was expected to act as the directing
group),8 to our surprise, we witnessed C2-biarylation of 3-
sulfonylindoles when iodobenzene was employed as the aryl
source. The consequent biarylated indole (3aa) that has both
biaryl and indole units own high synthetic value.1,9 Thus far,
metal-mediated cross-coupling reactions that use prefunction-
alized indoles are the common way to construct such C2-
biarylated indole derivatives.9 Hitherto, the realization of C2-
biarylated indole derivatives using direct C−H functionaliza-
tion strategy is an unreported outcome, and we wish to
account our new finding in this note.10
The reaction between 3-sulfonylated indole (1a) with
iodobenzene (2a, 2 equiv) in the presence of Pd(OAc)2(20
mol %) using DBU (1 equiv) as a base, trifluoroacetic acid11
(TFA, 1 mL) and silver(I) salts3d,12 such as Ag2O (1 equiv) as
additives in DCE at 110 °C furnished a mixture of C2-
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Control reactions in the absence of either Ag2CO3 or catalyst
resulted in a trace amount of product formation or no reaction,
respectively (entries 15 and 16). Furthermore, the reaction
without TFA produced only a trace amount of product (entry
17). These results signify that the above-mentioned
components are indispensable for the facile C2-biarylation
reaction.
Table 2. Substrate Scope of Palladium-Catalyzed C2-
Biarylation of Indoles
a,b
With the optimal reaction conditions in hand, next, we
explored the substrates scope of various 3-sulfonylated indole
derivatives using 2a as the aryl source (Table 2). 3-phenyl
sulfonyl indoles bearing a variety of N-alkyl substituents such
as benzyl, methyl, and ethyl substituents (1a-1c) rendered the
products 3aa-3ca in 88%, 83%, and 63%, respectively.
Sulfonylated indole carrying a methoxy substituent at 5-
position (1d) furnished a mixture of products 3da (34%) and
4da (36%). Indoles (1e and 1f) connected to a halogen
substituent at 5- and 6-position afforded the respective
products (3ea and 3fa) in good yields. No product formation
observed when 3-sulfonylated 7-azaindole derivative (1g) was
subjected for arylation reaction under the optimized reaction
conditions, presumably due to the catalyst arrest caused by the
Lewis basic nitrogen present on the indole core. When two
equivalents of Sc(OTf)3 was employed as the sacrificial Lewis
acid to prevent the catalyst arrest,14 the required product (3ga)
was isolated in 37% yield. Besides, the reaction with 3-
sulfonylated indole bearing electron-withdrawing group such as
an ester functionality at 5-position (1h) underwent a facile
biarylation reaction to give the analogous product (3ha) in
75%, albeit it required an extended reaction time. Whereas the
indole carrying a nitro group at the same position (1i) gave 3ia
in 24% yield along with a trace amount of 4ia.
With regards to the scope of the sulfonyl group, a broad
range of 3-sulfonylated indoles were studied. The aryl sulfonyl
group decorated with electron-donating (1j-1l), halogen (1m),
and electron-withdrawing (1n) substituents at various position
produced the corresponding products (3ja-3na) in the range
of admissible to good yields. Sulfonyl group holding aliphatic
substituent such as (3-methylsulfonyl) indole derivative (1o)
and (3-benzylsulfonyl) indole derivative (1p) also worked well
and furnished the required products (3oa and 3pa) in 61% and
34% yields, respectively. Next, we explored the scope of aryl
iodide source with various 3-sulfonylated indole derivatives
under the same reaction conditions. The use of 4-iodotoluene
(2b) as the aryl source with various 3-sulfonylindoles like (1a,
1f, 1h, 1j, 1k, 1l, and 1m) gave the corresponding biarylated
indoles (3ab, 3fb, 3hb, 3jb, 3kb, 3lb, and 3mb) in the extent
of moderate to good yields, whereas in the case of substrate 1i,
a mixture of products (3ib and 4ib) was observed.
Interestingly, the reaction between aryl iodide such as 1-
bromo-4-iodobenzene (2c) and 1a afforded the respective
product (3ac) in 54% yield. It is noteworthy that the C−I
bond underwent selective coupling reaction in the presence of
Pd(II)-catalyst, and the C−Br bond was intact, and it provides
an opportunity to postsynthetic modification with the C−Br
bond. Moreover, the evaluation of meta-substituted aryl iodide
such as 3-iodoanisole (2d) delivered the associate product
(3ad) albeit in moderate yield. However, ortho-substituted aryl
iodides, and aryl iodides having electron-withdrawing sub-
stituents are poor substrates for this reaction.
a
Initially, we thought that C2-biarylation occurs via two
successive C−H arylation steps. For example, in path A of
Scheme 2; first, the formation of 4lb is directed by the weak
coordination of the sulfonyl group. Then, 4lb undergoes
Unless otherwise noted, all reactions were carried out with 1a−1p (1
equiv), 2a−2d (10 equiv), Pd(OAc)2 (20 mol %), Ag2CO3 (2.5
equiv), and TFA (10 equiv) in HFIP (0.12 M) at 70 °C for 24 h.
b
c
Yield of isolated product. Pd(OAc)2 (10 mol %) was employed.
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C2-biarylation may not proceed via two successive C−H
arylation steps. Furthermore, to validate the possibility of
oxidative C2-biarylation3b of 1a with biphenyl,15 a test reaction
was set up using biphenyl (2e) as the aryl source under the
optimized reaction conditions; however, no reaction took place
in the aforementioned case (Scheme 3c). Besides, a control
reaction was set up using 2-iodobiphenyl (2f) and 1a as the
starting precursors to probe whether 2-iodobiphenyl is the
competent coupling partner in this reaction. However, no
product formation was observed (Scheme 3d).
Scheme 2. Structural Analysis of C2-Biarylated Indole
Obtained from Substituted Iodoarene and 3-Sulfonylindole
A competition experiment between the indole bearing an
electron-donating group (1d) and the indole bearing an
electron-withdrawing group (1h) furnished the target products
3da and 3ha in 33% and 15% yields respectively along with
C2-monoaryl product (4da) in 24% yield (Scheme 4). This
Scheme 4. Competition Experiment
further C−H activation on the aryl ring at the C2-position to
form the C2-biarylated product 5lb (Scheme 2, Path A).
However, the single-crystal structure of C2-biarylated com-
pound 3lb (Scheme 2, Path B) obtained from 1l and 2b
corroborates that C2-biarylation does not proceed as
mentioned in Path A. Also, similar structural pattern was
observed in compounds like 3fb, 3jb, and 3ad (Table 2) which
were derived from substituted iodoarenes. To understand the
precise sequence of reaction mechanism, we performed a few
control reactions using 4aa as the precursor, 2b and ethyl
acrylate (2g) as the coupling partner under identical reaction
conditions (Scheme 3a and 3b). However, we did not observe
the formation of the corresponding C2-biarylated product
(5ab) or alkenylated product (5ag). These results suggest that
outcome implies that indole bearing an electron-donating
group (1d) reacts faster than its counterpart (1h), and the rate
of the reaction largely depends on the electronic factors of the
indole precursor. Therefore, we speculate that the C−H
activation takes place via the electrophilic metalation pathway
(after coordination of the metal to the sulfonyl group).
However, the mechanism for the C2-biarylation step is not
fully understood, which requires further studies.
Scheme 3. Control Experiments
Like rotationally hindered biaryl compounds, the C2-
biarylated-3-sulfonylindoles also possess two rotationally
hindered biaryl axes. The dihedral angle measured (using X-
ray crystal structural analysis) for both biaryl axes of various
C2-biarylated-3-sulfonylindoles were either higher or in line
with the established dihedral angle of twisted biaryl systems
(see Supporting Information).16 Moreover, the higher rota-
tional energy barrier calculated using theoretical analysis for
the selected compounds of C2-biarylated-3-sulfonylindoles
(see Supporting Information) shows that these biaryl
compounds may display atropisomerism at room temper-
ature.17
To explore the synthetic importance of the C2-biarylated-3-
sulfonylindoles, we performed a photophysical study1,9 on
selected compounds. We found that the molecules like 3ab,
3ja, 3lb, 3mb, and 3na exhibited interesting photophysical
properties (See Supporting Information for more details).
To illustrate the practical utility of the present method, we
performed a larger scale reaction using 1a and 2a as the
substrates, and the target product 3aa was isolated in 82% yield
at 90 °C (Scheme 5a).18a Next, we focused on N-
debenzylation of C2-biarylated product (3aa) in the presence
of KOtBu in DMSO, and the corresponding debenzylated
indole 5aa was attained in excellent yields (Scheme 5b).18b
In summary, we have demonstrated a single-step palladium-
promoted synthesis of C2-biarylated-3-sulfonylindoles from 3-
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resulting blackish red reaction mixture was attached with reflux
condenser and stirred at 60 °C for 3 days. Then the reaction mixture
was cooled to room temperature and diluted with ethyl acetate. The
mixture was washed with 5% Na2S2O3, water, and brine and then
dried over anhydrous Na2SO4. The combined organic layer was
concentrated under reduced pressure to afford the brown solid. The
crude product was purified by column chromatography using ethyl
acetate/hexane to afford the desired product.
Scheme 5. (a) Large-Scale Experiment. (b) N-Debenzylation
of 3aa
B. General Procedure for Oxidation of Thioether Derivatives. In a
100 mL two-neck round-bottom flask equipped with a rubber septum
and a magnetic bead was placed thioether (1 equiv). To this was
added NaHCO3 (0.2 M) aqueous solution with acetone (1:1 by
volume), and Oxone (2.5 equiv) was added portionwise. The reaction
mixture was stirred at room temperature under open air for 3 days.
Excess solvent was removed using rotary evaporator, and then the
crude mixture was poured into ice-cold water and extracted with
EtOAc. The organic layer was washed with water and brine and dried
over anhydrous Na2SO4. The combined organic layer was
concentrated under reduced pressure to afford the crude sulfonyl
derivative. The crude product was isolated by column chromatog-
raphy using ethyl acetate/hexane to afford the desired product.
C. General Procedure for Protection of Sulfonyl Derivatives. A
flame-dried round-bottom (RB) flask equipped with a magnetic
stirring bar was charged with sulfonyl derivatives (1 equiv) in DMF,
and it was cooled to 0 °C. NaH (2 equiv) was added in portionwise
and stirred for 30 min followed by the addition of appropriate alkyl
halide (1.1 equiv). The reaction mixture was stirred at 0 °C for 10
min, brought to room temperature, and then further stirred for 3−4 h.
The reaction mixture was diluted with water and extracted with
EtOAc. The organic layer was washed with water and brine and dried
over Na2SO4. The combined organic layer was concentrated under
reduced pressure and then purified by column chromatography using
ethyl acetate/hexane to afford the desired product.
sulfonylindoles and iodoarenes via a C−H activation strategy.
An N-benzyl substituent on the C2-biarylated 3-sulfonylindole
was readily removed under mild reaction conditions to obtain
the respective free indole. We have calculated the rotational
energy barrier and the dihedral angle for the selected C2-
biarylated indoles. In addition, we have uncovered the
interesting UV/visible absorption and fluorescence properties
of newly synthesized C2-biarylated-3-sulfonylindoles. Further
study to understand the reaction mechanism is currently
ongoing in our laboratory.
EXPERIMENTAL SECTION
3-(Phenylthio)-1H-indole (1a-Int-1).20 The title compound was
prepared as described in general procedure A using indole (17.07
mmol, 1 equiv) as starting material. Yield: 3.5 g, 91%, pale yellow
■
General Information. All reactions were carried out using
standard Schlenk techniques under argon condition. Solvents were
obtained from Merck, Alfa Aesar, and Spectrochem. All solvents were
dried as per standard purification techniques and then stored under
appropriate conditions. HFIP was purchased from TCI and used
without any further purification. Iodobenzene and trifluoroacetic acid
were purchased from Spectrochem and used without any further
purification. Analytical thin-layer chromatography was performed by
using aluminum TLC sheets 0.25 mm silica gel 60-F254. Visualization
was carried out under UV light. Column chromatography was carried
out with silica gel 230−400 mesh (Merck). 1H and 13C{1H}
NMRspectra were measured using CDCl3 and DMSO-d6 as solvents
in Bruker 500 MHz NMR instruments. Chemical shifts were set in
parts per million (ppm) to 0.0 ppm for TMS or 7.26 ppm for CDCl3
and DMSO-d6 2.50 ppm. The multiplicities of spectra were denoted
by s = singlet, d = doublet, t = triplet, dd = doublet of doublet, td =
triplet of doublet, dt = doublet of triplet, q = quartet, m = multiplet,
and bs = broad singlet. Coupling constants (J) are reported in hertz
(Hz). Mass spectra were measured using Thermo Scientific Q-
Exactive HRMS and Xevo G2-XS QTof (Quadrupole Time-of-Flight)
Mass Spectrometry. FT-IR spectra were recorded using a Bruker
Alpha II spectrometer. CHNS was analyzed by a varioMICRO CHNS
instrument. The crystal structure was determined using a Bruker AXS
Kappa Apex II ScXRD instrument. Absorption spectra were recorded
using a quartz cuvette of 10 mm path length on a Shimadzu UV-3600
vis−NIR spectrometer. Steady-state fluorescence spectra were
recorded on Horiba Jobin Yvon Fluorimeter equipped with a
thermostat Peltier cell holder in a quartz cuvette of 10 mm path
length. Origin 9.0 Pro. Software was used for structure drawing and
data analysis.
1
solid. H NMR (500 MHz, CDCl3): δ (ppm) δ 8.42 (bs, 1H), 7.66
(d, J = 7.9 Hz, 1H), 7.51 (d, J = 2.1 Hz, 1H), 7.47 (d, J = 8.1 Hz, 1H),
7.33−7.29 (m, 1H), 7.22−7.18 (m, 3H), 7.15 (d, J = 7.4 Hz, 2H),
7.09 (t, J = 7.2 Hz, 1H).
3-(Phenylsulfonyl)-1H-indole (1a-Int-2). The title compound was
prepared as described in procedure B using 1a-Int-1 (4.44 mmol, 1
equiv) as starting material. Yield: 960 mg, 84%, off-white solid. Mp:
1
146.2−154.3 °C. H NMR (500 MHz, CDCl3) δ (ppm): 9.34 (bs,
1H), 8.02−8.00 (m, 2H), 7.90−7.88 (m, 1H), 7.85 (d, J = 3.1 Hz,
1H), 7.50−7.42 (m, 3H), 7.40−7.38 (m, 1H), 7.26−7.22 (m, 2H).
13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 143.1, 136.4, 132.8,
130.2, 129.2, 126.8, 124.1, 123.6, 122.7, 119.5, 116.5, 112.5. IR
(CH2Cl2, cm−1) 3344, 3308, 1588, 1425, 1295, 1147. HRMS (ESI)
m/z calcd for C14H11NO2S [M + H]+; 258.0583, found: 258.0581.
1-Benzyl-3-(phenylsulfonyl)-1H-indole (1a). The title compound
was prepared as described in procedure C using 1a-Int-2 (3.109
mmol, 1 equiv) as starting material. Yield: 640 mg, 59%, off-white
1
solid. Mp: 204.1−214.2 °C. H NMR (500 MHz, CDCl3): δ (ppm)
8.03−8.01 (m, 2H), 7.96−7.92 (m, 1H), 7.82 (s, 1H), 7.51−7.44 (m,
3H), 7.35−7.29 (m, 4H), 7.27−7.23 (m, 2H), 7.14 (d, J = 6.6 Hz,
2H), 5.31 (s, 2H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm)
143.5. 137.1, 135.2, 133.1, 132.6, 129.3, 129.1, 128.6, 127.4, 126.8,
124.6, 123.9, 122.7, 120.1, 115.8, 111.0, 51.1. IR (CH2Cl2, cm−1)
2940, 2870, 1746, 1466, 1151. HRMS (ESI) m/z calcd for
C21H17NO2S [M + H]+; 348.1052, found: 348.1051.
1-Methyl-3-(phenylsulfonyl)-1H-indole (1b). The title compound
was prepared as described in general procedure C using 1a-Int-2
(1.943 mmol, 1 equiv) as starting material. Yield: 452 mg, 86%, off-
A. General Procedure for Synthesis of 3-(Phenylthio)-1H-indole
Derivatives. Thioether derivatives were prepared following a modified
procedure:19 To a solution of 1H-indole (1 equiv) and thiophenol
derivatives (1.1 equiv) in ethanol (20 mL) was added a solution of
potassium iodide (1.1 equiv) and iodine (1.1 equiv) in 3:1 (v/v)
water/ethanol (20 mL) at room temperature under open air. The
1
white solid. Mp: 160.5−165.4 °C. H NMR (500 MHz, CDCl3): δ
(ppm) 8.04−8.01 (m, 2H), 7.95 (m, 1H), 7.77 (s, 1H), 7.50−7.43
(m, 3H), 7.35−7.31 (m, 2H), 7.30−7.27 (m, 1H), 3.83 (s, 3H).
13C{1H} NMR (125 MHz, CDCl3): 143.7, 137.4, 133.8, 132.5, 129.1,
126.8, 124.4, 123.8, 122.6, 120.0, 115.2, 110.4, 33.8. IR (neat, cm−1)
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3082, 2875, 1526, 1310, 1151, 757, 622. HRMS (ESI) m/z calcd for
C15H13NO2S [M + H] ; 272.0739, found: 272.0735.
128.8, 127.3, 127.1, 126.8, 126.1, 122.7, 116.4, 115.6, 112.5, 51.4. IR
(CH2Cl2, cm−1): 3124, 1519, 1314, 1153, 699, 588. HRMS (ESI) m/z
calcd for C21H16BrNO2S [M + 2]+; 428.0130, found: 428.0130.
6-Bromo-3-(phenylthio)-1H-indole (1f-Int-1).23 The title com-
pound was prepared as described in general procedure A using 6-
Bromo indole (5.1 mmol, 1 equiv) as starting material. Yield: 1.2 g,
+
1-Ethyl-3-(phenylsulfonyl)-1H-indole (1c). The title compound
was prepared as described in general procedure C using 1a-Int-2
(1.943 mmol, 1 equiv) as starting material. Yield: 500 mg, 90%, off-
1
white solid. Mp: 139.4−146.2 °C. H NMR (500 MHz, CDCl3): δ
1
(ppm) 8.03 (d, J = 6.9 Hz, 2H), 7.94 (d, J = 7.7 Hz, 1H), 7.84(s, 1H),
7.49−7.43 (m, 3H), 7.36 (d, J = 8 Hz, 1H), 7.31−7.25 (m, 2H), 4.20
(q, 7.3 Hz, 2H), 1.52 (t, J = 7.3 Hz, 3H). 13C{1H} NMR (125 MHz,
CDCl3): δ (ppm) 143.7, 136.6, 132.5, 132.1, 129.1, 126.8, 124.6,
123.6, 122.5, 120.1, 115.2, 110.5, 42.0, 15.1. IR (CH2Cl2, cm−1):
3086, 2995, 1522, 1313, 1150, 751. HRMS (ESI) m/z calcd for
C16H15NO2S [M + H]+; 286.0896, found: 286.0892.
77%, white solid. H NMR (500 MHz, CDCl3): δ (ppm) 8.41 (bs,
1H), 7.61 (d, J = 1.5 Hz, 1H), 7.47 (d, J = 2.5 Hz, 1H), 7.45 (d, J =
8.4 Hz, 1H), 7.26 (dd, J = 8.4 Hz, 1.7 Hz, 1H), 7.18−7.15 (m, 2H),
7.07 (d, J = 8.1 Hz, 3H).
6-Bromo-3-(phenylsulfonyl)-1H-indole (1f-Int-2). The title com-
pound was prepared as described in general procedure B using 1f-Int-
1 (0.986 mmol, 1 equiv) as starting material. Yield: 300 mg, 91%, off-
white solid. Mp: 240.2−245.2 °C. 1H NMR (500 MHz, DMSO-d6): δ
(ppm) 12.40 (s, 1H), 8.24 (s, 1H), 7.98 (dd, J = 7 Hz, 1.5 Hz, 2H),
7.74 (d, J = 8.5 Hz, 1H), 7.71 (d, J = 1.5 Hz, 1H), 7.64−7.56 (m,
3H), 7.37 (dd, J = 8.5 Hz, 1.7 Hz, 1H). 13C{1H} NMR (125 MHz,
DMSO-d6): δ (ppm) 143.1, 137.3, 132.9, 132.6, 129.4, 126.2, 124.8,
122.2, 120.3, 115.9, 115.5, 115.0. IR (CH2Cl2, cm−1): 3263, 3227,
1289, 1146, 731, 592. HRMS (ESI) m/z calcd for C14H10BrNO2S
[M]+; 335.9688, found: 335.9687.
5-Methoxy-3-(phenylthio)-1H-indole (1d-Int-1).21 The title com-
pound was prepared as described in general procedure A using 5-
methoxy indole (6.794 mmol, 1 equiv) as starting material. Yield: 1.5
g, 86%, dark green oil. 1H NMR (500 MHz, CDCl3): δ ppm 8.30 (bs,
1H), 7.35 (d, J = 2.6 Hz, 1H), 7.24 (d, J = 8.7 Hz, 1H), 7.15−7.12
(m, 2H), 7.09−7.07 (m, 2H), 7.05−7.03 (m, 2H), 6.89 (dd, J = 8.8
Hz, 2.4 Hz, 1H), 3.74 (s, 3H).
5-Methoxy-3-(phenylsulfonyl)-1H-indole (1d-Int-2). The title
compound was prepared as described in general procedure B using
1d-Int-1 (1.958 mmol, 1 equiv) as starting material. Yield: 330 mg,
59%, off-white solid. Mp: 151.5−158.4 °C. 1H NMR (500 MHz,
DMSO-d6): δ (ppm) 12.15 (s, 1H), 8.11 (d, J = 3 Hz, 1H), 7.98 (dt, J
= 6.5 Hz, 1.3 Hz, 2H), 7.61−7.53 (m, 3H), 7.40 (d, J = 8.9 Hz, 1H),
7.20 (d, J = 2.4 Hz, 1H), 6.88 (dd, J = 8.8 Hz, 2.4 Hz, 1H), 3.78 (s,
3H). 13C{1H} NMR (125 MHz, DMSO-d6): δ (ppm) 155.2, 143.5,
132.6, 131.7, 131.2, 129.3, 126.1, 123.9, 114.1, 113.8, 113.1, 100.2,
55.4. IR (CH2Cl2, cm−1): 3352, 3289, 1485, 1292, 1141. HRMS
(ESI) m/z calcd for C15H13NO3S [M + H]+; 288.0688, found:
288.0685.
1-Benzyl-6-bromo-3-(phenylsulfonyl)-1H-indole (1f). The title
compound was prepared as described in general procedure C using
1f-Int-2 (0.595 mmol, 1 equiv) as starting material. Yield: 150 mg,
59%, off-white solid. Mp: 204.5−211.3 °C. 1H NMR (500 MHz,
CDCl3): δ (ppm) 8.49 (s, 1H), 7.97 (d, J = 7.3 Hz, 2H), 7.90 (s, 1H),
7.73 (d, J = 8.4 Hz, 1H), 7.62−7.56 (m, 3H), 7.39−7.29 (m, 6H),
5.53 (s, 2H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 143.2,
137.8, 134.7, 133.5, 132.8, 129.4, 129.2, 128.8, 127.3, 126.8, 126.1,
123.4, 121.4, 117.8, 116.4, 114.0, 51.2. IR (CH2Cl2, cm−1): 3129,
3077, 1521, 1313, 1157, 750, 599. HRMS (ESI) m/z calcd for
C21H16BrNO2S [M + 2]+; 428.0130, found: 428.0130.
3-(Phenylthio)-1H-pyrrolo[2,3-b]pyridine (1g-Int-1).21 The title
compound was prepared as described in procedure A using 7-aza
indole (4.23 mmol, 1 equiv) as starting material. Yield: 695 mg, 72%,
1-Benzyl-5-methoxy-3-(phenylsulfonyl)-1H-indole (1d). The title
compound was prepared as described in general procedure C using
1d-Int-2 (0.696 mmol, 1 equiv) as starting material. Yield: 235 mg,
1
1
off-white solid. H NMR (500 MHz, CDCl3): δ (ppm) 12.10 (bs,
89%, pale pink solid. Mp: 184.2−188.1 °C. H NMR (500 MHz,
1H), 8.42 (d, J = 4.6 Hz, 1H), 7.97 (d, J = 7.8 Hz, 1H), 7.72 (s, 1H),
7.17 (q, J = 7.5 Hz, 3H), 7.12−7.07 (m, 3H).
CDCl3): δ (ppm) 8.03−8.0 (m, 2H), 7.76 (s, 1H), 7.52−7.45 (m,
3H), 7.37 (d, J = 2.4 Hz, 1H), 7.35−7.31 (m, 3H), 7.17 (d, J = 9 Hz,
1H), 7.14−7.12 (m, 2H), 6.88 (dd, J = 9 Hz, 2.5 Hz, 1H), 5.28 (s,
2H), 3.85 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm)
156.3, 143.7, 135.2, 133.2, 132.6, 132.0, 129.2, 129.1, 128.6, 127.3,
126.7, 125.5, 115.0, 114.4, 111.9, 101.4, 56.0, 51.3. IR (CH2Cl2,
cm−1): 3134, 3048, 1519, 1304, 1229, 1151. HRMS (ESI) m/z calcd
for C22H19NO3S [M + H]+; 378.1158, found: 378.1154.
3-(Phenylsulfonyl)-1H-pyrrolo[2,3-b] pyridine (1g-Int-2). The
title compound was prepared as described in general procedure B
using 1g-Int-1 (1.77 mmol, 1 equiv) as starting material. Yield: 320
mg, 70%, pale violet solid. Mp: 257.9−259.8 °C. 1H NMR (500 MHz,
DMSO-d6): δ (ppm) 12.89 (bs, 1H), 8.36 (dd, J = 4.7 Hz, 1.3 Hz,
1H), 8.35 (s, 1H), 8.18 (dd, J = 8.0 Hz, 1.4 Hz, 1H), 8.0 (d, J = 7.8
Hz, 2H), 7.62−7.55 (m, 3H), 7.27 (dd, J = 8.0 Hz, 4.7 Hz, 1H).
13C{1H} NMR (125 MHz, DMSO-d6): δ (ppm) 148.3, 145.0, 143.1,
133.1, 132.2, 129.6, 127.4, 126.4, 118.2, 115.8, 113.8. IR (CH2Cl2,
cm−1): 3152, 3026, 2938, 1591, 1417, 1310, 1152. HRMS (ESI) m/z
calcd for C13H10N2O2S [M + H]+; 259.0532, found: 259.0532.
1-Benzyl-3-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (1g). The
title compound was prepared as described in general procedure C
using 1g-Int-2 (0.774 mmol, 1 equiv) as starting material. Yield: 240
mg, 89%, off-white solid. 1H NMR (500 MHz, CDCl3): δ (ppm) 8.43
(d, J = 3.6 Hz, 1H), 8.23 (d, J = 7.8 Hz, 1H), 7.98 (d, 7.4 Hz, 2H),
7.88 (s, 1H), 7.51 (t, J = 7.2 Hz, 1H), 7.46 (t, J = 7.4 Hz, 2H), 7.33
(d, J = 6.8 Hz, 3H), 7.27−7.23 (m, 3H), 5.49 (s, 2H). 13C{1H} NMR
(125 MHz, CDCl3): δ (ppm) 147.7, 145.2, 143.1, 135.7, 132.9, 132.5,
129.3, 129.2, 128.5, 128.4, 128.2, 126.8, 118.7, 117.0, 114.7, 48.8. IR
(CH2Cl2, cm−1): 3137, 3076, 1522, 1312, 1154, 740. HRMS (ESI)
m/z calcd for C20H16N2O2S [M + H]+; 349.1005, found: 349.1002.
Methyl 3-(Phenylthio)-1H-indole-5-carboxylate (1h-Int-1).20 The
title compound was prepared as described in general procedure A
using methylindole-5-carboxylate (2.854 mmol, 1 equiv) as starting
material. Yield: 700 mg, 86%, white solid. 1H NMR (500 MHz,
CDCl3): δ (ppm) 8.81 (bs, 1H), 8.39 (s, 1H), 7.98 (dd, J = 8.6 Hz,
1.1 Hz, 1H), 7.55 (d, J = 2.4 Hz, 1H), 7.45 (d, J = 8.6 Hz, 1H), 7.17
(t, J = 7.6 Hz, 2H), 7.10−7.05 (m, 3H), 3.90 (s, 3H).
5-Bromo-3-(phenylthio)-1H-indole (1e-Int-1).20 The title com-
pound was prepared as described in general procedure A using 5-
Bromo indole (5.1 mmol, 1 equiv) as starting material. Yield: 1.5 g,
1
97%, pale yellow solid. H NMR (500 MHz, CDCl3): δ (ppm) 8.43
(bs, 1H), 7.76 (d, J = 1.7 Hz, 1H), 7.49 (d, J = 2.6 Hz, 1H), 7.35 (dd,
J = 8.6 Hz, 1.8 Hz, 1H), 7.31 (d, J = 8.5 Hz, 1H), 7.20−7.16 (m, 2H),
7.09−7.07 (m, 3H).
5-Bromo-3-(phenylsulfonyl)-1H-indole (1e-Int-2). The title com-
pound was prepared as described in general procedure B using 1e-Int-
1 (1.644 mmol, 1 equiv) as starting material. Yield: 430 mg, 78%,
yellow solid. Mp: 147.3−152.4 °C. 1H NMR (500 MHz, DMSO-d6):
δ (ppm) 12.49 (bs, 1H), 8.27 (d, J = 3.0 Hz, 1H), 7.97 (d, J = 7.0 Hz,
2H), 7.88 (s, 1H), 7.62−7.56 (m, 3H), 7.49 (d, J = 8.7 Hz, 1H), 7.38
(dd, J = 8.6 Hz, 1.6 Hz, 1H). 13C{1H} NMR (125 MHz, DMSO-d6):
δ (ppm) 143.1, 135.2, 133.1, 132.9, 129.5, 126.2, 126.1, 126.0, 124.8,
120.6, 120.5, 115.1, 114.5, 114.3. IR (CH2Cl2, cm−1): 3321, 3296,
3135, 1455, 1420, 1302, 1146, 731, 609. HRMS (ESI) m/z calcd for
C14H10BrNO2S [M]+; 335.9688, found: 335.9687.
1-Benzyl-5-bromo-3-(phenylsulfonyl)-1H-indole (1e). The title
compound was prepared as described in general procedure C using
1e-Int-2 (1.487 mmol, 1 equiv) as starting material. Yield: 530 mg,
83%, white solid. Mp: 147.3−152.4 °C. 1H NMR (500 MHz,
CDCl3): δ (ppm) 8.10 (d, J = 1.8 Hz, 1H), 8.02−7.99 (m, 2H), 7.80
(s, 1H), 7.55−7.47 (m, 3H), 7.35−7.33 (m, 4H), 7.16 (d, J = 8.8 Hz,
1H), 7.13−7.11 (m, 2H), 5.30 (s, 2H). 13C{1H} NMR (125 MHz,
CDCl3): δ (ppm) 143.2, 135.7, 134.7, 134.0, 132.9, 129.4, 129.3,
Methyl 3-(Phenylsulfonyl)-1H-indole-5-carboxylate (1h-Int-2).
The title compound was prepared as described in general procedure
B using 1h-Int-1 (1.765 mmol, 1 equiv) as starting material. Yield:
10843
https://doi.org/10.1021/acs.joc.1c01123
J. Org. Chem. 2021, 86, 10838−10851

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
1
500 mg, 90%, off-white solid. Mp: 201.9−205.3 °C. H NMR (500
MHz, DMSO-d6): δ (ppm) 12.65 (bs, 1H), 8.45 (d, J = 1.1 Hz, 1H),
8.37 (d, J = 1.8 Hz, 1H), 7.97−7.95 (m, 2H), 7.86 (dd, J = 8.6 Hz, 1.6
Hz, 1H), 7.62−7.58 (m, 4H), 3. 87 (s, 3H). 13C{1H} NMR (125
MHz, DMSO-d6): δ (ppm) 166.6, 143.2, 139.0, 133.9, 133.0, 129.6,
126.1, 124.1, 123.4, 122.9, 120.7, 115.7, 113.2, 52.1. IR (CH2Cl2,
cm−1): 3357, 3277, 1700, 1309, 1148. HRMS (ESI) m/z calcd for
C16H13NO4S [M + H]+; 316.0638, found: 316.0633.
equiv) as starting material. Yield: 190 mg, 84%, off-white solid. Mp:
175.5−181.2 °C. H NMR (500 MHz, CDCl3): δ (ppm) 7.93−7.90
1
(m, 3H), 7.80 (s, 1H), 7.35−7.28 (m, 4H), 7.26−7.23 (m, 4H),
7.15−7.14 (m, 2H), 5.31 (s, 2H), 2.36 (s, 3H). 13C{1H} NMR (125
MHz, CDCl3): δ (ppm) 143.4, 140.6, 137.1, 135.3, 132.9, 129.8,
129.2, 128.5, 127.3, 126.9, 124.6, 123.9, 122.6, 120.1, 116.3, 110.9,
51.1, 21.6. IR (CH2Cl2, cm−1): 3130, 3078, 1523, 1151, 746, 679.
HRMS (ESI) m/z calcd for C22H19NO2S [M + H]+; 362.1209, found:
362.1203.
Methyl 1-Benzyl-3-(phenylsulfonyl)-1H-indole-5 carboxylate
(1h). The title compound was prepared as described in general
procedure C using 1h-Int-2 (0.634 mmol, 1 equiv) as starting
material. Yield: 200 mg, 78%, white solid. Mp: 209.9−213.8 °C. H
3-(o-Tolylthio)-1H-indole (1k-Int-1).22 The title compound was
prepared as described in general procedure A using indole (4.268
mmol, 1 equiv) as starting material. Yield: 580 mg, 57%, white solid.
1H NMR (500 MHz, CDCl3): δ (ppm) 8.38 (bs, 1H), 7.60 (d, J = 7.9
Hz, 1H), 7.45 (d, J = 9.5 Hz, 2H), 7.29 (t, J = 8.1 Hz, 1H), 7.19−7.14
(m, 2H), 6.99 (t, J = 7.1 Hz, 1H), 6.91 (t, J = 7.3 Hz, 1H), 6.74 (d, J
= 7.8 Hz, 1H), 2.51 (s, 3H).
1
NMR (500 MHz, CDCl3): δ (ppm) 8.68 (d, J = 1 Hz, 1H), 8.04 (td, J
= 6.8 Hz, 1.2 Hz, 2H), 7.96 (dd, J = 8.7 Hz, 1.6 Hz, 1H), 7.87 (s,
1H), 7.54−7.46 (m, 3H), 7.35−7.33 (m, 4H), 7.15−7.13 (m, 2H),
5.34 (s, 2H), 3.94 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ
(ppm) 167.3, 143.2, 139.4, 134.7, 134.5, 134.4, 132.9, 129.4, 129.3,
128.8, 127.4, 126.9, 125.3, 124.9, 124.2, 122.7, 117.5, 110.8, 52.3,
51.4. IR (CH2Cl2, cm−1): 3075, 2967, 1725, 1320, 1254, 1154. HRMS
(ESI) m/z calcd for C23H19NO4S [M + H]+; 406.1107, found:
406.1100.
3-(o-Tolylsulfonyl)-1H-indole (1k-Int-2). The title compound was
prepared as described in general procedure B using 1k-Int-1 (0.418
mmol, 1 equiv) as starting material. Yield: 112 mg, 99%, off-white
1
solid. Mp: 189.3−193.8 °C. H NMR (500 MHz, CDCl3): δ (ppm)
9.45 (bs, 1H), 8.26 (d, J = 7.7 Hz, 1H), 7.86 (d, J = 3 Hz, 1H), 7.69
(d, J = 7.9 Hz, 1H), 7.43−7.35 (m, 3H), 7.24−7.15 (m, 3H), 2.54 (s,
3H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 140.4, 137.7,
136.4, 133.2, 132.8, 130.7, 128.7, 126.5, 124.1, 123.5, 122.5, 119.3,
115.7, 112.4, 20.1. IR (CH2Cl2, cm−1): 3380, 3313, 1295, 1146, 687,
584. HRMS (ESI) m/z calcd for C15H13NO2S [M + H]+; 272.0739,
found: 272.0737.
5-Nitro-3-(phenylthio)-1H-indole (1i-Int-1).20 The title com-
pound was prepared as described in general procedure A using 5-
nitroindole (6.167 mmol, 1 equiv) as starting material. Yield: 1.4 g,
1
84%, pale yellow solid. H NMR (500 MHz, CDCl3) δ (ppm) 8.90
(bs, 1H), 8.57 (d, J = 2.1 Hz, 1H), 8.17 (dd, J = 9.0 Hz, 2.2 Hz, 1H),
7.66 (d, J = 2.5 Hz, 1H), 7.51 (d, J = 8.9 Hz, 1H), 7.21−7.18 (m,
2H), 7.13−7.10 (m, 3H).
1-Benzyl-3-(o-tolylsulfonyl)-1H-indole (1k). The title compound
was prepared as described in general procedure C using 1k-Int-2
(0.368 mmol, 1 equiv) as starting material. Yield: 117 mg, 88%, off-
5-Nitro-3-(phenylsulfonyl)-1H-indole (1i-Int-2). The title com-
pound was prepared as described in general procedure B using 1i-Int-
1 (3.699 mmol, 1 equiv) as starting material. Yield: 700 mg, 63%, pink
solid. Mp: 241.1−242.8 °C. 1H NMR (500 MHz, DMSO-d6): δ
(ppm) 12.94 (bs, 1H), 8.64 (d, J = 2.2 Hz, 1H), 8.52 (s, 1H), 8.12
(dd, J = 9.0 Hz, 2.2 Hz, 1H), 8.02−8.00 (m, 2H), 7.71 (d, J = 9 Hz,
1H), 7.64−7.57 (m, 3H). 13C{1H} NMR (125 MHz, DMSO-d6)
142.8, 142.7, 139.5, 135.7, 133.2, 129.7, 126.3, 122.6, 118.6, 116.9,
115.0, 114.0. IR (CH2Cl2, cm−1): 3113, 2872, 1526, 1340, 1144.
HRMS (ESI) m/z calcd for C14H10N2O4S [M + H]+; 303.0434,
found: 303.0432.
1
white solid. Mp: 175.9−183.3 °C. H NMR (500 MHz, CDCl3): δ
(ppm) 8.27 (dd, J = 7.7 Hz, 1.2 Hz, 1H), 7.87 (s, 1H), 7.72 (d, J = 7.9
Hz, 1H), 7.41 (td, J = 7.4 Hz, 1.4 Hz, 1H), 7.37 (d, J = 7.4 Hz, 1H),
7.35−7.30 (m, 4H), 7.25−7.22 (m, 1H), 7.20−7.15 (m, 4H), 5.35 (s,
2H), 2.54 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm)
140.7, 137.6, 137.0, 135.4, 133.7, 133.0, 132.7, 129.3, 128.8, 128.6,
127.3, 126.5, 124.6, 123.9, 122.6, 120.0, 115.1, 110.9, 51.1, 20.1. IR
(CH2Cl2, cm−1): 3074, 2940, 1522, 1309, 1158. HRMS (ESI) m/z
calcd for C22H19NO2S [M + H]+; 362.1209, found: 362.1203.
3-((4-Methoxyphenyl)thio)-1H-indole (1l-Int-1).21 The title com-
pound was prepared as described in general procedure A using indole
(4.268 mmol, 1 equiv) as starting material. Yield: 350 mg, 32%, off-
white solid. 1H NMR (500 MHz, CDCl3): δ (ppm) 8.31 (s, 1H), 7.62
(d, J = 7.9 Hz, 1H), 7.43 (d, J = 2.5 Hz, 1H), 7.39 (d, J = 8.1 Hz, 1H),
7.25−7.22 (m, 1H), 7.16−7.12 (m, 3H), 6.73 (d, J = 8.8 Hz, 2H),
3.72 (s, 3H).
1-Benzyl-5-nitro-3-(phenylsulfonyl)-1H-indole (1i). The title
compound was prepared as described in general procedure C using
1i-Int-2 (0.992 mmol, 1 equiv) as starting material. Yield: 250 mg,
64%, yellow solid. Mp: 208−210.7 °C. 1H NMR (500 MHz, CDCl3):
δ (ppm) 8.84 (d, J = 2.1 Hz, 1H), 8.12 (dd, J = 9.1 Hz, 2.2 Hz, 1H),
8.03 (t, J = 7.8 Hz, 2H), 7.97 (s, 1H), 7.57−7.49 (m, 3H), 7.39−7.35
(m, 4H), 7.16−7.14 (m, 2H), 5.38 (s, 2H). 13C{1H} NMR (125
MHz, CDCl3): δ (ppm) 143.9, 142.6, 139.7, 135.9, 134.1, 133.3,
129.5, 129.1, 127.4, 127.0, 124.0, 119.4, 118.8, 117.1, 111.4, 51.7. IR
(CH2Cl2, cm−1): 3128, 3074, 1528, 1343, 1153, 737. HRMS (ESI)
m/z calcd for C21H16N2O4S [M + H]+; 393.0903, found: 393.0903.
3-(p-Tolylthio)-1H-indole (1j-Int-1).21 The title compound was
prepared as described in general procedure A using indole (4.268
mmol, 1 equiv) as starting material. Yield: 500 mg, 49%, white solid.
1H NMR (500 MHz, CDCl3): δ (ppm) 8.38 (bs, 1H), 7.62 (d, J = 7.9
Hz, 1H), 7.48 (d, J = 2.6 Hz, 1H), 7.43 (d, J = 8.1 Hz, 1H), 7.28−
7.24 (m, 1H), 7.16 (t, J = 7.5 Hz, 1H), 7.03 (d, J = 6.4 Hz, 2H), 6.98
(d, J = 8.1 Hz, 2H), 2.25 (s, 3H).
3-((4-Methoxyphenyl)sulfonyl)-1H-indole (1l-Int-2). The title
compound was prepared as described in general procedure B using
1l-Int-1 (0.783 mmol, 1 equiv) as starting material. Yield: 167 mg,
74%, off-white solid. Mp: 154.6−162.8 °C. 1H NMR (500 MHz,
DMSO-d6): δ (ppm) 9.41 (bs, 1H), 7.94 (dt, J = 8.9 Hz, 2.9 Hz, 2H),
7.88−7.85 (m, 1H), 7.81 (d, J = 3.0 Hz, 1H), 7.40−7.37 (m, 1H),
7.25−7.20 (m, 2H), 6.90 (dt, J = 8.9 Hz, 2.8 Hz, 2H), 3.79 (s, 3H).
13C{1H} NMR (125 MHz, DMSO-d6): δ (ppm) 163.0, 136.5, 134.8,
129.8, 129.0, 124.0, 123.4, 122.5, 119.4, 117.1, 114.4, 112.5, 55.7. IR
(CH2Cl2, cm−1): 3340, 1602, 1506, 1267, 1142. HRMS (ESI) m/z
calcd for C15H13NO3S [M + H]+; 288.0688, found: 288.0684.
1-Benzyl-3-((4-methoxyphenyl)sulfonyl)-1H-indole (1l). The title
compound was prepared as described in general procedure C using 1l-
Int-2 (0.348 mmol, 1 equiv) as starting material. Yield: 125 mg, 95%,
3-Tosyl-1H-indole (1j-Int-2). The title compound was prepared as
described in general procedure B using 1j-Int-1 (0.794 mmol, 1
equiv) as starting material. Yield: 200 mg, 93%, white solid. Mp:
1
172.5−178.7 °C. H NMR (500 MHz, DMSO-d6): δ (ppm) 12.23
1
pink solid. Mp: 168.1−178.5 °C. H NMR (500 MHz, CDCl3): δ
(bs, 1H), 8.16 (s, 1H), 7.85 (d, J = 8.2 Hz, 2H), 7.76 (d, J = 7.8 Hz,
1H), 7.49 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.0 Hz, 2H), 7.25−7.17
(m, 2H), 2.30 (s, 3H). 13C{1H} NMR (125 MHz, DMSO-d6): δ
(ppm) 143.1, 140.6, 136.4, 131.3, 129.7, 126.3, 123.1, 121.7, 118.6,
115.0, 112.8, 20.9. IR (CH2Cl2, cm−1): 3341, 3307, 1604, 1425, 1294,
1146, 687. HRMS (ESI) m/z calcd for C15H13NO2S [M + H]+;
272.0739, found: 272.0736.
(ppm) 7.99 (d, J = 8.0 Hz, 2H), 7.94−7.93 (m, 1H), 7.83 (s, 1H),
7.38−7.31 (m, 4H), 7.29−7.26 (m, 2H), 7.17 (d, J = 6.7 Hz, 2H),
6.95 (d, J = 9.5 Hz, 2H), 5.33 (s, 2H), 3.83 (s, 3H). 13C{1H} NMR
(125 MHz, CDCl3): δ (ppm) 162.9, 137.0, 135.3, 135.2, 132.7, 129.2,
129.0, 128.5, 127.3, 124.4, 123.8, 122.5, 120.0, 116.6, 114.3, 110.9,
55.7, 51.0. IR (CH2Cl2, cm−1): 3131, 2949, 2853, 1602, 1521, 1265,
1147, 744. HRMS (ESI) m/z calcd for C22H19NO3S [M + H]+;
378.1158, found: 378.1157.
1-Benzyl-3-tosyl-1H-indole (1j). The title compound was prepared
as described in general procedure C using 1j-Int-2 (0.626 mmol, 1
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3-((4-Bromophenyl)thio)-1H-indole (1m-Int-1).22 The title com-
pound was prepared as described in general procedure A using indole
(8.536 mmol, 1 equiv) as starting material. Yield: 320 mg, 12%, off-
(1.536 mmol, 1 equiv) as starting material. Yield: 290 mg, 66%, off-
white solid. Mp: 132.0−136.4 °C. H NMR (500 MHz, CDCl3): δ
1
(ppm) 7.97−7.94 (m, 1H), 7.74 (s, 1H), 7.40−7.32 (m, 6H), 7.18 (d,
J = 7 Hz, 2H), 5.34 (s, 2H), 3.17 (s, 3H). 13C{1H} NMR (125 MHz,
CDCl3): δ (ppm) 137.0, 135.2, 132.9, 129.3, 128.6, 127.5, 124.6,
124.0, 122.8, 119.8, 115.3, 111.1, 51.1, 45.6. IR (CH2Cl2, cm−1):
3129, 3052, 2940, 1525, 1306, 1142, 757. HRMS (ESI) m/z calcd for
C16H15NO2S [M + H]+; 286.0896, found: 286.0891.
1
white solid. H NMR (500 MHz, CDCl3): δ (ppm) 8.41 (bs, 1H),
7.56 (d, J = 7.9 Hz, 1H), 7.47 (d, J = 2.6 Hz, 1H), 7.43 (d, J = 8.2 Hz,
1H), 7.29−7.24 (m, 3H), 7.17 (t, J = 7.5 Hz, 1H), 6.95 (d, J = 8.6 Hz,
2H).
3-((4-Bromophenyl)sulfonyl)-1H-indole (1m-Int-2). The title
compound was prepared as described in general procedure B using
1m-Int-1 (0.986 mmol, 1 equiv) as starting material. Yield: 280 mg,
84%, off-white solid. Mp: 187.0−188.7 °C. 1H NMR (500 MHz,
CDCl3): δ (ppm) 12.34 (bs, 1H), 8.21 (d, J = 3.1 Hz, 1H), 7.89 (dd, J
= 6.8 Hz, 1.7 Hz, 2H), 7.76 (d, J = 8.5 Hz, 3H), 7.51 (d, J = 8 Hz,
1H), 7.27−7.19 (m, 2H). 13C{1H} NMR (125 MHz, CDCl3): δ
(ppm) 142.7, 136.5, 132.5, 132.0, 128.3, 126.6, 123.3, 123.0, 122.0,
118.5, 114.0, 113.0. IR (CH2Cl2, cm−1): 3326, 3136, 1713, 1581,
1425, 1147, 749. HRMS (ESI) m/z calcd for C14H10BrNO2S [M +
2]+; 337.9660, found: 337.9660.
1-Benzyl-3-((4-bromophenyl)sulfonyl)-1H-indole (1m). The title
compound was prepared as described in general procedure C using
1m-Int-2 (0.654 mmol, 1 equiv) as starting material. Yield: 250 mg,
90%, off-white solid. Mp: 180.7−185.1 °C. 1H NMR (500 MHz,
CDCl3): δ (ppm) 7.92−7.89 (m, 1H), 7.87 (dt, J = 8.6 Hz, 2.4 Hz,
2H), 7.80 (s, 1H), 7.59 (dt, J = 8.6 Hz, 2.4 Hz, 2H), 7.36−7.31 (m,
4H), 7.29−7.26 (m, 2H), 7.16−7.14 (m, 2H), 5.32 (s, 2H). 13C{1H}
NMR (125 MHz, CDCl3): δ (ppm) 142.6, 137.1, 135.1, 133.2, 132.4,
129.3, 128.7, 128.4, 127.6, 127.4, 124.5, 124.1, 122.9, 119.9, 115.4,
111.1, 51.2. IR (CH2Cl2, cm−1): 3126, 3082, 1521, 1318, 1152, 748.
HRMS (ESI) m/z calcd for C21H16BrNO2S [M + 2]+; 428.0130,
found: 428.0130.
3-(Benzylthio)-1H-indole (1p-Int-1).25 The title compound was
prepared as described in general procedure A using indole (8.536
mmol, 1 equiv) as starting material. Yield: 1.3 g, 64%, off-white solid.
1H NMR (500 MHz, CDCl3) δ (ppm) 7.93 (bs, 1H), 7.68 (d, J = 7.4
Hz, 1H), 7.22−7.13 (m, 6H), 7.04−7.02 (m, 2H), 6.83 (d, J = 2.5 Hz,
1H).
3-(Benzylsulfonyl)-1H-indole (1p-Int-2). The title compound was
prepared as described in general procedure B using 1p-Int-1 (3.51
mmol, 1 equiv) as starting material. Yield: 700 mg, 73%, off-white
solid. Mp: 153.8−156.2 °C. 1H NMR (500 MHz, DMSO-d6): δ
(ppm) 12.14 (bs, 1H), 7.75 (d, J = 3.0 Hz, 1H), 7.59 (d, J = 8 Hz,
1H), 7.52 (d, J = 8.2 Hz, 1H), 7.29−7.21 (m, 4H), 7.15 (t, J = 7.6 Hz,
1H), 7.09 (d, J = 7.0 Hz, 2H), 4.54 (s, 2H). 13C{1H} NMR (125
MHz, DMSO-d6): δ (ppm) 136.1, 132.1, 130.8, 129.6, 128.1, 124.0,
123.0, 121.5, 118.9, 112.7, 112.2, 62.2. IR (CH2Cl2, cm−1): 3356,
3321, 1516, 1299, 1117. HRMS (ESI) m/z calcd for C15H13NO2S [M
+ H]+; 272.0735, found: 272.0734.
1-Benzyl-3-(benzylsulfonyl)-1H-indole (1p). The title compound
was prepared as described in general procedure C using 1p-Int-2
(1.842 mmol, 1 equiv) as starting material. Yield: 650 mg, 97%, off-
1
white solid. Mp: 161.1−162.4 °C. H NMR (500 MHz, CDCl3) δ
(ppm) 7.78 (d, J = 7.1 Hz, 1.5 Hz, 1H), 7.33−7.30 (m, 4H), 7.29−
7.23 (m, 4H), 7.17 (t, J = 7.6 Hz, 2H), 7.05−7.02 (m, 4H), 5.23 (s,
2H), 4.40 (s, 2H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm)
136.7, 135.3, 134.4, 130.8, 129.5, 129.2, 128.5, 127.2, 125.1, 123.9,
122.8, 120.0, 111.8, 110.9, 63.2, 51.0. IR (CH2Cl2, cm−1): 3051, 2935,
1523, 1311. HRMS (ESI) m/z calcd for C22H19NO2S [M + H]+;
362.1203, found: 362.1201.
3-((4-Nitrophenyl)thio)-1H-indole (1n-Int-1).19 The title com-
pound was prepared as described in general procedure A using indole
(8.536 mmol, 1 equiv) as starting material. Yield: 2.23 g, 97%, yellow
solid. 1H NMR (500 MHz, CDCl3): δ (ppm) 8.62 (bs, 1H), 8.0 (dt, J
= 9 Hz, 2.6 Hz, 2H), 7.55−7.50 (m, 3H), 7.32 (t, J = 7.6 Hz, 1H),
7.20 (t, J = 7.5 Hz, 1H), 7.13 (dt, J = 9 Hz, 2.6 Hz, 2H).
5-Nitro-3-(phenylsulfonyl)-1H-indole (1n-Int-2). The title com-
pound was prepared as described in general procedure B using 1n-Int-
1 (3.699 mmol, 1 equiv) as starting material. Yield: 700 mg, 63%, off-
white solid. Mp: 241.1−242.8 °C. 1H NMR (500 MHz, DMSO-d6) δ
(ppm): δ (ppm) 12.46 (bs, 1H), 8.35 (d, J = 8.8 Hz, 2H), 8.30 (d, J =
3.1 Hz, 1H), 8.22 (d, J = 8.8 Hz, 2H), 7.79 (d, J = 7.7 Hz, 1H), 7.52
(d, J = 7.9 Hz, 1H), 7.28−7.22 (m, 2H). 13C{1H} NMR (125 MHz,
DMSO-d6) 149.7, 148.6, 136.5, 132.8, 127.8, 124.8, 123.5, 123.1,
122.2, 118.4, 113.1, 113.0. HRMS (ESI) m/z calcd for C14H10N2O4S
[M + H]+; 303.0434, found: 303.0432.
1-Benzyl-3-((4-nitrophenyl)sulfonyl)-1H-indole (1n). The title
compound was prepared as described in general procedure C using
1n-Int-2 (1.654 mmol, 1 equiv) as starting material. Yield: 619 mg,
95%, yellow solid. Mp: 145.4−150.0 °C. 1H NMR (500 MHz,
CDCl3): δ (ppm) 8.29 (dt, J = 8.9 Hz, 2.2 Hz, 2H), 8.18 (dt, J = 8.9
Hz, 2.2 Hz, 2H), 7.95−7.92 (m, 1H), 7.84 (s, 1H), 7.38−7.34 (m,
4H), 7.33−7.30 (m, 2H), 7.17−7.15 (m, 2H), 5.34 (s, 2H): 13C{1H}
NMR (125 MHz, CDCl3): δ (ppm) 150.0, 149.2, 137.2, 134.8, 133.9,
129.4, 128.8, 128.1, 127.4, 124.5, 124.4, 123.3, 119.7, 114.2, 111.3,
51.3. IR (CH2Cl2, cm−1): 3126, 3052, 2873, 1536, 1356, 1156, 746.
HRMS (ESI) m/z calcd for C21H16N2O4S [M + H]+; 393.0903,
found: 393.0902.
D. General Experimental Procedure for C2-Biarylation of Indole
Derivatives. To a 15 mL flame-dried sealed tube equipped with a
magnetic stir bar were added indole derivatives (30 mg, 1 equiv), and
then, the tube was evacuated and refilled with argon. To this were
added Pd(OAc)2 (20 mol %), Ag2CO3 (2.5 equiv), aryl iodide (10
equiv), HFIP (0.12 M), and TFA (10 equiv). Then, the reaction
mixture was stirred at 70 °C in preheated oil bath for 24 h. The
resulting mixture was cooled to room temperature, quenched with
saturated NaHCO3(5 mL), and diluted with EtOAc (5 mL). The
crude mixture was washed with brine solution (10 mL), extracted
with ethyl acetate (3 × 5 mL), and dried over anhydrous Na2SO4.
The combined organic layer was evaporated under reduced pressure,
and the crude product was purified by column chromatography using
ethyl acetate/hexane.
2-([1,1′-Biphenyl]-2-yl)-1-benzyl-3-(phenylsulfonyl)-1H-indole
(3aa). The title compound was prepared as described in general
procedure D using 1a (0.086 mmol, 1 equiv) and iodobenzene (2a,
0.86 mmol) as starting materials and purified by column
chromatography using 10% ethyl acetate/hexane. Yield: 38 mg,
88%, white solid. Mp: 129.2−135.4 °C. 1H NMR (500 MHz,
CDCl3): δ (ppm) 8.38 (d, J = 8.1 Hz, 1H), 7.74 (d, J = 8 Hz, 2H),
7.58 (t, J = 7.5 Hz, 1H), 7.50 (d, J = 7.7 Hz, 1H), 7.44 (t, J = 6.9 Hz,
1H), 7.36 (t, J = 7.3 Hz, 3H),7.31−7.27 (m, 2H), 7.15−7.02 (m, 7H),
6.96−6.92 (m, 3H), 6.58 (d, J = 7.5 Hz, 2H), 4.70 (d, J = 16.3 Hz,
1H), 4.56 (d, J = 16.3 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3): δ
(ppm) 144.2, 144.1, 142.2, 139.9, 135.8, 135.4, 133.5, 132.6, 130.7,
130.4, 130.2, 128.9, 128.7, 128.5, 127.6, 127.4, 127.1, 126.9, 126.4,
125.7, 123.5, 122.8, 120.8, 114.5, 111.3, 47.9. IR (CH2Cl2, cm−1):
3078,1461, 1328, 1152, 748. HRMS (ESI) m/z calcd for C33H25NO2S
[M + H]+; 500.1678, found: 500.1678.
3-(Methylsulfonyl)-1H-indole (1o-Int-2). The title compound was
prepared as described in the reported procedure24 with indole (4.268
mmol, 1 equiv) as starting material. Yield: 350 mg, 42%, off-white
1
solid. Mp: 161.8−164 °C. H NMR (500 MHz, CDCl3): δ (ppm)
9.06 (bs, 1H), 7.93 (d, J = 7.3 Hz, 1H), 7.80 (d, J = 1.8 Hz, 1H)7.48
(d, J = 7.5 Hz, 1H), 7.35−7.30 (m, 2H), 3.18 (s, 3H). 13C{1H} NMR
(125 MHz, CDCl3): δ (ppm) 136.3, 129.8, 124.3, 123.7, 122.8, 119.4,
116.5, 112.4, 45.5. IR (CH2Cl2, cm−1): 3143.7, 1424.9, 1298, 1130,
759.3. HRMS (ESI) m/z calcd for C9H9NO2S [M + H]+; 196.0426,
found: 196.0426.
2-([1,1′-Biphenyl]-2-yl)-1-methyl-3-(phenylsulfonyl)-1H-indole
(3ba). The title compound was prepared as described in general
procedure D using 1b (0.11 mmol, 1 equiv) and iodobenzene (2a, 1.1
mmol) as starting materials and purified by column chromatography
1-Benzyl-3-(methylsulfonyl)-1H-indole (1o). The title compound
was prepared as described in general procedure C using 1o-Int-1
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using 20% ethyl acetate/hexane. Yield: 39 mg, 83%, white solid. Mp:
178.2−161.7 °C. 1H NMR (500 MHz, CDCl3): δ (ppm) 8.35 (d, J =
8.0 Hz, 1H), 7.71 (d, J = 7.3 Hz, 2H), 7.63−7.60 (m, 1H), 7.53−7.51
(m, 1H), 7.47−7.40 (m, 2H), 7.36−7.31 (m, 4H), 7.26 (t, J = 8.0 Hz,
1H), 7.12 (d, J = 8.2 Hz, 1H), 7.08 (t, J = 7.3 Hz, 1H), 7.02 (t, J = 7.4
Hz, 2H), 6.88 (d, J = 7.2 Hz, 2H), 3.01 (s, 3H). 13C{1H} NMR (125
MHz, CDCl3): δ (ppm) 144.2, 144.1, 142.5, 140.0, 135.8, 133.1,
132.5, 130.6, 130.0, 128.9, 128.5, 128.4, 127.3, 127.2, 126.9, 126.7,
125.4, 123.4, 122. 7, 120. 7, 113. 5, 110.0, 30.7. IR (CH2Cl2, cm−1):
3076, 2942, 1469, 1310, 1153. HRMS (ESI) m/z calcd for
C27H21NO2S [M + H]+; 424.1365, found: 424.1363.
2-([1,1′-Biphenyl]-2-yl)-1-ethyl-3-(phenylsulfonyl)-1H-indole
(3ca). The title compound was prepared as described in general
procedure D using 1c (0.105 mmol, 1 equiv) and iodobenzene (2a,
1.05 mmol) as starting materials and purified by column
chromatography using 20% ethyl acetate/hexane. Yield: 29 mg,
63%, white solid. Mp: 182.4−194.6 °C. 1H NMR (500 MHz,
CDCl3): δ (ppm) 8.37 (d, J = 7.9 Hz, 1H), 7.74−7.72 (m, 2H), 7.62
(td, J = 8.7 Hz, 1.15 Hz, 1 H), 7.54 (d, J = 7.7 Hz, 1H), 7. 43 (td, J =
8.6 Hz, 1.2 Hz, 2H), 7.36−7.31 (m, 3H), 7.28−7.27 (m, 2H), 7.20 (d,
J = 8.1 Hz, 1H), 7.12−7.01 (m, 5H), 3.56 (q, J = 14.5 Hz, 2 H), 0.87
(t, J = 7.2 Hz, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm)
143.7, 136.6, 132.5, 132.1, 129.1, 126.8, 124.6, 123.6, 122.5, 120.1,
115.2, 110.5, 42.0, 15.1. IR (CH2Cl2, cm−1): 3076, 2992, 2946, 1309,
1151. HRMS (ESI) m/z calcd for C28H23NO2S [M + H]+; 438.1522,
found: 438.1522.
2-([1,1′-Biphenyl]-2-yl)-1-benzyl-5-methoxy-3-(phenylsulfonyl)-
1H-indole (3da). The title compound was prepared as described in
general procedure D using 1d (0.08 mmol, 1 equiv) and iodobenzene
(2a, 0.80 mmol) as starting materials and purified by column
chromatography using 15−20% ethyl acetate/hexane. Yield: 14.3 mg,
34%, white solid. Mp: 201.4−204.7 °C. 1H NMR (500 MHz,
CDCl3): δ (ppm) 7.86 (d, J = 2.4 Hz, 1H), 7.72 (d, J = 8.3 Hz, 2H),
7.57 (td, J = 8.95 Hz, 1.4 Hz, 1H), 7.49−7.43 (m, 2H), 7−37−7.34
(m, 3H), 7.29 (dd, J = 7.6 Hz, 1.2 Hz, 1H), 7.14−7.02 (m, 7H),
6.89−6.88 (m, 2H), 6.81 (d, J = 8.9 Hz, 1H), 6.77 (dd, J = 8.9 Hz, 2.4
Hz, 1H), 6.57 (d, J = 6.8 Hz, 2H), 4.66 (d, J = 16.3 Hz, 1H), 4.48 (d,
J = 16.3 Hz, 1H), 3.92 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ
(ppm) 156.2, 144.2, 144.1, 142.2, 139.9, 135.8, 133.6, 132.6, 130.6,
130.3, 130.1, 128.9, 128.7, 128.5, 127.6, 127.4, 127.1, 126.9, 126.8,
126.5, 126.3, 114.1, 113.9, 112.2, 102.0, 56.0, 48.0. IR (CH2Cl2,
cm−1): 3075, 2944, 2849, 1460, 1296, 1150, 732, 598. HRMS (ESI)
m/z calcd for C34H27NO3S [M + H]+; 530.1784, found: 530.1781.
1-Benzyl-5-methoxy-2-phenyl-3-(phenylsulfonyl)-1H-indole
(4da). The title compound was prepared as described in general
procedure D using 1d (0.08 mmol, 1 equiv) and iodobenzene (2a,
0.80 mmol) as starting materials and purified by column
chromatography using 15−20% ethyl acetate/hexane. Yield: 13 mg,
36%, white solid. Mp: 151.8−156.6 °C. 1H NMR (500 MHz,
CDCl3): δ (ppm) 7.84 (d, J = 2.4 Hz, 1H), 7.62−7.60 (m, 2H),
7.48−7.40 (m, 2H), 7.38−7.35 (m, 2H), 7.32−7.29 (m, 2H), 7.22−
7.19 (m, 5H), 7.09 (d, J = 8.9 Hz, 1H), 6.89 (dd, J = 8.9 Hz, 2.5 Hz,
1H), 6.83−6.82 (m, 2H), 5.06 (s, 2H), 3.94 (s, 3H). 13C{1H} NMR
(125 MHz, CDCl3): δ (ppm) 156.4, 144.7, 144.2, 136.3, 132.3, 131.0,
130.7, 129.9, 129.0, 128.9, 128.7, 128.2, 127.8, 126.6, 126.2, 126.1,
114.4, 113.5, 112.0, 102.2, 56.0, 48.0. IR (CH2Cl2, cm−1): 3077, 2951,
2849, 1454, 1296, 1149. HRMS (ESI) m/z calcd for C28H23NO3S [M
+ H]+; 454.1471, found: 454.1466.
134.0, 133.5, 132.8, 130.9, 130.2, 129.0, 128.8, 128.5, 127.8, 127.5,
127.2, 127.1, 127.0, 126.7, 126.5, 126.3, 123.4, 116.5, 114.3, 112.8,
48.0. IR (CH2Cl2, cm−1): 3078, 2940, 1458, 1393, 1320, 1151, 743,
591. HRMS (ESI) m/z calcd for C33H24BrNO2S [M]+; 578.0783,
found: 578.0768.
2-([1,1′-Biphenyl]-2-yl)-1-benzyl-6-bromo-3-(phenylsulfonyl)-
1H-indole (3fa). The title compound was prepared as described in
general procedure D using 1f (0.070 mmol, 1 equiv) and iodobenzene
(2a, 0.70 mmol) as starting materials and purified by column
chromatography using 15−20% ethyl acetate/hexane. Yield: 30.2 mg,
74%, white solid. Mp: 101.1−109.6 °C. 1H NMR (500 MHz,
CDCl3): δ (ppm) 8.29 (d, J = 8.6 Hz, 1H), 7.71−7.69 (m, 2H), 7.59
(td, J = 7.6 Hz, 1.4 Hz, 1H), 7.50 (dd, J = 7.8 Hz, 0.9 Hz, 1H), 7.46
(tt, J = 7.5 Hz, 1.2 Hz, 1H), 7.41−7.35 (m, 4H), 7.29 (dd, J = 7.6 Hz,
1.1 Hz, 1H), 7.15−7.08 (m, 5H), 7.06−7.03 (m, 2H), 6.85 (d, J = 7.4
Hz, 2H) 6.57 (d, J = 1.4 Hz, 2H), 4.66 (d, J = 16.3, 1H), 4.48 (d, J =
16.3 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 144.7,
143.7, 142.1, 139.7, 137.6, 136.2, 135.2, 133.5, 132.8, 130.9, 130.4,
130.2, 129.0, 128.8, 128.5, 127.8, 127.6, 127.0, 126.9, 126.5, 126.3,
126.1, 124.6, 122.2, 117.2, 115.0, 114.1, 47.9. IR (CH2Cl2, cm−1):
3076, 2938, 1456, 1151, 740, 696, 601. HRMS (ESI) m/z calcd for
C33H24BrNO2S [M + 2]+; 580.0742, found: 580.0743.
2-([1,1′-Biphenyl]-2-yl)-1-benzyl-3-(phenylsulfonyl)-1H-pyrrolo-
[2,3-b]pyridine (3ga). The title compound was prepared by following
a modified general procedure D: A 10 mL flame-dried RB flask was
equipped with 1g (0.0861 mmol, 1 equiv), and the flask was
evacuated and refilled with argon. To this were added Sc(OTf)3
(0.172 mmol, 2 equiv) and HFIP (0.4 mL), and the mixture was
stirred for 30 min at room temperature. Then the reaction mixture
was transferred to a sealed tube containing Pd(OAc)2 (0.017 mmol,
20 mol %), Ag2CO3 (0.215 mmol, 2.5 equiv), iodobenzene (0.86
mmol, 10 equiv), and HFIP (0.3 mL). TFA was added to this
combined mixture (0.86 mmol, 10 equiv), and then the reaction
mixture was stirred at 70 °C in a preheated oil bath for 24 h. The
resulting mixture was cooled to room temperature, quenched with
saturated NaHCO3(5 mL), and diluted with EtOAc (5 mL). The
crude mixture was washed with brine solution (10 mL), extracted
with ethyl acetate (3 × 5 mL), and dried over anhydrous Na2SO4.
The combined organic layer was evaporated under reduced pressure,
and the crude product was purified by column chromatography using
20−30% ethyl acetate/hexane. Yield: 16.1 mg, 37%, white solid. Mp:
200−210.9 °C. 1H NMR (500 MHz, CDCl3): δ (ppm) 8.10 (dd, J =
4.7 Hz, 1.5 Hz, 1H), 8.00 (dd, J = 7.9 Hz, 1.5 Hz, 1H), 7.94 (d, J =
7.8 Hz, 2H), 7.55−7.53 (m, 1H), 7.52−7.48 (m, 4H), 7.38 (s, 1H),
7.32 (d, J = 7.6 Hz, 2H), 7.11−7.09 (m, 4 H), 7.04−7.01 (m, 6H),
5.43 (s, 2H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 147.1,
144.1, 143.5, 140.3, 132.8, 131.8, 130.3, 130.1 129.2, 128.7, 128.5,
128.1, 127.7, 127.2, 126.8, 118.2, 116.2, 114.1, 43.3. IR (CH2Cl2,
cm−1): 3072, 2937, 1521, 1399, 1316, 1156. HRMS (ESI) m/z calcd
for C32H24N2O2S [M + H]+; 501.1631, found: 501.1627.
Methyl 2-([1,1′-Biphenyl]-2-yl)-1-benzyl-3-(phenylsulfonyl)-1H-
indole-5-carboxylate (3ha). The title compound was prepared as
described in general procedure D using 1h (0.074 mmol, 1 equiv) and
iodobenzene (2a, 0.74 mmol) as starting materials with an extended
reaction time (72 h) and purified by column chromatography using
15−20% ethyl acetate/hexane. Yield: 31 mg, 75%, white solid. Mp:
122.3−124.4 °C. 1H NMR (500 MHz, CDCl3): δ (ppm) 9.13 (d, J =
1.3 Hz, 1H), 7.85 (dd, J = 8.7 Hz, 1.6 Hz, 1H), 7.75 (d, J = 7.9 Hz,
2H), 7.61 (td, J = 7.6 Hz, 1.3 Hz, 1H), 7.51 (d, J = 7.7 Hz, 1H), 7.46
(t, J = 7.1 Hz, 1H), 7.41−7.36 (m, 3H), 7.31 (dd, J = 7.6 Hz, 1.1 Hz,
1H), 7.14−7.06 (m, 4H), 7.02 (t, J = 7.7 Hz, 2H), 6.98 (d, J = 8.7 Hz,
1H), 6.86 (d, J = 7.8 Hz, 2H), 6.56 (d, J = 7.1 Hz, 2H), 4.69 (d, J =
16.3 Hz, 1H), 4.54 (d, J = 16.3 Hz, 1H), 3.96 (s, 3H). 13C{1H} NMR
(125 MHz, CDCl3): δ (ppm) 167.7, 145.7, 143.6, 142.1, 139.6, 137.8,
137.3, 135.3, 133.5, 132.9, 130.9, 130.2, 129.0, 128.8, 128.6, 128.5,
127.8, 127.6, 127.1, 126.5, 126.3, 125.2, 125.0, 123.4, 115.9, 111.2,
52.2, 48.0. IR (CH2Cl2, cm−1): 3078, 2968, 1723, 1321, 1246, 1151.
HRMS (ESI) m/z calcd for C35H27NO4S [M + H]+; 558.1733, found:
558.1727.
2-([1,1′-Biphenyl]-2-yl)-1-benzyl-5-bromo-3-(phenylsulfonyl)-
1H-indole (3ea). The title compound was prepared as described in
general procedure D using 1e (0.070 mmol, 1 equiv) and
iodobenzene (2a, 0.70 mmol) as starting materials with extended
reaction time (36 h) and purified by column chromatography using
10−15% ethyl acetate/hexane. Yield: 30.5 mg, 75%, white solid. Mp:
1
130.3−133.3 °C. H NMR (500 MHz, CDCl3): δ (ppm) 8.59 (s,
1H), 7.71 (d, J = 7.8 Hz, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.50−7.45 (m,
2H), 7.39−7.36 (m, 3H), 7.31 (d, J = 7.6 Hz, 1H), 7.22 (d, J = 8.7
Hz, 1H), 7.14−7.02 (m, 6H), 6.84−6.78 (m, 3H), 6.55 (d, J = 7.2 Hz,
2H), 4.67 (d, J = 16.2 Hz, 1H), 4.47 (d, J = 16.3 Hz, 1H). 13C{1H}
NMR (125 MHz, CDCl3): δ (ppm) 145.1, 143.6, 142.1, 139.6, 135.3,
10846
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Note
2-([1,1′-Biphenyl]-2-yl)-1-benzyl-5-nitro-3-(phenylsulfonyl)-1H-
indole (3ia). The title compound was prepared as described in
general procedure D using 1i (0.076 mmol, 1 equiv) and iodobenzene
(2a, 0.76 mmol) as starting materials with an extended reaction time
(72 h) and purified by column chromatography using 15−20% ethyl
acetate/hexane. Yield: 10 mg, 24%, white solid. Mp: 140.6−145.6 °C.
1H NMR (500 MHz, CDCl3): δ (ppm) 9.34 (d, J = 2.2 Hz, 1H), 8.02
(dd, J = 9.1 Hz, 2.2 Hz, 1H), 7.74−7.72 (m, 2H), 7.64 (td, J = 7.6 Hz,
1.3 Hz, 1H), 7.55−7.52 (m, 1H), 7.49 (tt, J = 7.4 Hz, 1.1 Hz, 1H),
7.45−7.35 (m, 4H), 7.17−7.09 (m, 4H), 7.04 (t, J = 7.7 Hz, 2H),
6.99 (d, J = 9.1 Hz, 1H), 6.82−6.80 (m, 2H), 6.56 (d, J = 7.1 Hz,
2H), 4.72 (d, J = 16.2 Hz, 1H), 4.51 (d, J = 16.3 Hz, 1H). 13C{1H}
NMR (125 MHz, CDCl3): δ (ppm) 147.3, 144.0, 143.0, 142.1, 139.4,
138.0, 137.6, 137.4, 134.8, 133.5, 133.2, 131.3, 130.4, 129.2, 129.0,
128.6, 128.5, 128.1, 127.8, 127.6, 127.2, 126.3, 125.9, 125.1, 119.1,
118.0, 117.2, 111.6, 48.4. IR (CH2Cl2, cm−1): 3081, 2943, 1530, 1343,
1153. HRMS (ESI) m/z calcd for C33H24N2O4S [M + H]+; 545.1529,
found: 545.1529.
2-([1,1′-Biphenyl]-2-yl)-1-benzyl-3-((4-bromophenyl) sulfonyl)-
1H-indole (3ma). The title compound was prepared as described in
general procedure D using 1m (0.070 mmol, 1 equiv) and
iodobenzene (2a, 0.70 mmol) as starting materials and purified by
column chromatography using 15−20% ethyl acetate/hexane. Yield:
1
29 mg, 71%, white solid. Mp: 195.2−211.1 °C. H NMR (500 MHz,
CDCl3): δ (ppm) 8.31 (d, J = 8.1 Hz, 1H), 7.60−7.57 (m, 3H),
7.53−7.49 (m, 3H), 7.36 (td, J = 7.5 Hz, 1.2 Hz, 1H), 7.30 (t, J = 7.4
Hz, 1H), 7.20 (dd, J = 7.7 Hz, 1.1 Hz, 1H), 7.18−7.13 (m, 3H),
7.12−7.06 (m, 5H), 7.01−6.98 (m, 3H), 6.60 (d, J = 6.9 Hz, 2H),
4.75 (d, J = 16.2 Hz, 1H), 4.64 (d, J = 16.3 Hz, 1H). 13C{1H} NMR
(125 MHz, CDCl3): δ (ppm) 144.5, 143.2, 142.3, 139.8, 135.6, 135.5,
133.0, 132.2, 130.7, 130.3, 128.7, 128.5, 128.4, 127.6, 127.5, 127.1,
127.0, 126.4, 125.6, 123.7, 122.9, 120.6, 113.8, 111.5, 48.0. IR
(CH2Cl2, cm−1): 3075, 3047, 2943, 1394, 1330, 1150, 744. HRMS
(ESI) m/z calcd for C33H24BrNO2S [M + 2]+; 580.0742, found:
580.0765.
2-([1,1′-Biphenyl]-2-yl)-1-benzyl-3-((4-nitrophenyl)sulfonyl)-1H-
indole (3na). The title compound was prepared as described in
general procedure D using 1n (0.076 mmol, 1 equiv) and
iodobenzene (2a, 0.76 mmol) as starting materials and purified by
column chromatography using 15−20% ethyl acetate/hexane. Yield:
26.9 mg, 65%, yellow solid. Mp: 109−111.2 °C. 1H NMR (500 MHz,
CDCl3): δ (ppm) 8.29 (d, J = 8.1 Hz, 1H), 8.18 (d, J = 8.8 Hz, 2H),
7.86 (d, J = 8.7 Hz, 2H), 7.62 (t, J = 7.5 Hz, 1H), 7.54 (d, J = 7.7 Hz,
1H), 7.39−7.32 (m, 2H), 7.22−7.10 (m, 6H), 7.09−7.03 (m, 3H),
6.97 (d, J = 7.4 Hz, 2H), 6.62 (d, J = 7.2 Hz, 2H), 4.78 (d, J = 16.3
Hz, 1H), 4.69 (d, J = 16.3 Hz, 1H). 13C{1H} NMR (125 MHz,
CDCl3): δ (ppm) 149.9, 149.6, 145.2, 142.2, 139.7, 135.7, 135.4,
132.7, 131.0, 130.5, 128.8, 128.6, 128.0, 127.8, 127.7, 127.1, 126.8,
126.4, 125.5, 124.2, 124.1, 123.3, 120.4, 112.6, 111.7, 48.1. IR
(CH2Cl2, cm−1): 3117, 3076, 1536, 1354, 1152, 744. HRMS (ESI)
m/z calcd for C33H24N2O4S [M + H]+; 545.1529, found: 545.1512.
2-([1,1′-Biphenyl]-2-yl)-1-benzyl-3-(methylsulfonyl)-1H-indole
(3oa). The title compound was prepared as described in general
procedure D using 1o (0.105 mmol, 1 equiv) and iodobenzene (2a,
1.05 mmol) as starting materials and purified by column
chromatography using 10−15% ethyl acetate/hexane. Yield: 28 mg,
61%, white solid. Mp: 121.2−124.2 °C. 1H NMR (500 MHz,
CDCl3): δ (ppm) 8.00 (d, J = 8.0 Hz, 1H), 7.57−7.52 (m, 2H), 7.34
(td, J = 8.5 Hz, 1.6 Hz, 1H), 7.31−7.26 (m, 2H), 7.24−7.21 (m, 1H),
7.20−7.15 (m, 9H), 6.77−6.76 (m, 2H), 5.01 (s, 2H), 2.66 (s, 3H).
13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 143.9, 142.4, 140.4,
2-([1,1′-Biphenyl]-2-yl)-1-benzyl-3-tosyl-1H-indole (3ja). The
title compound was prepared as described in general procedure D
using 1j (0.083 mmol, 1 equiv) and iodobenzene (2a, 0.83 mmol) as
starting materials at 100 °C with an extended reaction time (48 h)
and purified by column chromatography using 15−20% ethyl acetate/
1
hexane. Yield: 36 mg, 84%, white solid. Mp: 153.4−155.8 °C. H
NMR (500 MHz, CDCl3): δ (ppm) 8.37 (d, J = 8.1 Hz, 1H), 7.65 (d,
J = 8.1 Hz, 2H), 7.58 (td, J = 7.6 Hz, 1.1 Hz, 1H), 7.51 (d, J = 7.5 Hz,
1H), 7.37 (t, J = 7.5 Hz, 1H), 7.29 (t, J = 7.4 Hz, 2H), 7.17−7.04 (m,
9H), 6.98−6.94 (m, 3H), 6.58 (d, J = 7.3 Hz, 2H), 4.71 (d, J = 16.3
Hz, 1H), 4.58 (d, J = 16.3 Hz, 1H), 2.33 (s, 3H). 13C{1H} NMR (125
MHz, CDCl3): δ (ppm) 144.0, 143.3, 142.2, 141.3, 139.9, 135.8,
135.4, 133.4, 130.6, 130.2, 129.5, 128.8, 128.7, 128.4, 127.5, 127.4,
127.2, 127.0, 126.9, 126.4, 125.7, 123.4, 122.6, 120.8, 114.8, 111.3,
47.8, 21.6. IR (CH2Cl2, cm−1): 3072, 2937, 1462, 1149. HRMS (ESI)
m/z calcd for C34H27NO2S [M + H]+; 514.1835, found: 514.1833.
2-([1,1′-Biphenyl]-2-yl)-1-benzyl-3-(o-tolylsulfonyl)-1H-indole
(3ka). The title compound was prepared as described in general
procedure D using 1k (0.083 mmol, 1 equiv) and iodobenzene (2a,
0.83 mmol) as starting materials with an extended reaction time (48
h) and purified by column chromatography using 15−20% ethyl
acetate/hexane. Yield: 22.5 mg, 53%, white solid. Mp: 144.5−145.9
°C. 1H NMR (500 MHz, CDCl3): δ (ppm) 8.40 (d, J = 8.1 Hz, 1H),
7.50 (td, J = 7.6 Hz, 1.4 Hz, 1H), 7.44 (d, J = 7.5 Hz, 1H), 7.39 (d, J
= 7.3 Hz, 1H), 7.30−7.27 (m, 2H), 7.23 (td, J = 7.6 Hz, 1.2 Hz, 1H),
7.18 (d, J = 7.7 Hz, 2H), 7.16−7.09 (m, 5H), 7.06−7.00 (m, 4H),
6.86 (d, J = 7.7 Hz, 2H), 6.60 (d, J = 7.3 Hz, 2H), 4.69 (d, J = 16.5
Hz, 1H), 4.56 (d, J = 16.3 Hz, 1H), 2.55 (s, 3H). 13C{1H} NMR (125
MHz, CDCl3): δ (ppm) 144.0, 142.2, 141.7, 139.8, 138.1, 135.9,
135.0, 133.9, 132.6, 132.3, 130.5, 130.0, 128.8, 128.7, 128.5, 128.4,
127.6, 127.4, 126.9, 126.6, 126.5, 126.3, 125.9, 123.4, 122.7, 121.3,
113.7, 111.3, 47.8, 20.5. IR (CH2Cl2, cm−1): 3074, 2947, 1462, 1307,
1154, 746, 702. HRMS (ESI) m/z calcd for C34H27NO2S [M + H]+;
514.1835, found: 514.1835.
2-([1,1′-Biphenyl]-2-yl)-1-benzyl-3-((4-methoxyphenyl) sulfonyl)-
1H-indole (3la). The title compound was prepared as described in
general procedure D using 1l (0.080 mmol, 1 equiv) and iodobenzene
(2a, 0.80 mmol) as starting materials and purified by column
chromatography using 15−20% ethyl acetate/hexane. Yield: 23.2 mg,
55%, white solid. Mp: 183.5−186.9 °C. 1H NMR (500 MHz,
CDCl3): δ (ppm) 8.36 (d, J = 8.1, 1H), 7.69 (d, J = 8.9 Hz, 2H), 7.58
(td, J = 7.6 Hz, 1.3 Hz, 1H), 7.51 (d, J = 7.6 Hz, 1H), 7.36 (td, J = 7.5
Hz, 1.2 Hz, 1H), 7.28 (t, J = 7.6 Hz, 2H), 7.15−7.05 (m, 7H), 7.00
(d, J = 7.9 Hz, 2H), 6.95 (d, J = 8.3 Hz, 1H), 6.83 (d, J = 8.9 Hz, 2H),
6.58 (d, J = 7.0 Hz, 2H), 4.71 (d, J = 16.3 Hz, 1H), 4.58 (d, J = 16.3
Hz, 1H), 3.78 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm)
162.9, 143.7, 142.2, 140.0, 136.2, 135.9, 135.4, 133.5, 130.6, 130.2,
129.1, 128.8, 128.7, 128.5, 127.5, 127.4, 127.3, 126.9, 126.4, 125.6,
123.4, 122.6, 120.8, 115.2, 114.1, 111.3, 55.7, 47.8. IR (CH2Cl2,
cm−1), 30778, 2951, 2856, 1602, 1462, 1327, 1265, 1145. HRMS
(ESI) m/z calcd for C34H27NO3S [M + H]+; 530.1784, found:
530.1790.
137.6, 135.9, 135.8, 131.9, 130.5, 130.4, 129.0, 128.9, 128.5, 127.8,
127.5, 127.2, 126.5, 125.2, 123.8, 122.7, 120.1, 113.2, 111.5, 48.0,
44.8. IR (CH2Cl2, cm−1): 3075, 2941, 1462, 1308, 1140, 738, 703.
HRMS (ESI) m/z calcd for C28H23NO2S [M + H]+; 438.1522, found:
438.1521.
2-([1,1′-Biphenyl]-2-yl)-1-benzyl-3-(benzylsulfonyl)-1H-indole
(3pa). The title compound was prepared as described in general
procedure D using 1p (0.083 mmol, 1 equiv) and iodobenzene (2a,
0.83 mmol) as starting materials and purified by column
chromatography using 10−15% ethyl acetate/hexane. Yield: 14.6
1
mg, 34%, white solid. Mp: 219.3−222.9 °C. H NMR (500 MHz,
CDCl3): δ (ppm) 7.74 (d, J = 7.7 Hz, 1H), 7.47−7.42 (m, 2H), 7.34
(t, J = 7.4 Hz, 1H), 7.26−7.23 (m, 3H), 7.21−7.15 (m, 9H), 7.09−
7.05 (m, 2H), 7.01 (d, J = 7.2 Hz, 2H), 6.69 (d, J = 6.7 Hz, 2H), 6.16
(d, J = 7.5 Hz, 1H), 4.86 (s, 2H) 4.24 (d, J = 13.6 Hz, 1H), 4.08 (d, J
= 13.6 Hz, 1H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 145.1,
142.4, 140.4, 136.1, 135.6, 131.4, 131.3, 130.2, 130.0, 129.5, 129.0,
128.7, 128.6, 128.5, 127.7, 127.5, 127.4, 126.7, 126.3, 125.6, 123.6,
122.6, 120.1, 111.3, 110.7, 62.9, 47.8. IR (CH2Cl2, cm−1): 2936, 2879,
1463, 131, 1120, 747. HRMS (ESI) m/z calcd for C34H27NO2S [M +
H]+; 514.1835, found: 514.1835.
1-Benzyl-2-(4,4′-dimethyl-[1,1′-biphenyl]-2-yl)-3-(phenylsulfon-
yl)-1H-indole (3ab). The title compound was prepared as described
in general procedure D using 1a (0.086 mmol, 1 equiv) and 4-
iodotoluene (2b, 0.86 mmol) as starting materials and purified by
column chromatography using 15−20% ethyl acetate/Hexane. Yield:
1
42 mg, 92%, white solid. Mp: 189.7−193.9 °C. H NMR (500 MHz,
10847
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Note
1
CDCl3): δ (ppm) 8.42 (d, J = 8.1 Hz, 1H), 7.76 (d, J = 8 Hz, 2H),
7.47 (t, J = 7.4 Hz, 1H), 7.39−7.34 (m, 4H), 7.32−7.29 (m, 1H),
7.16−7.09 (m, 2H), 7.07−7.04 (m, 2H), 6.96 (d, J = 8.3 Hz, 1H),
6.89−6.82 (m, 5H), 6.55 (d, J = 7.3 Hz, 2H), 4.70 (d, J = 16.3 Hz,
1H), 4.62 (d, J = 16.3 Hz, 1H), 2.29 (s, 3H), 2.22 (s, 3H). 13C{1H}
NMR (125 MHz, CDCl3): δ (ppm) 144.8, 144.3, 139.3, 137.0, 136.8,
136.2, 135.9, 135.4, 133.8, 132.5, 131.3, 130.0, 129.2, 128.8, 128.6,
128.5, 127.4, 126.9, 126.8, 126.4, 125.8, 123.4, 122.7, 120.8, 114.2,
111.4, 47.9, 21.1, 21.0. IR (CH2Cl2, cm−1): 3075, 2937, 1459, 1328,
1151. HRMS (ESI) m/z calcd for C35H29NO2S [M + H]+; 528.1991,
found: 528.1989.
1-Benzyl-6-bromo-2-(4,4′-dimethyl-[1,1′-biphenyl]-2-yl)-3-(phe-
nylsulfonyl)-1H-indole (3fb). The title compound was prepared as
described in general procedure D using 1f (0.070 mmol, 1 equiv) and
4-iodotoluene (2b, 0.70 mmol) as starting materials and purified by
column chromatography using 15−20% ethyl acetate/hexane. Yield:
33.5 mg, 78%, white solid. Mp: 221.5−234.8 °C. 1H NMR (500 MHz,
CDCl3): δ (ppm) 8.31 (d, J = 8.6 Hz, 1H), 7.71 (d, J = 7.8 Hz, 2H),
7.47 (t, J = 7.4 Hz, 1H), 7.42−7.36 (m, 5H), 7.15−7.12 (m, 2H),
7.10−7.07 (m, 2H), 6.88 (s, 1H), 6.85 (d, J = 8.1 Hz, 2H), 6.79 (d, J
= 8.1 Hz, 2H), 6.54 (d, J = 7.2 Hz, 2H), 4.64 (d, J = 16.3 Hz, 1H),
4.52 (d, J = 16.3 Hz, 1H), 2.29 (s, 3H), 2.24 (s, 3H). 13C{1H} NMR
(125 MHz, CDCl3): δ (ppm) 145.3, 143.9, 139.2, 137.0, 136.8, 136.4,
136.2, 135.3, 133.9, 132.7, 131.6, 130.0, 129.3, 128.9, 128.7, 128.4,
127.7, 127.0, 126.4, 126.3, 126.0, 124.7, 122.2, 117.0, 114.6, 114.2,
48.0, 21.2, 21.0. IR (CH2Cl2, cm−1): 3047, 2968, 2936, 1152. HRMS
(ESI) m/z calcd for C35H28BrNO2S [M + 2]+; 608.1096, found:
608.1076.
hexane. Yield: 10 mg, 27%, off-white solid. Mp: 217.1−221.3 °C. H
NMR (500 MHz, CDCl3): δ (ppm) 9.28 (d, J = 2.1 Hz, 1H), 8.25
(dd, J = 9.1 Hz, 2.2 Hz, 1H), 7.78 (s, 1H), 7.64 (d, J = 9.1 Hz, 1H),
7.55 (d, J = 7.9 Hz, 2H), 7.46−7.33 (m, 7H), 7.29−7.22 (m, 4H),
5.24 (d, J = 14.3 Hz, 1H), 4.81 (d, J = 14.3 Hz, 1H), 2.51 (s, 3H).
13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 144.9, 143.8, 143.4,
138.6, 137.4, 136.8, 135.9, 135.8, 134.3, 132.7, 131.9, 131.3, 129.7,
129.5, 129.4, 128.7, 128.4, 127.2, 126.5, 125.9, 119.1, 118.7, 115.1,
109.7, 47.6, 21.2. IR (neat, cm−1): 3046, 2938, 1527, 1342, 1151.
Elemental analysis calculated (%): C 69.69, H 4.60, N 5.81, S 6.64;
found: C 64.37, H 4.05, N 5.20, S 5.81. QTof (ESI) m/z calcd for
C28H22N2O4S [M-H]+; 481.1228, found: 481.1212.
1-Benzyl-2-(4,4′-dimethyl-[1,1′-biphenyl]-2-yl)-3-tosyl-1H-indole
(3jb). The title compound was prepared as described in general
procedure D using 1j (0.083 mmol, 1 equiv) and 4-iodotoluene (2b,
0.83 mmol) as starting materials and purified by column
chromatography using 15−20% ethyl acetate/hexane. Yield: 40 mg,
89%, white solid. Mp: 211.3-218.1 °C. 1H NMR (500 MHz, CDCl3):
δ (ppm) 8.39 (d, J = 8.1 Hz, 1H), 7.66 (d, J = 8.2 Hz, 2H), 7.38−7.33
(m, 2H), 7.29 (t, J = 7.5, 1H), 7.18−7.15 (m, 2H), 7.13−7.09 (m,
2H), 7.07−7.04 (m, 2H), 6.96−6.92 (m, 3H), 6.84 (d J = 8.2 Hz,
3H), 6.54 (d, J = 7.3 Hz, 2H), 4.70 (d, J = 16.2 Hz, 1H), 4.63 (d, J =
16.3 Hz, 1H), 2.35 (s, 3H), 2.29 (s, 3H), 2.23 (s, 3H). 13C{1H} NMR
(125 MHz, CDCl3): δ (ppm) 144.6, 143.2, 141.6, 139.3, 137.0, 136.8,
136.2, 135.9, 135.4, 133.8, 131.3, 130.0, 129.4, 129.2, 128.7, 128.5,
127.3, 127.0, 126.4, 125.8, 123.3, 122.5, 120.8, 114.5, 111.3, 47.9,
21.6, 21.1, 21.0. IR (CH2Cl2, cm−1): 3044, 2934, 1462, 1329, 1150,
819, 747, 584. HRMS (ESI) m/z calcd for C36H31NO2S [M + H]+;
542.2148, found: 542.2148.
1-Benzyl-2-(4,4′-dimethyl-[1,1′-biphenyl]-2-yl)-3-(o-tolylsulfon-
yl)-1H-indole (3kb). The title compound was prepared as described in
general procedure D using 1k (0.083 mmol, 1 equiv) and 4-
iodotoluene (2b, 0.83 mmol) as starting materials with extended
reaction time (48 h) and purified by column chromatography using
15−20% ethyl acetate/Hexane. Yield: 29.5 mg, 66%, white solid. Mp:
149.5−152.3 °C. 1H NMR (500 MHz, CDCl3): δ (ppm) 8.45 (d, J =
8.1 Hz, 1H), 7.50 (d, J = 7.9 Hz, 1H), 7.33−7.25 (m, 4H), 7.20 (d, J
= 7.5 Hz, 1H), 7.16−7.03 (m, 5H), 6.98 (d, J = 8.3 Hz, 1H), 6.85 (s,
4H), 6.68 (s, 1H), 6.56 (d, J = 6.9 Hz, 2H), 4.68 (d, J = 16.3 Hz, 1H),
4.60 (d, J = 16.3 Hz, 1H), 2.55 (s, 3H), 2.23 (s, 3H), 2.16 (s, 3H).
13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 144.6, 142.1, 139.4,
Methyl 1-Benzyl-2-(4,4′-dimethyl-[1,1′-biphenyl]-2-yl)-3-(phe-
nylsulfonyl)-1H-indole-5-carboxylate (3hb). The title compound
was prepared as described in general procedure D using 1h (0.074
mmol, 1 equiv) and 4-iodotoluene (2b, 0.74 mmol) as starting
materials with an extended reaction time (48 h) and purified by
column chromatography using 15−20% ethyl acetate/hexane. Yield:
1
30 mg, 69%, white solid. Mp: 205.2−208.1 °C. H NMR (500 MHz,
CDCl3): δ (ppm) 9.15 (d, J = 1.3 Hz, 1H), 7.86 (dd, J = 8.7 Hz, 1.6
Hz, 1H), 7.76 (d, J = 8.3 Hz, 2H), 7.48 (tt, J = 7.4 Hz, 1.1 Hz, 1H),
7.40−7.37 (m, 4H), 7.13−7.10 (m, 1H), 7.08−7.05 (m, 2H), 6.98 (d,
J = 8.7 Hz, 1H), 6.90 (s, 1H), 6.82 (s, 4H), 6.53 (d, J = 7.3 Hz, 2H),
4.69 (d, J = 16.3 Hz, 1H), 4.60 (d, J = 16.3 Hz, 1H), 3.96 (s, 3H),
2.30 (s, 3H), 2.22 (s, 3H). 13C{1H} NMR (125 MHz, CDCl3): δ
(ppm) 167.7, 146.3, 143.8, 139.2, 137.8, 137.0, 136.7, 136.4, 135.4,
133.8, 132.8, 131.6, 130.1, 129.3, 128.9, 128.6, 128.5, 127.6, 127.1,
126.4, 126.3, 125.3, 124.9, 124.8, 123.3, 115.6, 111.2, 52.2, 48.11,
21.1, 21.0. IR (CH2Cl2, cm−1): 3043, 2964, 1723, 1320, 1245, 1151.
HRMS (ESI) m/z calcd for C37H31NO4S [M + H]+; 586.2046, found:
586.2046.
138.1, 137.4, 136.9, 136.8, 136.2, 136.0, 135.0, 134.1, 132.5, 132.2,
131.2, 129.9, 129.1, 128.9, 128.6, 128.5, 127.4, 126.6, 126.4, 126.3,
125.8, 123.2, 122.6, 121.3, 113.5, 111.3, 47.9, 21.1, 21.08, 20.5. IR
(CH2Cl2, cm−1): 3069, 2939, 1461, 1306, 1154, 743. HRMS (ESI)
m/z calcd for C36H31NO2S [M + H]+; 542.2148, found: 542.2130.
1-Benzyl-2-(4,4′-dimethyl-[1,1′-biphenyl]-2-yl)-3-((4-
methoxyphenyl)sulfonyl)-1H-indole (3lb). The title compound was
prepared as described in general procedure D using 1l (0.0795 mmol,
1 equiv) and 4-iodotoluene (2b, 0.79 mmol) as starting materials and
purified by column chromatography using 15−20% ethyl acetate/
1-Benzyl-2-(4,4′-dimethyl-[1,1′-biphenyl]-2-yl)-5-nitro-3-(phe-
nylsulfonyl)-1H-indole (3ib). The title compound was prepared as
described in general procedure D using 1i (0.076 mmol, 1 equiv) and
4-iodotoluene (2b, 0.76 mmol) as starting materials with an extended
reaction time (72 h) and purified by column chromatography using
15−20% ethyl acetate/hexane. Yield: 11 mg, 25%, off-white solid. Mp:
229−238.4 °C. 1H NMR (500 MHz, CDCl3): δ (ppm) 9.36 (s, 1H),
8.02 (d, J = 9.0 Hz, 1H), 7.74 (d, J = 7.7 Hz, 2H), 7.51 (t, J = 7.4 Hz,
1H), 7.42−7.40 (m, 4H), 7.16−7.07 (m, 3H), 7.00 (d, J = 9.0 Hz,
1H), 6.94 (s, 1H), 6.83 (d, J = 7.7 Hz, 2H), 6.76 (d, J = 7.6 Hz, 2H),
6.52 (d, J = 7.5 Hz, 2H), 4.71 (d, J = 16.2 Hz, 1H), 4.57 (d, J = 16.3
Hz, 1H), 2.33 (s, 3H), 2.22 (s, 3H). 13C{1H} NMR (125 MHz,
CDCl3): δ (ppm) 147.9, 144.0, 143.3, 139.2, 138.0, 137.3, 136.7,
136.5, 134.9, 133.8, 133.1, 132.0, 130.2, 129.4, 129.1, 128.8, 128.4,
127.9, 127.3, 126.4, 125.7, 125.2, 118.9, 117.9, 116.9, 111.7, 48.4,
21.1, 21.06. IR (CH2Cl2, cm−1): 2937, 2870, 1527, 1340, 1153.
HRMS (ESI) m/z calcd for C35H28N2O4S [M + H]+; 573.1843,
found: 573.1840.
1
hexane. Yield: 34.2 mg, 77%, white solid. Mp: 197.8−200.3 °C. H
NMR (500 MHz, CDCl3): δ (ppm) 8.38 (d, J = 8.1 Hz, 1H), 7.69
(dt, J = 5.0 Hz, 2.8 Hz, 2H), 7.38−7.32 (m, 2H), 7.29 (t, J = 7.3 Hz,
1H), 7.15−7.09 (m, 2H), 7.07−7.04 (m, 2H), 6.96−6.94 (m, 3H),
6.87−6.83 (m, 5H), 6.55 (d, J = 7.25 Hz, 2H), 4.66 (q, J = 16.3 Hz,
2H), 3.80 (s, 3H), 2.30 (s, 3H), 2.23 (s, 3H). 13C{1H} NMR (125
MHz, CDCl3): δ (ppm) 162.8, 144.3, 139.4, 137.1, 136.8, 136.4,
136.2, 136.0, 135.4, 133.8, 131.3, 130.0, 129.2, 129.1, 128.7, 128.5,
127.4, 127.1, 126.5, 125.7, 123.3, 122.5, 120.8, 115.0, 114.0, 111.3,
55.7, 47.9, 21.1, 21.0. IR (CH2Cl2, cm−1): 3044, 2935, 2857, 1603,
1145. HRMS (ESI) m/z calcd for C36H31NO3S [M + H]+; 558.2097,
found: 558.2095.
1-Benzyl-3-((4-bromophenyl)sulfonyl)-2-(4,4′-dimethyl-[1,1′-bi-
phenyl]-2-yl)-1H-indole (3mb). The title compound was prepared as
described in general procedure D using 1m (0.070 mmol, 1 equiv)
and 4-iodotoluene (2b, 0.70 mmol) as starting materials and purified
by column chromatography using 15−20% ethyl acetate/hexane.
Yield: 36 mg, 84%, white solid. Mp: 227.7−242.1 °C. 1H NMR (500
MHz, CDCl3): δ (ppm) 8.34 (d, J = 8.1 Hz, 1H), 7.60 (dt, J = 8.6 Hz,
1-Benzyl-5-nitro-3-(phenylsulfonyl)-2-(p-tolyl)-1H-indole (4ib).
The title compound was prepared as described in general procedure
D using 1i (0.076 mmol, 1 equiv) and 4-iodotoluene (2b, 0.76 mmol)
as starting materials with an extended reaction time (72 h) and
purified by column chromatography using 15−25% ethyl acetate/
10848
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pubs.acs.org/joc
Note
2.2 Hz, 2H), 7.50 (dt, J = 8.6 Hz, 2.2 Hz, 2H), 7.40 (d, J = 7.8 Hz,
1H), 7.35 (dd, J = 8.0 Hz, 1.2 Hz, 1H), 7.31 (t, J = 7.6 Hz, 1H),
7.18−7.12 (m, 2H), 7.10−7.06 (m, 2H), 7.01 (d, J = 8.3 Hz, 1H),
6.93 (d, J = 8.1 Hz, 2H), 6.87 (d, J = 8.0 Hz, 2H), 6.80 (s, 1H), 6.57
(d, J = 7.2 Hz, 2H), 4.72 (q, J = 16.3 Hz, 2H), 2.29 (s, 3H), 2.24 (s,
3H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 145.0, 143.4,
139.4, 137.0, 136.9, 136.3, 135.7, 135.5, 133.4, 132.0, 131.4, 130.2,
129.3, 128.6, 128.5, 127.5, 127.4, 126.8, 126.5, 125.7, 123.6, 122.8,
120.6, 113.5, 111.5, 48.0, 21.2, 21.0. IR (CH2Cl2, cm−1): 3070, 2939,
2878, 1331, 1149, 746. HRMS (ESI) m/z calcd for C35H28BrNO2S
[M + 2]+; 608.1096, found: 608.1076.
(CH2Cl2, cm−1): 3078,1461, 1328, 1152, 748. HRMS (ESI) m/z
calcd for C33H25NO2S [M + H]+; 500.1678, found: 500.1678.
F. Deprotection of N-Benzyl Group.18b To a flame-dried two-neck
RB flask equipped with a magnetic stirring bar were added 3aa (0.40
mmol, 1 equiv) and KOtBu (2.8 mmol, 7 equiv) in DMSO (5 mL),
and then the reaction mixture was heated at 80 °C for 8 h under
oxygen atmosphere (1 atm). The resulting mixture was cooled to
room temperature, quenched with 0.1 M HCl (10 mL), and diluted
with ethyl (acetate (10 mL). The reaction mixture was extracted with
ethyl acetate (10 mL × 5), washed with water (10 mL) and brine
solution (10 mL), and then dried over anhydrous NaSO4. The
combined organic layer was evaporated under reduced pressure, and
the crude product was purified by column chromatography using 20−
30% ethyl acetate/hexane to afford 5aa. Yield: 161 mg, 98%, white
1-Benzyl-2-(4,4′-dibromo-[1,1′-biphenyl]-2-yl)-3-(phenylsulfon-
yl)-1H-indole (3ac). The title compound was prepared as described in
general procedure D using 1a (0.0863 mmol, 1 equiv) and 1-bromo-
4-iodobenzene (2c, 0.863 mmol) as starting materials at 100 °C and
purified by column chromatography using 15−20% ethyl acetate/
1
solid. Mp: 191.6−198.8 °C. H NMR (500 MHz, CDCl3): δ (ppm)
8.30 (d, J = 8.1 Hz, 1H), 7.94 (bs, 1H), 7.74 (d, J = 8 Hz, 2H), 7.64
(d, J = 6.6 Hz, 1H), 7.57 (td, J = 7.6 Hz, 1.2 Hz, 1H), 7.47−7.43 (m,
3H), 7.35 (t, J = 7.7 Hz, 2H), 7.29 (t, J = 7.6 Hz, 1H), 7.21 (t, J = 7.6
Hz, 1H), 7.13−7.09 (m, 2H), 7.04 (t, J = 7.5 Hz, 2H), 6.82 (d, J = 7.9
Hz, 2H). 13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 144.1, 142.2,
141.7, 139.9, 134.4, 133.4, 132.6, 130.4, 130.3, 128.9, 128.7, 128.5,
128.2, 127.4, 126.9, 126.7, 125.4, 123.9, 122.6, 120.9, 114.4, 111.2. IR
(CH2Cl2, cm−1): 3305, 3079, 2938, 1688, 1543, 1457, 1410, 1310,
1143, 730. HRMS (ESI) m/z calcd for C26H19NO2S [M + H]+;
410.1209, found: 410.1205.
1
hexane. Yield: 30.8 mg, 54%, white solid. Mp: 229.2−235.9 °C. H
NMR (500 MHz, CDCl3): δ (ppm) 8.40 (d, J = 8.1 Hz, 1H), 7.82 (d,
J = 7.5 Hz, 2H), 7.69 (dd, J = 8.2 Hz, 1.9 Hz, 1H), 7.54 (t, J = 7.3 Hz,
1H), 7.47 (t, J = 7.6 Hz, 2H), 7.36−7.32 (m, 2H), 7.22−7.17 (m,
3H), 7.14 (d, J = 7.3 Hz, 1H), 7.09 (t, J = 7.5 Hz, 2H), 7.03−7.00 (m,
4H), 6.47 (d, J = 7.4 Hz, 2H), 4.72 (dd, J = 16.5 Hz, 6.4 Hz, 2H).
13C{1H} NMR (125 MHz, CDCl3): δ (ppm) 144.1, 141.8, 140.3,
137.7, 135.7, 135.2, 135.1, 133.8, 132.9, 131.9, 131.6, 130.4, 129.4,
129.2, 128.8, 127.6, 126.8, 126.0, 125.4, 124.1, 123.2, 122.4, 121.1,
120.8, 115.4, 111.5, 48.1. IR (CH2Cl2, cm−1): 3071, 2937, 2864, 1462,
1152, 735, 599. HRMS (ESI) m/z calcd for C33H23Br2NO2S [M +
Na]+; 679.9688, found: 679.9683.
ASSOCIATED CONTENT
* Supporting Information
■
sı
1-Benzyl-2-(3,3′-dimethoxy-[1,1′-biphenyl]-2-yl)-3-(phenylsul-
fonyl)-1H-indole (3ad). The title compound was prepared as
described in general procedure D using 1a (0.0863 mmol, 1 equiv)
and 3-iodoanisole (2d, 0.863 mmol) as starting materials and purified
by column chromatography using 15−20% ethyl acetate/hexane.
Yield: 17 mg, 35%, white solid. Mp: 196.9−201.5 °C. 1H NMR (500
MHz, CDCl3): δ (ppm) 8.20 (d, J = 8.1 Hz, 1H), 7.85 (d, J = 8.1 Hz,
2H), 7.51−7.44 (m, 2H), 7.39 (t, J = 7.4 Hz, 2H), 7.26−7.23 (m,
1H), 7.14−7.06 (m, 7H), 7.02 (d, J = 8.2 Hz, 1H), 6.89 (d, J = 7.5
Hz, 1H), 6.78 (d, J = 8.3 Hz, 1H), 6.72−6.69 (m, 3H), 4.73 (dd, J =
16.2 Hz, 4.8 Hz, 2H), 3.51 (s, 3H), 3.16 (s, 3H). 13C{1H} NMR (125
MHz, CDCl3): δ (ppm) 159.4, 158.0, 144.3, 144.1, 141.3, 141.1,
136.0, 132.1, 131.5, 129.2, 128.6, 128.5, 127.4, 126.8, 126.0, 123.1,
122.5, 122.4, 121.4, 120.3, 116.9, 114.8, 114.3, 113.4, 111.3, 109.3,
55.5, 54.6, 48.0. IR (CH2Cl2, cm−1): 3072, 2955, 2849, 1268, 1149.
HRMS (ESI) m/z calcd for C35H29NO4S [M + H]+; 560.1890, found:
560.1887.
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c01123.
General experimental procedures, characterization, X-ray
crystal structure data, and copies of the 1H and 13CNMR
spectra of all new compounds (PDF)
Accession Codes
CCDC 2068424, 2068426−2068428, and 2068430−2068431
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge via www.ccdc.ca-
m.ac.uk/data_request/cif, or by emailing data_request@ccdc.
cam.ac.uk, or by contacting The Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax:
+44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
E. Large-Scale Reaction for the Synthesis of 2-([1,1′-Biphenyl]-2-
yl)-1-benzyl-3-(phenylsulfonyl)-1H-indole (3aa). To a 250 mL
flame-dried sealed tube equipped with a magnetic stir bar were
added 1a (2.5 mmol, 868.5 mg, 1 equiv), and then the tube was
evacuated and refilled with argon. To this were added Pd(OAc)2 (0.5
mmol, 112.2 mg, 20 mol %), Ag2CO3 (6.25 mmol, 1.72 g, 2.5 equiv),
iodobenzene (25 mmol, 2.77 mL, 10 equiv), HFIP (15 mL), and TFA
(25 mmol, 1.87 mL 10 equiv). Then the reaction mixture was stirred
at 90 °C in preheated oil bath for 24 h. The resulting mixture was
cooled to room temperature, quenched with saturated NaHCO3(20
mL), and diluted with EtOAc (25 mL). The crude mixture was
washed with brine solution (50 mL), extracted with ethyl acetate (3 ×
20 mL), and dried over anhydrous Na2SO4. The combined organic
layer was evaporated under reduced pressure, and the crude product
was purified by column chromatography using ethyl acetate/hexane
(10−15%). Yield: 1.02 g, 82%, off-white solid. Mp: 129.2−135.4 °C.
1H NMR (500 MHz, CDCl3): δ (ppm) 8.38 (d, J = 8.1 Hz, 1H), 7.74
(d, J = 8 Hz, 2H), 7.58 (t, J = 7.5 Hz, 1H), 7.50 (d, J = 7.7 Hz, 1H),
7.44 (t, J = 6.9 Hz, 1H), 7.36 (t, J = 7.3 Hz, 3H),7.31−7.27 (m, 2H),
7.15−7.02 (m, 7H), 6.96−6.92 (m, 3H), 6.58 (d, J = 7.5 Hz, 2H),
4.70 (d, J = 16.3 Hz, 1H), 4.56 (d, J = 16.3 Hz, 1H). 13C{1H} NMR
(125 MHz, CDCl3): δ (ppm) 144.2, 144.1, 142.2, 139.9, 135.8, 135.4,
133.5, 132.6, 130.7, 130.4, 130.2, 128.9, 128.7, 128.5, 127.6, 127.4,
127.1, 126.9, 126.4, 125.7, 123.5, 122.8, 120.8, 114.5, 111.3, 47.9. IR
■
Alagiri Kaliyamoorthy − School of Chemistry, Indian Institute
of Science Education and Research Thiruvananthapuram,
Vithura, Kerala 695551, India; orcid.org/0000-0002-
5183-8191; Email: alagiri@iisertvm.ac.in
Authors
Tamilarasu Murugesan − School of Chemistry, Indian
Institute of Science Education and Research
Thiruvananthapuram, Vithura, Kerala 695551, India
Chinraj Sivarajan − School of Chemistry, Indian Institute of
Science Education and Research Thiruvananthapuram,
Vithura, Kerala 695551, India
Chithra Mohan Jayakumari − School of Chemistry, Indian
Institute of Science Education and Research
Thiruvananthapuram, Vithura, Kerala 695551, India
Rajat Kumar Singh − School of Chemistry, Indian Institute of
Science Education and Research Thiruvananthapuram,
Vithura, Kerala 695551, India
Sivaranjana Reddy Vennapusa − School of Chemistry, Indian
Institute of Science Education and Research
10849
https://doi.org/10.1021/acs.joc.1c01123
J. Org. Chem. 2021, 86, 10838−10851

The Journal of Organic Chemistry
pubs.acs.org/joc
Note
T. W.; Sheridan, T.; Turnbull, D.; Whitwood, A. C.; Fairlamb, I. J. S.
Mild and Regioselective Pd(OAc)2-Catalyzed C-H Arylation of
Tryptophans by [ArN2]X, Promoted by Tosic Acid. ACS Catal.
2017, 7, 5174−5179. (e) Wang, S.; Yu, B.; Liu, H.-M. Pd(II)-
Catalyzed Intramolecular C(sp2)-H Arylation of Tryptamines Using
the Nonsteric NH2 as a Directing Group. Org. Lett. 2021, 23, 42−48.
(7) (a) Silvestri, R.; Martino, G. D.; Regina, G. L.; Artico, M.; Massa,
S.; Vargiu, L.; Mura, M.; Loi, A. G.; Marceddu, T.; Colla, P. L. Novel
Indolyl Aryl Sulfones Active against HIV-1 Carrying NNRTI
Resistance Mutations: Synthesis and SAR Studies. J. Med. Chem.
Thiruvananthapuram, Vithura, Kerala 695551, India;
orcid.org/0000-0002-8252-9586
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.joc.1c01123
Author Contributions
The manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
2003, 46, 2482−2493. (b) Richter, H.; Beckendorf, S.; Mancheno, O.
̃
Notes
G. Modifiable Sulfur Tethers as Directing Groups for Aromatic CH
Acetoxylation Reactions. Adv. Synth. Catal. 2011, 353, 295−302.
(c) Chen, D.; Xing, G.; Zhou, H. Sulfone promoted Rh(III)-catalyzed
C-H activation and base assisted 1,5-H shift strategy for the
construction of seven-membered rings. Org. Chem. Front. 2015, 2,
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Rhodium-catalyzed directortho-alkenylation of phenyl sulfones with
alkynes utilizing sulfonyl function as modifiable directing group.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors thank the Science and Engineering Research
Board (SERB), Government of India (File No. EEQ/2016/
000231) for financial support, IISER Thiruvananthapuram for
the facilities, and Alex Andrews P for solving the X-ray
structures.
Tetrahedron 2015, 71, 6506−6512. (e) Eisold, M.; Muller-Deku, A.;
̈
Reiners, F.; Didier, D. Parallel Approaches for the Functionalization
of Thietes: α-Metalation versus C-H Activation. Org. Lett. 2018, 20,
4654−4658. (f) Kerr, W. J.; Knox, G. J.; Reid, M.; Tuttle, T.; Bergare,
J.; Bragg, R. A. Computationally-Guided Development of a Chelated
NHC-P Iridium(I) Complex for the Directed Hydrogen Isotope
Exchange of Aryl Sulfones. ACS Catal. 2020, 10, 11120−11126.
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of Ketone Directing Group as a Key To Control C-2 vs C-4
Alkenylation of Indoles. Org. Lett. 2016, 18, 5496−5499. (b) Leitch, J.
A.; Bhonoah, Y.; Frost, C. G. Beyond C2 and C3: Transition-Metal-
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