K2S2O8 -Activated Friedel-Crafts Type Alkylation of Indoles with α-Amido Sulfones

Article abstract of DOI:10.1055/s-0036-1589073

A K ₂ S ₂ O ₈ -activated regioselective alkylation of α-amido sulfones at the C-3 position of indoles is reported. The protocol developed herein provides an alternative new strategy to the previous approach by using Lewis acid, clay, and resin as catalyst for this Friedel-Crafts type alkylation of indoles with α-amido sulfones. The formed product bears a versatile transformable sulfone group and an amino group. The reaction condition is tolerant to a wide range of substrates, including a series of indoles with electron-withdrawing and electron-donating groups at different positions. Moreover, a variety of α-substituted phenylamido sulfones and some α-aliphatic amido sulfones also give the desired products in modest yield. Furthermore, a preliminary mechanism study was performed and the plausible reaction mechanism is discussed.

Full text of DOI:10.1055/s-0036-1589073

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–H
paper
A
en
X. Wu et al.
Paper
Synthesis
K2S2O8-Activated Friedel–Crafts Type Alkylation of Indoles with
α-Amido Sulfones
Xiaoyan Wu
Lu Xue
R1
SO2Ph
NHBoc
SO2Ph
K2S2O8
Shilong Luo
Shiqi Jia
R1
+
R2
R2
N
toluene, r.t., 48 h
H
NH
24 examples
Jun Ao
transition-metal-free
easy handling procedure
mild reaction conditions
Wenling Qin*
up to 99% yield
Innovative Drug Research Centre, School of Pharmaceutical
Sciences, Chongqing University, No.55 Daxuecheng, South
Rd., Shapingba, Chongqing 401331, P. R. of China
wenling.qin@cqu.edu.cn
Received: 20.04.2017
Accepted after revision: 14.06.2017
Published online: 25.07.2017
symmetric or asymmetric alkylation of indoles to produce
3-amido- or 3-sulfonyl-substituted indoles, which bear a
broad scope for further transformation.4 Up to the present,
some efficient and practical procedures have been devel-
oped for the C-3 alkylation of indoles. Among these proce-
dures, Lewis acids, such as InBr3,5 B(C6F5)3,6 Yb(OTf)3,7 and
FeCl3·6H2O8 catalyzed Friedel–Crafts reactions of α-amido
sulfones with indoles for the synthesis of 3-substituted in-
doles were well investigated. Meanwhile, clay, represented
by Montmorillonite K-10, had been demonstrated to be an
efficient catalyst for this type of reaction.9 Moreover,
Kadam and co-workers reported that ion-exchange resin
Amberlyst-15 could also catalyze this Friedel–Crafts type
reaction.10
DOI: 10.1055/s-0036-1589073; Art ID: ss-2017-h0266-op
Abstract A K2S2O8-activated regioselective alkylation of α-amido sul-
fones at the C-3 position of indoles is reported. The protocol developed
herein provides an alternative new strategy to the previous approach by
using Lewis acid, clay, and resin as catalyst for this Friedel–Crafts type
alkylation of indoles with α-amido sulfones. The formed product bears a
versatile transformable sulfone group and an amino group. The reac-
tion condition is tolerant to a wide range of substrates, including a se-
ries of indoles with electron-withdrawing and electron-donating groups
at different positions. Moreover, a variety of α-substituted phenylamido
sulfones and some α-aliphatic amido sulfones also give the desired
products in modest yield. Furthermore, a preliminary mechanism study
was performed and the plausible reaction mechanism is discussed.
Apart from the catalyst scavenge for the efficiency of
the addition reaction of α-amido sulfones to indole ring, the
regioselectivity caused by different additives was investi-
gated by Blay.11 The results indicated that the basic addi-
tives led to the formation of N-substituted adducts, where-
as the acidic one led to the C-3 alkylated products. This in-
teresting result inspired us to envisage that other catalysts
(or additives) might also be used as efficient additives for
this reaction. Hence, we turned our attention to gather the
approaches for the activation of the C-3 position of indoles
and started to search for activation approaches. Besides the
Lewis acids and other interesting reagents, catalysts for oxi-
dative activation of the C-3 position of indoles was also dis-
closed by several groups.12 Among them, K2S2O8 had been
demonstrated as an efficient reagent for activation of the C-
3 position of the indole ring, which usually contains a radi-
cal involved mechanism. Nevertheless, to the best of our
knowledge, no investigations on K2S2O8-activated alkylation
of indoles with α-amido sulfones have been reported.
Key words K2S2O8, indole alkylation, α-amido sulfone, Friedel–Crafts
reaction
Substitution of indoles is an evergreen attractive topic
for organic chemists due to the versatile biological and
pharmaceutical interests of indole derivatives.1 Electron en-
richment of the indole ring makes it a good counterpart of
various nucleophiles, and the studies focused on this field
are abundant and fruitful.2 Moreover, the alkylation at C-3
position of indole ring has been extensively studied due to
the pharmaceutical applications of the corresponding ad-
ducts.3 Various reagents have been utilized for the alkyla-
tion at C-3 position of indole ring. Recently, N-acyliminium
ions derived from α-amido sulfones have been used as the
objects of several nucleophilic addition protocols. The for-
mation of N-acyliminium ions ordinarily occurs in an acidic
ambient and our interest was directed towards their appli-
cations on indole ring addition reactions. According to liter-
ature reports, α-amido sulfones have been utilized in either
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–H

B
X. Wu et al.
Paper
Synthesis
Table 1 Screening of the Reaction Conditionsa
We initiated our exploration by investigating oxidants
for indole alkylation reaction with α-amido sulfone. K2S2O8
was demonstrated to be the best oxidative activator for this
reaction and gave only C-3 alkylated products (Table 1, en-
try 1). Oxone gave a modest yield for the same reaction (en-
try 2). Nevertheless, other oxidants displayed poor perfor-
mance for the reaction and none of them led to the forma-
tion of N-substituted adducts. Encouraged by this result,
the influence of solvents was investigated for this indole C-
3 alkylation reaction with α-amido sulfones by using
K2S2O8 as the activator.
As shown in Table 1, toluene as solvent gave the best
yield at room temperature (Table 1, entry 1). Dichlorometh-
ane as reaction solvent gave a slightly lower yield than tolu-
ene (entry 7). Acetonitrile, THF, and DMF as the solvents re-
sulted in a modest yield (entries 8–10). However, water as
the solvent gave only a trace amount of the desired product
(entry 11).
NHBoc
SO2Ph
oxidant
SO2Ph
+
N
solvent, r.t., 48 h
NH
H
1a
2a
3aa
Entries
Solvent
Oxidant
Yield (%)b
1
2
toluene
toluene
toluene
toluene
toluene
toluene
CH2Cl2
MeCN
THF
K2S2O8
Oxone
m-CPBA
H2O2
84
69
41
51
27
26
79
51
61
61
4
3
4
5
MnO2
I2
6
7
K2S2O8
K2S2O8
K2S2O8
K2S2O8
K2S2O8
8
9
With the optimal reaction condition in our hand, the
substrate scope of this K2S2O8-activated indole C-3 alkyla-
tion reaction with α-amido sulfones was investigated. A se-
ries of substituted indoles were evaluated first, indoles
bearing electron-withdrawing and electron-donating
groups gave the desired C-3 alkylation products bearing
sulfone substitutions in good yields (Scheme 1). No obvious
10
11
DMF
H2O
a Reaction conditions: 1a (0.2 mmol), 2a (0.2 mmol), oxidant (0.4 mmol) in
solvent (1.2 mL) at r.t. for 48 h, unless otherwise specified.
b Isolated yield.
R1
SO2Ph
NHBoc
K2S2O8
R1
SO2Ph
+
N
toluene, r.t. , 48 h
H
NH
1a–l
2a
3
SO2Ph
Me
SO2Ph
Cl
SO2Ph
SO2Ph
NH
NH
NH
NH
3aa
3ba
3ca
3da
84%
43%
81%
99%
F
Cl
Br
SO2Ph
SO2Ph
SO2Ph
SO2Ph
F
NH
NH
NH
NH
3ea
3fa
3ga
3ha
99%
62%
75%
76%
Me
SO2Ph
SO2Ph
SO2Ph
SO2Ph
Br
Cl
Br
NH
NH
NH
NH
Me
3ia
3ja
3ka
3la
86%
99%
83%
44%
Scheme 1 Scope of indoles. Reagents and conditions: indoles 1a–l (0.2 mmol), α-amido sulfone 2a (0.2 mmol), K2S2O8 (0.4 mmol) in solvent (1.2 mL) at
r.t. for 48 h, unless otherwise specified.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–H

C
X. Wu et al.
Paper
Synthesis
SO2Ph
NHBoc
K2S2O8
R2
+
R2
N
H
SO2Ph
toluene, r.t. , 48 h
NH
1a
2b–m
3
Me
SO2Ph
SO2Ph
SO2Ph
SO2Ph
Me
MeO
NH
NH
NH
NH
MeO
3ab
3ac
3ad
3ae
84%
94%
92%
81%
SO2Ph
SO2Ph
SO2Ph
SO2Ph
MeO
MeO
NH
NH
NH
NH
Cl
Br
OMe
3ah
76%
3ai
97%
3af
72%
3ag
94%
SO2Ph
SO2Ph
SO2Ph
SO2Ph
S
NH
NH
NH
NH
3am
99%
3aj
66%
3ak
44%
3al
46%
Scheme 2 Scope of α-amido sulfones. Reagents and conditions: indoles 1a (0.2 mmol), α-amido sulfone 2b–m (0.2 mmol), K2S2O8 (0.4 mmol) in sol-
vent (1.2 mL) at r.t. for 48 h, unless otherwise specified.
pattern was found in the relationships between the nature
of substitution on indoles and the reaction yields. The sub-
stitution on different positions of indole ring influenced the
reaction yield. This regio-effect was manifested by products
3ba and 3la, in which a substitution at C-2 position caused
a sterically hindered circumstance and led to a relatively
lower yield.
Furthermore, the scope of α-amido sulfones was inves-
tigated. First, different substitutions on the α-substituted
phenylamido sulfones were well tolerant to our reaction
conditions, including electron-withdrawing and -donating
groups. Moreover, the substitution position did not influ-
ence the reaction performance. α-Aliphatic-substituted
amido sulfones 3ak, 3al gave the desired C-3 adducts in a
lower yield because the electron-donating nature of ali-
phatic groups decreased the transformation ability of α-
amido sulfones into the corresponding acyliminium forms
(Scheme 2). The reaction with N-carbobenzyloxy (N-Cbz)-
protected α-amido sulfone afforded the desired alkylation
product 3aa in 51% yield, while with the corresponding
benzamide and p-toluenesulfonamide, no Friedel–Crafts al-
kylation product was observed.
After the substrate scope had been investigated, some
control experiments were performed to get an insight into
the reaction mechanism. It is known that K2S2O8 has the po-
tential to hydrolysis and give acidic products,13a meanwhile
presence of this acid is sufficient for the alkylation of in-
doles with α-amido sulfones. So first a control experiment
was performed in which sulfuric acid was used as additive
for the reaction as shown in Scheme 3. The C-3 alkylated
product 3aa and side product 4a were obtained in a very
low yield even after 96 hours. It indicated that the role of
K2S2O8 in this indole alkylation reaction was not merely as a
source of acid, but also serves as an additive to accelerate
the reaction.
Inspired by the control experiments and the work of
K2S2O8-mediated aerobic oxysulfonylation of olefins by
Chawla et al.12b a mechanism involving a radical intermedi-
SO2Ph
Ph
NHBoc
H2SO4
+
+
SO2Ph
NH
N
toluene, r.t., 96 h
NH
HN
H
1a
2a
4a
3aa
5%
2%
Scheme 3 Control experiment. Reagents and conditions: 1a (0.2 mmol), 2a (0.2 mmol), H2SO4 (0.4 mmol) in toluene (1.2 mL) at r.t. for 96 h.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–H

D
X. Wu et al.
Paper
Synthesis
ate is proposed. To prove this deduction, a radical trapping
experiment was performed. As shown in Scheme 4, under
the optimized reaction conditions and using TEMPO
(2,2,6,6-tetramethyl-1-piperidinyloxy) as a radical scaven-
ger, the indole C-3 alkylation product 3aa was detected, in-
dicating that radical was not involved in the reaction.
which can be isolated in some cases from the reaction sys-
tem. The presence of K2S2O8 resulted in the formation of po-
tassium benzenesulfinate and accelerates its reaction with
intermediate D. Furthermore, we have performed the reac-
tion by using intermediate B as the starting material, to re-
act with α-amido sulfone and potassium benzenesulfinate
in the presence of K2S2O8. The target product was success-
fully formed while the yields (36% and 20%, respectively)
decreased compared to the original procedure (84%).
NHBoc
SO2Ph
SO2Ph
TEMPO, K2S2O8
toluene, r.t., 48 h
+
N
In conclusion, we have developed a K2S2O8-activated C-3
alkylation of indoles by α-amido sulfones. This method pro-
vides an alternative new strategy to the previous approach
by using Lewis acid, clay, and resin as catalyst. In particular,
this protocol can be performed at ambient temperature and
allows gentle reaction conditions, meanwhile with excel-
lent regioselectivity at C-3 of indole ring. Particularly, α-ali-
phatic amido sulfones are suitable substrates for this reac-
tion. The product bears a versatile transformable sulfone
group and amino group. The reaction conditions showed
the high tolerance to a wide range of indoles and α-amido
sulfones. A radical trapping experiment revealed that this
K2S2O8-activated alkylation at C-3 of indole by α-amido sul-
fones did not involve a radical process. Further investiga-
tions to elucidate the detailed mechanism and synthetic ap-
plications of this efficient and practical protocol are cur-
rently underway in our laboratory.
NH
H
1a
2a
3aa
80%
Scheme 4 Radical trapping experiment of the K2S2O8-activated alkyla-
tion of α-amido sulfones with indoles. Reagents and conditions: 1a (0.2
mmol), 2a (0.2 mmol), TEMPO (0.05 mmol), K2S2O8 (0.4 mmol) in tolu-
ene (1.2 mL) at r.t. for 48 h.
Based on the above experimental results and literature
reports,13 a plausible reaction mechanism for the K2S2O8-
activated alkylation of indoles by α-amido sulfones is de-
picted in Scheme 5. First, the acyliminium benzenesulfinate
A was formed under the reaction conditions, and then after
the deprotonation and addition to indole ring gives the in-
dole carbamate B, potassium benzenesulfinate, and HS2O8
in the presence of K2S2O8.
Intermediate B is then converted into D through C in the
presence of HS2O8 . Along with the addition of previously
–
–
generated one molecule of benzenesulfinic acid potassium
salt into D, the final product 3 is formed. Notably, interme-
diate D, the 3-alkeneindole, may undergo an alkylation with
another equivalent of indole to give the side product 4,
All reagents were obtained from Adamas, Accela, or Acros and used
without further purification, unless otherwise noted. The products
were purified by column chromatography with Huanghai Silica Gel
50–75 μm, ultrapure silica gel. 1H NMR and 13C NMR spectra were re-
R2
K2S2O8
NHBoc
NHBoc
SO2Ph
NHBoc
PhSO2
R2
N
H
R2
N
A
B
H
H
R2
NHBoc
R2
SO2Ph
2–
S2O8
PhSO2
K
+
HS2O8
2
N
H
N
H
C
3
R2
R2
fast
N
2–
S2O8
2
N
HN
NH
slow
H
D
4
Scheme 5 Plausible mechanism of K2S2O8-activated alkylation of α-amido sulfones with indoles
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–H

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X. Wu et al.
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Synthesis
corded in DMSO-d6 or CDCl3 on an Agilent 400MR DD2 (400 MHz)
spectrometer. The chemical shifts were reported in ppm relative to
Me4Si as an internal standard. High-resolution mass spectra (HRMS)
were performed on Bruker solarix 7.0T spectrometer. Melting points
were determined on a micro melting point apparatus in open capil-
laries and are uncorrected. All reactions were carried out under N2 at-
mosphere in oven-dried glassware with magnetic stirring.
13C NMR (100 MHz, CDCl3): δ = 138.23, 136.79, 133.54, 133.37,
130.40, 128.81, 128.63, 128.38, 126.05, 125.08, 123.16, 122.72,
121.39, 110.59, 106.84, 67.62.
HRMS (ESI): m/z calcd for [C21H16ClNO2SNa, M + Na]+: 404.04824;
found: 404.04816.
4-Bromo-3-[phenyl(phenylsulfonyl)methyl]-1H-indole (3ea)
White crystals; yield: 84.4 mg (99%); mp 161.0–162.1 °C.
K2S2O8-Activated Friedel–Crafts Type Alkylation of Indoles with α-
Amido Sulfones; General Procedure
1H NMR (400 MHz, CDCl3): δ = 9.04 (s, 1 H), 7.97 (d, J = 2.2 Hz, 1 H),
7.70 (d, J = 7.8 Hz, 2 H), 7.52–7.41 (m, 3 H), 7.35 (t, J = 7.6 Hz, 2 H),
7.29–7.20 (m, 3 H), 7.18–7.09 (m, 2 H), 7.02 (s, 1 H), 6.84 (t, J = 7.8 Hz,
1 H).
13C NMR (100 MHz, CDCl3): δ = 138.20, 136.68, 133.43, 133.38,
130.43, 128.78, 128.65, 128.37, 126.57, 124.86, 124.14, 122.98,
112.85, 111.27, 106.87, 66.74.
To a 10 mL flame-dried Schlenk tube equipped with a stirring bar, in-
dole 1 (0.2 mmol), α-amido-sulfone 2 (0.2 mmol), and K2S2O8 (108.1
mg, 0.4 mmol) were added. Toluene (1.2 mL) was injected into the
tube at r.t. After stirring for 48 h, the mixture was purified by silica gel
chromatography to afford the desired product 3.
3-[Phenyl(phenylsulfonyl)methyl]-1H-indole (3aa)
HRMS (ESI): m/z calcd for [C21H16BrNO2SNa, M + Na]+: 447.99773;
found: 447.99768.
Pink powder; yield: 58.4 mg (84%); mp 177.5–179.5 °C.
1H NMR (400 MHz, DMSO-d6): δ = 11.32 (s, 1 H), 7.72 (d, J = 7.9 Hz, 3
H), 7.69–7.59 (m, 3 H), 7.53 (t, J = 7.3 Hz, 1 H), 7.42 (t, J = 7.6 Hz, 2 H),
7.37–7.26 (m, 4 H), 7.06 (t, J = 7.5 Hz, 1 H), 6.95 (t, J = 7.4 Hz, 1 H), 6.27
(s, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 138.57, 135.30, 133.94, 133.33,
130.20, 128.63, 128.34, 128.12, 126.92, 125.41, 121.47, 118.90,
118.61, 111.48, 106.28, 66.46.
5-Fluoro-3-[phenyl(phenylsulfonyl)methyl]-1H-indole (3fa)
Pink powder; yield: 45.3 mg (62%); mp 188.6–189.6 °C.
1H NMR (400 MHz, DMSO-d6): δ = 11.45 (s, 1 H), 7.81 (d, J = 2.4 Hz, 1
H), 7.71 (d, J = 7.6 Hz, 2 H), 7.64 (d, J = 6.3 Hz, 2 H), 7.55 (t, J = 7.4 Hz, 1
H), 7.49 (dd, J = 10.3, 2.2 Hz, 1 H), 7.43 (t, J = 7.7 Hz, 2 H), 7.37–7.25
(m, 4 H), 6.91 (td, J = 9.2, 2.3 Hz, 1 H), 6.29 (s, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 158.13, 155.83, 138.45, 133.81,
133.39, 131.94, 130.15, 128.65, 128.38, 128.20, 127.54, 127.50,
127.39, 112.59, 112.50, 109.85, 109.58, 106.64, 106.60, 103.61,
103.37, 66.15.
HRMS (ESI): m/z calcd for [C21H16FNO2SNa, M + Na]+: 388.07779;
found: 388.07783.
HRMS (ESI): m/z calcd for [C21H17NO2SNa, M + Na]+: 370.08722;
found: 370.08717.
2-Phenyl-3-[phenyl(phenylsulfonyl)methyl]-1H-indole (3ba)
White crystals; yield: 36.4 mg (43%); mp 219.2–219.9 °C.
1H NMR (400 MHz, DMSO-d6): δ = 11.58 (s, 1 H), 8.14 (d, J = 7.6 Hz, 1
H), 7.63 (d, J = 6.7 Hz, 2 H), 7.58 (t, J = 7.2 Hz, 1 H), 7.52–7.43 (m, 3 H),
7.43–7.24 (m, 8 H), 7.17 (pent, J = 6.8 Hz, 2 H), 7.06 (d, J = 5.4 Hz, 2 H),
5.75 (s, 1 H).
5-Chloro-3-[phenyl(phenylsulfonyl)methyl]-1H-indole (3ga)
Pink powder; yield: 57.3 mg (75%); mp 171.1–172.0 °C.
1H NMR (400 MHz, CDCl3): δ = 8.82 (s, 1 H), 7.70 (s, 1 H), 7.63 (d, J =
6.8 Hz, 2 H), 7.50 (t, J = 6.0 Hz, 1 H), 7.47–7.39 (m, 2 H), 7.39–7.31 (m,
3 H), 7.30–7.22 (m, 3 H), 7.18 (d, J = 8.5 Hz, 1 H), 7.05 (d, J = 8.3 Hz, 1
H), 5.60 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 137.90, 133.78, 133.56, 132.99,
129.96, 128.93, 128.70, 128.65, 128.57, 128.07, 126.23, 125.85,
122.81, 117.64, 112.50, 106.71, 68.86.
13C NMR (100 MHz, DMSO-d6): δ = 139.82, 138.24, 136.19, 133.62,
133.27, 131.05, 129.75, 128.80, 128.68, 128.60, 128.35, 127.72,
126.14, 122.30, 121.89, 119.75, 111.58, 103.00, 69.55.
HRMS (ESI): m/z calcd for [C27H21NO2SNa, M + Na]+: 446.11852;
found: 446.11841.
4-Methyl-3-[phenyl(phenylsulfonyl)methyl]-1H-indole (3ca)
HRMS (ESI): m/z calcd for [C21H16ClNO2SNa, M + Na]+: 404.04824;
found: 404.04830.
Brown power; yield: 58.6 mg (81%); mp 174.5–175.5 °C.
1H NMR (400 MHz, CDCl3): δ = 8.50 (s, 1 H), 8.00 (d, J = 2.5 Hz, 1 H),
7.68 (d, J = 7.6 Hz, 2 H), 7.49 (t, J = 7.4 Hz, 1 H), 7.43–7.31 (m, 4 H),
7.29–7.25 (m, 3 H), 7.17 (d, J = 8.2 Hz, 1 H), 7.00 (t, J = 7.6 Hz, 1 H),
6.75 (d, J = 7.1 Hz, 1 H), 6.14 (s, 1 H), 2.57 (s, 3 H).
6-Fluoro-3-[phenyl(phenylsulfonyl)methyl]-1H-indole (3ha)
Pink powder; yield: 55.5 mg (76%); mp 161.1–162.3 °C.
1H NMR (400 MHz, CDCl3): δ = 8.50 (s, 1 H), 7.67 (d, J = 2.3 Hz, 1 H),
7.63 (d, J = 7.5 Hz, 2 H), 7.50 (t, J = 7.5 Hz, 1 H), 7.46–7.42 (m, 2 H),
7.34 (t, J = 7.9 Hz, 3 H), 7.30–7.26 (m, 3 H), 6.98 (dd, J = 9.4, 2.0 Hz, 1
H), 6.84–6.78 (m, 1 H), 5.64 (s, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 160.05, 157.71, 138.44, 135.22,
135.09, 133.77, 133.40, 130.17, 128.67, 128.37, 128.19, 126.18,
126.15, 123.76, 119.91, 119.80, 107.64, 107.39, 106.61, 97.56, 97.31,
66.24.
13C NMR (100 MHz, CDCl3): δ = 138.53, 135.66, 133.60, 133.33,
130.50, 129.38, 128.84, 128.65, 128.44, 125.37, 124.83, 122.29,
122.11, 109.70, 107.42, 69.58, 20.80.
HRMS (ESI): m/z calcd for [C22H19NO2SNa, M + Na]+: 384.10287;
found: 384.10290.
4-Chloro-3-[phenyl(phenylsulfonyl)methyl]-1H-indole (3da)
White crystals; yield: 75.6 mg (99%); mp 156.5–158.5 °C.
HRMS (ESI): m/z calcd for [C21H16FNO2SNa, M + Na]+: 388.07779;
found: 388.07776.
1H NMR (400 MHz, CDCl3): δ = 8.93 (s, 1 H), 7.99–7.94 (m, 1 H), 7.68
(d, J = 7.9 Hz, 2 H), 7.52–7.40 (m, 3 H), 7.35 (t, J = 7.5 Hz, 2 H), 7.25 (s,
3 H), 7.14 (d, J = 6.9 Hz, 1 H), 6.98–6.90 (m, 2 H), 6.78 (s, 1 H).
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6-Bromo-3-[phenyl(phenylsulfonyl)methyl]-1H-indole (3ia)
HRMS (ESI): m/z calcd for [C22H19NO2SNa, M + Na]+: 384.10287,
found: 384.10282.
Pink powder; yield: 73.3 mg (86%); mp 174.5–176.5 °C.
1H NMR (400 MHz, DMSO-d6): δ = 11.48 (s, 1 H), 7.78 (d, J = 2.4 Hz, 1
H), 7.72 (d, J = 7.5 Hz, 2 H), 7.68–7.59 (m, 3 H), 7.58–7.52 (m, 2 H),
7.43 (t, J = 7.7 Hz, 2 H), 7.35–7.25 (m, 3 H), 7.10 (dd, J = 8.5, 1.5 Hz, 1
H), 6.32 (s, 1 H).
13C NMR (100 MHz, DMSO-d6): δ = 138.38, 136.20, 133.67, 133.43,
130.17, 128.68, 128.37, 128.21, 126.65, 126.02, 121.84, 120.58,
114.23, 114.10, 106.74, 66.12.
3-[(Phenylsulfonyl)(m-tolyl)methyl]-1H-indole (3ac)
White crystals; yield: 68.0 mg (94%); mp 149.9–151.1 °C.
1H NMR (400 MHz, CDCl3): δ = 8.51 (s, 1 H), 7.68 (d, J = 2.5 Hz, 1 H),
7.64 (d, J = 7.3 Hz, 2 H), 7.45 (t, J = 7.4 Hz, 1 H), 7.38 (d, J = 8.0 Hz, 1 H),
7.34–7.23 (m, 5 H), 7.18–7.10 (m, 2 H), 7.10–7.05 (m, 1 H), 7.02 (t, J =
7.5 Hz, 1 H), 5.66 (s, 1 H), 2.25 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 138.25, 138.08, 135.41, 133.26,
133.03, 130.80, 129.30, 128.93, 128.48, 128.30, 127.15, 126.96,
124.85, 122.36, 119.95, 118.10, 111.37, 107.13, 68.98, 21.33.
HRMS (ESI): m/z calcd for [C21H16BrNO2SNa, M + Na]+: 447.99773;
found: 447.99769.
HRMS (ESI): m/z calcd for [C22H19NO2SNa, M + Na]+: 384.10287;
found: 384.10280.
7-Chloro-3-[phenyl(phenylsulfonyl)methyl]-1H-indole (3ja)
Red powder; yield: 75.6 mg (99%); mp 161.5–163.0 °C.
1H NMR (400 MHz, CDCl3): δ = 8.71 (s, 1 H), 7.79 (d, J = 2.4 Hz, 1 H),
7.64 (d, J = 7.7 Hz, 2 H), 7.50–7.40 (m, 3 H), 7.35–7.29 (m, 3 H), 7.29–
7.21 (m, 3 H), 7.12 (d, J = 7.6 Hz, 1 H), 6.95 (t, J = 7.8 Hz, 1 H), 5.66 (s, 1
H).
13C NMR (100 MHz, CDCl3): δ = 137.94, 133.43, 132.93, 132.73,
130.01, 128.89, 128.65, 128.59, 128.50, 128.35, 125.47, 121.84,
120.83, 117.05, 116.73, 108.40, 68.95.
3-[(3-Methoxyphenyl)(phenylsulfonyl)methyl]-1H-indole (3ad)
Red powder; yield: 69.5 mg (92%); mp 83.0–85.0 °C.
1H NMR (400 MHz, CDCl3): δ = 8.74 (s, 1 H), 7.63 (d, J = 7.7 Hz, 2 H),
7.53 (s, 1 H), 7.43 (d, J = 7.8 Hz, 1 H), 7.36 (t, J = 7.3 Hz, 1 H), 7.27–7.16
(m, 3 H), 7.13 (t, J = 7.9 Hz, 1 H), 7.10–6.96 (m, 4 H), 6.78 (d, J = 7.9 Hz,
1 H), 5.70 (s, 1 H), 3.62 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 159.30, 137.93, 135.39, 134.57,
133.28, 129.33, 128.74, 128.46, 126.79, 125.08, 122.42, 122.15,
119.77, 117.95, 115.70, 113.94, 111.55, 106.35, 68.94, 55.06.
HRMS (ESI): m/z calcd for [C21H16ClNO2SNa, M + Na]+: 404.04824;
found: 404.04831.
HRMS (ESI): m/z calcd for [C22H19NO3SNa, M + Na]+: 400.09778;
found: 400.09781.
7-Bromo-3-[phenyl(phenylsulfonyl)methyl]-1H-indole (3ka)
Pink crystals; yield: 70.8 mg (83%); mp 167.8–168.5 °C.
1H NMR (400 MHz, CDCl3): δ = 8.62 (s, 1 H), 7.81 (s, 1 H), 7.64 (d, J =
7.7 Hz, 2 H), 7.51–7.39 (m, 3 H), 7.39–7.20 (m, 7 H), 6.91 (t, J = 7.8 Hz,
1 H), 5.65 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 137.96, 134.15, 133.44, 132.91,
130.02, 128.91, 128.66, 128.60, 128.51, 128.05, 125.37, 124.86,
121.24, 117.67, 108.63, 104.80, 68.97.
3-[(4-Methoxyphenyl)(phenylsulfonyl)methyl]-1H-indole (3ae)
Pink powder; yield: 61.1 mg (81%); mp 73.5–75.0 °C.
1H NMR (400 MHz, CDCl3): δ = 8.70 (s, 1 H), 7.52 (d, J = 7.7 Hz, 2 H),
7.46 (s, 1 H), 7.35–7.22 (m, 4 H), 7.19–7.06 (m, 3 H), 6.96 (t, J = 7.4 Hz,
1 H), 6.89 (t, J = 7.3 Hz, 1 H), 6.64 (d, J = 7.6 Hz, 2 H), 5.58 (s, 1 H), 3.58
(s, 3 H).
HRMS (ESI): m/z calcd for [C21H16BrNO2SNa, M + Na]+: 447.99773;
found: 447.99770.
13C NMR (100 MHz, CDCl3): δ = 159.61, 138.07, 135.43, 133.20,
131.28, 128.74, 128.46, 126.81, 124.94, 122.13, 119.73, 118.04,
113.75, 111.52, 106.75, 68.38, 55.10.
HRMS (ESI): m/z calcd for [C22H19NO3SNa, M + Na]+: 400.09778;
2,5-Dimethyl-3-[phenyl(phenylsulfonyl)methyl]-1H-indole (3la)
Light yellow powder; yield: 33.0 mg (44%); mp 179.6–181.0 °C.
found: 400.09775.
1H NMR (400 MHz, CDCl3): δ = 7.90 (s, 1 H), 7.76 (d, J = 6.7 Hz, 2 H),
7.54 (d, J = 7.7 Hz, 2 H), 7.49 (s, 1 H), 7.43 (t, J = 7.4 Hz, 1 H), 7.35–7.28
(m, 3 H), 7.24 (d, J = 7.7 Hz, 2 H), 7.06 (d, J = 8.2 Hz, 1 H), 6.91 (d, J = 8.1
Hz, 1 H), 5.63 (s, 1 H), 2.38 (s, 3 H), 1.99 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 138.91, 135.44, 133.29, 133.08,
132.92, 129.89, 129.16, 128.62, 128.38, 128.28, 128.09, 127.43,
123.05, 120.52, 109.89, 103.46, 69.59, 21.66, 11.98.
3-[(4-Isopropylphenyl)(phenylsulfonyl)methyl]-1H-indole (3af)
Light yellow crystals; yield: 56.1 mg (72%); mp 172.5–174.0 °C.
1H NMR (400 MHz, CDCl3): δ = 8.49 (s, 1 H), 7.70 (d, J = 2.1 Hz, 1 H),
7.63 (d, J = 7.8 Hz, 2 H), 7.47–7.36 (m, 4 H), 7.32–7.22 (m, 3 H), 7.16–
7.07 (m, 3 H), 7.02 (t, J = 7.5 Hz, 1 H), 5.67 (s, 1 H), 2.91–2.79 (m, 1 H),
1.19 (d, J = 6.8 Hz, 6 H).
HRMS (ESI): m/z calcd for [C23H21NO2SNa, M + Na]+: 398.11852;
found: 398.11849.
13C NMR (100 MHz, CDCl3): δ = 149.35, 138.34, 135.40, 133.20,
130.33, 130.06, 128.90, 128.44, 126.98, 126.54, 124.80, 122.37,
119.95, 118.20, 111.33, 107.37, 68.75, 33.73, 23.83.
HRMS (ESI): m/z calcd for [C24H23NO2SNa, M + Na]+: 412.13417;
3-[(Phenylsulfonyl)(o-tolyl)methyl]-1H-indole (3ab)
Brown powder; yield: 60.7 mg (84%); mp 150.2–152.0 °C.
found: 412.13420.
1H NMR (400 MHz, CDCl3): δ = 8.62 (s, 1 H), 7.95 (d, J = 7.6 Hz, 1 H),
7.69 (d, J = 2.3 Hz, 1 H), 7.65 (d, J = 7.5 Hz, 2 H), 7.47 (t, J = 7.4 Hz, 1 H),
7.36–7.26 (m, 4 H), 7.26–7.20 (m, 1 H), 7.16 (t, J = 7.0 Hz, 1 H), 7.11 (t,
J = 7.5 Hz, 1 H), 7.05–6.99 (m, 2 H), 6.04 (s, 1 H), 2.17 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 138.66, 136.94, 135.36, 133.37,
132.01, 130.33, 129.65, 128.88, 128.55, 128.40, 127.09, 126.38,
125.19, 122.33, 119.96, 117.84, 111.44, 107.49, 63.71, 19.62.
3-[(4-Chlorophenyl)(phenylsulfonyl)methyl]-1H-indole (3ag)
Pink powder; yield: 71.8 mg (94%); mp 97.5–99.2 °C.
1H NMR (400 MHz, CDCl3): δ = 8.56 (s, 1 H), 7.68–7.60 (m, 3 H), 7.47
(t, J = 7.4 Hz, 1 H), 7.42–7.25 (m, 6 H), 7.25–7.19 (m, 2 H), 7.13 (t, J =
7.5 Hz, 1 H), 7.03 (t, J = 7.5 Hz, 1 H), 5.68 (s, 1 H).
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13C NMR (100 MHz, CDCl3): δ = 137.95, 135.46, 134.64, 133.54,
131.77, 131.39, 128.87, 128.69, 128.64, 126.75, 124.80, 122.56,
120.12, 118.05, 111.49, 106.66, 68.27.
HRMS (ESI): m/z calcd for [C21H16ClNO2SNa, M + Na]+: 404.04824;
found: 404.04821.
3-[Cyclohexyl(phenylsulfonyl)methyl]-1H-indole (3al)
Light yellow powder; yield: 32.5 mg (46%); mp 152.5–153.5 °C.
1H NMR (400 MHz, CDCl3): δ = 8.45 (s, 1 H), 7.53 (d, J = 7.6 Hz, 2 H),
7.41–7.21 (m, 4 H), 7.16 (t, J = 7.6 Hz, 2 H), 7.08 (t, J = 7.5 Hz, 1 H), 6.95
(t, J = 7.3 Hz, 1 H), 4.38 (d, J = 5.2 Hz, 1 H), 2.78–2.63 (m, 1 H), 2.19–
1.98 (m, 2 H), 1.79–1.65 (m, 2 H), 1.60 (d, J = 12.5 Hz, 1 H), 1.34 (dq, J =
26.0, 12.6 Hz, 2 H), 1.23–0.95 (m, 3 H).
3-[(4-Bromophenyl)(phenylsulfonyl)methyl]-1H-indole (3ah)
13C NMR (100 MHz, CDCl3): δ = 139.38, 135.16, 132.68, 128.21,
128.15, 127.70, 125.50, 122.06, 119.80, 118.07, 111.09, 106.07, 68.38,
38.00, 32.37, 29.77, 26.22, 25.97, 25.87.
Pink powder; yield: 64.8 mg (76%); mp 170.9–172.3 °C.
1H NMR (400 MHz, CDCl3): δ = 8.50 (s, 1 H), 7.68–7.62 (m, 3 H), 7.49
(t, J = 7.4 Hz, 1 H), 7.42–7.27 (m, 8 H), 7.14 (t, J = 7.5 Hz, 1 H), 7.03 (t,
J = 7.5 Hz, 1 H), 5.66 (s, 1 H).
HRMS (ESI): m/z calcd for [C21H23NO2SNa, M + Na]+: 376.13417;
13C NMR (100 MHz, CDCl3): δ = 137.98, 135.45, 133.55, 132.30,
131.69, 131.62, 128.89, 128.70, 126.75, 124.74, 122.91, 122.62,
120.17, 118.09, 111.44, 106.75, 68.32.
found: 376.13412.
3-[(Phenylsulfonyl)(thiophen-2-yl)methyl]-1H-indole (3am)
HRMS (ESI): m/z calcd for [C21H16BrNO2SNa, M + Na]+: 447.99773;
Pink solid; yield: 70.0 mg (99%); mp 86.5–88.1 °C.
1H NMR (400 MHz, CDCl3): δ = 8.96 (s, 1 H), 7.60 (d, J = 7.6 Hz, 2 H),
7.50–7.37 (m, 3 H), 7.34–7.20 (m, 5 H), 7.11 (t, J = 7.4 Hz, 1 H), 7.06–
7.00 (m, 1 H), 5.83 (s, 1 H).
found: 447.99770.
3-[(Phenylsulfonyl)(3,4,5-trimethoxyphenyl)methyl]-1H-indole
(3ai)
13C NMR (100 MHz, CDCl3): δ = 137.82, 135.54, 133.29, 128.78,
128.62, 128.46, 126.74, 126.08, 125.75, 125.54, 122.22, 119.90,
118.42, 111.48, 106.54, 64.72.
HRMS (ESI): m/z calcd for [C19H15NO2S2Na, M + Na]+: 376.04364;
found: 376.04360.
Light yellow powder; yield: 84.9 mg (97%); mp 85.0–87.0 °C.
1H NMR (400 MHz, CDCl3): δ = 9.03 (s, 1 H), 7.64 (d, J = 7.1 Hz, 3 H),
7.51–7.39 (m, 2 H), 7.27 (dd, J = 14.0, 7.6 Hz, 3 H), 7.09 (t, J = 7.4 Hz, 1
H), 7.02 (t, J = 7.4 Hz, 1 H), 6.68 (s, 2 H), 5.67 (s, 1 H), 3.78 (s, 3 H), 3.68
(s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 152.75, 137.91, 137.91, 135.51,
133.23, 128.76, 128.70, 128.43, 126.72, 124.94, 122.18, 119.74,
118.11, 111.48, 107.26, 106.36, 69.18, 60.64, 55.87.
HRMS (ESI): m/z calcd for [C24H23NO5SNa, M + Na]+: 460.11891;
found: 460.11893.
3,3′-(Phenylmethylene)bis(1H-indole) (4a) (Scheme 3)
Red powder; yield: 3.2 mg (5%); mp 94.5–96.4 °C.
1H NMR (400 MHz, CDCl3): δ = 7.59 (s, 2 H), 7.35 (d, J = 7.9 Hz, 2 H),
7.30 (d, J = 7.1 Hz, 2 H), 7.27–7.20 (m, 4 H), 7.18 (d, J = 7.2 Hz, 1 H),
7.13 (t, J = 7.6 Hz, 2 H), 6.97 (t, J = 7.5 Hz, 2 H), 6.48 (s, 2 H), 5.83 (s, 1
H).
3-[Naphthalen-2-yl(phenylsulfonyl)methyl]-1H-indole (3aj)
13C NMR (100 MHz, CDCl3): δ = 143.95, 136.54, 128.65, 128.17,
Brown powder; yield: 52.5 mg (66%); mp 165.4–166.0 °C.
126.96, 126.08, 123.59, 121.83, 119.84, 119.49, 119.14, 111.03, 40.09.
1H NMR (400 MHz, DMSO-d6): δ = 11.33 (s, 1 H), 8.49 (d, J = 8.4 Hz, 1
H), 8.23 (d, J = 7.3 Hz, 1 H), 7.86 (dd, J = 14.7, 7.8 Hz, 4 H), 7.76 (d, J =
2.4 Hz, 1 H), 7.62–7.42 (m, 5 H), 7.40–7.31 (m, 3 H), 7.08–7.02 (m, 2
H), 6.92 (t, J = 7.5 Hz, 1 H).
HRMS (ESI): m/z calcd for [C24H26N2O3SNa, M + Na]+: 445.15563;
found: 445.15523.
tert-Butyl [(1H-Indol-3-yl)(phenyl)methyl]carbamate (Intermedi-
13C NMR (100 MHz, DMSO-d6): δ = 138.79, 135.45, 133.35, 133.23,
131.46, 130.13, 128.73, 128.62, 128.58, 128.52, 127.94, 126.76,
126.55, 126.17, 125.66, 125.16, 123.29, 121.49, 119.03, 118.57,
111.58, 106.92, 61.48.
ate B)
Intermediate B was prepared following the literature procedure
(Scheme 6).11
NHBoc
SO2Ph
HRMS (ESI): m/z calcd for [C25H19NO2SNa, M + Na]+: 420.10287;
found: 420.10284.
NHBoc
K2CO3
+
N
CH2Cl2, r.t., 72 h
H
HN
3-[3-Phenyl-1-(phenylsulfonyl)propyl]-1H-indole (3ak)
1a
2a
intermediate B
65%
Light yellow powder; yield: 33.0 mg (44%); mp 49.0–51.0 °C.
1H NMR (400 MHz, CDCl3): δ = 8.55 (s, 1 H), 7.50 (d, J = 7.5 Hz, 2 H),
7.41 (t, J = 7.4 Hz, 1 H), 7.31–7.14 (m, 7 H), 7.11 (t, J = 7.5 Hz, 1 H),
7.05–6.93 (m, 4 H), 4.38 (d, J = 11.0 Hz, 1 H), 2.83–2.64 (m, 2 H), 2.58–
2.40 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 140.21, 137.38, 135.85, 133.19,
128.88, 128.45, 128.43, 128.41, 126.97, 126.17, 125.17, 122.27,
120.02, 118.76, 111.36, 106.52, 63.35, 32.61, 29.44.
Scheme 6 Preparation of intermediate B
To a 25 mL flame-dried Schlenk flask equipped with a stirring bar
were added indole 1a (117.2 mg, 1.0 mmol), α-amido sulfone 2a
(347.4 mg, 1.0 mmol), and K2CO3 (414.6 mg, 3.0 mmol). CH2Cl2 (12
mL) was injected into the flask at r.t. After stirring for 72 hours, the
mixture was purified by silica gel chromatography to afford the prod-
uct B; red powder; yield: 209.6 mg (65%); mp 136.2–138.0 C.
HRMS (ESI): m/z calcd for [C23H21NO2SNa, M + Na]+: 398.11852;
1H NMR (400 MHz, CDCl3): δ = 8.27 (s, 1 H), 7.49 (d, J = 7.6 Hz, 1 H),
7.36 (d, J = 7.2 Hz, 2 H), 7.31 (t, J = 7.2 Hz, 3 H), 7.28–7.22 (m, 1 H),
7.17 (t, J = 7.5 Hz, 1 H), 7.07 (t, J = 7.5 Hz, 1 H), 6.63 (s, 1 H), 6.27–6.10
(m, 1 H), 5.25 (s, 1 H), 1.45 (s, 9 H).
found: 398.11849.
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13C NMR (100 MHz, CDCl3): δ = 155.27, 142.00, 136.64, 128.31,
127.04, 126.77, 125.83, 123.30, 122.30, 119.68, 119.29, 117.63,
111.34, 79.56, 51.67, 28.38.
D.-M. Eur. J. Org. Chem. 2012, 4042. (e) Shi, Z.-H.; Sheng, H.;
Yang, K.-F.; Jiang, J.-X.; Lai, G.-Q.; Lu, Y.; Xu, L.-W. Eur. J. Org.
Chem. 2011, 66. (f) Tang, H.-Y.; Lu, A.-D.; Zhou, Z.-H.; Zhao, G.-
F.; He, L.-N.; Tang, C.-C. Eur. J. Org. Chem. 2008, 1406. (g) Yu, X.;
Lu, A.; Wang, Y.; Wu, G.; Song, H.; Zhou, Z.; Tang, C. Eur. J. Org.
Chem. 2011, 892. (h) Jia, Y.-X.; Xie, J.-H.; Duan, H.-F.; Wang, L.-
X.; Zhou, Q.-L. Org. Lett. 2006, 8, 1621. (i) McKeon, S. C.; Müller-
Bunz, H.; Guiry, P. J. Eur. J. Org. Chem. 2009, 4833. (j) Chen, L.-Y.;
He, H.; Chan, W.-H.; Lee, A. W. M. J. Org. Chem. 2011, 76, 7141.
(k) Bartoli, G.; Bosco, M.; Carlone, A.; Pesciaioli, F.; Sambri, L.;
Melchiorre, P. Org. Lett. 2007, 9, 1403. (l) Fleming, E. M.;
McCabe, T.; Connon, S. J. Tetrahedron Lett. 2006, 47, 7037.
(m) Zheng, C.; Sheng, Y.-F.; Li, Y.-X.; You, S.-L. Tetrahedron 2010,
66, 2875.
3-[Phenyl(phenylsulfonyl)methyl]-1H-indole (3aa)
Intermediate B reacted with α-amido sulfone 2a and potassium ben-
zenesulfinate as shown in Scheme 7.
NHBoc
SO2Ph
NHBoc
SO2Ph
K2S2O8
+
toluene
r.t., 48 h
HN
HN
3aa
36%
intermediate B
2a
(3) (a) Somei, M.; Yamada, F. Nat. Prod. Rep. 2004, 21, 278.
(b) O’Connor, S. E.; Maresh, J. J. Nat. Prod. Rep. 2006, 23, 532.
(4) (a) Zuo, Z.; Zhang, S.; Wang, R.; He, W.; Wu, S.; Xie, X.; Qin, D.;
Jing, L. Synthesis 2013, 45, 2832. (b) Wang, R.; Jing, L.; Qin, D.
Tetrahedron Lett. 2015, 56, 2867. (c) Cao, L.-L.; Li, X.-N.; Meng,
F.-Y.; Jiang, G.-F. Tetrahedron Lett. 2012, 53, 3873. (d) Jing, L.;
Wei, J.; Zhou, L.; Huang, Z.; Li, Z.; Wu, D.; Xiang, H.; Zhou, X.
Chem. Eur. J. 2010, 16, 10955. (e) Chen, P.; Lu, S.-m.; Guo, W.;
Liu, Y.; Li, C. Chem. Commun. 2016, 52, 96. (f) Ballini, R.;
Palmieri, A.; Petrini, M.; Torregiani, E. Org. Lett. 2006, 8, 4093.
(g) Li, Y.; Shi, F.-Q.; He, Q.-L.; You, S.-L. Org. Lett. 2009, 11, 3182.
(h) Shaikh, R. R.; Mazzanti, A.; Petrini, M.; Bartoli, G.;
Melchiorre, P. Angew. Chem. Int. Ed. 2008, 47, 8707. (i) Huang,
W.; Yang, J.; Li, X.; Yuan, L.; Ma, Y.; Zhou, Q.; Liang, D. Phospho-
rus, Sulfur Silicon Relat. Elem. 2016, 191, 772.
(5) Thirupathi, P.; Kim, S. S. J. Org. Chem. 2009, 74, 7755.
(6) Thirupathi, P.; Neupane, L. N.; Lee, K.-H. Tetrahedron 2011, 67,
7301.
(7) Kuhakarn, C.; Tangdenpaisal, K.; Kongsaeree, P.; Prabpai, S.;
Tuchinda, P.; Pohmakotr, M.; Reutrakul, V. Tetrahedron Lett.
2007, 48, 2467.
(8) Thirupathi, P.; Kim, S. S. Eur. J. Org. Chem. 2010, 1798.
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8, 4093.
NHBoc
SO2Ph
K2S2O8
toluene, r.t., 48 h
+
PhSO2K
HN
HN
3aa
20%
intermediate B
Scheme 7 Reactions of intermediate B
With α-Amido Sulfone: To a 10 mL flame-dried Schlenk tube equipped
with a stirring bar were added intermediate B (64.5 mg, 0.2 mmol), α-
amido sulfone 2a (69.5 mg, 0.2 mmol), and K2S2O8 (108.1 mg, 0.4
mmol). Toluene (1.2 mL) was injected into the tube at r.t. After stirring
for 48 h, the mixture was purified by silica gel chromatography to af-
ford the product 3aa; yield: 25.0 mg (36%).
With Potassium Benzenesulfinate: To a 10 mL flame-dried Schlenk
tube equipped with a stirring bar were added intermediate B (64.5
mg, 0.2 mmol), potassium benzenesulfinate (36.1 mg, 0.2 mmol), and
K2S2O8 (108.1 mg, 0.4 mmol). Toluene (1.2 mL) was injected into the
tube at r.t. After stirring for 48 h, the mixture was purified by silica gel
chromatography to afford the product 3aa; yield: 13.9 mg (20%).
(10) Kadam, S. T.; Thirupathi, P.; Kim, S. S. Tetrahedron 2009, 65,
10383.
Funding Information
(11) Blay, G.; Girón, R. M.; Montesinos-Magraner, M.; Pedro, J. R. Eur.
J. Org. Chem. 2013, 3885.
This work was supported by the Fundamental Research Funds for the
Central Universities (Grant No. 0903005203479), NSFC (21402016).
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–H