Iron-Catalyzed C-H Sulfonylmethylation of Indoles in Water-PEG400

Article abstract of DOI:10.1055/s-0039-1690675

An iron-catalyzed C-H sulfonylmethylation of indoles in water-PEG400 has been developed using p -toluenesulfonylmethyl isocyanide. This protocol enables direct regioselective construction of Csp ² -Csp ³ bond at the C3 position of indoles with a broad range of substrate compatibility in moderate to good yields, which is cost-effective and environmentally friendly.

Full text of DOI:10.1055/s-0039-1690675

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
© Georg Thieme Verlag Stuttgart · New York
2019, 30, A–E
letter
A
en
S. Lu et al.
Letter
Synlett
Iron-Catalyzed C–H Sulfonylmethylation of Indoles in Water–PEG400
Shuai Lu
R4
O
Yu-Shen Zhu
Ke-Xin Yan
Tian-Wei Cui
Xinju Zhu*
Xin-Qi Hao*
S
O
H
R2
R2
S
N
O
FeSO4•7H2O (15 mol%)
C
R3
R3
O
+
H2O/PEG400 = 3:2
110 °C, Ar, 24 h
R4
N
N
R1
0
0
0
0-0
0
0
3-1
9
6
6-
3
4
8
0
R1
R1 = H, Me, pyrimidyl
R
2 = Me, Ph
TosMIC
36 examples
up to 96% yields
Mao-Ping Song
R3 = H, OBn, OMe, Me, F, Cl, Br, COOMe, NO2
R4 = H, OMe, Me, F, Cl, CF3
College of Chemistry and Molecular Engineering, Zhengzhou
University, No. 100 of Science Road, Zhengzhou, 45000, P. R. of
China
zhuxinju@zzu.edu.cn
xqhao@zzu.edu.cn
Received: 18.06.2019
Accepted after revision: 23.08.2019
Published online: 10.09.2019
with propargylic alcohols19a and anilines19b (Scheme 1, d).
Considering the versatility of TosMIC in organic chemistry,
it is advisable to utilize TosMIC to realize other transforma-
tions.
DOI: 10.1055/s-0039-1690675; Art ID: st-2019-v0314-l
Abstract An iron-catalyzed C–H sulfonylmethylation of indoles in wa-
ter–PEG400 has been developed using p-toluenesulfonylmethyl isocya-
nide. This protocol enables direct regioselective construction of Csp2–
Csp3 bond at the C3 position of indoles with a broad range of substrate
compatibility in moderate to good yields, which is cost-effective and
environmentally friendly.
Previous work
a) TosMIC as the sulfonylating agent
R
R'
I2
CN
Ts
X
+
Ts
DMSO
Ar
R = H, Me
Ar
R' = H, I
Key words indoles, sulfonylmethylation, p-toluenesulfonylmethyl iso-
TosMIC
cyanide
X = H, COOH
b) TosMIC as the sulfinylating agent
R
R
O
As a representative nitrogen-containing heterocycle, in-
dole has served as a privileged scaffold in various natural
products, drugs, and functional molecules.1 Over the past
decades, considerable attention has been received in the
synthesis of indole skeleton2 and regioselective functional-
ization3 at the C2 and C3 position due to inherent reactivity
of the pyrrole core. Up to now, significant progress has been
made for arylation,4 alkenylation,5 alkynylation,6 amina-
tion,7 acylation,8 sulfuration,9 and alkylation10 of indoles.
On the other hand, sulfonyl methylated indoles11 are com-
mon pharmacophores with wide applications in pharma-
ceuticals.12 Meanwhile, the arylsulfonyl functionality is a
versatile synthetic intermediate, which can be utilized to
fulfill multiple transformations.13 However, the direct sul-
fonylmethylation of indoles are still less explored.14
BiBr3, AcOH
MeNO2
S
+
TosMIC
Ar
O
Ar
OH
c) TosMIC as the C1 building block
NHR
R
N
CuCl, TEMED
NMP
K2S
TosMIC
+
+
S
I
S
d) TosMIC as the amidating agent
O
Fe(OAc)2, TBHP
MeCN
N
+
TosMIC
N
Ar
N
Ts
Ar
H
Present work
e) TosMIC as the tosylmethylation agent
H
Ts
FeSO4•7H2O (15 mol%)
H2O–PEG400
p-Toluenesulfonylmethyl isocyanide (TosMIC) is
a
TosMIC
+
unique synthon in organic synthesis to access various het-
erocycles via 1,3-dipolar cycloadditions.15 Meanwhile, Tos-
MIC has also found to be a sulfonylating agent to access
benzoheteroles, -sulfonated carbonyl compounds, and vi-
nyl, allyl, and -iodo vinylsulfones (Scheme 1, a).16 Also, sul-
fination of alcohols with TosMIC has been reported
(Scheme 1, b).17 In addition, TosMIC can act as a C1 building
block to construct benzothiazolethiones (Scheme 1, c).18
Moreover, TosMIC was utilized to realize C–H amidation
N
N
H
H
Scheme 1 Different transformations of TosMIC
Our group has been interested in developing an efficient
methodology to achieve C–H functionalization of (hete-
ro)aromatics.20 Very recently, we have also reported C–H
arylation, alkylation of indoles, and C–H allylation of indo-
lines with arylboronic acids,21a maleimides,21b and vinyl-
© 2019. Thieme. All rights reserved. — Synlett 2019, 30, A–E
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
S. Lu et al.
Letter
Synlett
cyclopropanes.21c As a continuation of our previous work,
we herein describe the regioselective C3-sulfonylmethyla-
tion of indoles using TosMIC as the reaction partner
(Scheme 1, e). This work presents a supplement and im-
provement of a previous report,20c wherein unprotected
1H-indole gave a poor yield. Specially, the current protocol
utilizes iron salt as the catalyst, and a mixture of water and
PEG400 was utilized as the nontoxic media, which is more
cost-effective and environmentally benign.
To begin with, 1-H indole (1a) and TosMIC (2a) were uti-
lized as the model substrates to optimize the reaction con-
ditions (Table 1). To our delight, the desired C3-tosylmeth-
ylated indole 3a was obtained in 58% yield in the presence
of FeCl3 (30 mol%) in mixture solvent of H2O and PEG400
(v/v = 7:3) at 130 °C for 24 h. Subsequently, various iron
salts were screened, which indicated that FeSO4·7H2O was
the best choice to afford product 3a in 73% yield (Table 1,
entries 1–6). Next, the amount of FeSO4·7H2O was adjusted,
and the yield (68%) was not significantly decreased using 15
mol% FeSO4·7H2O (Table 1, entry 8). A survey of mixed sol-
vent ratios revealed that H2O/PEG400 (v/v = 3:2) was bene-
ficial to give 3a in 81% yield (Table 1, entry 10). To further
improve the reaction efficiency, the reaction temperature
was modulated. Product 3a could be isolated in 86% yield at
110 °C, while conducting the reaction at 100 °C led to a de-
creased yield (Table 1, entries 11 and 12). Moreover, it was
found that either shortening or extending the reaction time
would provide 3a in a decreased yield (Table 1, entries 13
and 14). When the reaction was carried out under air or ox-
ygen atmosphere, 3a was generated in 68% and 35% yields,
respectively (Table 1, entries 15 and 16). Moreover, other
nonaqueous solvents, namely toluene, DMF, and MeOH,
with different polarity and protic nature, were evaluated
(Table 1, entries 17–19). No product was detected when tol-
uene and DMF were utilized, while product 3a was ob-
tained in 55% yield in MeOH, suggesting an SN1-type mech-
anism might be involved. Finally, other metal-based Lewis
acids were also investigated, which all gave inferior results
(see Table S1 in the Supporting Information).
With the optimized conditions in hand, the substrate
scope of indoles was investigated (Scheme 2).22 In general, a
wide range of functional groups, including fluoro (3b, 3k,
3o), chloro (3c), ester (3d, 3l), methoxy (3e, 3j, 3q), and
Table 1 Optimization of Reaction Conditions for C3-Sulfonylmethylindolesa
Ts
iron salts
TosMIC
+
H2O/PEG400, 24 h
N
N
H
H
1a
2a
3a
Entry
Catalyst (mol%)
Solvent (ratio)
Atmosphere Temp (°C)
Time (h)
Yield (%)b
1
FeCl3 (30)
H2O/PEG400 (7:3)
H2O/PEG400 (7:3)
H2O/PEG400 (7:3)
H2O/PEG400 (7:3)
H2O/PEG400 (7:3)
H2O/PEG400 (7:3)
H2O/PEG400 (7:3)
H2O/PEG400 (7:3)
H2O/PEG400 (7:3)
H2O/PEG400 (3:2)
H2O/PEG400 (3:2)
H2O/PEG400 (3:2)
H2O/PEG400 (3:2)
H2O/PEG400 (3:2)
H2O/PEG400 (3:2)
H2O/PEG400 (3:2)
toluene
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
Ar
air
O2
Ar
Ar
Ar
130
130
130
130
130
130
130
130
130
130
110
100
110
110
110
110
110
110
110
24
24
24
24
24
24
24
24
24
24
24
24
12
36
24
24
24
24
24
58
73
55
66
16
46
67
68
60
81
86
80
67
75
68
35
–
2
FeSO4·7H2O (30)
FeC2O4 (30)
3
4
FeCl2·4H2O (30)
Fe(acac)3 (30)
5
6
Fe(NO3)3·9H2O (30)
FeSO4·7H2O (20)
FeSO4·7H2O (15)
FeSO4·7H2O (10)
FeSO4·7H2O (15)
FeSO4·7H2O (15)
FeSO4·7H2O (15)
FeSO4·7H2O (15)
FeSO4·7H2O (15)
FeSO4·7H2O (15)
FeSO4·7H2O (15)
FeSO4·7H2O (15)
FeSO4·7H2O (15)
FeSO4·7H2O (15)
7
8
9
10
11
12
13
14
15
16
17
18
19
DMF
–
MeOH
55
a Reaction conditions: 1a (0.1 mmol), 2a (0.3 mmol), iron salt, solvent (2 mL). Isolated yields.
Thieme. All rights reserved. — Synlett 2019, 30, A–E

C
S. Lu et al.
Letter
Synlett
this protocol, a gram-scale reaction was conducted using
1H-indole (1a) and TosMIC (2a) as the substrate, which de-
livered product 3a in 57% yield.
Ts
R2
FeSO4•7H2O (15 mol%)
R3
R2
TosMIC
+
R3
N
R1
H2O/PEG400 = 3:2
110 °C, Ar, 24 h
Finally, we also attempted to achieve chelation-assisted
functionalization, which unfortunately gave C3-tosylmeth-
ylated product 3w in 14% yield. Luckily, the absolute config-
uration of 3w was confirmed by X-ray diffraction (Figure S1
in the Supporting Information). To evaluate the synthetic
utility of this protocol, a gram-scale reaction was conduct-
ed using 1H-indole (1a) and TosMIC (2a) as the substrate,
which delivered product 3a in 57% yield.
Encouraged by the above results, the scope of the sulfo-
nylmethylation reaction was further extended to different
TosMIC derivatives (Scheme 3). It was found that para-sub-
stituted TosMICs bearing both electron-withdrawing (F, Cl,
and CF3) and electron-donating (OMe) groups could react
with indoles smoothly to deliver products 4a–m in 37–84%
yields.
To explore the reaction mechanism, a set of control ex-
periments were carried out (Scheme 4). Without Fe-
SO4·7H2O, the C3-sulfonylmethylated product could not be
detected, indicating the necessity of iron salt. Next, the rad-
ical scavenger reactions were performed under the opti-
mized conditions. It was found that C3-sulfonylmethylated
product 3a could still be isolated in 34% and 77% yield, re-
spectively, when excess TEMPO (3 equiv) and BHT (3 equiv)
was introduced into the catalytic system. Considering the
preliminary results obtained in Table 1 (entries 17–19), it
was postulated that an SN1-type C–C bond formation would
be the key step.
N
R1
1
2a
3
F
Cl
COOMe
Ts
Ts
Ts
Ts
N
N
N
N
H
H
H
H
3a, 86% (57%a)
3b, 93%
3c, 65%
3d, 29%
OMe
OBn
Ts
Ts
Ts
Ts
Ts
F
Br
N
N
H
N
H
N
H
H
3e, 60%
O2N
3f, 76%
3g, 29%
3h, 20%
Ts
Ts
F
Ts
MeO
N
N
H
N
H
N
MeOOC
Ts
H
H
3l, 48%
3i, 16%
3j, 59%
3k, 84%
Ts
Ts
Ts
N
N
H
H
N
N
Me
BnO
H
H
F
Me
3m, 82%
3n, 53%
3o, 90%
3p, 71%
Ts
Ts
Ts
Ts
Me
Ph
N
H
N
N
H
N
H
OMe
Me
3q, 67%
3r, 73%
3s, 96%
3t, 89%
Ts
Ts
Me
Iron metals could coordinate with isocyanides to form
mixed ligand complexes, which underwent facile C–N
cleavage to form carbon cation species due to the strong
binding ability between iron and cyanide.23 On the basis of
the control experiments and previous reports,20c,23 a plausi-
ble mechanism was proposed (Scheme 5). The catalytic cy-
cle initiates with the activation of TosMIC (2a) with Fe2+ to
produce the electrophilic species A, which was converted
into intermediate B. Next, nucleophilic substitution of in-
termediate B by 1H-indole (1a) results in the formation of
intermediate C. Finally, the desired product 3a was achieved
via H+ elimination.
In summary, we herein disclosed iron-catalyzed sulfo-
nylmethylation of indoles with TosMIC in a nontoxic medi-
um. A wide range of indoles and substituted TosMIC pro-
ceeded smoothly to afford products in moderate to good
yield. This methodology is environmentally benign, cost-ef-
fective, and additive-free.
Ts
Ph
N
N
N
pyrimidyl
3w, 14%
H
Me
3u, 21%
3v, 31%
Scheme 2 Substrate scope of indoles. Reagents and conditions: 1 (0.1
mmol), 2a (0.3 mmol), FeSO4·7H2O (15 mol%), H2O/PEG400 = 3:2 (2 mL),
under Ar, 110 °C, 24 h. a Scale-up: 1a (10 mmol, 1.17 g), 2a (30 mmol,
5.86 g).
benzyloxy (3f, 3n) at various positions of the benzene core
were well tolerated under the current protocol. For C5-sub-
stituted indoles, products 3g–i were isolated in low yields.
Next, C2-methyl- and phenyl-substituted indoles were also
tested to give the corresponding products 3r and 3s in 73%
and 96% yields, respectively. Apart from 1H-indoles, N-me-
thylindole was also proved to be the ideal substrate to pro-
vide product 3t and 3u in 89% and 21% yields. Interestingly,
when the C3 position of indole was occupied, the C2-tosyl-
methylated product 3v was obtained in 31% yield. Finally,
we also attempted to achieve chelation-assisted functional-
ization, which unfortunately gave C3-tosylmethylated
product 3w in 14% yield. Luckily, the absolute configuration
of 3w was confirmed by X-ray diffraction (Figure S1 in the
Supporting Information). To evaluate the synthetic utility of
Funding Information
Financial support from the National Natural Science Foundation of
China (Grant No. 21672192 and 21803059), the China Postdoctoral
Science Foundation (Grant No. 2016M602254 and 2016M600582),
the Program for Science & Technology Innovation Talents in Universi-
Thieme. All rights reserved. — Synlett 2019, 30, A–E

D
S. Lu et al.
Letter
Synlett
R4
O
S
O
O
FeSO4•7H2O (15 mol%)
S
N
+
C
O
H2O/PEG400 = 3:2
110 °C, Ar, 24 h
N
R1
N
R1
R4
O
2
1
4
O
F
Cl
O
O
O
F
Cl
Cl
S
S
S
S
S
O
O
O
O
O
N
N
N
N
N
Me
H
H
H
Me
4b, 84%
Me
4a, 63%
4c, 66%
4d, 68%
4e, 37%
O
S
Cl
O
S
O
O
O
S
S
S
O
O
O
O
O
N
H
N
N
N
N
H
F
Me
OMe
H
H
Me
4g, 70%
4i, 39%
4j, 44%
4f, 59%
4h, 77%
O
S
O
S
CF3
O
OMe
S
O
O
O
N
H
N
N
H
OMe
Me
4m, 61%
4k, 69%
4l, 73%
Scheme 3 Substrate scope of the substituted TosMIC. Reagents and conditions: 1 (0.1 mmol), 2 (0.3 mmol), FeSO4·7H2O (15 mol%), H2O/PEG400 = 3:2
(2 mL), under Ar, 110 °C, 24 h.
Ts
Supporting Information
standard conditions
Supporting information for this article is available online at
TosMIC
+
N
N
H
https://doi.org/10.1055/s-0039-1690675.
S
u
p
p
orti
n
gInformati
o
n
S
u
p
p
orti
n
gInformati
o
n
H
1a
2a
3a, 86%
NR
w/o FeSO4•7H2O
References and Notes
w/ TEMPO (3 equiv)
34%
(1) (a) Ishikura, M.; Abe, T.; Choshi, T.; Hibino, S. Nat. Prod. Rep.
2013, 30, 694. (b) Lancianesi, S.; Palmieri, A.; Petrini, M. Chem.
Rev. 2014, 114, 7108. (c) Ishikura, M.; Abe, T.; Choshi, T.; Hibino,
S. Nat. Prod. Rep. 2015, 32, 1389. (d) Zhang, M.-Z.; Chen, Q.;
Yang, G.-F. Eur. J. Med. Chem. 2015, 89, 421.
w/ BHT (3 equiv)
77%
Scheme 4 Control experiments
(2) (a) Cacchi, S.; Fabrizi, G. Chem. Rev. 2011, 111, 215. (b) Platon,
M.; Amardeil, R.; Djakovitch, L.; Hierso, J.-C. Chem. Soc. Rev.
2012, 41, 3929. (c) Inman, M.; Moody, C. J. Chem. Sci. 2013, 4, 29.
(d) Guo, T.; Huang, F.; Yu, L.; Yu, Z. Tetrahedron Lett. 2015, 56,
296.
ties of Henan Province (Grant No. 17HASTIT004), the Aid Project for
the Leading Young Teachers in Henan Provincial Institutions (Grant
No. 2015GGJS-157), and the Natural Science Foundation of Henan
Province (Grant No. 182300410255) is gratefully appreciated.
N
ati
o
n
a
l
N
atura
l
S
c
i
e
n
c
e
F
o
u
n
d
ati
o
n
of
C
h
i
n
a(2
1
6
7
2
1
9
2)Nati
o
n
a
l
N
atura
l
S
c
i
e
n
c
e
F
o
u
n
d
ati
o
n
of
C
h
i
n
a(2
1
8
0
3
0
5
9)C
h
i
n
a
P
ostd
o
ctora
l
S
c
i
e
n
c
e
F
o
u
n
d
ati
o
n(2
0
1
6
M
6
0
0
5
8
2)C
h
i
n
a
P
ostd
o
ctora
l
S
c
i
e
n
c
e
F
o
u
n
d
ati
o
n(2
0
1
6
M
6
0
2
2
5
4)Natura
l
S
c
i
e
n
c
e
F
o
u
n
d
ati
o
n
of
H
e
n
a
n
Pro
v
i
n
c
e(1
8
2
3
0
0
4
1
0
2
5
5)
Ts
Ts
N
Fe2+
H2O
1a
C
2a
Ts CH2
Fe2+
3a
– H3O+
N
A
Fe2+ + CN–
B
H
C
Scheme 5 Proposed reaction mechanism
Thieme. All rights reserved. — Synlett 2019, 30, A–E

E
S. Lu et al.
Letter
Synlett
(3) (a) Bandini, M.; Eichholzer, A. Angew. Chem. Int. Ed. 2009, 48,
9608. (b) Sandtorv, A. H. Adv. Synth. Catal. 2015, 357, 2403.
(c) Petrini, M. Chem. Eur. J. 2017, 23, 16115. (d) Ping, L.; Chung,
D. S.; Bouffard, J.; Lee, S.-G. Chem. Soc. Rev. 2017, 46, 4299.
(4) (a) Reay, A. J.; Hammarback, L. A.; Bray, J. T. W.; Sheridan, T.;
Turnbull, D.; Whitwood, A. C.; Fairlamb, I. J. S. ACS Catal. 2017, 7,
5174. (b) Chen, J.; Wu, J. Angew. Chem. Int. Ed. 2017, 56, 3951.
(c) Yang, Y.; Gao, P.; Zhao, Y.; Shi, Z. Angew. Chem. Int. Ed. 2017,
56, 3966. (d) Yang, Y.; Li, R.; Zhao, Y.; Zhao, D.; Shi, Z. J. Am.
Chem. Soc. 2016, 138, 8734. (e) Yang, Y.; Qiu, X.; Zhao, Y.; Mu, Y.;
Shi, Z. J. Am. Chem. Soc. 2016, 138, 495.
(5) (a) Inoue, F.; Saito, T.; Semba, K.; Nakao, Y. Chem. Commun.
2017, 53, 4497. (b) Moselage, M.; Sauermann, N.; Richter, S. C.;
Ackermann, L. Angew. Chem. Int. Ed. 2015, 54, 6352. (c) Zhou, X.;
Luo, Y.; Kong, L.; Xu, Y.; Zheng, G.; Lan, Y.; Li, X. ACS Catal. 2017,
7, 7296. (d) Xu, L.; Zhang, C.; He, Y.; Tan, L.; Ma, D. Angew. Chem.
Int. Ed. 2016, 55, 321. (e) Lv, J.; Wang, B.; Yuan, K.; Wang, Y.; Jia,
Y. Org. Lett. 2017, 19, 3664.
(15) (a) Qiu, G.; Ding, Q.; Wu, J. Chem. Soc. Rev. 2013, 42, 5257.
(b) Boyarskiy, V. P.; Bokach, N. A.; Luzyanin, K. V.; Kukushkin, V.
Y. Chem. Rev. 2015, 115, 2698. (c) Kaur, T.; Wadhwa, P.; Sharma,
A. RSC Adv. 2015, 5, 52769.
(16) (a) Liu, J.; Liu, Z.; Liao, P.; Bi, X. Org. Lett. 2014, 16, 6204.
(b) Chen, J.; Guo, W.; Wang, Z.; Hu, L.; Chen, F.; Xia, Y. J. Org.
Chem. 2016, 81, 5504. (c) Kadari, L.; Palakodety, R. K.;
Yallapragada, L. P. Org. Lett. 2017, 19, 2580. (d) Chu, X.-Q.; Ge,
D.; Loh, T.-P.; Shen, Z.-L. Org. Chem. Front. 2019, 6, 835.
(17) (a) Li, H.-J.; Wang, R.; Gao, J.; Wang, Y.-Y.; Luo, D.-H.; Wu, Y.-C.
Adv. Synth. Catal. 2015, 357, 1393. (b) Kadari, L.; Krishna, P. R.;
Prapurna, Y. L. Adv. Synth. Catal. 2016, 358, 3863. (c) Ji, Y.-Z.;
Wang, M.; Li, H.-J.; Liu, Y.; Wu, Y.-C. Eur. J. Org. Chem. 2016, 23,
4077.
(18) Dang, P.; Zeng, W.; Liang, Y. Org. Lett. 2015, 17, 34.
(19) (a) Liu, J.; Liu, Z.; Wu, N.; Liao, P.; Bi, X. Chem. Eur. J. 2014, 20,
2154. (b) Guerrero, I.; Segundo, M. S.; Correa, A. Chem. Commun.
2018, 54, 1627.
(6) (a) Zhang, Z.-Z.; Liu, B.; Wang, C.-Y.; Shi, B.-F. Org. Lett. 2015, 17,
4094. (b) Sauermann, N.; González, M. J.; Ackermann, L. Org.
Lett. 2015, 17, 5316.
(7) (a) Greulich, T. W.; Daniliuc, C. G.; Studer, A. Org. Lett. 2015, 17,
254. (b) Chen, S.; Feng, B.; Zheng, X.; Yin, J.; Yang, S.; You, J. Org.
Lett. 2017, 19, 2502. (c) Kim, Y.; Park, J.; Chang, S. Org. Lett.
2016, 18, 1892.
(8) (a) Wu, J.-C.; Song, R.-J.; Wang, Z.-Q.; Huang, X.-C.; Xie, Y.-X.; Li,
J.-H. Angew. Chem. Int. Ed. 2012, 51, 3453. (b) Shi, Q.; Li, P.; Zhu,
X.; Wang, L. Green Chem. 2016, 18, 4916. (c) Jeong, T.; Han, S.;
Mishra, N. K.; Sharma, S.; Lee, S.-Y.; Oh, J. S.; Kwak, J. H.; Jung, Y.
H.; Kim, I. S. J. Org. Chem. 2015, 80, 7243.
(20) (a) Zhang, L.-B.; Hao, X.-Q.; Zhang, S.-K.; Liu, Z.-J.; Zheng, X.-X.;
Gong, J.-F.; Niu, J.-L.; Song, M.-P. Angew. Chem. Int. Ed. 2015, 54,
272. (b) Du, C.; Li, P.-X.; Zhu, X.; Suo, J.-F.; Niu, J.-L.; Song, M.-P.
Angew. Chem. Int. Ed. 2016, 55, 13571. (c) Lu, S.; Zhu, X.; Li, K.;
Guo, Y.-J.; Wang, M.-D.; Zhao, X.-M.; Hao, X.-Q.; Song, M.-P. J.
Org. Chem. 2016, 81, 8370. (d) Zhu, X.; Shen, X.-J.; Tian, Z.-Y.; Lu,
S.; Tian, L.-L.; Liu, W.-B.; Song, B.; Hao, X.-Q. J. Org. Chem. 2017,
82, 6022. (e) Guo, Y.-J.; Lu, S.; Tian, L.-L.; Huang, E.-L.; Hao, X.-
Q.; Zhu, X.; Shao, T.; Song, M.-P. J. Org. Chem. 2018, 83, 338.
(f) Lu, S.; Tian, L.-L.; Cui, T.-W.; Zhu, Y.-S.; Zhu, X.; Hao, X.-Q.;
Song, M.-P. J. Org. Chem. 2018, 83, 13991. (g) Tian, L.-L.; Lu, S.;
Zhang, Z.-H.; Huang, E.-L.; Yan, H.-T.; Zhu, X.; Hao, X.-Q.; Song,
M.-P. J. Org. Chem. 2019, 84, 5213. (h) Zhao, X.-M.; Huang, E.-L.;
Zhu, Y.-S.; Li, J.; Song, B.; Zhu, X.; Hao, X.-Q. Org. Biomol. Chem.
2019, 17, 4869.
(21) (a) Zhu, X.; Su, J.-H.; Du, C.; Wang, Z.-L.; Ren, C.-J.; Niu, J.-L.;
Song, M.-P. Org. Lett. 2017, 19, 596. (b) Liu, S.-L.; Li, Y.; Guo, J.-
R.; Yang, G.-C.; Li, X.-H.; Gong, J.-F.; Song, M.-P. Org. Lett. 2017,
19, 4042. (c) Wang, Q.; Zhi, C.-L.; Lu, P.-P.; Liu, S.; Zhu, X.; Hao,
X.-Q.; Song, M.-P. Adv. Synth. Catal. 2019, 361, 1253.
(22) General Procedure for Preparation of Products 3 and 4
To a 15 mL two-necked Schlenk tube fitted with glass stopper
were added indoles 1 (0.1 mmol), TosMIC derivatives 2 (0.3
mmol), and FeSO4·7H2O (0.015 mmol, 4.2 mg) in a mixed solvent
of H2O and PEG400 (v/v = 3:2, 2 mL) under an Ar atmosphere
using the standard Schlenk techniques. The Schlenk tube was
capped and heated at 110 °C for 24 h. The reaction mixture was
then cooled to room temperature and concentrated directly. After
removal of solvent, the residue was purified by preparative thin-
layer chromatography (petroleum ether/EtOAc = 1:1) to give the
desired product 3 and 4.
(9) (a) Xiao, F.; Xie, H.; Liu, S.; Deng, G.-J. Adv. Synth. Catal. 2014,
356, 364. (b) Xiao, F.; Chen, H.; Xie, H.; Chen, S.; Yang, L.; Deng,
G.-J. Org. Lett. 2014, 16, 50. (c) Gensch, T.; Klauck, F. J. R.;
Glorius, F. Angew. Chem. Int. Ed. 2016, 55, 11287. (d) Gandeepan,
P.; Koeller, J.; Ackermann, L. ACS Catal. 2017, 7, 1030. (e) Maity,
S.; Karmakar, U.; Samanta, R. Chem. Commun. 2017, 53, 12197.
(10) (a) Dalpozzo, R. Chem. Soc. Rev. 2015, 44, 742. (b) Gao, X.; Wu,
B.; Huang, W.-X.; Chen, M.-W.; Zhou, Y.-G. Angew. Chem. Int. Ed.
2015, 54, 11956. (c) Liang, Y.-F.; Massignan, L.; Liu, W.;
Ackermann, L. Chem. Eur. J. 2016, 22, 14856. (d) Cabrero-
Antonino, J. R.; Adam, R.; Junge, K.; Beller, M. Chem. Sci. 2017, 8,
6439. (e) Yan, S.-Y.; Zhang, Z.-Z.; Shi, B.-F. Chem. Commun. 2017,
53, 10287. (f) Xia, J.; Huang, Z.; Zhou, X.; Yang, X.; Wang, F.; Li, X.
Org. Lett. 2018, 20, 740.
(11) Palmieri, A.; Petrini, M. Chem. Rec. 2016, 16, 1353.
(12) (a) Yamada, M.; Ichikawa, T.; Li, M.; Itoh, K.; Tamura, N.;
Kitazaki, T. Bioorg. Med. Chem. 2008, 16, 3941. (b) Marsilje, T. H.;
Alper, P. B.; Lu, W.; Mutnick, D.; Michellys, P.-Y.; He, Y.;
Karanewsky, D. S.; Chow, D.; Gerken, A.; Lao, J.; Kim, M.-J.;
Seidel, H. M.; Tian, S.-S. Bioorg. Med. Chem. Lett. 2008, 18, 5259.
(13) (a) Lancianesi, S.; Palmieri, A.; Petrini, M. Adv. Synth. Catal.
2012, 354, 3539. (b) Matsuzaki, K.; Furukawa, T.; Tokunaga, E.;
Matsumoto, T.; Shiro, M.; Shibata, N. Org. Lett. 2013, 15, 3282.
(c) Luo, J.; Wu, B.; Chen, M.-W.; Jiang, G.-F.; Zhou, Y.-G. Org. Lett.
2014, 16, 2578. (d) Liu, Z.-S.; Li, W.-K.; Kang, T.-R.; He, L.; Liu, Q.
Org. Lett. 2015, 17, 150. (e) Ohmatsu, K.; Furukawa, Y.;
Nakaguro, D.; Ooi, T. Chem. Lett. 2015, 44, 1350. (f) Chen, P.; Lu,
S.-M.; Guo, W.; Liu, Y.; Li, C. Chem. Commun. 2016, 52, 96.
(14) (a) Ballini, R.; Palmieri, A.; Petrini, M.; Torregiani, E. Org. Lett.
2006, 8, 4093. (b) Huang, W.; Yang, J.; Li, X.; Yuan, L.; Ma, Y.;
Zhou, Q.; Liang, D. Phosphorus, Sulfur Silicon Relat. Elem. 2016,
191, 772.
4-Fluoro-3-(tosylmethyl)-1H-indole (3b)
Brown solid (28.3 mg, 93%), mp 162–163 °C. 1H NMR (600 MHz,
CDCl3):  = 8.70 (s, 1 H), 7.59 (d, J = 7.4 Hz, 2 H), 7.18–7.16 (m, 3
H), 7.07–7.06 (m, 1 H), 7.01–6.98 (m, 1 H), 6.60 (t, J = 9.2 Hz, 1
H), 4.64 (s, 2 H), 2.36 (s, 3 H). 13C{1H} NMR (150 MHz, CDCl3):
 = 156.7 (d, J = 244.9 Hz), 144.5, 138.3 (d, J = 10.8 Hz), 135.5,
129.2, 128.5, 126.2, 122.8 (d, J = 8.0 Hz), 116.0 (d, J = 18.8 Hz),
107.6 (d, J = 3.6 Hz), 105.2 (d, J = 19.2 Hz), 100.6, 54.8, 21.6. 19
F
NMR (565 MHz, CDCl3):  = –124.6. HRMS (positive ESI): m/z
[M + Na]+ calcd for C16H14FNNaO2S+: 326.0621; found: 326.0621.
(23) (a) Dance, I. G.; Dean, P. A. W.; Fisher, K. J.; Harris, H. H. Inorg.
Chem. 2002, 41, 3560. (b) Halbauer, K.; Dönnecke, D.; Görls, H.;
Imhof, W. Z. Anorg. Allg. Chem. 2006, 632, 1477. (c) Tennent, C.
L.; Jones, W. L. Can. J. Chem. 2005, 83, 626.
Thieme. All rights reserved. — Synlett 2019, 30, A–E