Copper-Catalyzed Methylthiolation of Aryl Iodides and Bromides with Dimethyl Disulfide in Water

Article abstract of DOI:10.1055/s-0040-1707131

An efficient route to aryl methyl sulfides through the copper-catalyzed coupling reaction of aryl iodides or bromides with dimethyl disulfide in water is described. Electron-donating and electron-withdrawing functional groups in the substrates were tolerated, and the corresponding products were obtained in moderate to good yields.

Full text of DOI:10.1055/s-0040-1707131

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Georg Thieme Verlag Stuttgart · New York
2020, 31, A–E
letter
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Synlett
Y.-y. Wang et al.
Letter
Copper-Catalyzed Methylthiolation of Aryl Iodides and Bromides
with Dimethyl Disulfide in Water
Ying-yu Wang
Xiang-mei Wu*
Ming-hua Yang
Cu(OAc)2·H2O
KOH
X
SMe
R
+
MeSSMe
R
TBAB
H2O, 100 °C
X = I, Br
2
1
9 examples
5–80% yield
R = H, OMe, SMe, Me, NH2
halo, NO2, CN, etc.
Department of Chemistry, Lishui University,
Lishui, Zhejiang 323000, P. R. of China
lswxm7162@163.com
mhyang@lsu.edu.cn
1
8
Received: 06.02.2020
Accepted after revision: 23.04.2020
Published online: 02.07.2020
olation surrogate for coupling with aryl halides, arylcar-
19
20
boxylic acids, arenes, or heteroarenes. Although various
sulfur-transferring reagents can be used in the preparation
of aryl methyl sulfides, dimethyl disulfide, a commercial
food additive and sulfidation agent, continues to attract at-
tention due to its high reactivity and relative stability com-
pared with gaseous methanethiol. Accordingly, Taniguchi
reported alkyl- or arylthiolations of aryl iodides with di-
methyl disulfide and other disulfide compounds in the
presence of a nickel catalyst and zinc under neutral condi-
tions.21 Morales-Morales and co-workers developed a simi-
lar procedure for aryl iodides or bromides catalyzed by a
fluorinated bisimino nickel NNN pincer complex along with
zinc.22 Atom-economic directed ortho-lithiations of aryl C–
DOI: 10.1055/s-0040-1707131; Art ID: st-2020-u0076-l
Abstract An efficient route to aryl methyl sulfides through the copper-
catalyzed coupling reaction of aryl iodides or bromides with dimethyl
disulfide in water is described. Electron-donating and electron-with-
drawing functional groups in the substrates were tolerated, and the
corresponding products were obtained in moderate to good yields.
Key words methylthiolation, aryl halides, dimethyl disulfide, aryl
methyl sulfides, copper catalysis
Aryl methyl sulfide fragments commonly occur as key
units in a variety of pharmaceuticals and biologically active
molecules potentially useful in the treatment of such dis-
eases as diabetes, inflammatory disease, Alzheimer’s dis-
2
3
H bonds have been developed by Stanetty et al., who used
1,1-dimethylethyl phenylcarbamate, and by Fort and Ro-
driquez, who used 2-chloropyridyl group complexation fol-
lowed by electrophilic substitution with dimethyl disulfide.
The use of dialkyl hydrazides for directed ortho-metalations
1
ease, or Parkinsonism. In addition, these compounds can
act as effective electrophiles for some transition-metal-cat-
2
3
4
alyzed C–C, C–N, or C–B coupling reactions, or can serve
as reactants for carbothiolation of terminal alkynes.5 Al-
though considerable progress has been made in the conven-
tional construction of C(aryl)–S bonds by cross-coupling of
thiols with aryl halides or pseudohalides with various tran-
25
was reported by Wuts and co-workers. Subsequently, Yu
and co-workers reported a Cu(OAc) -mediated methylthio-
lation of the C–H bond of 2-phenylpyridine with dimethyl
disulfide under an air atmosphere.26 Another direct thiola-
tion of aryl C–H bonds with disulfides under palladium and
2
6
7
8
9
sition metals such as palladium, nickel, copper, cobalt, or
10
27
indium as catalysts, the synthesis of aryl methyl ana-
logues in this fashion is challenging, presumably because of
the instability and high volatility of methanethiol. Reliable
approaches for the synthesis of aryl methyl sulfides include
copper co-catalysis was reported by Nishihara’s group.
Several other elegant protocols that apparently meet
the requirements of green and sustainable chemistry have
also been recently developed. For example, Wangelin and
co-workers developed a mild metal-free synthesis of aryl
methyl sulfides from arenediazonium salts and dimethyl
disulfide in the presence of the organic dye eosin Y and vis-
ible-light irradiation or a weak and environmentally benign
1
1
the reduction of the corresponding sulfoxides; treatment
of aryl thiols with iodomethane, dimethyl carbonate,13 or
12
other sulfur-containing reagents such as sodium methan-
14
15
ethiolate, sulfur powder, or S-methylisothiourea sul-
16
28
fate; and the combination of masked inorganic sulfur and
base. At about the same time, we reported a transition-
17
dimethyl carbonate with aryl halides. In addition, dimeth-
yl sulfoxide has recently emerged as an effective methylthi-
metal-free C–S bond formation from arylboronic acids and
dimethyl disulfide under neutral conditions.29 Moreover, a
©
2020. Thieme. All rights reserved. Synlett 2020, 31, A–E
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Synlett
Y.-y. Wang et al.
Letter
unified method for the thiolation of aryl or vinyl iodides
with dimethyl disulfide by using the visible-light photocat-
Table 1 Screening of Reaction Conditions for C–S Coupling of p-Iodo-
anisole and Dimethyl Disulfidea
30
alyst fac-Ir(ppy) has been reported by Polyzos’s group.
3
catalyst
base
I
SMe
Nevertheless, each of the procedures discussed above
entails various disadvantages, such as the need to use ex-
pensive metals, stoichiometric amounts of transition-metal
sources, appropriate ligands, prefunctionalized substrates,
organic peroxides, environmentally damaging organic sol-
vents, or harsh reaction conditions. Undoubtedly, an effi-
cient and environmentally benign synthetic procedure
would still be much appreciated. Considering that aryl io-
dides and bromides are readily accessible, inexpensive, and
compatible with numerous functional groups, and that wa-
ter is an ideal and ecofriendly solvent due to its lack of tox-
icity and wide availability, we wish to report a route to aryl
methyl sulfides through the copper-catalyzed coupling of
aryl iodides or bromides with dimethyl disulfide in neat
water as a reaction medium.
+
MeSSMe
H2O, 100 °C
MeO
MeO
b
Entry
Catalyst
Base
Additive
Yield (%)
1
2
Cu(acac)
Cu(acac)
2
2
Na
Na
Na
Na
2
2
2
2
CO
3
3
3
3
3
3
3
3
3
3
–
<5
40
48
35
38
36
35
28
25
–
CO
CO
CO
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAF
TBAC
PEG-400
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
TBAB
3
Cu(OAc)
CuSO ·5H
CuCl ·2H O
2 2
·H O
4
4
2
O
5
2
2
2
Na CO
6
CuBr
2
Na
Na
Na
Na
Na
2
2
2
2
2
CO
CO
CO
CO
CO
7
CuI
CuBr
CuCl
–
8
9
We began our investigations by coupling of p-iodoan-
10
11
isole with dimethyl disulfide in the presence of Cu(acac) as
2
Cu(OAc) ·H O
K2CO3
Cs CO
PO ·H
50
55
35
25
78
75
–
2
2
2
2
2
2
2
2
2
2
a catalyst and Na CO as a base in a sealed tube with neat
2
3
12
13
14
15
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
·H
·H
·H
·H
O
O
O
O
2
3
water as solvent under air. Although only a trace of the de-
sired product was detected under these conditions (Table 1,
entry 1), 4-(methoxy)thioanisole was obtained in 40% yield
when 5 mol% of tetrabutylammonium bromide (TBAB) was
added as a phase-transfer reagent at 100 °C for 12 hours
K
3
4
2
O
KF
KOH
16
Cu(OAc) ·H O
2
2
2
2
2
2
2
2
2
2
2
2
NaOH
–
(entry 2). Encouraged by this result, we attempted to opti-
17
18
19
20
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
·H
·H
·H
·H
·H
O
O
O
O
Oc
mize the reaction conditions further. First, we screened
several Cu(II) salts [Cu(OAc) ·H O, CuSO ·5H O, CuCl ·2H O,
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
KOH
74
75
<5
70
78
77
72
77
78
65
79
78
2
2
4
2
2
2
and CuBr ] and various Cu(I) compounds (CuI, CuBr and Cu-
2
Cl) as catalysts for this transformation (entries 3–9).
Cu(OAc) ·H O as catalyst provided a markedly higher yield
21
22
2
2
than any of the other copper sources. Under otherwise
identical conditions, none of the target product was detect-
ed in the absence of a copper catalyst (entry 10). Subse-
quently, several bases were tested (entries 11–16), and the
results suggested that KOH is the most suitable base for this
transformation, furnishing in the product in 78% yield (en-
try 15). The reaction was sluggish in the absence of any
base (entry 17). On replacement of TBAB with tetrabu-
tylammonium fluoride (TBAF) or tetrabutylammonium
chloride (TBAC), the methylthiolation product was obtained
in comparable yields (entries 18 and 19), whereas only a
small amount of desired product was detected when po-
ly(ethylene glycol) (PEG-400) was used as the phase-trans-
fer agent (entry 20). The effect of the amount of
Cu(OAc) ·H O was then examined, and it was found that the
Cu(OAc) ·H O
d
2
2
2
2
2
2
2
2
2
2
2
2
Oe
2
2
2
2
3
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
·H
·H
·H
·H
·H
4f
5g
6h
O
O
O
O
27i
28
j
Cu(OAc) ·H O
2
2
9k
2
Cu(OAc)
2
·H
2
O
a
Reaction conditions: p-iodoanisole (1.0 mmol), dimethyl disulfide (1.2
2
mmol), catalyst (0.1 mmol), base (2 mmol), additive (0.05 mmol), H O
(
2.0 mL), under air, 12h, 100 °C.
b
c
d
e
f
Isolated yield.
mol%.
15 mol%.
0 mol%
5
2
2
2
Dimethyl disulfide (1.0 mmol).
Dimethyl disulfide (1.5 mmol).
Dimethyl disulfide (2.0 mmol).
g
h
i
yield fell slightly on decreasing the amount of this catalyst
but remained almost the same when 10 or 15mol% of the
catalyst was used (entries 21–23). In addition, we found
that the optimal amount of dimethyl disulfide relative to p-
iodoanisole was 1.2 equivalents (entries 24–26). The yield
dropped noticeably at a lower temperature (entry 27),
while a comparable yield was obtained at a higher tempera-
ture (entry 28), so the optimal temperature for the current
80 °C.
j
120 °C.
Under N .
2
k
reaction is 100 °C. Moreover, changing the atmosphere
from air to nitrogen did not increase the conversion (entry
29), making the reaction manipulatively simple and conve-
©
2020. Thieme. All rights reserved. Synlett 2020, 31, A–E

C
Synlett
Y.-y. Wang et al.
Letter
nient. On the basis of these results, it appeared that the op-
timal conditions for the cross-coupling of p-iodoanisole
with dimethyl disulfide in water involve the use of
Cu(OAc) ·H O as catalyst, KOH as base, and TBAB as phase-
Table 2 Methylthiolation of Aryl Iodides with Dimethyl Disulfidea,32
Cu(OAc)2·H2O
KOH
ArI
+
MeSSMe
ArSMe
TBAB
2
2
H2O, 100 °C
transfer reagent at 100 °C for 12 hours under air.
To further explore the generality and scope of this pro-
tocol, a wide array of aryl iodides were examined. Specifi-
cally, iodobenzene and aryl iodides with electron-donating
b
Entry
Ar
Yield (%)
1
2
3
4
5
6
7
8
9
Ph
4-MeOC
3-MeOC H
76
78
75
58
70
72
68
45
77
70
50
71
60
78
67
48
50
65
58
52
80
78
74
70
65
60
substituents, including OMe, SMe, Me, or NH groups, were
6
H
4
4
4
2
compatible with this procedure and afforded the corre-
sponding methylthiolation products in satisfactory yields
6
2-MeOC
6
H
(Table 2, entries 1–10). Notably, the preserved amino group
3-MeSC
6
H
4
is attractive because most arylamines can be easily trans-
formed into various arenediazonium salts that have superi-
or reactivity to the corresponding aryl halides and can con-
sequently serve as useful partners in palladium-catalyzed
carbon–carbon or carbon–heteroatom cross-coupling reac-
4-MeC
3-MeC
6
6
H
4
4
3
H
2,4,6-Me
6 2
C H
4-H NC H
2
6
4
4
31
tions. Moreover, the reaction was highly chemoselective
towards other halogen groups of aryl iodides. In other
words, the respective desired products were obtained in
good yields while fluoro, chloro, or bromo groups remained
intact, which might facilitate further functionalization of
the phenyl ring (entries 11–20). In the case of 1,4-diiodo-
benzene, the monomethylthiolation product was obtained
together with the bismethylthiolation product, even though
an excess of dimethyl disulfide was used. Aryl iodides with
electron-withdrawing substituents such as NO2 and CN
groups were also good coupling partners (entries 21–24). It
is noteworthy that, like para- or meta-substituted aryl io-
dides, the corresponding ortho-substituted substrates also
reacted smoothly with dimethyl disulfide, albeit giving the
desired products in moderate yields. The hetaryl analogues
10
11
12
13
2-H
2
NC
6
H
6 4
4-IC H
4-BrC
6
H
H
4
3-BrC
6
4
14
4-ClC
3-ClC
2-ClC
6
6
6
H
H
H
4
4
4
15
16
17
18
19
2 6 3
3,5-Cl C H
4-FC
3-FC
6
H
4
4
4
6
H
20
6
2-FC H
21
22
23
24
4-O
3-O
2
NC
NC
6
H
4
4
2
6
H
2- and 3-iodopyridine reacted readily to provide the corre-
4-NCC
6
6
H
4
4
sponding hetaryl methyl sulfides which are of much inter-
est for their biological activities (entries 25 and 26).
Further experiments showed that bromobenzene and p-
tolyl bromide were not very reactive under our reaction
conditions, whereas aryl bromides with electron-with-
3-NCC
H
25
2-pyridyl
3-pyridyl
26
a
Reaction conditions: ArI (1.0 mmol), dimethyl disulfide (1.2 mmol),
drawing substituents such as NO or CN showed better re-
Cu(OAc)
2
·H
2
O (0.1 mmol), KOH (2.0 mmol), TBAB (0.05 mmol), H
2
O (2.0
2
mL), 100 °C, 12 h.
activity for this transformation (Table 3, entries 1–5). To our
delight, the hetaryl analogues 2-bromopyridine, 3-bro-
mopyridine, 3-bromoquinoline, and 4-bromoisoquinoline
reacted readily to afford the desired products in acceptable
yields (entries 6–9). Furthermore, although the yield from
p-iodoanisole did not change markedly on increasing the
temperature above 100 °C, elevating the reaction tempera-
ture to 130 °C significantly improved the yields from aryl
bromides. As expected, only a trace of amount of product
was detected when 1-chloro-4-nitrobenzene was used as
substrate under the standard conditions (entry 10).
b
Isolated yield.
Cu(OAc)2·H2O (0.1 equiv)
KOH (2 equiv)
I
SMe
+
MeSSMe
1.2 equiv
TBAB (0.05 equiv)
H2O (10 mL), 100 °C, 12 h
MeO
MeO
(0.56 g, 73%)
(
5 mmol, 1.17 g)
Scheme 1 Gram-scale reaction
To further demonstrate the synthetic utility of this
strategy, a representative gram-scale reaction of p-iodoan-
isole with dimethyl disulfide was explored, and the expect-
ed product was obtained in a satisfactory 73% yield
To investigate the reaction mechanism, we performed a
radical-trap experiment. In the presence of an excess of the
radical scavenger 2,2,6,6-tetramethylpiperidine N-oxide
(TEMPO) or butylated hydroxytoluene (BHT), coupling of p-
iodoanisole with dimethyl disulfide under otherwise iden-
(Scheme 1).
©
2020. Thieme. All rights reserved. Synlett 2020, 31, A–E

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Synlett
Y.-y. Wang et al.
Letter
Table 3 Methylthiolation of Aryl Bromides with Dimethyl Disulfidea,32
um. This procedure dispenses with a ligand, an inert atmo-
sphere, and a dry nonaqueous solvent, and is tolerant of
structurally diverse substrates, making it a powerful com-
plement to common approaches to the synthesis of a broad
range of aryl methyl sulfides.
Cu(OAc)2·H2O
Br
SMe
KOH
R
+
MeSSMe
R
TBAB
H2O, 100 °C
b
Entry
Ar
Yield (%)
Funding Information
1
2
3
4
5
6
7
8
9
H
15 (38)
12 (35)
55 (70)
48 (65)
45 (66)
38 (60)
32 (52)
30 (48)
35 (52)
(8)
4-MeC
6
H
4
We are grateful for financial support from the Natural Science Foun-
dation of Zhejiang Province (No. LY18B020004) and the National Nat-
ural Science Foundation of China (No. 21572094).
4-O
2-O
2
2
NC
6
H
4
4
N
atural S
c
i
e
n
c
e
F
o
u
n
d
ati
o
n
of
Z
h
e
j
i
a
n
g
Pro
v
i
n
c
e
(L
Y
1
8
B
0
2
0
0
0
4)Nati
o
n
a
l Natural S
c
i
e
n
c
e
F
o
u
n
d
ati
o
n
of
C
h
i
n
a
(2
1
5
7
2
0
9
4)
NC
6
H
6 4
4-NCC H
Supporting Information
2-pyridyl
3-pyridyl
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1707131.
quinolin-3-yl
S
u
p
p
orit
n
g Inform ati
o
n
S
u
p
p
orit
n
g Inform ati
o
n
isoquinoline-4-yl
2-O NC
Reaction conditions: aryl halide (1.0 mmol), dimethyl disulfide (1.2
1
0c
2
6
H
4
References and Notes
a
(1) (a) Kalgutkar, A. S.; Kozak, K. R.; Crews, B. C.; Marnett, L. J.
mmol), Cu(OAc)
2
·H O (0.1 mmol), KOH (2.0 mmol), TBAB (0.05 mmol),
O (2.0 mL), 100 °C, 12 h.
2
H
2
J. Med. Chem. 1998, 41, 4800. (b) Laufer, S. A.; Striegel, H.-G.;
Wagner, G. K. J. Med. Chem. 2002, 45, 4695. (c) Laufer, S. A.;
Zimmermann, W.; Ruff, K. J. J. Med. Chem. 2004, 47, 6311.
b
Isolated yield. Yields obtained at 130 °C are shown in parentheses.
2
c
2 6 4
-O NC H Cl.
(d) Gallardo-Godoy, A.; Fierro, A.; McLean, T. H.; Castillo, M.;
Cassels, B. K.; Reyes-Parada, M.; Nichols, D. E. J. Med. Chem.
tical conditions still took place. These results suggested that
the current methylthiolation does not involve radicals. On
the basis of the above results and reports in the litera-
2
2
005, 48, 2407. (e) Pradhan, T. K.; De, A.; Mortier, J. Tetrahedron
005, 61, 9007.
(2) (a) Dubbaka, S. R.; Vogel, P. Angew. Chem. Int. Ed. 2005, 44, 7674.
(b) Peña-Cabrera, E.; Aguilar-Aguilar, A.; González-Domínguez,
M.; Lager, E.; Zamudio-Vázquez, R.; Godoy-Vargas, J.;
Villanueva-García, F. Org. Lett. 2007, 9, 3985. (c) Prokopcová, H.;
Kappe, C. O. Angew. Chem. Int. Ed. 2009, 48, 2276. (d) Metzger,
A.; Melzig, L.; Despotopoulou, C.; Knochel, P. Org. Lett. 2009, 11,
4228. (e) Melzig, L.; Metzger, A.; Knochel, P. J. Org. Chem. 2010,
75, 2131. (f) Melzig, L.; Metzger, A.; Knochel, P. Chem. Eur. J.
2011, 17, 2948. (g) Ookubo, Y.; Wakamiya, A.; Yorimitsu, H.;
Osuka, A. Chem. Eur. J. 2012, 18, 12690. (h) Modha, S. G.; Mehta,
V. P.; Van der Eycken, E. V. Chem. Soc. Rev. 2013, 42, 5042.
20b,d,g,33
ture,
a plausible reaction pathway for the reaction
was proposed (Scheme 2). Initially, in the presence of base,
KSMe is generated from dimethyl disulfide, along with
–
HOSMe. The reactive sulfhydryl ion intermediate MeS then
reacts with Cu(OAc) to form species A, which adds to the
2
aryl halide and oxidatively produces intermediate B togeth-
–
er with a halide ion X . Reaction of B with KSMe provides
the desired product together with KX, completing the cata-
lytic cycle.
(i) Hooper, J. F.; Young, R. D.; Pernik, I.; Weller, A. S.; Willis, M. C.
Chem. Sci. 2013, 4, 1568. (j) Liu, J.; Liu, Y.; Du, W.; Dong, Y.; Liu,
J.; Wang, M. J. Org. Chem. 2013, 78, 7293. (k) Pan, F.; Wang, H.;
Shen, P.-X.; Zhao, J.; Shi, Z.-J. Chem. Sci. 2013, 4, 1573. (l) Wang,
L.; He, W.; Yu, Z. Chem. Soc. Rev. 2013, 42, 599. (m) Pan, F.; Shi,
Z.-J. ACS Catal. 2014, 4, 280. (n) Otsuka, S.; Fujino, D.; Murakami,
K.; Yorimitsu, H.; Osuka, A. Chem. Eur. J. 2014, 20, 13146.
(o) Quan, Z.-J.; Lv, Y.; Jing, F.-Q.; Jia, X.-D.; Huo, C.-D.; Wang, X.-
C. Adv. Synth. Catal. 2014, 356, 325. (p) Zhu, F.; Wang, Z.-X. Org.
Lett. 2015, 17, 1601.
MeSSMe
HOSMe
+
KOH
KSMe
Cu(OAc)2
KOAc
(
AcO) Cu¢òSMe
ArX
A
ArSMe
KX
KSMe X–
+
(3) (a) Ram, V. J.; Agarwal, N. Tetrahedron Lett. 2001, 42, 7127.
(
b) Sugahara, T.; Murakami, K.; Yorimitsu, H.; Osuka, A. Angew.
(AcO)
SMe
Ar
Cu¢ó
Chem. Int. Ed. 2014, 53, 9329. (c) Wang, X.; Tang, Y.; Long, C.-Y.;
Dong, W.-K.; Li, C.; Xu, X.; Zhao, W.; Wang, X.-Q. Org. Lett. 2018,
B
2
0, 4749.
4) (a) Uetake, Y.; Niwa, T.; Hosoya, T. Org. Lett. 2016, 18, 2758.
b) Bhanuchandra, M.; Baralle, A.; Otsuka, S.; Nogi, K.;
Scheme 2 Plausible mechanism for the methylthiolation
(
(
Yorimitsu, H.; Osuka, A. Org. Lett. 2016, 18, 2966.
In conclusion, a practical protocol for methylthiolation
of aryl iodides or bromides with dimethyl disulfide has
been developed that uses neat water as the reaction medi-
(
5) (a) Hooper, J. F.; Chaplin, A. B.; González-Rodríguez, C.;
Thompson, A. L.; Weller, A. S.; Willis, M. C. J. Am. Chem. Soc.
2012, 134, 2906. (b) Arambasic, M.; Hooper, J. F.; Willis, M. C.
©
2020. Thieme. All rights reserved. Synlett 2020, 31, A–E

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Synlett
Y.-y. Wang et al.
Letter
Org. Lett. 2013, 15, 5162. (c) Iwasaki, M.; Topolovčan, N.; Hu, H.;
Nishimura, Y.; Gagnot, G.; Nanakorn, R.; Yuvacharaskul, R.;
Nakajima, K.; Nishihara, Y. Org. Lett. 2016, 18, 1642.
Xu, L.-W. RSC Adv. 2015, 5, 30389. (f) Xu, Y.; Cong, T.; Liu, P.;
Sun, P. Org. Biomol. Chem. 2015, 13, 9742. (g) Ravi, C.; Mohan, D.
C.; Adimurthy, S. Org. Biomol. Chem. 2016, 14, 2282.
(21) Taniguchi, N. J. Org. Chem. 2004, 69, 6904.
(22) Baldovino-Pantaleón, O.; Hernández-Ortega, S.; Morales-
Morales, D. Adv. Synth. Catal. 2006, 348, 236.
(
6) (a) Migita, T.; Shimizu, T.; Asami, Y.; Shiobara, J.-i.; Kato, Y.;
Kosugi, M. Bull. Chem. Soc. Jpn. 1980, 53, 1385. (b) Mann, G.;
Baranano, D.; Hartwig, J. F.; Rheingold, A. L.; Guzei, I. A. J. Am.
Chem. Soc. 1998, 120, 9205. (c) Li, G. Y.; Zheng, G.; Noonan, A. F.
J. Org. Chem. 2001, 66, 8677. (d) Itoh, T.; Mase, T. Org. Lett. 2004,
(23) Stanetty, P.; Koller, H.; Mihovilovic, M. J. Org. Chem. 1992, 57,
6833.
6
, 4587. (e) Mispelaere-Canivet, C.; Spindler, J.-F.; Perrio, S.;
(24) Fort, Y.; Rodriguez, A. L. J. Org. Chem. 2003, 68, 4918.
(25) Pratt, S. A.; Goble, M. P.; Mulvaney, M. J.; Wuts, P. G. M. Tetrahe-
dron Lett. 2000, 41, 3559.
Beslin, P. Tetrahedron 2005, 61, 5253. (f) Fernández-Rodríguez,
M. A.; Shen, Q.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 2180.
(
g) Dahl, T.; Tornøe, C. W.; Bang-Andersen, B.; Nielsen, P.;
(26) Chen, X.; Hao, X.-S.; Goodhue, C. E.; Yu, J.-Q. J. Am. Chem. Soc.
2006, 128, 6790.
(27) Iwasaki, M.; Iyanaga, M.; Tsuchiya, Y.; Nishimura, Y.; Li, W.; Li,
Z.; Nishihara, Y. Chem. Eur. J. 2014, 20, 2459.
Jørgensen, M. Angew. Chem. Int. Ed. 2008, 47, 1726. (h) Lee, C.-F.;
Liu, Y.-C.; Badsara, S. S. Chem. Asian J. 2014, 9, 706.
(
7) (a) Cristau, H. J.; Chabaud, B.; Chêne, A.; Christol, H. Synthesis
1
1
981, 1981, 892. (b) Percec, V.; Bae, J.-Y.; Hill, D. H. J. Org. Chem.
995, 60, 6895. (c) Millois, C.; Diaz, P. Org. Lett. 2000, 2, 1705.
(28) (a) Majek, M.; Wangelin, A. J. V. Chem. Commun. 2013, 49, 5507.
(b) Koziakov, D.; Majek, M.; von Wangelin, A. J. Org. Biomol.
Chem. 2016, 14, 11347.
(29) Wu, X.-m.; Lou, J.-m.; Yan, G.-b. Synlett 2016, 27, 2269.
(30) Czyz, M. L.; Weragoda, G. K.; Monaghan, R.; Connell, T. U.;
Brzozowski, M.; Scully, A. D.; Burton, J.; Lupton, D. W.; Polyzos,
A. Org. Biomol. Chem. 2018, 16, 1543.
(
d) Zhang, Y.; Ngeow, K. C.; Ying, J. Y. Org. Lett. 2007, 9, 3495.
8) (a) Kwong, F. Y.; Buchwald, S. L. Org. Lett. 2002, 4, 3517.
b) Bates, C. G.; Gujadhur, R. K.; Venkataraman, D. Org. Lett.
002, 4, 2803. (c) Enguehard-Gueiffier, C.; Thery, I.; Gueiffier,
(
(
2
A.; Buchwald, S. L. Tetrahedron 2006, 62, 6042. (d) Carril, M.;
SanMartin, R.; Dominguez, E.; Tellitu, I. Chem. Eur. J. 2007, 13,
(31) Roglans, A.; Pla-Quintana, A.; Moreno-Mañas, M. Chem. Rev.
2006, 106, 4622.
5
2
100. (e) Zhang, H.; Cao, W.; Ma, D. Synth. Commun. 2007, 37,
5. (f) Chen, Y.-J.; Chen, H.-H. Org. Lett. 2006, 8, 5609. (g) Verma,
(32) (Het)aryl Methyl Sulfides; General Procedure
A 25-mL sealable tube was charged with the appropriate aryl
iodide or bromide (1.0 mmol), dimethyl disulfide (1.2 mmol),
Cu(OAc) ·H O (0.1 mmol), KOH (2.0 mmol), TBAB (0.05 mmol),
A. K.; Singh, J.; Chaudhary, R. Tetrahedron Lett. 2007, 48, 7199.
h) Lv, X.; Bao, W. J. Org. Chem. 2007, 72, 3863.
9) Wong, Y.-C.; Jayanth, T. T.; Cheng, C.-H. Org. Lett. 2006, 8, 5613.
(
(
2
2
(
10) (a) Reddy, V. P.; Swapna, K.; Kumar, A. V.; Rao, K. R. J. Org. Chem.
009, 74, 3189. (b) Reddy, V. P.; Swapna, K.; Kumar, A. V.;
and H O (2.0 mL). The mixture was stirred at 100 °C (130 °C for
bromides) for 12 h under air then cooled to r.t. The mixture was
2
2
Swapna, K.; Rao, K. R. Org. Lett. 2009, 11, 1697.
diluted with H O (5 mL) and extracted with EtOAc (4 × 10 mL).
2
(11) (a) Kukushkin, V. Y. Coord. Chem. Rev. 1995, 139, 375.
The extracts were combined, washed with brine (3 × 10 mL),
(b) Fernandes, A. C.; Fernandes, J. A.; Romão, C. C.; Veiros, L. F.;
dried (MgSO ), filtered, and concentrated. The residue was puri-
4
Calhorda, M. J. Organometallics 2010, 29, 5517. (c) Cardoso, J. M.
S.; Royo, B. Chem. Commun. 2012, 48, 4944.
fied by chromatography [silica gel, EtOAc–hexane (1:30 to
1:100)].
(
(
12) Basu, B.; Paul, S.; Nanda, A. K. Green Chem. 2010, 12, 767.
13) Glasnov, T. N.; Holbrey, J. D.; Kappe, C. O.; Seddon, K. R.; Yan, T.
Green Chem. 2012, 14, 3071.
14) Testaferri, L.; Tiecco, M.; Tingoli, M.; Bartoli, D.; Massoli, A. Tet-
rahedron 1985, 41, 1373.
15) Jiang, Y.; Qin, Y.; Xie, S.; Zhang, X.; Dong, J.; Ma, D. Org. Lett.
4-(Methylsulfanyl)aniline (Table 2, entry 9)
Yellow oil; yield: 107 mg (77%). H NMR (300 MHz, CDCl ):
1
3
 = 7.16 (d, J = 8.7 Hz, 2 H), 6.60 (d, J = 8.4 Hz, 2 H), 3.62 (s, 2 H),
13
(
(
(
2.39 (s, 3 H). C NMR (75 MHz, CDCl ):  = 145.2, 131.1, 125.7,
3
115.9, 18.8. GC/MS (EI): m/z = 139 [M+].
1-Methoxy-4-(methylsulfanyl)benzene; Gram-Scale Synthesis
A 50 mL sealable tube was charged with p-iodoanisole (5 mmol,
1.17 g), dimethyl disulfide (6 mmol, 0.56 g), Cu(OAc) ·H O (0.5
2009, 11, 5250.
16) Zhang, C.; Zhou, Y.; Huang, J.; Tu, C.; Zhou, X.; Yin, G. Org.
Biomol. Chem. 2018, 16, 6316.
2
2
mmol, 100 mg), KOH (10 mmol, 5.6 g), TBAB (0.25 mmol, 81
(
(
17) Wang, M.; Qiao, Z.; Zhao, J.; Jiang, X. Org. Lett. 2018, 20, 6193.
18) (a) Luo, F.; Pan, C.; Li, L.; Chen, F.; Cheng, J. Chem. Commun.
mg), and H O (10 mL). The mixture was stirred at 100 °C for 12 h
2
under air, then cooled to r.t., diluted with H O (5 mL), and
2
2011, 47, 5304. (b) Joseph, P. J. A.; Priyadarshini, S.; Kantam, M.
extracted with EtOAc (4 × 15 mL). The extracts were combined
L.; Sreedhar, B. Tetrahedron 2013, 69, 8276. (c) Ghosh, K.; Ranjit,
S.; Mal, D. Tetrahedron Lett. 2015, 56, 5199.
19) (a) She, J.; Jiang, Z.; Wang, Y. Tetrahedron Lett. 2009, 50, 593.
and washed with brine (3 × 15 mL), dried (MgSO ), filtered, and
4
concentrated. The residue was purified by chromatography
[silica gel, EtOAc–hexane (1:30)] to give a pale-yellow oil; yield:
0.56 g (73%).
(
(b) Fu, Z.; Li, Z.; Xiong, Q.; Cai, H. Eur. J. Org. Chem. 2014, 2014,
7
798.
(33) (a) Xu, H.-J.; Zhao, Y.-Q.; Feng, T.; Feng, Y.-S. J. Org. Chem. 2012,
77, 2878. (b) Wang, F.; Chen, C.; Deng, G.; Xi, C. J. Org. Chem.
2012, 77, 4148. (c) He, G.; Huang, Y.; Tong, Y.; Zhang, J.; Zhao,
D.; Zhou, S.; Han, S. Tetrahedron Lett. 2013, 54, 5318.
(d) Taniguchi, N. Eur. J. Org. Chem. 2014, 2014, 5691. (e) Rostami,
A.; Rostami, A.; Ghaderi, A. J. Org. Chem. 2015, 80, 8694. (f) Liu,
Z.; Ouyang, K.; Yang, N. Org. Biomol. Chem. 2018, 16, 988.
(
20) (a) Chu, L.; Yue, X.; Qing, F.-L. Org. Lett. 2010, 12, 1644. (b) Dai,
C.; Xu, Z.; Huang, F.; Yu, Z.; Gao, Y.-F. J. Org. Chem. 2012, 77,
4414. (c) Patil, S. M.; Kulkarni, S.; Mascarenhas, M.; Sharma, R.;
Roopan, S. M.; Roychowdhury, A. Tetrahedron 2013, 69, 8255.
(d) Sharma, P.; Rohilla, S.; Jain, N. J. Org. Chem. 2015, 80, 4116.
(e) Zou, J.-F.; Huang, W.-S.; Li, L.; Xu, Z.; Zheng, Z.-J.; Yang, K.-F.;
(g) Deng, K.-Z.; Zhang, L.-L.; Chen, Y.-F.; Xie, H.-X.; Xu, X.-B.; Xia,
C.-C.; Ji, Y.-F. Org. Biomol. Chem. 2019, 17, 7055.
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