Phenyldithiocarbamates: Efficient Sulfuration Reagents in the Chan–Lam Coupling Reaction

Article abstract of DOI:10.1002/ejoc.201701631

The Chan–Lam coupling reaction starting from phenyldithiocarbamates and phenylboronic acids is reported. To avoid using the volatile, hazardous, and foul-smelling thiols, which are sometimes expensive and not sufficiently available, phenyldithiocarbamates can be employed. They are demonstrated to be good sulfuration reagents in the Chan–Lam coupling to prepare biaryl sulfides. By using this protocol, dithiocarbamate substrates with a wide range of functional groups including electron-rich and electron-deficient ones are explored to obtain the desired substituted biaryl sulfides smoothly. This method is ligand-free, has a broad substrate scope, enables good yields, and is easy to perform. It provides a facile and convenient preparation of biaryl sulfides.

Full text of DOI:10.1002/ejoc.201701631

A Journal of
Accepted Article
Title: Phenyldithiocarbamates: Efficient Sulfuration Reagents in Chan-
Lam Coupling Reaction
Authors: Zhi-Bing Dong, Yu Cheng, and Xing Liu
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201701631
Link to VoR: http://dx.doi.org/10.1002/ejoc.201701631
Supported by

10.1002/ejoc.201701631
European Journal of Organic Chemistry
FULL PAPER
Phenyldithiocarbamates: Efficient Sulfuration Reagents in Chan-
Lam Coupling Reaction
Yu Cheng,[a][+] Xing Liu,[a][+] Zhi-Bing Dong*[a][b]
Abstract: The Chan-Lam coupling reaction starting from
phenyldithiocarbamates and phenylboronic acids is reported. By
avoiding use of the volatile, hazardous and foulsmelling thiols, which
to overcome the defects of thiols, other thiol surrogates have
also been developed, such as disulfides,[10] N-thioimides,[11]
thioamides,[12] and 2-thiobenzamides[13] [Scheme
1
(a)].
are
sometimes
expensive
and
less
available,
However, long reaction time, moderate yields and use of ligand
are the most common issues that caused inconveniences in
undertaking many of these methods for Chan-Lam coupling.
Hence, the development of new protocols for the synthesis of
biarylsulfides is highly imperative. Recently, we described the
synthesis of aryl dithiocarbamates catalyzed by copper,[14] and
the Nickel-catalyzed synthesis of diaryl sulfides starting from
phenyldithiocarbamates and iodobenzenes.[15] As part of our
longstanding interest in developing phenyldithiocarbamates and
the relevant applications,[16] hereby we report an efficient
protocol for the synthesis of biarylsulfides by using Chan-Lam
type reaction starting from phenylboronic acids and
phenyldithiocarbamates as thiol surrogates [Scheme 1 (b)].
phenyldithiocarbamates are found to be good sulfuration reagents in
Chan-Lam coupling to prepare biarylsulfides. By using this protocol,
dithiocarbamate substrates with a wide range of functional groups
including electron-rich and electron deficient ones are explored,
giving the desired subsituted biarylsulfides smoothly. Ligand-free,
broad substrate scope, good yields and easy performance are
important features of this method. The method provides a facile and
convenient preparation of biarylsulfides.
Introduction
Organic dithiocarbamates have received considerable attention
due to their occurrence in a variety of biologically active
compounds,[1] their pivotal role in agriculture[2] and as versatile
synthetic intermediates in organic synthesis.[3] Therefore,
dithiocarbamate compounds bear high potentials for the
improvement of known sulfuration reactions. In addition,
establishing efficient C-S coulpling for constructing the
biarylsulfides is currently an active area in organic synthesis.
Diaryl sulfides are not only important parts in natural products,[4]
material chemistry[5] and pharmaceuticals[6] but also applied as
intermediates in organic synthesis[7] and as ligands in transition-
metal-catalyzed reactions.[8] Their important natures prompted
attentions in the synthesis of these compounds. Conventional
methods for the preparation of biarylsulfides through the
condensation of thiols with organic halides. However, the direct
use of the volatile, hazardous and foulsmelling thiols, which are
sometimes expensive and less available, makes these reactions
potentially hazardous and less attractive towards large-scale
operations. Thus, the development of new protocols which are
practical, cheap and environmentally benign for the synthesis of
biarylsulfides is highly desirable. Recently, the Chan-Lam
coupling reaction has emerged as a highly efficient and valuable
to traditional methods for the construction of biarylsulfides due to
the wide variety of commercially available boronic acids
derivatives and the mildness of the reaction conditions.[9] In order
sulfur source +
R
B(OH)
R
S R'
2
(b) this work:
(a) previous reports:
thiol surrogates:
thiol surrogates:
RSSR, SN(COR')
2
1
S
N
CONHR
N
S
X
S
2
SR
R
2
R
= acyl, alkyl
X = C, N
Scheme 1. Transformation of boronic acids into biarylsulfides.
Results and Discussion
To optimize the reaction conditions, the effects of different
solvents, reaction temperature, and the amount of catalysts and
ligands on the cross-coupling reaction were investigated using
phenyldithiocarbamate (1a) and phenylboronic acid (2a) (Table
1). Inspired by the fact that copper salts are effective in
mediating or catalyzing the carbon-sulfur formation reactions,[17]
we employed a number of readily accessible copper salts (10
mol%) and ligands (equal amount) to catalyze the model
reaction, which proceeded in N, N-dimethylformamide (DMF) in
a sealed tube at 120 oC (Table 1, entries 1-15). Among the
catalysts survey, Cu(OAc)2 was found to be the most efficient
(Table 1, entry 5). By increasing the amount of catalyst and
pyridine (120 mol%), the yield of 3a was improved significantly
(from 42% to 85%, Table 1, entries 5 and 9). It was found that
using more than 120 mol% of catalyst did not further improve
the yield. We also tested other N-containing ligands (Table 1,
entries 11-14), the yield of product 3a was almost the same or
slightly decreased. To our delight, product 3a was obtained in
good yield (Table 1, entry 15) without ligand addition, which
demonstrated that ligand was not crucial for the reaction.
Further investigation for the solvents revealed that N, N-
dimethylformamide (DMF) was the best solvent (Table 1,
[a]
School of Chemistry and Environmental Engineering, Wuhan
Institute of Technology, Wuhan 430205, China
E-mail: dzb04982@wit.edu.cn
http://cee.wit.edu.cn/info/1052/1538.htm
Key Laboratory of Green Chemical Process, Ministry of Education,
Wuhan Institute of Technology, Wuhan 430205, China
These authors contributed equally to this work.
[b]
[+]
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701631
European Journal of Organic Chemistry
FULL PAPER
entries 16-19). The screening for the reaction temperature
showed that 110 C was the best (Table 1, entries 20-23). The
optimal reaction parameters were summarized in entry 21.
this protocol. It is noteworthy that 3-furanboronic acid was also
suitable to react with phenyldithiocarbamate, giving product 3j
with reasonable yield (Table 2, entry 10).
o
Table 2. Synthesis of biarylsulfides starting from phenyldithiocarbamates and
Table 1. Optimization of the reaction conditions.[a]
phenylboronic acids.[a]
OH
S
S
S
B
OH
OH
+
S
S
S
Cu(OAc)2 (1.2 equiv.)
DMF, 110 oC, 6 h
B
N
OH
+
N
R2
R1
3a
1a
2a
R1
R2
1
3
2
Entry
1
Catalyst
(mol%)
Ligand
(mol%)
Solvent
Temp
(°C)
Yield[b]
(%)
Entry
Substrate 1
Substrate 2
Product 3; Yield[b]
CuBr (10%)
CuI (10%)
Py (10%)
Py (10%)
DMF
DMF
120
120
25
30
S
S
S
OH
B
OH
2
N
1
2
3
Cu2O (10%)
CuO (10%)
Py (10%)
Py (10%)
Py (10%)
Py (10%)
Py (50%)
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMAC
DMSO
PhCH3
PhNO2
DMF
DMF
DMF
DMF
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
120
130
110
100
80
29
30
42
mess
55
75
85
85
84
84
82
80
85
84
84
82
80
85
85
80
72
1a
2a
3a: 85%
4
5
Cu(OAc)2
(10%)
CuSO4
(10%)
Cu(OAc)2
(50%)
Cu(OAc)2
(100%)
Cu(OAc)2
(120%)
Cu(OAc)2
(140%)
Cu(OAc)2
(120%)
Cu(OAc)2
(120%)
Cu(OAc)2
(120%)
Cu(OAc)2
(120%)
Cu(OAc)2
(120%)
Cu(OAc)2
(120%)
Cu(OAc)2
(120%)
Cu(OAc)2
(120%)
Cu(OAc)2
(120%)
S
S
S
OH
B
OH
N
6
2b
1a
7
3b: 87%
8
Py
(100%)
Py
(120%)
Py
OH
S
S
S
B
OH
N
9
3
4
10
11
12
13
14
15
1a
3c: 79%
(140%)
Bpy
2c
OH
(120%)
1,10-phen
(120%)
L-proline
(120%)
TED
S
B
OH
S
S
N
1a
2d
3d: 82%
(120%)
--
--
--
--
--
OH
S
B
S
S
OH
16
17
18
N
5
6
HO
OH
1a
2e
3e: 86%
OH
19
20
B
S
S
S
OH
OH
Cu(OAc)2
(120%)
Cu(OAc)2
(120%)
Cu(OAc)2
(120%)
Cu(OAc)2
(120%)
N
N
--
HO
21
--
1a
2f
3f: 80%
22
23
--
--
S
S
S
OH
OH
F
B
F
7
8
9
[a]Reaction conditions: 1a (1.0 mmol), 2a (1.4 mmol), [Cat.], solvent (1.5 mL),
stirred for 6 h. [b]Isolated yields.
2g
2h
2i
1a
3g: 85%
In the presence of 120 mol% Cu(OAc)2,
a series of
S
S
S
OH
B
OH
Cl
phenylboronic acids smoothly underwent sulfuration with
N
Cl
phenyldithiocarbamates in N, N-dimethylformamide (DMF) at
o
1a
110 C to give structurally diverse biarylsulfides in good yields
3h: 86%
(Table 2). It was found that both electron-withdrawing and
electron-donating groups were successfully introduced into the
aromatic rings of the products by employing the corresponding
phenylboronic acids and phenyldithiocarbamates (Table 2,
entries 1-19). In general, the electronic nature of the
phenyldithiocarbamates and phenylboronic acids played either
little or no effect on the reaction, which revealed the versatility of
S
S
S
OH
Br
B
N
OH
Br
1a
3i: 88%
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701631
European Journal of Organic Chemistry
FULL PAPER
oxidized by Cu(OAc)2 to regenerate the copper(II) to complete
the catalytic cycle.
O
S
S
S
OH
O
B
N
S
OH
10
3j: 63%
1a
2j
S
S
S
S
OH
OH
B
N
n
n
Bu
Bu
11
12
13
2a
3k: 86%
1b
1c
1c
S
S
OH
B
OH
N
2b
2c
3l: 85%
Scheme 2. Possible reaction mechanism.
S
OH
S
n
Bu
B
n
N
Bu
OH
Conclusions
3m: 84%
In summary, we have successfully developed an efficient and
practical method for the synthesis of diaryl sulfides through
Chan-Lam type coupling reaction. By using Cu(OAc)2 as catalyst,
phenylboronic acids reacted with phenyldithiocarbamates in N,
N-dimethylformamide (DMF) at 110 oC smoothly to give the
corresponding diaryl sulfides in good yields. The protocol
features ligand-free, broad substrate scope, good yields and
easy performance. Further investigation of this protocol and the
related applications are currently under research in our
laboratory.
OH
B
S
S
S
OH
N
14
15
16
1c
3n: 80%
2d
OH
S
S
S
B
OH
N
Cl
Cl
1c
3o: 88%
2k
OH
B
S
S
S
OH
Experimental Section
N
CF3
CF
3
Gerneral Remarks: Nuclear magnetic resonance (NMR) spectra were
1c
obtained on a Bruker AC 400 MHz spectrometer (1H NMR at 400 Hz, 13
C
3p: 80%
2l
NMR at 100 Hz) in CDCl3 using tetramethylsilane as an internal standard.
Chemical shifts are given in ppm and coupling constants (J) are given in
Hz. Electrospray ionization-high-resolution mass spectra (ESI-HRMS)
were determined on an Ion Spec (7.0 T) spectrometer. All reactions were
performed under dried glassware with septums. All starting materials
were purchased from commercial suppliers and used without further
purification unless otherwise stated. Yield refers to isolated compounds
estimated to be > 95% pure as determined by 1H NMR and capillary GC
analysis.
S
S
S
S
OH
OH
B
N
F3C
F3C
17
18
2b
2m
2b
1d
1e
3q: 81%
S
S
OH
n
Bu
B
N
S
n
OH
HO
Bu
HO
3r: 81%
Typical
procedure (TP): Phenylboronic acid (1.4 mmol),
OH
phenyldithiocarbamate (1 mmol), Cu(OAc)2 (1.2 mmol) were added in a
dried sealed tube, DMF (N,N-dimethylformamide, 1.5 mL) was then
added. The mixture was stirred at 110 oC and checked by TLC until the
starting material was finished (about 6 h). The reaction was cooled down
to room temperature, quenched with water (5 mL) and then extracted
with ethyl acetate (3 × 10 mL). The crude solution was dried over
anhydrous Na2SO4 and evaporated under vacuum. The residue was
purified by flash column chromatography to afford the desired product.
S
OH
OH
S
B
OH
N
19
3s: 70%
1f
[a]Reaction conditions: 1 (1.0 mmol), 2 (1.4 mmol), Cu(OAc)2 (1.2 mmol), DMF
(1.5 mL), 110oC, stirred for 6 h. [b]Isolated yields.
On the basis of the experimental observations and related
literatures,[17], [9c] we proposed the reaction mechanism as shown
in Scheme 2. Initially, boronic acid reacted with Cu(OAc)2 to give
Cu(II) intermediate A, which is ready for the transmetallation
with B furnishing intermediate C. Reductive elimination of C
ensued to form the product D and Cu(0) species, which is then
Diphenyl sulfide (3a). According to TP, the residue was purified by flash
chromatography on silica gel (eluent: petroleum ether) to give the target
compound 3a (yield = 85%) as a colorless oil. 1H NMR (400 MHz, CDCl3)
δ: 7.43-7.29 (m, 10H); 13C NMR (100 MHz, CDCl3) δ: 135.8, 131.1,
129.2, 127.1; HRMS (ESI): calcd for C13H12S (186.0503); found 186.0522.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701631
European Journal of Organic Chemistry
FULL PAPER
1-Methyl-4-phenylsulfanyl-benzene (3b). According to TP, the residue
was purified by flash chromatography on silica gel (eluent: petroleum
ether) to give the target compound 3b (yield = 87%) as a colorless oil. 1H
NMR (400 MHz, CDCl3) δ: 7.04-6.85 (m, 9H), 2.06 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ: 137.6, 137.1, 132.3, 131.3, 130.1, 129.8, 129.1,
126.4, 21.1; HRMS (ESI): calcd for C13H12S (200.0660); found 200.0672.
3-Phenylsulfanyl-furan (3j). According to TP, the residue was purified
by flash chromatography on silica gel (eluent: petroleum ether) to give
the target compound 3j (yield = 63%) as a colorless oil. 1H NMR 400 MHz,
CDCl3) δ: 7.50 (d, J = 4 Hz, 3H), 7.32-7.20 (m, 5H); 13C NMR (100 MHz,
CDCl3) δ: 137.0, 129.1, 127.5, 127.1; HRMS (ESI): calcd for C10H8OS
(176.0296), found: 176.0305.
1-Methyl-2-phenylsulfanyl-benzene (3c). According to TP, the residue
was purified by flash chromatography on silica gel (eluent: petroleum
ether) to give the target compound 3c (yield = 79%) as a colorless oil. 1H
NMR (400 MHz, CDCl3) δ: 7.27-7.07 (m, 9H), 2.34 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ: 139.9, 136.2, 133.7, 133.0, 130.6, 129.6, 129.1,
127.9, 126.7, 126.3, 20.6; HRMS (ESI): calcd for C13H12S (200.0660);
found 200.0674.
1-Butyl-4-phenylsulfanyl-benzene (3k). According to TP, the residue
was purified by flash chromatography on silica gel (eluent: petroleum
ether) to give the target compound 3k (yield = 86%) as a colorless oil. 1H
NMR 400 MHz, CDCl3) δ: 7.31-7.10 (m, 9H), 2.57 (t, J = 8 Hz, 2H),
1.62-1.54 (m, 2H), 1.39-1.30 (m, 2H), 0.92 (t, J = 8 Hz, 3H); 13C NMR
(100 MHz, CDCl3) δ: 142.6, 137.2, 132.2, 131.7, 130.0, 129.5, 129.2,
126.5, 35.4, 33.6, 22.5, 14.1; HRMS (ESI): calcd for C16H18S (242.1129),
found: 242.1135.
1,3-Dimethyl-5-phenylsulfanyl-benzene (3d). According to TP, the
residue was purified by flash chromatography on silica gel (eluent:
petroleum ether) to give the target compound 3d (yield = 82%) as a
colorless oil. 1H NMR 400 MHz, CDCl3) δ: 7.30-7.16 (m, 5H), 6.98 (s,
2H), 6.84 (s, 1H), 2.22 (s, 6H); 13C NMR (100 MHz, CDCl3) δ: 138.9,
136.5, 134.8, 130.5, 129.2, 129.2, 129.1, 126.7, 21.2; HRMS (ESI): calcd
for C14H14S (214.0816); found 214.0831.
1-Methyl-4-(4-methylphenyl)thio-benzene (3l). According to TP, the
residue was purified by flash chromatography on silica gel (eluent:
petroleum ether) to give the target compound 3l (yield = 85%) as a white
solid. Mp: 56-58 oC. 1H NMR (400 MHz, CDCl3) δ: 7.21 (d, J = 8 Hz,
4H), 7.07 (d, J = 8 Hz, 4H), 2.29 (s, 6H); 13C NMR (100 MHz, CDCl3) δ:
136.8, 132.6, 131.0, 129.9, 21.0; HRMS (ESI): calcd for C14H14
S
(214.0816), found: 214.0828.
1-Hydroxyl-4-phenylsulfanyl-benzene (3e). According to TP, the
residue was purified by flash chromatography on silica gel (eluent:
petroleum ether) to give the target compound 3e (yield = 86%) as a
colorless oil. 1H NMR (400MHz, CDCl3) δ: 7.32 (d, J = 8Hz, 2H), 7.23-
7.10 (m, 5H), 6.79 (d, J = 8Hz, 2H), 5.09 (brs, 1H); 13C NMR (100 MHz,
CDCl3) δ: 155.8, 138.2, 135.5, 129.0, 128.3, 125.9, 124.5, 116.6; HRMS
(ESI): calcd for C12H10OS (202.0452); found 202.0461.
1-Butyl-4-(4-methylphenyl)thio-benzene (3m). According to TP, the
residue was purified by flash chromatography on silica gel (eluent:
petroleum ether) to give the target compound 3m (yield = 84%) as a
white solid. Mp: 56-58 oC. 1H NMR (400 MHz, CDCl3) δ: 7.24-7.19 (m,
4H), 7.08 (d, J = 8 Hz, 4H), 2.56 (t, J = 8 Hz, 2H), 2.30 (s, 3H), 1.56 (t, J
= 8 Hz, 2H), 1.33 (d, 2H), 0.91 (t, J = 8 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ: 141.8, 136.9, 132.9, 132.5, 131.2, 130.8, 129.9, 129.2, 35.2,
33.5, 22.3, 21.0, 13.9; HRMS (ESI): calcd for C17H20S (256.1286), found:
256.1292.
1-Hydroxyl-2-phenylsulfanyl-benzene (3f). According to TP, the
residue was purified by flash chromatography on silica gel (eluent:
petroleum ether) to give the target compound 3f (yield = 80%) as a
colorless oil. 1H NMR (400MHz, CDCl3) δ: 7.49-6.87 (m, 1H), 6.52 (brs,
1H); 13C NMR (100 MHz, CDCl3) δ: 157.3, 136.9, 135.9, 132.3, 129.2,
126.9, 126.1, 121.3, 116.3, 115.6; HRMS (ESI): calcd for C12H10OS
(202.0452); found 202.0466.
1,3-Dimethyl-5-(4-methylphenyl)thio-benzene (3n). According to TP,
the residue was purified by flash chromatography on silica gel (eluent:
petroleum ether) to give the target compound 3n (yield = 80%) as a
colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.08 (d, J = 8 Hz, 2H), 6.91
(d, J = 8 Hz, 2H), 6.74 (s, 2H), 6.63 (s, 1H), 2.13 (s, 3H), 2.05 (s, 6H); 13
C
NMR (100 MHz, CDCl3) δ: 138.7, 137.1, 136.1, 131.8, 131.7, 129.9,
128.5, 127.9, 21.2, 21.1; HRMS (EI): calcd for C15H16S (228.0973), found:
228.0981.
1-Fluoro-4-phenylsulfanyl-benzene (3g). According to TP, the residue
was purified by flash chromatography on silica gel (eluent: petroleum
ether) to give the target compound 3g (yield = 85%) as a colorless oil. 1H
NMR (400MHz, CDCl3) δ: 7.44-7.41 (m, 2H), 7.33 (d, J = 4 Hz, 4H),
7.26 (d, J = 8 Hz, 1H), 7.06 (t, J = 8 Hz, 2H); 13C NMR (100 MHz, CDCl3)
δ: 162.4 (d, J = 246 Hz), 136.7, 134.1 (d, J = 8 Hz), 130.3 (d, J = 4 Hz),
130.0, 129.2, 126.8, 116.4 (d, J = 22 Hz); HRMS (ESI): calcd for C12H9FS
(204.0409); found 204.0416.
1-Chlorophenyl-2-(4-methylphenyl)thio-benzene (3o). According to
TP, the residue was purified by flash chromatography on silica gel (eluent:
petroleum ether) to give the target compound 3o (yield = 88%) as a
colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.34-7.29 (m, 3H), 7.16 (d, J
=8 Hz, 2H), 7.03-7.00 (m, 2H), 6.83-6.81 (m, 1H), 2.34 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ: 138.9, 137.6, 134.2, 132.0, 130.4, 129.5, 128.8,
128.3, 127.0, 126.5, 21.2; HRMS (ESI): calcd for C13H11ClS (234.0270),
found: 234.0283.
1-Chloro-4-phenylsulfanyl-benzene (3h). According to TP, the residue
was purified by flash chromatography on silica gel (eluent: petroleum
ether) to give the target compound 3h (yield = 86%) as a colorless oil. 1H
NMR 400 MHz, CDCl3) δ: 7.42-7.30 (m, 9H); 13C NMR (100 MHz, CDCl3)
δ: 135.2, 134.7, 133.0, 132.1, 131.4, 129.4, 129.4, 127.5; HRMS (ESI):
calcd for C12H9ClS (220.0113); found 222.0121.
1-trifluoromethyl-3-(4-methylphenyl)thio-benzene (3p). According to
TP, the residue was purified by flash chromatography on silica gel (eluent:
petroleum ether) to give the target compound 3p (yield = 80%) as a
colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.36 (s, 1H), 7.28-7.21 (m,
5H), 7.08 (d, J =8 Hz, 2H), 2.26 (s, 3H); 13C NMR (100 MHz,CDCl3) δ:
139.7, 138.8, 133.5, 131.6, 131.4 (q, J = 32 Hz), 130.5, 129.3, 129.1,
125.4 (q, J = 270 Hz), 125.1 (d, J = 3 Hz), 122.6 (q, J = 3 Hz), 21.2;
HRMS (ESI): calcd for C14H11F3S (268.0554), found: 268.0543.
1-Bromo-4-phenylsulfanyl-benzene (3i). According to TP, the residue
was purified by flash chromatography on silica gel (eluent: petroleum
ether) to give the target compound 3i (yield = 88%) as a yellow oil. 1H
NMR 400 MHz, CDCl3) δ: 7.30-7.16 (m, 7H), 7.06 (d, J = 8Hz, 2H); 13C
NMR (100 MHz, CDCl3) δ: 135.5, 134.8, 132.2, 132.2, 131.6, 129.4,
127.6, 120.9; HRMS (ESI): calcd for C12H9BrS (263.9608), found:
263.9621.
1-trifluoromethyl-4-(4-methylphenyl)thio-benzene (3q). According to
TP, the residue was purified by flash chromatography on silica gel (eluent:
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701631
European Journal of Organic Chemistry
FULL PAPER
petroleum ether) to give the target compound 3q (yield = 81%) as a white
solid. Mp: 91-93 oC. 1H NMR (400 MHz, CDCl3) δ: 7.48-7.41 (m, 4H),
7.24-7.21 (m, 4H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 143.9,
139.2, 134.3, 130.5, 128.2, 127.5 (q, J = 33 Hz), 127.3, 125.7 (q, J = 4
Hz), 124.2 (q, J = 270 Hz), 21.2; HRMS (ESI): calcd for C14H11F3S
(268.0544), found: 268.0541.
(5)
(6)
a) T. Mori, T. Nishimura, T. Yamamoto, I. Doi, E. Miyazaki, I. Osaka, K.
Takimiya, J. Am. Chem. Soc. 2013, 135, 13900-13913; b) T. Okamoto,
C. Mitsui, M. Yamagishi, K. Nakahara, J. Soeda, Y. Hirose, K. Miwa, H.
Sato, A. Yamano, T. Matsushita, Adv. Mater. 2013, 25, 6392-6397; c) K.
Takimiya, S. Shinamura, I. Osaka, E. Miyazaki, Adv. Mater. 2011, 23,
4347-4370.
a) G. De Martino, G. La Regina, A. Coluccia, M.C. Edler, M. C. Barbera,
A. Brancale, E. Wilcox, E. Hamel, M. Artico, R. Silvestri, J. Med. Chem.
2004, 47, 6120-6123; b) J. Krapcho, E. R. Spitzmiller, C. F. Turk, J.
Med. Chem. 1963, 6, 544-546; c) S. F. Nielsen, E. Nielsen, G. M. Olsen,
T. Liljefors, D. Peters, J. Med. Chem. 2000, 43, 2217-2226; d) S.
Pasquini, C. Mugnaini, C. Tintori, M. Botta, A. Trejos, R. K. Arvela, M.
Larhed, M. Witvrouw, M. Michiels, F. Christ, J. Med. Chem. 2008, 51,
5125-5129.
1-Butyl-4-(4-hydroxylphenyl)thio-benzene (3r). According to TP, the
residue was purified by flash chromatography on silica gel (eluent:
petroleum ether) to give the target compound 3r (yield = 81%) as a
colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.20 (d, J = 8 Hz, 2H), 7.04
(d, J = 8 Hz, 2H), 6.97 (d, J = 12 Hz, 2H), 6.69 (d, J = 12 Hz, 2H), 5.80
(brs, 1H), 2.45 (t, J = 8 Hz, 2H), 1.49-1.42 (m, 2H), 1.28-1.17 (m, 2H),
0.81 (t, J = 8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 142.6, 137.2,
132.2, 131.7, 130.0, 129.5, 129.2, 126.5, 35.4, 33.6, 22.5, 14.1; HRMS
(ESI): calcd for C16H18OS (258.1078), found: 258.1083.
(7)
a) J. J. Boruah, S. P. Das, S. R. Ankireddy, S. R. Gogoi, N. S. Islam,
Green Chem. 2013, 15, 2944-2959; b) J. L. Garcia Ruano, J. Alemán,
C. Fajardo, A. Parra, Org. Lett. 2005, 7, 5493-5496; c) K. Kamata, T.
Hirano, N. Mizuno, Chem. Commun. 2009, 3958-3960; d) A. Rostami, J.
Akradi, Tetrahedron Lett. 2010, 51, 3501-3503.
1-Methyl-4-(2-hydroxylphenyl)thio-benzene (3s). According to TP, the
residue was purified by flash chromatography on silica gel (eluent:
petroleum ether) to give the target compound 3s (yield = 70%) as a
colorless oil. 1H NMR (400 MHz, CDCl3) δ: 7.41 (d, J = 8 Hz, 1H), 7.24 (t,
J = 8 Hz, 1H), 6.96-6.90 (m, 5H), 6.82 (t, J = 8 Hz, 1H), 6.44 (s, 1H), 2.17
(s, 3H); 13C NMR (100 MHz, CDCl3) δ: 157.0, 136.6, 136.2, 132.1, 131.9,
129.9, 127.4, 121.1, 117.1, 115.4, 20.9; HRMS (ESI): calcd for C13H12OS
(216.0609), found: 216.0621.
(8)
(9)
a) Y. Li, M. H. Xu, Chem. Commun. 2014, 50, 3771-3782; b) M. Mellah,
A. Voituriez, E. Schulz, Chem. Rev. 2007, 107, 5133-5209.
a) Y. Lin, M. Cai, Z. Fang, H. Zhao, Tetrahedron 2016, 72, 3335-3343;
b) J. X. Qiao, P. Y. Lam, Synthesis 2011, 2011, 829-856; c) H. J. Xu, Y.
Q. Zhao, T. Feng, Y. S. Feng, J. Org. Chem. 2012, 77, 2878-2884.
(10) a) J. Krouželka, I. Linhart, Eur. J. Org. Chem. 2009, 2009, 6336-6340;
b) A. Kumar, S. Kumar, Tetrahedron 2014, 70, 1763-1772; c) P. S. Luo,
F. Wang, J. H. Li, R. Y. Tang, P. Zhong, Synthesis 2009, 921-928; d) N.
Taniguchi, Synlett. 2006, 1351-1354; e) N. Taniguchi, J. Org. Chem.
2007, 72, 1241-1245.
Acknowledgements
(11) a) R. Pluta, P. Nikolaienko, M. Rueping, Angewandte Chemie. 2014,
126, 1676-1679; b) C. Savarin, J. Srogl, L. S. Liebeskind, Org. Lett.
2002, 4, 4309-4312.
We thank the foundation support from National Natural
Science Foundation of China (21302150), foundation of
Chen-Guang program from Hubei Association for Science
and Technology, foundation of Chutian distinguished fellow
from Hubei Provincial Department of Education, foundation
of High-end Talent Cultivation Program from Wuhan
Institute of Technology. Z.-B. D. acknowledges the
Humboldt Foundation and China Scholarship Council for a
fellowship.
(12) a) A. K. Bakkestuen, L. L. Gundersen, Tetrahedron Lett. 2003, 44,
3359-3362; b) A. Lengar, C. O. Kappe, Org. Lett. 2004, 6, 771-774; c)
H. Prokopcova, C. O. Kappe, Adv. Synth. Catal. 2007, 349, 448-452; d)
H. Prokopcova, C. O. Kappe, J. Org. Chem. 2007, 72, 4440-4448.
(13) a) A. Henke, J. Srogl, Chem. Commun. 2011, 47, 4282-4284; b) J. M.
Villalobos, J. Srogl, L. S. Liebeskind, J. Am. Chem. Soc. 2007, 129,
15734-15735.
(14) a) Z. B. Dong, X. Liu, C. Bolm, Org. Lett. 2017, 19, 5916-5919; b) M. T.
Zeng, W. Xu, Xing Liu, C. Z. Chang, H. Zhu, Z. B. Dong, Eur. J. Org.
Chem. 2017, 6060-6066.
Keywords: Dithiocarbamates
• Boronic acid • Chan-Lam
(15) X. Liu, Q. Cao, W. Xu, M. T. Zeng, Z. B. Dong, Eur. J. Org. Chem. 2017,
5795-5799.
coupling • Diaryl Sulfides • Synthesis
(16) a) W. Xu, M. T. Zeng, M. Liu, S. S. Liu, Y. S. Li, Z. B. Dong, Synthesis
2017, 49, 3084-3090; b) W. Xu, M. T. Zeng, M. Liu, X. Liu, C. Z. Chang,
H. Zhu, Y. S. Li, Z. B. Dong, Chem. Lett. 2017, 46, 641-643; c) M. T.
Zeng, W. Xu, M. Liu, X. Liu, C. Z. Chang, H. Zhu, Z. B. Dong, SynOpen
2017, 1, 1-7; d) H. Zhu, X. Liu, C. Z. Chang, Z. B. Dong, Synthesis
2017, 49, 5211-5216; e) Z. B. Dong, M. Wang, H. Zhu, X. Liu, C. Z.
Chang, Synthesis 2017, 49, 5258-5262; f) M. Liu, M. T. Zeng, W. Xu, L.
Wu, Z. B. Dong, Tetrahedron Lett. 2017, 58, 4352-4356; g) W. Xu, M. T.
Zeng, S. S. Liu, Y. S. Li, Z. B. Dong, Tetrahedron Lett. 2017, 58, 4289-
4292; h) X. Liu, M. Liu, W. Xu, M. T. Zeng, H. Zhu, C. Z. Chang, Z. B.
Dong, Green Chem. 2017, 19, 5591-5598.
(1)
(2)
a) M. D'hooghe, N. De Kimpe, Tetrahedron 2006, 62, 513-515; b) A. W.
Erian, S. M. Sherif, Tetrahedron 1999, 55, 7957-8024; c) A. Goel, S. J.
Mazur, R. J. Fattah, T. L. Hartman, J. A. Turpin, M. Huang, W. G. Rice,
E. Appella, J. K. Inman, Bioorg. Med. Chem. Lett. 2002, 12, 767-770.
a) C. Len, D. Postel, A. Gino Ronco, P. Villa, C. Goubert, E. Jeufrault, A.
Bernard Mathon, H. Simon, J. Agr. Food Chem. 1997, 45, 3-6; b) C.
Rafin, E. Veignie, M. Sancholle, D. Postel, C. Len, P. Villa, G. Ronco, J.
Agr. Food Chem. 2000, 48, 5283-5287.
(3)
(4)
a) U. Boas, H. Gertz, J. B. Christensen, P. M. Heegaard, Tetrahedron
Lett. 2004, 45, 269-272; b) A. K. Mukerjee, R. Ashare, Chem. Rev.
1991, 91, 1-24.
(17) a) P. S. Herradura, K. A. Pendola, R. K. Guy, Org. Lett. 2000, 2, 2019-
2022; b) N. Sun, H. Zhang, W. Mo, B. Hu, Z. Shen, X. Hu, Synlett. 2013,
24, 1443-1447; c) L. Wang, W. Y. Zhou, S. C. Chen, M. Y. He, Q. Chen,
Synlett. 2011, 3041-3045.
a) H. Liu, T. Fujiwara, T. Nishikawa, Y. Mishima, H. Nagai, T. Shida, K.
Tachibana, H. Kobayashi, R. E. Mangindaan, M. Namikoshi,
Tetrahedron 2005, 61, 8611-8615; b) T. Nakazawa, J. Xu, T. Nishikawa,
T. Oda, A. Fujita, K. Ukai, R. E. Mangindaan, H. Rotinsulu, H.
Kobayashi, M. Namikoshi, J. Nat. Prod. 2007, 70, 439-442.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201701631
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents (Please choose one layout)
Layout 1:
FULL PAPER
Text for Table of Contents
Key Topic*
Author(s), Corresponding Author(s)*
Page No. – Page No.
Title
((Insert TOC Graphic here: max.
width: 5.5 cm; max. height: 5.0 cm;
NOTE: the final letter height should
not be less than 2 mm.))
*one or two words that highlight the emphasis of the paper or the field of the study
Layout 2:
FULL PAPER
Chan-Lam Coupling
Yu Cheng, Xing Liu, Zhi-Bing Dong*
B(OH)
S
N
1
2
2
R
R
Page No. – Page No.
2
Cu(OAc) ( 120 mol% )
2
1
R
R
+
S
Phenyldithiocarbamates: Efficient
Sulfuration Reagents in Chan-Lam
Coupling Reaction
o
S
DMF, 110 C, 6 h
19 examples
yields up to 88%
Text for Table of Contents
*one or two words that highlight the emphasis of the paper or the field of the study
A Chan-Lam type coupling reaction for the synthesis of diaryl sulfides is reported. By using Cu(OAc)2 as catalyst,
o
phenylboronic acids reacted with phenyldithiocarbamates in N, N-dimethylformamide (DMF) at 110 C smoothly to give the
corresponding diaryl sulfides in good yields.
This article is protected by copyright. All rights reserved.