An efficient protocol for the carbon-sulfur cross-coupling of sulfenyl chlorides with arylboronic acids using a palladium catalyst

Article abstract of DOI:10.1055/s-0033-1340841

An efficient protocol for carbon-sulfur bond formation is developed, which involves the cross-coupling of sulfenyl chlorides and arylboronic acids catalyzed by a novel palladium-Schiff base complex. Good to high product yields, short reaction times, and mild reaction conditions are important features of this new method. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0033-1340841

866▌
LETTER
lAettner Efficient Protocol for the Carbon–Sulfur Cross-Coupling of Sulfenyl Chlo-
rides with Arylboronic Acids using a Palladium Catalyst
Palladium-Catalyzed Carbon–Sulfur Cross-Couplings
Prasanta Gogoi,* Mukul Kalita, Pranjit Barman
Department of Chemistry, National Institute of Technology, Silchar 788010, Assam, India
E-mail: prasantanits.11@gmail.com
Received: 11.12.2013; Accepted after revision: 27.01.2014
The novel palladium catalyst 1a was prepared by treat-
Abstract: An efficient protocol for carbon–sulfur bond formation
ment of N-[2-(benzylthio)phenyl]-4-bromosalicylaldi-
mine Schiff base ligand HL1 with sodium
tetrachloropalladate (Na2PdCl4), in ethanol at 90 °C, to
is developed, which involves the cross-coupling of sulfenyl chlo-
rides and arylboronic acids catalyzed by a novel palladium–Schiff
base complex. Good to high product yields, short reaction times,
and mild reaction conditions are important features of this new give a complex of the type [Pd(L1)Cl] (Scheme 1). The
method.
crystal structure shows that the complex is a distorted
square-planar structure in which the palladium(II) center
is bonded to the oxygen of the salicylaldehyde, the nitro-
gen of the imine, and the sulfur of the thioether (Figure 1).
In this case, the ligand binding the palladium atom is in a
tridentate (ONS) disposition, which gives rise to five- and
Key words: arylboronic acids, sulfenyl chlorides, palladium catal-
ysis
Organic sulfides are useful synthetic intermediates for the
construction of various chemically and biologically active
molecules.1,2 For example, sulfide derivatives have been
proposed as treatments for HIV, obesity, cancer, heart dis-
eases, and allergies.3,4 Commonly used methods for the
construction of aryl thioethers include cross-couplings of
aryl halides with thiols catalyzed by palladium, copper,
iron, or iodine,5 coupling of nitroarenes with thiols,6 nu-
cleophilic attack on disulfides,7 copper-catalyzed scission
of disulfides,8 reduction9 of aryl sulfones or aryl sulfox-
ides, and carbon–sulfur cross-coupling of arylboronic ac-
ids with thiols.10 Most of these methods use thiols or
disulfides as starting materials; however, we have investi-
X
X
O
Cl
Pd
ethanol
N
+
Na2PdCl4
OH
90 °C, 0.5 h
S
N
S
1a (X = Br)
1b (X = H)
HL1 (X = Br)
HL2 (X = H
gated an alternative method utilizing the coupling of aryl- Scheme 1 Synthesis of Pd–Schiff base complexes 1a,b
boronic acids with sulfenyl chlorides, which are
commercially available or can be easily prepared.11 In
2012, Xu and co-workers12 reported a mild method for the
S-arylation of thiols with boronic acids at room tempera-
ture using a copper catalyst, but this procedure was not
convenient for the synthesis of benzyl(phenyl)sulfide.
Previous efforts have been made to develop efficient cat-
alytic systems for the formation of aryl–sulfur bonds us-
ing transition-metal catalysts such as palladium(II) or
copper(II).13,14 In this regard, palladium complexes are
among the most commonly employed catalysts. Palladi-
um-catalyzed cross-coupling of arylsulfonyl chlorides
with arylboronic acids for the synthesis of sulfones has
been described;14 while an earlier attempt to prepare vinyl
sulfides via the palladium(0)-catalyzed cross-coupling of
sulfenyl chlorides with vinyl stannanes gave disulfides.15
We describe herein an efficient protocol for the synthesis
of diaryl sulfides via the cross-coupling of sulfenyl chlo-
rides with arylboronic acids, using novel palladium–
Schiff base complex 1a.16
SYNLETT 2014, 25, 0866–0870
Advanced online publication: 06.03.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
Figure 1 ORTEP view of Pd–Schiff base complex 1a (CCDC
955390)
DOI: 10.1055/s-0033-1340841; Art ID: ST-2013-D1128-L
© Georg Thieme Verlag Stuttgart · New York

LETTER
Palladium-Catalyzed Carbon–Sulfur Cross-Couplings
867
six-membered chelate rings. The fourth coordination site ble 1, entry 2) in the presence of catalyst 1a (1 mol%) and
is occupied by a chloride ion. Palladium catalyst 1b potassium carbonate (K2CO3). On increasing the amount
[Pd(L2)Cl] was prepared in a similar manner starting of catalyst (2 mol%), the yield of 4a improved from 65%
from ligand HL2. The complexes so prepared are air-sta- to 89%, and the reaction time decreased from eight to five
ble crystalline solids and can be stored under ambient con- hours (Table 1, entries 2 and 3). It was found that using
ditions for several months. They are insoluble in acetone, more than 2 mol% of catalyst 1a did not further improve
but are soluble in N,N-dimethylformamide, dichlorometh- the yield or the reaction time (Table 1, entry 4). The use
ane, and dimethyl sulfoxide. The structures of the new of other palladium catalysts [PdCl2, Pd(OAc)2 and
catalysts 1a and 1b were characterized by single crystal Pd2(dba)3] (Table 1, entries 11–13) resulted in lower
X-ray diffraction, IR, and elemental analysis.
yields, while Schiff base complexes such as palladium
complex 1b, and copper, cobalt, and nickel complex cata-
lysts (Table 1, entries 9 and 14–16) gave moderate yields
in longer reaction times. Among the catalysts surveyed,
Pd(L1)Cl (1a) was found to be the most efficient. With
these initial results in hand, a series of experiments was
performed in which the solvent was varied. Dimethyl sulf-
oxide, toluene, and tetrahydrofuran all gave moderate iso-
lated yields, but longer reaction times were required
(Table 1, entries 5, 6 and 8). However, the same reaction
in acetonitrile afforded 4a in a lower yield still (Table 1,
To optimize the reaction conditions, the effects of differ-
ent solvents, reaction times, and the amount of catalyst on
the cross-coupling reaction were investigated using ben-
zenesulfenyl chloride (2a) and phenylboronic acid (3a)
(Table 1). Treatment of benzenesulfenyl chloride (2a) (1
mmol) with phenylboronic acid (3a) in N,N-dimethyl-
formamide without a catalyst resulted in no reaction (Ta-
ble 1, entry 1). In contrast, a 65% yield of diphenyl sulfide
(4a) was obtained when a mixture of 2a and 3a was stirred
in N,N-dimethylformamide for eight hours at 90 °C (Ta-
1a (2 mol%), DMF
PhSAr
ArB(OH)2
PhSCl
+
K2CO3 (2 mmol), 90 °C
4
2a
3
S
S
S
S
S
Cl
F
Br
OMe
4a (89%)
4b (93%)
4c (70%)
4d (85%)
4e (80%)
S
S
S
S
S
CN
Cl
4f (63%)
4g (75%)
4h (62%)
4i (80%)
4j (82%)
S
Cl
S
S
S
S
t-Bu
Cl
4k (85%)
4l (67%)
4m (82%)
4n (60%)
4o (78%)
OMe
S
S
S
S
S
OMe
NO2
COOH
O
4p (69%)
4q (66%)
4r (73%)
4s (65%)
4t (60%)
NO2
S
F
S
S
S
NO2
S
S
4u (60%)
4v (40%)
4w (50%)
4x (66%)
4y (63%)
S
S
Cl
S
Br
S
CF3
S
N
S
Cl
Cl
Br
CF3
4z (69%)
4aa (61%)
4ab (59%)
4ac (72%)
4ad (45%)
Scheme 2 Substituent effects on the cross-coupling of phenylsulfenyl chloride (2a) with aryl boronic acids (3). Reagents and conditions: phen-
ylsulfenyl chloride (2a) (1 mmol), arylboronic acid 3 (1 mmol), K2CO3 (2 mmol), catalyst 1a (2 mol%), DMF (2 mL), 90 °C, N2 atm, 5 h.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 866–870

868
P. Gogoi et al.
LETTER
phenylboronic acid (60%), 3-nitrophenylboronic acid
(50%) and 3,5-bis(trifluoromethyl)phenylboronic acid
(61%) (4p,q,t,w and 4aa). The procedure also worked
with arylsulfenyl chlorides possessing electron-withdraw-
ing groups such as 2-nitrophenylsulfenyl chloride and 4-
nitrophenylsulfenyl chloride giving moderate yields of
products 4ae–ah over longer reaction times (Scheme 3).
Table 1 Optimization of the Reaction Conditions
catalyst, solvent
PhSCl
+
PhB(OH)2
PhSPh
K2CO3 (2 mmol)
2a
3a
4a
Entry
Catalyst (mol%)
Solvent
Time (h) Yield (%)a
1
2
–
DMF
DMF
DMF
DMF
DMSO
toluene
MeCN
THF
12
8
0
65
89
89
65
55
40
60
62
55
54
51
57
62
58
54
1a (2 mol%), DMF
1a (1)
Ar2B(OH)2
Ar1SCl
Ar1SAr2
+
K2CO3 (2 mmol), 90 °C
2
3
4
3
1a (2)
5
4
1a (3)
5
NO2
S
NO2
5
1a (2)
8
S
6
1a (2)
12
13
9
N
S
7
1a (2)
4aea (55 %)
4afb (60 %)
4agb (40 %)
8
1a (2)
9
1b (2)
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
7
S
10
11
12
13
14b
15b
16b
1b (3)
8
O2N
PdCl2 (2)
Pd(OAc)2 (3)
Pd2(dba)3 (3)
[CuL2]H2O (2)
[CoL2]H2O (2)
[NiL2]H2O (2)
9
4ahb (50 %)
10
7
Scheme 3 Substituent effects on the cross-coupling of arylsulfenyl
chlorides (2) with arylboronic acids 3. Reagents and conditions: aryl-
sulfenyl chloride 2 (1 mmol), arylboronic acid 3 (1 mmol), K2CO3 (2
mmol), catalyst 1a (2 mol%), DMF (2 mL), 90 °C, N2 atm, 5 h.
a Ar2 = Bn, b Ar2 = Ph
8
11
10
a Yield of isolated product.
It is important to mention that, in general, the reaction
time required using this procedure was shorter compared
to previously reported methods8,18 (12–48 h). With this
protocol, only cross-coupled products were obtained, and
self-coupling of the boronic acids or formation of diaryl
disulfides was not observed, even in trace amounts. The
mechanism of this coupling reaction is well-established14
and follows the typical catalytic pathway depicted in
Scheme 4.
b Catalysts [CuL2]H2O, [CoL2]H2O, and [NiL2]H2O were prepared as
reported in the literature.17
entry 7). Among the solvents examined, N,N-dimethyl-
formamide gave the desired sulfide 4a in the highest iso-
lated yield of 89% (Table 1, entry 3).
The optimized C–S coupling protocol was next utilized
with various arylsulfenyl chlorides and arylboronic acids.
The results summarized in Scheme 2 illustrate that the
method is compatible with a broad range of substituents
on the arylboronic acid, that is, both electron-rich and
electron-poor substrates. In general, the coupling reaction
was unaffected by steric hindrance and only affected mod-
erately by electronic factors. Sterically hindered substitut-
ed arylboronic acids such as 2,4,6-trimethyl-
phenylboronic acid (3n) and 2-naphthylboronic acid (3x),
and the unsubstituted boronic acid, phenylboronic acid
(3a), gave good yields of the expected products (4n,x,a)
in short reaction times. When boronic acids with electron-
donating substituents such as 4-methoxyphenylboronic
acid (3b) and 2-methoxyphenylboronic acid (3r) were
subjected to the coupling reaction, good (4r, 73%) to ex-
cellent (4b, 93%) yields were obtained in comparison to
those returned by electron-deficient aryl boronic acids, in-
cluding 4-nitrophenylboronic acid (69%), 4-carboxy-
phenylboronic acid (66%), 4-(methoxycarbonyl)-
Pd(II)
Ar1SAr2
Ar1SCl
Pd(0)
Ar1
S
Pd
Cl
Ar1
S
Pd
Ar2
Ar2B(OH)2
ClB(OH)2
Scheme 4 Outline of the probable reaction mechanism
Synlett 2014, 25, 866–870
© Georg Thieme Verlag Stuttgart · New York

LETTER
Palladium-Catalyzed Carbon–Sulfur Cross-Couplings
869
(7) Gogoi, P.; Gogoi, S. R.; Kalita, M.; Barman, P. Synlett 2013,
24, 873.
In conclusion, we have developed a highly efficient palla-
dium-catalyzed cross-coupling of arylsulfenyl chlorides
with arylboronic acids using a 2-[2-(benzylthio)phenyl-
iminomethyl]-4-bromophenol Schiff base palladium li-
gand as the catalyst. The ligands are readily prepared from
commercially available starting materials.
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The authors are grateful to Professor Franklin A. Davis, Department
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sions and suggestions, and Dr. Bipul Sarma, Department of Chemi-
cal Sciences, Tezpur University, India for assistance with X-ray
crystallography.
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(16) Ligands HL1 and HL2
The ligands, 2-[2-(benzylthio)phenyliminomethyl]-4-
bromophenol (HL1) and N-[2-(benzylthio)phenyl]salicyl-
aldimine (HL2) were synthesized according to the literature
method, see ref. 17.
[PdL1Cl] (1a)
Konstantinidis, A. K.; Brandt, M.; Daines, R. A.; Lonsdale,
J. T. J. Biol. Chem. 2001, 276, 30024.
2-[2-(Benzylthio)phenyliminomethyl]-4-bromophenol
(HL1) (199 mg, 0.50 mmol) was dissolved in EtOH (10 mL)
and a solution of sodium tetrachloropalladate (153 mg, 0.52
mmol) in EtOH (10 mL) was added dropwise. The mixture
was stirred in a water-bath at 90 °C for 0.5 h during which
the color of the solution changed to bright orange–yellow.
The solution was then allowed to stand for 2 h, which
resulted in the formation of orange–red needle-like crystals
suitable for X-ray diffraction. These were filtered, washed
with 25% EtOH–H2O and dried under vacuum (10–2 Torr).
The purity was assessed by TLC.
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Yield: 322 mg (86%); orange-red needles; mp 250 °C. IR
(KBr): 1620 (s), 1439 (s), 752 (s), 560 (s) cm–1. Anal. Calcd
for C20H15ONSPdBrCl: C, 44.55; H, 2.80; N, 2.60; S, 5.95.
Found: C, 44.75; H, 2.90; N, 2.57; S, 5.85.
[PdL2Cl] (1b)
Complex 1b was prepared from N-[2-(benzylthio)phenyl]-
salicylaldimine (HL2) using the same procedure as that
described for 1a.
(6) Bahekar, S. S.; Sarkate, A. P.; Wadhai, V. M.; Wakte, P. S.;
Shinde, D. B. Catal. Commun. 2013, 41, 123.
Yield: 274 mg (80%); orange–red crystals; mp 256 °C. IR
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 866–870

870
P. Gogoi et al.
LETTER
(KBr): 1600 (s), 1434 (s), 750 (s), 561 (s) cm–1. Anal. Calcd
for C20H16ONSPdCl: C, 52.18; H, 3.47; N, 3.04; S, 6.97.
Found: C, 52.23; H, 3.41; N, 3.16; S, 6.97.
The combined extracts were dried over anhydrous Na2SO4,
filtered and the solvent removed under reduced pressure.
The crude residue was purified by flash chromatography
over silica gel to provide product 4a (166 mg, 89%).
(17) Kalita, M.; Bhattacharjee, T.; Gogoi, P.; Barman, P.; Kalita,
R. D.; Sarma, B.; Karmakar, S. Polyhedron 2013, 60, 47.
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1420. (b) Tamizh, M. M.; Karvembu, R. Inorg. Chem.
Commun. 2012, 25, 30.
Sulfides 4; Typical Procedure
A sealed tube was charged with sulfenyl chloride 2a (219
mg, 1 mmol), phenylboronic acid (3a) (135 mg, 1 mmol),
K2CO3 (254 mg, 2 mmol), catalyst 1a (2 mol%, 10 mg) and
DMF (2 mL). The mixture was stirred at 90 °C under an N2
atm for 5 h. After completion of the reaction, the mixture
was cooled to r.t. and extracted with EtOAc (2 × 10 mL).
Synlett 2014, 25, 866–870
© Georg Thieme Verlag Stuttgart · New York