A highly efficient palladium-catalyzed one-pot synthesis of unsymmetrical aryl alkyl thioethers under mild conditions in water

Article abstract of DOI:10.1002/adsc.201100788

A palladium-catalyzed, one-pot synthesis of unsymmetrical aryl alkyl thioethers involving aryl halides (aryl bromides and chlorides), thiourea and alkyl bromides has been realized under mild conditions (room temperature to 50 °C) in water with polyoxyethanyl α-tocopheryl sebacate (PTS) as amphiphile. The PTS/water could be recycled in up to eight runs without an obvious change in its activity. Copyright

Full text of DOI:10.1002/adsc.201100788

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DOI: 10.1002/adsc.201100788
A Highly Efficient Palladium-Catalyzed One-Pot Synthesis of
Unsymmetrical Aryl Alkyl Thioethers under Mild Conditions in
Water
Liang Wang,a,* Wei-You Zhou,a Sheng-Chun Chen,a Ming-Yang He,a
and Qun Chena,*
a
Jiangsu Province Key Laboratory of Fine Petro-Chemical Technology, Changzhou University, Changzhou 213164,
Peopleꢀs Republic of China
Fax : (+86)-519-8633-0251; e-mail: lwcczu@126.com or chenqunjpu@yahoo.com
Received: October 14, 2011; Revised: December 15, 2011; Published online: March 7, 2012
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100788.
Abstract: A palladium-catalyzed, one-pot synthesis
of unsymmetrical aryl alkyl thioethers involving
aryl halides (aryl bromides and chlorides), thiourea
and alkyl bromides has been realized under mild
conditions (room temperature to 508C) in water
with polyoxyethanyl a-tocopheryl sebacate (PTS)
as amphiphile. The PTS/water could be recycled in
up to eight runs without an obvious change in its
activity.
al of these solvents is a major problem. To overcome
these problems, different thiol surrogates such as thio-
urea,[8] potassium thiocyanate,[9] potassium ethyl xan-
thogenate,[10] potassium thioacetate[11] have been em-
ployed to form aryl thiols in situ. Moreover, green sol-
À
vents have also been successfully applied in Caryl
S
bond formation reactions. For example, Firouzabadi[8]
et al. reported a copper-catalyzed S-arylation of di-
verse alkyl bromides with aryl halides using thiourea
as thiol surrogates in PEG200. Carril[6e] et al. reported
a recyclable catalytic system for S-arylation reactions
in the presence of water. Although these works pro-
vided us with good methods for the preparation of
thioethers, the development of an efficient and envi-
ronmentally benign process with a broad substrate
scope especially for aryl chlorides was still in demand.
Recently, reactions in aqueous media or “on
Keywords: aryl halides; micellar catalysis; polyox-
yethanyl a-tocopheryl sebacate (PTS)/water; thiour-
ea; unsymmetrical aryl alkyl thioethers
The formation of C S bonds represents a key step in water”[12] have gained wide interest since water is in-
the synthesis of many important molecules that are of expensive, non-toxic, and safe with respect to han-
biological, pharmaceutical, and material interest.[1] dling. Nevertheless, reactions especially the transition
À
À
Generally, the generation of C S bonds, especially metal-catalyzed coupling reactions “in water” have
Caryl S bonds involved the coupling reaction, the been extremely limited due to the insolubility of or-
[2]
À
SNAr reaction[3] and the electrophilic substitution re- ganic substrates. In this context, micellar catalysis is
action[4] of activated aryl halides with arenethiols. an efficient way to deal with the “bottle-neck”. Re-
À
S
Among them, the transition metal-catalyzed Caryl
cently, polyoxyethanyl a-tocopheryl sebacate (PTS,
bond formation reactions by direct coupling of aryl Scheme 1), a non-ionic amphiphile has been intro-
halides and arenethiols have received much attention, duced by Lipshutzꢀs group and proved to be a versatile
and various metal catalysts such as Pd,[5] Cu,[6] and “solubilizer” for organic molecules in water. Lipophil-
Fe[7] etc. have been successfully utilized for the syn- ic substrates and catalysts can efficiently enter the
thesis of aryl sulfides.
25 nm micelles formed by PTS in water leading to
While acknowledging the pioneering work in this cross-coupling reactions such as metathesis reac-
field, some drawbacks are still issues to be addressed. tion,[13] Heck reaction,[13] amination,[14] Suzuki–
For example, the direct use of thiols is environmental- Miyaura reaction,[15] Fujiwara–Moritani reaction,[16]
ly unfriendly due to their foul smell, volatility and and Sonogashira reaction[17] etc. at room temperature.
toxicity. In addition, most of the reported reactions Importantly, there is no need for a co-solvent to en-
proceeded in harmful organic solvents and the dispos-
Adv. Synth. Catal. 2012, 354, 839 – 845
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839

Liang Wang et al.
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À
Scheme 1. One-pot Caryl S bond formation in PTS/H2O.
Table 1. Effect of reaction parameters on the preparation of phenyl benzyl thioether.[a]
Entry
Pd source
PdCl2A(CH3CN)2
Ligand
Base
Additive
Conversion [%][b]
1
2
3
4
5
6
7
8
G
–
–
–
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
KOH
KO-t-Bu
K3PO4
Et3N
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
PTS
PTS
PTS
PTS
PTS
PTS
PTS
PTS
PTS
PTS
PTS
PTS
PEG-600
Trixon X-100
SDS
TBAB
–
<5
<5
29
21
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
Pd
G
G
R
E
N
N
1,10-Phen (1)
PPh3
40
86
A-taPhos (2)
Xphos (3)
DPEPhos (4)
Xphos (3)
Xphos (3)
Xphos (3)
Xphos (3)
Xphos (3)
Xphos (3)
Xphos (3)
Xphos (3)
Xphos (3)
97, 82[c], 95[d]
R
N
N
T
N
T
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
91
90
95
70
63
46
81
40
28
11[e]
9
10
11
12
13
14
15
16
17
N
ACHTUNGTRENNUNG
[a]
Reaction conditions: bromobenzene (1 mmol), benzyl bromide (1.1 mmol), thiourea (1.2 mmol), base (3 mmol), Pd preca-
talyst (0.5 mol%), ligand (1 mol%), 2% additive/H2O (2 mL), room temperature, 4 h.
Conversion based on GC/MS.
1% PTS/H2O.
3% PTS/H2O.
Reaction “on water” for 12 h.
[b]
[c]
[d]
[e]
hance the solubility of water-insoluble substrates in
these reactions.
The palladium precatalysts and ligands (Figure 1)
play important roles in the reaction. Among several
To the best of our knowledge, the transition metal- Pd precatalysts and ligands screened, those bearing
À
catalyzed Caryl S bond formation reactions, especially monodentate and bidentate phosphine ligands
those utilizing inactivated aryl halides in water are showed high activity, and Pd
A
rare. Hence, in continuation of our interest in green to be the best combination (Table 1, entries 5–8).
À
approaches for Caryl S bond formation, we herein However, extremely low conversion was detected in
report a Pd-catalyzed, one-pot synthesis of unsymmet- the absence of any ligands. When a Pd(0) source such
rical aryl alkyl thioethers by coupling of aryl bromides as Pd
or chlorides, thiourea and alkyl bromides under very creased to 29%. It could be concluded that the highly
mild conditions in water (Scheme 1). active Pd(0) catalyst was responsible for the results.
2ACHTUNGTERN(NUNG dba)3 was employed, the conversion was in-
An initial investigation focused on the reaction of In our catalytic system, the active Pd(0) catalyst was
thiourea, benzyl bromide with bromobenzene in readily generated in situ by water-promoted activation
2 wt% PTS/H2O at room temperature (Table 1).
of PdACTHNGUETRNU(NG OAc)2 in the presence of phosphine ligands,
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A Highly Efficient Palladium-Catalyzed One-Pot Synthesis of Unsymmetrical Aryl Alkyl Thioethers
(3%) offered no advantage, and conversions were
somewhat lower under identical conditions (Table 1,
entry 7).
Under the optimized conditions, a series of unsym-
metrical aryl alkyl thioethers could be successfully
synthesized from substituted bromobenzenes, thiour-
eas and alkyl halides at room temperature (Table 2).
Firstly, the substituted thioureas were checked and all
of them showed good activity, providing the corre-
sponding products in good to excellent yields. Among
them, thiourea appeared to be the best choice due to
its commercial availability and economic affordability.
The substituents on the aryl bromides, however, could
affect the reaction in terms of both reaction time and
conversion. The aryl bromides bearing electron-do-
nating groups such as OMe at the para position were
less effective; while electron-withdrawing groups, for
example, NO2, could effectively promote the reaction
in a very short time with nearly quantitative conver-
Figure 1. Ligands examined in this study.
which is consistent with observations by Buchwaldꢀs sion (Table 2, entry 7). Various alkyl halides, in addi-
group.[18]
tion, could participate in the reactions. As seen from
The base effect on the reaction was evaluated next. the results presented in Table 2, primary halides (io-
K2CO3, KOH and KO-t-Bu were all effective and up dides, bromides, chlorides) were easily converted to
to 97% conversion was achieved when K2CO3 was uti- the corresponding thioethers in good to excellent
lized. Both K3PO4 and Et3N were less effective, af- yields, although a slightly lower yield was observed
fording a moderate conversion. Different surfactants when an alkyl chloride was employed (Table 2, en-
were also investigated on the model reaction. As can tries 8–10). Considering the cost and activity, alkyl
be seen from Table 1, other surfactants including bromides were chosen as the best substrates. We have
PEG-600, Trixon X-100, SDS and TBAB, however, also investigated the applicability of our method using
were not as effective. In addition, the corresponding secondary and tertiary bromides (Table 2, entries 11
reaction “on water” gave the lowest level of conver- and 12). Under the optimized conditions, cyclohexyl
sion (Table 1, entry 17). It was worth noting that the bromide reacted with bromobenzene and thiourea
1–2% PTS in water was sufficient. A higher loading smoothly, affording the product 5f in 88% yield in
Table 2. One-pot synthesis of unsymmetrical aryl alkyl thioethers from aryl bromides.[a]
Entry
R1
R2-X
R3
Product
Time [h]
Yield [%][b]
1
2
3
4
5
6
7
8
H
H
H
H
PhCH2Br
PhCH2Br
PhCH2Br
PhCH2Br
PhCH2Br
PhCH2Br
PhCH2Br
n-C4H9I
n-C4H9Br
n-C4H9Cl
cyclohexyl bromide
tert-butyl bromide
H
5a
5a
5a
5a
5b
5c
5d
5e
5e
5e
5f
5g
4
4
4
4
4
6
2
6
6
6
6
12
97
90
88
85
92
87
99
91
90
83
88
76
Me
Et
Bn
H
H
H
H
H
H
H
4-CH3
4-OCH3
4-NO2
H
H
H
H
H
9
10
11
12
H
[a]
Reaction conditions: aryl bromide (1 mmol), alkyl halide (1.1 mmol), substituted thiourea (1.2 mmol), K2CO3 (3 mmol),
Pd(OAc)2 (0.5 mol%), XPhos 3 (1 mol%), 2% PTS/H2O (2 mL), room temperature.
Isolated yield.
ACHTUNGTRENNUNG
[b]
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Liang Wang et al.
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Table 3. One-pot synthesis of unsymmetrical aryl alkyl thioethers from aryl chlorides.[a]
96%, 508C, 12 h
97%, r.t., 12 h
46%, 508C, 12 h
92%, 508C, 16 h
90%, r.t., 12 h
83%, r.t., 12 h
87%, 508C, 16 h
91%, r.t., 12 h
93%, r.t., 12 h
91%, r.t., 12 h
71%, r.t., 16 h
92%, r.t., 12 h
90%, 508C, 16 h
95%, r.t., 12 h
88%, r.t., 12 h
87%, 508C, 16 h
89%, r.t., 12 h
91%, r.t., 12 h
[a]
Reaction conditions: aryl chloride (1 mmol), alkyl bromide (1.1 mmol), thiourea (1.2 mmol), K2CO3 (3 mmol), Pd
(0.5 mol%), XPhos 3 (1 mol%), 2% PTS/H2O (2 mL).
ACHTUNGTRENNUNG(OAc)2
6 h. However, tert-butyl bromide reacted sluggishly temperature and prolonged reaction time were re-
and a 76% yield was obtained by prolonging the reac- quired. It was worth noting that only 46% yield of
tion time.
product 6g was obtained under the optimized condi-
The transition metal-catalyzed coupling reactions tions and by-products were observed. Next, a series of
using aryl chlorides in water under mild conditions, in alkyl bromides including allyl bromide, cyclohexyl
particular at room temperature, are still a challenging bromide, n-octyl bromide and tert-butyl bromide was
task in this field. To probe the scope of our catalytic evaluated using 4-nitrochlorobenzene as substrate
system, we further extended this protocol to aryl (see products 6i–6o) and it can be seen that all the re-
chlorides.
actions proceeded smoothly to provide the corre-
As depicted in Table 3, the electronic property of sponding products in good to excellent yields. While
different substituents on the aryl chlorides affected the electron-rich aryl chlorides, for example, 4-chloro-
the reaction significantly. Those aryl chlorides bearing
ACHTUNGTRENaNGNU nisole furnished the corresponding products 6n and
electron-withdrawing groups such as NO2, COCH3, 6o in high yields, albeit at a slightly elevated tempera-
CN at the para position worked very well in this ture and prolonged reaction time. Heterocycles such
system at room temperature within 12 h, affording as 5-chloropyrimidine also showed high activity to
products in excellent yields. Those aryl chlorides bear- give 6p, 6q and 6r in 91%, 95% and 89% yields, re-
ing electron-donating groups such as CH3, OCH3, spectively.
NH2 were less effective. Generally, a slightly elevated
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A Highly Efficient Palladium-Catalyzed One-Pot Synthesis of Unsymmetrical Aryl Alkyl Thioethers
Table 4. Recycling of PTS/H2O.
Cycle:
Yield:
1
2
3
4
5
98%
6
97%
7
96%
8
97%
98%
98%
98%
96%
Another advantage of this protocol is the recycla- perature, although slightly elevated temperature and
bility of the aqueous phase due to the preferred solu- prolonged reaction time are necessary for electron-
bility of PTS in water, as opposed to common organic rich aryl chlorides. The mild conditions, environmen-
solvents (e.g., hydrocarbons, Et2O, and EtOAc). The tally benign thiol surrogates, water as solvent and re-
coupling reaction of bromobenzene, benzyl bromide cyclability of PTS/H2O make it more advantageous
and thiourea was conducted under the optimized con- than the methods previously reported. Studies on new
ditions for 4 h, followed by extraction with minimal applications of PTS/H2O in organic chemistry are cur-
amounts of EtOAc several times. After that, new rently underway in our laboratory.
starting materials, Xphos and K2CO3 were added to
the micellar palladium catalyst solution. As illustrated
in Table 4, almost the same conversion could be real- Experimental Section
ized even after 8 runs.
A
plausible mechanism is also presented General Remarks
(Scheme 2). In this reaction, two points should be
mentioned. Firstly, the highly active Pd(0) catalyst
was generated by reduction of PdACTHNUTRGENUG(N OAc)2 using X-
PdACTHNUTRGNE(NUG OAc)2, ligands and PTS (15 wt% in H2O) were obtained
from Aldrich. Water (HPLC grade) was purchased from
Acros and degassed by sparging with argon prior to use. The
solution of 15 wt% PTS (1 mL) was diluted with degassed
water (6.5 mL) to give the 2 wt% aqueous PTS solution
(7.5 mL). Other commercially available reagents were used
Phos ligand. The presence of water enormously pro-
moted the reduction process.[19] Secondly, the thiolate
ion was believed to be generated by hydrolysis of S-
alkylisothiouronium salt (7), which was generated in
situ from thiourea and alkyl bromide.[8,20] The thiolate
ion and aryl halide then underwent the classic palladi-
um-catalyzed oxidative addition and elimination reac-
tion in the presence of Pd(0) to produce the aryl alkyl
thioethers with urea as by-product.
1
without further purification. H and 13C NMR spectra were
recorded ion a 300 MHz spectrometer in CDCl3 using TMS
as internal standard. Chemical shifts are reported in ppm
(d), and coupling constants (J), in Hz. GC/MS analyses were
performed on a Saturn 2000GC/MS instrument. All the
products are known compounds and were identified by com-
paring of their physical and spectra data with those reported
in the literature.
In summary, a highly efficient protocol for the Pd-
catalyzed, one-pot synthesis of unsymmetrical aryl
alkyl thioethers in water has been developed. The mi-
cellar environment is mainly responsible for the high Typical Procedure for One-Pot synthesis of Aryl
reaction efficiency. The combination of Pd(OAc)2 and Alkyl Thioethers
AHCTUNGTRENNUNG
X-Phos shows extremely high catalytic activity for the
reaction, giving a series of thioethers in good to excel-
lent yields. Various functional groups are tolerated
and the aryl halides can react smoothly at room tem-
A three-necked flask was purged with N2 and then was
charged with Pd(OAc)2 (1.1 mg, 0.005 mmol), XPhos
(4.8 mg, 0.01 mmol), K2CO3 (414.6 mg, 3 mmol), aryl halide
(1 mmol), alkyl bromide (1.1 mmol) and thiourea (91 mg,
AHCTUNGTRENNUNG
Scheme 2. Plausible mechanism.
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1
1.2 mmol), followed by addition of degassed PTS solution
(2.0 mL, 2 wt%) via syringe. The mixture was then stirred at
room temperature or 508C for a certain time as monitored
by GC/MS. After completeion of the reaction, the mixture
was cooled to room temperature (if necessary), diluted with
brine and extracted with ethyl acetate. The combined organ-
ic extract was dried over anhydrous Na2SO4, filtered, and
concentrated by rotary evaporation to give a crude product.
Purification by silica gel chromatography eluting with
EtOAc/n-hexane afforded the pure thioether.
5g[26]: H NMR (300 MHz, CDCl3): d=7.53–7.50 (m, 2H),
7.33–7.31 (m, 3H), 1.26 (s, 9H); 13C NMR (75 MHz,
CDCl3): d=137.4, 132.7, 128.6, 128.4, 45.8, 30.9.
1
6e[27]: H NMR (300 MHz, CDCl3): d=7.36–7.17 (m, 7H),
6.88–6.79 (m, 2H), 4.02 (s, 2H), 3.81ACTHNUTRGNEUNG
(s, 3H); 13C NMR
(75 MHz, CDCl3): d=197.6, 144.6, 136.7, 134.6, 129.2, 129.1,
127.9, 127.3, 37.6, 26.8.
1
6f[27]: H NMR (300 MHz, CDCl3): d=7.57–7.42 (m, 2H),
7.40–7.22 (m, 7H), 4.21 (s, 2H); 13C NMR (75 MHz,
CDCl3): d=144.9, 136.1, 132.6, 129.2, 129.1, 128.1, 127.7,
119.2, 109.0, 37.5.
1
6g[27]: H NMR (300 MHz, CDCl3): d=7.30–7.12 (m, 7H),
6.62–6.54 (m, 2H), 3.98 (s, 2H), 3.71 (s, 2H); 13C NMR
(75 MHz, CDCl3): d=146.6, 138.9, 135.2, 129.3, 128.7, 127.3,
123.3, 115.8, 42.2.
Recycling Procedure
A three-necked flask was purged with N2 and then was
charged with PdACHTUNGTRENNUNG(OAc)2 (1.1 mg, 0.005 mmol), XPhos
6h[28]:1H NMR (300 MHz, CDCl3): d=7.26–7.21 (m, 5H),
7.20 (s, 4H), 4.07 (s, 2H); 13C NMR (75 MHz, CDCl3): d=
137.1, 134.7, 132.5, 131.5, 129.0, 128.8, 128.6, 127.3, 39.3.
(4.8 mg, 0.01 mmol), K2CO3 (414.6 mg, 3 mmol), bromoben-
zene (157.7 mg, 1 mmol), benzyl bromide (188.1 mg,
1.1 mmol) and thiourea (91 mg, 1.2 mmol), followed by ad-
dition of degassed PTS solution (2.0 mL, 2 wt%) via syringe.
The mixture was then stirred at room temperature for 4 h.
After completion of the reaction, ethyl acetate (3 mL) was
then added to the reaction mixture and stirred for 30 s. The
reaction mixture was then allowed to separate and the
EtOAc layer was removed by pipet. The aqueous layer was
successively washed with EtOAc (3ꢂ3 mL). The combined
EtOAc extract layers were dried over anhydrous Na2SO4,
filtered, concentrated by rotary evaporation and the residue
was purified by silica gel chromatography eluting with
EtOAc/n-hexane. For the second run, the fresh starting ma-
terials, Xphos and K2CO3 were added to the micellar palla-
dium catalyst solution and stirred at room temperature for
another 4 h. The work-up was conducted in exactly the same
way as described for the first cycle.
6i[29] 1H NMR (300 MHz, CDCl3): d=8.05–8.01 (d, J=
:
9.0 Hz, 2H), 7.60–7.22 (m, 7H), 6.58–6.03 (m, 2H), 3.81–
3.78 (d, J=6.5 Hz, 2H); 13C NMR (75 MHz, CDCl3): d=
152.8, 134.0, 132.3, 131.5, 129.1, 128.6, 126.9, 126.3, 123.9,
123.0, 33.9.
6j[8]: H NMR (300 MHz, CDCl3): d=8.05–7.99 (m, 2H),
1
7.29–7.23 (m, 2H),3.32–3.24 (m, 1H), 1.99–1.95 (m, 2H),
1.74–1.70 (m, 2H), 1.70–1.27 (m, 6H); 13C NMR (75 MHz,
CDCl3): d=145.9, 144.0, 126.5, 122.8, 43.7, 31.8, 24.8, 24.5.
1
6k[8]: H NMR (300 MHz, CDCl3): d=8.06–8.01 (m, 2H),
7.28–7.23 (m,2H), 3.70–3.65ACTHNUGRTNEUNG(m, 1H), 2.13–2.10 (m, 2H),
1.74–1.58 (m, 6H); 13C NMR (75 MHz, CDCl3): d=147.8,
145.8, 125.4, 122.8, 43.3, 32.3, 23.9.
1
6l[30]: H NMR (300 MHz, CDCl3): d=8.03–7.96 (m, 2H),
7.23–7.16 (m, 2H), 2.89 (t, J=7.5 Hz, 2H), 1.64–1.58 (m,
2H), 1.35–1.17 (m, 10H), 0.80–0.75 (m, 3H); 13C NMR
(75 MHz, CDCl3): d=148.2, 144.7, 125.8, 123.8, 31.8, 31.7,
29.1, 29.0, 28.8, 28.4, 22.6, 14.0.
Characterization Data of Compounds
6m[8]: 1H NMR (300 MHz, CDCl3): d=8.10–8.06 (d, J=
10.6 Hz, 2H), 7.60–7.56 (d, J=9.3 Hz, 2H),1.28 (s, 9H);
13C NMR (75 MHz, CDCl3): d=147.6, 142.2, 136.8, 123.2,
47.5, 31.0.
5a (6a)[21] 1H NMR (300 MHz, CDCl3): d=7.22–7.12 (m,
:
10H), 3.49 (s, 2H); 13C NMR (75 MHz, CDCl3): d=137.7,
136.9, 129.8, 129.4, 128.8, 127.7, 127.5, 126.6, 43.5.
1
5b (6b)[22]: H NMR (300 MHz, CDCl3): d=7.30–7.10 (m,
1
6n[31]: H NMR (300 MHz, CDCl3): d=7.32–7.26 (m, 2H),
10H), 6.98–6.95 (m, 2H), 4.13 (s, 2H), 2.21 (s, 3H);
13C NMR (75 MHz, CDCl3): d=136.7, 135.4, 131.4, 129.6,
128.5, 127.9, 127.4, 126.0, 125.9, 38.7, 20.0.
6.77–6.71 (m, 2H), 3.71 (s, 3H), 2.82 (m, 1H), 1.84–1.18 (m,
10H); 13C NMR (75 MHz, CDCl3): d=158.2, 134.5, 123.9,
115.3, 113.2, 54.2,46.8, 32.3, 28.6, 25.0, 24.7.
1
5c (6c)[23]: H NMR (300 MHz, CDCl3): d=7.17–7.08 (m,
1
6o[31]: H NMR (300 MHz, CDCl3): d=7.32–7.26 (m, 2H),
7H), 6.70–6.66 (m, 2H), 3.88 (s, 2H), 3.62 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=158.1, 137.0, 132.9, 127.8, 127.3, 125.9,
125.0, 113.3, 54.2, 40.1.
6.79–6.73 (m, 2H), 3.73 (s, 3H), 3.73–3.32 (m, 1H), 1.90–
1.86 (m, 2H), 1.70–1.68 (m, 2H), 1.56–1.46 (m, 4H),;
13C NMR (75 MHz, CDCl3): d=158.9, 138.1, 134.1, 116.3,
114.3, 55.2, 47.9, 33.4, 30.5, 24.6.
1
5d (6d)[8]: H NMR (300 MHz, CDCl3): d=8.02–7.97 (m,
2H), 7.32–7.17 (m, 7H), 4.16 (s,2H); 13C NMR (75 MHz,
CDCl3): d=147.2, 145.1, 135.4, 129.7, 128.8, 128.7,127.8,
126.5, 123.9, 36.9.
1
6p[8]: H NMR (300 MHz, CDCl3): d=8.03–7.96 (m, 2H),
7.23–7.16 (m, 2H), 2.89 (t, J=7.5 Hz, 2H), 1.64–1.58 (m,
2H), 1.35–1.17 (m, 10H), 0.80–0.75 (m, 3H); 13C NMR
(75 MHz, CDCl3): d=148.2, 144.7, 125.8, 123.8, 31.8, 31.7,
29.1, 29.0, 28.8, 28.4, 22.6, 14.0.
1
5e[24]: H NMR (300 MHz, CDCl3): d=7.30–7.17 (m, 4H),
7.13–7.07 (m, 1H), 2.88 (t, J=7.5 Hz, 2H), 1.62(p, J=7.5 Hz,
2H), 1.43 (sex, J=7.5 Hz, 2H), 0.93 (t, J=6.7 Hz, 3H);
13C NMR (75 MHz, CDCl3): d=136.9, 130.9, 129.1, 128.7,
126.9, 125.5, 33.1, 31.1, 21.9, 13.5.
1
6q[8]: H NMR (300 MHz, CDCl3): d=8.9 (s, 1H), 8.49 (s,
2H), 7.29–7.12 (m, 5H), 4.02 (s, 2H); 13C NMR (75 MHz,
1
5f[25]: H NMR (300 MHz, CDCl3): d=7.38 (d, J=12.0 Hz,
CDCl3): d=157.2, 155.4, 134.9, 127.8, 127.7, 126.7, 37.9.
6r[8]: H NMR (300 MHz, CDCl3): d=9.06 (s, 1H), 8.63 (s,
1
2H), 7.30–7.17 (m, 1H), 2.01–1.92 (m, 2H), 1.81–1.74 (m,
2H), 1.65–1.57 (m, 1H), 1.44–1.20 (m, 5H); 13C NMR
(75 MHz, CDCl3): d=135.1, 131.8, 128.7, 126.5, 46.5, 33.3,
26.0, 25.7.
2H), 3.59–3.48 (m, 1H), 1.75–1.70 (m, 2H), 1.61–1.51 (m,
6H); 13C NMR (75 MHz, CDCl3): d=157.2, 155.7, 133.4,
45.7, 33.7, 24.6.
844
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 839 – 845

A Highly Efficient Palladium-Catalyzed One-Pot Synthesis of Unsymmetrical Aryl Alkyl Thioethers
[11] a) N. Park, K. Park, M. Jang, S. Lee, J. Org. Chem.
Acknowledgements
2011, 76, 4371; b) K. M. Wager, M. H. Daniels, Org.
Lett. 2011, 13, 4052.
This project was funded by the Priority Academic Program
Development (PAPD) of Jiangsu Higher Education Institu-
tions which is fully acknowledged.
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H. C. Kolbe, K. B. Sharpless, Angew. Chem. 2005, 117,
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[13] B. H. Lipshutz, S. Ghorai, W. W. Y. Leong, B. R. Taft, J.
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asc.wiley-vch.de
845