Benzenesulfonyl chlorides: New reagents for access to alternative regioisomers in palladium-catalysed direct arylations of thiophenes

Article abstract of DOI:10.1039/c3sc52420e

The palladium-catalysed coupling of benzenesulfonyl chlorides with thiophene derivatives allows regioselective access to β-arylated thiophenes. The reaction proceeds with easily accessible catalyst, base and substrates, without oxidant or ligand and tolerates a variety of substituents on both the benzene and thiophene moieties.

Full text of DOI:10.1039/c3sc52420e

View Article Online
View Journal
Chemical Science
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: K. Yuan and H. Doucet, Chem. Sci.,
2013, DOI: 10.1039/C3SC52420E.
This is an Accepted Manuscript, which has been through the RSC Publishing peer
review process and has been accepted for publication.
Chemical Science
Accepted Manuscripts are published online shortly after acceptance, which is prior
www.rsc.org/chemicalscience
Volume 1 | Number 4 | 1 October 2010 | Pages 417–528
to technical editing, formatting and proof reading. This free service from RSC
Publishing allows authors to make their results available to the community, in
citable form, before publication of the edited article. This Accepted Manuscript will
be replaced by the edited and formatted Advance Article as soon as this is available.
To cite this manuscript please use its permanent Digital Object Identifier (DOI®),
which is identical for all formats of publication.
More information about Accepted Manuscripts can be found in the
Information for Authors.
ISSN 2041-6520
PERSPECTIVE
Barry M. Trost et al.
Catalytic asymmetric allylic alkylation
Andrew J. deMello, Joshua B. Edel et al. employing heteroatom nucleophiles:
Please note that technical editing may introduce minor changes to the text and/or
graphics contained in the manuscript submitted by the author(s) which may alter
content, and that the standard Terms & Conditions and the ethical guidelines
that apply to the journal are still applicable. In no event shall the RSC be held
responsible for any errors or omissions in these Accepted Manuscript manuscripts or
any consequences arising from the use of any information contained in them.
EDGE ARTICLE
Rapid cell extraction in aqueous two-
phase microdroplet systems
a powerful method for C–X bond
formation
2041-6520(2010)1:4;1-
X
www.rsc.org/chemicalscience
Registered Charity Number 207890

Page 1 of 6
Chemical Science
Journal Name
RSCPublishing
View Article Online
DOI: 10.1039/C3SC52420E
ARTICLE
Benzenesulfonyl chlorides: New reagents for
access to alternative regioisomers in palladium-
catalysed direct arylations of thiophenes
Cite this: DOI: 10.1039/x0xx00000x
Kedong Yuana and Henri Douceta*
Received 00th January 2012,
Accepted 00th January 2012
The palladium-catalysed coupling of benzenesulfonyl chlorides with thiophene
DOI: 10.1039/x0xx00000x
derivatives allows the regioselective access to
β-arylated thiophenes. The reaction
proceeds with easily accessible catalyst, base and substrates, without oxidant or
ligand and tolerates a variety of substituents both on the benzene and thiophene
moieties.
www.rsc.org/
Introduction
control the regioselectivity of the arylation.4,5 In 2009, Itami
and co-workers have established a catalytic system that
promotes the β-selective arylation of thiophene derivatives
In recent years, the metal-catalysed functionalization of
C-H bonds has emerged as a powerful method for the
simpler access to molecules useful to materials or
biological applications. If specific C–H bonds of
(hetero)arenes can be easily coupled with arenes, it
becomes one of the most simple way for access to
bi(hetero)arenes.1 From thiophene derivatives and aryl
with aryl iodides without directing group on the thiophenes.
These β-functionalisation were obtained using PdCl2
associated to a phosphite ligand using Ag2CO3 as the base
(Scheme 1, top).6 Glorius and co-workers have very recently
reported an heterogeneously catalyzed C−H arylation of
benzo[b]thiophenes.7 They demonstrated that, using Pd/C
catalyst without additional ligands or directing groups on
benzothiophene, but in the presence of 10 mol-% CuCl2, the
less reactive β-position of benzothiophenes was arylated with
an excellent selectivity. Studer and Itami have also developed
a method for the β-arylations of thiophenes with arylboronic
acids under Pd/TEMPO catalysis (Scheme 1, middle).8 The
same year, Bach et al. reported that thiophenes substituted at
C3 by CH2COOEt or CH2PO(OEt)2 undergo a regioselective
oxidative coupling reaction at C4 with various arylboronic
acids in the presence of silver oxide, cesiumtrifluoroacetate
[Cs(tfa)], benzoquinone (BQ), and Pd(tfa)2 catalyst in
trifluoroacetic acid.9 In 2012, Oi et al. described the direct
arylation of (benzo)thiophenes with aryltrimethylsilanes. The
use of PdCl2(MeCN)2 catalyst in the presence of CuCl2 as
oxidant also gives the β-arylated thiophenes (Scheme 1,
middle).10
halides as the coupling partners, the α-arylated products
were easily obtained using palladium catalysts under
various conditions (Fig. 1, left).1g,2 On the other hand,
until recently, relatively little effort has been expended
toward developing such metal-catalysed direct arylation
reactions for the synthesis of
β-arylated thiophenes (Fig.
1, right).3
H
H
Ar
[Pd]
[Pd]
ArX +
base
base
Ar
H
H
S
S
S
α-arylation
β-arylation
Most acidic
Figure 1.
A few examples of such β-arylations3 have been reported
using new catalysts, reactants and/or reaction conditions.4-9
Some of them employ a directing group on the thiophene
derivative such as a 2-pyridyl or a carboxanilide functions to
This journal is © The Royal Society of Chemistry 2013
J. Name., 2013, 00, 1‐3 | 1

Chemical Science
Page 2 of 6
Journal Name
ARTICLE
using Pd(OAc)2 catalyst and K2CO3 as the base only gave
decomposed benzenesulfonyl chloride (Table 1, entry 1). The
use of PdCl(C3H5)(dppb) or PdCl2 catalysts led VtoiewthAerticdleeOsinrliende
product 1b as trace (Table 1, entries 2 DaOnId: 130).1.03O9/nC3thSCe52o4t2h0eEr
hand, Pd(PhCN)2Cl2 catalyst in the presence of a mixture of
K2CO3/LiCl gave product 1b in 30% yield (Table 1, entry 4).
The addition of 1 equiv. of CuI to the reaction mixture or the
use of DMSO or toluene as the solvents resulted in very low
yields of 1b. The reaction temperature was found to be a
crucial factor for such couplings, as the use of 140°C instead
of 120°C allowed to increase the yield in 1b to 75% (Table 1,
2009 Itami6
R'
PdCl2 5 mol-%
P[OCH(CF3)2]3
10 mol-%
R'
Ar
Ar
Ar
+ ArI
R
S
R
Ag2CO3, m-xylene,
130 °C
S
S
S
2011 Studer, Itami8
R'
Pd(OAc)2 10 mol-%
bipy 10 mol-%
R'
entry 8).
Moreover, an excellent regioselectivity was
+ ArB(OH)2
observed, as 1b was produced in 99%. The desired product
1b was obtained in 43% yield using Li2CO3 without additive
in the presence of Pd(PhCN)2Cl2 catalyst; whereas similar
conditions using Pd(MeCN)2Cl2 catalyst gave 1b in 80%
yield (Table 2, entries 9 and 10). Then, we examined the
influence of several bases at 140°C using Pd(MeCN)2Cl2
catalyst. Lower yield in 1b were obtained using three equiv.
of K3PO4, KOAc, Na2CO3 or K2CO3 (Table 1, entries 11-14).
R
R
Tempo, C6H5CF3,
80 °C
S
2012 Oi10
R'
PdCl2(MeCN)2
5 mol-%
R'
CuCl2 2 eq.
+ ArSiMe3
R
S
R
ClCH2CH2Cl,
80 °C
A
complete decomposition of 4-methylbenzenesulfonyl
This work
R'
chloride, without formation of 1b, was observed in the
presence of Cs2CO3 (Table 1, entry 15). This difference
between carbonated bases might be due to the higher
solubility of Cs2CO3 than Li2CO3, Na2CO3 or K2CO3 in
dioxane. A longer reaction time allowed to increase the yield
in 1b to 84% with complete conversion of 4-
methylbenzenesulfonyl chloride (Table 1, entry 17). Finally,
the influence of a few other solvents was examined. NMP,
DMF and DMSO only gave decomposed benzenesulfonyl
chloride (Table 1, entries 18-20); whereas, ethylbenzene and
xylene gave 1b in very low yields (Table 1, entries 21 and
22).
PdCl2(MeCN)2
5 mol-%
R'
Ar
+ ArSO2Cl
R
S
R
base
S
Scheme 1. Procedures for Pd-catalysed β-arylations of thiophene
derivatives without directing group.
In 2009, Dong and co-workers reported the Pd-catalysed
coupling of 2-phenylpyridine with benzenesulfonyl chlorides
to prepare sulfones.11 However, in the course of this study
they also observed in one case, a desulfitative12 direct
arylation of a quinoline derivative when using elevated
temperature in the presence of Ag2CO3 and CuBr. The use of
benzenesulfonyl chlorides13-15 as the coupling partners for the
palladium-catalysed desulfitative direct arylation of
benzoxazoles derivatives has been recently described by
Cheng et al.16 Using 10 mol-% Pd(OAc)2 catalyst, K2CO3 as
base and 1 equiv. of CuI as additive, the 2-arylbenzoxazoles
were obtained in high yields. On the other hand, to our
knowledge, the desulfitative direct arylation of thiophenes
with benzenesulfonyl chlorides has not been reported.
Then, the scope of the substituents on the benzenesulfonyl
chloride moiety for reaction with 2-methylthiophene was
examined using 5 mol% Pd(MeCN)2Cl2 catalyst in the
presence of Li2CO3 (Scheme 2). We initially employed
electron-deficient benzenesulfonyl chlorides. Nitro- and
cyano-substituents at C4 of benzenesulfonyl chlorides gave
regioselectively (>98%) the 4-arylated 2-methylthiophenes 2
and 3 in 78% and 71% yields, respectively. It should be
noted that from 4-trifluoromethylbenzenesulfonyl chloride the
β-arylation product
regioselectivity.
3
was only obtained in 92%
Results and discussion
Good yields and high regioselectivities (98%) were also
obtained for the coupling of 4-chloro and 4-bromo-
benzenesulfonyl chlorides with 2-methylthiophene, as the
desired products 5 and 6 were isolated in 67% and 81%
yields, respectively. It should be noted that for these two
reactions, no cleavage of the C-Cl and C-Br bonds was
observed allowing further transformations. A good yield of
88% in 7 was also obtained from the slightly electron-
deficient 4-fluorobenzenesulfonyl chloride. On the other
hand, poor yields in 9 and 10 were produced from congested
naphthalene-1-sulfonyl chloride and from electron-rich 4-
methoxybenzenesulfonyl chloride.
Herein, we describe a novel access to β-arylated thiophene
derivatives using desulfitative palladium-catalysed C-H
functionalisation, from thiophenes and benzenesulfonyl
chlorides as the coupling partners (Scheme 1, bottom). The
influence of both the benzenesulfonyl chlorides and
thiophenes substituents is reported.
We first examined the influence of several reaction
conditions on the products formation (Table 1). The reaction
of 4-methylbenzenesulfonyl chloride with 2-methylthiophene
2 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 2012

Page 3 of 6
Chemical Science
Journal Name
RSCPublishing
View Article Online
DOI: 10.1039/C3SC52420E
ARTICLE
Table 1. Influence of the reaction conditions for the palladium-catalysed desulfitative coupling of 4-methylbenzenesulfonyl chloride with 2-
methylthiophene.
[Pd]
+
+
Cl
O
S
S
S
base, additive
O
1a
1b
S
Entry
Catalyst
Base (equiv.)
Additive (equiv.)
solvent
Temp. (°C)
Yield in 1b (%)
1
2
3
4
5
6
7
8
Pd(OAc)2
PdCl(C3H5)(dppb)
PdCl2
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (2)
K2CO3 (3)
Li2CO3 (2)
Li2CO3 (3)
K3PO4 (3)
KOAc (3)
Na2CO3 (3)
K2CO3 (3)
Cs2CO3 (3)
Li2CO3 (6)
Li2CO3 (3)
Li2CO3 (3)
Li2CO3 (3)
Li2CO3 (3)
Li2CO3 (3)
Li2CO3 (3)
-
-
dioxane
dioxane
dioxane
dioxane
dioxane
DMSO
toluene
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
NMP
120
120
120
120
120
120
120
140
140
140
140
140
140
140
140
140
140
140
140
140
0
<5
<5
30 (25)
<5
0
<5
75 (71)
43 (40)
80 (62)
48
56
41
LiCl (4)
LiCl (4)
LiCl (1) / CuI (1)
LiCl (1)
LiCl (1)
LiCl (2)
-
-
-
-
-
-
-
-
-
Pd(PhCN)2Cl2
Pd(MeCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(PhCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
Pd(MeCN)2Cl2
9
10
11
12
13
14
15
16
17
18
19
20
21
22
31
0
62 (60)[a]
84 (75)[a]
0
DMF
DMSO
Ethylbenzene 140
p-xylene 140
0
0
< 5%
< 5%
-
Conditions: [Pd] 5 mol-%, 4-methylbenzenesulfonyl chloride (1 equiv.), 2-methylthiophene (1.5 equiv.), yield determined by GC and crude 1H
NMR, 20 h, yields in parenthesis are isolated 1b. [a] 40 h.
The influence of the substituents at C2 on the thiophene
Pd(MeCN)2Cl2 5 mol-%
R
moiety was also evaluated (Scheme 3).
Three
+
Cl
O
S
benzenesulfonyl chlorides were coupled with 2-n-
S
R
Li2CO3, dioxane,
140 °C, 40 h
O
1.5 equiv.
butylthiophene. Again, satisfactory yields in 11 and 12
were obtained in the presence of 4-chloro or 4-methyl
substituents on the benzene ring; whereas, a 4-methoxy
substituent led to a poor yield of 13. The arylation of
S
1 equiv.
O2N
NC
F3C
Cl
Br
unsubstituted thiophene was also found to proceed at β-
position. However, moderate yields in 14 and 15 were
obtained due to some formation of 3,4-diarylated
thiophenes. Both chloro- or bromo-substituent at C2 of
thiophene were also tolerated, and the 4-arylated 2-
S
S
S
S
S
2 78%
3 71%
4 80%
5 67%
6 88%
F
MeO
halothiophenes 16-22 were obtained in moderate to high
yields. Even the use of protected 2-acetylthiophene led
to the desired products 23 and 24 with high
regioselectivity and moderate to good yields. The
S
S
S
S
reaction
benzenesulfonyl chlorides with [2,2']bithiophenyl also
afforded the desired -arylated compounds 25 and 26 in
78% and 60% yields, respectively.
of
4-trifluoromethyl-
or
4-bromo-
7 88%
8 81%
9 31%
10 41%
Scheme 2. Structural variation of the benzenesulfonyl chloride
β
partner.
This journal is © The Royal Society of Chemistry 2013
J. Name., 2013, 00, 1‐3 | 3

Chemical Science
Page 4 of 6
Journal Name
ARTICLE
Finally, we examined the regioselectivity of the arylation
of benzothiophene (Scheme 5). Glorius et al. have
View Article Online
recently reported that benzothiophenes can be arylated at
DOI: 10.1039/C3SC52420E
R3
1
R3
β
-position with aryl chlorides using an heterogeneous
Pd(MeCN)2Cl2 5 mol-%
R
+
palladium catalyst associated to copper.7
Cl
O
R2
R1
S
S
Li2CO3, dioxane,
140 °C, 40 h
O
R2
1.5 equiv.
S
1 equiv.
Using our reaction conditions, in all cases the
β-aryl-
Cl
Me
MeO
Me
MeO
benzothiophenes were regioselectively produced. Again
the best yields were obtained in the presence of electron-
deficient benzenesulfonyl chlorides. For example, the
use of 4-chloro- of 4-trifluoromethyl-benzenesulfonyl
chlorides led to 35 and 37 in 88% yields, respectively.
Again, from 4-trifluoromethylbenzenesulfonyl chloride
S
S
12 63%
Me
S
S
S
11 62%
13 43%
14 48% 15 34%
the
selectivity by GC/MS analysis.
chloride also reacts nicely with benzothiophene to give
32 in 83% yield. It is worth noting that 4-
α
-arylation product was also detected in 8%
Me
Cl
F3C
Benzenesulfonyl
Me
Me
bromobenzenesulfonyl chloride allows the formation of
36 in 83% yield. A reaction of benzothiophene with
methyl 3-chlorosulfonylthiophene-2-carboxylate gave 39
Br
Cl
Br
Cl
S
Br
S
Cl
S
S
S
S
16 41%* 17 69%
18 56%
19 53%* 20 80%
21 67%
F3C
Br
in 51% yield, due to an α:β arylation ratio of 11:89; but
Me
Br
without formation of bithiophene from self-coupling.
This lower regioselectivity might come from the steric
hindrance of this chlorosulfonyl derivative.
Me
Br
S
S
O
O
S
S
S
S
S
22 71%
23 61%**
25 78%
26 60%
24 29%***
1
Pd(MeCN)2Cl2 5 mol-% R
+
Cl
O
* From 2-halothiophene (1 equiv) and ArSO2Cl (2 equiv.)
** From 2-methyl-2-thiophen-2-yl-[1,3]dioxolane (1 equiv.) and PhSO2Cl (2 equiv.)
*** From 2-methyl-2-thiophen-2-yl-[1,3]dioxolane
1
S
S
R
Li2CO3, dioxane,
140 °C, 40 h
O
1.5 equiv.
S
1 equiv.
Me
MeO
Cl
Scheme 3. Variation of C2-substituents on the thiophene partner.
The 4-arylation of 3-substituted thiophenes was also
found to proceed under these reaction conditions
(Scheme 4). We first examined the reactivity of 3-
methylthiophene in the presence of two benzenesulfonyl
chlorides. A high yield of 86% in 27 was obtained using
S
S
S
S
32 83%
33 50%
34 62%
35 88%
Br
F C
3
NC
S
CO Me
2
benzenesulfonyl
chloride;
whereas
from
4-
methylbenzenesulfonyl chloride, 28 was isolated in only
55% yield. The coupling of benzenesulfonyl chlorides
with 3-chlorothiophene also produced the desired 4-
S
S
S
S
36 83%
37 88%
38 83%
39 51%
Scheme 5. β-Arylations of benzo[b]thiophene.
arylated 3-chlorothiophenes 29-31. It should be noted
that no cleavage of the C-Cl thiophene bond was
observed.
Although the mechanism cannot yet be elucidated, a catalytic
cycle shown on scheme 6 can be proposed. The first step of
the catalytic cycle is probably the oxidative addition of the
benzenesulfonyl chloride to Pd(II) to afford the Pd(IV)
intermediate A as for Dong reaction.11 Such oxidative
addition on Pd(II) have been found to proceed even at room
2
R
1
2
Pd(MeCN)2Cl2 5 mol-%
R
R
+
Cl
O
1
S
S
R
Li2CO3, dioxane,
140 °C, 40 h
O
1.5 equiv.
S
1 equiv.
temperature.11b
Then, after elimination of SO2,
the
Me
Me
MeO
coordination of thiophene gives B. The migration of the aryl
group to the β-carbon atom of thiophene gives C. Finally,
base-assisted proton abstraction gives the β-arylated
thiophene and regenerates the Pd(II) species.
Cl
Cl
Cl
S
S
S
S
S
27 86%
28 55%
29 62%
30 43%
31 61%
Scheme 4. Variation of C3-substituents on the thiophene partner.
4 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 2012

Page 5 of 6
Journal Name
Chemical Science
ARTICLE
We thank the ministère de la recherche for a fellowship
to K. Y. and the Centre National de la Recherche
Scientifique and “Rennes MetropoDOleI:”10.f1o03r9/Cp3rSoCv5i2d4i2n0gE
Ar
Cl
O
Ar
View Article Online
S
PdII
O
financial support.
Oxidative
Addition
S
Reductive
Elimination
LiHCO3/LiCl
Li2CO3
Notes and references
a
Cl
PdIV
S
Institut des Sciences Chimiques de Rennes, UMR 6226
O
CNRS-Université de Rennes
1 "Organométalliques:
Ar
O
Matériaux et Catalyse", Campus de Beaulieu, 35042
Rennes, France. Fax: (33) 0223236939. E-mail:
henri.doucet@univ-rennes1.fr
Cl
PdIV
Ar
A
H
S
C
Electronic Supplementary Information (ESI) available: Procedures and 1H
and 13C NMR. See DOI: 10.1039/b000000x/
SO2
Cl
PdIV
1
a) D. Alberico, M. E. Scott and M. Lautens, Chem. Rev. 2007, 107,
174-238; b) T. Satoh and M. Miura, Chem. Lett. 2007, 36, 200-205;
c) L.-C. Campeau, D. R. Stuart and K. Fagnou, Aldrichimica Acta
2007, 40, 35-41; d) I. V. Seregin and V. Gevorgyan, Chem. Soc. Rev.
2007, 36, 1173-1193; e) B.-J. Li, S.-D. Yang and Z.-J. Shi, Synlett
2008, 949-957; f) C. Lewis, R. G. Bergman and J. A. Ellman, Acc.
Chem. Res. 2008, 41, 1013-1025; g) F. Bellina and R. Rossi,
Tetrahedron 2009, 65, 10269-10310; h) L. Ackermann, R. Vicente
and A. Kapdi, Angew. Chem. Int. Ed. 2009, 48, 9792-9826; i) X.
Chen, K. M. Engle, D.-H. Wang and J.-Q. Yu, Angew. Chem. Int. Ed.
2009, 48, 5094-5115; j) O. Daugulis, H.-Q. Do and D. Skabashov,
Ar
S
S
B
Scheme 6. Proposed catalytic cycle
Experimental
General procedure for synthesis of arylated
(benzo)thiophenes:
To a 25 mL oven dried Schlenk tube, arylsulfonyl
chloride (1 mmol), thiophene derivative (1.5 mmol),
Li2CO3 (6 mmol, 0.444 g), 1,4–dioxane (2 mL) and
bis(acetonitrile)dichloropalladium(II) (0.05 mmol, 12.9
mg) were successively added. The reaction mixture was
evacuated by vacuum-argon cycles (5 times) and stirred
at 140 °C (oil bath temperature) for 40 hours. After
cooling the reaction at room temperature and
concentration, the crude mixture was purified by silica
column chromatography (Et2O/PE) to afford the C3 or
C4 arylated products.
Acc. Chem. Res. 2009, 42
, 1074-1086; k) L. Joucla and L.
Djakovitch, Adv. Synth. Catal. 2009, 351, 673-714; l) C.-L. Sun, B.-J.
Li and Z.-J. Shi, Chem. Commun. 2010, 46, 677-685; m) C.
Fischmeister and H. Doucet, Green Chem. 2011, 13, 741-753; n) L.
Ackermann, Chem. Rev. 2011, 111, 1315-1345; o) L. McMurray, F.
O’Hara and M. J. Gaunt, Chem. Soc. Rev. 2011, 40, 1885-1898; p) N.
Kuhl, M. N. Hopkinson, J. Wencel-Delord and F. Glorius, Angew.
Chem. Int. Ed. 2012, 51, 10236-10254; q) J. Yamaguchi, A. D.
Yamaguchi and K. Itami, Angew. Chem., Int. Ed. 2012, 51, 8960-
9009; r) S. R. Neufeldt and M. S. Sanford, Acc. Chem. Res. 2012, 45
,
,
936-946; s) J. Wencel-Delord and F. Glorius, Nature Chem. 2013,
5
Conclusions
369-375.
2
For Pd-catalysed arylation at C5 of thiophenes with aryl halides: a)
A. Ohta, Y. Akita, T. Ohkuwa, M. Chiba, R. Fukunaga, A. Miyafuji,
T. Nakata, N. Tani and Y. Aoyagi, Heterocycles 1990, 31, 1951-
1958; b) B. Liégault, I. Petrov, S. I. Gorelsky and K. Fagnou, J. Org.
Chem. 2010, 75, 1047-1060.
In summary, we report here the first palladium-catalysed
desulfitative arylation of thiophene derivatives. The
reaction was found to provide, in most cases, very
regioselectively (≥98%) the β-arylated thiophenes. The
reaction proceeds with easily accessible ligand-free
Pd(MeCN)2Cl2 catalyst and Li2CO3 as base and tolerates
3
4
J. Roger, A. L. Gottumukkala and H. Doucet, ChemCatChem 2010,
2
, 20-40.
a
wide variety of substituents both on the
a) T. Okazawa, T. Satoh, M. Miura and M. Nomura, J. Am. Chem.
Soc., 2002, 124, 5286-5287; b) K. Si Larbi, H. Y. Fu, N. Laidaoui, K.
Beydoun, M. Miloudi, D. El Abed, S. Djebbar and H. Doucet,
benzenesulfonyl chloride and thiophene moieties. Due to
the wide availability of diversely functionalised
benzenesulfonyl chlorides, such simple reaction
conditions (no expensive base and ligand) should be very
attractive to synthetic or material chemists for access to
ChemCatChem 2012, 4, 815-823.
5
a) S. Kirchberg, T. Vogler and A. Studer, Synlett 2008, 2841-2845; For
similar reaction with Rh catalyst: b) T. Vogler and A. Studer, Org.
Lett. 2008, 10, 129-131; For similar reaction with PhMgBr and an Fe
catalyst c) N. Yoshikai, S. Asako, T. Yamakawa, L. Ilies and E.
Nakamura, Chem Asian J. 2011, 6, 3059-3065, For similar reaction
with Ru catalyst: d) R. K. Chinnagolla and M. Jeganmohan, Org. Lett.
2012, 14, 5246-5249.
β
-arylthiophenes.
Acknowledgements
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1‐3 | 5

Chemical Science
Page 6 of 6
Journal Name
ARTICLE
6
a) S. Yanagisawa, K. Ueda, H. Sekizawa and K. Itami, J. Am. Chem.
Soc. 2009, 131, 14622-14623; b) K. Ueda, S. Yanagisawa, J.
View Article Online
DOI: 10.1039/C3SC52420E
Yamaguchi and K. Itami, Angew. Chem. Int. Ed. 2010, 49, 8946-8949.
D.-T. D. Tang, K. D. Collins and F. Glorius, J. Am. Chem. Soc. 2013,
135, 7450-7453.
7
8
a) S. Kirchberg, S. Tani, K. Ueda, J. Yamaguchi, A. Studer and K.
Itami, Angew. Chem. Int. Ed. 2011, 50, 2387-2391; b) K. Yamaguchi,
J. Yamaguchi, A. Studer and K. Itami, Chem. Sci., 2012, 3, 2165-2169;
c) K. Yamaguchi, H. Kondo, J. Yamaguchi and K. Itami, Chem. Sci.,
2013, 4, 3753-3757.
9
a) I. Schnapperelle, S. Breitenlechner and T. Bach, Org. Lett. 2011, 13,
3640-3643; b) I. Schnapperelle and T. Bach, ChemCatChem 2013,
DOI: 10.1002/cctc.201300167
10
11
K. Funaki, T. Sato and S. Oi, Org. Lett. 2012, 14, 6186-6189.
a) X. Zhao, E. Dimitrijevic and V. M. Dong, J. Am. Chem. Soc. 2009,
131, 3466-3467; b) X. Zhao and V. M. Dong, Angew. Chem., Int. Ed.
2011, 50, 932-934; c) For sulfonylations of quinolines using CuI as
catalyst: Z. Wu, H. Song, X. Cui, C. Pi, W. Du and Y. Wu, Org. Lett.
2013, 15, 1270-1273; For reviews on Pd(II)/Pd(IV) catalysis: d) K.
Muniz, Angew. Chem. Int. Ed. 2009, 48, 9412-9423; e) A. J. Canty,
Dalton Trans. 2009, 10409-10417; f) T. W. Lyons, M. S. Sanford,
Chem. Rev. 2010, 110, 1147-1169.
12
For desulfitative couplings using Ru catalysts: a) N. Kamigata, M.
Yoshikawa, and T. Shimizu, J. Fluorine Chem. 1998, 87, 91-95; b) D.
A. Nagib and D. W. C. MacMillan, Nature 2011, 480, 224-228.
For a review on transition-metal mediated C-S bond activation: L.
Wang, W. He and Z. Yu, Chem. Soc. Rev. 2013, 42, 599-621.
For Heck type reaction with benzenesulfonyl chlorides: a) M. Miura,
H. Hashimoto, K. Itoh and M. Nomura, Tetrahedron Lett. 1989, 30,
975-976; b) M. Miura, H. Hashimoto, K. Itoh and M. Nomura, J.
Chem. Soc., Perkin Trans. 1 1990, 2207.
13
14
15
16
For Stille, Negishi or Suzuki couplings with benzenesulfonyl
chlorides: a) S. R. Dubbaka and P. Vogel, J. Am. Chem. Soc. 2003,
125, 15292-15293; b) S. R. Dubbaka and P. Vogel, Org. Lett. 2004, 9,
95-98; c) S. R. Dubbaka and P. Vogel, Angew. Chem., Int. Ed. 2005,
44, 7674-7684.
a) M. Zhang, S. Zhang, M. Lui and J. Cheng, Chem. Commun. 2011,
47, 11522-11524; For reactions with sodium sulfinates: b) B. Liu, Q.
Guo, Y. Cheng, J. Lan and J. You, Chem. Eur. J., 2011, 17, 13415-
13419; c) R. Chen, S. Liu, X. Liu, L. Yang and G.-J. Deng, Org.
Biomol. Chem. 2011, 9, 7675-7679.
6 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 2012