Synthesis of symmetrical and unsymmetrical 1,3-diheteroarylbenzenes through palladium-catalyzed direct arylation of benzene-1,3-disulfonyl dichloride and 3-bromobenzenesulfonyl chlorides

Article abstract of DOI:10.1016/j.tet.2015.10.082

The palladium-catalyzed synthesis of unsymmetrical 1,3-diheteroarylbenzenes was investigated. The first synthetic pathway relies on the desymmetrization of benzene-1,3-disulfonyl dichloride through two successive palladium-catalyzed direct desulfitative arylations with two different heteroarenes. The second strategy employs the orthogonal functionalization of 3-bromobenzenesulfonylchloride using an iterative C-H bond arylation sequence, namely, palladium-catalyzed direct desulfitative arylation followed by a palladium-catalyzed direct arylation step using aryl bromide as the coupling partner. The synthesis of symmetrical 1,3-diheteroarylbenzenes was also investigated.

Full text of DOI:10.1016/j.tet.2015.10.082

Accepted Manuscript
Synthesis of Symmetrical and Unsymmetrical 1,3-Diheteroarylbenzenes Through
Palladium-Catalyzed Direct Arylation of Benzene-1,3-disulfonyl Dichloride and 3-
Bromobenzenesulfonyl Chlorides
Imane Idris, Fazia Derridj, Safia Djebbar, Jean-François Soulé, Henri Doucet
PII:
S0040-4020(15)30182-4
10.1016/j.tet.2015.10.082
TET 27254
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 14 September 2015
Revised Date: 23 October 2015
Accepted Date: 28 October 2015
Please cite this article as: Idris I, Derridj F, Djebbar S, Soulé J-F, Doucet H, Synthesis of Symmetrical
and Unsymmetrical 1,3-Diheteroarylbenzenes Through Palladium-Catalyzed Direct Arylation of
Benzene-1,3-disulfonyl Dichloride and 3-Bromobenzenesulfonyl Chlorides, Tetrahedron (2015), doi:
10.1016/j.tet.2015.10.082.
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Synthesis of Symmetrical and
Unsymmetrical 1,3-Diheteroarylbenzenes
Through Palladium-Catalyzed Direct
Arylation of Benzene-1,3-disulfonyl
Dichloride and 3-Bromobenzenesulfonyl
Chlorides
Leave this area blank for abstract info.
I. Idris, F. Derridj, S. Djebbar, J.-F. Soulé, H. Doucet

1
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Tetrahedron
journal homepage: www.elsevier.com
Synthesis of Symmetrical and Unsymmetrical 1,3-Diheteroarylbenzenes Through
Palladium-Catalyzed Direct Arylation of Benzene-1,3-disulfonyl Dichloride and 3-
Bromobenzenesulfonyl Chlorides
Imane Idris,a, b Fazia Derridj, a, b, c Safia Djebbar,c Jean-François Soulé, a, and Henri Doucet a,
aInstitut des Sciences Chimiques de Rennes, UMR 6226 CNRS-Université de Rennes 1 "Organométalliques, Matériaux et Catalyse", Campus de Beaulieu, 35042
Rennes, France
bDépartement de chimie, UMMTO, University, BP 17 RP, 15000 Tizi-Ouzou, Algeria
cLaboratoire d’hydrométallurgie et chimie inorganique moléculaire, Faculté de Chimie, U.S.T.H.B. Bab-Ezzouar, Algeria.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The palladium-catalyzed synthesis of unsymmetrical 1,3-diheteroarylbenzenes was investigated.
The first synthetic pathway relies on the desymmetrization of benzene-1,3-disulfonyl dichloride
through two successive palladium-catalyzed direct desulfitative arylations with two different
heteroarenes.
The second strategy employs the orthogonal functionalization of 3-
Available online
bromobenzenesulfonylchloride using an iterative C–H bond arylation sequence, namely,
palladium-catalyzed direct desulfitative arylation followed by a palladium-catalyzed direct
arylation step using aryl bromide as the coupling partner. The synthesis of symmetrical 1,3-
diheteroarylbenzenes was also investigated.
Keywords:
C–H Arylation
Catalysis
Desulfitative
Tridentate Ligand
Palladium
2009 Elsevier Ltd. All rights reserved
.
ligands such as N^C^N, which found many applications in
electronic devices or in catalysis.3 For example, the family of
complexes III, based on 1,3-bis-heteroazolylbenzenes ligand,
displays tunable color luminescent properties, which has plenty
of applications in the construction of organic light-emitting
(OLED) devices (Figure 1).4 1,3-Diheteroarylbenzenes are
generally synthesized from isophthalaldehydes via a double
condensation with 2-aminophenols or 2-aminobenzenethiols
(Figure 2A).5 However, this methodology is limited to the
synthesis of symmetrical compounds. A few examples of
preparation of unsymmetrical 1,3-diheteroarylbenzenes have
1. Introduction
Me
HN
NH2
O
HN
X
X
N
Pt
N
N
R
O
H
N
N
S
O
been reported starting from 3-bromobenzaldehydes via
a
X = O, S, or NAlkyl
I
II
III
condensation of the aldehyde function with amines followed by
palladium-catalyzed C–C bond formation (e.g., Negishi or
Suzuki reactions) (Figure 2B).6 An other synthetic pathway
involved double palladium-catalyzed C–C bond formation using
1,3-dibromobenzene and organometallic reagents (Figure 2C).7
This methodology is limited to the synthesis of symmetrical
compounds, albeit some reports focused on the desymmetrization
of 1,3-dibromobenzene using selective mono-coupling based on
Suzuki reaction.8 Dodd and co-workers reported the synthesis of
unsymmetrical 1,3-diheteroarylbenzenes using an one-pot
procedure involving double Suzuki reaction with two different
boronic acids.9 Since these last decades, palladium–catalyzed
Figure 1. Examples of uses of 1,3-diheteroarylbenzenes.
1,3-Diheteroarylbenzenes are an important class of molecules
in organic chemistry. Unsymmetrical 1,3-diheteroarylbenzenes,
such as molecule I, which contains 3-thienyl and 2-pyrrolyl
substituents, are useful agents in the treatment of diseases,
including inflammatory diseases, cancer, and AIDS (Figure 1).1
N-Quinuclidinyl-heteroaryl amide II, which contains both 2-furyl
and 2-pyrrolyl moieties, has shown potential pharmaceutical uses
in the treatment of neurological disorders (Figure 1).2 Moreover,
they are ubiquitous subunits embedded in number of tridentate
———
Corresponding author. Tel.: +33(0) 2 23 23 32 06; e-mail: jean-francois.soule@univ-rennes1.fr
Corresponding author. Tel.: +33(0) 2 23 23 63 84; e-mail: henri.doucet@univ-rennes1.fr

2
Tetrahedron
ACCEPTED MANUSCRIPT
direct arylation has emerged as one of the most eco-friendly
time (18 h) also furnished a high selectivity in favor of the
methods for the fast synthesis of complex molecules.10 Thanks to
this methodology, we recently synthesized symmetrical 1,3-
diheteroarylbenzenes from 1,3-dibromobenzenes (Figure 2C).11
However, this synthetic pathway does not allow the synthesis of
unsymmetrical compounds due to the very high reactivity of 1,3-
dibromobenzenes. Recently, based on the pioneering works
reported by Dong and co-workers,12 our group and others have
exploited the reactivity of benzenesulfonyl chlorides for direct
monoarylated product 1 (Table 1, entry 4). No reaction occurred
using polar and protic solvent such as DMF or butan-1-ol (Table
1, entries 5 and 6). Using these two optimized reaction
conditions, i.e., DEC at 140 ºC during 48 h and 1,4-dioxane at
110 ºC during 18 h, we achieved the synthesis of 1 in very high
yield (85-87%)19 using only 1.2 equivalents of benzene-1,3-
disulfonyl dichloride (Table 1, entries 7 and 8). It is important to
note that the use of a lower amount of benzene-1,3-disulfonyl
dichloride (1.1 equiv.) gave a slightly lower 1:2 ratio (Table 1,
entry 9). On the other hand, the diarylated product 2 has also
been synthesized in high yield using 3 equivalents of 2-n-
butylfuran and 6 equivalents of base in 1,4-dioxane as solvent at
140 ºC during 48 h (Table 1, entry 10).
regioselective arylation of several heteroarenes.13
desulfitative direct arylations were also reported using of
sodium arylsulfinates,14 and arylsulfonyl hydrazides.15
It
generally displays high reactivities and regioselectivities with
good tolerances to C–X bonds.16
In addition, the β-
Similar
regioselectivity for the arylation of (benzo)thiophenes is an
important advantage compared to other arylating agents.17 In the
course of our investigations, we found that the desulfitative C–H
bond arylations were highly dependent to the benzenesulfonyl
chloride electronic properties. As electron-poor benzenesulfonyl
chlorides react faster than electron-rich ones, we assumed that
with such reactants it should be possible to desymmetrize
benzene-1,3-disulfonyl dichloride to allow the synthesis of
Table 1. Effect of the reaction conditions on Pd-catalyzed
desulfitative coupling of benzene-1,3-disulfonyl dichloride with
2-n-butylfuran.
C4H9
C4H9
O
SO2Cl
+
PdCl2(CH3CN)2
(5 mol%)
O
O
+
C4H9
Li2CO3 (3 equiv.)
unsymmetrical 1,3-diheteroarylbenzenes.
Indeed, sulfonyl
solvent, T (ºC), t (h)
SO2Cl
(y equiv.)
chloride has an electron-withdrawing character in contrast to
heteroarenes which have electron-donating characters; hence the
first desulfitative arylation should be faster than the second one.
(Figure 2D). Moreover, thanks to the orthogonal reactivity of
desulfitative C–H bond arylations, which tolerates C–Br bonds,
we proposed a new synthetic approach to the construction of
(x equiv.)
SO2Cl
O
1
C4H9
2
Entry x:y
solvent
T (ºC) t (h)
Conv. (%)[a] 1 : 2 [b]
1
2
3
4
5
6
7
8
9
1.5:1 1,4-dioxane 140 48
100
100
72
45:55 (34% of 1)[a, b]
95:5 (83% of 1)[a, b]
87:13 (77%)of 1)[a, b]
95:5 (85% of 1)[a]
1.5:1 DEC
140 48
140 48
unsymmetrical
1,3-diheteroarylbenzenes
from
3-
1.5:1 CPME
bromobenzenesulfonyl chlorides through iterative direct
arylations (Figure 1E).
1.5:1 1,4-dioxane 110 18
100
0
1.5:1 DMF
1.5:1 BuOH
1.2:1 DEC
110 48
140 48
140 48
0
C
A
100
100
100
100
95:5 (87% of 1)[a]
94:6 (85% of 1)[a]
90:10 (76% of 1)[a]
9:91 (84% of 2)[d]
OHC
CHO
Br
Br
1.2:1 1,4-dioxane 110
48
Z
Z'
Y
1.1:1 1,4-dioxane 140 48
B
D
X
X'
10[c] 1:3 1,4-dioxane 140 48
Y
X, Y, Z, = C, O, S, N
[a] Based on 2-n-butylfuran; [b] Determined using GC-MS and 1H- NMR
analyses, [c] 6 equiv. of Li2CO3 were used. [d] based on benzene-1,3-
disulfonyl dichloride
E
ClO2S
SO2Cl
OHC
Br
this work
Next, we performed similar experiments with 1,3-
dibromobenzene as the aryl source using 0.5 mol% of Pd(OAc)2
in the presence of KOAc as base in DMA at 150 ºC (Table 2).
As seen previously,11a, 11b this substrate is very reactive and 2 was
obtained as the major product, except in the presence of a huge
amount (5 equiv.) of 1,3-dibromobenzene (Table 2, entries 1-3).
However, the monoarylated product 3 was isolated only 52%
yield. No reaction occurred at lower temperature (110 ºC), and
the use of DEC as solvent had almost no effect on the 3:2
selectivity (Table 2, entries 4 and 5).
ClO2S
this work
Br
Figure 2. Retrosynthetic pathways of 1,3-diheteroarylbenzenes.
2. Results and Discussion.
We started our investigation by studying the reactivity of
benzene-1,3-disulfonyl dichloride as arylating source for the C–H
bond arylation of 2-n-butylfuran (Table 1). First, we attempted
to prepare the monoarylated product 1 using our previous
optimized reaction conditions for the C–H bond arylation of
furans,13d (i.e., 5 mol% of PdCl2(CH3CN)2 in the presence of
Li2CO3 as base in 1,4-dioxane at 140 ºC during 48 h) with a
slight excess amount of benzene-1,3-disulfonyl dichloride (1.5
equiv.). As result, we obtained a mixture of monoarylated and
diarylated products 1 and 2 in 45:55 ratio (Table 1, entry 1). To
improve the yield in 1, both the solvent influence and the
temperature were screened. We had previously demonstrated
that the reaction could also be performed in green solvents such
as diethyl carbonate (DEC) or cyclopentylmethyl ether (CPME)
with comparable yields but with a lower reaction rates.18 When
the reaction was performed in DEC, the monoarylation product 1
was obtained in 95% selectivity with a full conversion of 2-n-
butylfuran (Table 1, entry 2). A lower selectivity and reactivity
was observed using CPME as solvent (87% of 1) (Table 1, entry
3). The use of 1,4-dioxane at only 110 ºC and a shorter reaction
Table 2. Effect of the reaction conditions on Pd-catalyzed direct
coupling 1,3-dibromobenzene with 2-n-butylfuran.
C4H9
C4H9
Br
Pd(OAc)2
(0.5 mol%)
O
O
O
+
+
C4H9
KOAc (2 equiv.)
DMA, T (ºC), 48 h
Br
(y equiv.)
(x equiv.)
Br
3
O
Entry x:y
T (ºC) Conv. (%)[a] 3 : 2[b]
1
2
3
4
1.5:1 150
100
100
100
0
21:79 (62% of 2)[a, b]
41:59 (47% of 2)[a, b]
77:33 (52% of 3)[a]
–
C4H9
2:1
5:1
5:1
150
150
110
150
2
5[c] 5:1
100
36:64 (52% of 2)[a, b]
[a] Based on 2-n-butylfuran; [b] ratio determined using GC-MS and 1H-
NMR analyses; [c] DEC was used as solvent.

3
In contrast to 1,3-dibromobenzene, we demonstrated that
benzenedisulfonyl chloride could be easily desymmetrized and
consequently it represents a suitable precursor of unsymmetrical
1,3-diheteroarylbenzenes. Then, we investigated the scope of the
direct desulfitative monoarylation of benzene-1,3-disulfonyl
dichloride with various heteroarenes in DEC at 140 ºC (Scheme
1). 2-Furyl-2-propanone, which contains an enolizable ketone,
was monoarylated to give 4 in 76% yield without any side
reaction. The C2-regioselective direct arylation of benzofuran is
challenging with other arylating partners.13e From benzene-1,3-
–namely, the addition of a stoichiometric amount of copper to
ACCEPTED MANUSCRIPT
the reaction mixture– were used. Using this methodology, the
benzene 15 bearing by two different pyrrole units (1-methyl- and
1-phenylpyrroles) was obtained in high yield. This approach also
allowed the synthesis of a benzene meta disubstituted by
thiophene and pyrrole units 16 in 81% yield.
Scheme 2. Scope of the second desulfitative direct arylations:
syntheses of unsymmetrical 1,3-diheteroarylbenzenes.
Z
Z
X
X
disulfonyl
dichloride,
3-(benzofuran-2-yl)benzenesulfonyl
PdCl2(CH3CN)2 (5 mol%)
X'
Z'
chloride (5) was isolated in 68% yield. N-protected pyrroles
were also suitable heteroarenes for the mono-desulfitative
arylation, as 6 and 7 were obtained in 74% and 69% yields,
respectively from 1-methylpyrrole and 1-phenylpyrrole.
Thiophene derivatives displayed a β-regioselectivity but with a
lower reactivity in such desulfitative coupling. To overcome this
poor reactivity, we performed the reaction in 1,4-dioxane at 140
ºC during 18 h. Under these conditions, we were pleased to find
that the reaction occurred, and from 2-methythiophene and 2-
bromothiophene the monoarylated products 8 and 9 were
obtained in 58% and 47% yields, respectively, without formation
of diarylated products. Benzothiophene has also been used as
heteroarene for the monodesulfitative arylation of benzene-1,3-
disulfonyl dichloride to afford 10 in moderate yield.
+
H
Li2CO3 (3 equiv.)
1,4-dioxane, 140 ºC, 48 h
SO2Cl
(1.5 equiv.)
X'
Z'
Ph
C4H9
O
N
N
O
O
O
N
N
N
N
13 68%[a]
(from 6)
11 82%
(from 1)
12 73%
(from 5)
14 63%[a]
(from 7)
Ph
N
S
Scheme 1. Scope of the Pd-catalyzed direct desulfitative
monoarylation of benzene-1,3-disulfonyl dichloride
Z
SO2Cl
X
X
Z
PdCl2(CH3CN)2 (5 mol%)
N
N
H
+
Li2CO3 (3 equiv.)
DEC, 140 ºC, 48 h
15 82%
(from 7)
16 81%
(from 8)
SO2Cl
SO2Cl
(1.2 equiv.)
[a] CuI (1 equiv.) was used as additive.
O
Ph
N
N
Having successfully achieved the synthesis of unsymmetrical
1,3-diheteroarylbenzenes through two successive C–H bond
desulfitative arylations from benzene-1,3-disulfonyl dichloride,
we turned our attention to the one-pot synthesis of symmetrical
1,3-diheteroarylbenzenes (Scheme 3). Using the optimized
reaction conditions for the diarylation (Table 1, entry 8), the
symmetrical compounds 17-21 were isolated in high yields.
Notably, a larger excess of heteroarene was required in the case
of 1-methylpyrrole in order to prevent the 2,5-diarylation of the
pyrrole unit. N-benzylpyrrole was also tolerated affording 19 in
79% yield.
O
O
SO2Cl
SO2Cl
SO2Cl
SO2Cl
4 76%
5 68%
6 74%
7 69%
Br
S
S
S
Scheme 3. Scope of the one-pot Pd-catalyzed direct desulfitative
diarylation of benzene-1,3-disulfonyl dichloride.
SO2Cl
8 12% (58%)[a, b]
SO2Cl
SO2Cl
9 47%[a, b]
10 63%[a]
X
Z
X
SO2Cl
SO2Cl
[a] reaction was performed in 1,4-dioxane. [b] 18 h.
X
Z
PdCl2(CH3CN)2 (5 mol%)
H
+
As for all these selective monoarylations of benzene-1,3-
disulfonyl dichloride, the second benzenesulfonyl chloride
function remained untouched, we investigated the reactivity of 1,
5-8 in a second desulfitative direct arylation for the synthesis of
Li2CO3 (6 equiv.)
1,4-dioxane, 140 ºC, 48 h
(3 equiv.)
Z
O
unsymmetrical 1,3-diheteroarylbenzenes (Scheme 2).
The
S
synthesis of the unsymmetrical 1,3-diheteroarylbenzene 11 was
achieved in 82% yield from 1 and 1.5 equivalents of 1-
methylpyrrole using the classical reaction conditions for
desulfitative direct arylation, namely, 5 mol% of PdCl2(CH3CN)2
in the presence of Li2CO3 as base in 1,4-dioxane at 140 ºC during
N
O
O
N
O
O
Ph
Ph
N
N
48 h.
Using the same reaction conditions, the 3-
S
heteroarylbenzenesufonyl chloride 5 was converted into 12 in
73% yield. Then, a benzoxazole moiety was introduced on 6 and
7 to afford the desired compounds 13 and 14 in 68% and 63%
yields, respectively. For these couplings, similar conditions to
those reported by Cheng for the direct arylation of benzoxazole13a
O
18 85%[a]
19 79%[a]
17 65%
20 83%
21 75%
[a] 5 equiv. of 1-methylpyrrole was used.

4
Tetrahedron
ACCEPTED MANUSCRIPT
On the other hand, we had previously shown that palladium-
diarylated products was obtained. The aryl bromide 25 reacted
catalyzed direct desulfitative arylation of heteroarenes was very
chemoselective and we also demonstrated that the C–Br bonds
are not involved in the catalytic cycle, allowing orthogonal
functionalizations.16 Here, we used the benefit of this unique
chemoselectivity for the construction of unsymmetrical 1,3-
with 2.5 equivalents of 4-ethyl-2-methylthiazole allowing the
formation of the unsymmetrical 1,3-diheteroarylbenzene 31 in
84% yield. No major electronic effect of the aryl bromide was
found in this reaction as 5-bromo-2-methoxybenzenesulfonyl
chloride displays
a
similar reactivity than 5-bromo-2-
diheteroarylbenzenes
from
5-bromo-2-substituted
methylbenzenesulfonyl chloride. Indeed, both unsymmetrical
compounds 32 and 33 were synthesized in high yields. It is
important to note that no homocoupling products of 26 and 27
resulting from an activation of pyrrolyl or benzofuranyl C–H
bonds were detected in the crude samples.
benzenesulfonyl chlorides via two successive direct arylations
(i.e., direct desulfitative arylation followed by direct arylation of
the C–Br bond) (Schemes 4 and 5). In a first step, we
synthesized a set of 1-bromo-3-heteroarylbenzenes using the
previous optimized conditions. In all case, no cleavage of the C–
Br bond was observed. The reaction between 2-methylthiophene
or 2-bromothiophene with 5-bromo-2-methylbenzenesulfonyl
gave the challenging C3-arylated thiophenes 22 and 23 in 47%
and 52% yields, respectively. 1-Methylpyrrole was arylated at
C2-position in 51% yield. Using 1 equivalent of CuI as additive,
the benzoxazole 24, in which the arylation occurred at C1
position, was isolated in 45% yield. A similar reactivity was
observed using 5-bromo-2-methoxybenzenesulfonyl chloride as
aryl source allowing the formation of the 1-bromo-3-
heteroarylbenzene derivatives 26-28 in good yields.
Scheme 5. Scope of the Pd-catalyzed direct arylation with 1-
bromo-3-heteroarylbenzene derivatives
X'
Z'
Br
PdCl(C3H5)(dppb) (2 mol%)
X'
Z'
H
+
KOAc (2 equiv.)
DMA, 150 ºC, 18 h
R
X
(2.5 equiv.)
R
X
Z
Z
N
S
O
O
N
Scheme 4. Scope of the Pd-catalyzed desulfitative direct
arylation with 5-bromo-2-methylbenzenesulfonyl chloride and 5-
bromo-2-methoxybenzenesulfonyl chloride.
N
Me
N
Br
Br
Me
O
Me
X
Z
PdCl2(CH3CN)2 (5 mol%)
S
N
H
+
Li2CO3 (3 equiv.)
1,4-dioxane, 140 ºC, 48 h
N
S
R
(2.5 equiv.)
R
SO2Cl
X
N
29 73%
(from 22)
S
N
30 79%
(from 24)
31 84%
(from 25)
Z
Br
Br
Br
Br
MeO
MeO
O
Me
Me
N
Me
Me
N
O
S
S
32 79%
(from 27)
33 86%
(from 28)
Br
23 52%
25 45%[a]
22 47%
24 51%
Br
Br
3. Conclusion
Br
In summary, we have developed two new routes for the eco-
friendly two steps synthesis of unsymmetrical 1,3-
diheteroarylbenzenes. The first strategy uses a desymmetrization
of benzene-1,3-disulfonyl dichloride through two successive Pd-
catalyzed desulfitative direct arylations of heteroarenes. The key
to stop the reaction at the monoarylation stage lies in the use of
diethyl carbonate (DEC) as solvent or to perform the reaction at a
moderate reaction temperature. A wide range of heteroarenes has
been used including thiophenes, with which the arylation
occurred at the β-position. Then, a second desulfitative arylation
MeO
MeO
N
MeO
O
O
N
28 38%[a]
26 62%
27 74%
[a] CuI (1 equiv.) was used as additive
After having performed the first desulfitative C–H bond
arylation, which gave 1-bromo-3-heteroarylbenzene derivatives
22-28, a second direct arylation was performed to deliver the
targeted unsymmetrical 1,3-disubstituted benzenes (Scheme 5).
We selected our previous reaction conditions,20 which have
already demonstrated to be efficient for the direct arylation of
heteroarenes with aryl bromides as coupling partners, i.e., 2
with
a different heteroarene delivered the desired 1,3-
disubstituted benzenes. The second strategy employs the
tolerance to C–Br bonds in the desulfitative coupling to perform
iterative C–H arylations with two different heteroarenes. The
combination of both strategies gives a robust access to
uncommon 1,3-diheteroarylbenzenes, which could find further
applications as tridentate ligands.
mol%
PdCl(C3H5)(dppb)
catalyst
[dppb
=
1,4-
bis(diphenylphosphino)butane] in the presence of KOAc as base
in dimethylacetamide (DMA) at 150 ºC during 16 h. When the
direct arylation was performed with 22 or 24 as aryl bromide
partners and benzoxazole, the desired 1,3-diheteroarylbenzenes
29 and 30 were obtained in excellent yields. We did not observe
any homocoupling reaction, although the compounds 22 and 24
contain reactive C–H bonds on the thienyl or pyrrolyl units.
However, from the aryl bromide 23, which contains two different
C–Br bonds, we did not observe a chemoselective reaction, and
an inseparable complex mixture of two mono-arylated and
4. Experimental Section
All reactions were carried out under argon atmosphere with
standard Schlenk techniques. 1,4-Dioxane, diethyl carbonate
(DEC), cyclopentylmethyl ether (CPME) and DMA were
purchased from Acros Organics and were not purified before use.
1,3-Benzenedisulfonyl chloride was purchased from TCI. The
other benzenesulfonyl chlorides were prepared from
bromobenzene by chlorosulfonylation (HSO3Cl) using a reported

5
procedure.21 1H NMR spectra were recorded on Bruker GPX
(400 MHz) spectrometer. Chemical shifts (δ) were reported in
parts per million relative to residual chloroform (7.26 ppm for
1H; 77.0 ppm for 13C), constants were reported in Hertz. 1H
NMR assignment abbreviations were the following: singlet (s),
doublet (d), triplet (t), quartet (q), doublet of doublets (dd),
doublet of triplets (dt), and multiplet (m). 13C NMR spectra were
recorded at 100 MHz on the same spectrometer and reported in
ppm.
6.10 (d, J = 3.2 Hz, 2H), 2.73 (t, J = 7.4 Hz, 4H), 1.72 (quint, J
ACCEPTED MANUSCRIPT
= 7.4 Hz, 4H), 1.46 (sext, J = 7.4 Hz, 4H), 0.99 (t, J = 7.4 Hz,
6H).
13C NMR (75 MHz, CDCl3) δ (ppm) 156.6, 152.0, 131.6, 128.8,
121.8, 118.2, 106.8, 106.0, 30.2, 27.9, 22.3, 13.8.
Elemental analysis: calcd (%) for C22H26O2 (322.45): C 81.95, H
8.13; found: C 82.17, H 8.01.
2-(3-Bromophenyl)-5-n-butylfuran (3): To a 5 mL oven
dried Schlenk tube, 2-n-butylfuran (124 mg, 1 mmol), 1,3-
dibromobenzene (1180 mg, 5 mmol), AcOK (100 mg, 1 mmol),
DMA (2 mL) and Pd(OAc)2 (1.1 mg, 0.005 mmol, 0.5 mol%)
were successively added. The reaction mixture was evacuated by
vacuum-argon cycles (5 times) and stirred at 150 °C (oil bath
temperature) for 16hours. After cooling the reaction at room
temperature and concentration, the crude mixture was purified by
silica column chromatography (SiO2, Pentane-AcOEt 90:10) to
afford the desired arylated product 3 (145 mg, 52%).
1H NMR (400MHz, CDCl3) δ (ppm) 7.79 (s, 1 H), 7.56 (d, J =
8.2 Hz, 1 H), 7.35 (d, J = 8.2 Hz, 1H), 7.23 (t, J = 7.8 Hz, 1H),
6.58 (d, J = 3.2 Hz, 1H), 6.09 (d, J = 3.2 Hz, 1H), 2.71 (t, J = 7.4
Hz, 2H), 1.69 (quint., J = 7.4 Hz, 2H), 1.43 (sext., J = 7.4 Hz, 2
H), 0.98 (t, J = 7.4 Hz, 3H).
Preparation of the PdCl(dppb)(C3H5) catalyst:22 An oven-
dried 40-mL Schlenk tube equipped with a magnetic stirring bar
under argon atmosphere, was charged with [Pd(C3H5)Cl]2 (182
mg, 0.5 mmol) and dppb (426 mg, 1 mmol). 10 mL of anhydrous
dichloromethane were added, then the solution was stirred at
room temperature for twenty minutes. The solvent was removed
in vacuum. The yellow powder was used without purification. 31
P
NMR (81 MHz, CDCl3) δ (ppm) = 19.3 (s).
Procedure A (desulfitative arylation): To a 5 mL oven
dried Schlenk tube, arylsulfonyl chloride (1.2 or 1 mmol),
heteroarenes derivatives (1-3 mmol), Li2CO3 (222 mg, 3 mmol or
444 mg,
6 mmol), 1,4-dioxane or DEC (3 mL) and
bis(acetonitrile)dichloropalladium(II) (12 mg, 0.05 mmol) were
successively added. The reaction mixture was evacuated by
vacuum-argon cycles (5 times) and stirred at 110 or 140 °C (oil
bath temperature) for 16-48 hours (see tables and schemes).
After cooling the reaction at room temperature and concentration,
the crude mixture was purified by silica column chromatography
to afford the desired arylated products.
This is a known compound and the spectral data are identical to
those reported in literature.16
3-(5-(2-Oxopropyl)furan-2-yl)benzenesulfonyl chloride (4):
Following the procedure A using 1-(furan-2-yl)propan-2-one
(124 mg, 1 mmol) and benzene-1,3-disulfonyl dichloride (330
mg, 1.2 mmol), the residue was purified by flash chromatography
on silica gel (SiO2, Pentane-AcOEt 85:15) to afford the desired
compound 4 (227 mg, 76%).
1H NMR (400 MHz, CDCl3) δ (ppm) 8.24 (t, J = 1.9 Hz, 1H),
7.94 (td, J = 1.9 and 7.6 Hz, 1H), 7.88 (td, J = 1.9 and 7.6 Hz,
1H), 7.61 (t, J = 7.9 Hz, 1H), 6.80 (d, J = 3.4 Hz, 1H), 6.37 (d, J
= 3.4 Hz, 1H), 3.83 (s, 2H), 2.26 (s, 3H).
Procedure B (direct arylation with aryl bromides): To a 5
mL oven dried Schlenk tube, heteroaryl (2.5-3 mmol), aryl
bromide (1 mmol), AcOK (200 mg, 2 mmol), DMA (2 mL) and
PdCl(C3H5)(dppb) (12 mg, 0.02 mmol,
2 mol%) were
successively added. The reaction mixture was evacuated by
vacuum-argon cycles (5 times) and stirred at 150 °C (oil bath
temperature) for 16-48 hours (see tables and schemes). After
cooling the reaction at room temperature and concentration, the
crude mixture was purified by silica column chromatography to
afford the desired arylated products.
13C NMR (75 MHz, CDCl3) δ (ppm) 203.1, 150.8, 149.7, 145.0,
132.4, 130.1, 129.6, 124.9, 121.6, 111.0, 108.9, 43.2, 29.5.
3-(5-Butylfuran-2-yl)benzenesulfonyl
chloride
(1):
Elemental analysis: calcd (%) for C13H11ClO4S (298.74): C
52.27, H 3.71; found: C 52.49, H 4.05.
Following the procedure A using 2-n-butylfuran (124 mg, 1
mmol) and benzene-1,3-disulfonyl dichloride (330 mg, 1.2
mmol), the residue was purified by flash chromatography on
silica gel (SiO2, Pentane-AcOEt 85:15) to afford the desired
compound 1 (260 mg, 87%).
1H NMR (400 MHz, CDCl3) δ (ppm) 8.23 (s, 1H), 7.92 (d, J =
7.9 Hz, 1H), 7.83 (d, J = 7.9 Hz, 1H), 7.58 (t, J = 7.9 Hz, 1H),
6.72 (d, J = 3.3 Hz, 1H), 6.13 (d, J = 3.3 Hz, 1H), 2.71 (t, J = 7.1
Hz, 2H), 1.69 (quint., J = 7.2 Hz, 2H), 1.43 (sext., J = 7.2 Hz,
2H), 0.97 (t, J = 7.2 Hz, 3H).
3-(Benzofuran-2-yl)benzenesulfonyl
chloride
(5):
Following the procedure A using benzofuran (118 mg, 1 mmol)
and benzene-1,3-disulfonyl dichloride (330 mg, 1.2 mmol), the
residue was purified by flash chromatography on silica gel (SiO2,
Pentane-AcOEt 85:15) to afford the desired compound 5 (199
mg, 68%).
1H NMR (400 MHz, CDCl3) δ (ppm) 8.50 (s, 1H), 8.18 (d, J =
7.9 Hz, 1H), 7.99 (d, J = 7.9 Hz, 1H), 7.69 (t, J = 7.9 Hz, 1H),
7.64 (d, J = 7.5 Hz, 1H), 7.56 (d, J = 7.9 Hz, 1H), 7.37 (dt, J =
1.4 and 7.9 Hz, 1H), 7.28 (t, J = 7.5 Hz, 1H), 7.20 (s, 1H).
13C NMR (75 MHz, CDCl3) δ (ppm) 157.0, 151.1, 137.6, 132.1,
129.3, 125.9, 122.7, 122.3, 107.0, 106.6, 30.2, 27.9, 22.3, 13.8.
13C NMR (100 MHz, CDCl3) δ (ppm) 155.2, 152.7, 145.2, 132.5,
130.9, 130.3, 128.6, 126.1, 125.6, 123.6, 123.0, 121.6, 111.5,
104.1.
Elemental analysis: calcd (%) for C14H15ClO3S (298.78): C
56.28, H 5.06; found: C 56.35, H 5.29.
1,3-Bis(5-butylfuran-2-yl)benzene (2): Following the
procedure A using 2-n-butylfuran (252 mg, 3 mmol) and
benzene-1,3-disulfonyl dichloride (275 mg, 1 mmol), the residue
was purified by flash chromatography on silica gel (SiO2,
Pentane-AcOEt 95:05) to afford the desired compound 2 (271
mg, 84%).
Elemental analysis: calcd (%) for C14H9ClO3S (292.73): C 57.44,
H 3.10; found: C 57.69, H 3.29.
3-(1-Methylpyrrol-2-yl)benzenesulfonyl
chloride
(6):
Following the procedure A using 1-methylpyrrole (81 mg, 1
mmol) and benzene-1,3-disulfonyl dichloride (330 mg, 1.2
mmol), the residue was purified by flash chromatography on
silica gel (SiO2, Pentane-AcOEt 90:10) to afford the desired
compound 6 (189 mg, 74%).
1H NMR (400 MHz, CDCl3) δ (ppm) 7.91 (s, 1H), 7.51 (d, J =
7.8 Hz, 2H), 7.37 (t, J = 7.8 Hz, 1H), 6.62 (d, J = 3.2 Hz, 2H),

6
Tetrahedron
1H NMR (400 MHz, CDCl3) δ (ppm) 8.08 (s, 1H), 7.95 (d, J =
13C NMR (100 MHz, CDCl3) δ (ppm) 145.0, 145.0, 140.7, 138.0,
ACCEPTED MANUSCRIPT
7.9 Hz, 1H), 7.79 (d, J = 8.9 Hz, 1H), 7.66 (t, J = 7.9 Hz, 1H),
6.82 (t, J = 2.3 Hz, 1H), 6.39 (dd, J = 1.8 and 3.7 Hz, 1H), 6.26
(dd, J = 2.7 and 3.7 Hz, 1H), 3.74 (s, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm) 144.5, 135.2, 134.4, 131.5,
137.0, 135.2, 135.1, 130.1, 126.8, 125.7, 125.6, 125.0, 123.2,
122.1.
Elemental analysis: calcd (%) for C14H9ClO2S2 (308.79): C
54.46, H 2.94; found: C 54.18, H 3.13.
129.7, 125.9, 125.5, 124.3, 110.6, 108.5, 35.2.
2-(3-(5-Butylfuran-2-yl)phenyl)-1-methylpyrrole
(11):
Elemental analysis: calcd (%) for C11H10ClNO2S (255.71): C
51.67, H 3.94; found: C 51.95, H 4.11.
Following the procedure using 3-(5-butylfuran-2-
A
yl)benzenesulfonyl chloride (1) (299 mg, 1 mmol) and 1-
methylpyrrole (203 mg, 2.5 mmol), the residue was purified by
flash chromatography on silica gel (SiO2, Pentane-AcOEt 80:20)
to afford the desired compound 11 (229 mg, 82%).
1H NMR (400 MHz, CDCl3) δ (ppm) 7.73 (s, 1H), 7.61 (d, J =
7.8 Hz, 1H), 7.42 (t, J = 7.8 Hz, 1H), 7.29 (d, J = 7.8 Hz, 1H),
6.77 (t, J = 2.1 Hz, 1H), 6.61 (d, J = 3.1 Hz, 1H), 6.32 (dd, J =
2.0 and 3.4 Hz, 1H), 6.27 (t, J = 3.1 Hz, 1H), 6.11 (d, J = 3.1 Hz,
1H), 3.72 (s, 3H), 2.73 (t, J = 7.6 Hz, 2H), 1.73 (quint., J = 7.6
Hz, 2H), 1.46 (sext., J = 7.2 Hz, 2H), 1.00 (t, J = 7.2 Hz, 3H).
3-(1-Phenylpyrrol-2-yl)benzenesulfonyl
chloride
(7):
Following the procedure A using 1-phenylpyrrole (143 mg, 1
mmol) and benzene-1,3-disulfonyl dichloride (330 mg, 1.2
mmol), the residue was purified by flash chromatography on
silica gel (SiO2, Pentane-AcOEt 80:20) to afford the desired
compound 7 (219 mg, 69%).
1H NMR (400 MHz, CDCl3) δ (ppm) 7.78 (d, J = 7.7 Hz, 1H),
7.73 (s, 1H), 7.49-7.33 (m, 5H), 7.18 (d, J = 8.3 Hz, 2H), 7.02
(dd, J = 1.7 and 2.8 Hz, 1H), 6.61 (dd, J = 1.7 and 3.7 Hz, 1H),
6.42 (dd, J = 2.8, 3.7 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ (ppm) 156.6, 151.8, 134.4, 133.6,
131.3, 128.5, 127.0, 123.7, 123.6, 121.7, 108.7, 107.7, 106.9,
105.9, 35.0, 30.2, 27.9, 22.3, 13.8.
13C NMR (100 MHz, CDCl3) δ (ppm) 144.2, 139.6, 134.8, 134.0,
130.8, 129.5, 129.3, 127.5, 126.1, 125.8, 125.8, 123.8, 112.3,
109.8.
Elemental analysis: calcd (%) for C19H21NO (279.38): C 81.68, H
7.58; found: C 81.51, H 7.76.
Elemental analysis: calcd (%) for C16H12ClNO2S (317.79): C
60.47, H 3.81; found: C 60.58, H 3.96.
2-(3-(Benzofuran-2-yl)phenyl)-1-methylpyrrole
(12):
Following the procedure using 3-(benzofuran-2-
A
3-(5-Methylthiophen-3-yl)benzenesulfonyl chloride (8):
Following the procedure A using 2-methylthiophene (98 mg, 1
mmol) and benzene-1,3-disulfonyl dichloride (330 mg, 1.2
mmol), the residue was purified by flash chromatography on
silica gel (SiO2, Pentane-AcOEt 85:15) to afford the desired
compound 8 (158 mg, 58%).
1H NMR (400 MHz, CDCl3) δ (ppm) 8.17 (s, 1H), 7.90-7.85 (m,
2H), 7.59 (t, J = 7.9 Hz, 1H), 7.34 (s, 1H), 7.09 (s, 1H), 2.54 (s,
3H).
yl)benzenesulfonyl chloride (5) (293 mg, 1 mmol) and 1-
methylpyrrole (203 mg, 2.5 mmol), the residue was purified by
flash chromatography on silica gel (SiO2, Pentane-AcOEt 70:30)
to afford the desired compound 12 (200 mg, 73%).
1H NMR (400 MHz, CDCl3) δ (ppm) 7.95 (s, 1H), 7.82 (d, J =
8.0 Hz, 1H), 7.62 (d, J = 7.4 Hz, 1H), 7.56 (d, J = 8.0 Hz, 1H),
7.50 (t, J = 7.6 Hz, 1H), 7.42 (d, J = 7.6 Hz, 1H), 7.32 (t, J = 7.5
Hz, 1H), 7.29-7.24 (m, 1H), 7.07 (s, 1H), 6.79 (dd, J = 1.8 and
2.8 Hz, 1H), 6.36 (td, J = 1.83 and 3.7 Hz, 1H), 6.29-6.27 (m,
1H), 3.74 (s, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm) 144.9, 141.9, 139.1, 138.0,
132.6, 130.1, 124.9, 124.3, 124.1, 120.3, 14.4.
13C NMR (100 MHz, CDCl3) δ (ppm) 155.7, 154.9, 134.0, 133.9,
130.6, 129.1, 128.8, 128.7, 125.1, 124.3, 123.9, 123.2, 122.9,
120.9, 111.2, 109.0, 107.9, 101.6, 35.1.
Elemental analysis: calcd (%) for C11H9ClO2S2 (272.76): C
48.44, H 3.33; found: C 48.67, H 3.58.
3-(5-Bromothiophen-3-yl)benzenesulfonyl chloride (9):
Following the procedure A using 2-bromothiophene (163 mg, 1
mmol) and benzene-1,3-disulfonyl dichloride (330 mg, 1.2
mmol), the residue was purified by flash chromatography on
silica gel (SiO2, Pentane-AcOEt 80:20) to afford the desired
compound 9 (159 mg, 47%).
1H NMR (400 MHz, CDCl3) δ (ppm) 8.15 (s, 1H), 7.96 (d, J =
8.0 Hz, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.65 (t, J = 8.0 Hz, 1H),
7.48 (s, 1H), 7.38 (s, 1H).
Elemental analysis: calcd (%) for C19H15NO (273.34): C 83.49, H
5.53; found: C 83.21, H 5.19.
2-(3-(1-Methylpyrrol-2-yl)phenyl)benzoxazole
(13):
Following the procedure using 3-(1-methylpyrrol-2-
A
yl)benzenesulfonyl chloride (6) (256 mg, 1 mmol), benzoxazole
(298 mg, 2.5 mmol) and CuI (190 mg, 1 mmol), the residue was
purified by flash chromatography on silica gel (SiO2, Pentane-
AcOEt 70:30) to afford the desired compound 13 (187 mg, 68%).
1H NMR (400 MHz, CDCl3) δ (ppm) 8.32 (s, 1H), 8.20 (td, J =
1.9 and 7.0 Hz, 1H), 7.80 (dd, J = 3.1 and 6.0 Hz, 1H), 7.62-7.63
(m, 3H), 7.37 (dd, J = 3.2 and 6.0 Hz, 2H), 6.77 (dd, J = 1.8 and
2.7 Hz, 1H), 6.37 (dd, J = 1.8 and 3.7 Hz, 1H), 6.25 (dd, J = 2.7
and 3.6 Hz, 1H), 3.75 (s, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm) 145.0, 139.8, 136.7, 132.5,
130.3, 128.6, 125.5, 124.3, 123.6, 114.3.
Elemental analysis: calcd (%) for C10H6BrClO2S2 (337.63): C
35.57, H 1.79; found: C 35.95, H 2.23.
13C NMR (100 MHz, CDCl3) δ (ppm) 162.8, 150.7, 142.1, 134.2,
133.4, 131.4, 129.0, 127.4, 127.3, 125.7, 125.1, 124.6, 124.3,
120.0, 110.6, 109.4, 108.0, 35.2.
3-(Benzothiophen-3-yl)benzenesulfonyl chloride (10):
Following the procedure A using benzothiophene (134 mg, 1
mmol) and benzene-1,3-disulfonyl dichloride (330 mg, 1.2
mmol), the residue was purified by flash chromatography on
silica gel (SiO2, Pentane-AcOEt 75:25) to afford the desired
compound 10 (195 mg, 63%).
1H NMR (400 MHz, CDCl3) δ (ppm) 8.27 (s, 1H), 8.08 (d, J =
8.0 Hz, 1H), 7.98-7.94 (m, 2H), 7.86-7.81 (m, 1H), 7.75 (t, J =
7.9 Hz, 1H), 7.56 (s, 1H), 7.48-7.33 (m, 2H).
Elemental analysis: calcd (%) for C18H14N2O (274.32): C 78.81,
H 5.14; found: C 79.06, H 4.87.
2-(3-(1-Phenylpyrrol-2-yl)phenyl)benzoxazole
(14):
Following the procedure using 3-(1-phenylpyrrol-2-
A
yl)benzenesulfonyl chloride (7) (318 mg, 1 mmol), benzoxazole
(298 mg, 2.5 mmol) and CuI (190 mg, 1 mmol), the residue was

7
purified by flash chromatography (SiO2, Pentane-AcOEt 70:30)
on silica gel to afford the desired compound 14 (212 mg, 63%).
benzene-1,3-disulfonyl dichloride (275 mg, 1 mmol), the
ACCEPTED MANUSCRIPT
residue was purified by flash chromatography on silica gel (SiO2,
Pentane-AcOEt 80:20) to afford the desired compound 18 (201
mg, 85%).
1H NMR (400 MHz, CDCl3) δ (ppm) 7.52-7.51 (m, 1H), 7.49-
7.46 (m, 2H), 7.41-7.39 (m, 1H), 6.80-6.79 (m, 2H), 6.34-6.33
(m, 2H), 6.29-6.28 (m, 2H), 3.76 (s, 6H).
1H NMR (400 MHz, CDCl3) δ (ppm) 8.22 (s, 1H), 8.07 (d, J =
7.7 Hz, 1H), 7.78 (dd, J = 3.0 and 6.3 Hz, 1H), 7.38-7.32 (m,
5H), 7.30 (d, J = 7.4 Hz, 2H), 7.23 (d, J = 7.4 Hz, 2H), 7.14 (d, J
= 6.4 Hz, 1H), 7.01 (t, J = 2.2 Hz, 1H), 6.61 (dd, J = 1.8 and 3.6
Hz, 1H), 6.42 (t, J = 3.2 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ (ppm) 162.9, 150.7, 142.1, 140.3,
133.8, 132.6, 131.2, 129.1, 128.5, 127.2, 126.8, 125.8, 125.4,
125.1, 124.9, 124.5, 120.0, 111.4, 110.5, 109.4.
This is a known compound and the spectral data are identical to
those reported in literature.23
1,3-Bis(1-benzylpyrrol-2-yl)benzene (19): Following the
procedure A using 1-benzylpyrrole (786 mg, 5 mmol) and
benzene-1,3-disulfonyl dichloride (275 mg, 1 mmol), the residue
was purified by flash chromatography on silica gel (SiO2,
Pentane-AcOEt 85:15) to afford the desired compound 19 (307
mg, 79%).
1H NMR (400 MHz, CDCl3) δ (ppm) 7.34 (s, 1H), 7.29-7.27 (m,
2H), 7.25-7.20 (m, 7H), 6.95 (dd, J = 1.7 and 7.5 Hz, 4H), 6.72
(dd, J = 1.9 and 2.8 Hz, 2H), 6.25 (t, J = 3.0 Hz, 2H), 6.23-6.21
(m, 2H), 5.08 (s, 4H).
Elemental analysis: calcd (%) for C23H16N2O (336.39): C 82.12,
H 4.79; found: C 82.17, H 5.01.
1-Methyl-2-(3-(1-phenylpyrrol-2-yl)phenyl)pyrrole (15):
Following the procedure
A
using 3-(1-phenylpyrrol-2-
yl)benzenesulfonyl chloride (7) (318 mg, 1 mmol) and 1-
methylpyrrole (203 mg, 2.5 mmol), the residue was purified by
flash chromatography on silica gel (SiO2, Pentane-AcOEt 75:25)
to afford the desired compound 15 (245 mg, 82%).
1H NMR (400 MHz, CDCl3) δ (ppm) 7.44-7.38 (m, 2H), 7.37-
7.32 (m, 2H), 7.31-7.26 (m, 4H), 7.17 (s, 1H), 7.02 (t, J = 2.4 Hz,
1H), 6.69 (t, J = 2.3 Hz, 1H), 6.56 (dd, J = 1.8 and 3.6 Hz, 1H),
6.46 (dd, J = 2.7 and 3.6 Hz, 1H), 6.21 (dd, J = 2.7 and 3.6 Hz,
1H), 6.13 (dd, J = 1.8 and 3.6 Hz, 1H), 3.39 (s, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm) 138.7, 134.6, 133.4, 129.2,
128.6, 128.4, 127.3, 127.3, 126.5, 123.0, 109.1, 108.5, 50.7.
Elemental analysis: calcd (%) for C28H24N2 (388.51): C 86.56, H
6.23; found: C 86.79, H 6.31.
13C NMR (100 MHz, CDCl3) δ (ppm) 140.6, 134.2, 133.5, 132.9,
129.1, 128.4, 128.3, 126.5, 126.5, 126.4, 125.8, 124.5, 123.5,
110.9, 109.3, 108.6, 107.6, 34.6.
1,1'-(1,3-Phenylenebis(furan-5,2-diyl))bis(propan-2-one)
(20): Following the procedure A using 1-(furan-2-yl)propan-2-
one (372 mg, 3 mmol) and benzene-1,3-disulfonyl dichloride
Elemental analysis: calcd (%) for C21H18N2 (298.39): C 84.53, H
6.08; found: C 84.72, H 5.98.
(275 mg, 1 mmol), the residue was purified by flash
chromatography on silica gel (SiO2, Pentane-AcOEt 85:15) to
afford the desired compound 20 (268 mg, 83%).
1-Methyl-2-(3-(5-methylthiophen-3-yl)phenyl)pyrrole (16):
Following the procedure
A
using 3-(5-methylthiophen-3-
1H NMR (400 MHz, CDCl3) δ (ppm) 7.89 (s, 1H), 7.51 (dd, J =
1.7 and 7.7 Hz, 2H), 7.37 (t, J = 77.7 Hz, 1H), 6.67 (d, J = 3.3
Hz, 2H), 6.31 (d, J = 3.3 Hz, 2H), 3.80 (s, 4H), 2.23 (s, 6H).
13C NMR (100 MHz, CDCl3) δ (ppm) 204.0, 153.3, 148.1, 131.1,
yl)benzenesulfonyl chloride (8) (273 mg, 1 mmol) and 1-
methylpyrrole (203 mg, 2.5 mmol), the residue was purified by
flash chromatography on silica gel (SiO2, Pentane-AcOEt 85:15)
to afford the desired compound 16 (205 mg, 81%).
1H NMR (400 MHz, CDCl3) δ (ppm) 7.62 (s, 1H), 7.50 (d, J =
7.5 Hz, 1H), 7.41 (t, J = 7.6 Hz, 1H), 7.32 (d, J = 7.6 Hz, 1H),
7.22 (s, 1H), 7.09 (s, 1H), 6.74 (t, J = 2.3 Hz, 1H), 6.29 (dd, J =
1.7 and 3.1 Hz, 1H), 6.24 (t, J = 2.8 Hz, 1H), 3.69 (s, 3H), 2.54
(s, 3Η).
129.0, 122.5, 118.6, 110.5, 106.5, 43.5, 29.2.
Elemental analysis: calcd (%) for C20H18O4 (322.36): C 74.52, H
5.63; found: C 74.89, H 5.37.
2-(3-(Benzofuran-2-yl)phenyl)benzofuran (21): Following
the procedure A using benzofuran (354 mg, 3 mmol) and
benzene-1,3-disulfonyl dichloride (275 mg, 1 mmol), the residue
was purified by flash chromatography on silica gel (SiO2,
Pentane-AcOEt 90:10) to afford the desired compound 21 (233
mg, 75%).
13C NMR (75 MHz, CDCl3) δ (ppm) 141.7, 140.5, 136.2, 134.4,
133.7, 128.6, 127.1, 126.6, 124.6, 124.5, 123.6, 118.2, 108.7,
107.8, 35.0, 15.4.
Elemental analysis: calcd (%) for C16H15NS (253.36): C 75.85, H
5.97; found: C 76.03, H 5.78.
1H NMR (400 MHz, CDCl3) δ (ppm) δ 8.38 (s, 1H), 7.84 (d, J =
7.6 Hz, 2H), 7.63-7.52 (m, 6H), 7.34-7.28 (m, 3H), 7.20 (s, 2H).
1,3-Bis(5-methylthiophen-3-yl)benzene (17): Following the
procedure A using 2-methylthiophene (294 mg, 3 mmol) and
benzene-1,3-disulfonyl dichloride (275 mg, 1 mmol), the residue
was purified by flash chromatography on silica gel (SiO2,
Pentane-AcOEt 70:30) to afford the desired compound 17 (176
mg, 65%).
1H NMR (400 MHz, CDCl3) δ (ppm) 7.73 (s, 1H), 7.48-7.44 (m,
2H), 7.38 (t, J = 7.9 Hz, 1H), 7.22 (s, 2H), 7.0.9 (s, 2H), 2.54 (s,
6H).
This is a known compound and the spectral data are identical to
those reported in literature.24
4-(5-Bromo-2-methylphenyl)-2-methylthiophene
(22):
Following the procedure A using 2-methylthiophene (245 mg,
2.5 mmol) and 5-bromo-2-methylbenzenesulfonyl chloride (270
mg, 1 mmol), the residue was purified by flash chromatography
on silica gel (SiO2, Pentane-AcOEt 80:20) to afford the desired
compound 22 (126 mg, 47%).
1H NMR (400 MHz, CDCl3) δ (ppm) 7.46 (s, 1H), 7.35 (d, J =
8.2 Hz, 1H), 7.12 (d, J = 8.2 Hz, 1H), 6.97 (s, 1H), 6.81 (s, 1H),
2.55 (s, 3H), 2.31 (s, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm) 142.0, 140.5, 136.6, 129.1,
124.9, 124.7, 124.3, 118.2, 15.4.
Elemental analysis: calcd (%) for C16H14S2 (270.40): C 71.07, H
5.22; found: C 71.25, H 4.98.
13C NMR (75 MHz, CDCl3) δ (ppm) 140.5, 139.5, 138.8, 134.5,
132.2, 131.9, 129.9, 126.8, 120.9, 119.1, 20.3, 15.3.
1,3-Bis(1-methylpyrrol-2-yl)benzene (18): Following the
procedure A using 1-methylpyrrole (405 mg, 5 mmol) and

8
Tetrahedron
ACCEPTED MANUSCRIPT
Elemental analysis: calcd (%) for C12H11BrS (267.18): C 53.94,
2-(5-Bromo-2-methoxyphenyl)-1-methylpyrrole
(27):
H 4.15; found: C 54.13, H 4.29.
Following the procedure A using 1-methylpyrrole (203 mg, 2.5
mmol) and 5-bromo-2-methoxybenzenesulfonyl chloride (286
mg, 1 mmol), the residue was purified by flash chromatography
on silica gel (SiO2, Pentane-AcOEt 85:15) to afford the desired
compound 27 (197 mg, 74%).
2-bromo-4-(5-bromo-2-methylphenyl)thiophene
(23):
Following the procedure A using 2-bromothiophene (408 mg, 2.5
mmol) and 5-bromo-2-methylbenzenesulfonyl chloride (270 mg,
1 mmol), the residue was purified by flash chromatography on
silica gel (SiO2, Pentane-AcOEt 80:20) to afford the desired
compound 23 (173 mg, 52%).
1H NMR (400 MHz, CDCl3) δ (ppm) 7.40 (d, J = 2.3 Hz, 1H),
7.36 (dd, J = 2.1 and 8.1 Hz, 1H), 7.13-7.07 (m, 3H), 2.27 (s,
3H).
1H NMR (400 MHz, CDCl3) δ (ppm) 7.49-7.44 (m, 2H), 6.87 (d,
J = 8.2 Hz, 1H), 6.77 (t, J = 2.3 Hz, 1H), 6.26 (t, J = 2.9 Hz, 1H),
6.20 (dd, J = 2.0 and 3.6 Hz, 1H), 3.83 (s, 3H), 3.53 (s, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm) 156.4, 134.6, 131.5, 129.5,
124.6, 122.9, 112.5, 112.4, 109.4, 107.6, 55.6, 34.5.
13C NMR (75 MHz, CDCl3) δ (ppm) 141.3, 137.5, 134.6, 132.1,
132.1, 131.1, 130.6, 124.4, 119.3, 112.3, 20.1.
Elemental analysis: calcd (%) for C12H12BrNO (266.14): C 54.16,
H 4.55; found: C 54.32, H 4.38.
Elemental analysis: calcd (%) for C11H8Br2S (332.05): C 39.79,
H 2.43; found: C 39.56, H 2.57.
2-(5-bromo-2-methoxyphenyl)benzoxazole (28): Following
the procedure A using benzoxazole (298 mg, 2.5 mmol) and CuI
(190 mg, 1 mmol), 5-bromo-2-methoxybenzenesulfonyl chloride
2-(5-Bromo-2-methylphenyl)-1-methylpyrrole
(24):
(286 mg,
1 mmol), the residue was purified by flash
Following the procedure A using 1-methylpyrrole (203 mg, 2.5
mmol) and 5-bromo-2-methylbenzenesulfonyl chloride (270 mg,
1 mmol), the residue was purified by flash chromatography on
silica gel (SiO2, Pentane-AcOEt 80:20) to afford the desired
compound 24 (128 mg, 51%).
1H NMR (400 MHz, CDCl3) δ (ppm) 7.40-7.37 (m, 2H), 7.13 (d,
J = 8.8 Hz, 1H), 6.70 (dd, J = 1.9 and 2.7 Hz, 1H), 6.2 (t, J = 3.2
Hz, 1H), 6.06 (dd, J = 1.9 and 3.6 Hz, 1H), 3.41 (s, 3H), 2.14 (s,
3H).
chromatography on silica gel (SiO2, Pentane-AcOEt 85:15) to
afford the desired compound 28 (116 mg, 38%).
1H NMR (400 MHz, CDCl3) δ (ppm) 8.27 (d, J = 2.7 Hz, 1H),
7.85-7.81 (m, 1H), 7.62-7.57 (m, 2H), 7.40-7.33 (m, 2H), 6.98 (d,
J = 9.1 Hz, 1H), 4.01 (s, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm) 159.9, 157.5, 135.3, 133.6,
125.4, 124.5, 120.4, 117.9, 113.9, 112.8, 110.5, 56.5.
Elemental analysis: calcd (%) for C14H10BrNO2 (304.14): C
55.29, H 3.31; found: C 55.63, H 3.18.
13C NMR (100 MHz, CDCl3) δ (ppm) 137.2, 135.2, 133.8, 131.7,
131.5, 130.8, 122.1, 118.8, 108.9, 107.5, 34.1, 19.6.
2-(4-Methyl-3-(5-methylthiophen-3-yl)phenyl)benzoxazole
(29): Following the procedure B using benzoxazole (298 mg, 2.5
mmol) and 4-(5-bromo-2-methylphenyl)-2-methylthiophene (22)
Elemental analysis: calcd (%) for C12H12BrN (250.14): C 57.62,
H 4.84; found: C 57.94, H 5.13.
(267 mg,
1 mmol), the residue was purified by flash
2-(5-Bromo-2-methylphenyl)benzoxazole (25): Following
the procedure A using benzoxazole (298 mg, 2.5 mmol) and CuI
(190 mg, 1 mmol), 5-bromo-2-methylbenzenesulfonyl chloride
chromatography on silica gel (SiO2, Pentane-AcOEt 85:15) to
afford the desired compound 29 (223 mg, 73%).
1H NMR (400 MHz, CDCl3) δ (ppm) 8.19 (s, 1H), 8.09 (dd, J =
1.9 and 7.9 Hz, 1H), 7.77 (dd, J = 2.9 and 4.5 Hz, 1H), 7.58-7.54
(m, 1H), 7.38 (d, J = 7.8 Hz, 1H), 7.36-7.321 (m, 2H), 7.06 (s,
1H), 6.82 (s, 1H), 2.55 (s, 3H), 2.43 (s, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm) 163.1, 150.6, 142.1, 140.8,
139.7, 139.5, 137.6, 131.1, 128.7, 127.0, 126.1, 124.9, 124.7,
124.5, 121.0, 119.8, 110.4, 21.0, 15.3.
(270 mg,
1 mmol), the residue was purified by flash
chromatography on silica gel (SiO2, Pentane-AcOEt 85:15) to
afford the desired compound 25 (130 mg, 45%).
1H NMR (300 MHz, CDCl3) δ (ppm) 8.34 (s, 1H), 7.83-7.79 (m,
1H), 7.53-7.57 (m, 1H), 7.51 (dd, J = 2.2 and 8.2 Hz, 1H), 7.42-
7.38 (m, 2H), 7.21 (d, J = 8.2 Hz, 1H), 2.76 (s, 3H).
13C NMR (75 MHz, CDCl3) δ (ppm) 161.8, 150.2, 141.9, 137.7,
133.6, 133.3, 132.4, 127.9, 125.4, 124.6, 120.3, 119.5, 110.5,
21.8.
Elemental analysis: calcd (%) for C19H15NOS (305.40): C 74.73,
H 4.95; found: C 74.62, H 5.12.
Elemental analysis: calcd (%) for C14H10BrNO (288.14): C 58.36,
H 3.50; found: C 58.14, H 3.88.
2-(4-methyl-3-(1-methylpyrrol-2-yl)phenyl)benzoxazole
(30): Following the procedure B using benzoxazole (298 mg, 2.5
mmol) and 2-(5-bromo-2-methylphenyl)-1-methylpyrrole (24)
2-(5-Bromo-2-methoxyphenyl)benzofuran (26): Following
the procedure A using benzofuran (295 mg, 2.5 mmol) and 5-
bromo-2-methoxybenzenesulfonyl chloride (286 mg, 1 mmol),
the residue was purified by flash chromatography on silica gel
(SiO2, Pentane-AcOEt 85:15)to afford the desired compound 26
(188 mg, 62%).
1H NMR (300 MHz, CDCl3) δ (ppm) 8.20 (d, J = 2.6 Hz, 1H),
7.63 (d, J = 7.5 Hz, 1H), 7.54 (d, J = 7.7 Hz, 1H), 7.41-7.35 (m,
2H), 7.34-7.23 (m, 2H), 6.81 (d, J = 8.8 Hz, 1H), 3.93 (s, 3H).
(250 mg,
1 mmol), the residue was purified by flash
chromatography on silica gel (SiO2, Pentane-AcOEt 85:15) to
afford the desired compound 30 (228 mg, 79%).
1H NMR (400 MHz, CDCl3) δ (ppm) 8.18-8.15 (m, 2H), 7.78-
7.75 (m, 1H), 7.58-7.54 (m, 1H), 7.44 (d, J = 8.5 Hz, 1H), 7.37-
7.32 (m, 2H), 6.75 (dd, J = 1.8 and 2.7 Hz, 1H), 6.25 (dd, J = 2.7
and 3.5 Hz, 1H), 6.15 (dd, J = 1.8 and 3.5 Hz, 1H), 3.47 (s, 3H),
2.30 (s, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm) 163.0, 150.7, 142.3, 142.1,
134.0, 132.0, 130.7, 130.3, 126.9, 124.9, 124.6, 124.5, 122.1,
119.9, 110.5, 109.0, 107.5, 34.2, 20.3.
13C NMR (75 MHz, CDCl3) δ (ppm) 107.4, 110.9, 112.6, 113.2,
121.1, 121.3, 122.8, 124.6, 129.4, 129.5, 131.5, 150.6, 153.9,
155.4, 55.7.
Elemental analysis: calcd (%) for C19H16N2O (288.35): C 79.14,
H 5.59; found: C 78.95, H 5.41.
Elemental analysis: calcd (%) for C15H11BrO2 (303.16): C 59.43,
H 3.66; found: C 59.23, H 3.61.
2-(5-(4-ethyl-2-methylthiazol-5-yl)-2-
methylphenyl)benzoxazole (32): Following the procedure B

9
Hasvold, L. A.; Pratt, J.; McDaniel, K. F.; Sheppard, G. S.; Liu, D.;
using 4-ethyl-2-methylthiazole (318 mg, 2.5 mmol) and 2-(5-
bromo-2-methylphenyl)benzoxazole (25) (288 mg, 1 mmol), the
residue was purified by flash chromatography on silica gel (SiO2,
Pentane-AcOEt 85:15) to afford the desired compound 31 (281
mg, 84%).
1H NMR (300 MHz, CDCl3) δ (ppm) 8.23 (d, J = 1.9 Hz, 1H),
7.85-7.78 (m, 1H), 7.63-7.58 (m, 1H), 7.45 (dd, J = 1.9 ans 7.9
Hz, 1H), 7.40 (s, 1H), 7.39-7.35 (m, 2H), 3.03 (q, J = 7.6 Hz,
2H), 2.84 (s, 3H), 2.51 (s, 3H), 1.42 (t, J = 7.6 Hz, 3H).
ACCEPTED MANUSCRIPT
Elmore, S. W.; Hubbard, R. D.; AbbVie Inc., USA . US Patent, no.
20140275079, 2014; c) Bhardwaj, V.; Gumber, D.; Abbot, V.; Dhiman, S.;
Sharma, P. RSC Adv. 2015, 5, 15233-15266.
2a) Meyers, J. K.; Rogers, B. N.; Groppi, V. E., Jr.; Piotrowski, D. W.;
Bodnar, A. L.; Jacobsen, E. J.; Corbett, J. W.; Pharmacia & Upjohn
Company, USA; PCT Int. Appl., no. WO2002015662A2, 2002; b) Myers, J.
K.; Rogers, B. N.; Groppi, V. E., Jr.; Piotrowski, D. W.; Bodnar, A. L.;
Jacobsen, E. J.; Corbett, J. W.; Pharmacia & Upjohn Company, USA; PCT
Int. Appl., no. WO2002016355A2, 2002.
3 Selander, N.; J. Szabó, K. Chem. Rev. 2011, 111, 2048-2076.
4 Chan, A. K.-W.; Lam, E. S.-H.; Tam, A. Y.-Y.; Tsang, D. P.-K.; Lam, W.
H.; Chan, M.-Y.; Wong, W.-T.; Yam, V. W.-W. Chem. Eur. J. 2013, 19,
13910-13924.
13C NMR (75 MHz, CDCl3) δ (ppm) 170.4, 162.7, 150.3, 147.4,
142.1, 138.2, 132.2, 131.3, 130.4, 129.8, 126.6, 125.2, 124.5,
120.2, 110.5, 26.9, 21.9, 16.1, 14.3.
5a) Suzuki, T.; Tsubata, Y.; Obana, Y.; Fukushima, T.; Miyashi, T.; Saito,
M.; Kawai, H.; Fujiwara, K.; Akiyama, K. Tetrahedron Lett. 2003, 44, 7881-
7884; b) Ameerunisha Begum, M. S.; Seewald, O.; Floerke, U.; Henkel, G.
Inorg. Chim. Acta 2008, 361, 1868-1874; c) Cheng, F.; Tang, N. Inorg.
Chem. Commun. 2008, 11, 506-508; d) Mukhopadhyay, C.; Tapaswi, P. K.
Tetrahedron Lett. 2008, 49, 6237-6240; e) Santella, J. B.; Gardner, D. S.;
Yao, W.; Shi, C.; Reddy, P.; Tebben, A. J.; DeLucca, G. V.; Wacker, D. A.;
Watson, P. S.; Welch, P. K.; Wadman, E. A.; Davies, P.; Solomon, K. A.;
Graden, D. M.; Yeleswaram, S.; Mandlekar, S.; Kariv, I.; Decicco, C. P.; Ko,
S. S.; Carter, P. H.; Duncia, J. V. Bioorg. Med. Chem. Lett. 2008, 18, 576-
585; f) Jain, A. K.; Reddy, V. V.; Paul, A.; Muniyappa, K.; Bhattacharya, S.
Biochemistry 2009, 48, 10693-10704; g) Mukhopadhyay, C.; Tapaswi, P. K.;
Drew, M. G. B. Tetrahedron Lett. 2010, 51, 3944-3950; h) Azizi, N.; Dado,
N.; Amiri, A. K. Can. J. Chem. 2012, 90, 195-198; i) Ban, X.; Jiang, W.;
Sun, K.; Xie, X.; Peng, L.; Dong, H.; Sun, Y.; Huang, B.; Duan, L.; Qiu, Y.
ACS Appl. Mater. Interfaces 2015, 7, 7303-7314.
Elemental analysis: calcd (%) for C20H18N2OS (334.44): C 71.83,
H 5.43; found: C 72.13, H 5.28.
4-Ethyl-5-(4-methoxy-3-(1-methylpyrrol-2-yl)phenyl)-2-
methylthiazole (32): Following the procedure B using 4-ethyl-2-
methylthiazole (318 mg, 2.5 mmol) and 2-(5-bromo-2-
methoxyphenyl)-1-methylpyrrole (27) (266 mg, 1 mmol), the
residue was purified by flash chromatography on silica gel (SiO2,
Pentane-AcOEt 80:20) to afford the desired compound 32 (247
mg, 79%).
1H NMR (300 MHz, CDCl3) δ (ppm) 7.43-7.34 (m, 2H), 6.99 (d,
J = 8.5 Hz, 1H), 6.75 (dd, J = 1.8 and 2.8 Hz, 1H), 6.24 (dd, J =
2.8 and 3.5 Hz, 1H), 6.18 (dd, J = 1.8 and 3.5 Hz, 1H), 3.85 (s,
3H), 3.54 (s, 3H), 3.01 (q, J = 7.6 Hz, 2H), 2.48 (s, 3H), 1.41 (t, J
= 7.6 Hz, 3H).
6a) Mejia, M. L.; Agapiou, K.; Yang, X.; Holliday, B. J. J. Am. Chem. Soc.
2009, 131, 18196-18197; b) Hong, X.; Mellah, M.; Bordier, F.; Guillot, R.;
Schulz, E. ChemCatChem 2012, 4, 1115-1121; c) Nguyen, M. T.; Holliday,
B. J. Chem. Commun. 2015, 51, 8610-8613.
7a) van Haare, J. A. E. H.; van Boxtel, M.; Janssen, R. A. J. Chem. Mater.
1998, 10, 1166-1175; b) Ishikawa, S.; Manabe, K. Chem. Lett. 2007, 36,
1304-1305; c) Cornacchio, A. L. P.; Price, J. T.; Jennings, M. C.; McDonald,
R.; Staroverov, V. N.; Jones, N. D. J. Org. Chem. 2009, 74, 530-544; d)
Idzik, K. R.; Beckert, R.; Golba, S.; Ledwon, P.; Lapkowski, M.
Tetrahedron Lett. 2010, 51, 2396-2399; e) Xia, J.; Yuan, S.; Wang, Z.;
Kirklin, S.; Dorney, B.; Liu, D.-J.; Yu, L. Macromolecules 2010, 43, 3325-
3330; f) Bolliger, J. L.; Frech, C. M. Chem. Eur. J. 2010, 16, 11072-11081;
g) Konidena, R. K.; Thomas, K. R. J.; Kumar, S.; Wang, Y.-C.; Li, C.-J.;
Jou, J.-H. J. Org. Chem. 2015, 80, 5812-5823.
8a) Sinclair, D. J.; Sherburn, M. S. J. Org. Chem. 2005, 70, 3730-3733; b)
Guillén, E.; Hierrezuelo, J.; Martínez-Mallorquín, R.; López-Romero, J. M.;
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Cariou, K.; Dodd, R. H. Eur. J. Org. Chem. 2014, 2942-2955.
9 Beaumard, F.; Dauban, P.; Dodd, R. H. Org. Lett. 2009, 11, 1801-1804.
10a) Bellina, F.; Cauteruccio, S.; Rossi, R. Curr. Org. Chem. 2008, 12, 774-
790; b) Kakiuchi, F.; Kochi, T. Synthesis 2008, 3013-3039; c) Ackermann,
L.; Vicente, R.; Kapdi, A. R. Angew. Chem. Int. Ed. 2009, 48, 9792-9826; d)
13C NMR (75 MHz, CDCl3) δ (ppm) 169.6, 156.7, 146.4, 132.9,
130.4, 130.3, 129.7, 124.7, 122.8, 122.7, 110.8, 109.2, 107.6,
55.5, 34.6, 26.9, 16.0, 14.3.
Elemental analysis: calcd (%) for C18H20N2OS (312.43): C 69.20,
H 6.45; found: C 69.47, H 6.59.
5-(3-(Benzofuran-2-yl)-4-methoxyphenyl)-4-ethyl-2-
methylthiazole (33): Following the procedure B using 4-ethyl-2-
methylthiazole (318 mg, 2.5 mmol) and 2-(5-bromo-2-
methoxyphenyl)benzofuran (26) (303 mg, 1 mmol), the residue
was purified by flash chromatography on silica gel (SiO2,
Pentane-AcOEt 80:20) to afford the desired compound 33 (300
mg, 86%).
1H NMR (300 MHz, CDCl3) δ (ppm) 8.12 (d, J = 2.3 Hz, 1H),
7.61 (dd, J = 1.5 and 7.5 Hz, 1H), 7.52 (d, J = 7.5 Hz, 1H), 7.40
(d, J = 0.9 Hz, 1H), 7.35 (dd, J = 2.4 and 8.5 Hz, 1H), 7.29 (dt, J
= 1.5 and 7.0 Hz, 1H), 7.23 (dt, J = 1.5 and 7.0 Hz, 1H), 7.03 (d,
J = 8.6 Hz, 1H), 4.03 (s, 3H), 3.03 (q, J = 7.6 Hz, 2H), 2.50 (s,
3H), 1.43 (t, J = 7.6 Hz, 3H)
Bellina, F.; Rossi, R. Chem. Rev. 2009, 110, 1082-1146; e) Bellina,
F.;
Rossi, R. Tetrahedron 2009, 65, 10269-10310; f) Chen, X.; Engle, K. M.;
Wang, D.-H.; Yu, J.-Q. Angew. Chem. Int. Ed. 2009, 48, 5094-5115; g)
Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147-1169; h) Beck,
E. M.; Gaunt, M. J. Top. Curr. Chem. 2010, 292, 85-121; i) Roger,
J.;
Gottumukkala, A. L.; Doucet, H. ChemCatChem 2010, 2, 20-40; j) Satoh, T.;
Miura, M. Synthesis 2010, 3395-3409; k) Sun, C.-L.; Li, B.-J.; Shi, Z.-J.
Chem. Commun. 2010, 46, 677-685; l) Cho, S. H.; Kim, J. Y.; Kwak, J.;
Chang, S. Chem. Soc. Rev. 2011, 40, 5068-5083; m) Kuhl, N.; Hopkinson,
M. N.; Wencel-Delord, J.; Glorius, F. Angew. Chem. Int. Ed. 2012, 51,
10236-10254; n) Li, B.-J.; Shi, Z.-J. Chem. Soc. Rev. 2012, 41, 5588-5598; o)
13C NMR (75 MHz, CDCl3) δ (ppm) 169.8, 155.9, 153.9, 151.4,
146.8, 130.3, 129.8, 129.6, 127.8, 125.0, 124.3, 122.7, 121.1,
119.5, 111.2, 110.9, 106.9, 55.6, 26.9, 16.0, 14.3.
Elemental analysis: calcd (%) for C21H19NO2S (349.45): C 72.18,
H 5.48; found: C 72.35, H 5.67.
White, M. C. Synlett 2012, 23, 2746-2748; p) Kozhushkov,
S.
I.;
Ackermann, L. Chem. Sci. 2013, 4, 886-896; q) He, M.; Soulé, J.-F.; Doucet,
H. ChemCatChem 2014, 6, 1824-1859; r) Rossi, R.; Bellina, F.; Lessi, M.;
Manzini, C. Adv. Synth. Catal. 2014, 356, 17-117; s) Yuan, K.; Soulé, J.-F.;
Doucet, H. ACS Catal. 2015, 5, 978-991; t) Yadav, M. R.; Rit, R. K.;
Shankar, M.; Sahoo, A. K. Asian J. Org. Chem. 2015, 4, 846-864.
11a) Baloch, M.; Roy, R. J.; Roy, D.; Beydoun, K.; Doucet, H. RSC Adv.
2011, 1, 1527-1536; b) Chen, L.; Roger, J.; Bruneau, C.; Dixneuf, P. H.;
Doucet, H. Chem. Commun. 2011, 47, 1872-1874; c) Fu, H. Y.; Doucet, H.
Eur. J. Org. Chem. 2011, 7163-7173.
12 Zhao, X.; Dimitrijević, E.; Dong, V. M. J. Am. Chem. Soc. 2009, 131,
3466-3467.
13a) Zhang, M.; Zhang, S.; Liu, M.; Cheng, J. Chem. Commun. 2011, 47,
11522-11524; b) Jafarpour, F.; Olia, M. B. A.; Hazrati, H. Adv. Synth. Catal.
2013, 355, 3407-3412; c) Yuan, K.; Doucet, H. Chem. Sci. 2014, 5, 392-396;
d) Beladhria, A.; Yuan, K.; Ben Ammar, H.; Soulé, J.-F.; Ben Salem, R.;
Acknowledgments
We thank “Rennes Metropole”, the CNRS, and French Scientific
Ministry of Higher Education for providing financial support.
References and notes
1a) Hall, A.; Atkinson, S.; Brown, S. H.; Chessell, I. P.; Chowdhury, A.;
Clayton, N. M.; Coleman, T.; Giblin, G. M. P.; Gleave, R. J.; Hammond, B.;
Healy, M. P.; Johnson, M. R.; Michel, A. D.; Naylor, A.; Novelli, R.;
Spalding, D. J.; Tang, S. P. Bioorg. Med. Chem. Lett. 2006, 16, 3657-3662; b)

10
Tetrahedron
Doucet, H. Synthesis 2014, 46, 2515-2523; e) Loukotova, L.; Yuan, K.;
ACCEPTED MANUSCRIPT
Doucet, H. ChemCatChem 2014, 6, 1303-1309; f) Jin,
R.;
Yuan,
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