A highly efficient palladium-catalyzed desulfitative arylation of azoles with sodium arylsulfinates

Article abstract of DOI:10.1016/j.tet.2011.12.072

A highly efficient palladium-catalyzed direct desulfitative arylation of azoles at C2-position has been developed using sodium arylsulfinates as aryl sources. Azoles including benzoxazoles, benzothiazoles, oxazoles, thiazoles, and 1,3,4-oxadiazoles reacted with sodium arylsulfinates smoothly to generate the corresponding products in good to excellent yields, and various substitution patterns were tolerated toward the reaction.

Full text of DOI:10.1016/j.tet.2011.12.072

Tetrahedron 68 (2012) 1926e1930
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A highly efficient palladium-catalyzed desulfitative arylation of azoles with
sodium arylsulfinates
,b,
Min Wang a, Dengke Li a, Wei Zhou a, Lei Wang a
*
a Department of Chemistry, Huaibei Normal University, 100 Dongshan Road, Huaibei, Anhui 235000, PR China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A highly efficient palladium-catalyzed direct desulfitative arylation of azoles at C2-position has been de-
veloped using sodium arylsulfinates as aryl sources. Azoles including benzoxazoles, benzothiazoles, ox-
azoles, thiazoles, and 1,3,4-oxadiazoles reacted with sodium arylsulfinates smoothly to generate the
corresponding products in good to excellent yields, and various substitution patterns were tolerated to-
ward the reaction.
Received 6 November 2011
Received in revised form 17 December 2011
Accepted 23 December 2011
Available online 31 December 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Pd(OAc)2
Desulfitative arylation
Azoles
Sodium arylsulfinates
CeH bond functionalization
1. Introduction
reactions in the literature.11 In 2011, palladium-catalyzed desulfi-
tative Heck-type reaction of arylsulfinic acids with alkenes,12 and
The heterocyclic compounds, especially those containing azole
skeletons represent a predominant structural motif in a wide array
of biologically active natural compounds, pharmaceuticals, and or-
ganic functional materials.1 Consequently, there is a considerable
attention from synthetic chemists in the development of practical
methods for the construction of this structural element of interest in
biology, pharmacology, optics, and electronics fields. In addition to
the traditional Pd- or Ni-catalyzed cross-coupling methodology
between aryl halides and organometallic reagents,2 the transition-
metal-catalyzed direct CeH bond functionalization of azoles has
become the focus of many researchers for the synthesis of these
kinds of compounds, owing to its sustainable and environmentally
benign features. Great progress has been achieved for the direct CeC
and CeN bond formations of azoles via CeH activation using various
electrophiles or nucleophiles catalyzed by transition-metal catalyst,
such as Pd-, Cu-, Ni-, Co-, Mn-, Fe-, or/and Rh systems.3e10 Among
them, Pd-, Ni-, Pd/Cu, or Rh-catalyzed direct arylation of azoles is
a useful synthetic method for preparing of the heterobiaryl com-
pounds using aryl halides, mesylates, triflates, organosilicons, and
arylboronic acids as the arylation reagents through CeH activation.4
It has been reported that arenesulfonyl chlorides can act as aryl
sources for CeC bond formations through the desulfitative/Heck-,
Negishi-, Suzuki-, Still-, and Sonogashira-type cross-coupling
desulfitative addition reaction of arylsulfinic acids to nitriles for the
synthesis of aryl ketones13 were developed by Wang et al. Com-
pared to the active and moisture-sensitive arylsulfonyl chlorides
and arylsulfinic acids, arylsulfinic acid salts are much more stable,
and may also serve as the aryl sources via the extrusion of SO2 for
CeC bond-forming reactions, although sulfinic acid salts are gen-
erally used as sulfonylation reagents for preparing compounds
containing sulfonyl groups14 and seldom worked as the aryl sources
via desulfitative reactions.15 Most recently, Deng and Li reported
the desulfitative arylation reactions of sodium arylsulfinates with
olefins,16 nitriles,17 and aldehydes.18
Driven by the need for expanding new arylating reagents for the
synthesis of 2-arylsubstituted azoles and our ongoing interest in
the CeH bond functionalization of azoles,19 herein we report
a highly efficient palladium-catalyzed desulfitative arylation re-
actions of arylsulfinic acid sodium salts with a wide range of azoles,
including thiazoles, oxazoles, benzothiazoles, benzoxazoles, and
oxadiazoles through a tandem desulfitation/CeH activation process
under mild reaction conditions (Scheme 1).
* Corresponding author. Tel.: þ86 561 3802 069; fax: þ86 561 3090 518; e-mail
Scheme 1.
address: leiwang@chnu.edu.cn (L. Wang).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.12.072

M. Wang et al. / Tetrahedron 68 (2012) 1926e1930
1927
2. Results and discussion
The effect of additive on this reaction was also investigated. In
most of the cases, CeH activation of azoles were carried out in the
presence of a strong base, such as LiOtBu, KOtBu, or CsOH.3e10 In the
beginning, various organic or inorganic bases were chosen as additive
to the reaction system for improvement of the product yield. How-
ever, the addition of LiOtBu, KOtBu, Et3N, or Cs2CO3 (1.0 equiv) to the
reactiondid notimprovetheproductyield, and conversely, restrained
the reactivity of the catalytic reaction (Table 1, entries 18e21). It
should be noted that the addition of LiOtBu, as a general effective base
in the CeH activation of azoles,7b,8d,9c could shut down the reaction
completely. Fortunately, the addition of CF3CO2H (1.0 equiv) to the
reaction system improved the product yield significantly, and to our
surprise, 3a was obtained in 81% yield (Table 1, entry 22). Other acids,
such as CH3CO2H, CF3SO3H, tBuCO2H, and concentrated H2SO4 were
less effective than that of CF3CO2H (Table 1, entries 23e26). With
respect to the amount of oxidant and additive used in the reaction,
2.0 equiv of Cu(OAc)2 and 1.0 equiv of CF3CO2H were found to be
optimal. The model reaction was not completed with less than
2.0 equiv of Cu(OAc)2,1.0 equivof CF3CO2H, and 5.0 mol % of Pd(OAc)2
used in the reaction, respectively (Table 1, entries 27e29).
As an initial experiment, a model reaction of benzoxazole (1a)
with sodium p-tolylsulfinate (2a) in the presence of 5.0 mol % of
Pd(OAc)2 as the catalyst and 2 equiv of Cu(OAc)2 as the oxidant in
dimethylglycol at 120 ꢀC for 24 h, to our delight, a desulfitative
arylation product, 2-(p-tolyl)benzoxazole (3a) was isolated in 35%
yield (Table 1, entry 1). This interesting preliminary result encour-
aged us to optimize the reaction conditions on the basis of palladium
catalyst. As the palladium sources, the comparable product yields
were obtained when PdCl2, Pd(PPh3)2Cl2, Pd(PPh3)4, and Pd(TFA)2
were used as the catalysts instead of Pd(OAc)2 (Table 1, entries 2e5).
The Pd-catalyst is essential in the model reaction and no 3a was
formed in the absence of Pd (Table 1, entry 6). Pd(OAc)2 was
employed as catalyst in our following investigation for its low cost
comparing with its complexes. Various Cu(II) salts, such as Cu(OAc)2,
CuCl2, and CuBr2 were examined as oxidants for this direct arylation
reaction, and Cu(OAc)2 displayed the highest reactivity. CuCl2, CuBr2,
and CuO were inferior, and Ag2O was ineffective oxidant in the re-
action (Table 1, entries 7e10). The replacement of Cu(II) salts by the
non-metallic oxidants was also examined and the results were also
provided in Table 1. Organic peroxides, such as tert-butyl hydro-
peroxide (TBHP), 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ),
and C6H5I(OAc)2, as well as inorganic oxidants, K2S2O8, and
(NH4)2S2O8, were no longer the effective oxidants in the reaction,
and no desired product 3a was detected (Table 1, entries 11e15).
Using oxygen as oxidant, 9% yield of 3a was formed, and the reaction
did not occur in the absence of oxidant (Table 1, entries 16 and 17).
Further screening of solvents revealed that dimethylglycol was
the optimal solvent. Other solvents, such as dioxane, DMF, and
CH3NO2 were harmful to this reaction, and DMSO, tBuOH, and
toluene were infeasible.
After the optimization of reaction conditions (5.0 mol % of
Pd(OAc)2 as catalyst, 2.0 equiv of Cu(OAc)2 as oxidant, 1.0 equiv of
CF3CO2H as additive, dimethylglycol as solvent at 120 ꢀC, 24 h),
several substituted benzoxazoles were then applied to the direct
desulfitative arylation reactions with sodium p-tolylsulfinate (2a).
As shown in Scheme 2, most of the benzoxazoles, both with
electron-donating substituents, such as CH3 and tC4H9 groups, and
with electron-withdrawing groups, such as NO2 and Cl, on the
benzene rings, could react smoothly with 2a to give the corre-
sponding products (3aeg) in good yields. Simple oxazoles (1hej),
and 1,3,4-oxadiazoles (1keo) with various substituents on the
heterocyclic were also employed for the reaction with 2a under the
optimized reaction conditions. The results indicated that the re-
action proceeded smoothly, and were tolerated a number of
substituted groups. The corresponding desulfitative arylation
products (3hej, and 3keo) of azoles at C2-position were obtained
in good to excellent yields. Notably, the reactions of ethyl oxazole-
5-carboxylate (1j) and 2-(p-tolyl)-1,3,4-oxadiazole (1l) with 2a
were highly efficient to generate the corresponding products 3j and
3l in 93 and 95% isolated yields, respectively. Moreover, benzo-
thiazole, substituted benzothiazoles, thiazole, and substituted thi-
azoles (1peu) could also undergo the desulfitative arylation with
2a under the present reaction conditions, and the corresponding
products (3peu) were isolated in good yields.
Additionally, the desulfitative arylation reaction between ben-
zoxazole (1a) with various sodium arylsulfinates was investigated
and the results are shown in Scheme 3. Sodium benzenesulfinate
was successfully reacted with 1a to give the corresponding product
(4a) in 80% yield. For sodium arylsulfinates with different func-
tional groups, including methyl, tert-butyl, methoxy, fluoro, chloro,
bromo, and cyano groups on the para- or meta-position of benzene
rings, also reacted with 1a smoothly to generate the desired
products (4b, and 4dei) in 70e83% yields. It is obvious that ortho-
position effect was observed (4c).
Table 1
Optimization of the reaction conditionsa
Entry
Pd catal.
Oxidant
Additive
Yieldb (%)
1
2
Pd(OAc)2
PdCl2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
CuCl2
CuBr2
CuO
Ag2O
TBHP
DDQ
C6H5I(OAc)2
K2S2O8
(NH4)2S2O8
O2
d
d
35
34
35
32
36
0
26
21
12
0
0
0
0
0
0
9
0
0
13
21
22
81
61
52
39
43
36
79
56
d
3
4
5
6
Pd(PPh3)2Cl2
Pd(PPh)4
Pd(TFA)2
d
d
d
d
d
7
8
9
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
d
d
d
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27c
28d
29e
d
d
d
d
d
d
d
d
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
LiOtBu
KOtBu
Et3N
Cs2CO3
CF3CO2H
CH3CO2H
CF3SO3H
tBuCO2H
H2SO4
CF3CO2H
CF3CO2H
CF3CO2H
Although the exact mechanism of this reaction is not clear,
a possible pathway was proposed and shown in Scheme 4. The first
step was presumably a ligand exchange between PdX2 (X¼OAc or
OTFA) with sodium arylsulfinate (2) to generate a Pd(II)-sulfinate
intermediate A, which subsequently underwent desulfitation to
form an aryl-Pd(II) species (ArPdX). Next, this ArPdX inserted the
CeN double bond of benzoxazole (1a) to generate the intermediate
a
Reaction conditions: 1a (0.50 mmol), 2a (1.0 mmol), Pd(OAc)2 (0.025 mmol),
oxidant (1.0 mmol), additive (0.50 mmol), dimethylglycol (2.0 mL) at 120 ꢀC for
24 h.
b
Isolated yields.
Cu(OAc)2 (0.50 mmol) was added.
Pd(OAc)2 (0.0125 mmol) was added.
CF3CO2H (0.25 mmol) was added.
c
d
e
B via a carbopalladation. After b-hydride elimination from B, the

1928
M. Wang et al. / Tetrahedron 68 (2012) 1926e1930
Scheme 4. Proposed reaction mechanism.
3. Conclusions
In conclusion, we have developed an efficient protocol for
the palladium-catalyzed direct desulfitative arylation of azoles at
C2-position using sodium arylsulfinates as the aryl sources.
Azoles including benzoxazoles, oxazoles, benzothiazole, thiazoles,
and 1,3,4-oxadiazoles could react with sodium arylsulfinates
smoothly to generate the corresponding products in good to ex-
cellent yields, and various substitution patterns were tolerated
toward the reaction.20 The extend investigation of this kind re-
action and detail reaction mechanism are currently underway in
our laboratory.
4. Experimental
a
Reaction conditions: azole (0.50 mmol), 2a (1.0 mmol), Pd(OAc)2
(0.025 mmol), Cu(OAc)2 (1.0 mmol), TFA (0.50 mmol), dimethylglycol (2.0
mL) at 120 ºC for 24 h. b Isolated yields.
4.1. General methods
Scheme 2. Palladium-catalyzed desulfitative C2-arylation of azoles with sodium
p-tolylsulfinate (2a).a
All reactions were carried out under nitrogen atmosphere. So-
dium arylsulfinates were prepared according to the literature,21
and other chemical reagents were purchased from commercial
suppliers and used without further purification. 1H NMR and 13C
NMR spectra were measured on a Bruker Avance NMR spectrom-
eter (400 MHz or 100 MHz, respectively) with CDCl3 as solvent and
recorded in parts per million relative to internal tetramethylsilane
standard. The peak patterns are indicated as follows: s, singlet; d,
doublet; t, triplet; m, multiplet; q, quartet. The coupling constants,
J, are reported in hertz (Hz). IR spectra were obtained by using
a Nicolet NEXUS 470 spectrophotometer. High resolution mass
spectroscopy data of the products were collected on a Waters
Micromass GCT instrument.
4.2. Typical procedure for palladium-catalyzed desulfitative
arylation of azoles with sodium arylsulfinates
Under nitrogen atmosphere, a sealable reaction tube equipped
with a magnetic stirrer bar was charged with azole (0.50 mmol),
sodium arylsulfinate (1.0 mmol), Pd(OAc)2 (0.025 mmol), Cu(OAc)2
(1.0 mmol), CF3COOH (0.50 mmol), and dimethylglycol (2.0 mL).
The rubber septum was then replaced by a Teflon-coated screw
cap, and the reaction vessel placed in an oil bath at 120 ꢀC for 24 h.
After the reaction was completed, it was cooled to room temper-
ature and the mixture was treated with K2CO3 solution (1.0 mol/L,
3.0 mL), then extracted with ethyl acetate. The resulting solution
was dried by Na2SO4 then concentrated under reduced pressure.
The residue was purified by flash chromatography on silica gel
(eluant: petroleum ether/ethyl acetate¼12:1, v/v) to give the
desired product.
a
Reaction conditions: 1a (0.50 mmol), sodium arylsulfinate (1.0 mmol),
Pd(OAc)2 (0.025 mmol), Cu(OAc)2 (1.0 mmol), TFA (0.50 mmol),
dimethylglycol (2.0 mL) at 120 ºC for 24 h. b Isolated yields.
Scheme 3. Palladium-catalyzed desulfitative C2-arylation of benzoxazole (1a) with
sodium arylsulfinates.a
final product 3 was obtained along with the generation of HPdX,
which generated Pd(0) via a reductive elimination. The generated
Pd(0) was reoxidized to Pd(II) by Cu(II), and a catalytic cycle was
completed.

M. Wang et al. / Tetrahedron 68 (2012) 1926e1930
1929
4.3. Analytical data for all products
d 164.74, 164.34, 142.26, 131.59, 129.76 (2C), 129.03, 126.89,
124.07, 121.19, 21.62.
4.3.1. Compound 3a. 1H NMR (CDCl3, 400 MHz):
d 8.15 (d,
J¼8.0 Hz, 2H), 7.77e7.75 (m, 1H), 7.58e7.55 (m, 1H), 7.35e7.32
4.3.12. Compound 3l. 1H NMR (CDCl3, 400 MHz):
d
8.00
(m, 4H) 2.44 (s, 3H); 13C NMR (CDCl3, 100 MHz):
d
163.31, 150.71,
(d, J¼8.0 Hz, 4H), 7.31 (d, J¼8.0 Hz, 4H), 2.42 (s, 6H); 13C NMR
142.20, 142.03, 129.63, 127.60, 124.84, 124.46, 124.44, 119.84,
110.47, 21.61.
(CDCl3, 100 MHz): d 164.42, 142.06, 129.67, 126.77, 121.21, 21.57.
4.3.13. Compound 3m. 1H NMR (CDCl3, 400 MHz):
d
8.04
4.3.2. Compound 3b. 1H NMR (CDCl3, 400 MHz):
d
8.11 (d, J¼8.0 Hz,
(d, J¼8.0 Hz, 2H), 7.97 (s, 1H), 7.93 (d, J¼7.6 Hz, 1H), 7.44e7.40 (m,
2H), 7.53 (s,1H), 7.41 (d, J¼8.4 Hz,1H), 7.30 (d, J¼8.4 Hz, 2H), 7.12 (d,
1H), 7.37e7.33 (m, 3H), 2.46 (s, 3H), 2.45 (s, 3H); 13C NMR (CDCl3,
J¼8.4 Hz, 1H), 2.47 (s, 3H), 2.42 (s, 3H); 13C NMR (CDCl3, 100 MHz):
100 MHz):
d 164.61, 164.45, 142.18, 138.88, 132.39, 129.72, 128.90,
d
163.37, 148.93, 142.38, 141.85, 134.25, 129.59, 127.51, 125.95,
127.35, 126.83, 123.99, 123.84, 121.16, 21.61, 21.31.
124.58, 119.77, 109.82, 21.61, 21.51.
4.3.14. Compound 3n. 1H NMR (CDCl3, 400 MHz):
d 8.05 (d,
4.3.3. Compound 3c. 1H NMR (CDCl3, 400 MHz):
d
8.13 (d, J¼8.4 Hz,
J¼8.8 Hz, 2H), 8.00 (d, J¼8.0 Hz, 2H), 7.31 (d, J¼8.0 Hz, 2H), 7.01 (d,
2H), 7.63 (d, J¼8.4 Hz,1H), 7.38 (s,1H), 7.33 (d, J¼8.0 Hz, 2H), 7.17 (d,
J¼8.8 Hz, 2H), 3.87 (s, 3H), 2.42 (s, 3H); 13C NMR (CDCl3, 100 MHz):
J¼8.0 Hz, 1H), 2.51 (s, 3H), 2.45 (s, 3H); 13C NMR (CDCl3, 100 MHz):
d
164.23 (2C), 162.22, 141.98, 129.67, 128.59, 126.72, 121.28, 116.53,
d
162.73, 150.91, 141.64, 139.94, 135.17, 129.49, 127.35, 125.59,
114.43, 55.40, 21.57.
124.54, 119.09, 110.59, 21.68, 21.50.
4.3.15. Compound 3o. 1H NMR (CDCl3, 400 MHz):
d 8.07 (d,
4.3.4. Compound 3d. 1H NMR (CDCl3, 400 MHz):
d
8.15 (d,
J¼8.4 Hz, 2H), 8.01 (d, J¼8.0 Hz, 2H), 7.51 (d, J¼8.4 Hz, 2H), 7.34 (d,
J¼8.4 Hz, 2H), 7.80 (d, J¼1.6 Hz, 1H), 7.49 (d, J¼8.4 Hz, 1H),
J¼8.0 Hz, 2H), 2.45 (s, 3H); 13C NMR (CDCl3, 100 MHz):
d 164.89,
7.42e7.40 (m, 1H), 7.34 (d, J¼8.0 Hz, 2H), 2.45 (s, 3H), 1.41 (s, 9H);
163.53, 142.46, 137.87, 129.81, 129.44, 128.13, 126.91, 122.52, 120.96,
21.65.
13C NMR (CDCl3, 100 MHz):
d 163.32, 148.64, 147.89, 142.06,
141.68, 129.49, 127.40, 124.56, 122.45, 116.30, 109.50, 34.83, 31.70,
21.49.
4.3.16. Compound 3p. 1H NMR (CDCl3, 400 MHz):
d 8.05 (d,
J¼8.0 Hz, 1H), 7.97 (d, J¼8.4 Hz, 2H), 7.87 (d, J¼8.4 Hz, 1H),
4.3.5. Compound 3e. 1H NMR (CDCl3, 400 MHz):
d
8.12 (d, J¼8.0 Hz,
7.49e7.45 (m, 1H), 7.37e7.33 (m, 1H), 7.28 (d, J¼8.4 Hz, 2H), 2.41 (s,
2H), 7.73 (d, J¼2.0 Hz, 1H), 7.48 (d, J¼8.4 Hz, 1H), 7.34 (d, J¼8.0 Hz,
3H); 13C NMR (CDCl3, 100 MHz):
d 168.18, 154.17, 141.36, 134.94,
130.97, 129.67, 127.46, 126.19, 124.95, 123.03, 121.51, 21.46.
2H), 7.31 (dd, J¼2.0, 8.4 Hz, 1H), 2.45 (s, 3H); 13C NMR (CDCl3,
100 MHz):
d 164.61, 149.27, 143.35, 142.53, 129.91, 129.69, 127.71,
125.07, 123.93, 119.78, 111.14, 21.65.
4.3.17. Compound 3q. 1H NMR (CDCl3, 400 MHz):
d 8.81 (d,
J¼2.0 Hz, 1H), 8.35 (dd, J¼2.4, 8.8 Hz, 1H), 8.10 (d, J¼8.8 Hz, 1H),
8.00 (d, J¼8.4 Hz, 2H), 7.34 (d, J¼8.0 Hz, 2H), 2.46 (s, 3H); 13C NMR
4.3.6. Compound 3f. 1H NMR (CDCl3, 400 MHz):
d 8.10 (d,
J¼8.0 Hz, 2H), 7.64 (d, J¼8.4 Hz, 1H), 7.56 (d, J¼2.0 Hz, 1H),
(CDCl3, 100 MHz): d 173.92, 157.91, 144.72, 143.01, 135.18, 130.06,
7.33e7.31 (m, 3H), 2.43 (s, 3H); 13C NMR (CDCl3, 100 MHz):
129.96, 127.85, 123.03, 121.83, 118.12, 21.62.
d
163.95, 150.85, 142.40, 140.97, 130.38, 129.69, 127.61, 125.14,
123.93, 120.25, 111.12, 21.64.
4.3.18. Compound 3r. 1H NMR (CDCl3, 400 MHz):
d
7.81 (d, J¼8.0 Hz,
2H), 7.21 (d, J¼8.4 Hz, 2H), 6.81 (s, 1H), 2.49 (s, 3H), 2.37 (s, 3H); 13C
4.3.7. Compound 3g. 1H NMR (CDCl3, 400 MHz):
d
8.59 (d, J¼2.0 Hz,
NMR (CDCl3, 100 MHz): d 167.74, 153.58, 139.90, 131.15, 129.49,
1H), 8.28 (dd, J¼2.4, 8.8 Hz, 1H), 8.12 (d, J¼8.0 Hz, 2H), 7.64 (d,
126.33, 112.84, 21.31, 17.21. IR (KBr, cmꢁ1):
n 3021, 2954, 2922, 2854,
J¼8.8 Hz, 1H), 7.35 (d, J¼8.0 Hz, 2H), 2.46 (s, 3H); 13C NMR (CDCl3,
2370, 1518, 1456, 1309, 1242, 1003, 818, 711, 573. HRMS (EI) ([M]þ
100 MHz):
d
166.19, 154.19, 145.35, 143.39, 142.64, 129.82, 127.97,
H)þ calcd for C11H12NS: 190.0685, found: 190.0684.
123.14, 120.83, 115.98, 110.50, 21.68.
4.3.19. Compound 3s. 1H NMR (CDCl3, 400 MHz):
d 7.86 (d,
4.3.8. Compound 3h. 1H NMR (CDCl3, 400 MHz):
d
7.99 (d,
J¼8.0 Hz, 2H), 7.84 (d, J¼3.2 Hz, 1H), 7.28 (d, J¼3.2 Hz, 1H), 7.25 (d,
J¼8.0 Hz, 2H), 7.57 (br, s, 4H), 7.43 (s, 1H), 7.29 (d, J¼8.0 Hz, 2H),
J¼8.4 Hz, 2H), 2.39 (s, 3H); 13C NMR (CDCl3, 100 MHz):
d 168.61,
2.46 (s, 3H); 13C NMR (CDCl3, 100 MHz):
d
161.66, 149.95, 140.86,
143.49, 140.20, 130.98, 129.62, 126.49, 118.28, 21.37.
132.10, 129.56, 127.04, 126.31, 125.55, 124.56, 123.85, 122.13,
21.54.
4.3.20. Compound 3t. 1H NMR (CDCl3, 400 MHz):
d 7.75 (d,
J¼8.0 Hz, 2H), 7.19 (d, J¼8.0 Hz, 2H), 2.36 (br, s, 9H); 13C NMR
4.3.9. Compound 3i. 1H NMR (CDCl3, 400 MHz):
d
8.29 (d, J¼8.0 Hz,
(CDCl3, 100 MHz): d 163.53, 149.01, 139.41, 131.32, 129.42, 125.99,
125.88, 21.28, 14.76, 11.38.
2H), 8.00 (d, J¼8.0 Hz, 2H), 7.83 (d, J¼8.0 Hz, 2H), 7.61 (s, 1H), 7.31
(d, J¼8.0 Hz, 2H), 2.43 (s, 3H); 13C NMR (CDCl3, 100 MHz):
d 162.99,
148.77, 146.97, 141.59, 133.77, 129.67, 126.88, 126.57, 124.48, 124.28,
124.05, 21.59.
4.3.21. Compound 3u. 1H NMR (CDCl3, 400 MHz):
d 8.16 (s,1H), 7.90
(d, J¼8.0 Hz, 2H), 7.28 (m, J¼8.0 Hz, 2H), 3.99 (s, 3H), 2.41 (s, 3H);
13C NMR (CDCl3, 100 MHz):
d
169.19, 162.00, 147.54, 141.12, 130.11,
4.3.10. Compound 3j. 1H NMR (CDCl3, 400 MHz):
d
8.03 (d,
129.64, 126.90, 126.88, 52.44, 21.43.
J¼8.0 Hz, 2H), 7.82 (s, 1H), 7.28 (d, J¼8.0 Hz, 2H), 4.41 (q, J¼7.2 Hz,
2H), 2.41 (s, 3H), 2.37 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz):
4.3.22. Compound 4a. 1H NMR (CDCl3, 400 MHz):
d 8.29e8.27 (m,
d
164.41, 157.87, 142.09, 141.98, 135.27, 129.56, 127.15, 123.67, 61.30,
2H), 7.81e7.79 (m, 1H), 7.61e7.59 (m, 1H), 7.55e7.54 (m, 3H),
7.38e7.36 (m, 2H); 13C NMR (CDCl3, 100 MHz):
163.05, 150.78,
142.13, 131.51, 128.91, 127.63, 127.20, 125.10, 124.57, 120.03, 110.59.
21.52, 14.23.
d
4.3.11. Compound 3k. 1H NMR (CDCl3, 400 MHz):
d 8.16e8.14
(m, 2H), 8.04 (d, J¼8.0 Hz, 2H), 7.56e7.54 (m, 3H), 7.35
4.3.23. Compound 4b. 1H NMR (CDCl3, 400 MHz):
8.05 (d, J¼7.6 Hz, 1H), 7.78e7.76 (m, 1H), 7.59e7.57 (m, 1H),
d 8.10 (s, 1H),
(d, J¼8.0 Hz, 2H), 2.45 (s, 3H); 13C NMR (CDCl3, 100 MHz):

1930
M. Wang et al. / Tetrahedron 68 (2012) 1926e1930
7.43e7.39 (m, 1H), 7.36e7.34 (m, 3H), 2.46 (s, 3H); 13C NMR (CDCl3,
100 MHz): 163.25, 150.74, 142.11, 138.73, 132.35, 128.81, 128.19,
127.03, 125.01, 124.76, 124.52, 119.95, 110.54, 21.33.
4442e4489; (h) Coqueron, P. Y.; Didier, C.; Ciufolini, M. A. Angew. Chem., Int. Ed.
2003, 42, 1411e1414; (i) Okamoto, K.; Eger, B. T.; Nishino, T.; Kondo, S.; Pai, E. F.;
Nishino, T. J. Biol. Chem. 2003, 278, 1848e1855.
2. (a) Topics in Current Chemistry; Miyaura, N., Ed.Cross-Coupling Reactions: A
Practical Guide; Springer: Berlin, 2002; Vol. 219; (b) Metal-Catalyzed Cross-
Coupling Reactions, 2nd ed.; de Meijere, A., Diederich, F., Eds.; Wiley-VCH:
Weinheim, 2004.
3. For recent reviews, see: (a) Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc.
Rev. 2011, 40, 5068e5083; (b) Armstrong, A.; Collins, J. C. Angew. Chem., Int. Ed.
2010, 49, 2282e2285; (c) McGlacken, G. P.; Bateman, L. M. Chem. Soc. Rev. 2009,
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4. For arylation of azoles, see: (a) So, C. M.; Lau, C. P.; Kwong, F. Y. Chem.dEur. J.
2011, 17, 761e765; (b) Ranjit, S.; Liu, X. Chem.dEur. J. 2011, 17, 1105e1108; (c)
Liu, B.; Qin, X.; Li, K.; Li, X.; Guo, Q.; Lan, J.; You, J. Chem.dEur. J. 2010, 16,
11836e11839; (d) Hachiya, H.; Hirano, K.; Satoh, T.; Miura, M. Angew. Chem., Int.
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Commun. 2010, 2471e2473; (f) Yanagisawa, S.; Ueda, K.; Sekizawa, H.; Itami, K.
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Fagnou, K. J. Am. Chem. Soc. 2008, 130, 10848e10849; (h) Lewis, J. C.; Berman, A.
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d
4.3.24. Compound 4c. 1H NMR (CDCl3, 400 MHz):
d 8.18 (d,
J¼7.6 Hz, 1H), 7.81 (dd, J¼3.2, 6.0 Hz, 1H), 7.59 (dd, J¼3.6, 6.6 Hz,
1H), 7.44e7.40 (m, 1H), 7.37e7.35 (m, 4H), 2.82 (s, 3H); 13C NMR
(CDCl3, 100 MHz):
d 163.41, 150.30, 142.13, 138.84, 131.77, 130.88,
129.94, 126.25, 126.05, 124.99, 124.35, 120.13, 110.47, 22.18.
4.3.25. Compound 4d. 1H NMR (CDCl3, 400 MHz):
d 8.20 (d,
J¼8.4 Hz, 2H), 7.78 (dd, J¼3.6, 7.6 Hz,1H), 7.60e7.58 (m, 1H), 7.56 (d,
J¼8.4 Hz, 2H), 7.38e7.35 (m, 2H), 1.39 (s, 9H); 13C NMR (CDCl3,
100 MHz):
d 163.24, 155.13, 150.73, 142.22, 127.47, 125.91, 124.85,
124.46, 124.36, 119.87, 110.51, 35.07, 31.16.
4.3.26. Compound 4e. 1H NMR (CDCl3, 400 MHz):
d 8.21 (d,
5. Foralkylation of azoles, see:(a) Yao, T.; Hirano, K.; Satoh, T.;Miura, M. Chem.dEur. J.
2010, 16, 12307e12311; (b) Vechorkin, O.; Proust, V.; Hu, X. Angew. Chem., Int. Ed.
2010, 49, 3061e3064.
J¼8.8 Hz, 2H), 7.76e7.74 (m, 1H), 7.58e7.56 (m, 1H), 7.35e7.32 (m,
2H), 7.05 (d, J¼8.8 Hz, 2H), 3.91 (s, 3H); 13C NMR (CDCl3, 100 MHz):
6. For benzylation and allylation of azoles, see: (a) Zhao, X.; Wu, G.; Zhang, Y.;
Wang, J. J. Am. Chem. Soc. 2011, 133, 3296e3299; (b) Mukai, T.; Hirano, K.; Satoh,
d
163.18, 162.34, 150.69, 142.30, 129.39, 124.59, 124.41, 119.73,
119.63, 114.37, 110.37, 55.45.
€
T.; Miura, M. Org. Lett. 2010, 12, 1360e1363; (c) Ackermann, L.; Barfusser, S.;
Pospech, J. Org. Lett. 2010, 12, 724e726; (d) Lapointe, D.; Fagnou, K. Org. Lett.
2009, 11, 4160e4163.
4.3.27. Compound 4f. 1H NMR (CDCl3, 400 MHz):
d 8.29e8.25 (m,
7. For alkynylation of azoles, see: (a) Kim, S. H.; Yoon, J.; Chang, S. Org. Lett. 2011, 13,
2H), 7.79e7.77 (m, 1H), 7.60e7.58 (m, 1H), 7.38e7.36 (m, 2H),
ꢀ
1474e1477; (b) Berciano, B. P.; Lebrequier, S.; Besselievre, F.; Piguel, S. Org. Lett.
7.25e7.21 (m, 2H); 13C NMR (CDCl3, 100 MHz):
d
164.82 (d,
2010, 12, 4038e4041; (c) Kim, S. H.; Chang, S. Org. Lett. 2010, 12, 1868e1871; (d)
Kitahara, M.; Hirano, K.; Tsurugi, H.; Satoh, T.; Miura, M. Chem.dEur. J. 2010, 16,
1772e1775.
J¼251.3 Hz), 162.17, 150.79, 142.08, 129.84 (d, J¼8.8 Hz), 125.13,
124.66, 123.52 (d, J¼3.3 Hz), 119.99, 116.18 (d, J¼22.8 Hz), 110.56.
8. For amination and amidation of azoles, see: (a) Wang, J.; Hou, J.-T.; Wen, J.;
Zhang, J.; Yu, X.-Q. Chem. Commun. 2011, 3652e3654; (b) Guo, S.; Qian, B.; Xie,
Y.; Xia, C.; Huang, H. Org. Lett. 2011, 13, 522e525; (c) Kim, J. Y.; Cho, S. H.;
Joseph, J.; Chang, S. Angew. Chem., Int. Ed. 2010, 49, 9899e9903; (d) Kawano, T.;
Hirano, K.; Satoh, T.; Miura, M. J. Am. Chem. Soc. 2010, 132, 6900e6901; (e)
Matsuda, N.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2011, 13, 2860e2863; (f)
Wang, Q.; Schreiber, S. L. Org. Lett. 2009, 11, 5178e5180; (g) Monguchi, D.;
Fujiwara, T.; Furukawa, H.; Mori, A. Org. Lett. 2009, 11, 1607e1610.
4.3.28. Compound 4g. 1H NMR (CDCl3, 400 MHz):
d 8.21 (d,
J¼8.4 Hz, 2H), 7.79e7.77 (m, 1H), 7.60e7.58 (m, 1H), 7.52 (d,
J¼8.4 Hz, 2H), 7.40e7.36 (m, 2H); 13C NMR (CDCl3, 100 MHz):
d
162.07, 150.76, 142.02, 137.77, 129.27, 128.85, 125.68, 125.34,
124.74, 120.09, 110.62.
9. For carboxylation and cyanation of azoles, see: (a) Zhang, L.; Cheng, J.; Ohishi,
T.; Hou, Z. Angew. Chem., Int. Ed. 2010, 49, 8670e8673; (b) Boogaerts, I. I. F.;
Fortman, G. C.; Furst, M. R. L.; Cazin, C. S. J.; Nolan, S. P. Angew. Chem., Int. Ed.
2010, 49, 8674e8677; (c) Do, H.-Q.; Daugulis, O. Org. Lett. 2010, 12, 2517e2519.
10. For dehydrogenative cross-coupling of azoles, see: (a) Han, W.; Mayer, P.; Ofial, A.
R. Angew. Chem., Int. Ed. 2011, 50, 2178e2182; (b) Kitahara, M.; Umeda, N.; Hirano,
K.; Satoh, T.; Miura, M. J. Am. Chem. Soc. 2011, 133, 2160e2162; (c) Malakar, C. C.;
Schmidt, D.; Conrad, J.; Beifuss, U. Org. Lett. 2011, 13, 1378e1381; (d) Xi, P.; Yang,
F.; Qin, S.; Zhao, D.; Lan, J.; Gao, G.; Hu, C.; You, J. J. Am. Chem. Soc. 2010, 132,
1822e1824; (e) Do, H.-Q.; Daugulis, O. J. Am. Chem. Soc. 2009, 131, 17052e17053.
11. (a) Dubbaka, S. R.; Vogel, P. Angew. Chem., Int. Ed. 2005, 44, 7674e7684; (b)
Dubbaka, S. R.; Vogel, P. J. Am. Chem. Soc. 2003, 125, 15292e15293; (c) Dubbaka,
S. R.; Vogel, P. Org. Lett. 2004, 6, 95e98; (d) Dubbaka, S. R.; Vogel, P. Chem.dEur.
J. 2005, 11, 2633e2641; (e) Dubbaka, S. R.; Vogel, P. Adv. Synth. Catal. 2004, 346,
1793e1797; (f) Dubbaka, S. R.; Zhao, D. B.; Fei, Z. F.; Rao Volla, C. M.; Dyson, P. J.;
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4.3.29. Compound 4h. 1H NMR (CDCl3, 400 MHz):
d 8.13 (d,
J¼8.4 Hz, 2H), 7.79e7.77 (m, 1H), 7.68 (d, J¼8.4 Hz, 2H), 7.60e7.58
(m, 1H), 7.39e7.37 (m, 2H); 13C NMR (CDCl3, 100 MHz):
d
162.14,
150.76, 142.02, 132.24, 129.00, 126.23, 126.12, 125.39, 124.76, 120.12,
110.64.
4.3.30. Compound 4i. 1H NMR (CDCl3, 400 MHz):
J¼8.8 Hz, 2H), 7.81e7.78 (m, 3H), 7.61e7.59 (m, 1H), 7.44e7.38 (m,
2H); 13C NMR (CDCl3, 100 MHz):
160.83, 150.82, 141.80, 132.59,
d 8.33 (d,
d
131.03, 127.87, 126.10, 125.06, 120.50, 118.07, 114.66, 110.80.
Acknowledgements
12. Wang, G.-W.; Miao, T. Chem.dEur. J. 2011, 17, 5787e5790.
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14. (a) Varela-Alvavez, A.; Markovic, D.; Vogel, P.; Sordo, J. J. Am. Chem. Soc. 2009,
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This work was financially supported by the National Science
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Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2011.12.072. These data in-
clude MOL files and InChIKeys of the most important compounds
described in this article.
16. Zhou, X.-Y.; Luo, J.-Y.; Liu, J.; Peng, S.-M.; Deng, G.-J. Org. Lett. 2011, 13,
1432e1435.
References and notes
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