First palladium-catalyzed denitrated coupling of nitroarenes with sulfinates

Article abstract of DOI:10.1016/j.tet.2014.09.087

The first example of palladium-catalyzed protocol for the denitrated coupling of nitroarenes with sulfinates was developed, achieving aryl and heterocyclic sulfones in moderate to excellent yields. The cyclopalladated ferrocenylimine (I) exhibited highly catalytic activity for this transformation with low catalyst loading (0.75 mol %). The efficiency of this reaction was demonstrated by compatibility with a wide range of groups. Thus, the method represents a simple and facile procedure to access aryl and heterocyclic sulfones.

Full text of DOI:10.1016/j.tet.2014.09.087

Tetrahedron 70 (2014) 9107e9112
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Tetrahedron
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First palladium-catalyzed denitrated coupling of nitroarenes with
sulfinates
*
*
Heng Tian, Aijuan Cao, Lijun Qiao, Ajuan Yu , Junbiao Chang, Yangjie Wu
The College of Chemistry and Molecular Engineering, Key Laboratory of Chemical Biology and Organic Chemistry of Henan, Zhengzhou University,
Zhengzhou 450052, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 10 August 2014
Received in revised form 18 September 2014
Accepted 29 September 2014
Available online 5 October 2014
The first example of palladium-catalyzed protocol for the denitrated coupling of nitroarenes with sul-
finates was developed, achieving aryl and heterocyclic sulfones in moderate to excellent yields. The
cyclopalladated ferrocenylimine (I) exhibited highly catalytic activity for this transformation with low
catalyst loading (0.75 mol %). The efficiency of this reaction was demonstrated by compatibility with
a wide range of groups. Thus, the method represents a simple and facile procedure to access aryl and
heterocyclic sulfones.
Keywords:
Cyclopalladated ferrocenylimines
Catalysis
Ó 2014 Elsevier Ltd. All rights reserved.
Denitrated
Nitroarene
Sulfinate
1. Introduction
Traditional methods for the preparation of these compounds
involve the oxidation of the corresponding sulfides, the sulfonyla-
Aryl sulfones and derivatives thereof, are ubiquitous structural
motifs that frequently occur in synthetic intermediates and phar-
macologically active compounds.1e3 For example, they have been
shown to possess antifungal, antibacterial, antitumor activities or
to inhibit HIV-1 reverse transcriptase (Fig. 1).4
tion of arenes,5 the reaction of organomagnesium halides or orga-
nolithium compounds with sulfonate esters,6 and the copper-
mediated displacement reaction of nonactivated aryl iodides with
arenesulfinates.7 However, these methods suffer from drawbacks
(e.g., limited substrates scope, often low yields, inferior tolerance of
functional groups and use of stoichiometric amounts copper) as
a result of limited application. Thus, the development of new
methods for the preparation of aryl sulfones and derivatives under
relatively mild reaction conditions has received much attention.
Recently, some improved methods have been reported for con-
structing aryl sulfones and derivatives in the presence of copper,
palladium and nickel catalytic systems (Scheme 1).8 Also metal-free
protocols have attracted considerable attention.9 Generally, aryl
halides or arylboronic acids are employed as coupling partners.
However, some shortcomings appear with them. For example, aryl
halides are not always easily available, which often involves tedious
steps, harsh reaction conditions, and waste production.10 Electron-
withdrawing arylboronic acids, which are less nucleophilic, and
hence transmetalate slowly, are prone to homocoupling and pro-
todeboronation side reactions.11 Thus, an alternative coupling
partner to aryl halide or arylboronic acid is still an extremely at-
tractive yet challenging goal.
OH
O
O
O
S
S
O
H2N
NH2
HO
Dapsone antibacterial
FabH inhibitors
Cl
O
O
S
HN
H2NOC
NO2
NPPS
S
O
O
IAS
Fig. 1. Examples of important biologically active sulfones.
Very recently, we have developed palladacycle-catalyzed (Fig. 2)
denitrated coupling reactions of nitroarenes with arylboronic acids
and phenols.12 As a continuation of our interest in the development
* Corresponding authors. E-mail address: yuajuan@zzu.edu.cn (A. Yu).
http://dx.doi.org/10.1016/j.tet.2014.09.087
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

9108
Previous work
H. Tian et al. / Tetrahedron 70 (2014) 9107e9112
Table 1
Optimization of reaction conditionsa
O
S
O
O O
S
Cp'Mo(CO)3Cl
[Pd]
Base, Solvent
Reflux, N2, 12 h
S
OHC
NO2
SO2Na
OHC
R1
R2
R1
R2
H2O2/NCMe or TBHP/CH2Cl2, rt
3aa
1a
2a
Entry
Catalyst
Base
Solvent
Yield (%)b
Zn or Ni*
ArSO2Cl
ArX
RX
ArSO2R
1c
2d
3
Pd(OAc)2
PdCl2
Palladacycle (I)
Palladacycle (II)
Palladacycle (III)
d
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
K3PO4
Cs2CO3
Et3N
NaOH
Quinoline
t-BuONa
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Toluene
Dioxane
DMF
38
26
88
84
73
0
79
73
63
40
0
X=Halogen
4e
5f
O O
S
Cu cat or Pd cat
Ar'SO2Na
Ar
Ar'
6
7
8
9
X=Br, I, OTf, B(OH)2
Palladacycle (I)
Palladacycle (I)
Palladacycle (I)
Palladacycle (I)
Palladacycle (I)
Palladacycle (I)
Palladacycle (I)
Palladacycle (I)
Palladacycle (I)
Palladacycle (I)
Palladacycle (I)
Palladacycle (I)
Palladacycle (I)
Palladacycle (I)
Palladacycle (I)
This work
10
11
12
13
14
15
16
17
18
19
20g
21h
O O
S
Palladacycle
base,solvent
16
0
0
ArNO2
Ar'SO2Na
Ar
Ar'
Scheme 1. Synthesis of sulfones.
0
75
51
0
0
0
DMAC
NMP
H2O
DMSO/H2O
DMSO
N
Pd
N
Fe
N
N
N
88
Pd Cl
Pd
Fe
Fe
Cl
a
PCy3
2
Unless otherwise noted, the reaction conditions were as follows: 4-
nitrobenzaldehyde (0.3 mmol), sodium p-toluenesulfinate (2 equiv), palladacycle
(I) (1 mol %), base (1 equiv) and solvent (2 mL), 12 h, 110 ꢀC, under N2.
III
I
II
b
Isolated yields.
Pd(OAc)2 (10 mol %).
PdCl2 (10 mol %).
Palladacycle (II) (1 mol %).
Palladacycle (III) (1 mol %).
DMSO (1 mL), H2O (1 mL).
Palladacycle (I) (0.75 mol %).
Fig. 2. Cyclopalladated ferrocenylimines.
c
d
e
f
of coupling of nitroarene with various coupling partners, herein we
describe a novel cyclopalladated ferrocenylimine-catalyzed deni-
trated coupling reaction of nitroarenes with sodium sulfinates,
affording aryl sulfones and derivatives in moderate to excellent
yields (Scheme 1).
g
h
as solvent achieved the best result (Table 1, entry 3 vs 14e19). Other
solvents, including DMF, DMAC, toluene, dioxane, NMP and H2O,
did not favor this reaction. Unfortunately, no desired product was
obtained when the reaction was carried out by employing H2O as
a cosolvent in addition to DMSO (1:1) (Table 1, entry 20). Further-
more, we were pleased to discover that the loading of palladacycle I
could be reduced to 0.75 mol % with no significant change in yield
(Table 1, entry 21).
2. Results and discussion
The coupling of p-nitrobenzaldehyde and sodium p-toluene-
sulfinate to give 4-(toluene-4-sulfonyl)-benzaldehyde 3aa was
chosen as a model reaction for initial reaction evaluation and
subsequent optimization studies. To realize the selective generation
of 3aa, we initially ran a series of trial experiments in the presence
of copper salts as catalysts by adjust reaction parameters. However,
little or no product 3aa was detected. We next investigated the
model reaction using palladium catalysts. To our delight, when 1a
and 2a were reacted in the presence of 10 mol % Pd(OAc)2 as well as
Having the optimized reaction conditions in hand, we next in-
vestigated the scope and generality of the coupling reaction using
sodium p-toluenesulfinate (1a) with various nitroarenes and the
results were summarized in Table 2. Generally, nitroarenes con-
taining electron-withdrawing groups (e.g., formacyl, acetyl, ben-
zoyl and cyano) on the phenyl ring afforded the corresponding
products in moderated to excellent yields under the standard re-
action conditions (Table 2, entries 1, 2, 3, 5, 6 and 9). Also the results
demonstrated that the reaction was not significantly affected by the
steric effect of the nitroarenes (Table 2, entry 1 vs 5). For example,
the coupling of 1a with ortho- and para-nitroarenes proceeded
smoothly, affording the corresponding products 3aa, 3ae in 88%
and 87% yields, respectively. Intriguingly, the mono-coupling
product 3ad was selectively produced in 85% yield when 1,4-
dinitrobenzene was employed as a coupling partner (Table 2, en-
try 4). It would be specially mentioned that heterocyclic nitroarene,
such as 2-methyl-4-nitropyridine and 5-nitro-thiophene-2-
carbaldehyde are good partners for this coupling reaction, and
afforded the desired product in 90% and 68% yields (Table 2, entries
7e8). However, nucleophilic displacement of the chloro and bromo
groups with sodium p-toluenesulfinate was observed when 2j and
2k were used under the standard conditions, affording 1-methyl-4-
[(4-nitrophenyl)sulfonyl]-benzene in 83% and 88% yields, re-
spectively (Table 2, entries 10e11).
10 mol % PdCl2, employing K2CO3 as base and DMSO as solvent at
110 C under nitrogen, the denitrated product 3aa was isolated in
ꢀ
38% and 26% yields, respectively (Table 1, entries 1e2). We were
pleased to discover that only when the model reaction was per-
formed in the presence of the cyclopalladated ferrocenylimine (I)
did the yield dramatically increase to 88% yield (Table 1, entries
3e5). No denitration of p-nitrobenzaldehyde to aryl sulfone 3aa
was observed under the reaction conditions in the absence of cat-
alyst (Table 1, entry 6). Encouraged by this promising result, we
further adjusted reaction parameters including bases and solvents.
The various reaction conditions were examined by fixing
1 mol % loading of palladacycle I. Screening revealed that the use of
K2CO3 as base achieved the best result. Other bases, including
Cs2CO3, Et3N, NaOH, Quinoline, t-BuONa, Na2CO3 and K3PO4 were
less efficient (Table 1, entries 7e13). With these partially optimized
denitrated conditions, the effects of the solvents were investigated
(Table 1, entries 14e20). The solvent also played an important role
for this kind of reaction. The results revealed that the use of DMSO

H. Tian et al. / Tetrahedron 70 (2014) 9107e9112
9109
Table 2
Scope of the coupling reaction of sodium p-toluenesulfinate with nitroarenesa
O
S
O
Palladacycle I, K2CO3
R1NO2
SO2Na
R1
DMSO, N2, 110 o
C
1a
2
3
Entry
1
R1NO2 (2)
Product (3)
Yield (%)b
88
2
3
65c
81
Fig. 3. X-ray crystal structure of 3ab. CCDC 1008677 contains the supplementary
Crystallographic data for this paper.
Table 3
Scope of the coupling reaction of sodium sulfinates with p-nitrobenzaldehydea
4
5
85
87
Entry
1
R2SO2Na (1)
Product (3)
Yield (%)b
88
6
7
57
90
2
83
3
4
5
82
83
76
8
68
76
9
6
7
74
69
10
83
88
11
a
Unless otherwise noted, the reaction conditions were as follows:1a (0.6 mmol),
2 (0.3 mmol), palladacycle I (0.75 mol %), K2CO3 (1 equiv) and DMSO (2 mL), 12 h,
110 ꢀC, under N2.
8
48
b
Isolated yields.
Gram scale.
c
9
51
87
0
In support of the application of this method, we conducted the
reaction on a gram scale, and it also showed good performance
(Table 2, entry 2). The structure of 3ab was characterized by X-ray
diffraction (Fig. 3), which confirms that the coupling occurs via CeS
bond formation.8c
10
11
Next, we explored the effects of the coupling of p-nitro-
benzaldehyde (2a) with various sodium sulfinates (1) (Table 3). As
expected, the reactions proceeded smoothly and tolerated a wide
range of functional groups, including aryl and alkyl sodium sulfinates.
First, the mono-substituent positions at the aryl moiety of sodium
sulfinates such as methyl, fluoro, bromo, chloro, tert-butyl, methoxy
and trifluoromethyl were evaluated. The electronic properties of the
groups on the phenyl ring of sodium sulfinates had some effect on
the reaction. In general, sodium sulfinate bearing an electron-
donating substituent afforded better yield of aryl sulfone than that
with an electron-withdrawing group (Table 3, entries 1, 2, 4, 10 vs 3,
6, 7, 9). It was noteworthy that the fluoro, chloro and bromo moieties
12
0
a
Unless otherwise noted, the reaction conditions were as follows: 1 (0.6 mmol),
2a (0.3 mmol) palladacycle I (0.75 mol %), K2CO3 (1 equiv) and DMSO (2 mL), 12 h,
110 ꢀC, under N2.
b
Isolated yields.
(commonly used for cross-coupling reactions) in sodium sulfinates
(1c, 1f, and 1g) were all tolerated and afforded a novel route to

9110
H. Tian et al. / Tetrahedron 70 (2014) 9107e9112
compounds (3ca, 3fa, and 3ga) in excellent yields, making further
elaborations of the corresponding biaryl sulfones (Table 3, entries 3,
6e7). However, the results demonstrated that steric effects of sub-
stituents had significant effects on the reaction. For example, the
coupling of 2a with para- and ortho-chlorobenzenesulfinic acid so-
dium salt was examined (Table 3, entries 3, 11), 82% of 3ca was
isolated, while no product of 3ka was detected. The same phenom-
enon was observed in the reaction of 2a with 1a and 1l (Table 3,
entries 1, 12). More substrate such as 2-naphthylsulfinic acid sodium
salt also efficiently reacted with p-nitrobenzaldehyde and gave the
product in 76% yield (Table 3, entry 5). Moreover, ethyl-substituted
substrate 1h possessing the sluggish group, was also tolerated and
afforded the product 3ha in 48% yield (Table 3, entry 8).
In order to understand the reaction more clearly, some control
experiments were carried out under the standard conditions as
shown in Scheme 2. Reaction of 4-nitrotoluene with sodium p-
toluenesulfinate failed to deliver the desired product under the
same reaction conditions. However, the reaction of p-nitro-
benzaldehyde with sodium p-toluenesulfinate afforded the desired
product in 88% yield.
catalyzed denitrated coupling of nitroarenes with sodium sulfi-
nates. The reaction proceeds without the use of a large number of
metal catalysts and other additives, which make it significantly
greener than current alternatives. Ongoing work seeks to gain
further mechanistic studies on cross-coupling processes mediated
by palladacycle I and extend the applications of the transformation
in organic synthesis in our laboratory.
4. Experimental
4.1. General experimental details
1H NMR, 13C NMR spectra were recorded on a Bruker DPX-400
spectrometer with CDCl3 as the solvent and TMS as an internal
standard. Melting points were measured using a WC-1 microscopic
apparatus and are uncorrected. High-resolution mass spectra were
ensured on a MALDI-FTMS. GC analysis was performed on Agilent
4890D gas chromatograph. Ethyl acetate and petroleum ether
(analytical grade) were used for column chromatography without
further purification. Other solvents were purified according to the
standard methods.
O
S
O
Palladacycle I, K2CO3
NO2
SO2Na
DMSO, N2, 110 o
C
4.2. General procedure for the preparation of sodium
0% yield
sulfinates
O
S
O
Palladacycle I, K2CO3
DMSO, N2, 110 o
OHC
OHC
NO2
SO2Na
C
4-Methoxybenzenesulfinic acid sodium salt (1j) was prepared
by heating 2.5
88% yield
g
of sodium sulfite, 2.06
g
of 4-
Scheme 2. Control experiments.
methoxybenzenesulphonyl chloride, and 1.68 g of sodium bi-
carbonate in 9.6 mL of water at 70e80 ꢀC for 4 h. After cooling to
room temperature, water was removed under vacuum and the
residue was extracted by ethanol, recrystallization as a white solid,
the yield was 67% (1.34 g). Similarly, other sodium arenesulfinates
were prepared from their corresponding sulphonyl chlorides.
Therefore, a possible mechanism for the formation of the aryl
sulfone was proposed as shown in Scheme 3. First, the palladacycle
was pre-activated to form a. Addition of nitroarene formed aryl-
palladium species b. Next, sodium arylsulfinate c could be con-
verted to the sulfonylpalladium intermediate d by nucleophile
displacement of a nitro group. The reductive elimination of d gave
the aryl sulfone e and regenerated the palladium catalyst a.
4.3. General procedure for the first palladium-catalyzed de-
nitrated coupling of nitroarenes with aryl sulfinates
Under N2 atmosphere, a reaction vessel was charged with
a mixture of sodium sulfinates 1 (0.6 mmol), nitroarenes 2
(0.3 mmol), palladacycle I (0.75 mol %) and K2CO3 (1.0 equiv) in
DMSO (2 ml) at room temperature. After that, the mixture was
heated to 110 ꢀC and incubated in an oil bath for 12 h under N2
atmosphere. After the completion of the reaction, the reaction
mixture was diluted with ethyl acetate and washed with brine
three times. The combined organic solution was dried with Na2SO4,
filtered and evaporated under reduced pressure. The residue was
purified by thin-layer chromatography on silica gel GF 254 (ethyl
acetate/petroleum ether) to give the pure product.
Palladacycle
pre-activated
Ar1NO2
O
Pd(0)
a
O
e
Ar1PdNO2
b
4.3.1. 4-(Toluene-4-sulfonyl)-benzaldehyde (CAS: 113823-55-5,
3aa).8c 1H NMR (CDCl3, 400 MHz)
d
2.39 (s, 3H), 7.31 (d, J¼8.0 Hz,
2H), 7.83 (d, J¼8.1 Hz, 2H), 7.97 (d, J¼8.1 Hz, 2H), 8.07 (d, J¼8.1 Hz,
2H), 10.05 (s, 1H); 13C NMR (CDCl3, 100 MHz)
130.2, 130.3, 137.6, 139.0, 144.9, 147.1, 190.8.
d 21.6, 128.0, 128.2,
Ar2SO2Na
Ar1PdSO2Ar2
c
4.3.2. 1-[4-(Toluene-4-sulfonyl)-phenyl]-ethanone (CAS: 129644-41-
d
3, 3ab).8c 1H NMR (CDCl3, 400 MHz)
d 2.39 (s, 3H), 2.61 (s, 3H), 7.31
(d, J¼8.0 Hz, 2H), 7.83 (d, J¼8.2 Hz, 2H), 8.00e8.05 (m, 4H); 13C
Scheme 3. Plausible reaction mechanism.
NMR (CDCl3, 100 MHz)
d 21.7, 27.0, 127.9, 128.0, 129.1, 130.2, 137.9,
140.2, 144.9, 145.9, 196.8.
3. Conclusions
4.3.3. 4-(Toluene-4-sulfonyl)-benzonitrile (CAS: 38111-56-7, 3ac).8-
c
1H NMR (CDCl3, 400 MHz)
d
2.41 (s, 3H), 7.33 (d, J¼7.9 Hz, 2H),
We have developed a new protocol for the synthesis of aryl
sulfones in moderate to excellent yields from the palladacycle-
7.77 (d, J¼8.2 Hz, 2H), 7.83 (d, J¼8.0 Hz, 2H), 8.03 (d, J¼8.2 Hz, 2H);

H. Tian et al. / Tetrahedron 70 (2014) 9107e9112
9111
13C NMR (CDCl3, 100 MHz)
133.1, 137.1, 145.3, 146.3.
d
21.7, 116.7, 117.3, 128.1, 128.2, 130.3,
J¼8.5 Hz, 2H), 7.87 (d, J¼8.5 Hz, 2H), 7.99 (d, J¼8.3 Hz, 2H), 8.10 (d,
J¼8.3 Hz, 2H), 10.06 (s, 1H); 13C NMR (CDCl3, 100 MHz)
d 31.0, 35.3,
126.6, 127.8, 128.3, 130.3, 137.5, 139.0, 147.0, 157.9, 190.9; HRMS-ESI
(positive ESI): m/z calcd for C17H18O3S [MþH]þ: 303.1049, found:
303.1050.
4.3.4. 1-Methyl-4-[(4-nitrophenyl)sulfonyl]-benzene (CAS: 4094-37-
5, 3ad).8c 1H NMR (CDCl3, 400 MHz)
2.40 (s, 3H), 7.34 (d, J¼8.1 Hz,
d
2H), 7.84 (d, J¼8.3 Hz, 2H), 8.10 (d, J¼8.8 Hz, 2H), 8.31 (d, J¼8.8 Hz,
2H); 13C NMR (CDCl3, 100 MHz)
137.0, 145.4, 147.8, 150.2.
d
21.7, 124.5, 128.1, 128.8, 130.4,
4.3.14. 4-(Naphthalene-2-sulfonyl)-benzaldehyde (CAS: 194668-82-
1, 3ea). 1H NMR (CDCl3, 400 MHz)
d
7.60e7.68 (m, 2H), 7.84e7.89
(m, 2H), 7.94e8.00 (m, 4H), 8.16 (d, J¼8.3 Hz, 2H), 8.60 (s, 1H), 10.05
(s, 1H); 13C NMR (CDCl3, 100 MHz)
122.6, 127.9, 128.0, 128.4, 129.5,
4.3.5. 2-(Toluene-4-sulfonyl)-benzaldehyde (CAS: 171503-27-8,
3ae).7a 1H NMR (CDCl3, 400 MHz)
d
d
2.39 (s, 3H), 7.31 (d, J¼8.2 Hz,
129.6, 129.7, 130.0, 130.4, 132.2, 135.3, 137.3, 139.1, 146.7, 190.8.
2H), 7.68e7.77 (m, 4H), 7.99 (dd, J1¼3.4 Hz, J2¼4.8 Hz, 1H), 8.15 (dd,
J1¼3.2 Hz, J2¼4.3 Hz, 1H), 10.84 (s, 1H); 13C NMR (CDCl3, 100 MHz)
4.3.15. 4-(4-Bromo-benzenesulfonyl)-benzaldehyde (CAS: 96462-
d
21.6, 127.5, 129.3, 129.4, 130.3, 133.7, 133.8, 134.1, 138.4, 142.7,
90-7, 3fa). 1H NMR (CDCl3, 400 MHz)
d
7.67 (d, J¼8.5 Hz, 2H), 7.82
145.0, 189.5.
(d, J¼8.5 Hz, 2H), 8.01 (d, J¼8.3 Hz, 2H), 8.09 (d, J¼8.3 Hz, 2H), 10.08
(s, 1H); 13C NMR (CDCl3, 100 MHz)
139.3, 139.6, 146.2, 190.7.
d 128.4, 129.3, 129.5, 130.5, 132.9,
4.3.6. Phenyl-[4-(toluene-4-sulfonyl)-phenyl]-methanone
(CAS:
d 2.42 (s, 3H), 7.35
97807-46-0, 3af).13 1H NMR (CDCl3, 400 MHz)
(d, J¼8.0 Hz, 2H), 7.49 (t, J¼6.0 Hz, 2H), 7.62 (t, J¼7.5 Hz, 1H), 7.76 (d,
4.3.16. 4-(4-Fluoro-benzenesulfonyl)-benzaldehyde (CAS: 81326-26-
J¼7.4 Hz, 2H), 7.88 (d, J¼7.6 Hz, 4H), 8.05 (d, J¼8.2 Hz, 2H); 13C NMR
3, 3ga).16 1H NMR (CDCl3, 400 MHz)
d
7.22 (t, J¼9.3 Hz, 2H),
(CDCl3, 100 MHz)
d
21.7,127.5,128.0,128.6,130.2,130.5,133.3,136.4,
7.98e8.03 (m, 4H), 8.10 (d, J¼8.1 Hz, 2H), 10.08 (s, 1H); 13C NMR
137.9, 141.6, 144.8, 145.1, 145.8, 195.3.
(CDCl3, 100 MHz)
d
117.0 (d, J¼22.7 Hz), 128.3, 130.5, 130.8 (d,
J¼9.8 Hz), 136.7 (d, J¼2.6 Hz), 139.3, 146.5, 165.8 (d, J¼225.5 Hz),
4.3.7. 2-Methyl-4-(toluene-4-sulfonyl)-pyridine
(3ag). Mp:
190.7.
83.7e84.6 ꢀC; 1H NMR (CDCl3, 400 MHz)
d 2.36 (s, 3H), 2.59 (s, 3H),
7.31 (d, J¼8.0 Hz, 2H), 7.51 (d, J¼4.8 Hz, 1H), 7.60 (s, 1H),7.81 (d,
4.3.17. 4-Ethanesulfonyl-benzaldehyde
(CAS:
50899-03-1,
J¼8.1 Hz, 2H),8.64 (d, J¼5.0 Hz, 1H); 13C NMR (CDCl3, 100 MHz)
3ha).17 1H NMR (CDCl3, 400 MHz)
d
1.28 (t, J¼7.4 Hz, 3H), 3.15 (q,
d
21.6, 24.6, 117.6, 119.9, 128.1, 130.2, 136.8, 145.3, 150.3, 150.5, 160.6;
J¼7.5 Hz, 2H), 8.07 (s, 4H), 10.12 (s, 1H); 13C NMR (CDCl3, 100 MHz)
HRMS-ESI (positive ESI): m/z calcd for C13H13NO2S (MþH)þ:
d 7.3, 50.5, 129.1, 130.3, 139.7, 143.5, 190.8.
248.0740, found: 248.0741.
4.3.18. 4-(4-Trifluoromethyl-benzenesulfonyl)-benzaldehyde
(3ia). Mp: 126.3e127.9 ꢀC; 1H NMR (CDCl3, 400 MHz)
7.83 (d,
J¼8.0 Hz, 2H), 8.05 (d, J¼8.0 Hz, 2H), 8.14 (t, J¼7.6 Hz, 4H), 10.10 (s,
1H); 13C NMR (CDCl3, 100 MHz)
J¼3.6 Hz), 128.6, 128.7, 130.6, 135.6 (q, J¼33.0 Hz), 139.6, 144.2,
145.6, 190.6; HRMS-ESI (positive ESI): m/z calcd for C14H9F3O3S
[MþH]þ: 315.0297, found: 315.0299.
4.3.8. 5-(Toluene-4-sulfonyl)-thiophene-2-carbaldehyde
1498230-90-2, 3ah).9b 1H NMR (CDCl3, 400 MHz)
(CAS:
2.42 (s, 3H),
d
d
7.34 (d, J¼8.0 Hz, 2H), 7.66 (s, 1H), 7.70 (s,1H), 7.88 (d, J¼8.2 Hz, 2H),
d
123.0 (q, J¼273.1 Hz), 126.7 (q,
9.92 (s, 1H); 13C NMR (CDCl3, 100 MHz)
134.8, 137.7, 145.5, 148.9, 151.8, 182.9.
d
21.8, 127.9, 130.3, 132.6,
4.3.9. 2,4-Bis-(toluene-4-sulfonyl)-benzonitrile
154.6e155.3 ꢀC; 1H NMR (CDCl3, 400 MHz)
(3ai). Mp:
d
2.44 (s, 6H), 7.38 (dd,
4.3.19. 4-(4-Methoxy-benzenesulfonyl)-benzaldehyde (CAS: 477256-
J1¼1.9 Hz, J2¼4.0 Hz, 4H), 7.87 (d, J¼8.3 Hz, 2H), 7.96 (t, J¼0.7 Hz,
37-4, 3ja).18 1H NMR (CDCl3, 400 MHz)
d 3.88 (s, 3H), 7.01 (d,
3H), 8.21 (dd, J1¼2.0 Hz, J2¼3.8 Hz, 1H), 8.81 (d, J¼1.7 Hz, 1H); 13C
J¼8.9 Hz, 2H), 7.90 (d, J¼8.9 Hz, 2H), 8.00 (d, J¼8.3 Hz, 2H), 8.11 (d,
NMR (CDCl3, 100 MHz)
d
21.6, 21.7, 114.5, 114.9, 128.1, 128.2, 128.9,
J¼8.3 Hz, 2H), 10.08 (s, 1H); 13C NMR (CDCl3, 100 MHz)
d 55.8, 114.8,
130.3, 130.6, 131.7, 135.4, 136.1, 136.6, 145.7, 146.0, 146.2, 147.1;
HRMS-ESI (positive ESI): m/z calcd for C21H17NO4S2 [MþH]þ:
412.0672, found: 412.0673.
128.0, 130.2, 130.3, 131.9, 138.9, 147.5, 163.9, 190.9.
Acknowledgements
4.3.10. 1-Methyl-4-[(4-nitrophenyl)sulfonyl]-benzene (CAS: 4094-
We are grateful to the National Natural Science Foundation of
China (21205107, 21172202, 21172200) and Postdoctoral Scholar-
ship of China (2012M511592) for financial support of this research.
37-5, 3aj, 3ak).8c 1H NMR (CDCl3, 400 MHz)
d 2.40 (s, 3H), 7.34 (d,
J¼8.1 Hz, 2H), 7.84 (d, J¼8.2 Hz, 2H), 8.10 (d, J¼8.7 Hz, 2H), 8.32 (d,
J¼8.7 Hz, 2H); 13C NMR (CDCl3, 100 MHz)
d 21.7, 124.5, 128.1, 128.8,
130.4, 137.0, 145.4, 147.8, 150.3.
Supplementary data
4.3.11. 4-Benzenesulfonyl-benzaldehyde (CAS: 66-39-7, 3ba).14 1H
NMR (CDCl3, 400 MHz)
7.38 (t, J¼7.6 Hz, 2H), 7.45 (t, J¼8.6 Hz, 1H),
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2014.09.087.
d
7.79 (d, J¼7.6 Hz, 2H), 7.86 (d, J¼8.4 Hz, 2H), 7.94 (d, J¼8.3 Hz, 2H),
9.90 (s, 1H); 13C NMR (CDCl3, 100 MHz)
133.6, 138.8, 140.1, 146.1, 190.6.
d 127.5, 127.9, 129.3, 130.0,
References and notes
1. (a) Patai, S.; Rappoport, Z.; Stirling, C. J. M. The Chemistry of Sulphones and
Sulphoxides; John Wiley: New York, NY, 1988, 3, p 56; (b) Otzen, T.; Wempe, E.
G.; Kunz, B.; Bartels, R.; Lehwark-Yvetot, G.; Hansel, W.; Schaper, K. J.; Seydel, J.
K. J. Med. Chem. 2004, 47, 240; (c) Harrak, Y.; Casula, G.; Basset, J.; Rosell, G.;
Plescia, S.; Raffa, D.; Cusimano, M. G.; Pouplana, R.; Pujol, M. D. J. Med. Chem.
2010, 53, 6560; (d) Carreno, M. C. Chem. Rev. 1995, 95, 1717; (e) Fernandez, I.;
Khiar, N. Chem. Rev. 2003, 103, 3651; (f) Wojaczynska, E.; Wojaczynski, J. Chem.
Rev. 2010, 110, 4303.
4.3.12. 4-(4-Chloro-benzenesulfonyl)-benzaldehyde (CAS: 77422-24-
3, 3ca).15 1H NMR (CDCl3, 400 MHz)
7.50 (d, J¼8.6 Hz, 2H), 7.89 (d,
d
J¼8.6 Hz, 2H), 8.00 (d, J¼8.4 Hz, 2H), 8.08 (d, J¼8.3 Hz, 2H), 10.07 (s,
1H); 13C NMR (CDCl3, 100 MHz)
139.3, 140.7, 146.2, 190.7.
d 128.4, 129.4, 129.9, 130.5, 139.1,
2. (a) Fumio, H.; Mitsuru, K. JP Patent 61271271, 1986; Chem. Abstr. 1987, 106,
213572; (b) Keiichi, S.; Toru, O.; Aki, S. JP Patent 04120050, 1992; Chem. Abstr.
1992, 117, 150703; (c) Mitchell, M.; Tomida, A. M.; Padias, A. B.; Hall, H. K.;
4.3.13. 4-(4-tert-Butyl-benzenesulfonyl)-benzaldehyde (3da). Mp:
125.5e125.9 ꢀC; 1H NMR (CDCl3, 400 MHz)
1.29 (s, 9H), 7.53 (d,
d

9112
H. Tian et al. / Tetrahedron 70 (2014) 9107e9112
Lackritz, H. S.; Robello, D. R.; Willand, C. S.; Williams, D. J. Chem. Mater. 1993, 5,
1044; (d) Toshiaki, T.; Takeshi, Y. JP Patent 2001260544, 2001; Chem. Abstr.
2001, 135, 264604.
8. (a) Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. M. Synlett 2003, 361; (b)
Beaulieu, C.; Guay, D.; Wang, Z. Y.; Evans, D. A. Tetrahedron Lett. 2004, 45, 3233;
(c) Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. M.; Bernini, R. J. Org. Chem.
2004, 69, 5608; (d) Huang, F.; Batey, R. A. Tetrahedron 2007, 63, 7667; (e) Yuan,
Y. Q.; Guo, S. R. Synlett 2011, 2750; (f) Xie, M. H.; Wang, J. L.; Gu, X. X.; Sun, Y.;
Wang, S. W. Org. Lett. 2006, 8, 431.
9. (a) Xiao, F. H.; Chen, H.; Xie, H.; Chen, S. Q.; Yang, L.; Deng, G. J. Org. Lett. 2014,
16, 50; (b) Liang, S.; Zhang, R. Y.; Xi, L. Y.; Chen, S. Y.; Yu, X. Q. J. Org. Chem. 2013,
78, 11874; (c) Katrun, P.; Mueangkaew, C.; Pohmakotr, M.; Reutrakul, V.; Jai-
petch, T.; Soorukram, D.; Kuhakarn, C. J. Org. Chem. 2014, 79, 1778; (d) Maloney,
K. M.; Kuethe, J. T.; Linn, K. Org. Lett. 2011, 13, 102; (e) Liang, S.; Zhang, R. Y.;
Wang, G.; Chen, S. Y.; Yu, X. Q. Eur. J. Org. Chem. 2013, 7050; (f) Yu, B.; Liu, A. H.;
He, L. N.; Li, B.; Diao, Z. F.; Li, Y. N. Green. Chem. 2012, 14, 957; (g) Gomez, M. V.;
Caballero, R.; Vazquez, E.; Moreno, A.; Hoz, A. D. L.; Ortiz, A. D. Green. Chem.
2007, 9, 331.
3. Simpkins, N. S. Sulfones in Organic Synthesis; Pergamon: Oxford, UK, 1993.
4. (a) Neamati, N.; Mazumder, A.; Zhao, H.; Sunder, S.; Burke, T. R.; Schultz, R. J.;
Pommier, Y. Antimicrob. Agents Chemother. 1997, 41, 385; (b) Artico, M.; Silvestri,
R.; Massa, S.; Loi, A. G.; Corrias, S.; Piras, G.; Colla, L. P. J. Med. Chem. 1996, 39,
522; (c) Silvestri, R.; Martino, G. D.; Regina, G. L.; Artico, M.; Massa, S.; Vargiu,
L.; Mura, M.; Loi, A. G.; Marceddu, T.; Colla, P. L. J. Med. Chem. 2003, 46, 2482; (d)
Williams, T. M.; Ciccarone, T. M.; MacTough, S. C.; Rooney, C. S.; Balani, S. K.;
Condra, J. K.; Emini, E. A.; Goldman, M. E.; Greenlee, W. J.; Kauffman, L. R.;
O’Brien, J. A.; Sardana, V. V.; Schleif, W. A.; Theoharides, A. D.; Anderson, P. A. J.
Med. Chem. 1993, 36, 1291; (e) McMahon, J. B.; Gulakowski, R. J.; Weislow, O. S.;
Schultz, R. J.; Narayanan, V. L.; Clanton, D. J.; Pedemonte, R.; Wassmundt, F. W.;
Buckheit, R. W.; Decker, W. D. Antimicrob. Agents Chemother. 1993, 37, 754; (f)
Santo, R. D.; Costi, R.; Artico, M.; Ragno, R.; Lavecchia, A.; Novellino, E.; Gav-
uzzo, E.; Torre, F. L.; Cirilli, R.; Cancio, R.; Maga, G. Chem. Med. Chem. 2006, 1, 82;
(g) Lopez de Compadre, R. L.; Pearlstein, R. A.; Hopfinger, A. J.; Seyde, J. K. J. Med.
Chem. 1987, 30, 900.
10. Hodgson, H. H. Chem. Rev. 1947, 40, 251.
11. Barder, T. E.; Walker, S. D.; Martinelli, J. R.; Buchwald, S. L. J. Am. Chem. Soc. 2005,
127, 4685.
12. (a) Peng, D. P.; Yu, A. J.; Wang, H. L.; Wu, Y. J.; Chang, J. B. Tetrahedron 2013, 69,
6884; (b) Wang, H. L.; Yu, A. J.; Cao, A. J.; Chang, J. B.; Wu, Y. J. Appl. Organomet.
Chem. 2013, 27, 611.
13. Russell, G. A.; Dedolph, D. J. Org. Chem. 1985, 50, 3878.
14. Ulman, A.; Urankar, E. J. Org. Chem. 1989, 54, 4691.
15. Marzabadi, M. R. U.S. Pat. Appl. Publ. 20060079683, 13 Apr 2006.
16. Mavrodin, A. An. Real Acad. Farm. 1985, 51, 401.
17. Wynne, G. M. PCT Int. Appl. 2009121623, 08 Oct 2009.
18. Sakurai, M. PCT Int. Appl. 2002094770, 28 Nov 2002.
5. (a) Graybill, B. M. J. Org. Chem. 1967, 32, 2931; (b) Ueda, M.; Uchiyama, K.; Kano,
T. Synthesis 1984, 323; (c) Umierski, N.; Manolikakes, G. Org. Lett. 2013, 15, 188;
(d) Yao, B.; Zhang, Y. Tetrahedron Lett. 2008, 49, 5385; (e) Jin, T.; Yang, M.; Feng,
G.; Li, T. Chin. J. Org. Chem. 2003, 23, 1438; (f) Gamelas, C. A.; Lourenc¸ o, T.; Costa,
~
A. P. D.; Simplício, A. L.; Royo, B.; Romao, C. C. Tetrahedron Lett. 2008, 49, 4708.
6. (a) Deeming, A. S.; Russell, C. J.; Hennessy, A. J.; Willis, M. C. Org. Lett. 2014, 16,
150; (b) Gilman, H.; Beaber, N. J.; Myers, C. H. J. Am. Chem. Soc. 1925, 47, 2047.
7. (a) Suzuki, H.; Abe, H. Tetrahedron Lett. 1995, 36, 6239; (b) Baskin, J. M.; Wang,
Z. Y. Org. Lett. 2002, 4, 4423.