Pummerer reaction of sulfoxides in acetic anhydride catalyzed by Al-MCM-41

Article abstract of DOI:10.1246/cl.150896

The Pummerer reaction of acetic anhydride with both alkyl aryl sulfoxides and dialkyl sulfoxides was efficiently promoted by a mesoporous aluminosilicate Al-MCM-41 to afford the corresponding α-acetoxy sulfides in high yields. The catalyst was easily reco

Full text of DOI:10.1246/cl.150896

CL-150896
Received: September 25, 2015 | Accepted: October 14, 2015 | Web Released: October 22, 2015
Pummerer Reaction of Sulfoxides in Acetic Anhydride Catalyzed by Al-MCM-41
Suguru Ito,*1,2 Yoshihiro Kubota,1 and Masatoshi Asami*1
1Department of Advanced Materials Chemistry, Graduate School of Engineering, Yokohama National University,
79-5 Tokiwadai, Hodogaya-ku, Yokohama, Kanagawa 240-8501
2Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences,
Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore
(E-mail: m-asami@ynu.ac.jp)
The Pummerer reaction of acetic anhydride with both alkyl
aryl sulfoxides and dialkyl sulfoxides was efficiently promoted
by a mesoporous aluminosilicate Al-MCM-41 to afford the
corresponding α-acetoxy sulfides in high yields. The catalyst
was easily recovered by filtration and could be reused three
times without a significant loss of catalytic activity.
Table 1. Pummerer reaction of sulfoxide 1a
Specific surface
Entry
Catalyst (Si/Al)
area (BET)
Yield/%a
¹1
/m2 g
The Pummerer reaction involves the reaction of a nucleo-
phile with a sulfonium ion generated from a sulfoxide to afford
the corresponding α-substituted sulfide.1 Many kinds of inter-
and intramolecular Pummerer reactions have been developed,
and the reaction is now recognized as a powerful tool for
constructing the skeleton of natural products and biologically
active compounds.1,2 In many cases, acetic anhydride is used
to activate a sulfoxide in the Pummerer reaction.3 Typically,
the reaction is performed under reflux in acetic anhydride, and
the addition of several reagents such as sodium acetate,3a,3b
trifluoroacetic anhydride,3c or p-toluenesulfonic acid3d,3e is
effective to reduce side reactions and improve the yields.
However, there has been no report on the Pummerer reaction of
acetic anhydride with sulfoxides catalyzed by heterogeneous
catalysts to the best of our knowledge. The development of the
environmentally benign heterogeneous catalytic systems has
become one of the most important themes in current organic
chemistry.4 Recently, aluminum-incorporated MCM-41 (Al-
MCM-41) was reported as an attractive heterogeneous solid
acid catalyst for several organic reactions because of their large
uniform pores (2-10 nm) and high surface areas.5 Although
the catalytic activities of Al-MCM-41 are often comparable to
that of amorphous silica-alumina,5a,5b it has been shown that
Al-MCM-41 expresses much higher catalytic activities than
amorphous silica-alumina.5c-5f However, the reported examples
were limited to the reaction using silyl nucleophiles for the
formation of carbon-carbon bond. Herein, we wish to report the
remarkable catalytic activities of Al-MCM-41 in the Pummerer
reaction to form a new carbon-oxygen bond.
Initially, Al-MCM-41 (Si/Al = 23) was synthesized by the
known procedure with a slight modification,6,7 and the catalytic
activity of Al-MCM-41 was examined in the reaction of acetic
anhydride with ethoxycarbonylmethyl phenyl sulfoxide (1a).8 In
the presence of Al-MCM-41 (100 mg mmol¹1), dried with a
heating gun in vacuo prior to use, 1a in acetic anhydride was
stirred at 60 °C for 2 h. The catalyst was filtered off and the filtrate
was evaporated to afford almost pure α-acetoxy sulfide 2a. After
silica-gel column chromatography, 2a was isolated in 95% yield
(Table 1, Entry 1).9 Although the Pummerer reaction sometimes
proceed by heating without any catalyst,1a the reaction did not
take place at the same reaction conditions without Al-MCM-41
1
2
Al-MCM-41 (23)
none
SiO2-Al2O3 (31)
MCM-41 (¹)
Al-MCM-41 (23)
1032
®
>95 (95)b
0
6
<5
>95
3c
4
385
1080
1032
5d
aDetermined by 1H NMR analysis of the crude product using
bromoform as an internal standard. bIsolated yield. cSiO2-Al2O3
(270 mg mmol¹1). dAl-MCM-41 (30 mg mmol¹1); reaction time was
8 h.
Table 2. Reuse of Al-MCM-41 in the reaction of acetic
anhydride with 1aa
Al-MCM-41
/mg
1a
/mmol
Time
/h
Run
Yield/%b
1
2
3
4
100
75
53
1.0
2
2
2
3
95
96
91
88
0.75
0.53
0.27
27
aIn the presence of Al-MCM-41 (100 mg mmol¹1), 1a in Ac2O (0.2 M)
was stirred at 60 °C. Isolated yield.
b
(Entry 2). The reaction was then examined by using a higher
amount (270 mg mmol¹1) of amorphous silica-alumina (SiO2-
Al2O3, Si/Al = 31) to unify the surface areas of Al-MCM-41
and SiO2-Al2O3. However, 2a was obtained only in 6% yield
(Entry 3). Furthermore, aluminum-free MCM-41 also gave the
product in poor yield (Entry 4). These results suggest that high
catalytic activity of Al-MCM-41 is achieved by the presence of
both mesoporous structure and aluminum moiety in the catalyst,
as was observed in the cases of Al-MCM-41-catalyzed reaction
of silyl nucleophiles.5c-5f The use of a lower amount of Al-MCM-
41 (30 mg mmol¹1) also afforded 2a quantitatively, although the
reaction required 8 h to complete (Entry 5).11
Next, the recovery and reuse of Al-MCM-41 were tested in
the reaction of acetic anhydride with 1a (Table 2).12 The catalyst
was recovered by filtration after the reaction. The recovered
catalyst was then dried at 60 °C for 15 min, and treated in the
same manner as the first run. As shown in Table 2, the catalyst
could be reused three times, although the catalytic activity was
slightly decreased after repeated use of the catalyst.
16 | Chem. Lett. 2016, 45, 16–18 | doi:10.1246/cl.150896
© 2016 The Chemical Society of Japan

Table 3. Pummerer reaction of acetic anhydride with various
sulfoxides catalyzed by Al-MCM-41
Table 4. Intramolecular Pummerer reaction catalyzed by Al-
MCM-41a
Time
/h
Yield
/%b
Entry
1
Sulfoxide
Product
Time
/h
Yield
/%a
Entry
R1
R2
2
2
3
8
96
95
73
96
1
2
Ph
Ph
Ph
Ph
Ph
Ph
CN
PhCO
4-BrC6H4CO
4-MeC6H4CO
4-MeOC6H4CO
Ac
PhCO
PhCO
PhCO
H
H
Ph
Ph
PhCO
PhCO
CO2Et
2
1
1
1
1
0.5
1
1
96
95
88
91
85
91
88
92
89
21
91
<10
13
82
94
95
3b
4
5
6
7
8
2
3
4
4-BrC6H4
4-MeC6H4
4-MeOC6H4
Ph
Ph
Ph
Ph
Me
Bn
Bn
9
1
10
11c
12
13c
14
15b
16
12
12
12
10
1
0.5
1
b
c
aIsolated yield. Ac2O (0.1 M). Reaction was carried out at 100 °C.
aReaction conditions: sulfoxide (0.2 mmol), Ac2O (1 mL), Al-MCM-41
b
(20 mg, Si/Al = 26), 60 °C (Entries 1-3) or 80 °C (Entry 4). Isolated
yield.
derivatives 7a-7c in good to high yields (Entries 1-3). 2-
Carboxybenzyl phenyl sulfoxide (8) reacted at 80 °C for 8 h to
afford 3-phenylthiophthalide (9) in 96% yield (Entry 4).
In conclusion, Al-MCM-41 was found to be a useful
heterogeneous catalyst for inter- and intramolecular Pummerer
reactions of various sulfoxides. The catalytic activity of Al-
MCM-41 was superior to that of amorphous silica-alumina or
aluminum-free MCM-41 for the reaction of acetic anhydride
with 1a. We assume that the higher catalytic activity of Al-
MCM-41 over amorphous silica-alumina is due to the concen-
tration effect of hydrophobic mesopores, which enables a more
efficient interaction between the organic substrate and the inner
surface of the catalyst.5d The catalyst was easily recovered by
filtration and could be reused at least three times.
Scheme 1. Al-MCM-41-catalyzed Pummerer reaction of 3.
The scope of Al-MCM-41-catalyzed α-acetoxylation of
various sulfoxides was then investigated (Table 3). Alkyl phenyl
sulfoxides containing electron-withdrawing groups at the α-
position of sulfoxide reacted quickly to give the corresponding
α-acetoxy sulfides in good yields within 2 h (Entries 1-9). It is
noted that the desired α-acetoxy sulfides were obtained from β-
keto sulfoxides in this solid acid-catalyzed reaction (Entries 2-9)
in contrast with the sodium acetate-promoted Pummerer reac-
tion, which affords the thioester of α-acetoxy carboxylic acid
from β-keto sulfoxides via α-acetoxy sulfides.3b The reaction of
methyl phenyl sulfoxide was sluggish at 60 °C, but the desired
product was obtained in high yield (91%) by stirring at 100 °C
for 12 h (Entries 10 and 11). The reaction of benzyl phenyl
sulfoxide was also sluggish, and the yield could not be improved
by the decomposition of the product at higher temperatures
(Entries 12 and 13). When dialkyl sulfoxides were used, the
reaction took place regioselectively at the α-carbon with
electron-withdrawing groups (Entries 14-16). In the case of α-
disubstituted sulfoxide 3, α-acetoxy sulfide 4 was obtained in
51% yield along with α,β-unsaturated sulfide 5 (26% yield),
whereas it was reported that 5 was the major product when
methanesulfonic acid was used in the reaction of 3 with acetic
anhydride (Scheme 1).3f
The authors are grateful to Prof. Koichi Narasaka for
valuable discussion on this chemistry. Y.K. thanks New Energy
and Industrial Technology Development Organization (NEDO)
for financial support.
Supporting Information is available on http://dx.doi.org/
10.1246/cl.150896.
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60 °C gave the corresponding 4H-benzo[d][1,3]oxathiin-4-one
Chem. Lett. 2016, 45, 16–18 | doi:10.1246/cl.150896
© 2016 The Chemical Society of Japan | 17

2
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9
In the previous paper, the amount of active sites of Al-
MCM-41 (30 mg) was evaluated to be <0.005 mmol by the
poisoning experiment using triethylamine.10 Therefore, the
active site of Al-MCM-41 (100 mg) should be <0.017 mmol,
and the current reaction is the catalytic reaction.
10 S. Ito, A. Hayashi, H. Komai, H. Yamaguchi, Y. Kubota, M.
Asami, Tetrahedron 2011, 67, 2081.
11 The use of a stoichiometric amount of Ac2O (2.0 equiv) in
toluene required harsh reaction conditions (100 °C, 17 h) to
give the product in good yield (76%).
12 Typical experimental procedure: Under an atmosphere of
nitrogen, a mixture of Al-MCM-41 (100 mg, dried prior to
use with heating gun under vacuum) and ethoxycarbonyl-
methyl phenyl sulfoxide (1a) (0.213 g, 1.0 mmol) in acetic
anhydride (5.0 mL) was stirred at 60 °C for 2 h. The catalyst
was filtered off and washed with dichloromethane (50 mL).
After the combined organic solution was concentrated under
reduced pressure, crude product was purified by silica-gel
column chromatography (hexane/Et2O = 10:1) to afford
ethyl 2-acetoxy-2-(phenylthio)acetate (2a) as a colorless oil
(0.242 g, 95%). The recovered catalyst was dried at 60 °C
for 15 min. The catalyst (75 mg) was then dried with heating
gun under vacuum and used in a second run. 2a: IR (neat):
4
5
6
7
8
C.-Y. Chen, H.-X. Li, M. E. Davis, Microporous Mater.
1993, 2, 17.
¯max 2981, 1748, 1474, 1441, 1371, 1325, 1258, 1209, 1042,
950, 910, 748, 692 cm
¹1
;
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The specific surface area (BET) and the average pore
7.57-7.52 (m, 2H), 7.38-7.31 (m, 3H), 6.19 (s, 1H), 4.13
(q, J = 7.3 Hz, 2H), 2.19 (s, 3H), 1.19 (t, J = 7.3 Hz, 3H);
13C NMR (100 MHz, CDCl3): ¤ 169.6, 165.8, 134.1, 129.9,
129.1, 129.0, 76.6, 62.0, 20.7, 13.9. HRMS (ESI) found:
255.0691, calcd for C12H15O4S [M + H]+ 255.0691.
¹1
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18 | Chem. Lett. 2016, 45, 16–18 | doi:10.1246/cl.150896
© 2016 The Chemical Society of Japan