Molecular-iodine-catalyzed aerobic oxidative synthesis of β-hydroxy sulfones from alkenes

Article abstract of DOI:10.1039/c3ra47863g

The synthesis of β-hydroxy sulfones from alkenes and sodium sulfinates under aerobic oxidative conditions was achieved in the presence of a catalytic amount of molecular iodine. Molecular oxygen in air serves as the terminal oxidant and the catalytic amount of molecular iodine acts as the sulfonyl radical initiator and peroxide reductant. This journal is the Partner Organisations 2014.

Full text of DOI:10.1039/c3ra47863g

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Molecular-iodine-catalyzed aerobic oxidative
synthesis of b-hydroxy sulfones from alkenes†
Cite this: RSC Adv., 2014, 4, 13191
Atsumasa Kariya,a Tomoaki Yamaguchi,a Tomoya Nobuta,a Norihiro Tada,a
b
a
*
Tsuyoshi Miura and Akichika Itoh
Received 21st December 2013
Accepted 26th February 2014
DOI: 10.1039/c3ra47863g
www.rsc.org/advances
The synthesis of b-hydroxy sulfones from alkenes and sodium sulfi-
On the other hand, we have developed various oxidation
nates under aerobic oxidative conditions was achieved in the presence methods using catalytic iodine sources and molecular oxygen as
of a catalytic amount of molecular iodine. Molecular oxygen in air the terminal oxidant under visible light irradiation.8 Molecular
serves as the terminal oxidant and the catalytic amount of molecular
iodine acts as the sulfonyl radical initiator and peroxide reductant.
Table 1 Optimization of reaction conditions for the aerobic oxidative
synthesis of b-hydroxy sulfonesa
Sulfur-containing compounds have been used in numerous
applications including as medicines, agrochemicals, dyes, and
semiconductors. Thus, construction of the C–S bond is impor-
tant, and many C–S-bond-forming reactions have been devel-
oped to date.1 In particular, b-hydroxy sulfones are not only one
of the most important structural motifs in bioactive compounds2
but also key reaction intermediates in organic synthesis.3 In
general, b-hydroxy sulfones are prepared via the nucleophilic
addition of sulnates to epoxides,4 the reduction of b-oxo-
sulfones,5 or the hydroxylation of a,b-unsaturated sulfones.6 In
addition, the oxysulfonylation of alkenes, which are easy to
handle and inexpensive substrates, using sulfonyl chloride or
sulfonylhydrazide as sulfone sources has been reported.7
Entry Iodine source Additive
Solvent (mL)
3aab (%)
1
I2
—
MeCN (1)
MeCN (1)
MeCN (1)
MeCN (1)
13
0
2
38
59
66
2
3
4
I2
I2
I2
Et3N
K2CO3
AcOH
5
I2
TsOH$H2O MeCN (1)
6
7
8
9
I2
I2
I2
I2
I2
I2
I2
I2
NIS
Nal
Mgl2
Cal2
Cl4
I2
I2
I2
—
I2
TFA
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
MeCN (1)
Hexane/AcOH (1/0.25) 60
CHCl3/AcOH (1/0.25)
EtOAc/AcOH (1/0.25)
THF/AcOH (1/0.25)
MeOH/AcOH (1/0.25)
AcOH (1.25)
MeCN/AcOH (1/0.25)
MeCN/AcOH (1/0.25)
MeCN/AcOH (1/0.25)
MeCN/AcOH (1/0.25)
MeCN/AcOH (1/0.25)
MeCN/AcOH (1/0.25)
MeCN/AcOH (1/0.4)
MeCN/AcOH (1/0.4)
MeCN/AcOH (1/0.4)
MeCN/AcOH (1/0.4)
MeCN/AcOH (1/0.4)
70
72
77
79
56
85
65
70
60
74
60
91
67
88 (93)
0
10
11
12
13
14
15
16
17
18
19
20c
21d
22d
23d,e
Scheme 1 Aerobic oxidative synthesis of b-hydroxy sulfones from
alkenes using a catalytic amount of molecular iodine.
aGifu Pharmaceutical University 1-25-4, Daigaku-nishi, Gifu 501-1196, Japan. E-mail:
itoha@gifu-pu.ac.jp
bTokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo
192-0392, Japan
37
† Electronic supplementary information (ESI) available: General procedure: a
solution of styrene (1a, 0.3 mmol), sodium benzenesulnate (2a, 2 equiv.) and
iodine (0.1 equiv.) in MeCN/AcOH (1 mL/0.4 mL) in a pyrex test tube was stirred
under air for 20 h. The reaction mixture was washed with aq. Na2S2O3 and
concentrated in vacuo. Purication of the crude product by a silica gel column
(hexane : EtOAc ¼ 3 : 1) provided 1-phenyl-2-(phenylsulfonyl)ethanol (3aa) (Rf ¼
0.29, 73.2 mg, 93%). See DOI: 10.1039/c3ra47863g
a
Reaction conditions: 1a (0.3 mmol), 2a (2 equiv.), iodine source (0.1
equiv.) and additive (1 equiv.) in solvent was stirred and irradiated
externally with a uorescent lamp for 20 h. b 1H NMR yields. Number
c
in parenthesis is isolated yield. The reaction was carried out in the
d
dark. The reaction was carried out without positive irradiation from
uorescent lamp. e The reaction was carried out under argon.
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oxygen is photosynthesized by plants and is an effective oxidant sulfone (3aa) was obtained in low yield (entry 1). Addition of
with atom efficiency higher than that of other oxidants such as protic acids, such as acetic acid, p-toluenesulfonic acid, and
toxic heavy metals and complex organic reagents. Through our triuoroacetic acid, provided increased yields of 3aa (entries 2–
study of aerobic photo-oxidation with iodine sources, we 6). Thus, the solvent and iodine source were investigated using
discovered the oxysulfonylation of alkenes. During the course of acetic acid as a cosolvent (entries 7–19), and the highest yield of
our present study, Lei and co-workers reported impressive 3aa was obtained using MeCN/AcOH (1 mL/0.4 mL) as the
results for the aerobic oxysulfonylation of alkenes using sulnic solvent and I2 as the catalyst (entry 19). Next, the necessity of
acids.9 However, this reaction requires sulnic acids, which are visible light irradiation was examined, and the reaction was
air sensitive, as well as a stoichiometric amount of triphenyl- found to be depressed in the dark (entry 20). On the other hand,
phosphine as the reductant. Herein, we report the synthesis of the reaction proceeded in high yield, even without positive
b-hydroxy sulfones from alkenes and sodium sulnates, which irradiation of visible light (entry 21). In addition, without an
are readily available and easily handled, using a catalytic iodine source and molecular oxygen, lower yields were obtained
amount of molecular iodine and molecular oxygen from air (entries 22 and 23).
(Scheme 1).
Next, the scope and limitations of the reaction of various
Table 1 shows the results of the optimization of the reaction alkenes (1) and aryl sulnates (2) under the optimized reaction
conditions. Styrene (1a) was chosen as the test substrate and conditions were investigated, and the results are presented in
reacted with sodium benzenesulnate (2a) in the model reac- Table 2. In general, b-hydroxy sulfones were obtained in good to
tion. When iodine was used as the catalyst and acetonitrile as high yields, regardless of the electron-donating or -withdrawing
the solvent under visible light irradiation conditions, hydroxy group on the aromatic ring of the styrene substrate (entries 1–7).
Table 2 Scope and limitations for the aerobic oxidative synthesis of b-hydroxy sulfonesa
Entry
1
Product
Yieldb (%)
93 (79)c
Entry
7
Product
Yieldb (%)
61d
2
3
4
5
80
72
87
86
8
94
79e
0f
9
10
11
91
6
93
12
93
a
Reaction conditions: 1 (0.3 mmol), 2 (2 equiv.), and I2 (0.1 equiv.) in MeCN/AcOH (1 mL/0.4 mL) was stirred for 20 h. b Isolated yields. c Styrene (1a:
10 mmol, 1.04 g), PhSO2Na (2a: 2 equiv.), I2 (0.1 equiv.), MeCN/AcOH (30 mL/14 mL) was stirred for 72 h. d The reaction was carried out for 72 h.
e
f
The reaction was carried out for 48 h. trans-(2-Iodocyclohexyl)sulfonylbenzene (22%) was obtained.
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In addition, a gram-scale reaction was carried out under the
optimized conditions, and the desired product was obtained in
good yield (entry 1). A longer reaction time was required for the
reaction of 4-methoxystyrene (1 g) because light absorption was
interrupted by 3ga, which is less soluble in the solvent (entry 7).
Furthermore, sterically hindered o-methylstyrene and a disub-
stituted styrene were good substrates (entries 8 and 9) for the
reaction. On the other hand, cyclohexene was a poor substrate,
and trans-(2-iodocyclohexyl)sulfonylbenzene was obtained in
just 22% yield (entry 10). Finally, sulnates other than sodium
benzenesulnate, including sodium 4-methylbenzenesulnate
and sodium 4-chlorobenzenesulnate, were suitable and
provided the desired products in high yields (entries 11 and 12).
To resolve the reaction mechanism, several control experi-
ments were then examined. Without quenching with aq.
Na2S2O3, b-hydroxy sulfone 3aa was detected in 72% yield, and
no b-hydroperoxysulfone 3aa0 was detected in the 1H NMR
spectrum (Scheme 2, eqn (1)). When 2,2,6,6-tetramethylpiper-
idine 1-oxyl (TEMPO) was added as a radical scavenger,
however, the reaction did not proceed (Scheme 2, eqn (2)). On
the other hand, when triethylborane instead of iodine was used
as radical initiator, the reaction proceed (Scheme 2, eqn (3)).
These results indicating that a radical mechanism is involved.
The b-iodo sulfone 4 was eliminated as a possible intermediate
when its reaction under the optimized conditions resulted in its
recovery (67% yield) and the formation of 3aa and 5 in low yield
(Scheme 2, eqn (4)).10
Scheme
3
Proposed reaction pathway for the aerobic oxidative
synthesis of b-hydroxy sulfones.
Conclusions
In conclusion, we reported the synthesis of b-hydroxy sulfones
from alkenes using molecular oxygen and molecular iodine.
This novel reaction is interesting because it uses a catalytic
amount of molecular iodine and molecular oxygen from the air
as the terminal oxidant without light irradiation.
A plausible reaction path for this oxidation, postulated on
the basis of all of the above mentioned results, is presented
in Scheme 3. A sulfone radical is generated from sodium
sulnate and molecular iodine via sulfonyl iodide 7 upon
exposure to light in the presence of acetic acid.10 This sulfone
radical adds to the substrate 1 to give benzyl radical species 9,
which traps molecular oxygen and is converted to peroxy
radical 10 and then hydroperoxide 30. Hydroperoxide 30 is
subsequently reduced to the b-hydroxy sulfone 3 by an iodide
species, such as sodium iodide, and the hypoiodite is
regenerated. Hypoiodite also serves as sulfone radical initi-
ator via sulfonyl iodide 7.
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