Selective aerobic oxidation of sulfides to sulfoxides catalyzed by coenzyme NAD+ models

Article abstract of DOI:10.1016/j.tet.2010.09.076

Coenzyme NAD⁺ models can be applied in the photooxygenation of sulfides to sulfoxides as organocatalysts at room temperature. A series of sulfoxides are synthesized easily with this protocol and the possible mechanism is discussed. This procedure provides a reliable approach to the clean production of useful sulfoxides in synthetic chemistry.

Full text of DOI:10.1016/j.tet.2010.09.076

Tetrahedron 66 (2010) 8823e8827
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Selective aerobic oxidation of sulfides to sulfoxides catalyzed by coenzyme
NADþ models
,
b
,
a
a
a
a,b,
*
Hua-Jian Xu a , Yi-Cheng Lin , Xin Wan , Chun-Yan Yang , Yi-Si Feng
*
a School of Chemical Engineering, Hefei University of Technology, Tunxi Road 193, Hefei 230009, PR China
b Anhui Key Laboratory of Controllable Chemical Reaction & Material Chemical Engineering, Hefei 230009, PR China
a r t i c l e i n f o
a b s t r a c t
Coenzyme NADþ models can be applied in the photooxygenation of sulfides to sulfoxides as organo-
catalysts at room temperature. A series of sulfoxides are synthesized easily with this protocol and the
possible mechanism is discussed. This procedure provides a reliable approach to the clean production of
useful sulfoxides in synthetic chemistry.
Article history:
Received 4 August 2010
Received in revised form 18 September 2010
Accepted 21 September 2010
Available online 24 September 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
development of more efficient, general, clean and catalytic aerobic
oxidation of sulfides under mild reaction conditions remains
a challenging task.
The coenzyme NADþ and its reduced form NADH play vital roles
in biological oxidation-reduction processes.1 NADþ models have
been successfully applied to selective oxygenation of
a-methyl-
2. Results and discussion
styrene,2 benzyl alcohol,3 p-xylene,4 4,40-dimethylbiphenyl,5 tet-
raphenylethylene,6 and 1,4-dihydropyridines7 as effective catalysts.
Owing to our interest in the reactions and mechanisms of co-
enzyme NADþ/NADH models,8 we envisioned that NADþ models
might be utilized in the oxidation of sulfides with O2. Herein we
wish to report an efficient, environmentally benign protocol in
which O2 has been used as the oxidant at room temperature in the
presence of NADþ models for the selective oxidation of sulfides.
Selective oxidation of sulfides to sulfoxides is an important
transformation in organic chemistry because organic sulfoxides
often perform a major function as therapeutic agents, such as anti-
ulcer (proton pump inhibitor),9 antibacterial, antifungal, anti-ath-
erosclerotic,10 antihypertensive,11 and cardiotonic agents,12 as well
as psychotonics13 and vasodilators.14 In addition, sulfoxides are
valuable synthons in synthetic organic chemistry for carbone
carbon bond formation15 and mediating DielseAlder reactions,16 as
chiral auxiliaries17 and metal-centered catalysis.18
A number of methods have been developed for the trans-
formation of sulfides to sulfoxides. Sulfoxides were obtained mainly
from the oxidation of sulfides with peroxides in most synthetic
protocols.19 However, as we known, oxygen, a cheap and clean
oxidant, can oxidize organic compounds with a high atom efficiency
without disposal of waste.20 Although some transformations of
sulfides to sulfoxides oxidated by oxygen were reported,21 but, the
Initially, we performed a set of preliminary experiments on the
oxidation of diphenyl sulfide 3 as a model substrate using 30%
aqueous hydrogen peroxide and molecular oxygen irradiated with
a 450 W high-pressure mercury lamp in the presence of catalytic
amounts of NADþ models at room temperature under different
solvent conditions. The results are depicted in Table 1.
In order to find the ideal catalyst, we evaluated the catalytic
activity of NADþ models 1 and 2 on the oxidation of 3 with O2 and
H2O2 or O2,22 no obvious difference on yield was observed in the
same conditions (Table 1, entries 1, 2 and 15, 16). It is well known
that the synthetic procedure of 2 is more inconvenient than 1, so 1
was selected as the catalyst in following research. Next, the reaction
was carried out in MeCN (Table 1, entries 3e6) using 5 mol % of
catalyst 1 and 4 from 17 to 53% yield was obtained after 48 h. In-
terestingly, a less amount of H2O2 could produce a higher.
Yield of 4. A 72% and 19% yield of 4 was obtained, respectively,
without H2O2 in the presence of O2 and with H2O2 in the absence of
O2 (Table 1, entries 7 and 8). Solvents also played important roles in
this reaction. The experimental results suggested that MeCN was
the best solvent among the screened ones, such as MeOH, CHCl3,
and AcOH (Table 1, entries 10e12). To our delight, when the amount
of MeCN was increased gradually, the yield of 4 was improved
synchronously (Table 1, entries 13e15) and a 99% yield of 4 was
obtained until the volume of MeCN was added to 12 mL.23
Only a slight decrease of yield of 4 was observed when the
amount of catalyst 1 was reduced to 3 mol % (Table 1, entry 17). It is
noteworthy that almost no reaction was observed under similar
* Corresponding authors. Tel.: þ86 551 2904405; fax: þ86 551 2901450; e-mail
address: hjxu@hfut.edu.cn (H.-J. Xu).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.09.076

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H.-J. Xu et al. / Tetrahedron 66 (2010) 8823e8827
Table 1
substituted diphenyl sulfides were determined and all results were
Optimization of reaction conditions for oxidation of 3
summarized in Scheme 2 and Scheme 3. As shown in Scheme 2,
good to excellent yield (80e97%) of corresponding sulfoxides
(14e30) were obtained when the substituents of phenyl ring
are methyl, fluoro, and chloro groups. Importantly, the reaction
does not appear to be significantly affected by steric effectsof
ortho-position substituent in the present procedure (17, 22e26,
30). However, the corresponding sulfoxides yields were decreased
dramatically passing from 4-methyl to 4-CO2Et, eCOMe, eNO2
(Scheme 3, 31e35). Clearly, the reactivity of the sulfide is strongly
reduced when the electron-withdrawing group (EWG) is directly
bonded to the phenyl ring. Low yields of 32e35 were gained except
that the moderate yield of 31 was observed. Low yields (35e46%)
were still obtained even though amount of 1 is added to 10 mol %
and MeCN is added to 20 mL.
Entry Catalyst (mol %) H2O2 (equiv) Solvent (mL) Time (h) Yielda (%)
1
1 (5)
2 (5)
1 (5)
1 (5)
1 (5)
1 (5)
1 (5)
1 (5)
1 (5)
1 (5)
1 (5)
1 (5)
1 (5)
1 (5)
1 (5)
2 (5)
1 (3)
d
1
MeCN (5)
MeCN (5)
MeCN (5)
MeCN (5)
MeCN (5)
MeCN (5)
MeCN (5)
MeCN (5)
MeCN (5)
MeOH (5)
CHCl3 (5)
AcOH(5)
24
24
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
20
18
45
17
51
53
72
19
d
2
1
3
1
4
2
5
6
7
0.5
0.25
d
1
d
d
d
d
d
d
d
d
d
d
8b
9b
10
11
12
13
14
15
16
17
18
61
48
65
86
94
99
95
90
d
MeCN (8)
MeCN (10)
MeCN (12)
MeCN (12)
MeCN (12)
MeCN (12)
Bold value ‘99’ is the highest yield.
a
GC yield.
Without addition of O2.
b
reaction conditions in the absence of O2 or 1 in two control ex-
periments (Table 1, entries 9 and 18). Therefore, the optimized
conditions employed 5 mol % 1 in MeCN at room temperature with
O2 under irradiation of a 450 W high-pressure mercury lamp.
To examine the reliability of this protocol, some of the alkyl
phenyl sulfides were screened under optimized reaction conditions
(Scheme 1). Excellent yields of corresponding products 5e13 were
obtained as the previous documented methods. So, this protocol
can be applied in the preparation of sulfoxides. It is always difficult
for selective oxygenation from diaryl sulfides to diarylsulfoxides in
documented methods. We wonder whether the selective oxygen-
ation can be achieved under our developed protocol. A series of
Scheme 2. The oxygenation of diaryl sulfides with methyl or halogen substituents.
aReaction time is reduced to 12 h.
Scheme 3. The oxygenation of diaryl sulfides with EWGs. aAmount of 1 is added to
10 mol %, MeCN is added to 20 mL.
We next examined the catalytic efficiency of NADþ/O2 system in
the oxidation of aryl disulfides. When the catalyst (7.5 mol %) was
employed, a selective oxygenation was also readily achieved upon
the control of equivalents of MeCN (20 mL). The corresponding
disulfoxides were produced in good yields (73e78%) with excellent
selectivity (Scheme 4).
It should be noted that sulfides can be oxygenated to the cor-
responding sulfoxides almost without over-oxidation products in
our protocol compared with other documented reaction systems.
Scheme 1. The oxygenation of alkyl phenyl sulfides.

H.-J. Xu et al. / Tetrahedron 66 (2010) 8823e8827
8825
selective, efficient, and green process for the selective oxygenation
of sulfides into corresponding sulfoxides using an organocatalyst. It
provides a reliable approach for the clean production of sulfoxides
in synthetic chemistry.
4. Experimental
4.1. General remarks
Diphenyl sulfide is obtained from Tokyo Chemical Industry Co.,
Ltd. Sulfides,26 catalyst 1 and 25 were prepared by literature pro-
cedures. Other reagents and solvents were pure analytical grade
materials purchased from commercial sources and were purified
according to the standard procedure before use. The 1H and 13C NMR
spectra were recorded in CDCl3 on a 300 MHz instrument with TMS
as internal standard. High-resolution mass spectra (HRMS) were
determined on a Micromass GCT-MS mass spectrometer. TLC was
carried out with 0.2 mm thick silica gel plates (GF254). The columns
were hand packed with silica gel 60 (200e300).
4.2. General reaction procedure
Scheme 4. The oxygenation of aryl disulfides.
A stirred solution of the sulfide (0.5 mmol) and the catalyst 1
(5 mol %) in acetonitrile (12 mL) was added to a 25 mL round-
bottom Pyrex flask sealed with a rubber septum was irradiated with
a 450 W high-pressure mercury lamp under an argon atmosphere
at room temperature. The irradiated solution was monitored by
TLC. After completion of the reaction, the resulted solution was
concentrated under reduced pressure and the residue followed by
column chromatography on silica gel using petroleum ether and
ethyl acetate (5:1) as eluent afforded the corresponding sulfoxide.
Unfortunately, some substituted diphenyl sulfides with EDG as
hydroxyl and amino couldn’t go well by virtue of this protocol,
because they are all strong radical inhibitors, which affect dra-
matically the reactivity.23
On the basis of these observations and by reference to the liter-
atures,24 a plausible mechanism could be drawn for the 1-catalyzed
ꢀ
photooxygenation of sulfides as shown in Scheme 5. R1R2Sþ is
produced by an electron transfer from lone pair electron of sulfur
atom of R1R2S to 1
, and it reacts with O2 to yield R1R2SOþ2 ꢀ followed
*
by an electron transfer to result in the regeneration of 1 and the
formation of R1R2SþOOꢁ, which reacts with additional R1R2S to yield
R1R2SO.25 Since the initial electron transfer is rate-determining,
electronic spin density of the sulfur atom will be the most important
factor for photooxidation of diaryl sulfides with O2. Thus Me-
substituted (EDG) diphenyl sulfides gave excellent yields, while NO2-
substituted (EWG) diphenyl sulfides could hardly be oxygenated.
4.2.1. Compound 427 1H NMR (300 MHz, CDCl3):
. d 7.66e7.63 (m,
5H), 7.46e7.44 (m, 5H) ppm. 13C NMR (75 MHz, CDCl3):
d 145.70,
131.11, 129.38, 124.83 ppm.
4.2.2. Compound 528 1H NMR (300 MHz, CDCl3):
. d 7.59e7.57 (m,
2H), 7.51e7.50 (m, 3H), 2.84 (m, 1H), 1.23 (d, J¼6.8 Hz, 3H), 1.14 (d,
J¼6.7 Hz, 3H) ppm. 13C NMR (75 MHz, CDCl3):
d 141.94, 131.03,
128.94, 125.08, 54.66, 15.95, 13.99 ppm.
4.2.3. Compound 629 1H NMR (300 MHz, CDCl3):
. d 7.48 (d,
J¼8.2 Hz, 2H), 7.30 (d, J¼4.6 Hz, 2H), 2.82e2.78 (m, 1H), 2.41 (s, 3H),
1.20e1.13 (m, 6H) ppm. 13C NMR (75 MHz, CDCl3):
d 141.44, 138.53,
129.62, 125.08, 54.56, 21.43, 15.77, 14.12 ppm.
4.2.4. Compound 7. 1H NMR (300 MHz, CDCl3):
d 7.54e7.46 (m, 4H),
2.80 (m, 1H), 1.22 (d, J¼6.9 Hz, 3H), 1.12 (d, J¼6.8 Hz, 3H) ppm. 13C
NMR (75 MHz, CDCl3): d 140.51, 137.29, 129.29, 126.49, 54.78, 15.86,
13.89 ppm. HRMS calcd C9H11ClOS: 202.0219. Found: 202.0211.
4.2.5. Compound 8. 1H NMR (300 MHz, CDCl3):
d
7.64e7.61 (m, 2H),
7.55e7.48 (m, 3H), 2.78 (m, 2H), 1.72e1.24 (m, 20H), 0.87 (t,
J¼6.7 Hz, 3H) ppm. 13C NMR (75 MHz, CDCl3):
d 144.18, 130.96,
129.25, 124.12, 57.45, 29.66, 29.57, 29.40, 29.23, 28.75, 22.75, 22.25,
14.18 ppm. HRMS calcd C18H30OS: 294.2017. Found: 294.2011.
4.2.6. Compound 9. 1H NMR (300 MHz, CDCl3):
d
7.90 (d, J¼7.1 Hz,
Scheme 5. The proposed mechanism for oxidation of sulfides to the corresponding
sulfoxides with O2 catalyzed by 1.
1H), 7.45e7.34 (m, 2H), 7.20 (d, J¼7.3 Hz, 1H), 2.72e2.66 (m, 2H),
2.37 (s, 3H),1.83e1.25 (m, 20H), 0.88 (t, J¼6.7 Hz, 3H) ppm. 13C NMR
3. Conclusion
(75 MHz, CDCl3):
d 142.69, 134.43, 130.68, 127.25, 123.98, 55.82,
31.98, 29.80e28.93, 28.79, 22.66, 18.29, 14.18 ppm. HRMS calcd
In conclusion, the present procedure demonstrates that sulfides
can be oxidized by O2 under mild conditions with the catalysis of
NADþ models. Moderate to excellent yields were obtained. Thus we
have developed a metal-free and simple protocol, which is a highly
C19H32OS: 308.2174. Found: 308.2178.
4.2.7. Compound 10. 1H NMR (300 MHz, CDCl3):
4H), 2.77 (t, J¼7.7 Hz, 2H), 1.74e1.25 (m, 20H), 0.88 (t, J¼6.7 Hz,
d 7.58e7.48 (m,

8826
H.-J. Xu et al. / Tetrahedron 66 (2010) 8823e8827
3H) ppm. 13C NMR (75 MHz, CDCl3):
d
142.66, 137.27, 129.61, 125.65,
d
143.38, 142.18, 141.15, 134.51, 131.93, 129.97, 126.14, 125.59,
57.48, 34.08, 32.00, 29.49, 28.75, 24.94, 22.78, 22.14, 14.20 ppm.
HRMS calcd C18H29ClOS: 328.1628. Found: 328.1620.
21.49 ppm. HRMS calcd C13H11ClOS: 250.0219. Found: 250.0211.
4.2.20. Compound 23. 1H NMR (300 MHz, CDCl3):
d 7.94 (d,
4.2.8. Compound 1130
.
1H NMR (300 MHz, CDCl3):
d
7.64e7.54 (m,
J¼6.2 Hz, 1H), 7.43e7.16 (m, 7H), 2.36 (s, 6H) ppm. 13C NMR
2H), 7.53e7.49 (m, 3H), 2.81e2.75 (m, 2H), 1.74e1.24 (m, 12H),
(75 MHz, CDCl3): d 144.42, 143.04, 139.55, 135.80, 131.99, 130.96,
0.85 (t, J¼5.2 Hz, 3H) ppm. 13C NMR (75 MHz, CDCl3):
d
142.16,
129.10, 127.14, 126.17, 124.75, 123.06, 21.42, 18.64 ppm. HRMS calcd
C14H14OS: 230.0765. Found: 230.0771.
137.27, 129.61, 125.65, 57.48, 29.69, 29.42, 28.75, 22.78, 22.14,
14.20 ppm.
4.2.21. Compound 24. 1H NMR (300 MHz, CDCl3):
1.6 Hz,1H), 7.59e7.47 (m, 2H), 7.46e7.33 (m, 3H), 7.32e7.17 (m, 2H),
2.62 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3):
142.29, 137.83, 132.10,
d
7.98 (dd, J¼7.8,
4.2.9. Compound 12. 1H NMR (300 MHz, CDCl3):
d 7.57e7.48 (m,
4H), 2.76 (t, J¼7.6 Hz, 2H), 1.85e1.50 (m, 2H), 1.48e1.08 (m, 10H),
d
0.86 (t, J¼6.4 Hz, 3H) ppm. 13C NMR (75 MHz, CDCl3):
d
142.89,
131.56, 130.95, 129.97, 127.88, 127.32, 126.49, 18.80 ppm. HRMS
calcd C13H11ClOS: 250.0219. Found: 250.0227.
137.22, 129.60, 125.61, 57.62, 31.79, 29.14, 28.75, 22.68, 22.14,
14.14 ppm. HRMS calcd C14H21ClOS: 272.1002. Found: 272.1008.
4.2.22. Compound 25. 1H NMR (300 MHz, CDCl3):
d 7.96 (d,
4.2.10. Compound 1331. 1H NMR (300 MHz, CDCl3):
2H), 7.49 (m, 3H), 2.61e2.52 (m, 1H), 1.85e1.12 (m, 10H) ppm. 13C
NMR (75 MHz, CDCl3): 141.86, 130.96, 128.94, 125.03, 63.16, 26.31,
25.98e25.09, 24.02 ppm.
d
7.60e7.50 (m,
J¼7.5 Hz, 1H), 7.55e7.30 (m, 2H), 7.24 (d, J¼8.1 Hz, 2H), 7.16 (d,
J¼7.3 Hz, 1H), 2.36 (s, 3H), 2.32 (s, 3H) ppm. 13C NMR (75 MHz,
d
CDCl3): d 143.18, 141.64, 135.66, 130.93, 130.06, 127.12, 126.19,
124.59, 21.45, 18.61 ppm. HRMS calcd C14H14OS: 230.0765. Found:
230.0760.
4.2.11. Compound 1432 1H NMR (300 MHz, CDCl3):
. d 7.66e7.60 (m,
4H), 7.47e7.44 (m, 3H), 7.17e7.11 (m, 2H) ppm. 13C NMR (75 MHz,
CDCl3): 166.07, 162.73, 145.51, 141.36, 131.32, 129.52, 127.32,
124.75, 116.91, 116.61 ppm.
4.2.23. Compound 2634
.
1H NMR (300 MHz, CDCl3):
d
7.90 (dd, J¼7.1,
d
1.9 Hz, 1H), 7.54 (dd, J¼6.7, 1.9 Hz, 2H), 7.49e7.33 (m, 4H), 7.19 (d,
J¼6.6 Hz, 1H), 2.36 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3):
d 143.27,
142.69, 137.26, 135.75, 131.20, 129.55, 127.21, 124.67, 18.54 ppm.
4.2.12. Compound 1528
.
1H NMR (300 MHz, CDCl3):
d
7.64e7.56 (m,
5H), 7.48e7.41 (m, 4H). 13C NMR (75 MHz, CDCl3):
d
145.36, 144.31,
4.2.24. Compound 27. 1H NMR (300 MHz, CDCl3):
4H), 7.47e7.38 (m, 2H), 7.33e7.21 (m, 2H), 2.37 (s, 3H). 13C NMR
(75MHz, CDCl3): 144.58,142.19,137.17,130.26,129.61,126.11,125.02,
21.48 ppm. HRMS calcd C13H11ClOS: 250.0219. Found: 250.0211.
d 7.58e7.50 (m,
137.32, 131.41, 129.60, 126.16, 124.76, 120.07 ppm.
d
4.2.13. Compound 1628
6H), 7.31e7.24 (m, 3H), 2.36 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3):
145.85, 142.51, 141.77, 131.00, 130.14, 129.37, 125.11, 124.81,
. d 7.65e7.33 (m,
1H NMR (300 MHz, CDCl3):
d
4.2.25. Compound 28. 1H NMR (300 MHz, CDCl3):
d 7.58 (d,
21.50 ppm.
J¼6.2 Hz, 2H), 7.45e7.39 (m, 4H), 7.37e7.32 (m, 1H), 7.25 (d,
J¼6.2 Hz, 1H), 2.38 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3):
d 145.15,
4.2.14. Compound 17. 1H NMR (300 MHz, CDCl3):
d
7.96e7.93 (m,
144.39, 139.82, 137.21, 132.27, 129.61, 129.32, 126.14, 124.96, 121.98,
21.45 ppm. HRMS calcd C13H11ClOS: 250.0219. Found: 250.0223.
1H), 7.58e7.45 (m, 2H), 7.43e7.30 (m, 5H), 7.17 (d, J¼7.1 Hz, 1H),
2.36 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3):
d
144.76, 143.11, 135.92,
131.17, 129.44, 127.28, 126.04, 124.89, 18.72 ppm. HRMS calcd
C13H12OS: 216.0609. Found: 216.0617.
4.2.26. Compound 2928 1H NMR (300 MHz, CDCl3):
. d 7.58e7.55 (m,
4H), 7.47e7.42 (m, 4H) ppm. 13C NMR (75 MHz, CDCl3):
d 143.98,
137.73, 129.87, 126.14 ppm.
4.2.15. Compound 18. 1H NMR (300 MHz, CDCl3):
2H), 7.48e7.40 (m, 5H), 7.33 (t, J¼7.6 Hz, 1H), 7.23 (d, J¼7.5 Hz, 1H),
2.37 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3):
145.72,145.43,139.59,
131.97, 131.00, 129.24, 124.90, 122.02, 21.43 ppm. HRMS calcd
C13H12OS: 216.0609. Found: 216.0615.
d 7.66e7.63 (m,
4.2.27. Compound 30. 1H NMR (300 MHz, CDCl3):
7.73e7.59 (m, 2H), 7.55e7.38 (m, 2H), 7.16e6.99 (m, 1H), 6.86e6.79
(m, 1H) ppm. 13C NMR (75 MHz, CDCl3):
166.81, 160.40, 157.08,
143.17, 137.89, 129.83, 126.82, 126.11, 113.05, 105.23, 104.88,
104.56 ppm. HRMS calcd C12H7ClF2OS: 271.9874. Found: 271.9862.
d 7.87 (m, 1H),
d
d
4.2.16. Compound 1929 1H NMR (300 MHz, CDCl3):
. d 7.51 (d,
J¼8.1 Hz, 4H), 7.37e6.96 (m, 4H), 2.36 (s, 6H) ppm. 13C NMR
4.2.28. Compound 31. 1H NMR (300 MHz, CDCl3):
d 8.13e8.10 (m,
(75 MHz, CDCl3):
d
142.86, 141.47, 130.02, 124.94, 21.42 ppm.
2H), 7.73e7.64 (m, 4H), 7.48e7.45 (m, 3H), 4.38 (q, J¼7.1 Hz, 2H),
1.38 (t, J¼7.1 Hz, 3H) ppm. 13C NMR (75 MHz, CDCl3):
d 165.62,
4.2.17. Compound 20. 1H NMR (300 MHz, CDCl3):
2H), 7.39 (d, J¼7.7 Hz, 1H), 7.32 (t, J¼7.5 Hz, 1H), 7.26e7.21 (m, 4H),
2.37 (s, 6H) ppm. 13C NMR (75 MHz, CDCl3):
145.72, 142.69, 141.61,
d
7.54e7.46 (m,
150.59, 145.27, 132.96, 131.62, 130.53, 129.66, 125.01, 124.49, 61.55,
14.37. HRMS calcd C15H14O3S: 274.0664. Found: 274.0654.
d
139.56, 131.83, 130.08, 129.13, 125.03, 121.99, 21.46 ppm. HRMS
calcd C14H14OS: 230.0765. Found: 230.0775.
4.2.29. Compound 3224
J¼8.4 Hz, 2H), 7.74e7.60 (m, 4H), 7.56e7.40 (m, 3H), 2.60 (s,
3H) ppm. 13C NMR (75 MHz, CDCl3):
197.10, 150.81, 145.18, 139.04,
131.68, 129.69, 129.23, 124.87, 26.84 ppm.
. d 8.02 (d,
1H NMR (300 MHz, CDCl3):
d
4.2.18. Compound 2133 1H NMR (300 MHz, CDCl3):
. d 7.65e7.60 (m,
2H), 7.51 (d, J¼8.2 Hz, 2H), 7.27 (d, J¼6.0 Hz, 2H), 7.14 (t,
J¼8.6 Hz, 2H), 2.38 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3):
4.2.30. Compound 3335 1H NMR (300 MHz, CDCl3):
d 8.31 (d,
.
d
165.85, 162.52, 142.33, 141.68, 130.11, 127.07, 124.82, 116.69,
J¼9.0 Hz, 2H), 7.83 (d, J¼9.0 Hz, 2H), 7.69e7.66 (m, 2H), 7.51e7.49
116.39, 21.36 ppm.
(m, 3H) ppm. 13C NMR (75 MHz, CDCl3):
129.92, 125.40, 125.00, 124.54 ppm.
d 153.11, 144.57, 132.12,
4.2.19. Compound 22. 1H NMR (300 MHz, CDCl3):
d
8.07 (dd, J¼7.8,
1.6 Hz,1H), 7.61 (d, J¼8.2 Hz, 2H), 7.51 (td, J¼7.6, 1.4 Hz,1H), 7.36 (m,
4.2.31. Compound 34. 1H NMR (300 MHz, CDCl3):
J¼4.1 Hz, 1H), 8.05 (d, J¼7.9 Hz, 1H), 7.90e7.79 (m, 3H), 7.46e7.44
d 8.55 (d,
2H), 7.29e7.15 (m, 2H), 2.36 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3):

H.-J. Xu et al. / Tetrahedron 66 (2010) 8823e8827
8827
(m, 3H), 7.32e7.28 (m,1H) ppm. 13C NMR (75 MHz, CDCl3):
d 165.92,
149.86, 144.18, 138.22, 131.23, 129.25, 124.88, 118.53 ppm. HRMS
calcd C11H9NOS: 203.0405. Found: 203.0419.
4. (a) Ohkubo, K.; Fukuzumi, S. Org. Lett. 2000, 2, 3647; (b) Ohkubo, K.; Mizush-
ima, K.; Iwata, R.; Souma, K.; Suzuki, N.; Fukuzumi, S. Chem. Commun. 2010, 601.
5. Suga, K.; Ohkubo, K.; Fukuzumi, S. J. Phys. Chem. A 2005, 109, 4339.
6. Ohkubo, K.; Nanjo, T.; Fukuzumi, S. Org. Lett. 2005, 7, 4265.
7. Fang, X.; Liu, Y. C.; Li, C. J. Org. Chem. 2007, 72, 8608.
4.2.32. Compound 3528 1H NMR (300 MHz, CDCl3):
. d 8.32 (d,
8. (a) Xu, H. J.; Dai, D. M.; Liu, Y. C.; Li, J.; Luo, S. W.; Wu, Y. D. Tetrahedron Lett.
2005, 46, 5739; (b) Xu, H. J.; Liu, Y. C.; Fu, Y.; Wu, Y. D. Org. Lett. 2006, 8, 3449;
(c) Xu, H. J.; Liu, Y. C.; Fu, Y. Chin. J. Chem. 2007, 25, 95; (d) Xu, H. J.; Liu, Y. C.; Fu,
Y. Chin. J. Chem. 2008, 26, 599; (e) Xu, H. J.; Xu, X. L.; Feng, Y. S. Chin. J. Org. Chem.
2009, 29, 289; (f) Fang, X. Q.; Xu, H. J.; Jiang, H.; Liu, Y. C.; Fu, Y.; Wu, Y. D.
Tetrahedron Lett. 2009, 50, 312.
J¼8.8 Hz, 2H), 7.82 (d, J¼8.8 Hz, 2H), 7.72e7.57 (m, 2H), 7.48 (d,
J¼8.5 Hz, 2H) ppm. 13C NMR (75 MHz, CDCl3):
d 152.68, 149.59,
138.53, 130.25, 126.33, 125.38, 124.71 ppm.
9. Lai, K. C.; Lam, S. K.; Chu, K. M.; Wong, B. C.; Hui, W. M.; Hu, W. H.; Lau, G. K.;
Wong, W. M.; Yuen, M. F.; Chan, A. O.; Lai, C. L.; Wong, J. N. N. Engl. J. Med. 2002,
346, 2033.
4.2.33. Compound 36. 1H NMR (300 MHz, CDCl3):
d 7.64e7.60 (m,
2H), 7.51e7.33 (m, 10H), 7.24 (t, J¼5.7 Hz, 2H) ppm. 13C NMR
10. Sovova, M.; Sova, P. Ceska Slov. Farm. 2003, 52, 82.
(75 MHz, CDCl3):
d 145.42, 143.07, 142.10, 133.40, 131.05, 129.61,
11. Kotelanski, B.; Grozmann, R. J.; Cohn, J. N. Clin. Pharmacol. Ther. 1973, 14, 427.
12. Schmied, R.; Wang, G. X.; Korth, M. Circ. Res. 1991, 68, 597.
13. Nieves, A. V.; Lang, A. E. Clin. Neuropharmacol. 2002, 25, 111.
14. Padmanabhan, S.; Lavin, R. C.; Durant, G. J. Tetrahedron 2000, 11, 3455.
15. (a) Carreno, M. Chem. Rev. 1995, 95, 1717; (b) Colobert, F.; Tito, A.; Khiar, N.;
Denni, D.; Medina, M. A.; Martin-Lomas, M.; Ruano, J. L. G.; Solladié, G. J. Org.
Chem. 1998, 63, 8918; (c) Carreno, M. C.; Ribagorda, M.; Posner, G. H. Angew.
Chem. 2002, 114, 2877; Angew. Chem., Int. Ed. 2002, 41, 2753.
129.32, 128.71, 125.48, 124.63 ppm. HRMS calcd C18H14O2S2:
326.0435. Found: 326.0423.
4.2.34. Compound 37. 1H NMR (300 MHz, CDCl3):
d 7.51e7.43 (m,
4H), 7.35 (d, J¼8.1 Hz, 2H), 7.26e7.16 (m, 6H), 2.37 (s, 6H) ppm. 13C
NMR (75 MHz, CDCl3):
d 143.00, 142.72, 142.31, 141.65, 139.18,
16. Khiar, N.; Fernández, I.; Alcudia, F. Tetrahedron Lett. 1993, 34, 123.
17. Fernández, I.; Khiar, N. Chem. Rev. 2003, 103, 3651.
134.20, 130.51, 130.06, 127.96, 125.39, 124.87, 21.36 ppm. HRMS
calcd C20H18O2S2: 354.0748. Found: 354.0742.
18. (a) Hiroi, K.; Suzuki, Y.; Abe, I.; Kawagishi, R. Tetrahedron 2000, 56, 4701; (b)
Hiroi, K.; Watanabe, K.; Abe, I.; Koseki, M. Tetrahedron Lett. 2001, 42, 7617; (c)
ꢀ
Priego, J.; Mancheno, O. G.; Cabrera, S.; Carretero, J. C. J. Org. Chem. 2002, 67,
4.2.35. Compound 38. 1H NMR (300 MHz, CDCl3):
3H), 7.40e7.29 (m, 2H), 7.25e7.21 (m, 6H), 7.18e7.14 (m,1H), 2.37 (s,
3H), 2.32 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3):
145.24, 143.00,
d 7.50e7.45 (m,
1346.
19. Representative examples for oxidation of sulfides to sulfoxides with peroxides,
see: (a) Adam, W.; Rodriguez, A. J. Am. Chem. Soc. 1980, 102, 404; (b) Murahashi,
S.; Oda, T.; Masui, Y. J. Am. Chem. Soc. 1989, 111, 5002; (c) Gelalcha, F. G.; Schulze,
B. J. Org. Chem. 2002, 67, 8400; (d) Baciocchi, E.; Gerini, M. F.; Lapi, A. J. Org.
Chem. 2004, 69, 3586; (e) Firouzabadi, H.; Iranpoor, N.; Jafari, A. A.; Riazy-
montazer, E. Adv. Synth. Catal. 2006, 348, 434; (f) Koo, D. H.; Kim, M.; Chang, S.
Org. Lett. 2005, 7, 5015; (g) Kerber, W. D.; Ramdhanie, B.; Goldberg, D. P. Angew.
Chem. 2007, 119, 3792; Angew. Chem., Int. Ed. 2007, 46, 3718; (h) Bordoloi, A.;
Vinu, A.; Halligudi, S. B. Chem. Commun. 2007, 4806; (i) Russoa, A.; Lattanzia, A.
Adv. Synth. Catal. 2009, 351, 521.
d
142.28, 139.54, 134.07, 131.91, 130.57, 129.46, 129.12, 128.67, 125.47,
124.84, 121.85, 21.31 ppm. HRMS calcd C20H18O2S2: 354.0748.
Found: 354.0732.
Acknowledgements
20. Kerber, W. D.; Ramdhanie, B.; Goldberg, D. P. Angew. Chem. 2007, 119, 3792;
Angew. Chem., Int. Ed. 2007, 46, 3718.
We gratefully acknowledge financial support from the National
Natural Science Foundation of China (No. 20802015, 20772115). We
thank Ye Geng in this group for reproducing the results of com-
pounds 10, 22, and 29 in Schemes 1 and 2. This paper is dedicate to
Professor You-Cheng Liu, a pioneer physical organic chemist in
China, on the occasion of his 90th birthday.
21. Representative examples for oxidation of sulfides to sulfoxides with O2, see: (a)
Correa, P. E.; Riley, D. P. J. Org. Chem. 1985, 50, 1787; (b) Tsuboi, T.; Takaguchi, Y.;
Tsuboi, S. Chem. Commun. 2008, 76; (c) Baciocchi, E.; Giacco, T. D.; Elisei, F.;
Gerini, M. F.; Guerra, M.; Lapi, A.; Liberali, P. J. Am. Chem. Soc. 2003, 125, 16444;
(d) Bonesi, S. M.; Manet, I.; Freccero, M.; Fagnoni, M.; Albini, A. Chem.dEur. J.
2006, 12, 4844; (e) Imada, Y.; Iida, H.; Ono, S.; Masui, Y.; Murahashi, S. I.
Chem.dAsian. J. 2006, 1-2, 136.
22. AcrH2, a reduced form of AcrHþ, often is used as a model of coenzyme NADH.
So, AcrHþ is defined as a model of coenzyme NADþ in this article.
23. Huang, R. L.; Goh, S. H.; Ong, S. H. The Chemistry of Free Radicals; Edward Ar-
nold: London, 1974.
Supplementary data
24. (a) Clennan, E. L.; Zhang, H. W. J. Am. Chem. Soc. 1995, 117, 4218; (b) Ohkubo, K.;
Nanjo, T.; Fukuzumi, S. Bull. Chem. Soc. Jpn. 2006, 79, 1489.
25. Nahm, K.; Foote, C. S. J. Am. Chem. Soc. 1989, 111, 1909.
Supplementary data associated with this article can be found in
online version at doi:10.1016/j.tet.2010.09.076.
26. (a) Xu, H. J.; Zhao, X. Y.; Fu, Y.; Feng, Y. S. Synlett 2008, 3063; (b) Xu, H. J.; Zhao,
X. Y.; Deng, J.; Fu, Y.; Feng, Y. S. Tetrahedron Lett. 2009, 50, 434; (c) Feng, Y. S.; Li,
Y. Y.; Tang, L.; Wu, W.; Xu, H. J. Tetrahedron Lett. 2010, 51, 2489.
27. Casarini, D.; Lunazzi, L.; Mazzanti, A. Angew. Chem. 2001, 113, 2604; Angew.
Chem., Int. Ed. 2001, 40, 2536.
28. Chandrasekaran, R.; Perumal, S.; Wilson, D. A. Magn. Reson. Chem. 1989, 27, 360.
29. Maitro, G.; Vogel, S.; Prestat, G.; Madec, D.; Poli, G. Org. Lett. 2006, 8, 5951.
30. Bellesia, F.; Ghelfi, F.; Pagnoni, U. M.; Pinetti, A. Synth. Commun. 1993, 23, 1759.
31. Johnson, C. R.; Kirchhoff, R. A.; Reischer, R. J.; Katekar, G. F. J. Am. Chem. Soc.
1973, 95, 4287.
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