Selective oxidation of glycosyl sulfides to sulfoxides with sodium hypochlorite and catalyzed by metalloporphyrins

Article abstract of DOI:10.1080/07328303.2010.483041

An efficient and selective method for oxidation of glycosyl sulfides to the corresponding glycosyl sulfoxides with metalloporphyrins as catalysts and sodium hypochlorite as oxidant was achieved under mild conditions. High chemoselectivity and diastereomeric excesses were obtained. Both acid-labile protected groups and carbon-carbon double bonds of allyl groups tolerated under these conditions. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/07328303.2010.483041

This article was downloaded by: [Northeastern University]
On: 26 October 2014, At: 10:33
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Journal of Carbohydrate Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lcar20
Selective Oxidation of Glycosyl Sulfides
to Sulfoxides with Sodium Hypochlorite
and Catalyzed by Metalloporphyrins
Jian-Ying Huang a , Shi-Jun Li b & Yan-Guang Wang c
a Department of Applied Chemistry , Zhejiang Gongshang
University , Hangzhou, 310035, P. R. China
b College of Material Chemistry and Chemical Engineering ,
Hangzhou Normal University , Hangzhou, 310027, P. R. China
c Department of Chemistry , Zhejiang University , Hangzhou,
310027, P. R. China
Published online: 02 Jun 2010.
To cite this article: Jian-Ying Huang , Shi-Jun Li & Yan-Guang Wang (2010) Selective Oxidation of
Glycosyl Sulfides to Sulfoxides with Sodium Hypochlorite and Catalyzed by Metalloporphyrins, Journal
of Carbohydrate Chemistry, 29:3, 142-153, DOI: 10.1080/07328303.2010.483041
To link to this article: http://dx.doi.org/10.1080/07328303.2010.483041
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Journal of Carbohydrate Chemistry, 29:142–153, 2010
ꢀ
C
Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328303.2010.483041
Selective Oxidation of Glycosyl
Sulfides to Sulfoxides with
Sodium Hypochlorite and
Catalyzed by
Metalloporphyrins
Jian-Ying Huang,1 Shi-Jun Li,2 and Yan-Guang Wang3
1Department of Applied Chemistry, Zhejiang Gongshang University,
Hangzhou 310035, P. R. China
2College of Material Chemistry and Chemical Engineering, Hangzhou Normal
University, Hangzhou 310027, P. R. China
3Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China
An efficient and selective method for oxidation of glycosyl sulfides to the correspond-
ing glycosyl sulfoxides with metalloporphyrins as catalysts and sodium hypochlorite as
oxidant was achieved under mild conditions. High chemoselectivity and diastereomeric
excesses were obtained. Both acid-labile protected groups and carbon–carbon double
bonds of allyl groups tolerated under these conditions.
Keywords Oxidation; Glycosyl sulfide; Glycosyl sulfoxide; Sodium hypochlorite;
Metalloporphyrin
INTRODUCTION
Sulfoxides are versatile synthetic intermediates in stereocontrol chem-
istry.[1] They can be used to prepare chemically and biologically significant
molecules,[2] including therapeutic agents such as antiulcer (proton pump
inhibitor),[3] antibacterial,[4] antifungal,[5] antiatherosclerotic,[6] antihyperten-
sive,[7] cardiotonic,[8] psychotropic,[9] and vasodilator agents.[10] In carbohy-
drate chemistry, glycosyl sulfoxides have been extensively used as important
glycosyl donors, which were commonly activated by Tf2O in acid scavengers
Received January 19, 2010; accepted March 31, 2010.
Address correspondence to Jian-Ying Huang, Department of Applied Chemistry,
Zhejiang Gongshang University, Hangzhou 310035, P. R. China. E-mail: huangjy@
mail.zjgsu.edu.cn; or Yan-Guang Wang, Department of Chemistry, Zhejiang University,
Hangzhou 310027, P. R. China. E-mail: orgwyg@zju.edu.cn
142

Selective Oxidation of Glycosyl Sulfides
143
such as 2,6-di-tert-butyl-4-methylpyridine (DTBMP).[11] This glycosylation
method has been developed as an important strategy for the preparation
of oligosaccharides[12] and glycoconjugates,[13] owing to its noticeable advan-
tages including mild reaction conditions, high donor activity, and excellent
anomeric stereocontrol.[14] The glycosylation with glycosyl sulfoxides as donors
could readily take place at low temperature, even in the presence of electron-
withdrawing protecting groups.[14a,14b] They could be applied not only for
the solution-phase synthesis,[11–15] but also for the solid-phase synthesis of
oligosaccharides.[16] Besides being used as glycosyl donors, glycosyl sulfoxides
could also be converted to glycosyl carbanions, which are very useful in the
stereospecific construction of C-glycosides, via sulfinyl-lithium exchange.[17]
The versatility of sulfoxides as organic reagents[18] and the high activ-
ity of glycosyl sulfoxides as donors[11–15] continually motivate the develop-
ment of efficient synthesis methods for sulfoxides and glycosyl sulfoxides.[11]
Although many methods for the synthesis of sulfoxides have been investi-
gated, selective oxidation of glycosyl sulfides to glycosyl sulfoxides still re-
mains a challenging task.[19] As one of the most successful methods, the oxi-
dation of glycosyl sulfides to sulfoxides was primarily achieved with m-CPBA
(m-chloroperbenzoic acid) in CH2Cl2.[19] However, this method suffers from
some shortcomings, such as the application of very low temperature to avoid
overoxidation of sulfoxides to sulfones and insolubility of m-CPBA in the re-
action medium. In addition, it is difficult to completely remove the byproduct
m-chlorobenzoic acid from sulfoxides. Therefore, new oxidation protocols with
mild reaction conditions and convenient workup are needed. In recent years,
some efficient methods have been developed to meet these requirements, such
as H2O2/Ac2O/SiO2 in CH2Cl2,[19d] H2O2 in hexafluoro-2-propanol (HFIP) un-
der neutral conditions,[19c] silica gel-supported oxone,[19a] tert-butyl hydroper-
oxide (TBHP),[20] and magnesium monoperoxyphthalate (MMPP) as an oxidant
under microwave irradiation.[19b] Ultrasound was also used to enhance the rate
and selectivity of the oxidation toward sulfoxides.[21]
Metalloporphyrins have been widely used as biomimetic catalysts for ox-
idation during the past decades,[22] combining with various oxygen sources,
such as PhIO, NaOCl, H2O2, ROOH, KHSO5, O2, and electrons.[23] Fe- and
Mn-porphyrin complexes were developed to be effective catalysts for the trans-
fer of oxygen atoms with the formation of sulfoxides from sulfides.[24] Drago
and coworkers have demonstrated that manganese tetrakis(phenyl)porphyrin
(MnTPPCl) is capable of catalyzing the oxidation of n-butyl sulfide to corre-
sponding sulfoxide by NaOCl in a biphasic system.[25] The addition of MnTP-
PCl led to the complete conversion of n-butyl sulfide and made a sixfold in-
crease in initial rate. However, in addition to n-butyl sulfide and MnTPPCl,
other sulfides and metalloporphyrins have not been investigated. Recently,
iron tetrakis(pentafluorophenyl)porphyrin has been used as a catalyst for
the oxidation of sulfides with hydrogen peroxide, for which high yields and

J-Y. Huang et al.
144
O
C
H2
C
O
O
N
O
R
R
R
R
R
R
R
R
R
R
N
N
N
N
Cl
M
N
N
N
N
Cl
M
R
R
R
R
1a: R = H, M = Fe
1b: R = Cl, M = Fe
1c: R = H, M = Mn
1d: R = Cl, M = Mn
2a: R = H, M = Fe
2b: R = Cl, M = Fe
2c: R = H, M = Mn
2d: R = Cl, M = Mn
Figure 1: TEMPO-linked porphyrins and porphyrin complexes.
chemoselectivities were obtained.[24] Our group has reported the selective oxi-
dation of alcohols and sulfides with TEMPO-linked metalloporphyrins (Fig. 1)
as efficient catalysts using NaOCl as oxidant.[26] In view of the continual in-
terest in glycosyl sulfoxides,[11] it is worthwhile to carry out the further work
extension of the metalloporphyrin-catalyzed oxidation methodology to the oxi-
dation of glycosyl sulfides. Best of all, compared with reported approaches, this
method let the reaction system be homogeneous and almost neutral. Herein,
we report the detailed investigation on the selective oxidation of a variety of
sensitive functional group-containing glycosyl sulfides to glycosyl sulfoxides
with metalloporphyrins as catalysts using NaOCl as oxidant.
RESULTS AND DISCUSSION
Initially glycosyl sulfide 3a was chosen as the model substrate. Reactions were
carried out in a two-phase system (dichloromethane/saturated aq. NaHCO3)
in the presence of metalloporphyrins, tetrabutylammonium bromide, and
potassium bromide at 0◦C to 25◦C for 1.5 h. Oxidation of glycosyl sulfide
3a afforded the corresponding sulfoxide 4a and all metalloporphyrins gave
the same anomeric isomer ratio (10:1) (Table 1, entry 1). As shown in Ta-
ble 1, commercially available Mn-porphyrin complexes, such as MnTPPCl
and Mn(TDCPP)Cl (Fig. 1), exhibited high catalytic activities for selective

Selective Oxidation of Glycosyl Sulfides
145
Table 1: Metalloporphyrin-catalyzed oxidation of sulfide 3 with NaOCla.
O
O
Ph
Ph
O
O
metalloporphyrin
O
O
O
SPh
SPh
HO
HO
NaOCl, KBr, Bu4NBr
CH2Cl2 /aq. NaHCO3
OH
OH
4a
(isomer ratio = 10 : 1)
3a
Entry
Catalyst
Catalyst (mol%)
Yield (%)b,c
1
2
1a
1b
1c
1d
1
50
62
1
3
1
81
4
1
86
5
Mn(TPP)Cl
1
78
6
Mn(TDCPP)Cl
Mn(TDCPP)Cl
Mn(TDCPP)Cl
Mn(TDCPP)Cl
Fe(TPP)Cl
Fe(TDCPP)Cl
None
0.1
0.5
1
83
7
87
8
84
9
3
74 (6)
70
10
11
12
0.5
0.5
—
79
15
aCompound 3a (1 mmol) was oxidized by NaOCl (1.25 mmol) in the presence of metallopor-
phyrins, KBr (10 mol%), and Bu4NBr (5 mol%) in CH2Cl2/saturated aq. NaHCO3 = 1:1 (10 mL) at
0◦C for 1 h.
bIsolated yields.
cThe yield of sulfone is in parentheses.
oxidation of sulfides as well as TEMPO-linked Mn-porphyrins and TEMPO-
linked Fe-porphyrins (Fig. 1), which were synthesized according to the pub-
lished method.[26] The complexes of chlorinated porphyrin ligand and TEMPO-
linked Mn-porphyrins have higher catalytic activity, while the Fe complexes
with porphyrin and TEMPO-linked porphyrin ligands gave lower yields (Ta-
ble 1, entries 1, 2, 10, and 11) than the corresponding Mn complexes (Table 1,
entries 3–9). The amount of catalyst was also examined (Table 1, entries 6–9).
When the amount of Mn(TDCPP)Cl was increased from 0.1 mol% to 0.5 mol%,
a slightly higher yield was given, whereas further increasing the amount of
catalyst from 0.5 mol% to 1 mol% led to a slight reduction in yield. When the
catalyst was increased to 3 mol%, a part of sulfide was overoxidated to sulfone
and a lower yield was given (Table 1, entry 9).
The other glycosyl sulfides with various types of protecting groups
were further investigated to examine the generality of this oxidation proto-
col. Although TEMPO-linked Mn-porphyrins were efficient catalysts as was
Mn(TDCPP)Cl (Table 1, entries 3, 4, and 7–9), Mn(TDCPP)Cl was used for the
oxidation of these glycosyl sulfides because it is much easier to be prepared.
The results are shown in Table 2. Glycosyl sulfides were observed to undergo

J-Y. Huang et al.
146
Table 2: Oxidation of glycosyl sulfides to sulfoxidesa.
Entry
1
Substrate
Sulfoxide
Yield (%)b,c Time (min)d
87 (10:1)
89 (1:0)
89 (1:0)
70
70
90
2
3
4
93 (1:0)
90
5
6
97 (7:1)
84 (1:0)
75
90
7
8
87 (1:0)
80 (1:0)
90
75
9
85 (1:0)
80 (1:0)
60
75
10
11
12
83 (1:0)
81 (1:0)
75
75
aDifferent sulfide (1 mmol) was oxidized by NaOCl (1.25 mmol) in the presence of Mn(TDCPP)Cl
(0.5 mol%), KBr (10 mol%), and Bu4NBr (5 mol%) in CH2Cl2/saturated aq. NaHCO3 = 1:1 (10 mL)
at 0◦C for 1 h.
bIsolated yields.
cThe diastereomer ratios of glycosyl sulfoxides are in parentheses.
dBy monitoring the disappearance of the starting material glycosyl sulfides with TLC.

Selective Oxidation of Glycosyl Sulfides
147
smooth oxidation to the corresponding sulfoxides, with yields of over 80%. For
all of these sulfides no overoxidation to sulfone was found. Various protecting
groups and hydroxyl groups were not affected during the procedure. Compared
with the method using m-CPBA as oxidant, acid-labile protecting groups, such
as TBDMS, Tr, and benzylidene, were stable under the reaction conditions (Ta-
ble 2, entries 1, 2, 5, and 8–11). Interestingly, by monitoring the disappearance
of the starting material glycosyl sulfides with TLC during oxidation procedure,
polar substrates underwent faster oxidation (Table 2, entries 1, 2, and 8–12),
which may be due to their higher solubility in water. The electronic effect of
the protecting groups on the C-2 of the glycosyl sulfides also influenced the re-
action rates. Electron-donating groups (e.g., ethers) on C-2 resulted in much
higher reaction rates than electron-withdrawing groups (e.g., ester). In the
case of benzyl sulfides (Table 2, entries 5 and 9), no oxidation was observed
at the benzylic C H bonds. The carbon-carbon double bonds in the allyl group
also tolerated the oxidation of NaOCl (Table 2, entries 6 and 7). It was noted
that the yields for p-methyl-phenyl glycosyl sulfoxides were higher than for
phenyl glycosyl sulfoxides due to the electron-donating effect of methyl. This
protocol was applied for the oxidation of disaccharide sulfides (Table 2, entries
10–12). Good chemoselectivities and yields were obtained.
The oxidation of glycosyl sulfides may lead to two diastereoisomeric prod-
ucts because the prochiral sulfur center could accept the oxygen from two dif-
ferent sides.[12] And these diastereoisomeric glycosyl sulfoxides may have an
impact on further glycosylation due to steric hindrance. It is interesting that
the metalloporphyrin-catalyzed oxidation method gave high diastereomeric ex-
cesses of the corresponding glycosyl sulfoxides. For most of glycosyl sulfides,
only one isomer was observed. Oxidation of glycosyl sulfides 3a and 3e gave
high diastereomeric ratios, 10:1 (Table 2, entry 1) and 7:1 (Table 2, entry 5),
respectively. It has been reported that 3g was oxidized to glycosyl sulfoxide 4g
with 1:1 diastereomeric ratio when magnesium monoperoxyphthalate (MMPP)
was used as oxidant.[19b] Here only one configuration of 4g was obtained (Table
2, entry 7). It is reasonable to assume that the oxidation proceeds through the
metal-oxo species and the bulky porphyrin leads to the high diastereomeric
excesses.
CONCLUSION
We developed an efficient and selective method for oxidation of glycosyl sul-
fides to the corresponding glycosyl sulfoxides with metalloporphyrins as cata-
lysts and sodium hypochlorite as oxidant. The oxidation was achieved in high
yields and various O-protecting groups were not affected under these reaction
conditions. Using this protocol, the overoxidation to sulfone can be prevented
and high diastereoisomeric excesses were obtained.

J-Y. Huang et al.
148
EXPERIMENTAL
All reagents were purchased from commercial suppliers and used as received.
Disaccharide sulfides were prepared according to the published procedures.[27]
NMR spectra were recorded on a Bruker Advance DMX 500 spectrophotometer
or Varian Unity INOVA-400 spectrophotometer using the deuterated solvent
as the lock and the residual solvent or TMS as the internal reference. Low-
resolution electrospray ionization mass spectra (ESI-MS) were recorded on a
Bruker Esquire 3000 Plus spectrometer (Bruker-Franzen Analytik GmbH Bre-
men, Germany) equipped with an ESI interface and ion trap analyzer. High-
resolution mass spectra (HRMS) were obtained on a Bruker 7-tesla FT-ICRMS
equipped with an electrospray source (Billerica, MA, USA).
General Procedure for the Oxidation of Sulfides to Sulfoxides
To a stirred solution of the sulfides (1.0 mmol) and the catalyst metallopor-
phyrins (0.005 mmol) in CH2Cl2 (8 mL), Bu4NBr (0.05 mmol) and a saturated
aqueous NaHCO3 (5 mL) containing KBr (0.1 mmol) were added. Then, to this
cooled (0◦C) and well-stirred mixture, a solution of 0.73 M NaOCl (0.91 mL,
1.25 mmol) in saturated aq. NaHCO3 was added dropwise over a period of 10
min. The mixture was stirred for a further 1 h at 0◦C and 0.5 h at rt, and the
organic phase was separated. The aqueous phase was extracted with CH2Cl2
(3 × 5 mL) and the organic solution was combined, washed with H2O, brine,
dried over anhydrous Na2SO4, and filtered. The solvent was removed in vacuo
and the residue was purified by chromatography on silica gel with ethyl ac-
etate/hexane as an eluent to afford the pure products.
4a[26]
White solid, mp: 90–92◦C; 1H NMR (400 MHz, CDCl3): δ 7.78–7.70 (m, 2H),
7.59–7.48 (m, 3H), 7.48–7.41 (m, 2H), 7.32–7.20 (m, 3H), 5.55 (s, 1H), 4.31 (s,
1H), 4.28–4.19 (m, 2H), 4.12 (d, J = 9.4 Hz, 1H), 3.92 (t, J = 9.6 Hz, 1H), 3.75 (t,
J = 10.3 Hz, 1H), 3.62 (t, J = 9.4 Hz, 1H), 3.45–3.30 (m, 1H), 3.02 (s, 1 H); 13
C
NMR (125 MHz, CDCl3): δ 68.3, 71.0, 73.4, 74.4, 79.7, 93.8, 102.2, 124.8, 126.5,
128.6, 129.5, 129.6, 132.3, 136.9, 141.6; ESI-MS: m/z = 399 ([M + Na]+), 775
1
([2M + Na]+). Isomer, white solid, mp: 94–96◦C; H NMR (500 MHz, CDCl3):
δ 7.95–7.93 (d, J = 7.6 Hz, 2H), 7.74 (t, J = 7.5 Hz, 1H), 7.63–7.60 (m, 2H),
7.45–7.43 (m, 2H), 7.35–7.34 (m, 3H), 5.48 (s, 1H), 4.41 (d, J = 9.4 Hz, 1H),
4.25 (dd, J = 3.5, 10.1 Hz, 1H), 3.98–3.88 (m, 2H), 3.74 (s, 1H), 3.73–3.65 (m,
1H), 3.48–3.46 (m, 2H), 2.96 (s, 1H); ESI-MS: m/z = 399 ([M + Na]+), 775 ([2M
+ Na]+).

Selective Oxidation of Glycosyl Sulfides
149
4b[19b]
White solid, mp: 160–162◦C; 1H NMR (500 MHz, CDCl3): δ 7.60 (d, J = 8.4
Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H), 7.37–7.34 (m, 5H), 5.53 (s, 1H), 4.43 (s, 1H),
4.26–4.23 (m, 1H), 4.49–4.15 (m, 2H), 3.85 (t, J = 8.4 Hz, 1H), 3.72 (t, J = 10.2
Hz, 1H), 3.59 (t, J = 9.3 Hz, 1H), 3.41–3.38 (m, 1H), 3.29 (s, 1H), 2.45 (s, 3H,
CH3); 13C NMR (125 MHz, CDCl3): δ 143.0, 138.2, 136.9, 130.3, 129.5, 128.5,
126.5, 125.0, 102.2, 93.8, 79.7, 74.3, 73.3, 70.9, 68.3, 21.8; ESI-MS: m/z = 413
([M + Na]+), 803 ([2M + Na]+).
4c[19b]
1
White solid, mp: 54–56◦C; H NMR (400 MHz, CDCl3,): δ 7.72–7.53 (m,
5H), 5.35–5.21 (m, 2H), 5.02–4.92 (m, 1H), 4.45 (dd, J = 9.4, 9.2 Hz, 1H), 4.28
(d, J = 9.6 Hz, 1H), 3.73–3.68 (m, 2H), 2.12 (s, 3H), 2.06 (s, 3H), 1.96 (s, 3H),
1.95 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 170.3, 170.1, 169.3, 169.2, 138.9,
131.6, 128.8, 125.7, 92.2, 76.2, 73.5, 67.7, 67.4, 61.3, 20.6, 20.5, 20.45, 20.43;
ESI-MS: m/z = 457 ([M + Na]+).
4d[19a]
1
White solid, mp: 120–122◦C; H NMR (400 MHz, CDCl3,): δ 7.49 (d, J =
8.0 Hz, 2H), 7.25 (d, J = 7.6 Hz, 2H), 5.20–5.11 (m, 2H), 4.87 (t, J = 10.0 Hz,
1H), 4.34 (d, J = 9.6 Hz, 1H), 4.10–4.02 (m, 2H), 3.65–3.61 (m, 1H), 2.35 (s,
3H), 1.93 (s, 3H), 1.92 (s, 3H), 1.91 (s, 3H), 1.87 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 170.3, 170.0, 169.3, 169.2, 142.2, 135.4, 129.5, 125.9, 91.9, 76.1, 73.5,
67.5, 67.4, 61.2, 21.4, 20.5 (2 × C), 20.43, 20.40; ESI-MS: m/z = 493 ([M +
Na]+), 509 ([M + K]+).
4e
1
White solid, mp: 138–141◦C; H NMR (400 MHz, CDCl3,): δ 7.45–7.27 (m,
16H), 7.19–7.12 (m, 4H), 5.53 (s, 1H), 4.90 (t, J = 10.8 Hz, 2H), 4.72 (t, J =
10.8 Hz, 2H), 4.58 (d, J = 8.8 Hz, 1H), 4.42 (d, J = 8.4 Hz, 1H), 3.93 (s,
1H), 3.77–3.70 (m, 2H), 3.57–3.56 (m, 2H), 2.35 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 141.7, 137.9, 137.6, 137.0, 136.2, 129.5, 129.0, 128.5, 128.4, 128.2,
128.1, 128.0, 127.8, 127.5, 125.9, 125.5, 101.2, 95.3, 83.0, 81.0, 75.2, 74.9, 74.0,
70.0, 68.3, 21.3; ESI-MS: m/z = 593 ([M + Na]+); HRMS(ESI): m/z calcd
for C34H35O6S [M + H]+ 571.2154, found 571.2166. Isomer, white solid, mp:
1
139–142◦C; H NMR (400 MHz, CDCl3,): δ 7.52–7.50 (m, 2H), 7.44–7.43 (m,
2H), 7.38–7.27 (m, 15H), 5.54 (s, 1H), 5.03 (t, J = 10.0 Hz, 1H), 4.98 (d, J = 4.0
Hz, 1H), 4.94–4.92 (m, 0.5H), 4.90–4.87 (m, 0.5H), 4.84–4.81 (m, 1H), 4.75–4.69
(m, 0.5H), 4.60–4.58 (m, 0.5H), 4.17–4.12 (m, 1H), 4.06 (dd, J = 5.2, 10.4 Hz,
1H), 4.99 (d, J = 10.0 Hz, 1H), 3.82–3.75 (m, 2H), 3.33–3.27 (m, 1H), 2.43

J-Y. Huang et al.
150
(s, 3H); ESI-MS: m/z = 593 ([M + Na]+); HRMS(ESI): m/z calcd for C34H35O6S
[M + H]+ 571.2154, found 571.2167, error 2.2 ppm.
4f
1
White solid, mp: 134–137◦C; H NMR (400 MHz, CDCl3,): δ 7.72–7.71 (m,
2H), 7.514–7.510 (m, 3H), 5.78–5.70 (m, 1H), 5.22–5.12 (m, 2H), 4.86 (t, J = 9.6
Hz, 1H), 4.29–4.26 (m, 1H), 4.11–4.00 (m, 4H), 3.70–3.55 (m, 3H), 2.07 (s, 3H),
2.04 (s, 3H), 1.94 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 170.4, 169.4, 169.1,
138.8, 133.8, 131.6, 128.7, 126.2, 117.3, 92.5, 80.5, 76.4, 73.3, 69.2, 68.8, 61.6,
20.9, 20.7, 20.6; ESI-MS: m/z = 477 ([M + Na]+), 493 ([M + K]+), 931 ([2M
+ Na]+), 947 ([2M + K]+); HRMS(ESI): m/z calcd for C21H27O9S [M + H]+
455.1376, found 455.1370, error 1.3 ppm.
4g
1
White solid, mp: 140–143◦C; H NMR (400 MHz, CDCl3,): δ 7.60 (d, J =
8.0 Hz, 2H), 7.32–7.26 (m, 2H), 5.79–5.70 (m, 1H), 5.21–5.10 (m, 2H), 4.85 (t,
J = 9.6 Hz, 1H), 4.26 (d, J = 9.6 Hz, 1H), 4.09–3.99 (m, 4H), 3.70–3.54 (m, 3H),
2.41 (s, 3H), 2.08 (s, 3H), 2.04 (s, 3H), 1.95 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 170.4, 169.4, 169.1, 142.2, 135.4, 133.9, 129.5, 126.3, 117.3, 92.3, 80.5, 76.4,
73.4, 69.3, 68.8, 61.7, 21.4, 20.9, 20.7, 20.5; ESI-MS: m/z = 491([M + Na]+),
507 ([M + K]+); HRMS(ESI): m/z calcd for C22H29O9S [M + H]+ 469.1532,
found 469.1539, error 1.5 ppm.
4h
White solid, mp: 78–80◦C; 1H NMR (400 MHz, CDCl3,): δ 7.65–7.63 (m, 2H),
7.51–7.50 (m, 3H), 5.21 (t, J = 9.6 Hz, 1H), 5.12 (t, J = 9.2 Hz, 1H), 4.47 (d, J =
9.2 Hz, 1H), 3.93 (dd, J = 4.4, 10.4 Hz, 1H), 3.74 (dd, J = 5.6, 10.8 Hz, 1H),
3.68 (t, J = 8.8 Hz, 1H), 3.48–3.43 (m, 1H), 3.19 (s, 3H), 2.06 (s, 3H), 1.82 (s,
3H), 0.89 (s, 9H), 0.07 (s, 3H), 0.06 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 171.1,
169.5, 132.6, 132.3, 128.9, 128.0, 85.8, 78.5, 77.2, 71.2, 70.0, 64.3, 25.8, 20.8,
20.7, 18.2, –0.04, –5.52; ESI-MS: m/z = 509 ([M + Na]+), 995 ([2M + Na]+);
HRMS(ESI): m/z calcd for C22H35O8SSi [M + H]+ 487.1822, found 487.1827,
error 1.0 ppm.
4i
1
White solid, mp: 119–123◦C; H NMR (400 MHz, CDCl3,): δ 7.65–7.63 (m,
2H), 7.41–7.38 (m, 8H), 7.32–7.25 (m, 20H), 4.87 (s, 2H), 4.79 (s, 2H), 4.51 (d,
J = 9.2 Hz, 1H), 3.71–3.59 (m, 3H), 3.51–3.47 (m, 1H), 3.43–3.39 (m, 1H), 3.30
(dd, J = 3.6, 10.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 146.8, 143.5, 138.0,
137.6, 137.5, 131.3, 131.2, 128.8, 128.7, 128.69, 128.61, 128.55, 128.54, 128.0,

Selective Oxidation of Glycosyl Sulfides
151
127.9, 127.8, 127.7, 127.5, 127.2, 127.1, 126.9, 125.6, 95.1, 95.0, 86.7, 86.2,
82.0, 76.3, 75.4, 69.9, 62.2; ESI-MS: m/z = 733 ([M + Na]+), 749 ([M + K]+);
HRMS(ESI): m/z calcd for C45H43O6S [M + H]+ 711.2780, found 711.2766,
error 1.9 ppm.
4j
1
White solid, mp: 134–136◦C; H NMR (400 MHz, CDCl3,): δ 7.63–7.61 (m,
2H), 7.50–7.48 (m, 3H), 7.38–7.36 (m, 2H), 7.25–7.23 (m, 3H), 5.48 (s, 1H),
5.31–5.30 (m, 1H), 5.22 (dd, J = 3.6, 10.4 Hz, 1H), 5.16 (d, J = 1.2 Hz, 1H),
4.89 (t, J = 10.4 Hz, 1H), 4.19 (dd, J = 5.2, 10.4 Hz, 1H), 4.11–4.07 (m, 2H),
3.85 (t, J = 9.6 Hz, 1H), 3.68 (t, J = 10.4 Hz, 1H), 3.59 (t, J = 9.6 Hz, 1H),
3.40–3.31 (m, 1H), 2.04 (s, 3H), 1.91 (s, 3H), 1.87 (s, 3H), 0.75 (d, J = 6.0 Hz,
3H); 13C NMR (100 MHz, CDCl3): δ 170.1, 170.0, 169.8, 141.5, 136.8, 131.9,
129.3, 129.0, 128.0, 126.1, 124.4, 101.6, 97.8, 93.8, 77.8, 77.0, 73.7, 71.1, 71.0,
69.5, 69.1, 68.0, 66.0, 20.8, 20.7, 20.6, 16.7; ESI-MS: m/z = 671 ([M + Na]+);
HRMS(ESI): m/z calcd for C31H37O13S [M + H]+ 649.1955, found 649.1950,
error 0.8 ppm.
4k
1
White solid, mp: 146–148◦C; H NMR (500 MHz, CDCl3,): δ 7.58 (d, J =
8.1 Hz, 2H), 7.46–7.44 (m, 2H), 7.36 (d, J = 8.1 Hz, 2H), 7.33–7.31 (m, 3H),
5.56 (s, 1H), 5.39–5.38 (m, 1H), 5.30 (dd, J = 3.5, 10.1 Hz, 1H), 5.25 (d, J =
0.6 Hz, 1H), 4.97 (t, J = 10.0 Hz, 1H), 4.19 (t, J = 8.2 Hz, 1H), 4.26 (dd, J =
4.9, 10.4 Hz, 1H), 4.20–4.16 (m, 2H), 4.11 (d, J = 9.5 Hz, 1H), 3.93 (t, J = 9.4
Hz, 1H), 3.75 (t, J = 10.4 Hz, 1H), 3.67 (t, J = 9.5 Hz, 1H), 3.43–3.39 (m, 1H),
2.45 (s, 3H), 2.13 (s, 3H), 1.99 (s, 3H), 1.95 (s, 3H), 0.83 (d, J = 6.2 Hz, 1H);
13C NMR (100 MHz, CDCl3): δ 170.4, 170.3, 170.1, 143.0, 138.6, 137.1, 130.4,
129.3, 128.3, 126.4, 124.8, 101.9, 98.1, 94.0, 78.2, 77.3, 74.3, 71.4, 71.3, 69.8,
69.4, 68.3, 66.3, 21.8, 21.2, 21.0, 20.9, 17.0; ESI-MS: m/z = 685 ([M + Na]+);
HRMS(ESI): m/z calcd for C32H39O13S [M + H]+ 663.2111, found 663.2099,
error 1.8 ppm.
4l
1
White solid, mp: 127–127◦C; H NMR (500 MHz, CDCl3,): δ 7.62–7.59 (m,
2H), 7.49–7.43 (m, 3H), 5.19–5.12 (m, 4H), 5.03–4.98 (m, 1H), 4.69 (d, J = 2.0
Hz, 1H), 4.43 (d, J = 10.0 Hz, 1H), 4.19 (dd, J = 5.2 Hz, 12.4 Hz, 1H), 4.07–4.02
(m, 2H), 3.95–3.90 (m, 1H), 3.82 (dd, J = 3.6 Hz, 11.6 Hz, 1H); 13C NMR (100
MHz, CDCl3): δ 171.2, 170.6, 169.8, 169.7, 169.5, 169.2, 138.9, 131.4, 128.8,
125.2, 97.5, 92.5, 78.9, 69.1, 68.8, 68.3, 67.7, 66.8, 66.0, 65.9, 62.3, 60.2, 20.9,
20.7, 20.6, 20.58, 20.52, 20.4; ESI-MS: m/z = 725 ([M + Na]+); HRMS(ESI):
m/z calcd for C30H39O17S [M + H]+ 703.1908, found 703.1923, error 2.1 ppm.

J-Y. Huang et al.
152
ACKNOWLEDGMENTS
This work was supported by the Foundation of Zhejiang Gongshang University
(No.X-106).
REFERENCES
1. (a) Elliott, M.C.; El Sayed, N.N.E.; Ooi, L. Sulfoxide-directed desymmetrisation
of cyclohexa-1,4-dienes. Tetrahedron Lett. 2007, 48, 4561–4564. (b) Carren˜o, M.C.;
Herna´ndez-Torres, G.; Urbano, A.; Colobert, F. Sulfoxide-directed stereocontrolled ac-
cess to 2 H-chromans:total synthesis of the (S,R,R,R)-enantiomer of the antihyperten-
sive drug nebivolol. Eur. J. Org. Chem. 2008, 2035–2038.
2. Melzig, L.; Rauhut, C.B.; Knochel, P. 2,3-Functionalization of furans, benzofurans
and thiophenes via magnesiation and sulfoxide–magnesium exchange. Chem. Commun.
2009, 3536–3538.
3. Jiang, B.; Zhao, X.-L.; Dong, J.-J.; Wang, W.-J. Catalytic asymmetric oxidation
of heteroaromatic sulfides with tert-butyl hydroperoxide catalyzed by a titanium com-
plex with a new chiral 1,2-diphenylethane-1,2-diol ligand. Eur. J. Org. Chem. 2009, 7,
987–991.
4. Kyung, K.H.; Han, D.C.; Fleming, H.P. Antibacterial activity of heated cabbage
juice, S-methyl-L-cysteine sulfoxide and methyl methanethiosulfonate. J. Food Sci.
1997, 62, 406–409.
5. Liu, F.; Lou, X.-Q.; Song, B.-A.; Bhadury, P.S.; Yang, S.; Jin, L.-H.; Xue, W.;
Hu, D.-Y. Synthesis and antifungal activity of novel sulfoxide derivatives containing
trimethoxyphenyl substituted 1, 3, 4-thiadiazole and 1, 3, 4-oxadiazole moiety. Bioorg.
Med. Chem. 2008, 16, 3632–3640.
6. Hosseinpoor F., Golchoubian, H. Mn(III)-catalyzed oxidation of sulfides to sulfox-
ides with hydrogen peroxide. Tetrahedron Lett. 2006, 47, 5195–5197.
7. Ghosh, T.K.; Habib, M.J.; Childs, K.; Alexander, M. Transdermal delivery of meto-
prolol I: comparison between hairless mouse and human cadaver skin and effect of
n-decylmethyl sulfoxide. Int. J. Pharma. 1992, 88, 391–396.
8. Schmied, R.; Wang, G.X.; Korth, M. Intracellular Na+ activity and positive in-
otropic effect of sulmazole in guinea pig ventricular myocardium, comparison with a
cardioactive steroid. Circ. Res. 1991, 68, 597–604.
9. Nieves, A.V.; Lang, A.E. Treatment of excessive daytime sleepiness in patients
with Parkinson’s disease with modafinil. Clin. Neuropharmacol. 2002, 25, 111–114.
10. Padmanabhan, S.; Lavin, R.C.; Durant, G.J. Asymmetric synthesis of a neuropro-
tective and orally active N-methyl-D-aspartate receptor ion-channel blocker, CNS5788.
Tetrahedron: Asymm. 2000, 11, 3455–4357.
11. Yu, B.; Zhang, Y.; Tang, P. Carbohydrate chemistry in the total synthesis of
saponins. Eur. J. Org. Chem. 2007, 31, 5145–5161.
12. (a) Taylor, J.G.; Li, X.; Oberthu¨r, M.; Zhu, W.; Kahne, D.E. The total synthesis
of Moenomycin A. J. Am. Chem. Soc. 2006, 128, 15084–15085. (b) Crich, D.; Wu, B.;
Jayalath, P. Convergent synthesis of a β-(1–3)-mannohexaose. J. Org. Chem. 2007, 72,
6806–6815.
13. Bai, Y.; Lowary, T.L. 2,3-Anhydrosugars in glycoside bond synthesis. Application
to a α-D-galactofuranosides. J. Org. Chem. 2006, 71, 9658–9671.

Selective Oxidation of Glycosyl Sulfides
153
14. (a) Thompson, C.; Ge, M.; Kahne, D. Synthesis of vancomycin from the aglycon.
J. Am. Chem. Soc. 1999, 121, 1237–1244. (b) Sears, P.; Wong, C.-H. Toward auto-
mated synthesis of oligosaccharides and glycoproteins. Science 2001, 291, 2344–2350.
(c) Crich, D.; Wu, B. 1-Naphthylpropargyl ether group: a readily cleaved and steri-
cally minimal protecting system for stereoselective glycosylation. Org. Lett. 2006, 8,
4879–4882.
15. Lichtenthaler, F.W.; Oberthu¨r, M.; Peters, S. Directed and efficient synthesis of
β(1→4) linked galacto-oligosaccharides. Eur. J. Org. Chem. 2001, 20, 3849–3869.
16. Yan, L.; Taylor, C.M.; Goodnow, R.; Kahne, D. Glycosylation on the Merrifield resin
using anomeric sulfoxides. J. Am. Chem. Soc. 1994, 116, 6953–6954.
17. Casillas, M.; Barrio, A.; Gawel, A.; Lo´pez, J.C. Synthesis of pyranoid and furanoid
glycals from glycosyl sulfoxides by treatment with organolithium reagents. Eur. J. Org.
Chem. 2008, 23, 3933–3942.
18. (a) Kirihara, M.; Yamamoto, J.; Noguchi, T.; Hirai, Y. Selective synthesis of sul-
foxides and sulfones by tantalum(v) catalyzed oxidation of sulfides with 30% hydrogen
¨
peroxide. Tetrahedron Lett. 2009, 50, 1180–1183. (b) Ruff, F.; Fa´bia´n, A.; Farkas, O.;
´
Kucsman, A. Mechanism for the oxidation of sulfides and sulfoxides with periodates:
reactivity of the oxidizing species. Eur. J. Org. Chem. 2009, 13, 2102–2111.
19. (a) Noureddine, K. Determination of the absolute configuration of sulfinyl glyco-
sides: the role of the exo-anomeric effect. Tetrahedron Lett. 2000, 41, 9059–9063. (b) Vin-
cent, S.P.; Burkart, M.D.; Tsai, C.-Y.; Zhang, Z.; Wong, C.-H. Electrophilic fluorination-
nucleophilic addition reaction mediated by selectfluor: mechanistic studies and new
applications. J. Org. Chem. 1999, 64, 5264–5279. (c) Ravikumar, K.S.; Zhang, Y.M.;
Begue, J.-P.; Bonnet-Delpon, D. Role of hexafluroro-2-propanol in selective oxidation
of sulfide to sulfoxide: Efficient preparation of glycosyl sulfoxides. Eur. J. Org. Chem.
1998, 2937–2940. (d) Kakarla, R.; Dukina, R.G.; Hatzenbuhler, N.T.; Hui, Y.W.; Sofia,
M.J. Simple and efficient method for the oxidation of sulfides to sulfoxides: application
to the preparation of glycosyl sulfoxides. J. Org. Chem. 1996, 61, 8347–8349.
20. Breton, G.W.; Fields, J.D.; Kropp, P.J. Surface-mediated reactions. 5. Oxidation of
sulfides, sulfides, sulfoxides, and alkenes with tert-butyl hydroperoxide. Tetrahedron
Lett. 1995, 36, 3825–3828.
21. Mahamuni, N.N.; Gogate, P.R.; Pandit, A.B. Ultrasound-accelerated green and se-
lective oxidation of sulfides to sulfoxides. Ind. Eng. Chem. Res. 2006, 45, 8829–8836.
22. Meunier, B. Metalloporphyrins as versatile catalysts for oxidation reactions and
oxidative DNA cleavage. Chem. Rev. 1992, 92, 1411–1456.
23. Li, S.-J.; Wang, Y.-G. A novel and selective catalytic oxidation of hydrocar-
bons to ketones using chloramine-T/O2/Fe(TPP)Cl system. Tetrahedron Lett. 2005, 46,
8013–8015.
24. Baciocchi, E.; Gerini, M.F.; Lapi, A. Synthesis of sulfoxides by the hy-
drogen peroxide induced oxidation of sulfides catalyzed by Iron tetrakis
(pentafluorophenyl)porphyrin: scope and chemoselectivity. J. Org. Chem. 2004,
69, 3586–3589.
25. Ramsden, J.H.; Drago, R.S.; Riley, R. A kinetic study of sulfide oxidation by sodium
hypochlorite using phase transfer catalysis. J. Am. Chem. Soc. 1989, 111, 3958–3961.
26. Huang, J.-Y.; Li, S.-J.; Wang, Y.-G. TEMPO-linked metalloporphyrins as efficient
catalysts for selective oxidation of alcohols and sulfides. Tetrahedron Lett. 2006, 47,
5637–5640.
27. Zhou, F.Y.; She, J.; Wang, Y.G. Synthesis of a benzyl-protected analog of arenario-
side, a trisaccharide phenylpropanoid glycoside. Carbohydr. Res. 2006, 341, 2469–2477.