Oxidation reactions using polymer-supported 2-benzenesulfonyl-3-(4- nitrophenyl)oxaziridine

Article abstract of DOI:10.1016/j.tet.2011.08.058

A thermally stable polymer-supported oxidant has been developed. Polymer-supported 2-benzenesulfonyl-3-(4-nitrophenyl)oxaziridine was applied to microwave-assisted reactions that occurred at high temperatures and was shown to oxidize alkenes, silyl enol ethers, and pyridines to the corresponding epoxides and pyridine N-oxides in excellent to good yields and with much shorter reaction times. It also enabled tetrahydrobenzimidazoles to be oxidatively rearranged to spiro fused 5-imidazolones in a more efficient manner. Recycling of the polymer-supported oxidant is also possible with minimal loss of activity after several reoxidations.

Full text of DOI:10.1016/j.tet.2011.08.058

Tetrahedron 67 (2011) 8353e8359
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journal homepage: www.elsevier.com/locate/tet
Oxidation reactions using polymer-supported 2-benzenesulfonyl-3-
(4-nitrophenyl)oxaziridine
*
Woen Susanto, Yulin Lam
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Singapore
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 May 2011
Received in revised form 4 August 2011
Accepted 22 August 2011
Available online 27 August 2011
A
thermally stable polymer-supported oxidant has been developed. Polymer-supported 2-
benzenesulfonyl-3-(4-nitrophenyl)oxaziridine was applied to microwave-assisted reactions that oc-
curred at high temperatures and was shown to oxidize alkenes, silyl enol ethers, and pyridines to the
corresponding epoxides and pyridine N-oxides in excellent to good yields and with much shorter re-
action times. It also enabled tetrahydrobenzimidazoles to be oxidatively rearranged to spiro fused 5-
imidazolones in a more efficient manner. Recycling of the polymer-supported oxidant is also possible
with minimal loss of activity after several reoxidations.
Keywords:
Polymer-supported 2-benzenesulfonyl-3-
(4-nitrophenyl)oxaziridine
Microwave
Ó 2011 Elsevier Ltd. All rights reserved.
Epoxide
Pyridine N-oxide
Spiro fused 5-imidazolone
1. Introduction
have been developed. Recently, we have reported the synthesis of
a soluble polymer-supported 2-phenylsulfonyloxaziridine (Davis
Advances in the use of polymers in organic synthesis1e3 have led
to the development of improved technologies for the preparation of
chemical libraries. In particular, the use of polymer-supported
reagents4e6 in what is commonly referred to as polymer-assisted
organic synthesis is an attractive technique that combines the ad-
vantages of solid-phase chemistry with those of solution-phase
synthesis. In this technique, a polymer-bound reagent is added to
a substrate in solution to effect a chemical transformation. At the
end of the reaction, the polymer-bound spent reagent can be sep-
arated via filtration, thus simplifying product purification. Fur-
thermore, since both the substrate and product are in solution
during the reaction, conventional solution-phase analytical tech-
niques, such as thin-layer chromatography, can be employed for
reaction monitoring. The versatility of this methodology facilitates
the process of library synthesis and has been the main stimulus for
the recent growth of interest in polymer-supported reagents and
catalysts.
reagent) 1 (Fig. 1) and its application to the oxidation of sulfides,
selenides, amines, phosphines, and enolates.16 Although polymer 1
effected clean and selective oxidation with high yields and simple
workup, it was not thermally stable and could only be applied to
reactions at ambient or low temperatures. To address the need of
some oxidation reactions that occur much slower and require
prolong heating for useful yields, we sought to develop a more
stable form of polymer 1.
O
O
O
O
N
N
S
S
NO2
O
O
1
2
Fig. 1. Polymer-supported 2-phenylsulfonyloxaziridines.
Davis and Sheppard had earlier reported the use of a thermally
more stable 2-(phenylsulfonyl)-3-(p-nitrophenyl)oxaziridine for
the oxidation of silyl enol ethers.17,18 We reasoned that a polymer-
supported version of this reagent would provide a thermally stable,
neutral, aprotic, and mild polymer-supported oxidant that could
contribute to a simpler and more convenient oxidative process.
Hence we herein present the synthesis of soluble polymer-
supported 2-benzenesulfonyl-3-(p-nitrophenyl)oxaziridine 2 and
its application in the oxidation of various substrate types.
To date, various polymer-supported variants of commonly used
reagents have been prepared and employed in numerous synthetic
strategies.3,7e10 Amongst them, a number of oxidants, such as IBX,11
trimethylamine N-oxide,12 dichromate,13 and Swern oxidants14,15
* Corresponding author. E-mail address: chmlamyl@nus.edu.sg (Y. Lam).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.058

8354
W. Susanto, Y. Lam / Tetrahedron 67 (2011) 8353e8359
2. Results and discussion
an impureproduct (as shownin the 1H NMR spectrum) and attempts
to purify it proved difficult as the product surprisingly underwent
hydrolysis when washed with cold methanol. This could be attrib-
uted to the presence of a Lewis acid in a protic solvent, which causes
the imine nitrogen to become protonated, thus resulting in hydro-
lysis. Attempts to use other Lewis acids, such as TFAA,20 FeCl3,21 and
Ti(OEt)422 gave very low loading levels of the product or no reaction
at all (entries 2, 4, and 5, Table 1). To circumvent this problem, we
converted 6 to 1-(diethyloxymethyl)-4-nitrobenzene 7, which was
then reacted neat with polymer 5 at 180 ꢁC to provide polymer 8.23
To prevent the hydrolysis of polymer 8, ethanol that formed as a by-
product was distilled off immediately. This procedure gave a 78%
conversion and the polymer 8 obtained was stable evenwhen it was
precipitated from cold methanol.
2.1. Synthesis of polymer 2
The synthesis of polymer 2 (Scheme 1) began with the conver-
sion of the sodium salt of 4-styrenesulfonic acid
3 to 4-
vinylbenzenesulfonamide 4. This was accomplished by first treat-
ing 3 with thionyl chloride to form the sulfonyl chloride, which was
then reacted with ammonium hydroxide to provide 4. Polymeri-
zation of 4 with styrene using standard AIBN initiated radical po-
lymerization afforded polymer 5 whose formation was amenable to
KBr FTIR analysis (i.e., the appearance of primary sulfonamide
bands at 3392 and 3269 cmꢀ1). From elemental analysis data, the
loading level of polymer 5 was calculated to be 1.20 mmol/g. This is
consistent with the loading level of polymer 5 (w1.2 mmol/g) de-
termined via gel permeation chromatography (molecular weight of
polymer 5¼26,093) and 1H NMR spectroscopy.
Polymer 8 was subsequently oxidized with m-CPBA in the
presence of KOH to polymer 2. Through 1H NMR spectroscopic
analysis of polymer 2 and elemental analysis, the loading of poly-
mer 2 was determined to be w1.00 mmol/g.
1. SO2Cl
SO3Na
SO2NH2
Styrene, THF
2.2. Oxidation of alkenes and silyl enol ethers
2. NH3 .H2O
3
4
AIBN, reflux,
48 h
Like peracids, 2-sulfonyloxaziridines epoxidize alkenes in a syn
stereospecific manner.25 However, compared to the peracids, oxi-
dation with 2-benzenesulfonyl-3-(p-nitrophenyl)oxaziridine oc-
curs much more slowly and a typical reaction requires 3e12 h of
heating at 60 ꢁC.26 With polymer 2 in our hands, we proceeded to
examine such reactions using trans-stilbene 9a. As observed in
solution-phase epoxidation, reaction of 9a with polymer 2 pro-
vided an observable change in color from an initial yellow solution
to an intense yellow solution and with 1.25 equiv of polymer 2, the
yield of 10a was 50% (entry 1, Table 2). To optimize the reaction, we
varied the amount of polymer 2, the solvent and reaction condition.
The best yield was obtained when the reaction was carried out in
CH2Cl2 under microwave irradiation for 15 min (entry 5, Table 2).
SO2NH2
5
[styrene: 4 = 6:1 (as
determined by 1H NMR)]
Et
Et
O 180 oC,
PPTS, EtOH
40 oC, 8 h
O2N
O2N
CHO
6 h
O
6
7
m-CPBA, KOH, CH2Cl2
SO2N
rt, 45 min
Table 2
Epoxidation of trans-stilbene 9a by polymer 2
NO2
8
O
O
S
O
N
O
2 (2 equiv)
NO2
2
[styrene: 2-(phenylsulfonyl)-3-(p-nitrophenyl)oxaziridine= 7:1
(as determined by 1H NMR)]
9a
10a
Entry
Solvent
Reaction condition
Yielda (%)
Scheme 1. Synthesis of polymer 2.
1
2
3
4
5
6
7
8
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
Reflux, 4 h
Reflux, 4 h
Reflux, 4 h
50b
73c
88
42
93
87
90
67
Following the synthesis of polymer 5, we initially attempted to
directly condense it with 4-nitrobenzaldehyde 6 to obtain polymer
8. Jennings and Lovely19 have shown that addition of TiCl4 to
a mixture of aromatic aldehyde, sulfonamide, and triethylamine in
CH2Cl2 gave the N-sulfonylimine after ca. 30 min at 0 ꢁC. However,
when the procedure was applied to 6 and polymer 5, the reaction
had tobe carried out under reflux in order for the reaction to proceed
(entry 1, Table 1). Polymer 8 that precipitated from cold hexane was
m
m
m
m
m
W, 100 ꢁC, 5 min
W, 100 ꢁC, 15 min
W, 100 ꢁC, 15 min
W, 100 ꢁC, 15 min
W, 100 ꢁC, 15 min
CHCl3
Toluene
a
Isolated yield.
b
c
Using 1.25 equiv of polymer 2.
Using 1.5 equiv of polymer 2.
Table 1
Synthesis of polymer 8 from polymer 5 and 4-nitrobenzaldehyde 6 or 1-(dieth-
yloxymethyl)-4-nitrobenzene 7
To demonstrate the applicability of polymer 2 to the oxidation of
alkenes, five other substrates were tested using the optimized re-
action condition and good yields were obtained for all cases (Table
3). This shows that polymer 2 is able to oxidize alkenes in good
yields and in a much shorter reaction time.
Encouraged by these results, we further explored the use of
polymer 2 in the oxidation of silyl enol ethers 11 (Scheme 2). Under
microwave irradiation at 100 ꢁC, the oxidation was completed in
Entry
Condition
Reaction time (h)
% Conversiona
1
TiCl4, Et3N, CH2Cl2, 6, reflux
FeCl3, EtOH, 6, rt
Amberlyst 15, 6, toluene, reflux
TFAA, 6, CH2Cl2, reflux
Ti(OEt)4, CH2Cl2, 6, reflux
7, 180 ꢁC
6
24
24
24
24
6
75
d
2
3b
4
25
30
25
78
5
6
20 min and the
a-silyl epoxide 12 that formed was isolated in
a
Determined by comparing the loading of polymer 5 with the loading of polymer
8. Loading of polymer 5 was determined by elemental analysis whilst loading of
polymer 8 was determined by 1H NMR.
quantitative yield. Compound 12 was then further treated with 2 M
HCl (Table 4) to afford the corresponding
yield (Table 5).
a-hydroxy ketone in good
b
Ref. 24.

W. Susanto, Y. Lam / Tetrahedron 67 (2011) 8353e8359
8355
Table 3
Table 5
Epoxidation of alkenes using 2
Oxidation of silyl enol ether using 2
Entry
Substrate
Product
Yielda (%)
Entry
1
Substrate
Product
Yielda,b (%)
O
TMSO
Ph
Ph
OH
93
Ph
O
Ph
1
93 (70b, 58c)
11a
13a
O
TMSO
Ph
10a
9a
9b
9c
OH
2
3
83
Ph
13b
O
11b
2
3
79
85
10b
OTMS
O
OH
O
89
92
13c
11c
10c
O
TMSO
Ph
O
4
5
75
72
4
Ph
13d
9d
10d
OH
Cl
Cl
11d
a
Isolated yield.
Purity of product ꢂ95%.
O
b
10e
9e
O
prepared by oxidation of pyridines with hydrogen peroxide, per-
acids, sodium perborate or sodium percarbonate in the presence of
catalysts.30e35 To carry out the oxidation in a more environmentally
friendly manner, various polymer-supported catalysts and solid-
state oxidative processes have been developed.36e38 However the
shortcomings of these methods are the requirement of higher
temperatures or catalyst loading and long reaction times. To our
knowledge, there are no earlier reports on the oxidation of pyri-
dines with polymer-supported 2-phenylsulfonyloxaziridines.
Hence in this work, we have investigated the performance of
polymer 2 on such an oxidative reaction.
4-Ethyl-pyridin-2-ylamine 14a was used as a model substrate
in the oxidation to the corresponding N-oxide with polymer 2
(2.5 equiv) employing the optimized conditions obtained by
varying solvent and reaction conditions (Table 6). Under micro-
wave irradiation at 100 ꢁC, oxidation of 14a was completed in
2 min and 4-ethyl-pyridin-2-ylamine N-oxide 15a was obtained in
quantitative yield (entry 3, Table 6). Application of this reaction
condition to other pyridine analogs also resulted in good yields
(Table 7).
6
88 (70b)
9f
10f
a
Yield of isolated product.
b
Solution-phase reaction yield using 2-(phenylsulfonyl)-3-(p-nitrophenyl)oxa-
ziridine (2 equiv), CHCl3, 60 ꢁC, 12 h (Ref. 25).
c
Using polymer 1 (2 equiv),
m
W, 100 ꢁC, CH2Cl2. Reaction was incomplete.
R3
TMSO
R1
R3
R2
O
TMSO
O
R3
R2
2 (2 equiv), CH2Cl2,
100 oC, µW, 20 min
2M HCl, THF
rt, 3.5 h
R2
OH
R1
R1
11
13
12
Scheme 2. Synthesis of
a
-hydroxy ketone from silyl enol ether.
Table 4
Conversion of 12a to 13a
O
TMSO
Ph
O
Ph
rt
Ph
Ph
OH
13a
12a
Entry
Solvent
Reaction condition
DDQ, 5 hb
2 M HCl, 3.5 h
5% HCl, 7 hd
Bu4NF, 2 h
Yielda (%)
Table 6
1
2
3
4
Wet EtOAc
THF
THF
67c
93
Oxidation of 4-ethyl-pyridin-2-ylamine 14a with 2
76e
56c
THF
2 (2.5 equiv)
a
Isolated yield.
Ref. 26.
Over-oxidation of benzoin observed.
Ref. 17.
TLC showed incomplete reaction.
N
NH2
N
NH2
b
c
O
15a
d
e
14a
Entry
Solvent
Reaction conditions
rt, 4 h
Yielda (%)
1
2
3
4
5
6
CH2Cl2
CH2Cl2
CH2Cl2
THF
CHCl3
CH2Cl2
93
98
99
89
96
96b
2.3. Oxidation of pyridine
m
m
m
m
m
W, 60 ꢁC, 25 min
W, 100 ꢁC, 2 min
W, 100 ꢁC, 25 min
W, 100 ꢁC, 7 min
W, 100 ꢁC, 14 min
Pyridine N-oxide derivatives are compounds of growing im-
portance as there has been increasing interest in them as chiral
controllers for asymmetric synthesis27 as well as inhibitors to the
human immunodeficiency virus (HIV),28 human SARS, and feline
infectious peritonitis coronavirus.29 These N-oxides are typically
a
Isolated yield.
Using 1.2 equiv of 2.
b

8356
W. Susanto, Y. Lam / Tetrahedron 67 (2011) 8353e8359
Table 7
2.4. Oxidative rearrangement
Oxidation of pyridines with 2
In our earlier work,16 we have reported the rearrangement of
tetrahydrobenzimidazoles to the corresponding 5-imidazolone
using polymer 1. Since polymer 1 was not thermally stable, the
rearrangement reaction had to be carried out at room temperature,
which required 24 h to complete and provided the product in
moderate yields (61e62%). To determine if the rearrangement
would proceed more favorably at higher temperatures, we applied
polymer 2 to the reaction. To begin, 1-methyl-4,5,6,7-tetrahydro-
1H-benzimidazole 16a was dissolved in CH2Cl2 and treated with
polymer 2 (2 equiv) under reflux for 6 h. To our delight, this gave
17a in 82% yield. Subsequently, we explored the reaction under
microwave irradiation and found that at 100 ꢁC, the reaction was
completed within 45 min providing 17a in 85% yield. Applying this
reaction condition to other analogs of 16 also resulted in good
yields of the oxidative rearranged product (Table 8).
2 (2.5 equiv), 100 o
CH2Cl2, µW, 2 min
R1
C
R1
N
O
15
N
14
Entry
1
Substrate
Product
Yielda (%)
92
O2N
O2N
O
N
N
14b
15b
2
91
82
N
N
N
O
15c
14c
2.5. Recycling of 2
Ph
Ph
The reduced product of the oxygen transfer reaction with
polymer 2 is polymer 8 (Scheme 3). To regenerate the oxidant, the
spent polymer was reoxidized with m-CPBA/KOH. With careful
repetitive regeneration of consumed 2, the loading levels could be
restored to 0.8e1.0 mmol/g.
N
O
3
O
O
14d
15d
a
Isolated yield.
O
O
N
Table 8
starting
S
m-CBA/KOH
Oxidation rearrangement of tetrahydrobenzimidazole 16 using 2
NO2
O
R1
2
O
R1
R2
2 (2.5 equiv)
100 oC, µW, 45 min
N
N
R2
[O]
[O]
N
N
17
N
16
SO2
product
m-CPBA/KOH
Entry
1
Substrate
Product
Yielda (%)
NO2
8
O
Me
N
Scheme 3. Recycling of polymer 2.
Me
N
85 (82b, 61c)
To determine the oxidative activity of regenerated 2, different
oxidative reactions were performed to demonstrate the recycling
possibility. Gratifyingly, the regenerated 2 was indistinguishable
from polymer 2 and showed a slow decline in oxidative activity
after multiple recovery steps (Table 9).
N
16a
N
17a
MOM
N
O
MOM
N
2
3
63 (50d)
N
16b
N
17b
3. Conclusion
Bn
N
In summary, we have developed a thermally stable polymer-
supported oxidant 2, which can be applied to reactions that oc-
curred at elevated temperatures. With polymer 2, the microwave-
assisted reactions at elevated temperatures generally required
much shorter reaction times and gave excellent to good yields of
the desired product. Polymer 2 was proven to be a potent oxidant,
effecting clean and selective oxidation of alkenes, silyl enol ethers,
and pyridines. It also enables tetrahydrobenzimidazoles to be oxi-
datively rearranged in an efficient manner to the spiro fused 5-
imidazolones.
O
Bn
N
85 (80b, 62c, 21e)
N
17c
N
16c
Bn
N
O
Bn
N3
77 (70f)
N
4
N3
N
16d
N
17d
a
Isolated yield.
b
Solution-phase oxidative rearrangement using 2-benzenesulfonyl-3-
4. Experimental
4.1. General
phenyloxaziridine (2 equiv), CHCl3 at room temperature for 4 h (Ref. 39).
c
Isolated yield when the oxidative rearrangement was carried out with polymer
1 (2 equiv) at room temperature for 24 h.
d
Solution-phase oxidative rearrangement using 2-benzenesulfonyl-3-
phenyloxaziridine (2 equiv), CHCl3 at 35 ꢁC for 24 h (Ref. 39).
All chemical reagents were obtained from Aldrich, Merck, Lan-
caster or Fluka and used without further purification. Moisture-
sensitive reactions were carried out under nitrogen with com-
mercially obtained anhydrous solvents. Analytical thin-layer
e
Isolated yield when the oxidative rearrangement was carried out with polymer
1 (2.5 equiv), 100 ꢁC,
mW, 45 min.
f
Solution-phase oxidative rearrangement using 2-(phenylsulfonyl)-3-(p-nitro-
phenyl)oxaziridine (2 equiv), CHCl3 at 35 ꢁC for 24 h (Ref. 39).

W. Susanto, Y. Lam / Tetrahedron 67 (2011) 8353e8359
8357
Table 9
argon for 30 min and then heated to reflux for 48 h. Thereafter, the
reaction mixture was concentrated and the resulting residue was
dissolved in THF (1 mL) and added slowly into vigorously stirred
hexane (10 mL). The resulting suspension that formed was filtered
by suction filtration and washed with cold methanol to afford
polymer 5 as a white powder. Yield: 0.267 g (80%). Loading calcu-
lated from elemental analysis data: 1.30 mmol/g; 1H NMR (CDCl3,
Recycling versus oxidative activity of 2
Recycling
Yielda (%)
2 (2 equiv)
O
MW, 100 oC,
15 min
500 MHz)
ArH). IR (KBr)
1163 cmꢀ1
d
1.43e1.84 (m, H2OþeCH2CHe), 6.58e7.60 (m, 40H,
9a
10a
n
¼3078, 3059, 2921, 2850, 1492, 1452, 1338,
Initial
First
Second
Third
Fourth
Fifth
93
93
91
90
89
86
.
4.4. Synthesis of 1-(diethoxymethyl)-4-nitrobenzene 7
Pyridinium p-toluenesulfonate (PPTS) (0.025 g, 0.1 mmol) was
added to a solution of 4-nitrobenzaldehyde 6 (0.151 g, 1 mmol) in
ethanol (10 mL). The solution mixture was heated for 12 h at 40 ꢁC
and then poured into brine solution and extracted with ethyl ace-
tate (3ꢃ5 mL). The combined organic extract was then dried over
MgSO4, concentrated, and purified by flash column chromatogra-
phy using 1:9 (EtOAc/hexane) system to give 7 as a yellow liquid
Bn
N
O
Bn
2 (2.5 equiv)
100 oC, MW, 45 min
N
R2
N
16c
N
17c
Initial
First
Second
Third
85
(Rf¼0.32). Yield: 0.192 g (85%). 1H NMR (CDCl3, 300 MHz)
d 1.23 (t,
83
82
80
79
6H, J¼7.0 Hz), 3.57 (m, 2H), 5.56 (s, 1H), 7.65 (d, 2H, J¼8.8 Hz), 8.20
(d, 2H, J¼8.8 Hz). 13C NMR (CDCl3, 75 MHz)
d 15.1, 61.3, 100.1, 123.4,
127.7, 146.1, 147.9. HRMS (EI): m/z¼225.1000, calcd for C11H15O4N:
Fourth
a
Isolated yield.
225.1001.
4.5. Synthesis of polymer-supported N-benzenesulfonamide-
p-nitro-benzylidene 8
chromatography (TLC) was carried out on precoated plates (Merck
silica gel 60, F254) and visualized with UV light or stained with the
Dragendorff-Munier and Hanessian stain. Flash column chroma-
tography was performed with silica (Merck, 230e400 mesh). NMR
spectra (1H and 13C) were recorded at 298 K on a Bruker ACF300,
DPX300 or AMX500 Fourier Transform spectrometers. Chemical
1-(Diethoxymethyl)-4-nitrobenzene 7 (1.54 g, 6.83 mmol) and
polymer-supported benzenesulfonamide 5 (8.45 g, 6.5 mmol) were
added into a 100-mL single-necked round-bottomed flask equip-
ped with short-path distilling head. The reaction mixture was
heated at 180 ꢁC in an oil bath until all the ethanol had ceased
distilling over (w6 h). After which, the reaction mixture was placed
under high vacuum and cooled to room temperature. The crude
solid product obtained was dissolved in CH2Cl2 (8 mL) and pre-
cipitated by slow addition into ice-cold CH3OH (25 mL). The sus-
pension was then filtered by suction filtration to afford polymer 8
as a yellow solid. Yield: 75e80%. 1H NMR (CDCl3, 500 MHz)
shifts are expressed in terms of d parts per million (ppm) relative to
the internal standard tetramethylsilane (TMS). Mass spectra were
performed on Finnigan TSQ 7000 for EI normal mode or Finnigan
MAT 95XL-T spectrometer under EI, ESI, and FAB techniques. All
infrared (IR) spectra were recorded on a Bio-Rad FTS 165 spec-
trometer. All isolated products are of ꢂ95% purity (by 1H NMR).
Microwave reactions were performed on the Biotage InitiatorÔ
microwave synthesizer.
d
1.41e1.77 (m, H2OþeCH2CHe), 6.55e8.32 (m, 40H, ArH), 9.13 (s,
1H, CH). IR (KBr)
n
¼3082, 3060, 2923, 1595, 1527, 1346, 1162 cmꢀ1
.
4.2. Synthesis of 4-vinylbenzenesulfonamide 4
4.6. Synthesis of polymer-supported 2-benzenesulfonyl-3-(p-
To an ice-cooled solution of the sodium salt of 4-styrenesulfonic
acid 3 (10.3 g, 50 mmol) in dimethylformamide (DMF) (83 mL)
under a nitrogen atmosphere was added thionyl chloride (30 mL,
413 mmol). The reaction mixture was stirred for 6 h and then left in
the fridge overnight. The solution was slowly poured into ice-water
(150 mL) and extracted with ether (70 mLꢃ3). The combined
washing was dried with MgSO4 and concentrated to give the in-
termediate product, a sulfonyl chloride, which was then reacted
with aqueous ammonium hydroxide (180 mL) for 2 h. Thereafter,
the reaction mixture was extracted with ether and the combined
ether extract was dried with MgSO4 and concentrated to give 4 as
nitrophenyl)oxaziridine 2
Polymer 8 (0.51 g, 0.5 mmol) was added to a white suspension of
m-CPBA (70e75% purity, 0.216 g, 1.25 mmol) and powdered KOH
(0.093 g, 1.65 mmol) in 5 mL of CH2Cl2 (previously prepared and
stirred for 30 min at room temperature) and stirred for another
45 min. The reaction mixture was then filtered though Celite and
the filter cake was washed with CH2Cl2 (10 mLꢃ3). The combined
filtrate and washings were concentrated to a small volume (w3 mL)
and added slowly into vigorously stirred ice-cold CH3OH (25 mL).
The resulting suspension was filtered by suction filtration and dried
in high vacuum to afford polymer 2 as a pale yellow powder; yield:
95e98%. Loading calcd by 1H NMR spectroscopy: 1.00 mmol/g and
elemental analysis: 1.04 mmol/g. 1H NMR (CDCl3, 500 MHz):
a white solid. Yield: 4.53 g (60%). 1H NMR (CDCl3, 500 MHz)
d 4.88
(s, 2H), 5.43 (d, 1H, J¼10.7 Hz), 5.88 (d, 1H, J¼17.7 Hz), 6.75 (dd, 1H,
J¼10.7 and 17.7 Hz), 7.52 (d, 2H, J¼8.2 Hz), 7.87 (d, 2H, J¼8.2 Hz). 13C
NMR (acetone-d6, 125 MHz) d 115.9, 126.0, 126.1, 135.2, 140.6, 142.9.
d
1.43e1.84 (m, H2OþeCH2CHe), 5.57 (s, 1H, CH), 6.57e8.25 (m,
40H, ArH); IR (KBr):
¼3061, 3024, 2920, 2850, 1604, 1490, 1444,
1354, 1174, 1083, 1022 cmꢀ1
HRMS (EI): m/z¼183.0354, calcd for C8H9O2NS: 183.0354.
n
.
4.3. Synthesis of polymer-supported benzenesulfonylamide 5
4.7. General procedure for alkene oxidation by polymer 2
To a mixture of styrene (0.34 mL, 3 mmol) and 4 (0.091 g,
0.5 mmol) in tetrahydrofuran (THF) (10 mL) was added AIBN
(0.0025 g, 0.015 mmol). The reaction mixture was purged with
Polymer 2 (0.6 mmol (based on the oxidizing equivalent)) was
added to a solution of the respective alkene 9 (0.3 mmol) in dry

8358
W. Susanto, Y. Lam / Tetrahedron 67 (2011) 8353e8359
CH2Cl2 (1.5 mL) placed in a sealed microwave vessel. The reaction
mixture was microwave irradiated (with the heating program
starting at 150 W) at 100 ꢁC for 15 min. When the reaction is
completed, the polymer-supported reagent was precipitated with
ice-cold CH3OH (25 mL) and filtered through filter paper. The filter
cake was then washed with ice-cold CH3OH (3ꢃ10 mL). The com-
bined filtrate and washing was concentrated to 2e3 mL and filtered
100 ꢁC for 45 min. When the reaction was completed, the polymer-
supported reagent was precipitated with cold methanol (25 mL)
and filtered through filter paper. The filter cake was washed with
cold methanol (3ꢃ10 mL) and the combined filtrate and washings
was concentrated to 2e3 mL and filtered through a MiniartÒ single
use syringe filter (pore size 0.2 mm) to remove any residual polymer.
The filtrate was concentrated and purified by a simple flash column
chromatography to give 17.
through a MiniartÒ single use syringe filter (pore size 0.2
mm) to
remove any residual polymer. The filtrate was concentrated and
purified using simple flash column chromatography to afford 10.
4.13. General procedure for the regeneration of polymer-
supported 2-benzenesulfonyl-3-(p-nitrophenyl)oxaziridine 2
4.8. Preparation of silyl enol ether 11
To a solution of m-CPBA (70e75% purity, 0.216 g, 1.25 mmol) in
CH2Cl2 (5 mL) was added powdered KOH (0.093 g, 1.65 mmol) and
the resulting suspension was stirred at room temperature for
30 min. Thereafter, the spent polymer (0.5 mmol) was added and
the mixture was stirred at room temperature for an additional
45 min. After this, the reaction mixture was filtered though Celite
and the filter cake was washed with CH2Cl2 (10 mLꢃ3). The com-
bined filtrate and washings were concentrated to a small volume
(w3 mL) and added slowly into vigorously stirred ice-cold CH3OH
(25 mL). The resulting suspension was filtered by suction filtration
and dried in high vacuum to afford polymer 2.
The compound was synthesized according to a literature
procedure.40
4.9. General procedure for silyl enol ether oxidation by
polymer 2
Polymer 2 (0.6 mmol (based on the oxidizing equivalent)) was
added to a solution of the respective silyl enol ether 11 (0.3 mmol) in
dryCH2Cl2 (1.5 mL) placed in asealed microwavevessel. Thereaction
mixture was then microwave irradiated (with the heating program
starting at 150 W) at 100 ꢁC for 20 min. When the reaction was
completed, the polymer-supported reagent was precipitated with
ice-cold CH3OH (25 mL) and filtered through a filter paper. The filter
cake was then washed with ice-cold CH3OH (3ꢃ10 mL). The com-
bined filtrate and washing was concentrated to 2e3 mL and filtered
Acknowledgements
The authors thank the National University of Singapore for the
financial support provided (R-143-000-399-112).
through a MiniartÒ single use syringe filter (pore size 0.2
mm) to
remove any residual polymer. The filtrate was concentrated to dry-
ness to afford the respective epoxide 12. The compound 12 was then
stirred in a mixture of 2 M of HCl (3 mL) and THF (5 mL) and the
hydrolysisreactionwasmonitoredusing TLC. Whenthe reactionwas
completed, the reaction mixture was diluted with EtOAc and the
aqueous phase was extracted with EtOAc (5 mL). The combined or-
ganic extract was washed with brine, dried over MgSO4, filtered,
concentrated, and purified by a simple flash column chromatogra-
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2011.08.058.
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