Facile method for solid-phase synthesis of vinyl sulfones using polystyrene-supported selenomethyl aryl sulfone

Article abstract of DOI:10.1081/SCC-200050950

Treatment of novel polystyrene-supported selenomethyl aryl sulfone with LDA followed by alkylation and oxidation elimination efficiently afforded vinyl sulfones in good yields and purities.

Full text of DOI:10.1081/SCC-200050950

This article was downloaded by: [The Aga Khan University]
On: 14 November 2014, At: 20:43
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
Synthetic Communications: An International
Journal for Rapid Communication of
Synthetic Organic Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lsyc20
Facile Method for Solid‐Phase Synthesis of
Vinyl Sulfones Using Polystyrene‐Supported
Selenomethyl Aryl Sulfone
a
a
b
a
Shou‐Ri Sheng , Wei Zhou , Ming‐Hua Zhong , Xiao‐Ling Liu & Hui‐Zong
a
Chen
a
Institutes of Chemistry , Jiangxi Normal University , Nanchang, P.R. China
b
Department of Chemistry , Hanshan Teacher's College , Chaozhou, P.R.
China
Published online: 20 Aug 2006.
To cite this article: Shou‐Ri Sheng , Wei Zhou , Ming‐Hua Zhong , Xiao‐Ling Liu & Hui‐Zong Chen (2005) Facile
Method for Solid‐Phase Synthesis of Vinyl Sulfones Using Polystyrene‐Supported Selenomethyl Aryl Sulfone,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
35:6, 815-821, DOI: 10.1081/SCC-200050950
To link to this article: http://dx.doi.org/10.1081/SCC-200050950
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

w
Synthetic Communications , 35: 815–821, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200050950
Facile Method for Solid-Phase Synthesis of
Vinyl Sulfones Using Polystyrene-Supported
Selenomethyl Aryl Sulfone
Shou-Ri Sheng and Wei Zhou
Institutes of Chemistry, Jiangxi Normal University, Nanchang,
P.R. China
Ming-Hua Zhong
Department of Chemistry, Hanshan Teacher’s College, Chaozhou,
P.R. China
Xiao-Ling Liu and Hui-Zong Chen
Institutes of Chemistry, Jiangxi Normal University, Nanchang,
P.R. China
Abstract: Treatment of novel polystyrene-supported selenomethyl aryl sulfone with
LDA followed by alkylation and oxidation elimination efficiently afforded vinyl
sulfones in good yields and purities.
Keywords: Polystyrene-supported selenomethyl aryl sulfone, solid-phase synthesis,
vinyl sulfone
Solid-phase synthesis has gained widespread acceptance in combinatorial
chemistry related to drug discovery in order to accelerate lead generation and
[
1]
lead optimization.
Synthesis on a polymer support shows a number
of advantages as compared to solution chemistry. The most salient one is the
possibility of applying excesses of reagents and removing them with-
out involving time-consuming separation techniques. Vinyl sulfones have
Received in Japan February 18, 2004
Address correspondence to Shou-Ri Sheng, Institutes of Chemistry, Jiangxi Normal
University, Nanchang 330027, P.R. China. E-mail: shengsr@163.com

8
16
S.-R. Sheng et al.
now become generally accepted useful intermediates in organic synthesis,
e.g., serving efficiently as both Michael acceptors and p partners in cyclo-
addition reaction. Many methods for preparing vinyl sufones have been
[
2]
developed. Among these methods, the ionic and radical addition of seleno-
[3]
sulfonate to alkenes and alkynes is an important procedure. However,
organic selenium reagents typically have a foul smell and are quite toxic, which
is often problematic in organic synthesis. Recently, polymer-bound selenides
have proven to be versatile traceless linkers, which give access to alkenes
[
4]
by oxidation elimination. Furthermore, the use of polymeric selenium
reagents has significant advantages, including decreased volatility, conven-
ience of handing, and simplification of product workup. In our previous com-
munication, we used polymer-supported b-selenopropionic acid to prepare
[
5]
acrylamides; we here wish to report a facile synthetic approach to vinyl
sulfones from polystyrene-supported selenomethyl aryl sulfone 3 (Scheme 1).
The resin 3a–3b was easily prepared in a few steps from crosslinked (1%)
[4a]
polystyrene by reaction of polystyrene-supported lithium selenide 2
with
chloromethyl phenyl sulfone and chloromethyl p-tolyl sulfone, respectively.
The formation of 3 could be monitored by FT-IR. There were two strong
2
characteristic sulfone stretches at 1317 and 1145 cm , with a loading
1
of 1.28 mmol/g (3a, Ar ¼ C H ) and a loading of 1.25 mmol/g (3b,
6
5
Ar ¼ p-CH C H ), as determined by elemental analysis. Resin 3 can be
3
6 4
stored at room temperature for long time without diminution of capacity or
the liberation of disagreeable odors.
As illustrated, reaction of the lithio derivative of resin 3 with representative
primary alkyl halides 4 furnished the a-selenylated alkyl aryl sulfone resin 5,
which could not be reliably analyzed with FT-IR. Hence we carried out the
next cleavage reaction directly after washing the resin 5 with solvents.
Treatment of resin 5 with 30% hydrogen peroxide at 08C and then at room
temperature afforded the corresponding vinyl sulfones 6 in good yields
(86–93%) and with good purities of crude materials (92–96%). The results
are summarized in Table 1. It should be noted that trans-1-alkenylsulfones
Scheme 1.

Solid-Phase Synthesis of Vinyl Sulfones
817
Table 1. Yields and purities of vinyl sulfones (6aa–6bf)
a
Yield (%)
b
Purity (%)
Resin
RCH
2
X (4)
Product
3a
3a
3a
3a
3a
3b
3b
3b
C
NCCH Cl (4b)
6
H
5
CH
2
Br (4a)
6aa
6ab
6ac
6ad
6ae
6ba
6bb
6bf
90
86
91
93
93
90
87
91
92
95
92
96
96
94
95
93
2
CH OCOCH Br (4c)
3
3
3
2
CH
CH
CH
I (4e)
2
Br (4d)
C H CH Br (4a)
5
6
2
NCCH
CH (CH ) Br (4f)
2
Cl (4b)
3
2 3
a
Yields were based on the functional loading of resin 3.
b
Purities of crude products were determined by HPLC.
are formed exclusively except for compound 6e. The residual resin,
polystyrene-supported phenylseleninic acid, was obtained as a by-product
[6]
whose infrared data was identical to the previously reported data and
showed no residual –SO – absorption, which indicated the oxidative
cleavage was complete.
2
In conclusion, we have developed a facile methodology for the solid-
phase construction of vinyl sulfones in good yields and purities employing a
selenium-based traceless linker strategy. Although an excess amount of
reagents is required, simple workup procedures take the place of the time-
consuming isolation and purification steps in the solution-phase synthesis.
EXPERIMENTAL
1
Melting points were not corrected. H NMR spectra were recorded on a Bruker
Avance 400 M Hz spectrometer in CDCl with TMS as internal standard.
3
FT-IR spectra were taken on a Perkin Elmer One instrument. Mass spectra
(
EI, 70 eV) were recorded on a HP5989B mass spectrometer. THF was
newly distilled from sodium/benzophenone before use. Polystyrene (100/
00 mesh, crosslinked with 1% divinylbenzene) for the preparation of poly-
styrene-supported selenium bromide according to the procedure described
2
[
4a]
by Nicolaou,
sulfone were purchased from Aldrich.
chloromethyl phenyl sulfone, and chloromethyl p-tolyl
Procedure for the Synthesis of Polystyrene-Supported
Selenomethyl Aryl Sulfone 3
Under a nitrogen atmosphere, LiBH (3 mmol) was added to polystyrene-
4
supported selenium bromide 1 (1.0 g, 1.50 mmol Br/g, the loading of

8
18
S.-R. Sheng et al.
functional Br was analyzed by elementary analysis) swelled in THF (10 mL)
for 30 min. After 1 h with stirring at room temperature, chloromethyl aryl
sulfone (3 mmol) in 2 mL of THF was added slowly and the mixture was
stirred for 10 h. The resin 3 was collected by filtration, washed successively
with H O (2 ꢀ 20 mL), THF (2 ꢀ 5 mL) and CH Cl (2 ꢀ 5 mL), and then
2
2
2
dried in a vacuum. 3a: 1.28 mmol S/g, IR n (KBr): 3022, 2921, 1600, 1495,
1
448, 1317, 1303, 1145, 1070, 810, 751, 696, 579, 526; 3b: 1.25 mmol S/g,
IR n (KBr): 3023, 2920, 1600, 1496, 1445, 1317, 1300, 1145, 1074, 821,
54, 700, 578, 530.
7
General Procedure for the Preparation of Vinyl Sulfones 6aa–6bf
Resin 3 (1.0 mmol) was swelled in THF (10 mL) at room temperature for
30 min. After cooling to 788C, a solution of LDA (0.6 mL, 2.0 M) was
added under nitrogen and the mixture was stirring at the same temperature
for 30 min. Then, a solution of primary alkyl halide 4a–4f (1.5 mmol) in
THF (2 mL) was added and the mixture was warmed up gradually to room
temperature and kept standing for 5 h. After neutralization with 1% hydro-
chloric acid, the resin 5aa–5bf was collected on a filter and washed succes-
sively with H O (3 ꢀ 15 mL), THF (3 ꢀ 5 mL), and Et O (3 ꢀ 5 mL),
2
2
suspended in THF (10 mL), and treated with 1.0 mL (11.6 mmol) of 30%
H O . After stirring for 20 min at 08C, and then for 20 min at room tempera-
2
2
ture, the residual resin was collected by filtration and washed CH Cl
(
2
2
4 ꢀ 5 mL). The filtrate was washed with water (2 ꢀ 30 mL), dried over
magnesium sulfate, and concentrated to give crude products, which were
purified by preparative TLC on silica gel or crystallization, affording the
1
final products 6aa–6bf for H NMR analysis.
[2j]
(E)-2-(Phenylsulfonyl)styrene (6aa)
1
White crystals; mp 75–768C (lit. 768C). H NMR: d 6.88 (d, J ¼ 15.3 Hz,
1H), 7.38–7.42 (m, 3H), 7.46–7.50 (m, 2H), 7.52–7.56 (m, 2H), 7.58–7.62
(
m, 1H), 7.70 (d, J ¼ 15.2 Hz, 1H), 7.87–7.96 (m, 2H). IR: nmax 3060,
2
6
925, 1615, 1577, 1494, 1447, 1308, 1145, 1085, 972, 856, 818, 746,
88 cm
2
1
.
(E)-3-(Phenylsulfonyl)acrylonitrile (6ab)
1
Colorless oil. H NMR: d 6.55 (d, J ¼ 15.6 Hz, 1H), 7.23 (d, J ¼ 15.6 Hz, 1H),
7
.61–7.65 (m, 2H), 7.73–7.76 (m, 1H), 7.89–7.95 (m, 2H). MS (m/e): 195
þ
þ
þ
(
M þ 2, 0.39), 194 (M þ 1, 1.90), 193 (M , 3.98), 141, 129, 127, 126,
1
1
25, 102, 97, 93, 77, 65, 51. IR: n
084, 936, 837, 755, 721, 686, 610 cm
3061, 2228, 1585, 1447, 1315, 1151,
max
2
1
.

Solid-Phase Synthesis of Vinyl Sulfones
819
Methyl (E)-3-(phenylsulfonyl)acrylate (6ac)
1
Colorless oil. H NMR: d 3.80 (s, 3H), 6.86 (d, J ¼ 15.2 Hz, 1H), 7.36
(
(
d, J ¼ 15.2 Hz, 1H), 7.58–7.63 (m, 2H), 7.69–7.73 (m, 1H), 7.89–7.94
þ þ þ
m, 2H). MS (m/e): 228 (M þ 2, 0.26), 227 (M þ 1, 1.30), 226 (M ,
.60), 195, 161, 150, 141, 131, 127, 126, 125, 118, 103, 97, 77, 51. IR:
nmax 3065, 2955, 1723, 1615, 1550, 1448, 1435, 1305, 1238, 1170, 1151,
1
2
1
1
086, 970, 821, 756, 738, 698, 680 cm
.
[
7]
(E)-1-(Phenylsulfonyl)propene (6ad)
1
White crystals; mp 67–688C (lit. 67–688C). H NMR: d 2.01 (dd, J ¼ 7.0,
1
1
3
6
.7 Hz, 3H), 6.33 (dq, J ¼ 15.0, 1.7 Hz, 1H), 6.90 (dq, J ¼ 15.0, 7.0 Hz,
H), 7.48–7.52 (m, 2H), 7.59–7.63 (m, 1H), 7.74–7.84 (m, 2H). IR: n
062, 2955, 1620, 1550, 1448, 1375, 1320, 1160, 1080, 971, 820, 756, 738,
max
2
1
95 cm
.
[
7]
Phenylsulphonylethene (6ae)
White crystals; mp 65–668C (lit. 67–688C). 5.72 (dd, J ¼ 10.1, 2.1 Hz, 1H),
6
.32 (dd, J ¼ 17.0, 10.1 Hz, 1H), 6.41 (dd, J ¼ 16.9, 2.1 Hz, 1H), 7.63–7.66
(m, 2H), 7.75–7.77 (m, 1H), 7.83–7.90 (m, 2H). IR: n 3060, 2955, 1615,
max
2
1
1
550, 1448, 1320, 1160, 1080, 991, 910, 756, 695 cm
.
[3a]
(E)-2-(p-Toluenesulfonyl)styrene (6ba)
1
White crystals; mp 121–1228C (lit. 121–1228C). H NMR: d 2.45 (s, 3H),
6
7
n
6
.86 (d, J ¼ 15.2 Hz, 1H), 7.35 (d, J ¼ 8.0 Hz, 2H), 7.36–7.41 (m, 3H),
.46–7.51 (m, 2H), 7.65 (d, J ¼ 15.4 Hz, 1H), 7.82 (d, J ¼ 8.1 Hz, 2H). IR:
3061, 2925, 1613, 1597, 1450, 1316, 1305, 1145, 1085, 973, 860, 746,
.
max
2
1
65, 635 cm
[3a]
(E)-3-(p-Toluenesulfonyl)acrylonitrile (6bb)
1
White crystals; mp 132–1338C (lit. 132–1348C). H NMR: d 2.50 (s, 3H),
6
2
1
.51 (d, J ¼ 15.7 Hz, 1H), 7.22 (d, J ¼ 15.7 Hz, 1H), 7.42 (d, J ¼ 8.0 Hz,
H), 7.79 (d, J ¼ 8.1 Hz, 2H). IR: n 3068, 2231, 1597, 1323, 1150,
max
2
1
086, 955, 836, 802, 666, 585 cm
.
[2d]
(E)-1-(p-Toluenesulfonyl)pentene (6bf)
1
Colorless oil. H NMR: d 0.92 (t, J ¼ 7.0 Hz, 3H), 1.43–1.54 (m, 2H), 1.92–
1
.98 (m, 2H), 2.51 (s, 3H), 6.32 (dt, J ¼ 15.1, 1.6 Hz,1H), 6.94 (dt, J ¼ 15.1,

8
20
S.-R. Sheng et al.
6
.9 Hz, 1H), 7.41 (d, J ¼ 8.1 Hz, 2H), 7.78 (d, J ¼ 8.1 Hz, 2H). IR: n
3064,
max
2
1
2
926, 2875, 1625, 1596, 1378, 1321, 1155, 1085, 976, 835, 800, 668 cm
.
ACKNOWLEDGMENT
We are grateful for the financial support from the Natural Science Foundation
of Jiangxi Province, China (No. 0420017).
REFERENCES
1
. (a) Shuttleworth, S. J.; Allin, S. M.; Sharma, P. K. Functionalized polymers:
Recent developments and new application in synthetic organic chemistry.
Synthesis 1997, 1217; (b) Guillier, F.; Orain, D.; Bradley, M. Linkers and
cleavage strategies in solid-phase organic synthesis and combinatorial
chemistry. Chem. Rev. 2000, 100, 2091; (c) Sammelson, R. E.; Kurth, M. J.
Carbon-carbon bond-forming solid-phase reactions. Part II. Chem. Rev. 2001,
101, 137; (d) Burnin, B. A. The Combinatorial Index; Academic Press:
San Diego, CA, 1998; p. 5.
2
. (a) Hopkins, P. B.; Fuchs, P. L. Chlorosulfenylation-dehydrochlorination reaction:
New and improved methodology for the synthesis of unsaturated aryl sulfides and
aryl sulfones. J. Org. Chem. 1978, 43, 1208; (b) Sas, W. The arenesulfonomercura-
tion of alkenes: A route to vinyl sulfones. J. Chem. Soc., Chem. Commun. 1984,
8
62; (c) Backvall, J.-E.; Najera, C.; Yus, M. Selenosulfonation of 1,3-dienes,
one-pot synthesis of 2-(phenylsulfonyl)-1,3-dienes. Tetrahedron Lett. 1988, 29,
445; (d) Kobayashi, T.; Tanaka, Y.; Ohtani, T.; Kinoshita, H.; Inomoata, J. K.;
1
Kotake, H. Regio- and stereoselective synthesis of (E) and (Z)-vinylic sulfones
and their conversion to the corresponding allylic sulfones. Chem. Lett. 1987,
1
209; (e) Bongini, D.; Savoia, D.; Umani-Ronchi, A. Synthesis and reactivity of
the 1,1-dilithio derivatives of phenyl sulfones and N,N-dimethylmethanesulfona-
mide. J. Organomet. Chem. 1976, 112, 1; (f) Eisch, J. J.; Galle, J. E. Generation
of a-sulfonylvinyllithium reagents by the lithiation of vinylic sulfones. J. Org.
Chem. 1979, 44, 3279; (g) Yamamoto, M.; Suzuki, K.; Tanaka, S.; Yamada, K.
Lithio styryl sulfones as an acryl anion synthon. Bull. Chem. Soc. Jpn. 1987, 60,
1
523; (h) Back, T. G.; Collins, S.; Law, K.-W. Selenosulfonation of acetylenes.
Substitution reactions of b-(phenylseleno)vinyl sulfones with organocuprates.
Tetrahedron Lett. 1984, 25, 1689; (i) Fiandanese, V.; Marchese, G.; Naso, F.
Variable stereochemical course in the reaction of 1-benzenesulfonyl-2-bromo-
and -2-fluoroethenes with dialkyl and diphenyl cuprates. Tetrahedron Lett. 1978,
5131; (j) Ager, D. J. Synthesis of alkenes via the Peterson reaction. J. Chem.
Soc., Perkin Trans. 1 1986, 183.
3
. (a) Back, T. G.; Collins, S. Selenosulfonation: Borontrifluoride catalyzed or
thermal addition of selenosulfonates to olefins: A novel regio- and stereocontrolled
synthesis of vinyl sulfones. J. Org. Chem. 1981, 46, 3249; (b) Back, T. G.;
Collins, S. “Selenosulfonation”: The addition of selenolsulfonates to olefins. Tet-
rahedron Lett. 1980, 21, 2215; (c) Back, T. G.; Brunner, K.; Krishna, M. V.;
Lai, E. K.Y.; Muralidharan, K. R. Heteroatom Chemistry; Block, E., Ed.; VCH:
New York, 1990; pp. 73–79.

Solid-Phase Synthesis of Vinyl Sulfones
821
4
. (a) Nicolaou, K. C.; Pastor, J.; Barluenga, S.; Winssinger, N. Polymer-supported
selenium reagents for organic synthesis. Chem. Commun. 1998, 1947;
b) Ruhland, T.; Andersen, K.; Pedersen, H. Selenium-linking strategy for
(
traceless solid-phase synthesis: Direct loading, aliphatic C-H bond formation
upon cleavage and reaction monitoring by gradient MAS NMR spectroscopy.
J. Org. Chem. 1998, 63, 9204; (c) Michels, R.; Kato, M.; Heitz, W. Polymere
ꢁ
reagenzien 5 , polymerereagenzien. Makromol. Chem. 1976, 177, 2311;
(
d) Fujita, K.; Watanabe, K.; Oishi, A.; Ikeda, Y.; Taguchi, Y. Preparation of
polymer-supported selenocyanates and their applications in solid-phase oxyselene-
nylation-deselenenylation. Synlett 1990, 1760; (e) Uehlin, L.; Wirth, T. Novel
polymer-bound chiral selenium electrophiles. Org. Lett. 2001, 3, 2931.
. Sheng, S.-R.; Wang, X.-C.; Liu, X.-L.; Song, C.-S. Selenium-linking strategy for
traceless solid-phase synthesis of acrylamides. Synth. Commun. 2003, 33, 2867.
. Zundel, G. Hydration structure and intermolecular interaction in polyelectrolytes.
Angew. Chem., Int. Ed. Engl. 1969, 8, 499.
5
6
7
. Parham, W. E.; Blake, F. D.; Theisson, D. R. The reactions of diazo compounds,
VIII: The reaction of diazomethane with a, b-unsaturated sulfones. J. Org. Chem.
1962, 27, 2415.