An approach toward the synthesis of β-hydroxy sulfones on water

Article abstract of DOI:10.1016/j.tetlet.2009.06.078

Various β-hydroxyl sulfones are prepared by regioselective ring opening of epoxides with sodium salt of sulfinate on water. This is an efficient protocol which avoids hazardous and moisture sensitive catalysts.

Full text of DOI:10.1016/j.tetlet.2009.06.078

Tetrahedron Letters 50 (2009) 5009–5011
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An approach toward the synthesis of b-hydroxy sulfones on water
*
S. Narayana Murthy, B. Madhav, V. Prakash Reddy, K. Rama Rao, Y. V. D. Nageswar
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Various b-hydroxyl sulfones are prepared by regioselective ring opening of epoxides with sodium salt of
sulfinate on water. This is an efficient protocol which avoids hazardous and moisture sensitive catalysts.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 12 May 2009
Revised 12 June 2009
Accepted 16 June 2009
Available online 18 June 2009
Oxirane ring opening with various potential nucleophiles is an
important strategy in organic synthesis because nucleophilic addi-
tion to the oxirane ring leads to 1,2-bifunctionalized systems
which are interesting structural motifs for the synthesis of a wide
variety of natural products. The great utility of b-hydroxy sulfones
in organic synthesis is due to their use as precursors of d2 and d3
reagents1 via corresponding metallation reaction.2 The dianions
of these b-hydroxy sulfones are subjected to the preparation of
lactones3a–d and 2,5-disubstituted tetrahydrofurans.3e On the other
way the anions of these versatile b-hydroxy sulfones react to form
vinyl sulfones by b-elimination reaction4 and olefins by reductive
elimination.5
The regioselective formation of b-hydroxy sulfones from the
epoxides is an important reaction in medicinal and organic chem-
istries as these are useful intermediates, which can be further
derivatized through the coined concept called Umpolung (any pro-
cess by which donor and acceptor reactivity of an atom is inter-
changed). In the literature sulfonyl group and its inherent
properties are well documented.6 So the chemistry of b-hydroxy
sulfones resembles typically that of an anion.
catalysts, tedious workup, and low regioselectivity. Thus in view
of these shortcomings there is a need to develop a greener
approach for the synthesis of b-hydroxy sulfones.
Water is a cheap, nontoxic, and most readily available reaction
medium, making it an environmentally benign solvent13 for green
chemistry protocols. To the best of our knowledge there are no
reports on regioselective oxirane ring opening with sodium sulfi-
nates on water without using any catalyst. Herein, we wish to
report regioselective ring opening of epoxides with sodium sulfi-
nates on water at 80 °C.
The generality of this approach toward the synthesis of b-hy-
droxy sulfones is established by reacting various epoxides with
the sodium salts of sulfinate, on water.14 Excellent yields of desired
b-hydroxy sulfones were obtained. In the case of aliphatic epox-
ides, attack occurred at the less-hindered site of the epoxide
(Scheme 1). In the case of aromatic epoxides, a mixture of regioi-
somers was obtained (Scheme 2).
Out of these two, the product formed by the attack at the least
substituted is the major one (up to 80%), and the attack at the
So far there are few reports on the synthesis of b-hydroxy sulf-
ones, by regioselective ring opening of oxiranes with various cata-
lytic systems. Najera and Sansano have reported the synthesis of
b-hydroxy sulfones by employing Grignard reagents.7 Bhattachar-
yya and Maiti synthesized various b-hydroxy sulfones in presence
of PEG as a catalyst.8 Recently, several methods using promoters or
catalysts in different organic solvents9 have been reported. These
methods include use of supercritical carbon dioxide,10a microwave
irradiation,10b hexafluoro-2-propanol,10c ionic liquid,10d Bi(OTf)3 in
water,10e and solvent-free conditions.9
OH O
O
Water
O
+
S
S
R
R1
R1
70-80 ºC
3-6 h
Na
O
O
-
+
R
1
2
R1=alkyl, aryl; R= H(2a),CH3(2b)
Scheme 1. Synthesis of b-hydroxy sulfones on water.
Although few reagents and catalysts have been reported for
efficient opening of epoxide through activation,11,12 these method-
ologies have a number of drawbacks such as longer reaction times,
low yields, difficulty in preparation and/or storage of reagents or
R2
OH
O
S
O
O
O
O
S
S
R2
O
OH
Na
+
O
-
R1
R1 = H, Cl, Br
R1
R2
R1
R2 = CH3
76-78%
9-13%
* Corresponding author. Tel.: +91 40 27191654; fax: +91 40 27160512.
E-mail address: dryvdnageswar@gmail.com (Y.V.D. Nageswar).
Scheme 2.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.06.078

5010
S. N. Murthy et al. / Tetrahedron Letters 50 (2009) 5009–5011
O
O
Table 1 (continued)
H
H
H
H
+
H
Entry Epoxide (1)
2
Productb
Yieldc (%)
81
O
H
OH
δ+
O
O
13
2a
O
S
-
O
R1
O
O N
S
OH
O
R2
Figure 1. Plausible mechanistic path way.
14
15
2b
85
O
S
O
OH
O
S
O
2b
78 (2b1)
76 (2b2)
77 (2b3)
Table 1
O
Synthesis of b-hydroxy sulfones on watera
R
R
R
Entry Epoxide (1)
2
Productb
Yieldc (%)
89
O
OH O
S
R = H (2b1),
Cl (2b2),
13 (2b1)
10 (2b2)
9 (2b3)
O
PhO
PhO
O
S
1
2a
OH
PhO
O
Br (2b3)
a
OH O
Reaction conditions: epoxide (1 equiv), sodium sulfinate (1.1 equiv), and water
(20 mL).
O
S
O
2
2b
2a
2b
92
86
91
PhO
Products were confirmed by 1H, 13C NMR, and direct comparison with authentic
b
samples for entries 13–15.
c
Yields of the isolated product.
OH O
O
O
O
O
O
S
3
O
benzylic position is the minor one. The probable reason for getting
mixture of products in case of styrene oxide is that, the water
molecule has a tendency to form hydrogen bonding with the
electronegative oxygen of the epoxide resulting in a partial positive
charge, this positive charge on oxygen appears to be localized on
more substituted benzylic carbon leading to the product, which
is minor. Whereas attack from the least-hindered side resulted in
the major product (Fig. 1). The product ratio suggests that in case
of aliphatic epoxides steric factors predominate over electronic fac-
tors, thereby resulting in the attack at the less-hindered carbon
atom of the epoxide ring. The results are summarized in (Table
1). The structures of all the products were determined from their
analytical and spectral (IR, 1H NMR, and 13C NMR) data15 and by
direct comparison with authentic samples.
In conclusion, we have demonstrated an ecofriendly and
catalyst-free protocol for the synthesis of b-hydroxy sulfones un-
der mild conditions on water. This method has several advanta-
ges over the existing methods such as high yields, ability to
proceed without catalyst or additives, and environmentally
friendly conditions. This protocol is an useful addition to the
green chemistry in the context of a higher demand for green
chemical processes.
OH O
O
S
O
4
OH O
O
O
O
O
O
O
S
5
2a
2b
85
89
O
MeO
MeO
OH O
S
O
6
MeO
MeO
O
OH O
O
O
S
O
7
2a
2b
84
87
OH O
O
O
O
S
O
8
9
OH O
O
O
O
O
O
O
S
2a
2b
84
87
O
Acknowledgment
We thank CSIR, New Delhi, India for awarding fellowships to
S.N.M., B.M., and V.P.R.
OH O
S
O
10
Supplementary data
OH O
O
O
O
O
S
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2009.06.078.
O
11
12
2a
2b
78
84
NO2
NO2
References and notes
OH O
O
O
S
O
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239.
NO2
2. Julia, M.; Uguen, D.; Callipolitis, A. Bull. Soc. Chim. Fr. 1976, 519.
NO2

S. N. Murthy et al. / Tetrahedron Letters 50 (2009) 5009–5011
5011
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sulfinate (0.180 g, 1.1 mmol) was added. The suspension was magnetically
stirred at 70–80 °C until reaction was complete (as monitored by TLC)
(Table 1). After completion of the reaction, the reaction mixture was
extracted with ethyl acetate (4 Â 10 mL). The extract was further washed
with water and saturated brine solution, dried over anhydrous Na2SO4,
and evaporated under reduced pressure to give b-hydroxy sulfones in 80–
94% yields. In case of styrene oxides, the product was further purified by
silica gel column chromatography using ethyl acetate and hexane (7:3) as
an eluent to afford the corresponding b-hydroxy sulfones (Table 1, entry
1) in 89% yield. Colorless oil; mmax (KBr) 3493, 2929, 1595, 1301, 1243,
1144 cmÀ1
; d 7.90 (d, 2H, J = 7.5 Hz,
1H NMR (300 MHz, CDCl3, TMS):
arom.), 7.60 (t, 1H, J = 7.5 Hz, arom.), 7.50 (t, 2H, J = 7.5 Hz, arom.), 7.21 (t,
2H, J = 7.5 Hz, arom.), 6.91 (t, 1H, J = 8.3 Hz, arom.), 6.82 (d, 2H, J = 7.5 Hz,
arom.), 4.51 (m, 1H, OCH2), 3.94 (m, 2H, OCH2 + CHOH), 3.49 (br s, OH),
6. Cram, D. J. Fundamentals of Carbanion Chemistry; Academic Press: New York,
1965.
7. Najera, C.; Sansano, J. M. Tetrahedron 1990, 46, 3993.
3.46 (m, 2H, CH2SO2); 13C NMR (75 MHz, CDCl3):
d 157.6, 139.5, 133.9,
8. Maiti, A. K.; Bhattacharyya, P. Tetrahedron 1994, 50, 10483.
129.4, 128.1, 121.6, 114.4, 70.0, 64.9, 59.2. Mass (ESI-MS): m/z 293
9. (a) Chini, M.; Crotti, P.; Macchia, F. Tetrahedron Lett. 1990, 31, 4661; (b)
Yamamoto, Y.; Asao, N.; Meguro, M.; Tsukade, N.; Nemoto, H.; Adayari, N.;
Wilson, J. G.; Nakamura, H. J. Chem. Soc., Chem. Commun. 1993, 1201; (c)
Meguro, M.; Asao, N.; Yamamoto, Y. J. Chem. Soc., Perkin Trans. 1 1994, 2597; (d)
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2004, 846–850; (k) Fan, R. H.; Hou, X. L. J. Org. Chem. 2003, 68, 726; (l) Kamal,
A.; Ramu, R.; Amerudin Azhar, M.; Ramesh Khanna, G. B. Tetrahedron Lett. 2005,
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Sundrarajan, G.; Vijayakrishna, K.; Varghese, B. Tetrahedron Lett. 2004, 45,
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(M+H)+.
15. Data for the representative examples of synthesized compounds: 1-(o-tolyloxy)-3-
tosylpropan-2-ol (Table 1, entry 4): Colorless oil; yield 0.291 g (91%);
mmax (KBr)
3464, 2933, 1598, 1498, 1293, 1248, 1143 cmÀ1 1H NMR (300 MHz, CDCl3,
;
TMS): d 7.79 (d, 2H, J = 8.0 Hz, arom.), 7.29 (d, 2H, J = 8.0 Hz, arom.), 7.06 (t, 2H,
J = 7.3 Hz, arom.), 6.82 (t, 1H, J = 7.3 Hz, arom.), 6.67 (d, 1H, J = 8.0 Hz, arom.),
4.46 (m, 1H, OCH2), 3.91 (m, 2H, OCH2 + CHOH), 3.43 (m, 2H, CH2SO2), 2.40 (s,
3H, CH3), 2.10 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3, TMS): d 155.8, 145.0,
136.3, 130.7, 129.7, 127.7, 126.6, 126.2, 120.8, 110.9, 69.7, 65.0, 59.3, 21.4,
15.9. Mass (ESI-MS): m/z 321 (M+H)+.
L
-Isopropoxy-3-tosylpropan-2-ol (Table 1, entry 8): Colorless oil; yield 0.236 g
(87%);
m
max (KBr) 3497, 2973, 1448, 1379, 1303, 1144 cmÀ1 1H NMR (300 MHz,
;
CDCl3, TMS): d 7.82 (d, 2H, J = 8.1 Hz, arom.), 7.37 (d, 2H, J = 7.9 Hz, arom.), 4.20
(m, 1H, OCH2), 3.55 (m, 1H, OCH2), 3.42 (d, 2H, J = 5.0 Hz, CHOH + CH2SO2), 3.28
(m, 2H, CH2SO2 + CH(CH3)2), 2.88 (br s, OH), 2.46 (s, 3H,CH3), 1.10 (s, 6H,
CH(CH3)2); 13C NMR (75 MHz, CDCl3, TMS): d 144.5,136.2, 129.4, 127.6, 71.8,
69.9, 65.1, 59.2, 21.5, 21.2. Mass (ESI-MS): m/z 273 (M+H)+.
L
-(2,4-Dimethylphenoxy)-3-tosylpropan-2-ol (Table 1, entry10): Colorless oil;
yield 0.290 g (87%); max (KBr) 3511, 2926, 1598, 1505, 1467, 1427, 1380, 1257,
1139 cmÀ1 1H NMR (300 MHz, CDCl3, TMS): d 7.81 (d, 2H, J = 8.2 Hz, arom.),
m
;
7.35 (d, 2H, J = 7.4 Hz, arom.), 6.84 (d, 2H, J = 8.2 Hz, arom.), 6.58(d, 1H,
J1 = 7.4 Hz, arom.), 4.41 (m, 1H, OCH2), 3.97 (q, 1H, J1 = 8.9 Hz, J2 = 4.4 Hz,
OCH2), 3.87 (q, 1H, J1 = 9.7 Hz, J2 = 5.9 Hz, CHOH), 3.46 (dd, 1H, J1 = 2.9 Hz,
J2 = 2.2 Hz, CH2SO2), 3.33 (m, 1H, CH2SO2), 2.47 (s, 3H, CH3), 2.23 (s, 3H, CH3),
2.07(s, 3H, CH3); 13C NMR (75 MHz, CDCl3, TMS): d 153.6, 144.3, 136.3, 131.1,
129.4, 127.6, 126.5, 125.7,111.0, 69.7, 64.8, 59.2, 21.4, 20.1,15.7. Mass (ESI-
MS): m/z 335 (M+H)+.
L
-(3-Nitrophenoxy)-3-(phenylsulfonyl)propan-2-ol (Table 1, entry 11): Colorless
oil; yield 0.262 g (78%);%); tmax (KBr) 3496, 3096, 2931, 1528, 1481, 1449,
1351, 1296, 1247, 1144 cmÀ1 1H NMR (300 MHz, CDCl3, TMS): d 7.96 (m, 2H,
13. (a) Jaeger, D. A.; Frey, M. R. J. Org. Chem. 1982, 47, 311; (b) Jaeger, D. A.;
Jamrozik, J.; Golich, T. G.; Clennan, M. W.; Mohebalian, J. J. Am. Chem. Soc. 1989,
111, 3001; (c) Jaeger, D. A.; Sayed, Y. M.; Dutta, A. K. Tetrahedron Lett. 1990, 31,
449.
;
arom.), 7.82 (dd, 1H, J1 = 8.3 Hz, J2 = 2.2 Hz, arom.), 7.68 (m, 2H, arom.), 7.60
(m, 2H, arom.), 7.41 (t, 1H, J = 8.3 Hz, arom.), 7.17 (dd, J1 = 8.3 Hz, J2 = 2.2 Hz,
1H, arom.), 4.55 (m, 1H, OCH2), 4.10 (m, 2H, OCH2 + CHOH), 3.41(m, 2H,
CH2SO2), 3.38 (br s, OH); 13C NMR (75 MHz, CDCl3, TMS): d 158.3, 148.9, 134.1,
129.7, 129.1, 127.5, 120.9, 116.1, 108.7, 70.2, 64.5, 58.7. Mass (ESI-MS): m/z
338 (M+H)+.
14. General procedure for the synthesis of b-hydroxy sulfones on water. Typical
example: 1-phenoxy-3-(phenylsulfonyl)propan-2-ol (Table 1, entry 1): To
a
flask containing the epoxide (0.150 g, 1 mmol) in water (20 mL), sodium