One-pot synthesis of β-hydroxysulfides from styrenes and disulfides using the Zn/AlCl3 system

Article abstract of DOI:10.1016/j.tetlet.2008.09.071

A simple, general, and highly regioselective procedure has been developed for the one-pot synthesis of β-hydroxysulfides in good yields from various styrenes and disulfides by cleavage of the S-S bond with a Zn/AlCl₃ system in aqueous acetonitr

Full text of DOI:10.1016/j.tetlet.2008.09.071

Tetrahedron Letters 49 (2008) 6712–6714
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
One-pot synthesis of b-hydroxysulfides from styrenes
and disulfides using the Zn/AlCl3 system
*
Barahman Movassagh , Mozhgan Navidi
Department of Chemistry, K.N. Toosi University of Technology, PO Box 16315-1618, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 July 2008
Revised 31 August 2008
Accepted 12 September 2008
Available online 17 September 2008
A simple, general, and highly regioselective procedure has been developed for the one-pot synthesis of
b-hydroxysulfides in good yields from various styrenes and disulfides by cleavage of the S–S bond with
a Zn/AlCl3 system in aqueous acetonitrile at 80 °C and in the presence of oxygen.
Ó 2008 Elsevier Ltd. All rights reserved.
b-Hydroxysulfides are important intermediates in organic
synthesis.1 These compounds are versatile building blocks for
synthesizing thioketones,2 allylic alcohols,1 cyclic sulfides,3
benzothiazepines,4 and benzoxathiepines.5 They also exhibit great
synthetic utility in the field of pharmaceuticals6 and natural prod-
ucts.7 The most important synthetic procedure for the preparation
of b-hydroxysulfides is the thiolysis of epoxides in the presence or
absence of a catalyst.8 However, some of the procedures reported
were performed using Lewis acid catalysts, but these methods
suffer from various disadvantages such as lower yields, poor
regioselectivity, harsh reaction conditions, and undesirable
side products via rearrangement of oxiranes and oxidation of
thiols.9
As part of our interest in zinc chemistry,14,15 we continue to
seek novel applications of zinc thiolates and zinc selenolates in
chemical reactions. Very recently, we investigated a convenient,
catalyst-free method for the anti-Markovnikov addition of thiols
to styrenes at room temperature in water.16 We have now exam-
ined a new methodology for the synthesis of b-hydroxysulfides
via the anti-Markovnikov addition of thiolate anions, generated
in situ by reductive cleavage of diaryl disulfides in the presence
of Zn/AlCl3, to styrenes in aqueous acetonitrile in the presence
of oxygen (Scheme 1). To the best of our knowledge, no study
has been made using the reaction of thiolate anions (RSÀ) with
styrenes for the synthesis of b-hydroxysulfides.
The experiments were initially conducted with styrene and
diphenyl disulfide, as a model reaction, by varying the molar ratios,
solvents, and temperatures under ambient atmosphere. We found
that the reactants were converted readily to the corresponding
b-hydroxysulfide using the Zn/AlCl3 system with a molar ratio of
disulfide/AlCl3/Zn/styrene = 0.5:1:3.5:1.2 in acetonitrile/water
(4:1) at 80 °C.
The formation of b-hydroxysulfides may be explained as fol-
lows: the oxygen may complex with the styrene assisted by hydro-
gen bonding with the water hydroxyls,11 and this would be
followed by nucleophilic attack by zinc thiolate, (RS)2Zn, prepared
via reductive cleavage of the disulfide with Zn/AlCl3.15
Table 1 presents the results of the regioselective addition of
various diaryl disulfides to several substituted styrenes in an
anti-Markovnikov fashion leading to the corresponding b-hydroxy-
sulfides in good to high yields. The yields reported in Table 1 are of
Thiol–oxygen cooxidation (TOCO) reaction10 of olefins and reac-
tive arenes is another method commonly used for the straightfor-
ward synthesis of b-hydroxysulfides. Notable features of TOCO
reactions are their susceptibility to initiation by free-radical pre-
cursors, their propensity to afford high yields of products rapidly,
and their relative freedom from side reactions. However, these
reactions usually require a base catalyst, a large excess of thiol
and are initiated by UV irradiation or peroxides. Major drawbacks
of this methodology are undesirable side products, and low
regioselectivity and yields. Hence, the development of a direct
transformation of olefins to b-hydroxysulfides would be a useful
contribution to the preparation of this class of compounds. In
two recent reports, b-hydroxysulfides were synthesized from
11
alkenes and thiols in the presence of b-cyclodextrin/H2O/O2
12
and [bmim][BF4]/H2O/O2 in good to high yields. Also, combina-
tion of metal salts (Pb4+ and Cu2+) and disulfides provides a conve-
nient approach to hydroxysulfenylation of olefins via transfer of
the equivalent of RS+.13
OH
Zn/AlCl3 , O2
RS-SR
+
Ar
SR
CH3CN/H2O, 80 ˚C
Ar
* Corresponding author. Tel.: +98 21 22886575; fax: +98 21 22853650.
E-mail address: bmovass1178@yahoo.com (B. Movassagh).
Scheme 1.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.09.071

B. Movassagh, M. Navidi / Tetrahedron Letters 49 (2008) 6712–6714
6713
Table 1
Synthesis of b-hydroxysulfides from styrenes and disulfides (RS–SR) in the presence of the Zn/AlCl3 system in acetonitrile/water
Entry
Styrene
R
Product
Time (h)
Yielda (%)
80
Regioselectivityb
a/b:4/96
a
a
OH
Ph
b
b
1
Ph
2
SPh
OH
2
p-BrC6H4
2
75
a/b:15/85
Ph
Ph
SC6H4(p-Br)
a
OH
SC6H4(
OH
b
3
o-MeC6H4
2.4
2.2
2.5
3.7
3
63
73
71
66
61
70
65
65
66
63
60
—
a/b:10/90
a/b:25/75
a/b:19/81
a/b:4/96
a/b:17/83
a/b:10/90
a/b:18/82
a/b:13/87
a/b:33/67
a/b:9/91
a/b:17/83
—
o
-Me)
a
b
b
b
b
4
Ph
(p-Cl)C6H4
SPh
OH
Cl
Cl
Cl
Cl
a
a
a
5
p-BrC6H4
p-MeOC6H4
o-MeC6H4
Ph
(p-Cl)C6H4
(p-Cl)C6H4
SC6H4(p-Br)
OH
SC6H4(p-OMe)
OH
6
7
(p-Cl)C6H4
SC6H4(
o-Me)
a
OH
b
8
3.5
3.2
2.7
2.25
3.8
3.5
24
(
(
p
-OMe)C6H4
SPh
OH
MeO
MeO
a
b
9
p-BrC6H4
p
-OMe)C6H4
SC6H4(p-Br)
a
OH
b
10
11
12
13
Ph
(p-Me)C6H4
SPh
OH
Me
Me
Me
Me
a
b
b
b
p-BrC6H4
p-MeOC6H4
o-MeC6H4
Ph
(p-Me)C6H4
SC6H4(
OH
p
-Br)
a
a
(
p
-Me)C6H4
-Me)C6H4
SC6H4(
OH
SC6H4(
p
-OMe)
(p
o-Me)
14
No reaction
a
Yield of the isolated major product.
Refers to the ratio of thiolate anion attack at carbon-a and carbon-b determined by 1H NMR analysis of the crude reaction mixture.
b
the isolated major product. Also, the regioselectivity was evaluated
by 1H NMR analysis of the crude reaction mixture; the results
clearly show preferential attack at the b-position (carbon-b) by
the thiolate anion. However, under the same conditions, the much

6714
B. Movassagh, M. Navidi / Tetrahedron Letters 49 (2008) 6712–6714
less-reactive cyclohexene (Table 1, entry 14) did not produce the
expected product even after prolonged reaction time. Generally,
the reaction goes to completion in a short time (2–4 h). This proce-
dure is compatible with various substituted styrenes and substi-
tuted aromatic disulfides with functionalities such as methyl,
chloro, and methoxy. When the reaction was conducted, under
the same reaction conditions, but under an argon atmosphere,
the addition product, that is, the sulfide (PhCH2CH2SPh) alone
was formed in 44% yield. This indicates that aerial oxygen is in-
volved in the formation of the b-hydroxysulfides. All the products
are known,11 and the structures of the b-hydroxysulfides were
established from their IR, 1H, and 13C NMR spectral data.
In conclusion, we have shown that the addition of a thiolate an-
ion (RSÀ) to styrenes takes place regioselectively giving b-hydroxy-
sulfides in an anti-Markovnikov manner. This reaction is simple
and proceeds under relatively mild conditions with short reaction
times and high selectivity. To our knowledge, this is the first exam-
ple of the reaction of thiolate anions with styrenes for the synthesis
of b-hydroxysulfides. This protocol may lead to a new dimension in
terminal olefin functionalization.
Typical experimental procedure: A mixture of diphenyl disulfide
(109 mg, 0.5 mmol), zinc powder (229 mg, 3.5 mmol), and finely
ground anhydrous AlCl3 (133 mg, 1.0 mmol) was suspended in
MeCN (8 mL) and H2O (2 mL). The mixture was stirred at 80 °C
for 2 h, during which time the zinc powder was almost completely
consumed. Then, 4-methoxystyrene (161 mg, 1.2 mmol) was
added in one portion and stirring was continued at that tempera-
ture for 3.5 h in air. After completion of the reaction, the solution
was filtered, acetonitrile was evaporated, EtOAc (20 mL) was
added, and the mixture was washed with water (2 Â 10 mL), and
the organic layer was dried (Na2SO4). The solvent was evaporated
under reduced pressure, and the crude mixture was purified by
preparative TLC (silica gel; eluent, n-hexane/EtOAc = 4: 1) to afford
pure 1-(4-methoxyphenyl)-2-(phenylsulfanyl)-1-ethanol (182 mg,
Acknowledgments
We thank the K.N. Toosi University of Technology Research
Council and Iranian National Science Foundation (INSF, Grant No.
86063/21) for financial support.
References and notes
1. Kesavan, V.; Bonnet-Delpon, D.; Bégué, J. P. Tetrahedron Lett. 2000, 41, 2895.
2. Bégué, J. P.; Bonnet-Delpon, D.; Kornilov, A. Synthesis 1996, 529.
3. (a) Adger, B. M.; Barkley, J. V.; Bergeron, S.; Cappi, M. W.; Flowerdew, B. E.;
Jackson, M. P.; McCague, R.; Nugent, T. C.; Roberts, S. M. J. Chem. Soc., Perkin
Trans. 1 1997, 3501; (b) Ozaki, E.; Matsui, H.; Yoshinaga, H.; Kitagawa, S.
Tetrahedron Lett. 2000, 41, 2621.
4. Schwartz, A.; Madan, P. B.; Mohacsi, E.; O’Brien, J. P.; Todaro, E.; Coffen, D. L. J.
Org. Chem. 1992, 57, 851.
5. (a) Aifheli, C. G.; Kaye, P. T. Synth. Commun. 1996, 26, 4459; (b) Sugihara, H.;
Mabuchi, H.; Hirata, M.; Iamamoto, T.; Kawamatsu, Y. Chem. Pharm. Bull. 1987,
35, 1930.
6. Lucy, J. R.; Yi, N.; Soderquist, J.; Stein, H.; Cohen, J.; Perun, T. J.; Plattner, J. J. J.
Med. Chem. 1987, 30, 1609.
7. Corey, E. J.; Clark, D. A.; Goto, G.; Marfat, A.; Mioskowski, C.; Samuelsson, B.;
Hammarstrom, S. J. Am. Chem. Soc. 1980, 102, 3663.
8. (a) Movassagh, B.; Soleiman-Beigi, M. Synth. Commun. 2007, 37, 3239; (b)
Movassagh, B.; Sobhani, S.; Kheirdoush, F.; Fadaei, Z. Synth. Commun. 2003, 33,
3103; (c) Fringuelli, F.; Pizzo, F.; Tortoioli, S.; Vaccaro, L. Tetrahedron Lett. 2003,
44, 6785; (d) Fringuelli, F.; Pizzo, F.; Tortoioli, S.; Vaccaro, L. J. Org. Chem. 2003,
68, 8248; (e) Pironti, V.; Colonna, S. Green Chem. 2005, 7, 43.
9. Yadav, J. S.; Reddy, B. V. S.; Gakul, B. Chem. Lett. 2002, 906 and references
therein.
10. (a) Beckwith, A. L. J.; Wagner, R. D. J. Org. Chem. 1981, 46, 3638; (b) Szmant, H.
H.; Mata, A. J.; Namis, A. J.; Panthananickal, A. M. Tetrahedron 1976, 32, 2665.
11. Surendra, K.; Krishnaveni, N. S.; Sridhar, R.; Rao, K. R. J. Org. Chem. 2006, 71,
5819.
12. Kamal, A.; Reddy, D. R.; Rajendar J. Mol. Cat. A: Chem. 2007, 272, 26.
13. (a) Trost, B. M.; Ochiai, M.; McDougal, P. G. J. Am. Chem. Soc. 1978, 100, 7103;
(b) Bewick, A.; Mellor, J. M.; Milano, D.; Owton, W. M. J. Chem. Soc., Perkin
Trans.1 1985, 1045.
14. (a) Movassagh, B.; Mirshojaei, F. Monatsh. Chem. 2003, 134, 831; (b)
Movassagh, B.; Shamsipoor, M. Synlett 2005, 121; (c) Movassagh, B.;
Shamsipoor, M. Synlett 2005, 1316; (d) Movassagh, B.; Fazeli, A. Z.
Naturforsch., B: Chem. Sci. 2006, 61, 194; (e) Movassagh, B.; Tatar, A. Synlett
2007, 1954.
70%, Table 1, entry 8) as a pale yellow oil. IR (neat)
m 1513, 1584,
3429 cmÀ1 1H NMR (CDCl3, 300 MHz) d 2.82 (br s, 1H), 3.11 (dd,
;
15. (a) Movassagh, B.; Zakinezhad, Y. Chem. Lett. 2005, 34, 1330; (b) Movassagh, B.;
Mossadegh, A. Synth. Commun. 2004, 34, 1685; (c) Lakouraj, M.; Movassagh, B.;
Fadaei, Z. Synth. Commun. 2002, 32, 1237; (d) Movassagh, B.; Tavoosi, M.
Monatsh. Chem. 2008, 139, 251; (e) Movassagh, B.; Zakinezhad, Y. Z.
Naturforsch., B: Chem. Sci. 2006, 61, 47.
J = 13.7, 9.3 Hz, 1H), 3.30 (dd, J = 13.7, 3.7 Hz, 1H), 3.81 (s, 3H),
4.70 (dd, J = 9.3, 3.7 Hz, 1H), 6.89 (d, J = 8.6 Hz, 2H), 7.22–7.44 (m,
7H); 13C NMR (CDCl3, 75 MHz) d 43.87, 55.30, 71.34, 113.95,
126.70, 127.13, 129.11, 130.15, 134.29, 135.02, 159.36.
16. Movassagh, B.; Navidi, M. Arkivoc 2008, xv, 47.