Sm/I2-mediated selective cleavage of the S-S or C-S bonds of sodium (Z)-allyl thiosulfates in aqueous media: Selective formation of di(Z-allyl) bisulfides or (2E)-methyl cinnamic esters

Article abstract of DOI:10.1055/s-2006-950406

Selective cleavage of the S-S or C-S bonds in sodium (Z)-allyl thiosulfates in the presence of a Sm/I₂-system was achieved to form the corresponding di(Z-allyl) disulfides or (2E)-methyl cinnamic esters in moderate to good yields in aqueous med

Full text of DOI:10.1055/s-2006-950406

2492
LETTER
Sm/I2-Mediated Selective Cleavage of the S–S or C–S Bonds of Sodium
(Z)-Allyl Thiosulfates in Aqueous Media: Selective Formation of Di(Z-allyl)
Disulfides or (2E)-Methyl Cinnamic Esters
S
elective Formatio
u
nof
D
i(
Z
-all
n
yl)
D
isulfide
k
s
or (2
E
)-M
e
u
thyl
C
innam
i
ic Esters Liu,a Hui Zheng,a Danqian Xu,a Zhenyuan Xu,*a Yongmin Zhang*b,c
a
State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Zhejiang University of Technology,
Hangzhou, 310014, P. R. of China
b
c
Department of Chemistry, Zhejiang University, Xi-xi Campus, Hangzhou, 310028, P. R. of China
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai, 200032, P. R. of China
Fax +86(571)88320609; E-mail: chrc@zjut.edu.cn
Received 31 May 2006
Baylis–Hillman adducts have been reported, especially
those that provide good stereoselectivities.4,5
Abstract: Selective cleavage of the S–S or C–S bonds in sodium
(Z)-allyl thiosulfates in the presence of a Sm/I2-system was
achieved to form the corresponding di(Z-allyl) disulfides or (2E)-
methyl cinnamic esters in moderate to good yields in aqueous
media.
As part of our continued interest in the conversion of
Baylis–Hillman adducts into trisubstituted alkenes,6 we
have recently described a convenient synthesis of sodium
(Z)-allyl thiosulfates by treatment of Baylis–Hilman ace-
tates with sodium thiosulfate and reported their further
conversion to unsymmetrical diallylsulfides in a one-pot
manner.7 Following on from this we found that the S–S
and C–S bonds in sodium (Z)-allyl thiosulfates could be
selectively cleaved by samarium and a trace amount of I2
in aqueous media depending on the different substituents
(alkyl or aryl group) attached to them, thus affording di(Z-
allyl) disulfides or (2E)-methyl cinnamic esters in moder-
ate to good yields, respectively (Scheme 1).8
Key words: selective cleavage, sodium (Z)-allyl thiosulfates, di(Z-
allyl) disulfides, (2E)-methyl cinnamic esters, samarium metal
Recently, there has been a growing interest in metal-
mediated organic reactions in media containing water.1
Such aqueous reactions have a number of advantages over
conventional non-aqueous reactions, such as, simple
operation, environmentally benign process, and no re-
quirements for anhydrous organic solvents, etc. To date,
several metals, such as In, Zn, and Sn, have been widely
applied in aqueous media to conduct various reac-
tions.1b,1d,f Metallic samarium is stable in air and its reduc-
ing power (Sm3+/Sm = –2.41V) is similar to that of
magnesium (Mg2+/Mg = –2.37V) and superior to that of
zinc (Zn2+/Zn = –0.71V). However, the reactions promot-
ed by samarium in aqueous media have been investigated
less.2,3
Sodium (Z)-allyl thiosulfates 2 were synthesized in almost
quantitative yield via reaction of the Baylis–Hillman ace-
tates 1 with Na2SSO3·5H2O in anhydrous methanol at
room temperature.7,8 Our initial attempt was to obtain di-
allyl disulfides from the in situ generated 2 in a one-pot
strategy by treatment with Sm/I2 in aqueous media3a be-
cause diallyl disulfides are a class of useful and important
building blocks in organic synthesis as well as potential
bioactive compounds.9,10 Indeed, when 2 derived from
alkyl-substituted 111 were used as substrates, the reaction
proceeded smoothly and gave di(Z-allyl) disulfides 3 in
moderate to good yields (Table 1, entry 1–3). Upon for-
mation of 3 the Z configuration of the allylic moiety in 2
was entirely conserved, which was confirmed by NOESY
experiments.12
The Baylis–Hillman reaction has drawn much attention as
a useful carbon–carbon bond-forming reaction in the last
decades.4 The main attraction of this reaction lies in its
atom economy, catalytic process, and the high degree of
functionality present in the products for further transfor-
mations. Up to now, a number of novel reactions based on
COOMe
R = alkyl
OAc
R
S
2
COOMe
3
Na2SSO3·5H2O
Sm, I2 (trace)
COOMe
COOMe
R
anhyd MeOH
r.t., 4–8 h
THF–NH4Cl (aq)
r.t.
R = aryl
R
SSO3Na
+ 3
1
2
R
4
Scheme 1 Selective formation of the di(Z-allyl) disulfides or (2E)-methyl cinnamic esters.
SYNLETT 2006, No. 15, pp 2492–2494
1
8
.0
9
.2
0
0
6
Advanced online publication: 08.09.2006
DOI: 10.1055/s-2006-950406; Art ID: W11206ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Selective Formation of Di(Z-allyl) Disulfides or (2E)-Methyl Cinnamic Esters
2493
transferred to the substrate 2 to form the radical anion 5;
when R was an alkyl group, cleavage of the S–S bond was
preferred to form S-radical intermediate 6, which then
dimerized to afford the di(Z-allyl) disulfide 3; but when R
was an aryl group, cleavage of the C–S bond predominat-
ed to give allyl radical species 7 or 8. Radical 7 was fa-
vored over 8 due to the conjugated effect of the a,b-
double bond with the aromatic ring. Then 7 received an-
other electron from Sm to produce allyl anion intermedi-
ate 9. Here the attached aryl group on the allyl moiety may
be capable of stabilizing the allyl anion, so that the (2E)-
methyl cinnamic ester 4 could be formed by protonation
of the intermediate 9.
Table 1 Preparation of Di(Z-allyl) Disulfides or (2E)-Methyl
Cinnamic Estersa
Entry
R
Time (h)b Yield (%)c
3d,15
4d
e
1
2
3
4
5
6
7
8
9
Et (1a)
3
3
3
4
4
4
4
4
4
74 (3a)
82 (3b)
84 (3c)
<5
–
e
n-C7H15 (1b)
–
e
C6H5CH2CH2 (1c)
C6H5 (1d)
–
83 (4d)
85 (4e)
84 (4f)
80 (4g)
78 (4h)
77 (4i)
4-CH3C6H4 (1e)
4-ClC6H4 (1f)
2-ClC6H4 (1g)
2-CH3OC6H4 (1h)
3,4-OCH2OC6H3 (1j)
<5
trace
trace
<7
In summary, it was found that the Sm and a trace amount
of I2 could be used for the selective cleavage of the S–S or
C–S bonds in sodium (Z)-allyl thiosulfates depending on
the substituents to give the corresponding di(Z-allyl) di-
sulfides or (2E)-methyl cinnamic esters in moderate to
good yields in aqueous media. The notable advantages of
the reaction were its high regioselectivity, simple one-pot
operation, environmentally benign process, and mild
reaction conditions.
<5
a Reagents and conditions: 1 (1 mmol), Na2SSO3·5H2O (1 mmol),
MeOH (15 mL), r.t., 4–8 h, then Sm (1 mmol), I2 (trace), THF
(20 mL), sat. aq solution of NH4Cl (4 mL), r.t., 3–4 h.
b Time needed for Sm/I2-mediated reduction.
c Isolated yields.
d All new products were characterized by 1H NMR, MS, IR, and
elemental analysis.
References and Notes
e Not detected.
(1) (a) Lubineau, A.; Auge, J.; Queneau, Y. Synthesis 1994,
741. (b) Li, C. J. Chem. Rev. 1993, 93, 2023.
(c) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207.
(d) Li, C. J. Tetrahedron 1996, 52, 5643. (e) Chan, T. H.;
Isaac, M. B. Pure Appl. Chem. 1996, 68, 919. (f) Li, C. J.
Chem. Rev. 2005, 105, 3095.
Interestingly, when substrates 2, derived from aryl-substi-
tuted 1, were allowed to react in the same conditions, se-
lective cleavage of the C–S bonds predominated to give
(2E)-methyl cinnamic esters 413,14 in moderate to good
yields, while diallyl disulfides 3 from the cleavage of the
S–S bonds were only obtained in very small amounts
(Table 1, entries 4–9).
On the basis of previous reports,3c a possible mechanism
for the selective cleavage of the S–S or C–S bonds in 2 is
depicted in Scheme 2. Perhaps the Sm powder was acti-
vated by I2 and aqueous NH4Cl, thus an electron was
(2) For recent examples, see: (a) Yu, C. Z.; Liu, B.; Hu, L. Q. J.
Org. Chem. 2001, 66, 919. (b) Talukdar, S.; Fang, J. M. J.
Org. Chem. 2001, 66, 330. (c) Laskar, D. D.; Prajapati, D.;
Sandhu, J. S. Tetrahedron Lett. 2001, 42, 7883. (d) Wang,
L.; Li, P. H.; Zhou, L. Tetrahedron Lett. 2002, 43, 8141.
(e) Matsukawa, S.; Hinakubo, Y. Org. Lett. 2003, 5, 1221.
(3) (a) Wang, L.; Zhou, L. H.; Zhang, Y. M. Synlett 1999, 1065.
(b) Wang, L.; Zhang, Y. M. Tetrahedron 1999, 55, 10695.
(c) Liu, X.; Liu, Y. K.; Zhang, Y. M. Tetrahedron Lett. 2002,
43, 6787.
activate
Sm
R
[ Sm*]
COOMe
·
COOMe
R = alkyl
electron transfer
SET
COOMe
SSO3Na
R
SSO3Na
S–S Cleavage
·
R
S
5
6
R = aryl
C–S cleavage
2
double coupling
COOMe
COOMe
–
COOMe
COOMe
protonation
[ Sm*]
R
S
2
SET
R
3
R
R
·
4
7
8
9
COOMe
·
R
Scheme 2 Possible mechanism for the selective cleavage of the S–S or C–S bonds in 2 mediated by Sm/I2(trace) system.
Synlett 2006, No. 15, 2492–2494 © Thieme Stuttgart · New York

2494
Y. Liu et al.
LETTER
(4) For reviews, see: (a) Ciganek, E. Org. React. (N.Y.) 1997,
51, 201. (b) Basavaiah, D.; Rao, P. D.; Hyma, R. S.
Tetrahedron 1996, 52, 8001. (c) Basavaiah, D.; Rao, A. J.;
Satyanarayana, T. Chem. Rev. 2003, 103, 811.
(11) All Baylis–Hillman acetates were prepared according to the
literature: (a) Hoffman, H. M. R.; Rabe, J. Angew. Chem.,
Int. Ed. Engl. 1983, 22, 795. (b) David, H. O.; Kenneth, M.
N. J. Org. Chem. 2003, 68, 6427.
(5) For recent examples, see: (a) Chandrasekhar, S.; Basu, D.;
Rambabu, C. Tetrahedron Lett. 2006, 47, 3059.
(12) According to NOESY experiments, there is no NOE
correlation between the signal of the internal olefin proton
and the allylic methylene protons.
(b) Shanmugarn, P.; Rajasingh, P. Synlett 2005, 939.
(c) Das, B.; Majhi, A.; Banerjee, J.; Chowdhury, N.;
Venkateswarlu, K. Tetrahedron Lett. 2005, 46, 7913.
(d) Das, B.; Mahender, G.; Chowdhury, N.; Banerjee, J.
Synlett 2005, 1000. (e) Kabalka, G. W.; Venkataiah, B.;
Dong, G. Org. Lett. 2003, 5, 3803. (f) Kabalka, G. W.;
Venkataiah, B.; Dong, G. Tetrahedron Lett. 2003, 44, 4673.
(6) (a) Liu, Y. K.; Li, J.; Zheng, H.; Xu, D. Q.; Xu, Z. Y.; Zhang,
Y. M. Synlett 2005, 2999. (b) Liu, Y. K.; Xu, D. Q.; Xu, Z.
Y.; Zhang, Y. M. J. Zhejiang Univ. Science, B 2006, 7, 393.
(c) Li, J.; Wang, X. X.; Zhang, Y. M. Synlett 2005, 1039.
(d) Li, J.; Wang, X. X.; Zhang, Y. M. Tetrahedron Lett.
2005, 46, 5233.
(13) The trisubstituted cinnamic ester moiety manifests a
significant role in several biologically active compounds,
see: (a) Senokuchi, K.; Nakai, H.; Nakayama, Y.; Odagaki,
Y.; Sakaki, K.; Kato, M.; Maruyama, T.; Miyazaki, T.; Ito,
H.; Kamiyasu, K.; Kim, S.; Kawamura, M.; Hamanaka, N. J.
Med. Chem. 1995, 38, 4508. (b) Senokuchi, K.; Nakai, H.;
Nakayama, Y.; Odagaki, Y.; Sakaki, K.; Kato, M.;
Maruyama, T.; Miyazaki, T.; Ito, H.; Kamiyasu, K.; Kim, S.;
Kawamura, M.; Hamanaka, N. J. Med. Chem. 1995, 38,
2521. (c) Watanabe, T.; Hayashi, K.; Yoshimatsu, S.; Sakai,
K.; Takeyama, S.; Takashima, K. J. Med. Chem. 1980, 23,
50.
(7) Liu, Y. K.; Xu, X. S.; Zheng, H.; Xu, D. Q.; Xu, Z. Y.;
Zhang, Y. M. Synlett 2006, 571.
(14) (2E)-Methyl cinnamic eaters prepared from Baylis–Hillman
adducts or derivatives by other approaches, see:
(8) One-Pot Synthesis of Di(Z-allyl) Disulfides or (2E)-
Methyl Cinnamic Esters; General Procedure: In a 25-mL
flask were added Na2SSO3·5H2O (0.25 g, 1.0 mmol),
Baylis–Hillman acetate 1 (1.0 mmol), and anhyd MeOH
(15 mL). The mixture was stirred at r.t. for 4–8 h until the
sodium (Z)-allyl thiosulfates were formed.7 MeOH was
removed and THF (20 mL) was added under an inert
atmosphere. Then Sm (0.15 g, 1 mmol) and a trace amount
of I2 were added to the resulting mixture followed by the
addition of a sat. aq solution of NH4Cl (4 mL) dropwise. The
mixture was stirred at r.t. for the time given in Table 1. Upon
completion, the reaction mixture was quenched with dil. HCl
(5%, 15 mL), extracted with Et2O (2 × 30 mL), washed with
brine (15 mL), and dried over MgSO4. After evaporation of
the solvent, the residue was purified by chromatography
[cyclohexane–EtOAc (9:1) (R = alkyl groups) or
(a) Shadakshari, U.; Nayak, S. K. Tetrahedron 2001, 57,
4599. (b) Ravichandran, S. Synth. Commun. 2001, 31, 2055.
(c) Das, B.; Banerjee, J.; Majhi, A.; Mahender, G.
Tetrahedron Lett. 2004, 45, 9225. (d) Li, J.; Qian, W. X.;
Zhang, Y. M. Tetrahedron 2004, 60, 5793. (e) Li, J.; Xu,
H.; Zhang, Y. M. Tetrahedron Lett. 2005, 46, 1931.
(f) Chandrasekhar, S.; Chandrashekar, G.; Vijeender, K.;
Reddy, M. S. Tetrahedron Lett. 2006, 47, 3475.
(15) Compound 3a: IR (film): 1719, 1642 cm–1. 1H NMR (CDCl3,
400 MHz): d = 1.10 (t, 6 H, J = 7.2 Hz), 2.30–2.37 (m, 4 H),
3.69 (s, 4 H), 3.77 (s, 6 H), 6.93 (t, 2 H, J = 7.2 Hz). 13
C
NMR (CDCl3, 100 MHz): d = 13.34, 22.47, 35.00, 51.85,
127.44, 147.90, 166.97. MS (70 eV): m/z (%) = 318 (M+).
Anal. Calcd for C14H22O4S2: C, 52.80; H, 6.96. Found: C,
53.23; H, 6.90.
Compound 3b: IR (film): 1721, 1642 cm–1. 1H NMR
(CDCl3, 400 MHz): d = 0.88 (t, 6 H, J = 7.2 Hz), 1.25–1.47
(m, 20 H), 2.32 (q, 4 H, J = 7.2 Hz), 3.70 (s, 4 H), 3.77 (s, 6
H), 6.95 (t, 2 H, J = 7.2 Hz). 13C NMR (CDCl3, 100 MHz):
d = 22.59, 28.84, 29.09, 29.19, 29.24, 29.32, 31.71, 35.29,
51.89, 127.92, 146.78, 166.99. MS (70 eV): m/z (%) = 458
(M+). Anal. Calcd for C24H42O4S2: C, 62.84; H, 9.23. Found:
C, 62.51; H, 9.28.
cyclohexane–EtOAc (6:1) (R = aryl groups)].
(9) (a) Karchner, J. H. The Analytical Chemistry of Sulfur and its
Compounds; Wiley: New York, 1972. (b) Ogawa, A.
Tetrahedron Lett. 1987, 28, 3271. (c) Antebi, S.
Tetrahedron Lett. 1985, 26, 2609.
(10) (a) Parry, R. J. Tetrahedron 1983, 39, 1215. (b) Arora, A.;
Tripathi, C.; Shukla, Y. Curr. Cancer Ther. Rev. 2005, 1,
199. (c) Arora, A.; Seth, K.; Shukla, Y. Carcinogenesis
2004, 25, 941. (d) Thomas, R. D.; Green, M.; Wilson, C.;
Sadrud-Din, S. Carcinogenesis 2004, 25, 787. (e) Green,
M.; Wilson, C.; Newell, O.; Sadrud-Din, S.; Thomas, R.
Food Chem. Toxicol. 2005, 43, 1323.
Compound 3c: IR (film): 1716, 1643 cm–1. 1H NMR (CDCl3,
400 MHz): d = 2.62 (q, 4 H, J = 8.0 Hz), 2.78 (t, 4 H, J = 8.0
Hz), 3.62 (s, 4 H), 3.72 (s, 6 H), 6.98 (t, 2 H, J = 8.0 Hz),
7.19–7.32 (m, 10 H). 13C NMR (CDCl3, 100 MHz):
d = 31.32, 35.23, 35.38, 52.29, 126.49, 128.66, 128.77,
128.86, 141.01, 145.43, 167.13. MS (70 eV): m/z (%) = 470
(M+). Anal. Calcd for C26H30O4S2: C, 66.35; H, 6.42. Found:
C, 66.72; H, 6.48.
Synlett 2006, No. 15, 2492–2494 © Thieme Stuttgart · New York