Regioselective S -allylation of thiols with cyclic Baylis-Hillman acetates

Article abstract of DOI:10.1080/17415993.2013.809453

An efficient and mild S-allylation of thiols with cyclic Baylis-Hillman acetates with no need of a transition-metal-catalyst or an expensive additive is described. Allyl sulfides are prepared in good to excellent yields (60-97%) and a single regioisomer was observed in all cases.

Full text of DOI:10.1080/17415993.2013.809453

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Regioselective S-allylation of thiols with
cyclic Baylis–Hillman acetates
Imen Errayab, Julie Obleb, Giovanni Polib & Farhat Rezguia
a Laboratoire de Chimie Organique Structurale et
Macromoléculaire, Faculté des Sciences Campus Universitaire,
Université de Tunis El Manar, 2092 Tunis, Tunisie
b UMR 7201 – CNRS, Institut Parisien de Chimie Moléculaire,
Université Pierre et Marie Curie, Case 229 Bât F. 2e étage 4, Place
Jussieu, 75252 Paris Cedex 05, France
Published online: 10 Jul 2013.
To cite this article: Imen Erray, Julie Oble, Giovanni Poli & Farhat Rezgui (2014) Regioselective S-
allylation of thiols with cyclic Baylis–Hillman acetates, Journal of Sulfur Chemistry, 35:2, 128-136,
DOI: 10.1080/17415993.2013.809453
To link to this article: http://dx.doi.org/10.1080/17415993.2013.809453
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Journal of Sulfur Chemistry, 2014
Vol. 35, No. 2, 128–136, http://dx.doi.org/10.1080/17415993.2013.809453
Regioselective S-allylation of thiols with cyclic Baylis–Hillman
acetates
Imen Erraya,b, Julie Obleb, Giovanni Polib and Farhat Rezguia*
aLaboratoire de Chimie Organique Structurale et Macromoléculaire, Faculté des Sciences Campus Univer-
sitaire, Université de Tunis El Manar, 2092 Tunis, Tunisie; bUMR 7201 – CNRS, Institut Parisien de Chimie
Moléculaire, Université Pierre et Marie Curie, Case 229 Bât F. 2e étage 4, Place Jussieu, 75252 Paris Cedex
05, France
(Received 2 April 2013; final version received 23 May 2013)
An efficient and mild S-allylation of thiols with cyclic Baylis–Hillman acetates with no need of a transition-
metal-catalyst or an expensive additive is described. Allyl sulfides are prepared in good to excellent yields
(60–97%) and a single regioisomer was observed in all cases.
Keywords: Baylis–Hillman; nucleophilic substitution; conjugate addition; allyl sulfides; regioselectivity
1. Introduction
Nucleophilic allylic substitutions are useful transformations in organic chemistry that are often uti-
lized as powerful tools for the construction of carbon–carbon and carbon-heteroatom bonds in the
synthesis of complex organic molecules.[1] Highly reactive allylic substrates smoothly react with
a large variety of nucleophiles with no need for catalysts[2] while less reactive ones first require
activation toward substitution reactions using transition metal catalysts such as palladium ([3]
and references therein) and ruthenium.[4–6] In this context, a large number of synthetic methods
involving carbon, nitrogen, and oxygen nucleophiles have been previously reported.[7–15] How-
ever, synthetic approaches, using transition metal-free or transition-metal-catalyzed S-allylation
of thiols, are not yet well-developed,[16] presumably due to the poisoning of metal catalysts by
coordinating-sulfur[17–19] and the low selectivity of such procedures.[20, 21]
Therefore, a clean and economical S-allylation is still a very attractive goal for the con-
struction of carbon–sulfur bonds, especially in functionalized allylic compounds such as
Baylis–Hillman (BH) adducts. As it so happens, reactions of acyclic BH acetates with
thiols,[22, 23] sulfonylhydrazides,[24] and thiolacetic acid,[25] under basic conditions, afforded
*Corresponding author. Email: rez_far@yahoo.fr
© 2013 Taylor & Francis

Journal of Sulfur Chemistry 129
the corresponding SN2ꢀ products whereas treatment of acyclic BH alcohols [22, 26] or their
corresponding tert-butyldimethylsilyl ethers [22] with thiols resulted in the formation of Michael
adducts.
In the course of our study on the chemistry of cyclic BH adducts, we have previously reported
the S-allylation of alkyl alcohols and thiols with 2-(hydroxymethyl)cyclohex-2-en-1-one in the
presence of p-TsOH [27] as well as the C-allylation of β-dicarbonyl compounds with either
cyclic BH acetates[28] or even with their corresponding alcohols,[29] through a Tsuji-Trost-type
reaction. To the best of our knowledge, the S-allylation of thiols with cyclic BH acetates has
not been extensively studied in the presence of a transition metal-catalyst or under catalyst-free
conditions. Hence, we wish to report in this paper an efficient highly regioselective transition
metal-free S-allylation of a variety of thiols with BH acetates 1a–c under mild reaction conditions
(THF at room temperature).
2. Results and discussions
In our preliminary attempt, a mixture of thiophenol and the BH acetate 1a in THF was carried
out without any additive, first at room temperature, then at reflux for 8 h. In this case, we have
observed that the starting materials were recovered, presumably because the thiophenol is not
sufficiently nucleophilic to convert the acetate 1a into the corresponding allylic sulfur compound
2a. Therefore, we investigated, in THF at room temperature, the behavior of the acetate 1a toward
sodium thiophenolate which would be more nucleophilic than the corresponding thiophenol.
Under these conditions, we have actually observed a catalyst-free total conversion of the acetate
1a into the SN2-type product 2a (For previous reports on α-(alkylthioalkyl)cyclic enones, see
[30–33]) in 72% yield (Table 1, Entry 1) (Scheme 1).
Scheme 1. S-allylation of thiols with BH acetates 1a–c.
According to our previous work[28, 29] and previous papers[31, 32, 34–36] on the allylic
nucleophilic substitutions of cyclic BH adducts, we believe that the reaction starts with a β-
conjugate addition of sodium thiolate to Michael acceptor 1a, followed by the elimination of
acetate ion, to afford the intermediate I. Subsequent βꢀ-conjugate addition of sodium thiolate to I
and elimination of the thiolate ion, provides the thermodynamically stable product 2a, which is
then the result of two consecutive SN2ꢀ reactions through a one pot addition-elimination sequence.
Another alternative reaction mechanism could be proposed for the reaction of allylic acetates
with thiols, suggesting an anchimeric assistance of the acetoxy moiety.[37]
In order to demonstrate the scope and the limitation of this interesting synthetic methodology,
we investigated, under the above reaction conditions (THF at room temperature) the reactivity of a
variety of sodium thiolatestoward theacetate 1a (Table1, Entries2–6)aswell aswithdifferentially
α-substituted BH acetates 1b–c (Table 1, Entries 7–14). Our results, listed in Table 1, showed the
total conversion of all acetates 1a–c into the corresponding allyl sulfides 2b–n in 60–97% yields.
Encouraged by these successful results on the allylation of thiols with BH acetates 1a–c,
under these mild conditions, we attempted to extend this simple synthetic methodology to ethane

130 I. Erray et al.
Table 1. S-allylation of thiols with BH acetates 1a–c.
Entry
R1
Thiol
Product 2
Yield (%)
72
1
H(1a)
PhSH
2
H(1a)
H(1a)
MeSH
EtSH
83
61
63
73
84
60
80
81
60
75
97
85
92
3
4
H(1a)
n-BuSH
5
H(1a)
EtO2CCH2SH
CH3(CH2)4CH2SH
PhSH
6
H(1a)
7
CH3(1b)
CH3(1b)
CH3(1b)
CH3(1b)
Ph(1c)
Ph(1c)
Ph(1c)
Ph(1c)
8
CH3(CH2)4CH2SH
CH3CH2CH2SH
n-BuSH
9
10
11
12
13
14
PhSH
CH3(CH2)4CH2SH
CH3CH2CH2SH
n-BuSH

Journal of Sulfur Chemistry 131
1,2-dithiolinasuspensionofNaHinTHF. Inthiscase, 0.5equivofsodiumethane1,2-bis(thiolate),
in situ generated from 0.5 equiv of ethane dithiol and 1 equiv of NaH at 0◦C, reacted with 1 equiv
of acetate 1a, at room temperature, in the same way as observed for the sodium thiolates, to give
the bis-SN2 type product 3 in 70% yield (Scheme 2).[32]
Scheme 2. Proposed mechanism for the conversion of 1a to 2a.
On the other hand, when 1 equiv of ethane 1,2-dithiol was left to react, under the previous
conditions, but with 1 equiv of NaH, the monosodium salt of ethane 1,2-dithiol was obtained;
its thiolate moiety further reacted, similarly to the above thiolates, with the acetate 1a, to give
the allyl sulfur adduct I. The latter, bearing a thiol moiety as a soft nucleophile, subsequently
reacted in an intramolecular 1,4-addition on the cyclic enone subunit, to finally afford the bicyclic
1,4-dithiane derivative 4 in 83% overall yield (Scheme 3).[32]
Scheme 3. Reactions of acetate 1a with ethane 1,2-dithiol.
3. Conclusions
We have developed a mild and highly regioselective catalyst-free S-allylation of thiols with BH
acetates in moderate to excellent yields. Moreover, the behavior of ethane 1,2-dithiol/NaH toward
the acetate 1a was investigated and we have disclosed that the sodium ethane 1,2-bis(thiolate)
gave the bis allylation compound 3 while the monosodium salt of ethane 1,2-dithiol afforded the
1,4-dithiane derivative 4.
4. Experimental section
4.1. General
IR spectra were recorded on a Bruker (IFS 66v/S) spectrometer. 1H NMR and 13C NMR spec-
1
tra were recorded on a Bruker AC-300 spectrometer (300 MHz for H and 75 MHz for 13C) in
CDCl3, using TMS as an internal standard (chemical shift in δ values, J in Hz). High resolution
mass spectra (HRMS) were recorded as ESI-HRMS on an Auto Spec Ultima/micromass mass
spectrometer.
Analytical thin layer chromatography was performed using Fluka Kieselgel 60 F254 precoated
silica gel plates. Visualization was achieved by UV light (254 nm). Flash chromatography was
performed using Merck silica gel 60 and a gradient solvent system (pet-ether/ether as eluent).

132 I. Erray et al.
4.2. Typical procedure for the preparation of sulfur compounds 2a–n
To a suspension of NaH (8 mmol, 192 mg), in dry THF (20 mL) at 0◦C, was added a solution
of thiol (8 mmol) in THF (2 mL). The reaction mixture was then stirred at room temperature for
30 min. the allyl acetate 1a (6 mmol, 1.008 g) in dry THF (10 mL) was added dropwise at 0◦C.
The resulting mixture was stirred at room temperature for a further 1 h. The reaction mixture was
partitioned between water (20 mL) and ether (30 mL). The aqueous phase was extracted with ether
(3 × 20 mL). The ether extracts were washed with brine, dried over MgSO4, and concentrated
under reduced pressure. The crude product was purified by column chromatography on silica gel
(ether/petroleum ether: 1/4).
4.2.1. 2-(Phenylthiomethyl)cyclohex-2-en-1-one (2a)
Yield = 72%; yellow oil; IR (CHCl3): 1680, 1590, 1480, 1440 cm−1; H NMR (300 MHz,
1
CDCl3): 7.33–7.00 (m, 5H), 6.67 (t, J = 4.0 Hz,1H), 3.67–3.53 (m, 2H), 2.50–1.67 (m, 6H);
13C NMR (75 MHz, CDCl3): 197.6, 147.3, 135.8, 134.6, 129.8, 128.4, 126.0, 37.9, 32.2, 25.6,
22.5; MS (EI): m/z (%) 53(46), 79(55.4), 81(98), 110(54.5), 185(36.6), 218(C13H14OS, M+, 100).
4.2.2. 2-(Methylthiomethyl)cyclohex-2-en-1-one (2b)
Yield = 83%; yellow oil; IR (CHCl3): 1670 cm−1; H NMR (300 MHz, CDCl3): 6.91 (t, J =
1
4.0 Hz, 1H), 3.25 (s, 2H), 2.48–2.42 (m, 4H), 2.03 (s, 3H), 2.06–1.98 (m, 2H); 13C NMR (75 MHz,
CDCl3): 197.5, 146.2, 135.1, 37.8, 31.6, 25.4, 22.4, 15.0; MS (EI): m/z (%) 53(41), 79(46),
141(38), 156 (C8H12OS, M+, 100).
4.2.3. 2-(Ethylthiomethyl)cyclohex-2-en-1-one (2c)
1
Yield = 61%; yellow oil; IR (CHCl3): 1660 cm−1; H NMR (300 MHz, CDCl3): 6.90 (t, J =
4.0 Hz, 1H), 3.30 (s, 2H), 2.50 (m, 6H), 2.00 (m, 2H), 1.26 (m, 3H); 13C NMR (75 MHz, CDCl3):
198.0, 146.5, 136.1, 38.1, 29.3, 25.8, 25.83, 22.8, 14.2; MS (EI): m/z (%) 53(52), 82(97), 110(91),
141(100), 170(C9H14OS, M+, 90).
4.2.4. 2-(Butylthiomethyl)cyclohex-2-en-1-one (2d)
1
Yield = 63%; yellow oil; IR (CHCl3): 1662 cm−1; H NMR (300 MHz, CDCl3): 6.90 (t, J =
4.0 Hz, 1H), 3.33 (s, 2H), 2.66–2.33 (m, 6H), 2.10–1.80 (m, 2H), 1.60–1.00 (m, 4H), 0.9 (t,
J = 4.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): 197.9, 146.4, 136.1, 38.1, 31.6, 31.1, 29.8, 25.7,
22.7, 21.7, 13.4; MS (EI): m/z (%) 53(63), 82(97), 110(100), 141(60), 198(C11H18OS, M+, 33).
4.2.5. 2-(Ethoxycarbonylmethylthiomethyl)cyclohex-2-en-1-one (2e)
Yield = 73%; yellow oil; IR (CHCl3): 1740, 1725, 1670 cm−1; 1H NMR (300 MHz, CDCl3): 6.93
(t, J = 4.1 Hz, 1H), 4.17 (q, J = 7.0 Hz, 2H), 3.40 (s, 2H), 3.15 (s, 2H), 2.67–1.80 (m, 6H), 1.27 (t,
J = 7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3): 197.8, 170.2, 147.4, 135.1, 61.1, 38.1, 33.0, 30.2,
25.8, 22.7, 14.0; MS (EI): m/z (%) 53(36.0), 79(72.7), 141(100), 182(45.7), 228(C11H16O3S,
M+, 20.53).

Journal of Sulfur Chemistry 133
4.2.6. 2-(Hexylthiomethyl)cyclohex-2-en-1-one (2f)
Yield = 84%; yellow oil; IR: 1673 cm−1; 1H NMR (300 MHz, CDCl3): 6.91 (t, J = 4.2 Hz, 1H),
3.29 (d, J = 3 Hz, 2H), 2.48–2.41 (m, 6H), 2.07–1.97 (m, 2H), 1.61–1.52 (m, 2H), 1.39–1.25
(m, 6H), 0.88 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3): 198.1, 146.6, 136.5, 38.4, 32.3,
31.5, 30.3, 29.7, 28.6, 26.1, 23.0, 22.8, 14.0; HRMS (ESI): calcd for C13H22OSNa [M + Na]+
249.1289, found 249.1284.
4.2.7. 2-(1-(Phenylthio)ethyl)cyclohex-2-en-1-one (2g)
Yield = 60%; yellow oil; IR: 1670 cm−1; 1H NMR (300 MHz, CDCl3): 7.34–7.19 (m, 5H), 6.85
(t, J = 3 Hz, 1H), 4.46 (q, J = 7.1 Hz, 1H), 2.42 (t, J = 7.5 Hz, 2H), 2.35–2.29 (m, 2H), 1.97–
1.9 (m, 2H), 1.34 (d, J = 7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3): 197.3, 145.7, 140.4, 135.0,
135.52, 128.6, 126.9, 39.0, 38.4, 25.9, 22.6, 20.8;HRMS(ESI):calcdforC14H16OSNa[M + Na]+
255.0819, found 255.0814.
4.2.8. 2-(1-(Hexylthio)ethyl)cyclohex-2-en-1-one (2h)
Yield = 80%; yellow oil; IR: 1674 cm−1; 1H NMR (300 MHz, CDCl3): 7.03 (t, J = 4.2 Hz, 1H),
4.05 (q, J = 7.1 Hz, 1H), 2.48–2.41 (m, 6H), 2.04–1.95 (m, 2H), 1.59–1.49 (m, 2H), 1.37–1.24
(m, 6H), 1.33 (d, J = 7.0 Hz, 3H), 0.88 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3): 197.5,
144.9, 142.0, 38.6, 36.0, 31.7, 31.5, 29.6, 28.67, 26.1, 22.9, 22.5, 21.5, 14.0; HRMS (ESI): calcd
for C14H24OSNa [M + Na]+ 263.1445, found 263.1440.
4.2.9. 2-(1-(Propylthio)ethyl)cyclohex-2-en-1-one (2i)
1
Yield = 81%; yellow oil; IR: 1670 cm−1; H NMR (300 MHz, CDCl3): 7.07 (t, J = 4.2 Hz,
1H), 4.02 (q, J = 7Hz, 1H), 2.49–2.39 (m, 6H), 2.04–1.95 (m, 2H), 1.61–1.51 (m, 2H), 1.35
(d, J = 7 Hz, 3H), 0.96 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3): 197.7, 145.1, 141.8,
38.6, 35.8, 33.64, 26.1, 22.9, 22.82, 21.4, 13.58; HRMS (ESI): calcd for C11H18OSNa [M + Na]+
221.0976, found 221.0971.
4.2.10. 2-(1-(Butylthio)ethyl)cyclohex-2-en-1-one (2j)
Yield = 60%; yellow oil; IR: 1672.02 cm−1; 1H NMR (300 MHz, CDCl3): 7.03 (t, J = 4.2 Hz,
1H), 4.04 (q, J = 7.0 Hz, 1H), 2.49–2.42 (m, 6H), 2.04–1.97 (m, 2H), 1.56–1.51 (m, 2H), 1.43–
1.39 (m, 2H), 1.34 (d, J = 7.0 Hz, 3H), 0.89 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3):
197.8, 145.2, 141.8, 38.9, 35.8, 31.6, 31.2, 26.1, 22.8, 22.1, 21.7, 13.7; HRMS (ESI): calcd for
C12H20OSNa [M + Na]+ 235.1133, found 235.1127.
4.2.11. 2-((Phenylthio)benzyl)cyclohex-2-en-1-one (2k)
Yield = 75%; yellow oil; IR: 1671.04 cm−1; 1H NMR (300 MHz, CDCl3): 7.38–7.08 (m, 11H),
5.69 (s, 1H), 2.40–2.29 (m, 4H), 1.91–1.82 (m, 2H); 13C NMR (75 MHz, CDCl3): 197.0, 148.1,
139.9, 138.9, 134.7, 132.7, 129.9, 129.5, 128.8, 128.5, 126.4, 48.6, 38.2, 26.0, 22.0; HRMS (ESI):
calcd for C19H18OSNa [M + Na]+ 317.0976, found 317.0971.

134 I. Erray et al.
4.2.12. 2-((Hexylthio)benzyl)cyclohex-2-en-1-one (2l)
1
Yield = 97%; yellow oil; IR: 1674.91 cm−1; H NMR (300 MHz, CDCl3): 7.39–7.16 (m, 5H),
7.11 (t, J = 4.0 Hz, 1H), 5.22 (s, 1H), 2.40–2.32 (m, 6H), 1.95–1.89 (m, 2H), 1.54–1.47 (m, 2H),
1.33–1.20 (m, 6H), 0.85 (t, J = 6.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): 197.0, 147.2, 142.7,
141.0, 128.4, 128.3, 126.9, 45.5, 38.3, 32.4, 31.3, 29.4, 29.2, 26.1, 22.6, 22.5, 13.6; HRMS (ESI):
calcd for C19H26OSNa [M + Na]+ 325.1602, found 325.1597.
4.2.13. 2-((Propylthio)benzyl)cyclohex-2-en-1-one (2m)
1
Yield = 85%; yellow oil; IR: 1672.02 cm−1; H NMR (300 MHz, CDCl3): 7.40–7.18 (m, 5H),
7.12 (t, J = 4.0 Hz, 1H), 5.22 (s, 1H), 2.44–2.31 (m, 6H), 1.99–1.89 (m, 2H), 1.58–1.49 (m, 2H),
0.92 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3): 197.1, 147.3, 142.7, 139.9, 128.3, 128.2,
127.9, 45.4, 38.4, 32.1, 26.1, 22.9, 22.8, 13.5; HRMS (ESI): calcd for C16H20OSNa [M + Na]+
283.1133, found 283.1127.
4.2.14. 2-((Butylthio)benzyl)cyclohex-2-en-1-one (2n)
1
Yield = 92%; yellow oil; IR: 1673.58 cm−1; H NMR (300 MHz, CDCl3): 7.40–7.19 (m, 5H),
7.12 (t, J = 4.2 Hz, 1H), 5.22 (s, 1H), 2.43–2.33 (m, 6H), 2.00–1.88 (m, 2H), 1.54–1.46 (m, 2H),
1.37–1.30 (m, 2H), 0.85 (t, J = 7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3): 197.2, 147.3, 143.0,
140.0, 128.3, 128.2, 127.9, 45.5, 38.4, 32.0, 31.1, 26.1, 22.6, 21.9, 13.6; HRMS (ESI): calcd for
C17H22OSNa [M + Na]+ 297.1289, found 297.1284.
4.2.15. 2,2ꢀ-((Ethane-1,2-diyl(disulfanyl)dimethyl)dicyclohex-2-en-1-one (3)
To a suspension of NaH (6 mmol, 144 mg) in dry THF (15 mL), was added, under nitrogen,
ethane 1,2-dithiol (3 mmol, 282 mg) dropwise at 0◦C. The reaction mixture was stirred at room
temperature for 30 min. 2-(Acetoxymethyl)cyclohex-2-en-1-one 1a (6 mmol, 1.008 g) in dry THF
(10 mL) was then added dropwise at 0◦C. The reaction mixture was stirred at room temperature for
a night and then partitioned between water (20 mL) and dichloromethane (40 mL). The aqueous
phase was extracted with dichloromethane (3 × 20 mL). The combined organic phase was washed
with brine, dried over MgSO4 and concentrated under reduced pressure. The crude product was
purified by column chromatography on silica gel (ether/light petroleum ether: 2/1). Yield = 70%;
yellow oil; IR (CHCl3): 1710, 1670, 1420 cm−1; 1H NMR (300 MHz, CDCl3): 6.94 (t, J = 4.2 Hz,
2H), 3.32 (d, J = 3.0 Hz, 4H), 2.67 (s, 4H), 2.49–2.42 (m, 8H), 2.04–1.99 (m, 4H); 13C NMR
(75 MHz, CDCl3): 198.0, 147.3, 136.0, 38.3, 31.9, 30.0, 26.0, 22.9; HRMS (ESI): calcd for
C16H22O2S2Na [M + Na]+ 333.0959, found 333.0953.
4.2.16. 2,5-Dithia-bicyclo[5.4.0]undecan-8-one (4)
To a suspension of NaH (6 mmol, 144 mg) in dry THF (15 mL), was added, under nitrogen,
ethane 1,2-dithiol (6 mmol, 564 mg) dropwise at 0◦C. The reaction mixture was stirred at room
temperature for 30 min. 2-(Acetoxymethyl)cyclohex-2-en-1-one 1a (6 mmol, 1.008 g) in dry THF
(10 mL) was then added dropwise at 0◦C. The reaction mixture was stirred at room temperature for
a night and then partitioned between water (20 mL) and dichloromethane (40 mL). The aqueous
phase was extracted with dichloromethane (3 × 20 mL). The combined organic phase was washed
with brine, dried over MgSO4 and concentrated under reduced pressure. The crude product was
purified by column chromatography on silica gel (ether/light petroleum ether: 2/1). Yield = 83%;

Journal of Sulfur Chemistry 135
mp = 150–152◦C; IR (CHCl3): 1710, 1410 cm−1; 1H NMR (300 MHz, CDCl3): 4.26–2.74 (m,
8H), 2.43–2.23 (m, 6H); 13C NMR (75 MHz, CDCl3): 208.9, 60.1, 55.1, 49.8, 41.7, 40.4, 39.2,
39.1, 36.8, 33.1, 32.8, 22.8; MS (EI) m/s: 97 (22.3), 110 (54.1), 174 (16.9), 202 (C9H14OS2, M+,
100).
Acknowledgements
We gratefully acknowledge financial support of this work by the Ministry of Higher Education of Tunisia.
References
[1] Trost BM, Crawley ML. Asymmetric transition-metal-catalyzed allylic alkylations: applications in total synthesis.
Chem Rev. 2003;103:2921–2943.
[2] Han X, Zhang Y, Wu J. Mild two-step process for the transition-metal-free synthesis of carbon-carbon bonds from
allylic alcohols/ethers and Grignard reagents. J Am Chem Soc. 2010;132:4104–4106.
[3] SatoY,Yoshino T, Mori, M. Pd-catalyzed allylic substitution using nucleophilic N-heterocyclic carbene as a ligand.
Org Lett. 2003;5:31–33.
[4] Kondo T, Morisaki Y, Uenoyama S-Y, Wada K, Mitsudo T-A. First ruthenium-catalyzed allylation of thiols enables
the general synthesis of allylic sulfides. J Am Chem Soc. 1999;121:8657–8658.
[5] Bayer A, Kazmaier U. Highly regioselective ruthenium-catalyzed allylic alkylations of chelated enolates. Org Lett.
2010;12:4960–4963.
[6] Kawatsura M, Sato M, Tsuji H, Ata F, Itoh T. Retention of regiochemistry and chirality in the ruthenium catalyzed
allylic alkylation of disubstituted allylic esters. J Org Chem. 2011;76:5485–5488.
[7] Evans PA, Nelson JD. Conservation of absolute configuration in the acyclic rhodium-catalyzed allylic alkylation
reaction: evidence for an enyl (σ + π) organorhodium intermediate. J Am Chem Soc. 1998;120:5581–5582.
[8] Companyo X, Valero G, Ceban V, Calvet T, Font-Bardia M, Moyano A, Rios R. Enantioselective organocat-
alytic asymmetric allylic alkylation. Bis(phenylsulfonyl)methane addition to MBH carbonates. Org Biomol Chem.
2011;9:7986–7989.
[9] Benfatti F, Cardillo G, Gentilucci L, Mosconi E, Tolomelli A. Synthesis of dehydro-β-amino esters via highly
regioselective amination of allylic carbonates. Org Lett. 2008;10:2425–2428.
[10] Liu Y-L, Liu L, Wang D, Chen Y-J. A highly α-regioselective In(OTf)3-catalyzed N-nucleophilic substitution of
cyclic Baylis–Hillman adducts with aromatic amines. Tetrahedron. 2009;65:3473–3479.
[11] Huang J-R, Cui H-L, Lei J, Sun X-H, Chen Y-C. Organocatalytic chemoselective asymmetric N-allylic alkylation
of enamides. Chem Commun. 2011;47:4784–4786.
[12] Garzon C, Attolini M, Maffei M. Synthesis of β-aminovinylphosphonates by organocatalytic nucleophilic
displacement of acetate with amines. Tetrahedron Lett. 2010;51:3772–3774.
−
[13] Kim H, Lee C. A Mild and efficient method for the stereoselective formation of C O Bonds: palladium-catalyzed
allylic etherification using Zinc(II) alkoxides. Org Lett. 2002;4:4369–4371.
[14] Saha A, Leazer J, Varma RS. O-Allylation of phenols with allylic acetates in aqueous media using a magnetically
separable catalytic system. Green Chem. 2012;14:67–71.
[15] Basavaiah D, Reddy BS, Badsara SS. Recent contributions from the Baylis-Hillman reaction to organic chemistry.
Chem Rev. 2010;110:5447–5674.
[16] Saha A, Ranu BC. Transition metal-free activation of allylic acetates toward regioselective S-allylation of thiols.
Tetrahedron Lett. 2010;51:1902–1905.
[17] Goux C, Lhoste P, Sinou, D. Palladium(0)-catalyzed alkylation of thiols. Tetrahedron. 1994;50:10321–10330.
[18] Komine N, Sako A, Hirahara S-Y, Hirano M, Komiya S. Selective allylation of arenethiols using water-soluble
palladium complex catalyst in recyclable water/hexane biphasic media. Chem Lett. 2005;34:246–247.
[19] Kondo T, Morisaki Y, Uenoyama S-Y, Wada K, Mitsudo T-A. First ruthenium-catalyzed allylation of thiols enables
the general synthesis of allylic sulfides. J Am Chem Soc. 1999;121:8657–8658.
[20] Tamura S, Shiomi A, Kaneko M, Ye Y, Yoshida M, Yoshikawa M, Kimura T, Kobayashi M, Murakami N. New
rev-export inhibitor fromAlpinia galanga and structure–activity relationship. Bioorg Med Chem Lett. 2009;19:2555–
2557.
[21] Gao N, Zheng S, Yang W, Zhao X. Carbon-sulfur bond formation via iridium-catalyzed asymmetric allylation of
aliphatic thiols. Org Lett. 2011;13:1514–1516.
[22] Kamimura A, Morita R, Matsuura K, Mitsudera H, Shirai M. A convenient stereoselective synthesis of β-lactams
from β-hydroxy-α-thioalkylesters prepared from Michael/aldol tandem reaction or stereoselective addition of thiols
to the Baylis–Hillman adducts. Tetrahedron. 2003;59:9931–9938.
[23] Das B, Chowdhury N, Damodar K, Banerjee J. A mild and efficient stereoselective synthesis of (Z)- and (E)-
allyl sulfides and potent antifungal agent, (Z)-3-(4-methoxybenzylidene)thiochroman-4-one from Morita–Baylis–
Hillman acetates. Chem Pharm Bull. 2007;55:1274–1276.
[24] Li X, Xu X, Tang Y. Tetrabutylammonium iodide catalyzed allylic sulfonylation of Baylis–Hillman acetates with
sulfonylhydrazides in water. Org Biomol Chem. 2013;11:1739–1742.

136 I. Erray et al.
[25] Cha MJ, Song YS, Lee K-J. Synthesis of symmetric diallyl disulfides from Baylis-Hillman acetates. Bull Korean
Chem Soc. 2006;27:1900–1902.
[26] Ramesh C, Lei P-M, Kavala V, Kuo C-W, Yao C-F. A convenient one-pot preparation of 2-methyl-3-(phenylthio-
methyl)quinolinesfromMorita-Baylis-Hillmanadductsandtheiroxidationtothecorrespondingsulfones. Molecules.
2012;17:5081–5094.
[27] Gatri R, Rezgui F, El Gaied MM. Regioselective reaction of a cyclic Baylis-Hillman adduct with alcohols and thiols.
J Chem Res. 2002;8:366–367.
[28] Rezgui F, El Gaied MM. Réaction régiospécifique des carbanions stabilisés avec la 2-(acétoxyméthyl)cyclohex-2-
én-1-one: Synthèse de diénones bicycliques. Tetrahedron. 1997;53:15711–15716.
[29] Mhasni O, Rezgui F. The first DMAP-mediated palladium-free Tsuji-Trost-type reaction of cyclic and acyclic
Baylis–Hillman alcohols with active methylene compounds. Tetrahedron Lett. 2010;51:586–587.
[30] Cohen T, Kosarych Z, Suzuki K, Yu L-C. [2,3]-Sigmatropic rearrangement of an in situ prepared ylide and a
thioether to thio ester conversion as key steps in short syntheses of sarkomycin and its phenylthio ester. J Org Chem.
1985;50:2965–2968.
[31] Tamura R, Tamai S, Suzuki H. New substitution reaction of allylic nitro compounds. Regioselective replacement of
nitro group in cyclic α-(nitroalkyl)enones by nucleophiles. Tetrahedron Lett. 1989;30:2413–2416.
[32] Tamura R, Katayama H, Watabe K, Suzuki H. Regioselective replacement of nitro or sulfonyl group in cyclic
α-(nitroalkyl)- or α-(phenylsulfonylalkyl)enones by nucleophiles. Tetrahedron. 1990;46:7557–7568.
[33] Baraldi PG, Achille B, Simoneta B, Piero PG, Vinicio Z. 2,3a,5,6,7,7a-Hexahydro-3h,4h-benzothiophene-3,4-dione
and cyclopenta [b]-tetrahydrothiophene-3,4-dione enolate anions as synthetic equivalents to cyclohex-2-enone and
cyclopent-2-enone c-2-carbanions. Tetrahedron Lett. 1984;25:4291–4294.
[34] Tamura R, Tamai S, Katayama H, Suzuki H. Me3SiCl promoted conjugate addition of organocuprates to base-
sensitive cyclic α-(nitroalkyl)enones. Tetrahedron Lett. 1989;30:3685–3688.
[35] Okamoto S, KobayashiY, Kato H, Hori K, Takahashi T, Tsuji J, Sato F. Prostaglandin synthesis via two-component
coupling. Highly efficient synthesis of chiral prostaglandin intermediates 4-alkoxy-2-alkyl-2-cyclopenten-1-one and
4-alkoxy-3-alkenyl-2-methylenecyclopentan-1-one. J Org Chem. 1988;53:5590–5592.
[36] Takahashi T, Hori K, Tsuji J. Regiospecific carbon-carbon bond formation at α and β positions in cyclic ketones via
double Michael addition to α-methylene-β-alkoxy cyclic ketone. Tetrahedron Lett. 1981;22:119–122.
[37] Nayak SK, Thijs L, Zwanenburg B. Baylis-Hillman reaction of N-trityl aziridine-2-(S)-carboxaldehyde. Tetrahedron
Lett. 1999;40:981–984.