Alkyl-and arylsulfanyl-substituted unsaturated carbonyl compounds

Article abstract of DOI:10.1080/17415993.2016.1215448

A method for the synthesis of captodative sulfanyl enals, enones and enoates via nucleophilic vinylic substitution of corresponding halogen-bearing derivatives has been developed. The one-pot treatment of the haloenoates, haloenones or haloenals with thiols in the presence of organic base leads either to vicinal dithiosubstituted carbonyl-bearing compound or captodative systems with good to excellent yield. The major reaction direction strongly depends on the type of base used.

Full text of DOI:10.1080/17415993.2016.1215448

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
Alkyl-and arylsulfanyl-substituted unsaturated
carbonyl compounds
Evgeniy V. Kondrashov, Alexey R. Romanov, Igor A. Ushakov & Alexander Yu.
Rulev
To cite this article: Evgeniy V. Kondrashov, Alexey R. Romanov, Igor A. Ushakov & Alexander Yu.
Rulev (2016): Alkyl-and arylsulfanyl-substituted unsaturated carbonyl compounds, Journal of
Sulfur Chemistry, DOI: 10.1080/17415993.2016.1215448
To link to this article: http://dx.doi.org/10.1080/17415993.2016.1215448
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Date: 09 August 2016, At: 00:14

JOURNAL OF SULFUR CHEMISTRY, 2016
http://dx.doi.org/10.1080/17415993.2016.1215448
Alkyl- and arylsulfanyl-substituted unsaturated carbonyl
compounds
Evgeniy V. Kondrashova, Alexey R. Romanova, Igor A. Ushakovb and Alexander Yu.
Ruleva
aA. E. Favorsky Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, Irkutsk, Russia;
bNational Research Irkutsk State Technical University, Irkutsk, Russia
ABSTRACT
ARTICLE HISTORY
Received 25 April 2016
Accepted 17 July 2016
A method for the synthesis of captodative sulfanyl enals, enones
and enoates via nucleophilic vinylic substitution of corresponding
halogen-bearing derivatives has been developed. The one-pot treat-
ment of the haloenoates, haloenones or haloenals with thiols in the
presence of organic base leads either to vicinal dithiosubstituted
carbonyl-bearing compound or captodative systems with good to
excellent yield. The major reaction direction strongly depends on the
type of base used.
KEYWORDS
Thiols; nucleophilic vinylic
substitution; thia-Michael;
unsaturated sulfides;
halogenophilic reaction
1. Introduction
Functionalized alkenyl sulfides are of both theoretical and practical interest because they
are widely present in many natural products and synthetic compounds exhibiting pro-
nounced biological properties.[1] Moreover, because of their multifunctionality and high
reactivity, they have potential application as important building blocks in the synthesis
of various compounds including heterocyclic and biologically active ones.[2] Recently,
it was shown that such type of derivatives have anticancer activity.[3] The nucleophilic
vinylic substitution of activated haloalkenes is one of the simplest and direct routes to these
derivatives. In fact, a number of nitrogen-bearing unsaturated systems (ketones, aldehy-
des, esters) have been successfully prepared based on this type of transformations.[4–10]
In contrast, the analogous reactions with the participation of chalcogen nucleophiles have
been hardly explored. Previously, it was reported that several α-bromo Michael acceptors
(esters and ketones) undergo ipso-substitution by thiols affording mainly α-sulfanyl esters
CONTACT Evgeniy V. Kondrashov
evgeny_irich@irioch.irk.ru
Supplemental data for this article can be accessed here. http://dx.doi.org/10.1080/17415993.2016.1215448
© 2016 Informa UK Limited, trading as Taylor & Francis Group

2
E. V. KONDRASHOV ET AL.
and ketones or their mixtures with corresponding dithiosubstituted derivatives.[11–13]
The tendency of cyclic α-haloenones to react with thiols giving the corresponding α-
sulfanyl derivatives as the only isolated products was also reported.[14] Similarly, α-
chlorocrotonaldehyde reacted with butanethiol leading to the ipso-substitution product in
moderate yield.[15] Interestingly that intracellular reactions of α-haloacrolyl containing
molecules with biological thiols in living organisms generate episulfonium ion interme-
diates, which are DNA-alkylating agents and play an important role in DNA-damaging
and cytotoxicity.[16] The synthesis of α-sulfanylenals from α-bromoenals was also suc-
cessfully carried out using N-heterocyclic carbenes as homogenous catalysts.[17] In con-
trast, a convenient one-step procedure for the construction of push-pull aroxyenones
via cine-substitution of α-haloenones with phenolic reagents has been developed very
recently.[18]
In continuation of our research towards the development of new method of synthesis
of captodative heteroatom-substituted alkenes, we report here the preparation of α-alkyl-
and arylsulfanyl enones and enals from corresponding already available electron-deficient
haloalkenes.
2. Results and discussion
To develop an efficient and general approach to captodative alkenyl sulfides, we firstly
focused our attention on exploring the activated haloalkenes bearing formyl group as
a model Michael acceptor for screening the reaction conditions. For this aim, β-mono-
(1a,b) and β,β-disubstituted haloenals 1c were used in the reaction with alkyl- and aryl
mercaptans.
We have found that conversion of the initial Michael acceptor unexpectedly achieved
only 50% when the haloenal 1a was treated with one equivalent of thiol in the presence
of triethylamine. Thus, a (1:1) mixture of starting enal 1a and dithioderivative 2a was
obtained when aldehyde 1a was treated with propane thiol in THF at room temperature
in the presence of Et3N (Scheme 1, Table 1, Entry 1). At the same time, the reactions of
Scheme 1. Interaction of α-bromoenals with thiols.
Table 1. Synthesis of vicinal dithioadducts 2.
Entry
1
R1
R2
R3
Ratio 1:R3SH
2
Yield, %a
1
2
3
4
1a
1a
1a
1b
Ph
Ph
Ph
Me
H
H
H
Pr
Pr
Bn
Pr
1.1
2.5
2.5
2.5
2a
2a
2b
2c
50
90
71
Me
15b
aIsolated yields.
bThe main reaction product was sulfanylenal 3g.

JOURNAL OF SULFUR CHEMISTRY
3
bromocinnamaldehyde 1a with excess of alkane thiols proceed smoothly under mild con-
ditions affording the corresponding dithioaldehydes 2 as a major reaction product (Table 1,
Entries 2, 3). In both cases the target captodative sulfanyl enals 3 are obtained in trace
amount or not formed at all.
In the absence of stronger bases, compounds 2a–2c are stable and can be stored at
room temperature without any changes for a long time. Evidently, their formation can be
explained in terms of a cascade of transformations including the formation of thia-Michael
adduct A, which transformed further into thiiranium salt B (as considered in some arti-
cles [13,16,17]) followed by nucleophilic attack by the second thiol molecule at the newly
generated saturated carbon center (Scheme 1, Table 1).
The target formylated alkenyl sulfides 3a–3i were prepared in good to high yields when
both mono- and disubstituted haloenals 1a–1c were treated with thiols as nucleophiles
under optimized reaction conditions (Scheme 2, Table 2). Obviously, a chemical equilib-
rium between vicinal dithioadducts 2 and sulfanylenals 3 is realized in the presence of
bases. The oxidation of eliminated thiol by iodine into a disulfide favors the formation of
sulfanylenals.
Sulfanylenals 3a–3f are formed with high stereoselectivity, Z/E ratio determined by 1H
NMR spectra of reaction mixtures is typically more than 20/1. It is very important to
note that the presence of two substituents at the β-carbon of the initial bromoenals did
not preclude the successful synthesis of target compounds (Table 2, Entries 8–10). The
corresponding sulfanyl enals 3g–3i were synthesized for the first time in moderate (for
thiophenol) to excellent yields (for alkane thiols) in the presence of the strong organic base
(DABCO).
The influence of the halogen atom in 1 on the reaction course was shown by the reac-
tions of α-bromo- and α-chlorocinnamaldedydes 1a,b with benzenethiol. We have found
Scheme 2. Synthesis of α-sulfanylenals 3.
Table 2. Reaction conditions for the synthesis of sulfanylenals 3.
Entry
1
R1
R2
R3
X
Base
3
Yield, %a
1
2
3
4
5
6
7
8
9
10
1a
1a
1a
1b
1c
1c
1c
1d
1d
1d
Ph
Ph
Ph
Ph
Pr
Pr
Pr
Me
Me
Me
H
H
H
H
H
H
H
Me
Me
Me
Pr
Bn
Ph
Ph
Pr
Bn
Ph
Pr
Br
Br
Br
Cl
Br
Br
Br
Br
Br
Br
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
DABCO
DABCO
Et3N
3a
3b
3c
3c
3d
3e
3f
3g
3h
3i
84
80
44
54
56
50
32
85
65
32
Bn
Ph
aIsolated yields.

4
E. V. KONDRASHOV ET AL.
that the use of chloroderivative 1b is more preferable: the target phenylsulfanylenal 3c was
isolated in a higher yield (Table 2, Entries 3 and 4).
It was interesting to know whether captodative thioenals 3 can add an equivalent of
thiol to give corresponding dithioderivatives 2. In separate experiments we have shown
that such a reaction easily occurs under mild conditions: compounds 2a and 2d were
isolated when thioenals 3a and 3b were treated with propane thiol in the presence of tri-
ethylamine (Scheme 3). Under the basic conditions no products of 1,2-addition (C) were
observed at all. Thus, this is the first time that the formation of captodative system 3 from
dithioderivative 2 was shown to be reversible.
So, in contrast to their nitrogen analogues which add different nucleophiles (particu-
larly, thiols) in 1,2-mode only,[19] α-sulfanylenals are good Michael acceptors and react
with thiols to give no expected thioacetals C but disulfanyl-substituted saturated aldehydes
2. This result is due to double bond polarity. Thus, for example, in the 13C NMR spectra
of α-sulfanylenals 3 the α-carbon atom resonates at a higher field than the β-carbon in
16–32 ppm. It is very important to note that the carbon–carbon double bond of thioe-
nals 3 has opposite polarity compared to α-aminoenals.[20] The data are unambiguously
indicative of high electrophilicity of the β-carbon and provide evidence for the possibility
of these compounds to undergo the conjugate nucleophilic addition.
Finally, we have found that the direct access to the sulfanylenals 3 is possible by treat-
ment of haloenals 1 with thiols in the presence of equimolar amount of very strong organic
base (such as DBU): in this case the target products 3 were formed in excellent yield (up
to 85% by 1H NMR) even in excess of thiol. So, the use of the strong base is an alterna-
tive way to shift the chemical equilibrium towards the unsaturated compound. The results
obtained enabled us to conclude that the nature of base used is an efficient switch of reaction
direction leading either to saturated sulfides 2 or captodative thioenals 3.
1
The geometry of formed sulfanyl enals 3a–3f was thoroughly determined by H–1H
2D homonuclear experiment NOESY. For example, in the spectrum of enal 3a the major
Z-isomer has a cross-peak between the resonance of the olefinic and formylic protons. In
contrast, the E-configuration of minor isomer 3a was confirmed by the presence of NOE
=
peak between the proton of CH moiety and α-protons of propylsulfanyl group.
Interestingly, the isomer (E)-3a is less stable and slowly transforms into (Z)-3a in chlo-
roform solution at room temperature. In fact, according to quantum-chemical calculations
(MP2, 6–311+G**), the formation energy of the Z-isomer 3a in gas phase is more favorable
for 3 kcal/mol (see Supplemental information).
Scheme 3. General conversion of compounds 2 and 3 in the presence of base.

JOURNAL OF SULFUR CHEMISTRY
5
Taking into account that the synthesis of captodative carbonyl-bearing alkenyl sulfides
proceeds as a cascade Michael addition – nucleophilic substitution – elimination pro-
cess and the electron-withdrawing power of the activated group plays an important role,
we expected that haloenones 4, 7 are slightly less reactive with thiols than haloenals 2.
In fact, in all cases the reactions of ketones with alkyl- and aryl mercaptans are more
complex and lead to the mixture of products. To find optimal reaction conditions, we per-
formed the reaction in different solvents in the presence of organic or mineral bases (Et3N,
DABCO, DBU, KHCO3). The research allowed us to conclude that target carbonyl-bearing
alkenyl sulfides can be successfully synthesized when strong organic bases and polar aprotic
solvents are used.
Reaction of terminal bromoenone 4 with alkanethiols proceeds readily at room temper-
ature leading to dithioderivatives 5 in high to quantitative yield (Scheme 4). Unfortunately,
the retro-Michael reaction is quite difficult in this case due to the lower acidity of α-proton.
Only trace amounts of target alkenyl sulfides 6 were detected by NMR spectroscopy (two
doublets at 5.50 and 6.13 ppm with 2JHH = 1.4 Hz) when ketones 5 were treated even with
DABCO/I2 or DBU/I2 systems.
It should be expected that the introduction of phenyl substituent in the β-position
adversely affects the access to the electrophilic center but favors the retro-Michael reac-
tion leading to enones 9. In fact, bromoenone 7 reacts with alkyl- and aryl mercaptans to
give mainly mono-9 or dithioderivatives 8 in moderate to good yield depending on the
base nature (Scheme 5, Table 3).
The result of the reaction of bromoenone 7 with thiols strongly depends on the nature of
base used. Thus, dithioderivatives 8 were the principal products in the presence of KHCO3
or Et3N (Table 3, Entries 1, 2, 4). In contrast, the use of DBU as a strong base results in a
dramatic decrease in the reaction time and leads exclusively to sulfanylenones 9 (Table 3,
Entries 3, 5).
Scheme 4. Synthesis of 3,4-bis(alkylsulfanyl)butan-2-ones 5.
Scheme 5. Interaction of 3-bromo-4-phenylbutenone 7 with thiols.

6
E. V. KONDRASHOV ET AL.
Table 3. Conditions for the interaction of 3-bromo-4-phenylbutenone 7 with thiols.
Yield, %a
Entry
RSH
Base
Conditions
8
9 (10)
11
12
1
2
3
4
5
6
Pr
Pr
Pr
Bn
Bn
Ph
DABCO
KHCO3
DBU
Et3N
DBU
Et2O, 72 h
acetone, 6 d
CH2Cl2, 1 h
THF, 60 h
CH2Cl2, 1 h
THF, 24 h
50
65b
0
45
0
6 (32)
10b
63
0
50
6
7b
0
46
0
0
18b
0
0
0
0
Et3N
0
36
0
aIsolated yields.
b1H NMR yields.
The halogenophilic reaction was the main side process when ketone 7 was treated
with thiols.[21,22] In this case the thia-Michael adduct D undergoes the SN2Hal reac-
tion. It is well known that α-haloketones are typical compounds for such type of
transformations.[21] In fact, enals 1 are not subjected by such type of reactions, whereas
enone 7 give β-sulfanyl ketones 11 or unsubstituted enone 12 as by-products (Table 3). The
analogous processes for the reaction of saturated α-haloketones with thiols were described
earlier.[12,23–25] The by-products 11a,b were determined in 1H NMR spectra of reaction
mixtures by characteristic signals of CH2-CHSR fragment (doublet at 3.2–3.5 ppm and
triplet at 4.2–4.5 ppm with 3JHH = 7 Hz) and further were isolated by column chromatog-
3
=
raphy. The two doublets of CH CH group at 6.7 and 7.7 ppm with JHH ∼ 16 Hz were
found in the reaction mixture and assigned as characteristic signals of reduction product
12 (Table 3, Entry 2).
Interestingly that captodative enone E-9a isolated in pure form by column chromatogra-
phy is slowly isomerized into Z-9a while standing in CDCl3 solution at room temperature.
The same isomerization was observed for push-pull enone 10: in this case Z-10 is slowly
transformed into thermodynamically more stable E-10.
Finally, we tried to apply this methodology to the synthesis of unsaturated α-sulfanyl
esters (Scheme 6, Table 4). The decrease of the electron-withdrawing ability of the acti-
vating group leads to the decrease of the Michael acceptor reactivity. As a consequence,
the bromoenoate 13 seems to be significantly less active in conjugate addition reactions.
Moreover, a very strong base will be required for all steps of the cascade of transforma-
tions. In fact, no addition occurred when ester 13 was treated with propane thiol in the
presence of Et3N or DABCO as a base (Table 4, Entries 1, 2). When a stronger base such as
DBU was used, mixtures of 14 and 15 were obtained (Table 4, Entries 3, 4). According to
data [13] the reaction of α-bromoacrylates with thiols proceeds under hard conditions
Scheme 6. Interaction of α-bromocinnamate 13 with thiols.

JOURNAL OF SULFUR CHEMISTRY
7
Table 4. Conditions for the interaction of a-bromocinnamate 13 with thiols.
Product, (yield, %)a
Entry
RSH
Conditions
14 15
1
2
3
4
5
Pr
Pr
Pr
Bn
Ph
THF, Et3N, rt, 24 h
THF, DABCO, rt, 24 h
CH2Cl2, DBU, rt, 1 h
CH2Cl2, DBU, rt, 1 h
CH2Cl2, DBU, rt, 1 h
No reaction
No reaction
56
22
78
27b
40
0
aIsolated yields.
b1H NMR yield.
(DMF, 120°C) through thiiranium indermediate. The captodative 14 and push-pull 15
thioenoates and in some cases geometric isomers of compounds 14 can be separated by
column chromatography.
3. Conclusion
In conclusion, an efficient sequential one-pot synthesis of captodative sulfanyl-bearing
unsaturated carbonyl compounds as well as saturated vicinal disulfides starting from cor-
responding α-haloderivatives has been developed. The reaction is applied for the range of
enals, α-bromo-4-phenylbutenone and α-bromocinnamic ester. A competitive formation
of saturated β-sulfanyl ketones due to SN2Hal reaction was observed.
4. Experimental
4.1. General methods
1H (400.1 MHz) and 13C (100.6 MHz) NMR spectra were recorded on Bruker AVANCE
400 MHz spectrometer. Chemical shifts (δ) are given in ppm; the coupling constants (J) are
given in Hertz. The concerted application of 1H-1H 2D homonuclear experiments NOESY
and COSY as well as 1H-13C 2D heteronuclear experiments heteronuclear multiple bond
correlation spectroscopy and heteronuclear single quantum correlation spectroscopy were
used for the distinction of the carbon and proton resonances. The IR spectra were recorded
with a Bruker Vertex 70 FT-IR spectrometer and with a portable Varian 3100 diamond
ATR/FT-IR spectrometer. The GC/MS analyses were performed with a Shimadzu GC-
MS-QP5050A instrument (EI, 70 eV). The silica gel used for column chromatography was
230–400 Mesh. All reagents were of reagent grade and were used as such or distilled prior
to use. All the solvents were dried according to standard procedures and freshly distilled
prior to use.
4.2. General procedure for the synthesis of α,β-disulfanyl aldehydes 2
Method A. Triethylamine (1 mmol) was added to a solution of α-haloenal 1 (1 mmol) and
thiol (2.5 mmol) in 5 mL of absolute THF or Et2O. The reaction mixture was stirred at rt
for 24 h. The precipitate was filtered off, and the solvent was evaporated in vacuum. The
purification of the residue by column chromatography (SiO2, Et2O:hexane = 1:3) afforded
dithioderivatives 2.

8
E. V. KONDRASHOV ET AL.
Method B. Triethylamine (0.5 mmol) was added to a solution of α-sulfanyl enal 3
(1 mmol) and thiol (1.2 mmol) in 3 mL THF or Et2O. The reaction mixture was stored at
rt for 24 h. The solvent was evaporated in vacuum and the residue was purified by column
chromatography (SiO2, Et2O:hexane = 1:3).
4.2.1. 3-Phenyl-2,3-bis(propylsulfanyl)propanal 2a
Yellow oil, 254 mg (90%), (1:2.3) mixture of diastereomers. 1H NMR (400 MHz, CDCl3):
major isomer:δ 0.75–0.90 (m, 6, 23), 1.31–1.50 (m, 4H, 2CH2), 2.16–2.45 (m, 4H, 2SCH2),
3.43 (dd, 3J = 5.7, 11.5 Hz, 1H, CH), 3.87 (d, 3J = 11.5 Hz, 1H, CH), 7.25–7.38 (m, 5H,
=
Ph), 9.20 (d, J = 5.7 Hz, 1H, CH O); minor isomer: δ 0.85–0.98 (m, 6, 23), 1.40–1.60
(m, 4H, 2CH2), 2.16–2.45 (m, 4H, 2SCH2), 3.54 (dd, 3J = 4.8, 9.8 Hz, 1H, CH), 4.18 (d,
3
3
=
J = 9.8 Hz, 1H, CH), 7.25–7.38 (m, 5H, Ph), 9.09 (d, J = 4.8 Hz, 1H, CH O). Anal.
Calcd for C15H22OS2: C 63.78; H 7.85. Found: C 63.98; H 7.80. MS (EI) m/z (relative
intensity): m/z (%): 282 (1, M+), 206 (8), 165 (100), 135 (27), 123 (33), 91 (26).
4.2.2. 2,3-Bis(benzylsulfanyl)-3-phenylpropanal 2b
Yellow oil, 269 mg (71%), (1:2) mixture of diastereomers. IR (film, cm−1): ν 1711 (C O),
=
1
1601, 1584 (Ph). H NMR (400 MHz, CDCl3): δ 3.25–3.61 (m, 5, 2SCH2, CH), 3.72 (d,
3J = 11.7 Hz, 1, major), 4.03 (d, J = 9.4 Hz, 1, minor), 6.98–7.35 (m, 15H, 3Ph), 9.03–9.14
(m, 1H, CH O). 13C NMR (100.6 MHz, CDCl3): major: δ 35.34 (CH2), 35.68 (CH2), 46.38
=
(C3), 55.90 (C2), 128.58–128.59 (four carbons), 128.64 (three carbons), 129.11, 129.35,
3
=
136.43, 137.23, 138.08, 189.32 (C O); minor: δ 34.85 (CH2), 35.41 (CH2), 47.01 (C ),
57.30 (C2), 127.26, 127.42, 127.56, 127.98, 128.22, 128.72, 128.77, 128.85, 129.39, 136.52,
=
137.41, 138.69 (Ph), 189.93 (C O). Anal. Calcd for C23H22OS2: C 72.97; H 5.86. Found:
C 73.15; H 5.95.
4.2.3. 3-Methyl-2,3-bis(propylsulfanyl)butanal 2c
Yellow oil, 35 mg (15%). 1H NMR (400 MHz, CDCl3): δ 0.90–0.97 (m, 6H, 2CH3), 1.35
(s, 3H, CH3), 1.45 (s, 3H, CH3), 1.46–1.64 (m, 4H, 2CH2), 2.29–2.43 (m, 2, S2), 2.47 (t,
=
J = 7.4 Hz, 2, S2), 3.00 (d, J = 6.7 Hz, 1H, CH), 9.24 (d, J = 6.7 Hz, 1H, CH O).
4.2.4. 2-(Benzylsulfanyl)-3-phenyl-3-(propylsulfanyl)propanal 2d
Yellow oil, 330 mg (100%), (1:2.4) mixture of diastereomers. IR (film, cm−1): ν 2821, 2872,
2930, 2962, 3029, 3062, 1713, 1689, 1586, 1568, 1495, 1454. 1H NMR (400 MHz, CDCl3):
major: δ 0.89–0.92 (m, 3, ), 1.42–1.57 (m, 2H, CH2), 2.17–2.39 (m, 2H, SCH2), 3.36
3
(dd, 3J = 5.7, 11.6 Hz, 1H, CH), 3.47–3.63 (2H, AB SCH2Ph), 3.91 (d, 1H, J = 11.6 Hz,
=
CH), 7.05–7.40 (m, 10H, 2Ph), 9.31 (d, 1H, J = 5.7 Hz, CH O); minor: 0.89–0.92 (m,
3, 3), 1.42–1.57 (m, 2H, CH2), 2.17–2.39 (m, 2H, SCH2), 3.47–3.63 (m, 2H, CH, A-part
of AB SCH2Ph), 3.74 (d, J = 12.9 Hz, 1H, B-part of AB SCH2Ph), 4.22 (d, J = 9.4 Hz,
CH), 7.05–7.40 (m, 10H, 2Ph), 9.19 (d, 1H, J = 4.6 Hz, CH O). 13C NMR (100.6 MHz,
=
CDCl3): major: δ 13.40, 22.47, 33.44, 35.37, 47.16, 55.96, 136.49, 138.52, 189.20; minor: δ
13.52, 22.44, 33.18, 35.22, 47.38, 57.63, 136.60, 139.17, 190.28; aromatic carbons for both
diastereomers: 127.43, 127.53, 127.83, 128.08, 128.34, 128.56 (two carbons), 128.56, 128.70,
128.81, 129.39 (two carbons). Anal. Calcd for C19H22OS2: C 69.05; H 6.71. Found: C 69.22;
H 6.54.

JOURNAL OF SULFUR CHEMISTRY
9
4.3. General procedure for the synthesis of α-sulfanyl enals 3
Method A. Appropriate base (Table 2) (1.2 mmol) was added to a solution of α-haloenal
1 (1 mmol) and thiol (2.5 mmol) in 5 mL of absolute THF or Et2O. The reaction mix-
ture was stirred at rt for 24 h. The precipitate was filtered off, and then base (2.5 mmol)
and solution of iodine (1 mmol) in ether (3 mL) were sequentially added to the filtrate.
The reaction mixture was stirred at rt for 6 h. The precipitate was filtered off, the solvent
was evaporated in vacuum and the residue was purified by column chromatography (SiO2,
Et2O:hexane = 1:3).
Method B. DBU (1.2 mmol) was added to a solution of α-haloenal 1 (1 mmol) and thiol
(1.2 mmol) in 5 mL of CH2Cl2. The reaction mixture was stored at rt for 1 h. The solvent
was evaporated in vacuum and the residue was purified by column chromatography (SiO2,
Et2O:hexane = 1:3).
4.3.1. (Z)-3-phenyl-2-(propylsulfanyl)prop-2-enal 3a
1
Yellow oil, 174 mg (84%). H NMR (400 MHz, CDCl3): δ 0.89 (t, J = 7.3 Hz, 3, ),
3
1.46–1.55 (m, 2H, CH2), 2.89 (t, J = 7.3 Hz, 2H, SCH2), 7.38–7.45 (m, 3H, Ph), 7.55 (s, 1H,
=
=
CH C), 7.90–7.95 (m, 2H, Ph), 9.55 (s, 1H, CH O). The spectral data of this compound
match those published earlier.[17]
4.3.2. (E)-3-phenyl-2-(propylsulfanyl)prop-2-enal 3a
1
Yellow oil, 30 mg (from 5 mmol 1a) (3%). H NMR (400 MHz, CDCl3): δ 1.07 (t,
J = 7.3 Hz, 3, 3), 1.67–1.77 (m, 2H, CH2), 2.81 (t, J = 7.3 Hz, 2H, SCH2), 7.28–7.33 (m,
2H), 7.38–7.44 (m, 3H), 7.57 (s, 1H, CH C), 9.81 (s, 1H, CH O). 13C NMR (100.6 MHz,
=
=
CDCl3): δ 13.73 (CH3), 22.08 (CH2), 33.23 (SCH2), 128.77, 129.36, 129.95, 134.32, 139.34
=
=
=
(CH C), 142.44 (CH C), 189.13 (C O). MS (EI) m/z (relative intensity): m/z (%): 206
(62, M+), 188 (22), 173 (29), 163 (48), 135 (98), 131 (90), 115 (27), 102 (28), 91 (100).
4.3.3. (Z)-2-benzylsulfanyl-3-phenylpropenal 3b
Yellow oil, 204 mg (80%). 1H NMR (400 MHz, CDCl3): δ 4.21 (s, 2, 2), 7.10–7.30 (m, 5H,
=
Ph), 7.37–7.50 (m, 3H, Ph), 7.56 (s, 1, ), 7.78–7.93 (m, 2H, Ph), 9.54 (s, 1H, CH O). MS
(EI) m/z (relative intensity): m/z (%): 254 (14, M+), 236 (6), 221 (8), 135 (9), 134 (16), 91
(100). The spectral data of this compound match those published earlier.[17]
4.3.4. (Z)-3-phenyl-2-phenylsulfanylpropenal 3c
Yellow oil, 130 mg (54%). 1H NMR (400 MHz, CDCl3): δ 7.18–7.32 (m, 5H, SPh), 7.44–7.46
=
=
(m, 3H, Ph), 7.90 (s, 1H, CH C), 7.98–8.00 (m, 2H, Ph), 9.56 (s, 1H, CH O). MS (EI) m/z
(relative intensity): m/z (%): 240 (100, M+), 211 (34), 178 (39), 167 (16), 147 (22), 131 (71).
The spectral data of this compound match those published earlier.[17]
4.3.5. (Z)-2-(propylsulfanyl)hex-2-enal 3d
Yellow oil, 96 mg (56%). IR (film, cm−1): ν 2962, 2933, 2874, 1693 (C O), 1599 (C C),
=
=
1459. 1H NMR (400 MHz, CDCl3): δ 0.85–0.95 (2t, 6H, 2CH3), 1.38–1.55 (m, 4, 22), 2.52
=
(m, 2H, CH2), 2.71 (t, J = 7.2 Hz, 2H, SCH2), 6.93 (t, J = 7.4 Hz, 1H, CH C), 9.37 (s,
1H, CH O). 13C NMR (100.6 MHz, CDCl3): δ 13.18 (CH3), 13.93 (CH3), 21.77 (CH2),
=
=
=
=
23.38 (CH2), 32.77 (CH2), 34.11 (CH2), 138.34 (CH C), 160.55 (CH C), 191.26 (C O).

10
E. V. KONDRASHOV ET AL.
Anal. Calcd for C9H16OS: C 62.74; H 9.36. Found: C 62.58; H 9.42. MS (EI) m/z (relative
intensity): m/z (%): 172 (100, M+), 130 (31), 129 (37), 101 (51), 95 (46), 81 (30), 67 (53).
4.3.6. (Z)-2-(benzylsulfanyl)hex-2-enal 3e
Yellow oil, 110 mg (50%). 1H NMR (400 MHz, CDCl3): δ 0.81 (t, J = 7.3 Hz, 3H, CH3),
1.23–1.35 (m, 2, 2), 2.29–2.39 (m, 2H, CH2), 3.97 (s, 2H, SCH2), 6.91 (t, J = 7.3 Hz, 1H,
=
=
CH C), 7.13–7.28 (m, 5H, Ph), 9.37 (s, 1H, CH O). MS (EI) m/z (relative intensity): m/z
(%): 220 (15, M+), 187 (4), 129 (4), 91 (100), 65 (10). The spectral data of this compound
match those published earlier.[17]
4.3.7. (Z)-2-phenylsulfanylhex-2-enal 3f
1
Yellow oil, 130 mg (32%). IR (film, cm−1): ν 1697 (C O), 1583, 1601 (C C, Ph). H
=
=
NMR (400 MHz, CDCl3): δ 1.00 (t, J = 7.3 Hz, 3, 3), 1.50–1.65 (m, 2H, CH2), 2.55–2.60
(m, 2H, CH2), 7.12–7.30 (m, 5H, Ph), 7.27 (s, 1, C), 9.49 (s, 1H, CH O). 13C NMR
=
=
(100.6 MHz, CDCl3): δ 14.03 (CH3), 21.79, 32.91, 126.51, 128.94, 129.13, 134.54, 136.87
=
=
=
(CH C), 160.87 (CH C), 190.31 (C O). Anal. Calcd for C12H14OS: C 69.86; H 6.84.
Found: C 69.50; H 6.67. MS (EI) m/z (relative intensity): m/z (%): 206 (100, M+), 135 (64),
110 (55), 99 (27), 91 (23), 65 (22).
4.3.8. 3-Methyl-2-(propylsulfanyl)but-2-enal 3g
Yellow oil, 134 mg (85%). IR (film, cm−1): ν 2963, 2931, 2872, 1675 (C O), 1587 (C C),
=
=
1
1455. H NMR (400 MHz, CDCl3): δ 0.89 (t, J = 7.3 Hz, 3H, CH3), 1.40–1.46 (m, 2H,
=
CH2), 2.23 (s, 3, ), 2.25 (s, 3, ), 2.56 (t, J = 7.3 Hz, 2H, SCH2), 9.98 (s, 1H, CH O).
3
3
13
=
C NMR (100.6 MHz, CDCl3): δ 13.37 (CH3), 21.30, 23.16, 26.43, 35.59, 131.32 (CH C),
=
=
163.65 (CH C), 188.52 (C O). Anal. Calcd for C8H14OS: C 60.71; H 8.92. Found: C 60.89;
H 8.95. MS (EI) m/z (relative intensity): m/z (%): 158 (100, M+), 159 (44), 129 (9), 125 (11),
116 (63), 98 (25), 87 (48), 82 (62), 67 (26).
4.3.9. 3-Methyl-2-(benzylsulfanyl)but-2-enal 3h
Yellow oil, 134 mg (65%). IR (film, cm−1): ν 3029, 2928, 2861, 1674 (C O), 1585, 1495,
=
1
=
1454 (C C, Ph). H NMR (400 MHz, CDCl3): δ 1.95 (s, 3, 3), 2.19 (s, 3, 3), 3.83 (s, 2H,
SCH2), 7.12–2.28 (m, 5H, Ph), 9.98 (s, 1H, CH O). 13C NMR (100.6 MHz, CDCl3): δ
21.21 (CH3), 26.24 (CH3), 38.02 (SCH2), 127.01, 128.36, 129.08, 130.27 (CH C), 138.28,
=
=
=
=
165.93 (CH C), 188.31 (C O). Anal. Calcd for C12H14OS: C 69.86; H 6.84. Found: C
69.95; H 5.65. MS (EI) m/z (relative intensity): m/z (%): 206 (15, M+), 188 (3), 173 (2), 163
(6), 91 (100), 65 (10).
4.3.10. 3-Methyl-2-phenylsulfanylbut-2-enal 3i
1
Yellow oil, 83 mg (22%). IR (film, cm−1): ν 1679 (C O), 1586, 1478 (C C, Ph). H NMR
=
=
=
(400 MHz, CDCl3): δ 2.28 (s, 3, 3), 2.40 (s, 3, 3), 7.08–7.25 (m, 5H, Ph), 9.91 (s, 1H, CH O).
13C NMR (100.6 MHz, CDCl3): δ 22.08 (CH3), 26.53 (CH3), 125.94, 127.75, 129.13, 129.49,
=
=
=
136.25 (CH C), 164.97 (CH C), 189.00 (C O). Anal. Calcd for C11H12OS: C 68.71; H
6.29. Found: C 68.55; H 6.17. MS (EI) m/z (relative intensity): m/z (%): 192 (100, M+), 159
(44), 148 (36), 129 (51), 110 (41), 91 (28), 83 (40).

JOURNAL OF SULFUR CHEMISTRY
11
4.3.11. 3,4-Bis(propylsulfanyl)butan-2-one 5a
Triethylamine (1.2 mmol) was added to a solution of α-bromoenone 4 (1 mmol) and
propanethiol (2.5 mmol) in 5 mL of absolute Et2O. The reaction mixture was stirred at
rt for 24 h. The precipitate was filtered off, and the solvent was evaporated in vacuum. No
additional purification is required.
1
Colorless oil, 220 mg (100%). H NMR (400 MHz, CDCl3): δ 0.89–0.99 (m, 6, 23),
1.48–1.63 (m, 4, 22), 2.29 (s, 3H, C(O)CH3), 2.35–2.46 (m, 2H, CH2), 2.47–2.53 (m, 2H,
CH2), 2.76 (dd, 2J = 13.4 Hz, 3J = 5.2 Hz, 1H, CH), 2.93 (dd, 2J = 13.4 Hz, 3J = 10.3 Hz,
1H, CH), 3.41 (dd, 3J = 10.3 Hz, 3J = 5.2 Hz, 1H, SCH). 13C NMR (100.6 MHz, CDCl3):
=
δ 13.44 (CH3), 13.48 (CH3), 22.83 (CH2), 23.03 (CH2), 26.97 (CH3C O), 32.17 (CH2),
32.34 (CH2), 34.90 (CH2), 53.06 (CH), 203.20 (C O). Anal. Calcd for C10H20OS2: C 54.50;
H 9.15. Found: C 54.32; H 9.17.
=
4.3.12. 3,4-Bis(benzylsulfanyl)butan-2-one 5b
A solution of triethylamine (1.41 mmol) and benzylthiol (2.22 mmol) in THF (1.5 mL) was
added to a solution of α-bromoenone 4 (1 mmol) in THF (1.5 mL). The reaction mixture
was stirred at rt for 20 h. The precipitate was filtered off, and the solvent was evaporated in
vacuum. The product was purified with column chromatography (SiO2, CHCl3).
1
Pale yellow oil, 208 mg (66%). IR (cm−1): ν 2963, 2931, 1708. H NMR (400 MHz,
CDCl3): δ 2.16 (s, 3, 3), 2.59 (dd, 2J = 13.3 Hz, 3J = 5.2 Hz, 1H, CH), 2.84 (dd,
2J = 13.3 Hz, 3J = 10.4 Hz, 1H, CH), 3.26 (dd, 3J = 10.4 Hz, 3J = 5.2 Hz, 1H, SCH), 3.61
(dd, J = 25.9 Hz, J = 13.1 Hz, 2H, PhCH2), 3.63 (s, 2H, PhCH2), 7.18–7.36 (m, 10H, Ph).
13C NMR (100.6 MHz, CDCl3): δ 26.94 (CH3), 31.30 (CH2), 35.23 (CH2), 36.75 (CH2),
52.32 (CH), 127.27, 127.48, 128.69 (two carbons), 128.94, 129.24, 137.27, 138.08 (Ph),
=
203.11 (C O).
4.3.13. 4-Phenyl-3,4-bis(propylsulfanyl)butan-2-one 8a
DABCO (1.5 mmol) was added to a solution of α-bromoenone 7 (1 mmol) and
propanethiol (3 mmol) in 5 mL of absolute Et2O. The reaction mixture was stirred at rt
for 48 h. The precipitate was filtered off, and the solvent was evaporated in vacuum. The
residue was purified by column chromatography (SiO2, Et2O:hexane = 1:3, Rf∼0.9).
Yellow oil, 148 mg (50%), (1:2) mixture of diastereomers. IR (cm−1): ν 2963, 2931, 1705,
1454, 1353. 1H NMR (400 MHz, CDCl3): major: 0.77–1.04 (m, 6H, 2CH3), 1.32–1.68 (m,
=
4H, 2 CH2), 2.11–2.78 (m, 4H, 2SCH2), 2.43 (s, 3 H, CH3C O), 3.59 (d, J = 11.9 Hz,
1H, CH), 4.01 (d, J = 11.9 Hz, 1, CH), 7.20–7.40 (m, 5H, Ph); minor: 0.77–1.04 (m, 6H,
=
2CH3), 1.32–1.68 (m, 4H, 2 CH2), 2.07 (s, 3H, CH3C O), 2.11–2.78 (m, 4H, 2SCH2),
3.72 (d, J = 11.3 Hz, 1H, CH), 4.26 (d, J = 11.3 Hz, 1H, CH), 7.20–7.40 (m, 5H, Ph). 13
C
NMR (100.6 MHz, CDCl3): major: δ 13.35, 13.51, 22.29, 22.58, 26.92, 32.91, 34.27, 49.13,
58.55, 127.74, 128.51, 128.51, 139.95, 202.23; minor: δ 13.63, 13.72, 22.39, 22.58, 27.68,
32.37, 33.14, 48.98, 58.85, 127.79, 128.46, 128.79, 140.43, 201.53. MS (EI) m/z (relative
intensity): m/z (%): 296 (1.3, M+), 220 (2), 179 (5), 165 (100), 135 (15), 123 (24), 103 (5),
91 (9), 43 (29).
4.3.14. 3,4-Bis(benzylsulfanyl)-4-phenylbutan-2-one 8b
Yellow oil, 177 mg (45%), (1:2) mixture of two diastereomers. 1H NMR (400 MHz, CDCl3):
major: δ 2.16 (s, 3, ), 3.25–3.64 (m, 5), 3.88 (d, J = 12.2 Hz, 1, ), 7.00–7.40 (m, 15H,
3

12
E. V. KONDRASHOV ET AL.
3Ph); minor: δ 1.93 (s, 3, ), 3.25–3.78 (m, 5), 4.21 (d, J = 11.2 Hz, 1, ), 7.00–7.40
3
(m, 15H, 3Ph).
4.4. General procedure for the synthesis of α-sulfanyl enones 9 and enoates 14, 15
DBU (1.2 mmol) was added to a solution of α-bromoenone 7 or α-bromocinnamate 13
(1 mmol) and thiol (1.2 mmol) in 3 mL CH2Cl2. The reaction mixture was stored at rt
for 1 h. The solvent was evaporated in vacuum and the residue was purified by column
chromatography (SiO2, CHCl3).
4.4.1. 4-Phenyl-3-(propylsulfanyl)but-3-en-2-one 9a mixture of Z/E isomers 7:1
Pure isomers can be isolated separately. Yellow oil, 139 mg (63%). IR (cm−1): ν 3059, 2964,
1
=
=
2931, 2873, 1586, 1567, 1490, 1446 (C C, Ph), 1679 (C O). H NMR (400 MHz, CDCl3):
Z-isomer (major): δ 0.88 (t, J = 7.3 Hz, 3, 3), 1.45–1.55 (m, 2H, CH2), 2.53 (s, 3H, CH3),
=
2.64 (t, J = 7.3 Hz, 2H, SCH2), 7.32–7.42 (m, 3H, Ph), 7.62 (s, 1, C), 7.80–7.85 (m, 2H,
Ph); E-isomer (minor): δ 1.03 (t, J = 7.3 Hz, 3, 3), 1.63–1.72 (m, 2H, CH2), 2.26 (s, 3H,
CH3), 2.68 (t, J = 7.3 Hz, 2H, SCH2), 6.86 (s, 1H, C), 7.20–7.37 (m, 5H, Ph). 13C NMR
=
=
(100.6 MHz, CDCl3): Z-isomer (major): δ 13.35 (CH3), 23.30 (CH2), 27.61 (CH3C O),
=
=
36.10 (CH2), 128.39, 129.57, 130.96, 134.96, 136.55 (CH C), 141.50 (CH C), 198.58
=
=
(C O); E-isomer (minor): δ 13.31 (CH3), 23.29 (CH2), 29.90 (CH3C O), 36.11 (CH2),
=
=
=
128.12, 128.20, 128.52, 131.88 (CH C), 137.60 (CH C), 202.83 (C O). Anal. Calcd for
C13H16OS: C 70.87; H 7.32. Found: C 70.72; H 7.41. MS (EI) m/z (relative intensity): m/z
(%): 220 (58, M+), 187 (13), 177 (47), 143 (38), 135 (62), 131 (52), 91 (50), 43 (100).
4.4.2. (Z)-3-(benzylsulfanyl)-4-phenylbut-3-en-2-one 9b
Yellow oil, 134 mg (50%). IR (cm−1): ν 3061, 3029, 2925, 1707, 1675, 1494, 1454. 1H NMR
(400 MHz, CDCl3): δ 2.37 (s, 3H, CH3), 3.92 (s, 2H, CH2), 7.15–7.40 (m, 8H, 2Ph), 7.64 (s,
1H, CH C), 7.73–775 (m, 2H, Ph). 13C NMR (100.6 MHz, CDCl3): δ 27.40 (CH3), 38.25
=
=
(CH2), 127.32, 128.42, 128.56, 129.23, 129.76, 130.91, 134.83, 135.64, 137.63 (CH C),
=
=
143.18 (CH C), 198.15 (C O). Anal. Calcd for C17H16OS: C 76.08; H 6.01. Found: C
75.82; H 6.05. MS (EI) m/z (relative intensity): m/z (%): 268 (20, M+), 235 (10), 191 (4),
177 (5), 134 (6), 91 (100), 65 (9), 43 (27).
4.4.3. 4-Phenyl-3-phenylsulfanylbut-3-en-2-one 9c
Yellow oil, m = 91 mg (36%); mixture of Z/E isomers 1:2.2. IR (cm−1): ν 1567, 1573, 1584,
1
=
=
1602 (C C, Ph), 1681, 1689 (C O). H NMR (400 MHz, CDCl3): E-isomer (major): δ 2.17
=
(s, 3, 3), 7.09 (s, 1, ), 7.10–7.35(m, 8H, Ph), 7.37–7.45 (m, 2H, Ph); Z-isomer (minor): δ
2.35 (s, 3, 3), 7.20–7.32 (m, 6H, Ph), 7.37–7.45 (m, 2H, Ph), 7.87–7.90 (m, 2H, Ph), 7.96 (s,
1, C). 13C NMR (100.6 MHz, CDCl3): E-isomer (major): δ 30.43 (CH3), 127.90, 128.71,
=
=
=
128.84, 129.06, 129.38, 131.35, 134.98, 135.40, 136.41, 136.75 (CH C), 144.38 (CH C),
201.64 (C O); Z-isomer (minor): δ 27.81 (CH3), 126.48, 127.86, 128.48, 129.48, 130.22,
130.98, 132.41, 134.32 (Ph), 132.85 (C ), 142.40 (C ), 199.14 (C O). Anal. Calcd for
C16H14OS: C 75.55; H 5.55. Found: C 75.22; H 5.41. MS (EI) m/z (relative intensity): m/z
(%): 254 (100, M+), 211 (78), 178 (67), 167 (24), 145 (20), 134 (18).
=
3
4
=

JOURNAL OF SULFUR CHEMISTRY
13
4.4.4. (Z)-4-phenyl-4-(propylsulfanyl)but-3-en-2-one 10
DABCO (1.5 mmol) was added to a solution of α-bromoenone 7 (1 mmol) and
propanethiol (3 mmol) in 5 mL of absolute Et2O. The reaction mixture was stirred at
rt for 48 h. The precipitate was filtered off, and the solvent was evaporated in vacuum.
The residue was purified by column chromatography (SiO2, Et2O:hexane = 1:3, Rf∼0.3)
affording Z-isomer which slowly isomerizes to E-isomer while standing at rt in solution of
CDCl3.
Yellow oil, 70 mg (32%). IR (cm−1): ν 2873, 2931, 2964, 3026, 3058, 1539, 1488, 1444
1
=
=
(C C, Ph), 1661 (C O). H NMR (400 MHz, CDCl3): Z-isomer: δ 0.80 (t, J = 7.4 Hz, 3,
3), 1.38–1.45 (m, 2H, CH2), 2.25 (s, 3H, CH3), 2.32 (t, J = 7.4 Hz, 2H, SCH2), 6.30 (s, 1,
=
C), 7.26–7.31 (m, 2H, Ph), 7.34–7.40 (m, 3H, Ph); E-isomer: δ 1.02 (t, J = 7.3 Hz, 3, 3),
=
1.64–1.74 (m, 2H, CH2), 1.76 (s, 3H, CH3), 2.74 (t, J = 7.3 Hz, 2H, SCH2), 6.05 (s, 1, C),
7.26–7.31 (m, 2H, Ph), 7.34–7.40 (m, 3H, Ph). 13C NMR (100.6 MHz, CDCl3): Z-isomer:
=
=
δ 13.47 (CH3), 23.06 (CH2), 30.87 (CH3C O), 34.92 (CH2), 123.81 (CH C), 128.20,
128.57, 128.61, 139.05, 160.62 (CH C), 196.11 (C O); E-isomer: δ 13.69 (CH3), 21.59
(CH3C O), 30.22 (CH2), 34.93 (CH2), 122.25 (CH C), 128.78, 128.85, 129.51, 137.89,
158.98 (CH C), 196.27 (C O). Anal. Calcd for C13H16OS: C 70.87; H 7.32. Found: C
70.68; H 7.25. MS (EI) m/z (relative intensity): m/z (%): 220 (23, M+), 205 (10), 177 (100),
121 (10), 103 (11), 91 (14), 43 (64).
=
=
=
=
=
=
4.4.5. 4-Propylsulfanyl-4-phenylbutan-2-one 11a
Colorless oil, 13 mg (6%). 1H NMR (400 MHz, CDCl3): δ 0.92 (t, J = 7.3 Hz, 3H, CH3),
1.46–1.60 (m, 2H, CH2), 2.11 (s, 3H, CH3), 2.23–2.37 (m, 2H, SCH2), 2.99 (d, J = 7.3 Hz,
2H, CH2), 4.33 (t, J = 7.3 Hz, 1H, CH), 7.25–7.38 (m, 5H, Ph). The spectral data of this
compound match those published earlier.[26]
4.4.6. 4-Benzylsulfanyl-4-phenylbutan-2-one 11b
Pale yellow oil, 125 mg (46%). 1H NMR (400 MHz, CDCl3): δ 2.03 (s, 3, 3), 2.89–3.02 (m, 2,
S2), 3.47 and 3.55 (2d, AB-system, 2J = 13.3 Hz, 2, S2), 4.23 (t, J = 7.2 Hz, 1, ), 7.20–7.36
(m, 10H, Ph). The spectral data of this compound match those published earlier.[26]
4.4.7. Methyl 3-phenyl-2-(propylsulfanyl)prop-2-enoate 14a
Pure Z,E-isomers can be isolated separately. Colorless oil, 132 mg (56%); (1:2) mixture of
Z,E-isomers. IR (cm−1): ν 2963, 2873, 1725, 1433, 1214. 1H NMR (400 MHz, CDCl3): E-
isomer (major): δ 1.06 (t, J = 7.3 Hz, 3, 3), 1.66–1.76 (m, 2H, CH2), 2.75 (t, J = 7.2 Hz,
=
2H, SCH2), 3.76 (s, 3H, OCH3), 6.97 (s, 1, ), 7.25–7.36(m, 5H, Ph); Z-isomer (minor):
0.93 (t, J = 7.3 Hz, 3, ), 1.54–1.60 (m, 2H, CH2), 2.78 (t, J = 7.2 Hz, 2H, SCH2), 3.90
3
=
(s, 3H, OCH3), 6.97 (s, 1, ), 7.35–7.45 (m, 3H, Ph), 7.84–7.86 (m, 3H, Ph), 7.90 (s, 1,
). 13C NMR (100.6 MHz, CDCl3): E-isomer (major): δ 13.41, 22.64, 35.15, 52.44, 128.07,
=
128.41, 128.57, 128.68, 134.96, 135.54, 167.86; Z-isomer (minor): δ 13.42, 23.25, 36.36,
52.86, 127.28, 128.36, 129.54, 131.05, 135.04, 143.44, 167.07. Anal. Calcd for C13H16O2S:
C 66.07; H 6.82. Found: C 66.15; H 6.65. MS (EI) m/z (relative intensity): m/z (%): 236 (85,
M+), 161 (12), 143 (13), 134 (100), 121 (58), 91 (16).

14
E. V. KONDRASHOV ET AL.
4.4.8. Methyl 3-phenyl-2-(benzylsulfanyl)prop-2-enoate 14b
Pure isomers can be isolated separately. Colorless oil, 63 mg (22%); (2:1) mixture of Z,E-
isomers. IR (cm−1): ν 3028, 2949, 1715, 1591, 1446, 1207. 1H NMR (400 MHz, CDCl3): Z-
isomer (major): 3.84 (s, 3H, OCH3), 4.00 (s, 2H, CH2), 7.17–7.35 (m, 8H, 2Ph), 7.64–7.67
=
(m, 2H, Ph), 7.86 (s, 1, ); E-isomer (minor): δ 3.71 (s, 3H, OCH3), 3.99 (s, 2H, CH2), 6.87
(s, 1, ), 7.15–7.35 (m, 10H, 2Ph); 13C NMR (100.6 MHz, CDCl3): Z-isomer (major): δ
=
38.78, 52.72, 126.53, 127.27, 128.23, 128.50, 129.13, 129.53, 130.85, 134.85, 137.52, 144.75,
166.76; E-isomer (minor): δ 38.45, 52.44, 127.41, 127.46, 128.20, 128.55, 128.67 (two car-
bons), 129.26, 135.38, 137.12, 137.99, 167.81. Anal. Calcd for C17H16O2S: C 71.80; H 5.67.
Found: C 71.52; H 5.58. MS (EI) m/z (relative intensity): m/z (%): 284 (21, M+), 192 (20),
161 (9), 149 (11), 134 (21), 91 (100).
4.4.9. Methyl (Z)-3-phenyl-2-(phenylsulfanyl)prop-2-enoate 14c
1
Yellow oil, 423 mg (78%). IR (film, cm−1): ν 1722 (C O), 1595, 1478 (C C, Ph). H NMR
=
=
(400 MHz, CDCl3): δ 3.65 (s, 3, O3), 7.05–7.40 (m, 8H, Ph), 7.75–7.84 (m, 2H, Ph), 8.10 (s,
13
=
=
1, H C). C NMR (100.6 MHz, CDCl3): δ 52.91 (OCH3), 125.38 ( C–S), 126.53, 128.52
=
=
(two carbons), 129.18, 130.18, 130.98, 134.46, 135.65 (Ph), 146.17 (CH ), 166.89 (C O).
Anal. Calcd for C16H14O2S: C 71.08; H 5.22. Found: C 71.21; H 5.23. MS (EI) m/z (relative
intensity): m/z (%): 270 (100, M+), 211 (73), 210 (25), 178 (31), 167 (22), 134 (14), 121
(90), 110 (15).
4.4.10. Methyl 3-phenyl-3-(propylsulfanyl)prop-2-enoate 15a
1
Mixture of Z,E-isomers 3:1 H NMR (400 MHz, CDCl3): Z-isomer (major): δ 0.83 (t,
J = 7.3 Hz, 3, ), 1.42–1.48 (m, 2H, CH2), 2.38 (t, J = 7.2 Hz, 2H, SCH2), 3.77 (s, 3H,
3
=
OCH3), 5.94 (s, 1, ), 7.25–7.40 (m, 5H, Ph); E-isomer (minor) 3.55 (s, 3H, OCH3),
5.78 (s, 1, ), 7.35–7.45 (m, 3H, Ph), 7.84–7.86 (m, 3H, Ph). 13C NMR (100.6 MHz,
=
CDCl3): Z-isomer (major): δ 13.42 (CH3), 23.13 (CH2), 34.79 (SCH2), 51.20 (OCH3),
115.63 (CH C), 128.12, 128.50, 128.89, 138.92, 161.11 (C O), 166.32 (CH C); E-isomer
(minor): δ 13.40 (CH3), 21.52 (CH2), 34.67 (SCH2), 52.40 (OCH3), 110.11 (CH C),
128.03, 128.29, 131.01, 133.30, 160.70 (C O), 164.89 (CH C). MS (EI) m/z (relative
intensity): m/z (%): 236 (25, M+), 205 (25), 194 (100), 162 (35), 134 (48), 121 (58), 102
(17), 91 (19).
=
=
=
=
=
=
4.4.11. Methyl 3-phenyl-3-(benzylsulfanyl)prop-2-enoate 15b
White solid, 114 mg (40%); (1:2.7) mixture of Z,E-isomers. IR (cm−1): ν 3029, 2951, 1720,
1698, 1574, 1332, 1193, 1172. 1H NMR (400 MHz, CDCl3): Z-isomer (major): δ 3.63 (s, 2H,
=
CH2), 3.74 (s, 3H, OCH3), 5.91 (s, 1, ), 6.98–7.01 (m, 2H, Ph), 7.16–7.38 (m, 8H, Ph);
E-isomer (minor): 3.53 (s, 3H, OCH3), 3.99 (s, 2H, CH2), 5.86 (s, 1, ), 7.16–7.38 (m, 10H,
=
2Ph). 13C NMR (100.6 MHz, CDCl3): Z-isomer (major): δ 37.55 (SCH2), 51.40 (OCH3),
115.97 (CH C), 160.28 (C O), 166.26 (CH C); E-isomer (minor): δ 37.75 (SCH2), 51.15
(OCH3), 111.10 (CH C), 159.99 (C O), 164.86 (CH C); aromatic carbons for both iso-
mers: 127.26, 127.80, 128.13, 128.31, 128.49, 128.51, 128.67, 128.90, 129.07 (three carbons),
129.15, 135.34, 137.04, 137.07, 138.75. Anal. Calcd for C17H16O2S: C 71.80; H 5.67. Found:
C 71.64; H 5.70. MS (EI) m/z (relative intensity): m/z (%): 284 (23, M+), 253 (8), 210 (12),
193 (72), 165 (12), 134 (12), 121 (19), 91 (100).
=
=
=
=
=
=

JOURNAL OF SULFUR CHEMISTRY
15
Acknowledgements
Spectroscopic and analytical data were obtained using instrumentation in the Baykal Analytical
Center for Collective Use SB RAS.
Disclosure statement
No potential conflict of interest was reported by the authors.
References
[1] Feng J, Lu G, Lv M, Cai C. Palladium-catalyzed odorless one-pot synthesis of vinyl sulfides
from organohalides, thiourea, and alkynes. Asian J Org Chem. 2014;3:77–81.
[2] Leonardão EJ, Silva MS, Lara RG, et al. Synthesis of vinyl sulfides using glycerol as a recyclable
solvent. Arkivoc. 2011;ii:272–282; and references therein.
[3] Kumar A, Tripathi VD, Kumar P, et al. Design and synthesis of 1,3-biarylsulfanyl derivatives as
new anti-breast cancer agents. Bioorg Med Chem. 2011;19:5409–5419.
[4] Rulev AY. Haloalkenes activated by geminal groups in reactions with N-nucleophiles. Usp
Khim. 1998;67:317–332; 279–293.
[5] Rulev AY. Captodative aminoalkenes. Usp Khim. 2002;71:225–254; Russ. Chem. Rev. Captoda-
tive aminoalkenes. 2002;71: 225–254; 195–221.
[6] Rulev AY, Muzalevskiy VM, Kondrashov EV, et al. Reaction of a-bromoenones with
1,2-diamines. Cascade assembly of 3-CF3-piperazine-2-ones via rearrangement. Org Lett.
2013;15:2726–2729.
[7] Rulev AY, Ushakov IA, Nenajdenko VG. One-pot synthesis of functionalized indenols from
2-bromoalkenyl trifluoromethyl ketones. Tetrahedron. 2008;64:8073–8077.
[8] Rulev AY, Ushakov IA, Nenajdenko VG, Balenkova ES, Voronkov MG. Domino transforma-
tions of gem-trifluoroacetyl(bromo)alkenes under the action of secondary amines. Eur J Org
Chem. 2007:6039–6045.
[9] Rulev AY, Maddaluno J. Thermal and hyperbaric addition of N,N- and N,O- binucleophiles on
cycloalkylidenic bromo esters. J Phys Org Chem. 2002;15:590–598.
[10] Rulev AY, Maddaluno J. Spiroaziridination of cycloalkylidene esters under high pressure. Eur
J Org Chem. 2001;2001:2569–2576.
[11] Rosnati V, Saba A, Salimbeni A. The reactions of phenolic reagents with α-bromo Michael
acceptors in the K2CO3-acetone system. A stereospecific AdSNE process. Tetrahedron Lett.
1981;22:167–168.
[12] Rosnati V, Saba A, Salimbeni A, Vettori U. The AdNSNE mechanism in the reaction of phenol
and benzenethiol with α-bromo Michael acceptors in the K2CO3-acetone system. Gazz Chim
Ital. 1981;111:249–256.
[13] Boucher J-L, Stella L. Dienophilie des olefines captodatives – VI1 syntheses et cycloadditions
de diels-alder des α-alkylthio-acrylates d’alkyle avec le cyclopentadine: influence des facteurs
steriquis sur la reactivite et sur la stereoselectivite. Tetrahedron. 1988;44:3595–3605.
[14] Xu X, Li X, Wang A, Sun Y, Schweizer WB, Prins R. Synthesis of 4,6-dimethyldibenzothiophene
and 1,2,3,4-tetrahydro-4,6-dimethyldibenzothiophene via tilak annulation. Helv Chim Acta.
2011;94:1754–1763.
[15] Keiko NA, Stepanova LG, Kalikhman ID, Voronkov MG. α-Organylthiocrotonaldehydes. Russ
Chem Bull. 1986;35:1524–1526.
[16] Fekry MI, Price NE, Zang H, et al. Thiol-activated DNA damage by α-bromo-2-
cyclopentenone. Chem Res Toxicol. 2011;24:217–228.
[17] He L, Guo H, Li Y-Z, Du G-F, Dai B. N-Heterocyclic carbene-catalyzed formal cross-coupling
reaction of α-haloenals with thiols: organocatalytic construction of sp2 carbon–sulfur bonds.
Chem Commun. 2014;50:3719–3721.
[18] Mareev AV, Ushakov IA, Rulev AY. Nucleophilic substitution of α-haloenones with phenols.
Tetrahedron. 2015;71:1971–1974.

16
E. V. KONDRASHOV ET AL.
[19] Rulev AY, Larina LI, Keiko NA, Voronkov MG. New convenient access to thioesters
of α-amino acids from N,N-disubstituted 2-aminoalk-2-enals. J Chem Soc Perkin Trans.
1999;1:1567–1570.
[20] Rulev AY, Mokov AS, Krivdin LB, Keiko NA, Voronkov MG. N,N-disubstituted α-amino-
1
α,β-unsaturated aldehydes and their derivatives: H and 13C NMR study. Magn Res Chem.
1997;35:533–537.
[21] Sazonov PK, Artamkina GA, Beletskaya IP. Nucleophilic substitution at the halogen atom
(halogenophilic reactions). Russ Chem Rev. 2012;81:317–335.
[22] Zefirov NS, Makhonkov DI. X-philic reactions. Chem Rev. 1982;82:615–624.
[23] Seshadri R, Pegg WJ, Israel M. Reaction of halomethyl ketones with thiols and selenols:
substitution vs. reduction. J Org Chem. 1981;46:2596–2598.
[24] Zimmerman HE, Linder LW. Enhanced endo-exo selectivity in the stereochemistry of
ketonization of enols. Part 201. J Org Chem. 1985;50:1637–1646.
[25] Öki M, Funakoshi W, Nakamura A. The reaction of α-carbonyl sulfides with bases. I. The
reaction between α-carbonyl sulfides with thiolates. Bull Chem Soc Jpn. 1971;44:828–832.
[26] Chu C-M, Huang W-J, Lu C, Wu P, Liu J-T, Yao C-F. The iron(III) chloride-mediated 1,4-
addition of mercaptans to α,β-unsaturated ketones and esters under solvent free conditions.
Tetrahedron Lett. 2006;47:7375–7380.