Convenient and Efficient Diastereoselective Preparation of Functionalized Z-Alkenyl Sulfides

Article abstract of DOI:10.1002/ejoc.201801181

We have developed an efficient and convenient regio- and stereoselective reduction of the alkynyl sulfides with pinacolborane in the presence of copper(I) chloride to produce (Z)-alkenyl sulfides in good and very good yields. The functionalized alkynyl sulfides are readily available based on the reaction of lithium acetylides with thiotosylates under mild conditions.

Full text of DOI:10.1002/ejoc.201801181

A Journal of
Accepted Article
Title: Convenient and efficient diastereoselective preparation of
functionalized Z-alkenyl sulfides
Authors: Justyna Doroszuk, Mateusz Musiejuk, Łukasz Ponikiewski,
and Dariusz Witt
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201801181
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10.1002/ejoc.201801181
European Journal of Organic Chemistry
FULL PAPER
Convenient and efficient diastereoselective preparation of
functionalized Z-alkenyl sulfides
Justyna Doroszuk,a Mateusz Musiejuk,a Łukasz Ponikiewskib and Dariusz Witta*
Abstract: We have developed an efficient and convenient regio- and
stereoselective reduction of the alkynyl sulfides with pinacolborane in
the presence of copper (I) chloride to produce (Z)-alkenyl sulfides in
good and very good yields. The functionalized alkynyl sulfides are
readily available based on the reaction of lithium acetylides with
thiotosylates under mild conditions.
Other practical procedures involve the reaction of a lithium
acetylide and an activated thiol or disulfide.[10]
Introduction
The continuously increasing range of applications for
organosulfur compounds has expanded into different fields, from
organic synthesis to material science.[1] Among S-containing
building blocks, one unique functional group is alkynyl sulfides,
which contain two carbon atoms connected by a triple bond that
are directly substituted with a sulfur atom. The reactivity of this
functionality can be useful in organic synthesis. Alkynes have
been applied in bulk chemical syntheses based on acetylene
gas,[2] in the stereoselective construction of the carbon backbones
of natural products[3] and in the metal complex-catalyzed
cyclization reactions.[4] In short, alkynyl sulfides can bring together
the advantages of sulfur atoms with the exceptionally rich
chemistry of alkynes.
Scheme 1. Previously reported methods for the synthesis of alkynyl sulfides (A-
Reported methods for the preparation of alkynyl sulfides include
reactions based on transition-metal catalysts, such as the copper-
catalyzed carbon sulfur coupling between terminal alkynes and
disulfides[5] or the use of catalytic rhodium for C-S bond formation
by C-H and S-S bond metathesis[6] (Scheme 1). Both alkyne and
thiol groups are inherently nucleophilic, thus the umpolung of one
of them is necessary for the construction of an alkynyl sulfide. This
often requires the use of unselective reagents and harsh reaction
conditions, which are not always compatible with sensitive
functional groups.[7] Recently, Waser and co-workers developed
a thiol-alkynylation procedure that uses hypervalent iodine
(ethynylbenziodoxolone, EBX) as the alkyne transfer reagent.[8]
This method is highly chemoselective, and a wide range of
functional groups are tolerated under the developed conditions.
However, the problems associated with the preparation of the
hypervalent iodine alkyne transfer reagents are the major
disadvantage of the designed transformation. There are also
scattered examples in the literature of alkynyl sulfides preparation
C) and our newly developed approach (D).
Results and Discussion
Previously, we demonstrated the synthesis of functionalized
alkynyl sulfides based on the reaction of lithium acetylides with
5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphorinan-2-disulfanyl
derivatives.[11] These disulfanyl derivatives of phosphorodithioic
acid are also convenient substrates for the preparation of α-
sulfenylated
carbonyl
compounds,[12]
functionalized
phosphorothioates[13] as well as symmetrical and unsymmetrical
trisulfanes.[14] The above transformations are based on the
electrophilicity of the disulfanyl derivatives, so we extended that
approach to the reaction of electrophilic thiotosylate derivatives
with lithium acetylides to obtain functionalized alkynyl sulfides
under mild conditions.
based on the reaction of thiotosylates with lithium acetylides[9, 10b]
.
Herein, we have developed a one-pot synthesis of alkynyl sulfides
from various lithium acetylides 1 and thiotosylates 2 (Table 1).
The lithium acetylides were generated from the corresponding
terminal alkynes and n-BuLi in the presence of N,N,N’,N’-
tetramethylethylenediamine (TMEDA) in THF. The additional
equivalent of n-BuLi was added in the case of terminal alkyne 1
and/or thiotosylate 2 possessing acidic functional group (1c, 1g
and/or 2c, 2d). TMEDA was used to prevent the aggregation of
lithium acetylides.
[a] Department of Organic Chemistry, Faculty of Chemistry, Gdansk
University of Technology, Narutowicza 11/12, 80-233 Gdansk, Poland.
Tel: +48 58 3471851; Fax: +48 58 3472694; e-mail:
dariusz.witt@pg.edu.pl
[b] Department of Inorganic Chemistry, Faculty of Chemistry, Gdansk
University of Technology, Narutowicza 11/12, 80-233 Gdansk, Poland.
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under
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10.1002/ejoc.201801181
European Journal of Organic Chemistry
FULL PAPER
(CH3)2CHCH2CH2-1d
(CH3)2CHCH2CH2-1d
(CH3)2CHCH2CH2-1d
EtO2C-1e
4-CH3-C6H4-2f
82 3df
71 3dg
74 3dh
82 3ea
71 3eb
79 3ec
76 3ed
89 3ee
73 3ef
72 3eg
81 3eh
81 3fa
72 3fb
69 3fc
74 3fd
80 3fe
80 3ff
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
4-CN-C6H4-CH2-2g
4-NO2-C6H4-CH2-2h
CH3(CH2)11-2a
Table 1. Reaction of lithium acetylides 1 with thiotosylates 2[a]
EtO2C-1e
CH2=CH(CH2)9-2b
HO2C(CH2)10-2c
HO(CH2)11-2d
EtO2C-1e
EtO2C-1e
Yield
(%)[b]
Entry
R1
R2
EtO2C-1e
C6H5CH2-2e
CH3(CH2)11-2a
CH2=CH(CH2)9-2b
HO2C(CH2)10-2c
HO(CH2)11-2d
90 3aa
87 3ab
89 3ac
75 3ad
83 3ae
77 3af
81 3ag
84 3ah
70 3ba
88 3bb
32 3bc
62 3bd
67 3be
74 3bf
73 3bg
68 3bh
80 3ca
30 3cb
60 3cc
61 3cd
85 3ce
83 3cf
65 3cg
61 3da
56 3db
90 3aa
72 3dc
77 3dd
EtO2C-1e
4-CH3-C6H4-2f
1
C6H5-1a
C6H5-1a
C6H5-1a
C6H5-1a
C6H5-1a
EtO2C-1e
4-CN-C6H4-CH2-2g
4-NO2-C6H4-CH2-2h
CH3(CH2)11-2a
2
EtO2C-1e
3
4-CH3O-2-CH3-C6H3-1f
4-CH3O-2-CH3-C6H3-1f
4-CH3O-2-CH3-C6H3-1f
4-CH3O-2-CH3-C6H3-1f
4-CH3O-2-CH3-C6H3-1f
4-CH3O-2-CH3-C6H3-1f
4-CH3O-2-CH3-C6H3-1f
4-CH3O-2-CH3-C6H3-1f
3-HO2C-C6H4-1g
3-HO2C-C6H4-1g
3-HO2C-C6H4-1g
3-HO2C-C6H4-1g
3-HO2C-C6H4-1g
3-HO2C-C6H4-1g
4
C6H5CH2-2e
CH2=CH(CH2)9-2b
HO2C(CH2)10-2c
HO(CH2)11-2d
5
4-CH3-C6H4-2f
6
C6H5-1a
C6H5-1a
4-CN-C6H4-CH2-2g
4-NO2-C6H4-CH2-2h
CH3(CH2)11-2a
7
C6H5CH2-2e
8
C6H5-1a
C6H5CH2OCH2-1b
C6H5CH2OCH2-1b
C6H5CH2OCH2-1b
C6H5CH2OCH2-1b
C6H5CH2OCH2-1b
C6H5CH2OCH2-1b
C6H5CH2OCH2-1b
C6H5CH2OCH2-1b
BocNHCH2-1c
4-CH3-C6H4-2f
9
CH2=CH(CH2)9-2b
HO2C(CH2)10-2c
HO(CH2)11-2d
4-CN-C6H4-CH2-2g
4-NO2-C6H4-CH2-2h
CH3(CH2)11-2a
84 3fg
82 3fh
68 3ga
56 3gb
59 3gc
54 3gd
62 3ge
68 3gf
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
C6H5CH2-2e
CH2=CH(CH2)9-2b
HO2C(CH2)10-2c
HO(CH2)11-2d
4-CH3-C6H4-2f
4-CN-C6H4-CH2-2g
4-NO2-C6H4-CH2-2h
CH3(CH2)11-2a
C6H5CH2-2e
4-CH3-C6H4-2f
[a] Conditions: lithium acetylide 1 (1.0 mmol), TMEDA (1.0 mmol), thiotosylates
2 (1.0 mmol), dry THF (10 mL), rt, 15 min, under N2.
[b] Isolated yield
BocNHCH2-1c
CH2=CH(CH2)9-2b
HO2C(CH2)10-2c
HO(CH2)11-2d
BocNHCH2-1c
BocNHCH2-1c
The developed method is quite versatile. The presence of
additional functional groups, including carbon-carbon double
bonds as well as carboxyl, hydroxy, cyano, nitro, amino and ester
groups, were well tolerated in the formation of corresponding
alkynyl sulfides 3. Moreover, both starting materials 1 and 2 are
readily available and the reaction can be carried out on a larger
scale (30-50 mmol) to provide alkynyl sulfides 3 (entries 1, 10, 24,
36, 45, 49) in similar (± 5%) yield reported in Table 1.
BocNHCH2-1c
C6H5CH2-2e
BocNHCH2-1c
4-CH3-C6H4-2f
BocNHCH2-1c
4-CN-C6H4-CH2-2g
CH3(CH2)11-2a
(CH3)2CHCH2CH2-1d
(CH3)2CHCH2CH2-1d
(CH3)2CHCH2CH2-1d
(CH3)2CHCH2CH2-1d
(CH3)2CHCH2CH2-1d
CH2=CH(CH2)9-2b
CH3(CH2)11-2a
HO2C(CH2)10-2c
HO(CH2)11-2d
(CH3)2CHCH2CH2-1d
C6H5CH2-2e
84 3de
29
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10.1002/ejoc.201801181
European Journal of Organic Chemistry
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Scheme 2. Proposed mechanism for the synthesis of alkynyl sulfide.
Proposed mechanism of these transformation is shown in
Scheme 2. Firstly, lithium acetylide is generated from terminal
alkyne and n-butyllithium. When substrates 1 or 2 with acidic
protons were used the additional equivalent of n-BuLi was added.
These lithium salts are stabilized by presence of N,N,N’,N’-
tetramethylethylenediamine (TMEDA). Subsequent nucleophilic
substitution on the electrophilic sulfur produced corresponding
alkynyl sulfide in good yield.
Scheme 3. (Z)-vinyl sulfide and disulfane.
Several methods have been developed for the stereoselective
synthesis of (E)-vinyl sulfides,[19] however, the (Z)-isomers are
more difficult to prepare. The simplest method for the preparation
of vinyl sulfides is based on the addition reactions of thiols or
disulfides to acetylenic hydrocarbons. Unfortunately, the addition
of disulfides[20] to alkynes usually gave mixture of Z and E isomers
(1 and 2), while anti-Markovnikov addition of arylthiols[21] provides
a mixture of Z and E compounds (3 and 4) (Scheme 4).
Single crystals of 3gf suitable for X-ray diffraction were grown
from a saturated chloroform solution (CCDC 1560122). The unit
cell of compound 3gf was a monoclinic system in the space group
P21/c with four molecules in its elementary cell. The triple bond
length between C9 and C8 was 1.207 Å (Figure 1). This is similar
to the acetylene bond length (1.203 Å). The angle between C8-
S1-C1 was 102.56°.
Scheme 4. The addition reactions of thiols and disulfides to terminal alkynes.
A more convenient methodology is based on hydrothiolations of
alkynes using catalysts[22] or on transition-metal-catalyzed cross-
coupling reactions.[23] In 2005, Yorimitsu and Oshima reported the
synthesis of (Z)-1-alkenyl sulfides via
a cesium-catalyzed
hydrothiolation of alkynes in the presence of 2,2,6,6-
tetramethylpiperidine-N-oxyl (TEMPO).[24] However, this synthetic
strategy is only applicable to alkylthiols. Recently, Tang and Li
reported the synthesis of (Z)-1-alkenyl sulfides by a copper-
catalyzed hydrothiolation of alkynes with diaryl disulfides, but the
reaction requires a large amount of Rongalite (4 eq) as the radical
initiator[25] and is limited to diaryl disulfides. There are also a few
methods for the synthesis of alkenyl sulfides via the reduction of
alkynyl sulfides. In 2013, Zheng et al. reported the stereoselective
preparation of alkenyl sulfides via syn-hydrozirconation of alkynyl
sulfides by Schwartz reagent.[26] This reaction was used for simple
alkynyl sulfides that did not contain additional functional groups.
Recently, hydrosilylations of alkynyl sulfides by silane and
[Cp*Ru(MeCN)3]PF6 as the catalyst have also been reported.
After subsequent protodesilylation, (Z)-vinyl sulfides were
obtained.[27]
Figure 1. Crystal structure of compound 3gf.
Due to the growing interest in compounds containing (Z)-vinylthio
moieties we developed a simple, regio- and stereoselective
reduction of alkynyl sulfides to (Z)-alkenyl sulfides. Alkenyl
sulfides are of interest because they can be used as versatile
reagents in organic synthesis.[14] In addition to their interesting
reactivity, the alkenyl sulfide functionality is present in many
pharmaceutical compounds.[16] The vinyl sulfide moiety is present
in ajoene and its derivatives, which are potent antithrombotic
agents isolated from garlic (Alluimsatiuum).[17] Moreover, a (Z)-
vinylthio functional group is present in clavulanic acid, which
showed β-lactamase-inhibitory activity[18] (Scheme 3). In all cases,
the (Z)-isomers show better activity than the (E)-isomers.
In our initial study, we employed alkynyl sulfide 3aa as a model
starting material (Table 2). The most promising reagents and
catalysts were examined. Excellent syn-addition was observed in
the reaction with pinacolborane (HBpin) and CuCl as the catalyst
in dry THF (Table 2, entry 5).
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10.1002/ejoc.201801181
European Journal of Organic Chemistry
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Table 2. Conversion of alkynyl sulfide to alkenyl sulfide.
18
19
20
4-CH3O-2-CH3-C6H3-
3-HO2C-C6H4-
4-CN-C6H4-CH2-
79 4s
60 4t
76 4u
100:0
CH3(CH2)11
-
100:0
100:0
3-HO2C-C6H4-
C6H5CH2-
[a]
Conditions: 3 (1.0 mmol), CuCl (0.1 mmol), PPh3 (0.1 mmol), NaOtBu (0.2
mmol), HBpin (3.0 mmol), dry THF (20 mL), 0°C, 15 min under N2, then MeOH
(6.0 mmol) reflux 1 h. [b] Isolated yield. [c] E/Z ratio of the product was determined
by 1H NMR spectroscopy
Yield
(%)[a]
Entry
Catalyst /reagent
Method
Z/E[b]
Based on the experimental results, possible catalytic cycles for
the Cu-catalyzed hydroboration using HBpin are shown in
Scheme 5. PPh3 and CuCl reacted with NaOtBu to afford
[Ph3PCu(OtBu)]. Subsequent reaction of [Ph3PCu(OtBu)] with
HBpin produced the active catalytic species, appropriate copper
hydride [Ph3PCuH]. Syn addition to alkynes sulfide afforded
alkenyl copper species that reacted with HBpin to produce
corresponding hydroboration product and regenerated active
catalytic species [Ph3PCuH].
Schwartz reagent (1 eq.)
<5c)
37d)
13
-
1
2
3
4
5
A
B
C
D
E
Hoveyd-Grubbs Catalyst 1st
Generation / HCO2H
-
CuCl / catecholborane
CuCl / pinacolborane
CuCl / pinacolborane
80:20
90:10
100:0
30
94
Methods: A dichloromethane, rt; B C28H45Cl2OPRu (0.1 eq), NaH (0.2 eq),
HCO2H (50 eq), THF reflux overnight; C (i) HBcat (3 eq), CuCl (0.1 eq), PPh3
(0.1 eq), NaOtBu (0.1 eq), dry THF, (ii) MeOH (6 eq) reflux 1 h; D (i) HBpin (3
eq), CuCl (0.1 eq), PPh3 (0.1 eq), NaOtBu (0.1 eq), dry toluene, 15 min; (ii)
MeOH (6 eq) reflux 1 h; E (i) HBpin (3 eq), CuCl (0.1 eq), PPh3 (0.1 eq),
NaOtBu (0.1 eq), dry THF, 0 °C, 15 min; (ii) MeOH (6 eq) reflux 1 h.
[a]
[b]
Isolated yield.
E/Z ratios of the products were determined by 1H NMR
[c]
[d]
spectroscopy. Almost no conversion was observed. Observed addition to
triple bond, thioester PhCH2C(O)SC12H25 was obtained
Under the optimized conditions, alkynyl sulfides 3 participated in
the reduction with good or very good efficiency and excellent
regio- and stereoselectivity (Table 3).
Table 3 . Preparation of (Z)-alkenyl sulfides 4 from alkynyl sulfides 3[a
Scheme 5. A possible catalytic cycle.
Finally, reaction of alkenyl borane with MeOH provided the (Z)-
alkenyl sulfide in very good yield and excellent diastereoselctivity.
Conclusions
The mild conditions used herein are tolerant of additional
functional groups, including esters (entries 3, 10 and 13-15),
ethers (entries 6,7 and 16-18), carbon-carbon double bonds
(entry 2), hydroxy group (entries 5, 9, and 11), carboxyl group
(entries 17 and 19-20), Boc-amino group (entries 8-9), nitro (entry
15), cyano (entries 7 and 18) and thiotosylate (entry 4). The latter
is convenient for the subsequent preparation of (Z)-alkenyl
disulfanes. The synthesis of unsymmetrical functionalized Z-
alkenyl disulfanes is under investigation. In conclusion, we
developed a convenient and efficient method for preparing alkynyl
sulfides under mild conditions based on readily available starting
materials. The subsequent reduction of alkynyl sulfides with
pinacolborane afforded Z-alkenyl sulfides with excellent
diastereoselectivity.
Entry
R1
R2
Yield
(%)b
Z/Ec
1
2
C6H5-
C6H5-
CH3(CH2)11
-
94 4a
75 4b
89 4c
50 4d
75 4e
90 4f
78 4g
62 4h
60 4i
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
100:0
CH2=CH(CH2)9-
3
C6H5-
CH3O2C(CH2)10
-
4
C6H5-
4-CH3C6H4-SO2-
5
C6H5-
HO(CH2)11
CH3(CH2)11
4-CN-C6H4-CH2-
CH3(CH2)11
HO(CH2)11
CH3O2C(CH2)10
-
6
C6H5CH2OCH2-
C6H5CH2OCH2-
BocNHCH2-
BocNHCH2-
(CH3)2CHCH2CH2-
(CH3)2CHCH2CH2
(CH3)2CHCH2CH2
EtO2C-
-
7
8
-
9
-
10
11
12
13
14
15
16
17
-
75 4j
HO(CH2)11
C6H5CH2-
-
61 4k
82 4l
CH3(CH2)11
4-CH3-C6H4-
4-NO2-C6H4-CH2-
CH3(CH2)11
HO2C(CH2)10
-
87 4m
87 4n
81 4o
62 4p
59 4r
EtO2C-
EtO2C-
4-CH3O-2-CH3-C6H3-
4-CH3O-2-CH3-C6H3-
-
-
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10.1002/ejoc.201801181
European Journal of Organic Chemistry
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Experimental Section
[12] E. Okragla, S. Demkowicz, J. Rachoń, D. Witt, Synthesis 2009, 10, 1720-
1724
[13] S. Lach, D. Witt, Synthesis 2011, 24, 3975-3978
[14] a) S. Lach, M. Sliwka-Kaszynska, D. Witt, Synlett 2010, 19, 2857-2860 b)
S. Lach, D. Witt, Synlett 2013, 24, 1927-1930.
General procedure for the preparation of alkynyl sulfides 3
[15] a) B. Bartels, R. Hunter, C. D. Simon, G. D. Tomlinson, Tetrahedron Lett.
1987, 28, 2985-2988 b) T. Satoh, D. Taguchi, C. Suzuki, S. Fujisawa,
Tetrahedron 2001, 57, 493-500 c) T. H. Morris, E. H. Smith, R. Walsh, J.
Chem. Soc., Chem. Commun. 1987, 964-965 d) T. Imanishi, T. Ohra, K.
Sugiyama, Y. Ueda, Y. Takemoto, C. Iwata, J. Chem. Soc., Chem. Commun.
1992, 269-270.
[16] E. Busi, G. Capozzi, S. Menichetti, C. Nativi, Synthesis 1992, 643-645.
[17] E. Block, S. Ahmad, J.L. Catalfamo, M.K. Jain, R. Apitz Castro, J. Am.
Chem. Soc. 1986, 108, 7045-7055.
To
a stirred solution of terminal alkyne 1a-g (1 mmol) and
tetramethylethylenediamine (TMEDA) (1 mmol) in anhydrous THF (10 mL)
at 0 ⁰C under an N2 atmosphere was added dropwise 0.4 mL of 2.5 M
solution of BuLi in hexane (1 mmol). After 5 min, the appropriate
thiotosylate (2a-h, 1 mmol) was added in one portion. The mixture was
stirred and warmed to rt for 15 min. Then, the solvent was evaporated, and
the residue was dissolved in Et2O (20 mL), washed with water (10 mL),
dried over MgSO4, filtered and concentrated under vacuum. The residue
was purified by column chromatography (SiO2) to provide corresponding
alkynyl sulfide 3 (Table 1).
[18] G. Brooks, K. Coleman, J. S. Davies and P. A. Hunter, J. Antibiot., 1988,
41, 892-898.
[19] a) B.C. Ranu, K.Chattopadhyay, S. Banerjee, J. Org. Chem. 2006, 71,
423-425; b) B. Boubia, C. Mioskowski, S. Manna, J.R. Falck, Tetrahedron Lett.
1989, 30, 6023-6026; c) Y. Ichinose, K. Wakamatsu, K. Nozaki, J.-L. Birbaum,
K Oshima, K. Utimato, Chem. Lett. 1987, 16, 1647-1650; d) M.Shahjahan,
M.L. Van Linn, A. Monte, J.M. Cook, Org. Lett. 2008, 10, 3363-3366.
[20] a) A. Heiba, R.M. Dessan, J. Org. Chem. 1967, 32, 3837-3840; b) V. A.
Potapov, S. V. Amosova, A. A. Starkova, A. R. Zhnikin, I. V. Doron’kina, I. P.
Beletskaya, L. Hevesi, Sulfur Lett. 2000, 23, 229-238.
[21] a) I. Johannsen, L. Hen- riksen, H. Eggert, J. Org. Chem. 1986, 51, 1657-
1663; b) A. K. Kondoh, K. Takami, H. Yorimitsu, K. Oshima, J. Org. Chem.
2005, 70, 6468-6473.
[22] a) H. Kunigasu, A. Ogawa, K. Sato, I. Ryu, N. Kambe, N. Sonoda, J. Am.
Chem. Soc. 1992, 114, 5902-5903; b) C. Cao, L.R. Fraser, J.A. Love, J. Am.
Chem. Soc. 2005, 127, 17614-17615
General procedure for the preparation of (Z)-alkenyl sulfides 4
To a mixture of CuCl (0.1 mmol, 0.01 g), PPh3 (0.1 mmol, 0.027 g), NaOtBu
(0.2 mmol, 0.02 g) cooled to 0 °C in dry THF (15 mL) was added HBpin (3
mmol, 0.44 mL). The mixture was stirred for 15 min at 0 °C, and a solution
of corresponding alkynyl sulfide 3 (1 mmol) in dry THF (5 mL) was added
dropwise. The reaction was monitored by TLC. When all the substrate had
been consumed (15 – 60 min), MeOH (6 mmol, 0.25 mL) was added. After
stirring at 60 °C for 1 h, the reaction mixture was concentrated, and the
residue was purified by column chromatography (SiO2) to provide Z-
alkenyl sulfide 4 (Table 3).
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We gratefully acknowledge the National Science Centre (NCN)
for financial support (grant no. 2015/19/B/ST5/03359)
Keywords: alkynyl sulfides; (Z)-alkenyl sulfides; hydroboration;
thiotosylates; thiols
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This article is protected by copyright. All rights reserved.

10.1002/ejoc.201801181
European Journal of Organic Chemistry
FULL PAPER
FULL PAPER
We have developed an efficient
and convenient regio- and
stereoselective reduction of the
alkynyl sulfides with
pinacolborane in the presence
of copper (I) chloride to produce
(Z)-alkenyl sulfides in good and
very good yields. The
(Z)-alkenyl sulfides
Justyna Doroszuk, Mateusz
Musiejuk, Łukasz Ponikiewski,
Dariusz Witt*
Page No. – Page No.
functionalized alkynyl sulfides
are readily available based on
the reaction of lithium acetylides
with thiotosylates under mild
conditions.
Convenient and efficient
diastereoselective preparation of
functionalized Z-alkenyl sulfides
This article is protected by copyright. All rights reserved.