Synthesis of Thiazolidine-2-thiones through a One-Pot A3-Coupling–Carbon Disulfide Incorporation Process

Article abstract of DOI:10.1002/ejoc.201601103

A copper-catalyzed two-step one-pot procedure for the synthesis of thiazolidine-2-thiones has been developed. The process involves a three-component coupling of an alkyne, an aldehyde, and an amine (A³-coupling) followed by trapping the resulting propargylamine with carbon disulfide and subsequent cyclization.

Full text of DOI:10.1002/ejoc.201601103

A Journal of
Accepted Article
Title: Synthesis of Thiazolidine-2-thiones via One-Pot A3-coupling /
Carbon Disulfide Incorporation Process
Authors: Anton A. Nechaev, Anatoly A. Peshkov, Kristof Van Hecke,
Vsevolod A. Peshkov, and Erik Van der Eycken
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201601103
Link to VoR: http://dx.doi.org/10.1002/ejoc.201601103
Supported by

10.1002/ejoc.201601103
European Journal of Organic Chemistry
FULL PAPER
Synthesis of Thiazolidine-2-thiones via One-Pot A3-coupling /
Carbon Disulfide Incorporation Process
Anton A. Nechaev,[a] Anatoly A. Peshkov,[a] Kristof Van Hecke,[b] Vsevolod A. Peshkov,*[c]
Erik V. Van der Eycken*[a]
Abstract: A copper-catalyzed two-step one-pot procedure for the
synthesis of thiazolidine-2-thiones was developed. The process
involves three-component coupling of an alkyne, an aldehyde, and
an amine (A3-coupling) followed by trapping of the resulting
propargylamine with carbon disulfide and subsequent cyclization.
imidazolidin-2-imines[6] or pyrimidin-2-imines[7] by choosing the
appropriate catalytic system. Propargylureas accessed from
propargylamines and isocyanates are even more versatile and
could be efficiently transformed into imidazol-2-ones,[8]
imidazolidin-2-ones,[9] pyrimidin-2-ones[10] and oxazolidin-2-
imines[11] in a chemo- and regioselective manner. Analogously,
isothiocyanate-derived propargylthioureas have been utilized to
prepare imidazol-2-thiones[12] and thiazolidin-2-imines.[13] Carbon
dioxide (CO2) can also be incorporated into heterocycles by
reacting with propargylamines 1[14] or propargylalcohols 2[15]
through a large number of synthetic protocols (Scheme 1a, left
part). In contrast, a very few examples are described for its
sulfur analogue carbon disulfide (CS2, Scheme 1a, right
part).[16,17] In this paper, we present a general approach towards
thiazolidine-2-thiones 5 via a copper-catalyzed three-component
coupling of a primary amine, an aldehyde and an alkyne (A3-
coupling) followed by the incorporation of CS2 (Scheme 1b).[18,19]
Introduction
Five-membered heterocycles containing nitrogen and sulfur
atoms such as rhodanines, 4-thiazolidinones, and 2,4-
thiazolidinediones proved to be promising scaffolds for
identifying potential antibacterial, antiviral, antidiabetic and
anticancer
agents.[1]
Chiral
oxazolidinethiones
and
thiazolidinethiones, sulfur-containing modifications of the well-
known Evans oxazolidinones, have found broad application as
highly selective and efficient chiral auxiliaries.[2] Therefore, the
development of novel synthetic approaches towards this class of
heterocycles continues to be well-justified.
Propargylic compounds such as propargylic alcohols and
propargylamines have recently emerged as useful building
blocks and intermediates in heterocyclic chemistry.[3] This can be
partially attributed to the recent progress in the development of
efficient catalytic methods for their synthesis. Most notable
transformations include transition metal-catalyzed additions of
terminal alkynes to imines and closely related three-component
coupling of alkynes, aldehydes, and amines (A3-coupling)
allowing to access various types of propargylamines.[4]
With respect to the synthesis of heterocycles, a lot of work has
been done on the addition of secondary propargylamines[5] to
various heteroallenes and subsequent transition metal-catalyzed
or
electrophile-mediated
cyclizations.
For
example,
propargylguanidines originated from propargylamines and
carbodiimides could be selectively converted into either
Scheme 1. Incorporation of carbon dioxide (CO2) and carbon disulfide (CS2)
into heterocycles by reacting with propargylic compounds.
[a]
Laboratory for Organic & Microwave-Assisted Chemistry (LOMAC),
Department of Chemistry
Results and Discussion
University of Leuven (KU Leuven)
Despite that the first A3-coupling step is a well studied
transformation, some adjustments were required to combine it
with the second CS2 incorporation step to develop a two-step
one-pot process for the generation of thiazolidine-2-thiones 5.
We have selected p-methoxybenzyl amine (7a), butyraldehyde
(8a) and phenyl acetylene (9a) as model substrates for the
optimization studies (Table 1). The first trial was conducted
using an excess of 8a and 9a, 10 mol% of CuBr as catalyst and
toluene as solvent. After carrying out the A3-coupling step at
100°C for 3 h, 2 equiv of CS2 were added and the reaction was
Celestijnenlaan 200F, B-3001 Leuven, Belgium
E-mail: erik.vandereycken@chem.kuleuven.be
XStruct, Department of Inorganic and Physical Chemistry
Ghent University
[b]
[c]
Krijgslaan 281 S3, B-9000 Ghent, Belgium
College of Chemistry, Chemical Engineering and Materials Science
Soochow University
Dushu Lake Campus, Suzhou, 215123, China
E-mail: vsevolod@suda.edu.cn
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601103
European Journal of Organic Chemistry
FULL PAPER
heated at 50°C for
2
h, allowing to obtain the desired
be beneficial (Table 1, entries 7 and 8) allowing to obtain 5a in
up to 56 % isolated yield (Table 1, entry 8). At the same time,
the use of prolonged reaction times of 7 h and 16 h in the A3-
coupling step led to diminished yields of 5a (Table 1, entries 9
and 10). Utilizing other copper salts as a catalyst (Table 1,
entries 11-13) or switching to other solvents (Table 1, entries 14-
16) failed to upgrade the reaction outcome. Besides, the yield of
5a could not be improved by the addition of organic base during
the second step of the process (Table 1, entry 17).
thiazolidine-2-thione 5a in 25 % NMR yield (Table 1, entry 1).
Increasing amounts of CuBr catalyst and CS2 up to 15 mol% and
3 equiv respectively led to an improved yield of 47 % (Table 1,
entry 2), while no further amplification was achieved by
increasing the excess of CS2 up to 4 equiv (Table 1, entry 3).
Varying the 7a:8a:9a ratio led to a decreased yield of 5a (Table
1, entries 4 and 5). On the other hand, some improvement was
made by elevating the reaction temperature in the CS2
incorporation step to 100°C (Table 1, entry 6). A slight increase
in the reaction time for both steps of the process also proved to
Table 1. Optimization of the reaction conditions[a]
Entry
7a:8a:9a ratio
Cu catalyst
Solvent
Time1 [h]
Temp [°C]
Time2 [h]
x
Yield [%][b]
1
1:1.25:2
1:1.25:2
1:1.25:2
1:1.25:2.5
1.25:1:2
1:1.25:2
1:1.25:2
1:1.25:2
1:1.25:2
1:1.25:2
1:1.25:2
1:1.25:2
1:1.25:2
1:1.25:2
1:1.25:2
1:1.25:2
1:1.25:2
CuBr (10 mol%)
CuBr (15 mol%)
CuBr (15 mol%)
CuBr (15 mol%)
CuBr (15 mol%)
CuBr (15 mol%)
CuBr (15 mol%)
CuBr (15 mol%)
CuBr (15 mol%)
CuBr (15 mol%)
CuCl (15 mol%)
CuI (15 mol%)
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
dioxane
MeCN
3
3
3
3
3
3
3
5
7
16
5
5
5
5
5
5
5
50
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
3
2
3
4
3
3
3
3
3
3
3
3
3
3
3
3
3
3
25 (19)[c]
47
2
50
3
50
45
4
50
36
5
50
40
6
100
100
100
100
100
100
100
100
100
100
100
100
53
7
54
8
62 (56)[c]
55
9
10
11
12
13
14
15
16
17[d]
32
47
38
CuBr2 (15 mol%)
CuBr (15 mol%)
CuBr (15 mol%)
CuBr (15 mol%)
CuBr (15 mol%)
44
53
37
EtOH
19
toluene
43
[a] The reactions were run on 0.8 mmol scale in 1 mL of solvent under argon atmosphere in a sealed screw-cap vials. [b] Yields were determined by 1H NMR using
3,4,5-trimethoxybenzaldehyde as internal standard. [c] Isolated yield is given in parentheses. [d] 0.5 equiv of Et3N were used as an additive in the second step.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601103
European Journal of Organic Chemistry
FULL PAPER
The structure of (Z)-5-benzylidene-3-(4-methoxybenzyl)-4-
propylthiazolidine-2-thione 5a, a product of the model reaction of
7a, 8a and 9a was ascertained by X-ray crystallographic
analysis (Figure 1).[20]
With these results at hand, we decided to evaluate the scope of
our process (Table 2). Testing various primary amines 7a-g in a
combination with butyraldehyde (8a) and phenyl acetylene (9a)
we were able to obtain thiazolidine-2-thiones 5a-g in yields
ranging from 37% to 70% (Table 2, entries 1-7). Exploring the
aldehyde component, we have found that the yield of the
Figure 1. X-ray crystallographic structure of 5a, showing thermal displacement
ellipsoids at the 50% probability level.
Table 2. Scope of the process[a]
Entry
Amine 7, R1
Aldehyde 8, R2
Alkyne 9, R3
Product 5
Yield [%][b]
1
7a, PMB
8a, Pr
9a, Ph
5a
5b
5c
5d
5e
5f
56
45
54
37
67
49
70
55
44
39
26
24
60
66
59
52
61
57
54
61
31
73
33
2
7b, Bn
8a, Pr
9a, Ph
3
7c, 4-FC6H4CH2
7d, 4-ClC6H4CH2
7e, PhCH2CH2
7f, MeOCH2CH2
7g, Pentyl
7a, PMB
8a, Pr
9a, Ph
4
8a, Pr
9a, Ph
5
8a, Pr
9a, Ph
6
8a, Pr
9a, Ph
7
8a, Pr
9a, Ph
5g
5h
5i
8
8b, Bu
8c, iBu
8d, Bn
8e, CH2=CH(CH2)7CH2
8f, Ph
9a, Ph
9
7a, PMB
9a, Ph
10
11
12
13
14
15
16
17
18
19
20
21
22
23
7a, PMB
9a, Ph
5j
7a, PMB
9a, Ph
5k
5l
7a, PMB
9a, Ph
7a, PMB
8a, Pr
9b, 4-MeC6H4
9c, 4-EtC6H4
9d, 4-PentylC6H4
9e, 4-tBuC6H4
9f, 3-MeC6H4
9g, 4-MeOC6H4
9h, 4-FC6H4
9i, 3-ClC6H4
9j, 4-CF3C6H4
9k, Thiophen-3-yl
9l, CyCH2
5m
5n
5o
5p
5q
5r
7a, PMB
8a, Pr
7a, PMB
8a, Pr
7a, PMB
8a, Pr
7a, PMB
8a, Pr
7a, PMB
8a, Pr
7a, PMB
8a, Pr
5s
5t
7a, PMB
8a, Pr
7a, PMB
8a, Pr
5u
5v
5w
7a, PMB
8a, Pr
7a, PMB
8a, Pr
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601103
European Journal of Organic Chemistry
FULL PAPER
[a] All reactions were run using CuBr (17 mg, 0.12 mmol), amine 7 (0.8 mmol), aldehyde 8 (1 mmol), acetylene 9 (1.6 mmol) and CS2 (183 mg, 2.4 mmol) in toluene
(1 mL) under argon atmosphere in a sealed screw-cap vials. [b] Isolated yields.
Scheme 2. Tentative reaction pathway and control experiments.
thiazolidine-2-thione 5 gradually drops as a result of increasing
bulk or the side-chain elongation. Thus, valeraldehyde 8d
furnished thiazolidine-2-thione 5h in 55% yield (Table 2, entry 8).
Branched isovaleraldehyde 8c (Table 2, entry 9) and 2-
phenylacetaldehyde 8d (Table 2, entry 10) delivered 5i and 5j in
44% and 39%, respectively (Table 2, entries 9 and 10). Undec-
10-enal 8e and aromatic benzaldehyde 8f were found to be the
least efficient (Table 2, entries 11 and 12). For the terminal
alkyne part, we first examined various aromatic acetylenes 9b-j
obtained by the deprotonation of B, reacts with imine A resulting
in the formation of the propargylamine 1 and the regeneration of
the copper catalyst. In the second step of the process
propargylamine 1 reacts with CS2 to give the adduct D that
further cyclizes into the final thiazolidine-2-thione 5. We have
found that the incorporation of CS2 can be accomplished in the
absence of the copper(I)-catalyst, if the overall process is
conducted in a stepwise manner. Furthermore, the control
experiments clearly demonstrate that the presence of copper(I)-
catalyst has no influence on the reaction of propargylamine 1
with CS2. On the other hand, the efficiency of the one-pot
procedure is significantly higher compared to the stepwise
approach.
bearing
a range of sterically and electronically different
substituents on the phenyl ring (Table 2, entries 13-21). These
reactions furnished thiazolidine-2-thiones 5m-t with consistently
good yields of 54% to 66% with an exception of thiazolidine-2-
thione 5u derived from electron-deficient 1-ethynyl-4-
(trifluoromethyl)benzene
(9j).
Heteroaromatic
3-
ethynylthiophene (9k) also worked well yielding thiazolidine-2-
thione 5v in 73% (Table 2, entry 22). Finally, we investigated the
reaction of aliphatic prop-2-ynylcyclohexane (9l) that afforded
product 5w in 33% yield (Table 2, entry 23).
A tentative reaction pathway is shown in Scheme 2. The first
step of the process constitutes the standard copper(I)-catalyzed
A3-coupling. Copper activates the triple bond of the alkyne 9 to
form the π-complex B while primary amine 7 and aldehyde 8
condense generating imine A. Next, the copper acetylide С,
Conclusions
In conclusion, we have established a general process for the
synthesis of thiazolidine-2-thiones starting from readily available
primary amines, aldehydes, terminal alkynes and carbon
disulfide. The developed one-pot procedure involving a copper-
catalyzed A3-coupling followed by carbon disulfide incorporation
is fast and operationally simple. The scope of the process was
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601103
European Journal of Organic Chemistry
FULL PAPER
examined with respect to all variable components allowing to
attain a set of title compounds in fair yields.
(Z)-5-benzylidene-3-(4-fluorobenzyl)-4-propylthiazolidine-2-thione
(5c).
Experimental Section
Yield: 156 mg (54%); yellow oil.
1H and 13C NMR spectra were recorded with 400 and 100 MHz
respectively using BrukerAvance instrument. The 1H and 13C chemical
shifts are reported in parts per million relative to tetramethylsilane using
the residual solvent signal as the internal reference. Melting points were
recorded on a Reichert Thermovar apparatus. HRMS ESI spectra were
acquired on a quadrupole orthogonal acceleration time-of-flight mass
spectrometer (Synapt G2 HDMS, Waters, Milford, MA). Samples were
infused at 3µL/min and spectra were obtained in positive ionization mode
with a resolution of 15000 (FWHM) using leucine enkephalin as lock
mass.
1H NMR (400 MHz, CDCl3): δ 7.40-7.30 (m, 4H), 7.27-7.19 (m, 3H), 7.09-
7.01 (m, 2H), 6.35 (d, J = 1.2 Hz, 1H), 5.91 (d, J = 15.0 Hz, 1H), 4.80-
4.73 (m, 1H), 4.24 (d, J = 15.0 Hz, 1H), 2.09-1.96 (m, 1H), 1.81-1.69 (m,
1H), 1.53-1.28 (m, 2H), 0.92 (t, J = 7.3 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 193.8, 162.7 (d, J = 247.3 Hz), 135.3,
132.3, 130.8 (d, J = 3.3 Hz), 130.0 (d, J = 8.2 Hz), 128.9, 128.1, 127.6,
120.0, 116.1 (d, J = 21.6 Hz), 72.5, 48.8, 36.5, 16.0, 14.0.
HRMS (ESI, [M+H]+) for C20H21FNS2+ calcd. 358.1094, found 358.110.
General procedure for the synthesis of thiazolidine-2-thiones 5
(Table 2)
(Z)-5-benzylidene-3-(4-chlorobenzyl)-4-propylthiazolidine-2-thione
(5d).
Copper (I) bromide catalyst (17 mg, 0.12 mmol) was placed in a screw
cap vial followed by addition of dry toluene (1mL), amine 7 (0.8 mmol),
aldehyde 8 (1 mmol), and acetylene 9 (1.6 mmol). The resulting mixture
was flushed with nitrogen, sealed and stirred at 100 °C for 5 h. Then
carbon disulfide (183 mg, 2.4 mmol) was added and the mixture was
stirred at 100 °C for 3 h. The resulting mixture was diluted with DCM,
concentrated with silica and subjected to column chromatography on
silicagel with heptane-EtOAc (15%) as eluent to give the desired
thiazolidine-2-thione 5. Products 5f,h,l,o,r,s,u,v were additionally washed
with pentane after column chromatography.
Yield: 110 mg (37%); brownish oil.
1H NMR (400 MHz, CDCl3): δ 7.40-7.32 (m, 4H), 7.32-7.20 (m, 5H), 6.35
(d, J = 1.0 Hz, 1H), 5.94 (d, J = 15.1 Hz, 1H), 4.78-4.72 (m, 1H), 4.22 (d,
J = 15.1 Hz, 1H), 2.08-1.96 (m, 1H), 1.80-1.69 (m, 1H), 1.54-1.26 (m, 2H),
0.93 (t, J = 7.3 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 194.0, 135.3, 134.4, 133.5, 132.3, 129.6,
129.4, 128.9, 128.1, 127.7, 120.1, 72.5, 48.9, 36.5, 16.1, 14.0.
(Z)-5-benzylidene-3-(4-methoxybenzyl)-4-propylthiazolidine-2-thione
(5a).
HRMS (ESI, [M+H]+) for C20H21ClNS2+ calcd. 374.0798, found 374.0805.
(Z)-5-benzylidene-3-phenethyl-4-propylthiazolidine-2-thione (5e).
Yield: 190 mg (67%); orange solid; mp 56–58 °C.
Yield: 165 mg (56%); yellow solid; mp 98–101 °C.
1H NMR (400 MHz, CDCl3): δ 7.39-7.31 (m, 2H), 7.28 (d, J = 8.5 Hz, 2H),
7.25-7.19 (m, 3H), 6.88 (d, J = 8.6 Hz, 2H), 6.32 (d, J = 1.2 Hz, 1H), 5.93
(d, J = 14.8 Hz, 1H), 4.79-4.73 (m, 1H), 4.15 (d, J = 14.8 Hz, 1H), 3.79 (s,
3H), 2.10-1.98 (m, 1H), 1.79-1.67 (m, 1H), 1.52-1.29 (m, 2H), 0.92 (t, J =
7.3 Hz, 3H).
1H NMR (400 MHz, CDCl3): δ 7.43-7.19 (m, 10H), 6.29 (d, J = 1.5 Hz,
1H), 4.62-4.47 (m, 2H), 3.48 (ddd, J = 13.5, 8.7, 7.3 Hz, 1H), 3.23-3.07
(m, 1H), 3.04-2.90 (m, 1H), 2.06-1.89 (m, 1H), 1.80-1.65 (m, 1H), 1.52-
1.24 (m, 2H), 0.92 (t, J = 7.3 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 193.3, 159.7, 135.4, 132.7, 129.7, 128.8,
128.1, 127.6, 126.9, 119.7, 114.5, 72.4, 55.5, 49.1, 36.5, 16.0, 14.1.
13C NMR (100 MHz, CDCl3): δ 192.5, 138.2, 135.4, 133.0, 128.92,
128.86, 128.1, 127.6, 127.0, 119.8, 74.8, 48.5, 36.9, 32.8, 16.3, 14.0.
HRMS (ESI, [M+H]+) for C21H24NOS2+ calcd. 370.1294, found 370.1325.
(Z)-3-benzyl-5-benzylidene-4-propylthiazolidine-2-thione (5b).
Yield: 122 mg (45%); yellow solid; mp 95–97 °C.
HRMS (ESI, [M+H]+) for C21H24NS2+ calcd. 354.1345, found 354.1342.
(Z)-5-benzylidene-3-(2-methoxyethyl)-4-propylthiazolidine-2-thione
(5f).
Yield: 121 mg (49%); pale yellow solid; mp 63–65 °C.
1H NMR (400 MHz, CDCl3): δ 7.41-7.30 (m, 7H), 7.28-7.21 (m, 3H), 6.34
(d, J = 1.0 Hz, 1H), 6.01 (d, J = 15.0 Hz, 1H), 4.81-4.76 (m, 1H), 4.24 (d,
J = 15.0 Hz, 1H), 2.11-1.99 (m, 1H), 1.80-1.69 (m, 1H), 1.55-1.29 (m, 2H),
0.93 (t, J = 7.3 Hz, 3H).
1H NMR (400 MHz, CDCl3): δ 7.42-7.33 (m, 2H), 7.30-7.21 (m, 3H), 6.43
(d, J = 1.6 Hz, 1H), 5.22-5.12 (m, 1H), 4.57 (ddd, J = 14.2, 4.0, 3.3 Hz,
1H), 3.77 (ddd, J = 10.2, 8.9, 3.2 Hz, 1H), 3.62 (dt, J = 10.2, 4.1, 3.5 Hz,
1H), 3.51 (ddd, J = 14.2, 8.9, 3.5 Hz, 1H), 3.35 (s, 3H), 2.18-2.01 (m, 1H),
1.86-1.70 (m, 1H), 1.55-1.22 (m, 2H), 0.95 (t, J = 7.3 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 193.7, 135.4, 134.9, 132.6, 129.1, 128.9,
128.4, 128.3, 128.1, 127.6, 119.8, 72.5, 49.6, 36.5, 16.0, 14.0.
13C NMR (100 MHz, CDCl3): δ 192.9, 135.6, 133.3, 128.9, 128.1, 127.5,
119.6, 75.5, 70.3, 59.2, 46.5, 36.7, 16.2, 14.1.
HRMS (ESI, [M+H]+) for C20H22NS2+ calcd. 340.1188, found 340.1189.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601103
European Journal of Organic Chemistry
FULL PAPER
HRMS (ESI, [M+H]+) for C16H22NOS2+ calcd. 308.1137, found 308.1151.
(Z)-5-benzylidene-3-pentyl-4-propylthiazolidine-2-thione (5g).
Yield: 178 mg (70%); brownish oil.
HRMS (ESI, [M+H]+) for C25H24NOS2+ calcd. 418.1294, found 418.1281.
(Z)-5-benzylidene-4-(dec-9-enyl)-3-(4-methoxybenzyl)thiazolidine-2-
thione (5k).
Yield: 97 mg (26%); yellow oil.
1H NMR (400 MHz, CDCl3): δ 7.40-7.33 (m, 2H), 7.29-7.21 (m, 3H), 6.43
(d, J = 1.5 Hz, 1H), 4.99-4.92 (m, 1H), 4.39 (ddd, J = 13.7, 9.6, 6.6 Hz,
1H), 3.25 (ddd, J = 13.7, 9.2, 5.2 Hz, 1H), 2.09-1.96 (m, 1H), 1.85-1.61
(m, 3H), 1.55-1.27 (m, 6H), 0.95 (t, J = 7.4 Hz, 3H), 0.92 (d, J = 7.1 Hz,
3H).
1H NMR (400 MHz, CDCl3): δ 7.40-7.32 (m, 2H), 7.31-7.19 (m, 5H), 6.88
(d, J = 8.5 Hz, 2H), 6.32 (s, 1H), 5.92 (d, J = 14.8 Hz, 1H), 5.79 (ddt, J =
16.9, 10.2, 6.7 Hz, 1H), 5.03-4.88 (m, 2H), 4.80-4.73 (m, 1H), 4.16 (d, J =
14.8 Hz, 1H), 3.80 (s, 3H), 2.11-1.96 (m, 3H), 1.82-1.64 (m, 1H), 1.48-
1.20 (m, 12H).
13C NMR (100 MHz, CDCl3): δ 192.2, 135.5, 133.1, 128.8, 128.1, 127.5,
119.6, 73.7, 46.6, 36.9, 29.0, 26.4, 22.4, 16.1, 14.04, 14.01.
13C NMR (100 MHz, CDCl3): δ 193.3, 159.7, 139.2, 135.5, 132.7, 129.7,
128.8, 128.1, 127.6, 126.9, 119.7, 114.5, 114.3, 72.5, 55.4, 49.2, 34.3,
33.9, 29.6, 29.48, 29.46, 29.1, 29.0, 22.5.
HRMS (ESI, [M+H]+) for C18H26NS2+ calcd. 320.1501, found 320.1505.
HRMS (ESI, [M+H]+) for C28H36NOS2+ calcd. 466.2233, found 466.2237.
(Z)-5-benzylidene-4-butyl-3-(4-methoxybenzyl)thiazolidine-2-thione
(5h).
(Z)-5-benzylidene-3-(4-methoxybenzyl)-4-phenylthiazolidine-2-thione
(5l).
Yield: 170 mg (55%); orange-red solid; mp 85–88 °C.
1H NMR (400 MHz, CDCl3): δ 7.40-7.33 (m, 2H), 7.31-7.20 (m, 5H), 6.89
(d, J = 8.6 Hz, 2H), 6.33 (d, J = 1.4 Hz, 1H), 5.95 (d, J = 14.8 Hz, 1H),
4.80-4.74 (m, 1H), 4.15 (d, J = 14.8 Hz, 1H), 3.81 (s, 3H), 2.13-2.01 (m,
1H), 1.81-1.69 (m, 1H), 1.49-1.21 (m, 4H), 0.90 (t, J = 7.0 Hz, 3H).
Yield: 77 mg (24%); yellow solid; mp 116–119 °C.
1H NMR (400 MHz, CDCl3): δ 7.50-7.39 (m, 3H), 7.35-7.27 (m, 4H), 7.24-
7.11 (m, 5H), 6.87 (d, J = 8.6 Hz, 2H), 6.14 (d, J = 1.8 Hz, 1H), 5.95 (d, J
= 14.5 Hz, 1H), 5.62 (d, J = 1.9 Hz, 1H), 3.82 (s, 3H), 3.68 (d, J = 14.6 Hz,
1H).
13C NMR (100 MHz, CDCl3): δ 193.4, 159.7, 135.5, 132.7, 129.8, 128.9,
128.1, 127.6, 126.9, 119.7, 114.5, 72.4, 55.5, 49.1, 34.1, 24.6, 22.7, 14.1.
13C NMR (100 MHz, CDCl3): δ 193.2, 159.7, 138.5, 135.4, 132.8, 130.1,
129.7, 129.6, 128.8, 128.1, 127.6, 127.5, 126.7, 121.8, 114.4, 76.6, 55.5,
49.2.
HRMS (ESI, [M+H]+) for C22H26NOS2+ calcd. 384.1450, found 384.1447.
(Z)-5-benzylidene-4-isobutyl-3-(4-methoxybenzyl)thiazolidine-2-
thione (5i).
HRMS (ESI, [M+H]+) for C24H22NOS2+ calcd. 404.1137, found 404.1135.
(Z)-3-(4-methoxybenzyl)-5-(4-methylbenzylidene)-4-
propylthiazolidine-2-thione (5m).
Yield: 136 mg (44%); brownish oil.
1H NMR (400 MHz, CDCl3): δ 7.40-7.32 (m, 2H), 7.30-7.18 (m, 5H), 6.89
(d, J = 8.6 Hz, 2H), 6.32 (s, 1H), 5.98 (d, J = 14.8 Hz, 1H), 4.72-4.65 (m,
1H), 4.12 (d, J = 14.8 Hz, 1H), 3.81 (s, 3H), 1.97-1.79 (m, 2H), 1.65 (ddd,
J = 13.4, 8.5, 3.1 Hz, 1H), 0.97 (d, J = 6.5 Hz, 3H), 0.93 (d, J = 6.4 Hz,
3H).
Yield: 185 mg (60%); yellow solid; mp77-79 °C.
1H NMR (400 MHz, CDCl3): δ7.29 (d, J= 8.6 Hz, 2H), 7.17 (d, J = 8.3 Hz,
2H), 7.12 (d, J = 8.3 Hz, 2H), 6.89 (d, J = 8.7 Hz, 2H), 6.30 (d, J = 1.6 Hz,
1H), 5.94 (d, J = 14.8 Hz, 1H), 4.80-4.70 (m, 1H), 4.15 (d, J = 14.8 Hz,
1H), 3.81 (s, 3H), 2.34 (s, 3H), 2.12-1.95 (m, 1H), 1.81-1.65 (m, 1H),
1.56-1.25 (m, 2H), 0.93 (t, J = 7.3 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 193.1, 159.8, 135.3, 132.9, 129.8, 128.8,
128.2, 127.7, 127.0, 120.7, 114.5, 71.4, 55.5, 49.2, 42.1, 23.8, 23.6, 22.6.
13C NMR (100 MHz, CDCl3): δ 193.4, 159.7, 137.5, 132.6, 131.3, 129.7,
HRMS (ESI, [M+H]+) for C22H26NOS2+ calcd. 384.1450, found 384.1446.
129.5, 128.0, 126.9, 119.7, 114.5, 72.3, 55.4, 49.1, 36.5, 21.3, 16.0, 14.0.
(Z)-4-benzyl-5-benzylidene-3-(4-methoxybenzyl)thiazolidine-2-thione
(5j).
HRMS (ESI, [M+H]+) for C22H26NOS2+ calcd. 384.1450, found 384.1449.
(Z)-5-(4-ethylbenzylidene)-3-(4-methoxybenzyl)-4-propylthiazolidine-
2-thione (5n).
Yield: 130 mg (39%); yellow oil.
1H NMR (400 MHz, CDCl3): δ 7.38-7.17 (m, 8H), 7.10-7.04 (m, 4H), 6.91
(d, J = 8.6 Hz, 2H), 6.02 (d, J = 14.9 Hz, 1H), 5.80 (s, 1H), 4.79 (ddd, J =
7.4, 4.4, 1.1 Hz, 1H), 4.23 (d, J = 14.9 Hz, 1H), 3.82 (s, 3H), 3.23 (dd, J =
13.6, 4.3 Hz, 1H), 3.08 (dd, J = 13.6, 7.5 Hz, 1H).
Yield: 210 mg (66%); brownish oil.
1H NMR (400 MHz, CDCl3): δ7.28 (d, J = 8.6 Hz, 2H), 7.20 (d, J = 8.2 Hz,
2H), 7.15 (d, J = 8.2 Hz, 2H), 6.89 (d, J = 8.6 Hz, 2H), 6.30 (d, J = 1.3 Hz,
1H), 5.95 (d, J = 14.8 Hz, 1H), 4.79-4.71 (m, 1H), 4.15 (d, J = 14.8 Hz,
1H), 3.81 (s, 3H), 2.64 (q, J = 7.5 Hz, 2H), 2.10-1.97 (m, 1H), 1.78-1.66
13C NMR (100 MHz, CDCl3): δ 193.6, 159.8, 135.2, 134.9, 131.3, 130.0,
129.8, 128.78, 128.77, 128.1, 127.7, 127.5, 126.9, 121.4, 114.6, 73.6,
55.5, 49.7, 40.3.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601103
European Journal of Organic Chemistry
FULL PAPER
(m, 1H), 1.53-1.27 (m, 2H), 1.23 (t, J = 7.6 Hz, 3H), 0.92 (t, J = 7.4 Hz,
(Z)-3-(4-methoxybenzyl)-5-(4-methoxybenzylidene)-4-
3H).
propylthiazolidine-2-thione (5r).
13C NMR (100 MHz, CDCl3): δ 193.5, 159.7, 143.9, 132.9, 131.4, 129.7,
128.4, 128.1, 127.0, 119.7, 114.5, 72.3, 55.5, 49.1, 36.5, 28.7, 16.0, 15.6,
14.1.
Yield: 183 mg (57%); yellow solid; mp 68–70 °C.
1H NMR (400 MHz, CDCl3): δ7.28 (d, J = 8.8 Hz, 2H), 7.16 (d, J = 8.7 Hz,
2H), 6.89 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.7 Hz, 2H), 6.26 (d, J = 1.6 Hz,
1H), 5.95 (d, J = 14.8 Hz, 1H), 4.76-4.69 (m, 1H), 4.14 (d, J = 14.8 Hz,
1H), 3.81 (s, 3H), 3.81 (s, 3H), 2.10-1.95 (m, 1H), 1.79-1.64 (m, 1H),
1.53-1.25 (m, 2H), 0.92 (t, J = 7.3 Hz, 3H).
HRMS (ESI, [M+H]+) for C23H28NOS2+ calcd. 398.1607, found 398.1629.
(Z)-3-(4-methoxybenzyl)-5-(4-pentylbenzylidene)-4-
propylthiazolidine-2-thione (5o).
13C NMR (100 MHz, CDCl3): δ 193.5, 159.7, 159.0, 129.9, 129.7, 129.5,
128.2, 127.0, 119.4, 114.5, 114.3, 72.3, 55.49, 55.47, 49.1, 36.5, 16.1,
14.1.
Yield: 208 mg (59%); yellow solid; mp 51–53 °C.
1H NMR (400 MHz, CDCl3): δ7.28 (d, J = 8.6 Hz, 2H), 7.18 (d, J = 8.3 Hz,
2H), 7.14 (d, J = 8.3 Hz, 2H), 6.89 (d, J = 8.6 Hz, 2H), 6.30 (d, J = 1.4 Hz,
1H), 5.95 (d, J = 14.8 Hz, 1H), 4.78-4.71 (m, 1H), 4.14 (d, J = 14.8 Hz,
1H), 3.81 (s, 3H), 2.63-2.52 (m, 2H), 2.10-1.97 (m, 1H), 1.78-1.66 (m,
1H), 1.66-1.23 (m, 8H), 0.92 (t, J = 7.4 Hz, 3H), 0.89 (t, J = 6.9 Hz, 3H).
HRMS (ESI, [M+H]+) for C22H26NO2S2+ calcd. 400.1399, found 400.1401.
(Z)-5-(4-fluorobenzylidene)-3-(4-methoxybenzyl)-4-
propylthiazolidine-2-thione (5s).
13C NMR (100 MHz, CDCl3): δ 193.5, 159.7, 142.7, 132.8, 131.4, 129.7,
128.9, 128.0, 127.0, 119.8, 114.5, 72.3, 55.5, 49.1, 36.5, 35.8, 31.6, 31.1,
22.7, 16.0, 14.2, 14.1.
Yield: 168 mg (54%); yellow solid; mp 104–106 °C.
1H NMR (400 MHz, CDCl3): δ 7.28 (d, J = 8.6 Hz, 2H), 7.24-7.15 (m, 2H),
7.09-7.01 (m, 2H), 6.89 (d, J = 8.7 Hz, 2H), 6.28 (d, J = 1.2 Hz, 1H), 5.94
(d, J = 14.8 Hz, 1H), 4.77-4.71 (m, 1H), 4.14 (d, J = 14.8 Hz, 1H), 3.81 (s,
3H), 2.11-1.96 (m, 1H), 1.79-1.66 (m, 1H), 1.53-1.27 (m, 2H), 0.93 (t, J =
7.3 Hz, 3H).
HRMS (ESI, [M+H]+) for C26H34NOS2+ calcd. 440.2076, found 440.2068.
(Z)-5-(4-tert-butylbenzylidene)-3-(4-methoxybenzyl)-4-
propylthiazolidine-2-thione (5p).
13C NMR (100 MHz, CDCl3): δ 193.0, 161.9 (d, J = 248.8 Hz), 159.8,
132.6 (d, J = 2.2 Hz), 131.7 (d, J = 3.3 Hz), 129.8 (d, J = 8.1 Hz), 129.7,
126.9, 118.6, 115.9 (d, J = 21.7 Hz), 114.5, 72.3, 55.5, 49.1, 36.4, 16.0,
14.1.
Yield: 176 mg (52%); yellow solid; mp 45–46 °C.
1H NMR (400 MHz, CDCl3): δ7.39 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.6 Hz,
2H), 7.17 (d, J = 8.4 Hz, 2H), 6.89 (d, J = 8.7 Hz, 2H), 6.30 (d, J = 1.6 Hz,
1H), 5.95 (d, J = 14.8 Hz, 1H), 4.79-4.70 (m, 1H), 4.14 (d, J = 14.8 Hz,
1H), 3.81 (s, 3H), 2.13-1.96 (m, 1H), 1.79-1.62 (m, 1H), 1.52-1.18 (m,
11H), 0.91 (t, J = 7.3 Hz, 3H).
HRMS (ESI, [M+H]+) for C21H23FNOS2+ calcd. 388.1200,found 388.1210.
(Z)-5-(3-chlorobenzylidene)-3-(4-methoxybenzyl)-4-
propylthiazolidine-2-thione (5t).
13C NMR (100 MHz, CDCl3): δ 193.5, 159.7, 150.8, 132.6, 131.5, 129.7,
127.9, 127.0, 125.8, 119.6, 114.5, 72.4, 55.5, 49.1, 36.5, 34.8, 31.4, 16.0,
14.1.
Yield: 197 mg (61%); brownish oil.
1H NMR (400 MHz, CDCl3): δ 7.33-7.24 (m, 3H), 7.23-7.17 (m, 2H), 7.14-
7.07 (m, 1H), 6.89 (d, J = 8.6 Hz, 2H), 6.25 (d, J = 1.3 Hz, 1H), 5.94 (d, J
= 14.8 Hz, 1H), 4.79-4.72 (m, 1H), 4.14 (d, J = 14.8 Hz, 1H), 3.81 (s, 3H),
2.11-1.99 (m, 1H), 1.78-1.67 (m, 1H), 1.52-1.23 (m, 2H), 0.93 (t, J = 7.3
Hz, 3H).
HRMS (ESI, [M+H]+) for C25H32NOS2+ calcd. 426.1920, found 426.1917.
(Z)-3-(4-methoxybenzyl)-5-(3-methylbenzylidene)-4-
propylthiazolidine-2-thione (5q).
13C NMR (100 MHz, CDCl3): δ 192.7, 159.8, 137.3, 134.91, 134.87,
130.1, 129.8, 128.1, 127.6, 126.8, 126.0, 118.2, 114.5, 72.4, 55.5, 49.2,
36.5, 16.0, 14.1.
Yield: 186 mg (61%); brownish oil.
1H NMR (400 MHz, CDCl3): δ7.28 (d, J = 8.6 Hz, 2H), 7.26-7.21 (s, 1H),
7.09-6.99 (m, 3H), 6.89 (d, J = 8.7 Hz, 2H), 6.30 (d, J = 1.7 Hz, 1H), 5.95
(d, J = 14.8 Hz, 1H), 4.79-4.71 (m, 1H), 4.14 (d, J = 14.8 Hz, 1H), 3.81 (s,
3H), 2.35 (s, 3H), 2.12-1.96 (m, 1H), 1.80-1.65 (m, 1H), 1.56-1.25 (m,
2H), 0.93 (t, J = 7.3 Hz, 3H).
+
HRMS (ESI, [M+H]+) for C21H23ClNOS2 calcd. 404.0904, found
404.0892.
(Z)-3-(4-methoxybenzyl)-4-propyl-5-(4-
13C NMR (100 MHz, CDCl3): δ 193.5, 159.7, 138.6, 135.4, 132.3, 129.7,
128.8, 128.7, 128.4, 126.9, 125.3, 119.9, 114.5, 72.3, 55.5, 49.1, 36.5,
21.6, 16.0, 14.1.
(trifluoromethyl)benzylidene)thiazolidine-2-thione (5u).
Yield: 110 mg (31%); yellow solid; mp 105–108 °C.
HRMS (ESI, [M+H]+) for C22H26NOS2+ calcd. 384.1450, found 384.1451.
1H NMR (400 MHz, CDCl3): δ7.61 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.2 Hz,
2H), 7.29 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.6 Hz, 2H), 6.34 (d, J = 0.8 Hz,
1H), 5.95 (d, J = 14.8 Hz, 1H), 4.82-4.75 (m, 1H), 4.15 (d, J = 14.8 Hz,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601103
European Journal of Organic Chemistry
FULL PAPER
1H), 3.81 (s, 3H), 2.14-2.01 (m, 1H), 1.81-1.69 (m, 1H), 1.53-1.27 (m,
2H), 0.94 (t, J = 7.3 Hz, 3H).
Keywords: Multicomponent reactions • Synthetic methods • C1
building blocks • Thiazolidine-2-thiones
13C NMR (100 MHz, CDCl3): δ 192.4, 159.8, 138.9, 136.3, 129.8, 129.2
(q, J = 32.7 Hz), 128.2, 126.7, 125.8 (q, J = 3.8 Hz), 124.1 (q, J = 271.9
Hz), 118.1,114.6, 72.6, 55.5, 49.2, 36.5, 16.0, 14.0.
[1]
O. Devinyak, B. Zimenkovsky, R. Lesyk Curr. Top. Med. Chem. 2012,
12, 2763–2784.
[2]
[3]
F. Velàzquez, H. F. Olivo Curr. Org. Chem. 2002, 6, 303–340.
For a focused review on the synthesis of heterocycles from propargylic
precursors, see: W. Jia-Jie, Y. Zhu, Z.-P. Zhan Asian J. Org. Chem.
2012, 1, 108–129.
+
HRMS (ESI, [M+H]+) for C22H23F3NOS2 calcd. 438.1168, found
438.1177.
[4]
For relevant reviews, see: a) W.-J. Yoo, L. Zhao, C.-J. Li Aldrichimica
Acta 2011, 44, 43–51; b) L. Zani, C. Bolm Chem. Commun. 2006,
4263–4275; c) C.-J. Li Acc. Chem. Res. 2010, 43, 581–590; d) V. V.
Kouznetsov, L. Y. Vargas Méndez Synthesis 2008, 491–506; e) V. A.
Peshkov, O. P. Pereshivko, E. V. Van der Eycken Chem. Soc. Rev.
2012, 41, 3790–3807.
(Z)-3-(4-methoxybenzyl)-4-propyl-5-(thiophen-3-
ylmethylene)thiazolidine-2-thione (5v).
Yield: 219 mg (73%); brownish solid; mp 90–91 °C.
[5]
For the synthesis of secondary propargylamines, see: a) C.-J. Li, C.
Wei Chem. Commun. 2002, 268–269; b) C. Wei, J. T. Mague, C.-J. Li
Proc. Nat. Acad. Sci. 2004, 101, 5749–5754; c) J. B. Bariwal, D. S.
Ermolat’ev, E. V. Van der Eycken Chem. Eur. J. 2010, 16, 3281–3284;
d) O. P. Pereshivko, V. A. Peshkov, E. V. Van der Eycken Org. Lett.
2010, 12, 2638–2641; e) C. E. Meyet, C. J. Pierce, C. H. Larsen Org.
Lett. 2012, 14, 964–967.
1H NMR (400 MHz, CDCl3): δ 7.34-7.30 (m, 1H), 7.28 (d, J = 8.6 Hz, 2H),
7.16-7.13 (m, 1H), 7.09-7.05 (m, 1H), 6.89 (d, J = 8.6 Hz, 2H), 6.35 (d, J
= 1.4 Hz, 1H), 5.95 (d, J = 14.8 Hz, 1H), 4.75-4.70 (m, 1H), 4.13 (d, J =
14.8 Hz, 1H), 3.81 (s, 3H), 2.09-1.98 (m, 1H), 1.77-1.64 (m, 1H), 1.52-
1.24 (m, 2H), 0.92 (t, J = 7.3 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ 193.0, 159.7, 137.0, 131.8, 129.7, 127.4,
126.9, 126.3, 123.3, 114.5, 114.0, 71.8, 55.5, 49.2, 36.4, 16.0, 14.1.
[6]
a) D. S. Ermolat’ev, J. B. Bariwal, H. P. L. Steenackers, S. C. J. De
Keersmaecker, E. V. Van der Eycken Angew. Chem. Int. Ed. 2010, 49,
9465–9468; b) O. P. Pereshivko, V. A. Peshkov, D. S. Ermolat′ev, S.
Van Hove, K. Van Hecke, L. Van Meervelt, E. V. Van der Eycken
Synthesis 2011, 1587–1594; c) Y. Wang, H. Shen, Z. Xie Synlett 2011,
969–973; d) P. Fedoseev, N. Sharma, R. Khunt, D. S. Ermolat'ev, E. V.
Van der Eycken RSC Adv. 2016, 6, 75202–75206.
HRMS (ESI, [M+H]+) for C19H22NOS3+ calcd. 376.0858, found 376.0862.
(Z)-5-(2-cyclohexylethylidene)-3-(4-methoxybenzyl)-4-
propylthiazolidine-2-thione (5w).
[7]
[8]
M. J. Gainer, N. R. Bennett, Y. Takahashi, R. E. Looper Angew. Chem.
Int. Ed. 2011, 50, 684–687.
Yield: 102 mg (33%); brownish oil.
V. A. Peshkov, O. P. Pereshivko, S. Sharma, T. Meganathan, V. S.
Parmar, D. S. Ermolat’ev, E. V. Van der Eycken J. Org. Chem. 2011,
76, 5867–5872.
1H NMR (400 MHz, CDCl3): δ7.26 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.6 Hz,
2H), 5.90 (d, J = 14.8 Hz, 1H), 5.35 (td, J = 7.4, 1.6 Hz, 1H), 4.57-4.50 (m,
1H), 4.08 (d, J = 14.8 Hz, 1H), 3.80 (s, 3H), 1.99-1.76 (m, 3H), 1.74-1.54
(m, 6H), 1.46-1.04 (m, 6H), 0.97-0.83 (m, 5H).
[9]
a) O. P. Pereshivko, V. A. Peshkov, J. Jacobs, L. Van Meervelt, E. V.
Van der Eycken Adv. Synth. Cat. 2013, 355, 781–789; b) A. La-Venia,
N. S. Medran, V. Krchꢀák, S. A. Testero ACS Comb. Sci. 2016, 18,
482−489.
13C NMR (100 MHz, CDCl3): δ 193.8, 159.6, 132.6, 129.7, 127.1, 119.6,
114.4, 70.0, 55.5, 49.2, 39.2, 38.1, 35.9, 33.2, 33.1, 26.5, 26.3, 16.1,
14.1.
[10] a) M. Yang, S. J. Odelberg, Z. Tong, D. Y. Li, R. E. Looper Tetrahedron
2013, 69, 5744–5750; b) O. P. Pereshivko, V. A. Peshkov, A. A.
Peshkov, J. Jacobs, L. Van Meervelt, E. V. Van der Eycken Org.
Biomol. Chem. 2014, 12, 1741–1750.
HRMS (ESI, [M+H]+) for C22H32NOS2+ calcd. 390.1920, found 390.1917.
[11] M. J. Campbell, F. D. Toste Chem. Sci. 2011, 2, 1369–1378.
[12] A. Ranjan, R. Yerande, P. B. Wakchaure, S. G. Yerande, D. H. Dethe
Org. Lett. 2014, 16, 5788–5791.
[13] a) A. Ranjan, A. Mandal, S. G. Yerande, D. H. Dethe Chem. Commun.
2015, 51, 14215–14218; b) C. Madaan, S. Saraf, G. Priyadarshani, P.
P. Reddy, S. K. Guchhait, A. C. Kunwar, B. Sridhar Synlett 2012, 23,
1955–1959.
Acknowledgements
Support was provided by the Research Foundation – Flanders
(FWO) and by the Research Fund of the University of Leuven
(KU Leuven). A. A. N. is grateful to the European Community
Mobility Programme “Erasmus Mundus Action 2, Strand 1” for
providing a doctoral scholarship. A. A. P. is grateful to the
Erasmus Mundus External Cooperation Window (EMECW) –
Triple I for providing a doctoral scholarship. K. V. H. thanks the
Hercules Foundation (project AUGE/11/029 "3D-SPACE: 3D
Structural Platform Aiming for Chemical Excellence") and the
Research Foundation - Flanders for funding. Mass spectrometry
was made possible by the support of the Hercules Foundation of
the Flemish Government (grant 20100225–7).
[14] For the synthesis of oxazolidin-2-ones
3 involving trapping of
propargylamines 1 with CO2, see: a) P. García-Domínguez, L. Fehr, G.
Rusconi, C. Nevado Chem. Sci. 2016, 7, 3914–3918; b) M.-Y. Wang,
Q.-W.Song, R. Ma, J.-N. Xie, L.-N. He Green Chem. 2016, 18, 282–
287; c) J. Hu, J. Ma, Q. Zhu, Z. Zhang, C. Wu, B. Han Angew. Chem.
Int. Ed. 2015, 54, 5399–5403; d) J. Zhao, H. Huang, C. Qi, H. Jiang Eur.
J. Org. Chem. 2012, 5665–5667; e) H. Feng, D. S. Ermolat’ev, G. Song,
E. V. Van der Eycken Adv. Synth. Cat. 2012, 354, 505–509; f) M.
Yoshida, T. Mizuguchi, K. Shishido Chem. Eur. J. 2012, 18, 15578–
15581; g) S. Yoshida, K. Fukui, S. Kikuchi, T. Yamada, Chem. Lett.
2009, 38, 786–787; h) W.-J. Yoo, C.-J. Li Adv. Synth. Cat. 2008, 350,
1503–1506; i) Y. Kayaki, M. Yamamoto, T. Suzuki, T. Ikariya Green
Chem. 2006, 8, 1019–1021; j) R. Maggi, C. Bertolotti, E. Orlandini, C.
Oro, G. Sartori, M. Selva Tetrahedron Lett. 2007, 48, 2131–2134; k) M.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601103
European Journal of Organic Chemistry
FULL PAPER
Costa, G. P. Chiusoli, D. Taffurelli, G. Dalmonego J. Chem. Soc.,
Perkin Trans. 1 1998, 1541–1546.
1351–1357; b) K. Tomita, M. Nagano Chem. Pharm. Bull. 1968, 16,
1324–1329.
[15] For the synthesis of dioxolan-2-ones
4
involving trapping of
[18] For recent multicomponent and one-pot approaches towards
thiazolidine-2-thiones, see: a) A. Alizadeh, N. Zohreh, H. Sabahnoo, Z.
Noaparast Tetrahedron 2011, 67, 1709–1715; b) F. Nasiri, A. Zolali, M.
Ahmadiazar J. Sulfur Chem. 2014, 35, 412–417; c) K. D. Safa, M.
Alyari Synthesis 2015, 47, 256–262; d) A. Ziyaei-Halimehjani, K.
Marjani, A. Ashouri Tetrahedron Lett. 2012, 53, 3490–3492.
propargylalcohols 2 with CO2, see: a) M. Cui, Q. Qian, Z. He, J. Ma, X.
Kang, J. Hu, Z. Liu, B. Han Chem. Eur. J. 2015, 21, 15924–15928; b) R.
Ugajin, S. Kikuchi, T. Yamada Synlett 2014, 25, 1178–1180; c) Y.-B.
Wang, Y.-M. Wang, W.-Z. Zhang, X.-B. Lu J. Am. Chem. Soc. 2013,
135, 11996–12003; d) S. Yoshida, K. Fukui, S. Kikuchi, T. Yamada J.
Am. Chem. Soc. 2010, 132, 4072–4073; e) W. Yamada, Y. Sugawara,
H. M. Cheng, T. Ikeno, T. Yamada Eur. J. Org. Chem. 2007, 2604–
2607; f) J. Fournier, C. Bruneau, P. H. Dixneuf Tetrahedron Lett. 1989,
30, 3981–3982; g) H. Laas, A. Nissen, A. Nürrenbach Synthesis 1981,
958–959.
[19] For recent examples of utilizing CS2 in the multicomponent processes
leading to sulfur-containing heterocycles, see: a) T. Schlüter, A. Ziyaei
Halimehjani, D. Wachtendorf, M. Schmidtmann, J. Martens ACS Comb.
Sci. 2016, 18, 456–460; b) A. Ziyaei Halimehjani, S. Hosseinkhany
Synthesis 2015, 47, 3147–3152; c) Z. Hossaini, F. Rostami-Charati, S.
Seyfi, M. Ghambarian Chin. Chem. Lett. 2013, 24, 376–378; d) A.
Ziyaei Halimehjani, M. Hajiloo Shayegan, M. Mahmoodi Hashemi, B.
Notash Org. Lett. 2012, 14, 3838–3841.
[16] For the base-promoted synthesis of some thiazolidine-2-thiones 5 from
propargylamines 1 and CS2, see: a) J. W. Batty, B. C. L. Weedon J.
Chem. Soc. 1949, 786–789; b) V. L. Hurtubise, J. M. McArdle, S.
Naeem, A. Toscani, A. J. P. White, N. J. Long, J. D. E. T. Wilton-Ely
Inorg. Chem. 2014, 53, 11740−11748.
[20] CCDC 1502521 contains the supplementary crystallographic data for
this paper and can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html.
[17] For the synthesis of oxathiolane-2-thiones 6 from propargylalcohols 2
and CS2, see: a) D. Villemin, A. Ben Alloum Synth. Commun. 1992, 22,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201601103
European Journal of Organic Chemistry
FULL PAPER
FULL PAPER
Multicomponent reactions
Anton A. Nechaev, Anatoly A. Peshkov,
Kristof Van Hecke, Vsevolod A.
Peshkov,* Erik V. Van der Eycken*
Page No. – Page No.
A copper-catalyzed two-step one-pot procedure involving A3-coupling followed by
carbon disulfide incorporation was developed to provide a diversity-oriented access
to thiazolidine-2-thiones.
Synthesis of Thiazolidine-2-thiones
via One-Pot A3-coupling / Carbon
Disulfide Incorporation Process
This article is protected by copyright. All rights reserved.