Regio- and Stereoselective Synthesis of Dithiocarbonates under Ambient and Solvent-Free Conditions

Article abstract of DOI:10.1002/cctc.201600242

Herein, we report on the utilization of readily available lithium tert-butoxide as an efficient catalyst for the addition of carbon disulfide to terminal and internal epoxides under ambient conditions. Notably, the reaction proceeds regio- and stereoselectively. By applying the optimized conditions, 14 terminal and internal epoxides were converted. The desired cyclic dithiocarbonates were isolated in yields up to 95 % after simple filtration over silica. NMR spectroscopy experiments to identify the mode of activation were performed, and they indicated activation of carbon disulfide by the catalyst. The reaction of cis-2,3-butyleneoxide gave only the trans-dithiocarbonate, whereas the conversion of (R)-propylen oxide gave the respective thiocarbonate stereoselectively as one enantiomer (>99 % ee) in 87 % yield.

Full text of DOI:10.1002/cctc.201600242

DOI: 10.1002/cctc.201600242
Communications
Regio- and Stereoselective Synthesis of Dithiocarbonates
under Ambient and Solvent-Free Conditions
[
a]
Johannes Diebler, Anke Spannenberg, and Thomas Werner*
Herein, we report on the utilization of readily available lithium
tert-butoxide as an efficient catalyst for the addition of carbon
disulfide to terminal and internal epoxides under ambient con-
ditions. Notably, the reaction proceeds regio- and stereoselec-
tively. By applying the optimized conditions, 14 terminal and
internal epoxides were converted. The desired cyclic dithiocar-
bonates were isolated in yields up to 95% after simple filtra-
tion over silica. NMR spectroscopy experiments to identify the
mode of activation were performed, and they indicated activa-
tion of carbon disulfide by the catalyst. The reaction of cis-2,3-
butyleneoxide gave only the trans-dithiocarbonate, whereas
the conversion of (R)-propylen oxide gave the respective thio-
carbonate stereoselectively as one enantiomer (>99%ee) in
Notably, cyclic dithiocarbonates 2 have attracted much at-
[
5]
tention owing to their radioprotective activity and utilization
[
6]
in polymer synthesis. Despite the complexity of this reaction,
there have been several excellent accounts on the develop-
ment of catalytic systems for the conversion of epoxides
1 with carbon disulfide. This includes reports on catalysts
[
7]
[3]
based on Lewis and Brønsted bases, alkali metal salts, as
[
4,8]
well as transition-metal complexes.
Even though advances
have been made, those catalysts often require cocatalysts, sol-
vents, long reaction times, and/or elevated temperatures. The
latter leads to unwanted byproducts, for example, trithio- or
poly(thio)carbonates. Thus, the selective synthesis of cyclic di-
thiocarbonates 2 from epoxides 1 and carbon disulfide under
mild and solvent-free conditions is still a challenging task. Re-
cently, we reported on various efficient one- and two-compo-
nent catalytic systems for the conversion of carbon dioxide
8
7% yield.
[
9]
In recent years, efforts have been intensified to utilize carbon
with epoxides. As an extension of this work, we were inter-
ested in the selective addition of carbon disulfide to epoxides
1 to yield dithiocarbonates 2. Notably, the carbon center of
dioxide as a C building block, because it is regarded as readily
1
[
1]
available, inexpensive, and an abundant carbon source. In
this context, atom-efficient carbon dioxide fixation and valori-
zation into cyclic carbonates is an elegant and frequently stud-
CS is more electrophilic than the carbon center of carbon di-
2
oxide and is, therefore, more reactive. Thus, the coupling of
[
2]
ied reaction. Carbon disulfide is an isoelectronic analogue of
carbon dioxide. It can be produced through the reaction of,
for example, charcoal from plants and sulfur from power plant
fuel gases, and thus, carbon disulfide can also be considered
CS with epoxides 1 might be conducted under comparatively
2
milder reaction conditions. As a test reaction, we chose the ad-
dition of CS to 1,2-butyleneoxide (1a), which was studied at
2
room temperature with a reaction time of 5 h to identify suita-
ble catalysts for this reaction (Table 1). Initially, we utilized cata-
as a sustainable and inexpensive C building block. In contrast
1
to the coupling of carbon dioxide with epoxides 1, the atom-
economic reaction with carbon disulfide leads to complex re-
action mixtures, especially at elevated temperatures owing to
lysts that are known to facilitate the conversion of CO with
2
[
9c–e,g]
epoxides (Table 1, entries 1–3).
These bifunctional onium
salts proved to be very active in CO coupling reactions at ele-
2
[3]
[9d,g]
oxygen/sulfur scrambling (Scheme 1). This phenomenon was
observed in the pioneering works of this field by Endo, North,
vated temperatures.
However, the application of tri-n-butyl-
(2-hydroxyethyl)ammonium iodide and tri-n-butyl-(2-hydroxye-
thyl)phosphonium iodide at room temperature did not result
in the formation of desired cyclic dithiocarbonate 2a (Table 1,
entry 1). Similar results were obtained with the two-compo-
nent catalyst system consisting of triethanolamine and potassi-
[
3,4]
and co-workers.
um iodide, which showed high activity in the coupling of CO
2
[
9e]
to epoxides (Table 1, entry 2). In the presence of tetra-n-bu-
tylphosphonium bromide and tetra-n-butylammonium bro-
mide, again no conversion to desired product 2a was ob-
served (Table 1, entry 3). Given that the conversion of 1a into
cyclic dithioester 2a was not possible in the presence of those
2
Scheme 1. Products obtained by the cycloaddition of epoxides with CS .
catalysts under the test conditions, we envisioned CS activa-
2
tion by applying potassium tert-butoxide, which subsequently
[
10]
[
a] J. Diebler, Dr. A. Spannenberg, Dr. T. Werner
Leibniz-Institut für Katalyse an der Universität Rostock e.V.
Albert-Einstein Str. 29a, 18059 Rostock (Germany)
E-mail: thomas.werner@catalysis.de
enabled the conversion with 1a. Unfortunately, no conver-
sion was observed in the presence of 5 mol% of the alkoxide
(
Table 1, entry 4). LiBr, which was reported by Endo et al. as
a catalyst for this reaction, gave 21% conversion and desired
Supporting Information and the ORCID identification number(s) for the
author(s) of this article can be found under http://dx.doi.org/10.1002/
cctc.201600242.
[
3]
product 2a with 76% selectivity (Table 1, entry 5). We con-
ceived the dual activation of epoxide 1a by LiBr and CS by an
2
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Table 1. Catalyst screening for the addition of CS
n.
2
to 1a as a test reactio-
2
Table 2. Evaluation of the substrate scope for the coupling of CS with
epoxides 1 under optimized conditions.
[a]
[a]
Entry
Catalyst
Conversion of 1a
Selectivity to 2a
[%]
Entry
1
Substrate
Product
Yield of 2
[%]
Yield of 3
[%]
[
b]
[b]
[b]
[c]
[
%]
[
c]
c]
1
2
3
4
5
6
7
8
9
1
[HO(CH
[HO(CH
2
)
)
2
2
PBu
3
]I
11 (11)
0 (0)
0
0 (0)
0
76
81
2
3
] N/KI
0
0 (4)
3
1a
1b
1c
86
92
7
7
[
[Bu
4
P]Br
KOtBu
LiBr
LiOtBu, LiBr
LiOtBu
LiOtBu
21
>99
>99
>99
>99
>99
2
3
78
88
80
16
84
–
1
[
[
d]
[e]
[d]
4
d,f]
[g]
LiOtBu
LiOtBu
[
d,h]
0
90
5
6
1d
1e
93
92
4
–
[
2
a] Reaction conditions: 1a (2.5 mmol), catalyst (5 mol%), CS (1.2 equiv.),
THF (2.5 mL), RT, 5 h. [b] Conversions (of 1a) and selectivity (to 2a) were
determined by GC with n-hexadecane as an internal standard. [c] For the
conversion and selectivity in parentheses the respective ammonium salt
was used. [d] Solvent-free. [e] Thiirane 3a was observed as the only by-
product in 8% yield. [f] Catalyst (2.5 mol%). [g] Besides a 5% yield of 3a,
7
1 f
93
5
2
an oligomeric byproduct was obtained. [h] CS (2 equiv.).
8
9
1g
1h
89
90
–
4
alkoxide. Thus, we combined LiBr and lithium tert-butoxide
and observed a significant improvement in selectivity to 81%
(
Table 1, entry 6). Notably, similar results were obtained in the
absence of LiBr (Table 1, entry 7). The selectivity was further
improved by performing the reaction under solvent-free condi-
tions by utilizing 5 mol% of lithium tert-butoxide (Table 1,
entry 8). Thiocarbonate 2a was obtained with 88% selectivity,
whereas the only observed byproduct was thiirane 3a. Even
though full conversion was achieved in the presence of
1
0
1i
1j
95
65
1
11
24
2
.5 mol% of lithium tert-butoxide, the formation of considera-
ble amounts of an oligomeric byproduct was observed
Table 1, entry 9). Nevertheless, the best result was achieved by
utilizing 5 mol% of lithium tert-butoxide as the catalyst and
equivalents of CS , which yielded 90% of desired product 2a
[e]
1
2
1k
48 (23)
37 (65)
(
13
14
–
69
–
6
[f]
1
l
2
2
(
Table 1, entry 10).
[
5
a] Reaction conditions: 1 (2.5 mmol), LiOtBu (5 mol%), CS
h. [b] Yield of isolated product. [c] Determined by H NMR spectroscopy.
2
(2 equiv.), RT,
Subsequently, we evaluated the substrate scope for terminal
1
and internal epoxides 1a–l (Table 2). Under the optimized reac-
tion conditions, desired products 2a–l were isolated by simple
filtration over silica gel. Terminal alkyl-substituted epoxides
[
d] t=24 h, yield of trithiocarbonate: 5%. [e] cis-2,3-Butyleneoxide (cis-
1k); the values in parentheses were obtained for the trans isomer (trans-
k). [f] T=908C, t=24 h.
1
1
a–c were efficiently converted with CS into corresponding
2
dithiocarbonates 2a–c in high yields up to 92% (Table 2, en-
tries 1–4). Full conversions of 1,2-epoxybutane (1a) and 1,2-ep-
oxyhexene (1b) were achieved after 5 h and yields of 86% for
was obtained in 5% yield. The reaction of benzyl-substituted
oxirane 1d with CS showed high selectivity towards respec-
2
2
a and 92% for 2b were obtained (Table 2, entries 1 and 2). In
tive dithiocarbonate 2d, which was isolated in 93% yield
(Table 2, entry 5). Furthermore, tert-butyl glycidyl ether (1e)
was converted with excellent selectivity into 2e (Table 2,
entry 6). In this case, the formation of thiirane 3e was not ob-
served. Moreover, unsaturated substrates 1 f–h were convert-
ed, and desired unsaturated cyclic dithiocarbonates 2 f–h were
obtained in yields ꢀ89% (Table 2, entries 7–9). Glycidyl metha-
crylate derivative 2g is of particular interest, because it might
be an interesting monomer for novel polymers and materials
both cases, corresponding thiirane 3 was observed in 7%
yield. The application of propylene oxide (1c) as the substrate
yielded 2c in only 16% yield after 5 h (Table 2, entry 3). How-
ever, prolonging the reaction time from 5 to 24 h resulted in
full conversion of 1c, and 2c was isolated in 84% yield
(
Table 2, entry 4). In this case, byproduct 3c was formed in
only 1% yield. However, respective trithiocarbonate 4c, which
was presumably obtained by the conversion of 3c with CS2,
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[
11]
(
Table 2, entry 8). Yet, sterically more demanding substrates
h and 1i, that is, those disubstituted at the a-carbon atom,
1
were converted to give 2h in 90% yield and 2i in 95% yield,
respectively (Table 2, entries 9 and 10). Furthermore, we em-
ployed internal oxiranes 1j and 1k to gain insight into the
mechanism and the stereochemistry of the reaction (Table 2,
entries 11 and 12). Cyclohexene oxide (1j) was fully converted
within 5 h to give cyclic xanthogenate 2j in 65% yield and
thiirane 3j in 24% yield (Table 2, entry 11). Additionally, small
amounts of oligomeric byproducts were observed. The config-
uration of product 2j is, in accordance with literature and
spectroscopic data of the isolated compound, identified as
[
3,8a]
trans-2j.
desired product 2k was isolated as the trans stereoisomer in
8% yield (Table 2, entry 12). Respective byproduct 3k was ob-
Upon employing cis-2,3-butylene oxide (cis-1k),
1
3
Figure 2. Sections of the C NMR spectra in [D
6
]DMSO: A) neat CS
2
,
B) LiClO /CS (1:1), C) neat LiOtBu, and D) LiOtBu/CS
4
2
2
(1:1).
4
tained as the cis isomer in 37% yield. Notably, trans-1k gave
cis-2k and trans-3k in yields of 23 and 65%, respectively. The
inversion of the configuration of one of the two stereogenic
carbon centers by applying cis-2,3-butylene oxide (cis-1k) indi-
cates nucleophilic attack of an in situ formed xanthogenate at
the oxirane. Finally, we studied the conversion of highly substi-
tuted substrate 1l. By applying the standard reaction condi-
tions, no conversion to the desired product was observed.
However, at a higher temperature and with a longer reaction
time (908C, 24 h), 2l was isolated in 69% yield. After recrystalli-
zation of 2l, crystals suitable for X-ray crystallographic analysis
were obtained (Figure 1). Owing to strong ring strain, the
newly fused heterocycle of 2l differs clearly from planarity.
teristic chemical shift of the quaternary carbon atom at d=
192.5 ppm. As expected, no shift occurred in the presence of
the non-nucleophilic lithium salt LiClO compared to pure CS2
4
in [D ]DMSO (Figure 2B). Those observations are in accordance
6
[
3]
13
with the literature. Figure 2C depicts the C NMR spectrum
of neat LiOtBu. The resonances at d=35.3 and 65.9 ppm are
assigned to the primary carbon atoms and the quaternary
carbon atom of the tert-butyl group, respectively. A significant
13
downfield shift in the C NMR spectra for the resonances of
CS and the ÀC(CH ) moiety as well as an upfield shift for the
2
3
resonances of the methyl groups ÀC(CH ) for a 1:1 mixture of
3
LiOtBu/CS is observed. This distinctly indicates the in situ acti-
2
vation of CS by the alkoxide.
2
We postulate that the reaction proceeds through an SN2
mechanism. Thereby, nucleophilic attack of in situ formed xan-
thogenate 8 occurs most probably at the sterically less hin-
dered carbon atom of epoxide 1. Consequently, the conversion
of enantiomerically pure (R)-1c gave product ent-2c with
>
99% enantiomeric excess (ee) (Scheme 2). This suggests an
S 2 mechanism, as an S 1 reaction at the higher substituted
N
N
carbon atom would lead to partial racemization and, thus, to
a lower enantiomeric excess value of the product.
Figure 1. Molecular structure of 2l in the crystal. Only one of the four mole-
cules of the asymmetric unit is depicted. Displacement ellipsoids are drawn
at the 30% probability level. (See the Supporting Information for crystallo-
graphic data).
The activation of CS in this reaction by various nucleophiles,
2
8a]
[
[12]
[13]
2
Scheme 2. Stereo- and regioselective conversion of (R)-1b with CS .
for example, amines, amidines, and carbenes, has been
reported. Thus, we assume initial activation of CS by nucleo-
2
philic attack of tert-butyl alkoxide and thus the in situ forma-
tion of xanthogenate 8 (see also Scheme 3). To obtain evidence
for this hypothesis, we initially converted lithium tert-butoxide
On the basis of the conversion of cis-2,3-butyleneoxide (cis-
1k), we propose the mechanism depicted in Scheme 3. The ini-
tial step is activation of CS by LiOtBu. Subsequent nucleophilic
2
with equimolar amounts of CS to yield 8. Unfortunately, all at-
attack of formed xanthogenate 8 leads to 9. This step might
also be facilitated by additional Lewis acid activation of the ox-
irane by the lithium ion, similar to the activation by bimetallic
aluminum(salen) complexes reported by North and co-worker-
2
tempts to isolate lithium xanthogenate 8 were not successful.
1
3
Furthermore, we performed C NMR spectroscopy experiments
with equimolar mixtures of CS and lithium tert-butoxide as
2
[
8a]
well as non-nucleophilic LiClO in [D ]DMSO (Figure 2). Fig-
s. However, the attack occurs from the backside of the oxir-
4
6
13
ure 2A shows the C NMR spectrum of neat CS with a charac-
ane ring, and as a result, 9 is formed with the relative stereo-
2
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Nutzung von CO : Technologien für Nachhaltigkeit und Klima-
2
schutz, grant 01RC1004A).
Keywords: carbon disulfide · cycloaddition · dithiocarbonate ·
homogenous catalysis · stereoselectivity
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Acknowledgements
Received: February 29, 2016
Revised: March 29, 2016
T.W. is grateful to the Federal Ministry of Research and Education
(
BMBF) for financial support (Chemische Prozesse und stoffliche
Published online on May 25, 2016
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