1,8-Diazabicyclo[5.4.0]undec-7-ene-Catalyzed Carbonylative Cyclization of Propargylic Alcohols with Elemental Sulfur

Article abstract of DOI:10.1002/ejoc.201701813

A carbonylation procedure involving the cyclization of propargylic alcohols with elemental sulfur was developed. With 1,8-diazabicyclo[5.4.0]undec-7-ene as the catalyst, elemental sulfur and carbon monoxide are activated and incorporated into propargylic

Full text of DOI:10.1002/ejoc.201701813

A Journal of
Accepted Article
Title: DBU-Catalyzed Carbonylative Cyclization of Propargylic Alcohols
with Elemental Sulfur
Authors: Xiao-Feng Wu, Yuya Hu, Zhiping Yin, Thomas Werner, and
Anke Spannenberg
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201701813
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10.1002/ejoc.201701813
European Journal of Organic Chemistry
COMMUNICATION
DBU-Catalyzed Carbonylative Cyclization of Propargylic Alcohols
with Elemental Sulfur
Yuya Hu,[a] Zhiping Yin,[a] Thomas Werner,[a] Anke Spannenberg,[a] Xiao-Feng Wu*[a,b]
Abstract: A novel carbonylation procedure on the cyclization of
propargylic alcohols with elemental sulfur has been developed. With
DBU as the catalyst, elemental sulfur and carbon monoxide can be
Results and Discussion
activated and incorporated into the propargylic alcohols. Good to
excellent yields of the desired sulfur containing heterocyles can be
produced at room temperature.
Initially, we choose 2-methyl-4-phenylbut-3-yn-2-ol as the model
substrate to establish this transformation. In the presence of
sulfur powder, promoted by one equivalent of DBU, using
toluene as reaction media at room temperature for 12 hours,
93% of the desired (Z)-4-benzylidene-5,5-dimethyl-1,3-
oxathiolan-2-one was isolated (Table 1, entry 1). Similar amount
of yield can be obtained with 0.5 equivalent of DBU (Table 1,
entry 2). However, no target molecule could be detected with
NEt3, NaOAc or Na2CO3 as the promotor (Table 1, entries 3-5).
The loading of DBU can even be decreased to 10 mol%,
however, only 20% of product can be obtained with 5 mol% of
DBU (Table 1, entries 6 and 7). With 10 mol% of DBU as the
catalyst, decreased yield was observed under 5 bar of CO
(Table 1, entry 8). In the testing of reaction solvents, improved
yield can be achieved in MeCN with 97% of isolated yield while
the other tested solvents were all inferior (Table 1, entries 9-13).
Then we turn back to looking for possible replacer again. Due to
the relatively low pKa of DABCO, DiPEA and DMAP, no reaction
occurred with them as the catalyst (Table 1, entries 14-16).
However, as we expected, quantitative yield of the target
product can be formed with DBN or TBD as the catalyst (Table 1,
entries 17 and 18). Moreover, the chemical structure of the
obtained product was confirmed by X-ray analysis as well
(Figure 1).
Introduction
Sulfur-containing molecules are important moieties in general
organic synthesis, and have been reported with many
applications in the materials science and also pharmaceuticals.1
Hence, numerous methodologies have been developed in recent
years for their constructions. A variety of sulfuration agents,
such as thiols, sulfides and their oxidized derivatives and so on
have been applied.2 Among them, sulfur powder (S8) is
considered as an ideal reagent due to its low cost, nontoxic,
odorless, high stability and easy-handling characters.3 Studies
have been performed for introducing sulfur atoms into organic
molecules, including multi-components coupling reactions,
polymerizations and fabrication of S-containing organometallic
complexes.4 Not surprisingly, sulfur assisted carbonylation
reactions have been studied as well.5 Various S-alkyl
carbonothioates,
2,4-dioxo-I,2,3,4-tetrahydroquinazolines,
thiocarbamateds and etc. can be produced selectively. Among
the known sulfur-containing heterocycles, 1,3-oxathiolan-2-ones
are useful building blocks in organic chemistry, polymer
sciences, and also present in biological active compounds such
as quercetin-oxathiolanone, an effective inhibitor of xanthine
oxidase.6 Carbonylative procedures using epoxides as the
substrates and catalyzed by NaH have been established as
well.7,8 Processes based on carbonyl sulfide gas (SCO) and
react with various substrates have also been achieved. Herein,
we wish to report our new results on the synthesis of 4-
alkylidene-1,3-oxathiolan-2-ones with DBU as the catalyst. Good
to excellent yields of the desired products can be formed from
propargylic alcohols and sulfur powder at room temperature.
Table 1. Carbonylative cyclization of propargylic alcohol.a
Entry
Base
Solvent
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
DMSO
Yieldb
93%c
93%
0
DBU (1 equiv.)
DBU (50 mol%)
NEt3 (50 mol%)
NaOAc (50 mol%)
Na2CO3 (50 mol%)
1
2
3
4
0
5
0
[a]
Y. Hu, Z.Yin, Dr. T. Werner, Dr. A. Spannenberg, Prof. Dr. X.-F. Wu
Leibniz-Institut für Katalyse e. V. an der Universität Rostock, Albert-
Einstein-Straβe 29a, 18059 Rostock, Germany
6
DBU (10 mol%)
DBU (5 mol%)
DBU (10 mol%)
DBU (10 mol%)
DBU (10 mol%)
88%
20%
47%d
34%
43%
E-mail: xiao-feng.wu@catalysis.de
https://www.catalysis.de/mitarbeiter/wu-xiao-feng/
7
[b]
Prof. Dr. X.-F. Wu
8
Department of Chemistry, Zhejiang Sci-Tech University, Xiasha
Campus, Hangzhou 310018, People’s Republic of China
9
Supporting information for this article is given via a link at the end of
the document.
10
THF
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10.1002/ejoc.201701813
European Journal of Organic Chemistry
COMMUNICATION
11
12
13
14
15
16
17
18
DBU (10 mol%)
DBU (10 mol%)
DBU (10 mol%)
DABCO (10 mol%)
DiPEA (10 mol%)
DMAP (10 mol%)
DBN (10 mol%)
TBD (10 mol%)
DMF
tBuOH
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
21%
8%
97%c
0
2
3
91%
98%
0
0
98%
98%
4
5
75%
74%
[a] Reaction conditions: 1a (0.5 mmol), S8 (0.25 mmol), base, solvent (2 mL),
25 oC, CO (10 bar), 12 h. [b] Yield of 2a was determined by GC using
tetradecane as internal standard. [c] Isolated yield. [d] CO (5 bar). DBU: 1,8-
diazabicyclo[5.4.0]undec-7-ene.
DABCO:
1,4-diazabicyclo[2.2.2]octane.
DiPEA: N-ethyldiisopropylamine. DMAP: N,N-dimethylpyridin-4-amine. DBN:
1,5-diazabicyclo[4.3.0]non-5-ene.
TBD:
1,3,4,6,7,8-hexahydro-2H-
pyrimido[1,2-a]pyrimidine.
6
7
8
85%
73%
71%
Figure 1. X-ray crystal structure analysis of product 2a.9
With the best reaction conditions in our hand, different
substituted propargylic alcohols were tested with DBU as the
catalyst subsequently (Table 2). To our delight, good to excellent
yields of various 4-alkylidene-1,3-oxathiolan-2-ones were
obtained from the corresponding propargylic alcohols
successfully. Both secondary and tertiary alcohols are applicable.
However, no desired product could be detected with primary
propargylic alcohol, such as 3-phenylprop-2-yn-1-ol. The
substrate added decomposed. Concerning the reaction pathway,
based on literature,5,7 we believe the reaction proceeds via the in
suit formation of SCO from CO and S8 (Scheme 1).
9
61%
0%
10
[a] Reaction conditions: DBU (10 mol%), propargylic alcohols (0.5 mmol), S8
(0.25 mmol), MeCN (2 mL), CO (10 bar), 25 oC, 12 h, isolated yield.
Table 2. DBU-catalyzed carbonylative cyclization of propargylic alcohols.a
Entry
1
Substrate
Product
Yield
97%
Scheme 1. Proposed reaction mechanism.
Conclusions
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10.1002/ejoc.201701813
European Journal of Organic Chemistry
COMMUNICATION
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In conclusion, in this short communication, we described our
new results on DBU-catalyzed carbonylative cyclization of
propargylic alcohols with elemental sulfur. The desired 4-
alkylidene-1,3-oxathiolan-2-ones were produced in good to
excellent yields at room temperature.
Experimental Section
Under an open atmosphere, a 4 mL screw-cap vial was charged with
elemental sulfur (S8, 0.25 mmol), propargylic alcohol (0.50 mmol), MeCN
(2 mL), DBU (10 mol%) and an oven-dried stirring bar. The vial was
closed by Teflon septum and phenolic cap and purged with Ar through a
needle. Then the vial was fixed in an alloy plate and put into Paar 4560
series autoclave (300 mL). At room temperature, the autoclave was
flushed with carbon monoxide for three times and 10 bar of carbon
monoxide was charged. The autoclave was placed on a heating plate
equipped with magnetic stirring and an aluminum block. The reaction
was stirred at room temperature for 24 hours. Afterwards, the autoclave
was removed and the pressure was carefully released. After removal of
solvent under reduced pressure, pure product was obtained by column
chromatography on silica gel (eluent: pentane/ethyl acetate = 50:1).
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Acknowledgements
The analytic supports of Dr. W. Baumann, Dr. C. Fisher, S.
Buchholz, and S. Schareina are gratefully acknowledged. We
also appreciate the general supports from Professors Matthias
Beller and Armin Börner in LIKAT.
Keywords: carbonylation • cyclization • sulfur • heterocycle
synthesis • 1,3-oxathiolan-2-ones
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European Journal of Organic Chemistry
COMMUNICATION
COMMUNICATION
Carbonylation
Yuya Hu, Zhiping Yin, Thomas Werner,
Anke Spannenberg, Xiao-Feng Wu*
Page No. – Page No.
DBU-Catalyzed Carbonylative
Cyclization of Propargylic Alcohols
with Elemental Sulfur
A novel carbonylation procedure on the cyclization of propargylic alcohols with
elemental sulfur has been developed. With DBU as the catalyst, elemental sulfur
and carbon monoxide can be activated and incorporated into the propargylic
alcohols. Good to excellent yields of the desired 1,3-oxathiolan-2-ones can be
produced at room temperature.
This article is protected by copyright. All rights reserved.