DBU-promoted carbonylative synthesis of 1,3-oxathiolan-2-ones from propargylic alcohols with TFBen as the CO source

Article abstract of DOI:10.1039/c7ob03145a

A DBU-promoted carbonylative cyclization of propargylic alcohols with sulfur was developed. Various 1,3-oxathiolan-2-ones were produced in 61-98% yields under mild conditions in the absence of metal catalysts. TFBen (benzene-1,3,5-triyl triformate) as an efficient and solid CO surrogate and S₈ as an ideal sulfur source were employed and incorporated.

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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DBU-Promoted Carbonylative Synthesis of 1,3-Oxathiolan-2-ones
from Propargylic Alcohols with TFBen as the CO source
Jun Ying,a Chao Zhou,a and Xiao-Feng Wu*a,b
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A DBU-promoted carbonylative cyclization of propargylic alcohols reactor systems have been designed and applied as well, such
with sulfur has been developed. Various 1,3-oxathiolan-2-ones as two-chamber system and In-Ex tube.15 In addition, TFBen
were produced in 61-98% yields under mild conditions in the (benzene-1,3,5-triyl triformate), a solid, stable, efficient, and
absence of metal catalysts. TFBen (benzene-1,3,5-triyl triformate) convenient CO surrogate, has recently been developed in our
as an efficient and solid CO surrogate and S8 as an ideal sulfur group.16,17 Herein, we wish to report our newly developed
source were employed and incorporated.
procedure for 1,3-oxathiolan-2-ones preparation with TFBen
as the CO source. With DBU as the promotor, propargylic
alcohols were carbonylatively cyclized with sulfur, which is an
inexpensive and odorless sulfurization reagent, under mild
reaction conditions.18,19 Notably, no metal catalyst is needed
here.
1,3-Oxathiolan-2-ones are useful building blocks in organic1
and polymer sciences,2 as well as important structural motifs
in biologically active compounds such as quercetin-
oxathiolanone,3 an effective inhibitor of xanthine oxidase.
Consequently, extensive efforts have been devoted to the
study of a convenient synthesis of 1,3-oxathiolan-2-ones.
There are a couple of methods have been reported including
the cyclization of t-hydroxyl thiol with phosgene, the reaction
of epoxides with sulfur and carbon monoxide (CO), the
coupling reaction of epoxides with carbonyl sulfide (COS), the
base-catalyzed cyclization of the imidazolide derivative, and
the acid-assisted cyclization of 2-hydroxyethyl thiocarbonate
(Scheme 1). It is obvious that these methods have some
obvious drawbacks: including (1) the use of toxic gases
(phosgene, CO, COS, etc.); (2) the use of odorous sulfurization
reagents (thiols, etc.); (3) limited substrates scope due to the
harsh reaction conditions (high temperature and/or high
pressure).4-12
On the other hand, carbonylation chemistry is an attractive
topic from both academia and industry.13 For the conveniences
on small scale applications, many efforts have been attracted
on in-situ CO generation, due to the high toxicity and
flammable of CO gas.14 Based on the researches from different
research groups, a number of CO surrogates have been
developed such as metal carbonyls, formaldehyde, alcohols,
formic acid, formates, formamides, etc. Additionally, new
Scheme 1. Selected examples for the synthesis of 1,3-
oxathiolan-2-ones.
Initially, we investigated the reaction of propargylic alcohol
1a with TFBen and sulfur in the presence of base, and the
results are summarized in Table 1. Treatment of compound 1a
with S8 (0.5 equiv.), TFBen (1.0 equiv.) and DBU (2.0 equiv.) at
30 oC afforded the product 2a in 49% yield as a Z-isomer (Table
1, entry 1). Raising the reaction temperature to 60 oC
enhanced the yield of 2a (79%; Table 1, entry 2). When the
amount of DBU was reduced to 1.0 equivalent, the yield was
dramatically decreased to 58% (Table 1, entry 3). No product
was observed without the addition of DBU, which indicates
that DBU as a base is crucial to initiate this sulfur-involved
a.Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou
ïíììíôU tꢀ}‰oꢀ[• wꢀ‰µꢁo]ꢂ }( /Z]vꢃ
b.Leibniz-Institut für Katalyse e. V. an der Universität Rostock, Albert-Einstein-
Strate 29a, 18059 Rostock, Germany, E-mail:xiao-feng.wu@catalysis.de
Electronic Supplementary Information (ESI) available: [general comments, general
procedure, analytic data and NMR spectrums]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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carbonylative cyclization (Table 1, entry 4). Also, decreasing carbocycle unit were tested, excellent yields up to 98% of
the amount of S8 (0.25 equiv.) or shortening the reaction time products 2o-2q were achieved. Furthermore, the reactions of
(24 h) gave a remarkably decreased yield (Table 1, entries 5 propargylic alcohols with linear alkyl substituents (R2, R3 = alkyl)
and 6). Then, a variety of solvents were examined (Table 1, proceeded to give the corresponding products 2r-2u in 81-97%
entries 7-12). It shows that the reaction using CH3CN provided yields. Gratifyingly, treatment of a thiophene substituted
an excellent yield (over 99%, isolated yield 87%), while other propargylic alcohol led to the formation of product 2v in 79%
solvents (DMSO, DMF, THF, DCM, and 1,4-dioxane) were yield. Compound with no substituent on the alkyne carbon (R1
inferior. Moreover,
a series of bases were tested and = H) can also cyclize to form product 2w in 85% yield.
decreased yields were obtained in comparison with DBU
(Table 1, entries 13-16). Notably, the yield of the desired Scheme 2 Carbonylative synthesis of 1,3-oxathiolan-2-ones.a
product decreased to 61% when 0.5 equivalent of TFBen was
used.
Table 1 Screening of optimal reaction conditions a
Entry
S8
Base
Solvent
Toluene
Toluene
Toluene
Yieldb
49%c
79%
1
2
3
0.5 eq
0.5 eq
0.5 eq
2.0 eq DBU
2.0 eq DBU
1.0 eq DBU
58%
4
0.5 eq
ş
Toluene
0
5
6
7
8
9
0.25 eq
0.5 eq
0.5 eq
0.5 eq
0.5 eq
2.0 eq DBU
2.0 eq DBU
2.0 eq DBU
2.0 eq DBU
2.0 eq DBU
Toluene
Toluene
DMSO
DMF
51%
48%d
83%
9%
THF
86%
>99%
(87%)e
0
10
0.5 eq
2.0 eq DBU
CH3CN
11
12
13
0.5 eq
0.5 eq
0.5 eq
2.0 eq DBU
2.0 eq DBU
2.0 eq Et3N
DCM
Dioxane
CH3CN
51%
60%
a Reaction conditions: substrate
1 (0.5 mmol), S8 (0.5 equiv.),
TFBen (1.0 equiv.), DBU (2.0 equiv.), CH3CN (2 mL), 60 oC, 48 h.
14
15
16
0.5 eq
0.5 eq
0.5 eq
2.0 eq DABCO
2.0 eq tBuOK
2.0 eq NaOH
CH3CN
CH3CN
CH3CN
86%
12%
0
On the basis of the above experimental results and
previous reports,18,19
a
possible mechanism for this
carbonylative cyclization of propargylic alcohol with S8 is
proposed in Scheme 3. Initially, S8 was activated by DBU and
a Reaction conditions: 1a (0.5 mmol), solvent (2 mL), TFBen (1
equiv.), 60 oC, 48 h. b The yield of 2a was determined by GC
analysis using n-dodecane as internal standard. c 30 oC. d 24 h. e
Isolated yield.
the sulfur anion
monoxide, generated in situ from TFBen, gives the carbonyl
sulfide . Elimination of can afford the key intermediate COS.
In the presence of DBU, deprotonation of propargylic alcohol
followed by the nucleophilic attack of its oxygen anion to COS
generates the carbonothioate . Subsequent intramolecular
cycloaddition of leads to the formation of the final product
The stereoselectivity of product (Z-isomer) can be explained
3 was formed. The reaction of 3 with carbon
4
4
1
Subsequently, various propargylic alcohols
1
were
5
prepared and subjected to the optimal reaction conditions.
The results are shown in Scheme 2. It was found that the
electron-donating para-substituted propargylic alcohols 2b-2e
gave yields relatively higher than that of compounds
containing electron-withdrawing para-substituents 2f-2g. The
reactions of substrates bearing ortho- and meta-Me group
afforded the desired product 2i and 2j in good yields.
Compounds having an alkyl group on the triple bond could
undergo carbonylative cyclization smoothly to give the desired
products 2k-2n in high yields (73-87%). When substrates with a
5
2.
2
by a backside attack of the thionate anion to a carbon-carbon
triple bond coordinating with the bulky base DBU. Notably,
two sulfur atoms from S8 can be transformed before it forms a
stable complex with DBU.
2 | J. Name., 2012, 00, 1-3
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Scheme 3. Possible reaction mechanism.
In conclusion, we have developed a facile and convenient
approach for the synthesis of 1,3-oxathiolan-2-ones via
carbonylative cyclization of propargylic alcohols with sulfur
promoted by DBU. The reactions proceed under mild
conditions, affording Z-isomer products in high yields (61-98%).
This method has some obvious advantages, including metal
catalyst-free; with TFBen as a benign CO surrogate; with S8 as a
desirable sulfur source. Further investigation will be focused
on synthetic application and mechanistic study of this strategy.
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Acknowledgements
The authors thank the financial supports from NSFC
(21472174), Zhejiang Natural Science Fund for Young Scholars
(LQ18B020008) and Zhejiang Natural Science Fund for
Distinguished Young Scholars (LR16B020002). The preliminary
studies from Yuya Hu in LIKAT are appreciated. We also
appreciate the general supports from Professors Matthias
Beller and Armin Börner in LIKAT.
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