Selective Synthesis of Non-Aromatic Five-Membered Sulfur Heterocycles from Alkynes by using a Proton Acid/N-Chlorophthalimide System

Article abstract of DOI:10.1002/anie.202010889

A multicomponent strategy to achieve two different regioselectivities from alkynes, isothiocyanates and H₂O with a proton acid/N-chlorophthalimide (NCPI) system is described to selectively obtain non-aromatic five-membered sulfur heterocycles (1,3-oxathiol-2-imines/thiazol-2(3H)-one derivatives) through multiple bond formations. The process features readily available starting materials, mild reaction conditions, broad substrate scope, good functional-group tolerance, high regio- and chemo- selectivities, gram-scale synthesis and late-stage modifications. Mechanistic studies support the proposal that the transformation process includes a combination of H₂O and isothiocyanate, free-radical formation, carbonation and intramolecular cyclization to give the products. Furthermore, the 1,3-oxathiol-2-imine derivatives possess unique fluorescence characteristics and can be used as Pd²⁺ sensors with a “turn-off” response, demonstrating potential applications in environmental and biological fields.

Full text of DOI:10.1002/anie.202010889

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Selective Synthesis of Non-Aromatic Five-Membered
Sulfur Heterocycles from Alkynes with a Proton Acid/N-
Chlorophthalimide System
Authors: Huanfeng Jiang, Wentao Yu, Baiyao Zhu, Peiqi Zhou,
Wanqing Wu, and Fuxing Shi
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202010889
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10.1002/anie.202010889
Angewandte Chemie International Edition
RESEARCH ARTICLE
Selective Synthesis of Non-Aromatic Five-Membered Sufur
Heterocycles
from
Alkynes
with
a
Proton
Acid/N-
Chlorophthalimide System
Wentao Yu,[a] Baiyao Zhu,[a] Fuxing Shi,[b] Peiqi Zhou,[a] Wanqing Wu,*[a] Huanfeng Jiang*[a]
Dedication ((optional))
Abstract: Described here is a multicomponent strategy to achieve
convenient and practical approaches for the construction of
other types of heterocycles, such as non-aromatic five-
membered sulfur heterocycles, have been rarely reported
despite of its great value. Consequently, the development of
general strategies for the selective synthesis of these
compounds from readily available materials is highly desirable,
which still remains a challange.
two different regioselectivities from alkynes, isothiocyanates and
H2O with
selectively
a
proton acid/N-chlorophthalimide (NCPI) system,
obtaining non-aromatic five-membered sulfur
heterocycles: 1,3-oxathiol-2-imines/thiazol-2(3H)-one derivatives
through multiple bond formations. The process features readily
available starting materials, mild reaction conditions, broad substrate
scope, good functional group tolerance, high regio- and chemo-
selectivities, gram-scale synthesis and late-stage modifications.
Mechanistic studies support that the transformation process includes
a combination of H2O and isothiocyanate, free radical formation,
carbonation and intramolecular cyclization to give the products.
Furthermore, the 1,3-oxathiol-2-imine derivatives with unique
fluorescence characteristics, can be served as metal ions Pd2+
sensor with “turn-off” response, showing potential applications in
environmental and biological fields.
To mechanistically solve this problem, a combination of
unsaturated carbon-carbon bond and related π electron donor is
generally necessary. Alkyne,5 an important feedstock for
petrochemical industry, has been successfully used for the
preparation of various unsaturated functional heterocycles under
metal catalysis or organocatalysis. Nevertherless, owing to
aromatic driving force6 in thermodynamics, much attention has
been paid to the efficient incorportion of alkynes in different five-
4
membered heteroaromatic rings with Π3 molecule block (‘–
N=N–N–’, ‘–N=C(–R)–N–’, ‘–O–C(-R)=N–’ and ‘–S–C(–R)=N–’)
via two carbon-heteroatom bond formations, such as triazole,7
imidazole,8 oxazole,9 and thiazole10 (Scheme 1A). Only few
methods for other unsaturated non-aromatic heterocycles from
alkynes have been reported. Gulías’ group developed a Rh(III)-
catalyzed [5+2] cycloaddition to construct benzoxepines
straightforwardly from o-vinylphenol and internal alkyne.11 Hajra
et al. achieved the formation of benzo[b][1,4]-thiazine-4-
carbonitrile through copper(I)-catalyzed oxidative coupling of 2-
amino-benzothiazole and terminal alkyne.12 Matsubara reported
the nickel-catalyzed formal [5+2] cycloaddition of five-membered
benzothiophenes and alkynes, giving seven-membered
benzothiepines.13 To the best of our knowledge, the
multicomponent synthesis of unsaturated non-aromatic
heterocycles from simple alkyne is very limited. We envision that
Introduction
Heterocycles, especially five-membered sulfur heterocycles1, are
important building blocks wildly exsited in natural products,
pharmaceuticals, and materials chemistry. For example,
Isatoribine2 is a selective agonist of TLR7; Faropenem sodium3
is an oral absorbable penem antibiotic that effectively kills
mycobacterium tuberculosis; Benzoxathiole derivative BOT-644
is a novel NF-kB inhibitor (Scheme 1). In the past decades,
many efforts have been devoted to the synthesis of various
unsaturated heteroaromatic compounds. However, the
n
the other block of Π3 (n = 3, 5, 6) generated in situ attaching to
the carbon-carbon triple bond might engage in the novel
conjugated heterocycles incorporation. However, it is
unfavorable due to the high energy barrier as well as the kinetic
instability of tortile annulenes motif. Generally, nitrogen atom
keeps variable sp2-hybrid orbital mode, while sulfur or oxygen
atom provides unhybridized p orbital with a lone pair of electrons
when they participate in the pi system to form a continuous ring.
Thus, developing potential precursors from available materials
and forming relatively stable key intermediate are two important
issues.
Given our continuous interest in alkyne chemistry,14 we
successfully developed an efficient approach to selectively
construct non-aromatic five-membered sulfur heterocycles by
the introduction of novel pi system [‘–S–C(=N-)–O–’ or –S–
Scheme 1. Examples of biologically active molecules
[a]
[b]
Key Laboratory of Functional Molecular Engineering of Guangdong
Province, School of Chemistry and Chemical Engineering, South
China University of Technology, Guangzhou 510641, China.
E-mail: cewuwq@scut.edu.cn; jianghf@scut.edu.cn
State Key Laboratory of Chemical Resource Engineering, Institute
of Computational Chemistry, College of Chemistry, Beijing
University of Chemical Technology, Beijing
Supporting information for this article is available on the WWW
under http://www.angewandte.org.
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10.1002/anie.202010889
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RESEARCH ARTICLE
Scheme 2. Context of this work
C(=O)–N(–R)–’] from the coupling of isothiocyanates and water
with simple alkynes. Under a proton acid/N-chlorophthalimide
system, isothiocyanates, an important class of organic synthetic
intermediates15, could be activated with H2O and endowed with
new reactivity (Scheme 2B). Actually, due to the weak electron-
withdrawing properties of nitrogen and sulfur heteroatoms,
isothiocyanate was used to construct the thiourea intermediate,
which would further transform to other heterocycles. Recently,
some new modes have been established by the way of the
nucleophilic attack of nitrogen/carbon atom (such as pyridine,
amine, and arene) to activate either C=S or C=N bond. In
contrast, the transformation of isothiocyanate as a double-
heteroatom-donor is rarely reported. Herein, by a “solvent switch”
controlling the conformation of the –‘S C( N) O–’ intermediate,
non-aromatic five-membered sulfur heterocycles: 1,3-oxathiol-2-
imines and thiazol-2(3H)-one derivatives are obtained
respectively (Scheme 2C). Compared with the previous
methods16,17 with harsh reaction conditions, complex reagents,
expensive catalysts, highly toxic solvents, or limited substrates,
this method could afford functionalizable vectors with good
regio- and chemo- selectivities through multiple bond formations
in one step. Moreover, potential photophysical phenomenon on
1,3-oxathiol-2-imine derivates should broaden the utility on the
detection of Pd2+ metal ion.
Results and Discussion
Our work was initiated with the reaction of diphenyl acetylene 1,
ethyl isothiocyanate 2, and water in the presence of
3
Fe2(SO4)3·xH2O and BF3·Et2O in PhF at 90 oC (Table 1, entry 1).
After 12 h, a mixture of 4 and 5 was obtained in 8% yield. Then,
a series of additive screening revealed that the combination of
N-chlorophthalimide (NCPI) and trifluoromethanesulfonic acid
(HOTf) could afford product 4 in 84% yield by avoiding
hydration/halogenation of alkyne (entries 2-7). Different catalysts,
including CuCl, Fe2SO4·7H2O, and Zn(OTf)2 were screened
(entries 8-11) and Fe2(SO4)3·xH2O was found to be the most
efficient catalyst in this system. The choice of solvents had a
significant effect on the reaction (entries 12-14). Other solvents,
such as DMSO and toluene, led to the poor yields. The addition
of MeNO2 could suppress the formation of 4, and product 5 was
obtained in 18% yield. Further examination suggested that a
cosolvent system of MeNO2/HFIP under the addition of HCOOH
increased the yield (61%) (entries 15-17). More detailed reaction
conditions (catalyst, additive, temperature, and solvent) are
displayed in Table S1. To evaluate the aromaticity or non-
aromaticity of 4 and 5, the Nucleus-Independent Chemical
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10.1002/anie.202010889
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Table 1. Optimization of the Reaction Conditions[a]
Yield (%)
Entry
Catalyst
Additive 1
Additive 2
Solvent
4[b]
6
5
2
1
2
Fe2(SO4)3·xH2O
Fe2(SO4)3·xH2O
Fe2(SO4)3·xH2O
Fe2(SO4)3·xH2O
Fe2(SO4)3·xH2O
Fe2(SO4)3·xH2O
Fe2(SO4)3·xH2O
CuCl
-
BF3·OEt2
CF3COOH
PivOH
HCOOH
HOTf
PhF
PhF
NCPI
NCPI
NCPI
NCPI
NBS
33
35
10
14
9
3
PhF
4
PhF
16
5
PhF
84 (82)
12
8
N.D.
N.D.
N.D.
3
6
HOTf
PhF
7
NHPI
NCPI
NCPI
NCPI
NCPI
NCPI
NCPI
NCPI
NCPI
NCPI
NCPI
HOTf
PhF
8
HOTf
PhF
50
65
47
20
N.D.
20
8
9
Zn(OTf)2
HOTf
PhF
N.D.
7
10
11
12
13
14
15
16[c,d]
17[c,d]
FeSO4·7H2O
-
HOTf
PhF
HOTf
PhF
5
Fe2(SO4)3·xH2O
Fe2(SO4)3·xH2O
Fe2(SO4)3·xH2O
-
HOTf
DMSO
Toluene
MeNO2
MeNO2
MeNO2/TFE
MeNO2/HFIP
N.D.
2
HOTf
HOTf
18
HCOOH
HCOOH
HCOOH
3
31
-
4
55
-
5
61 (58)
[a] Reaction conditions: 1 (0.20 mmol), 2 (0.40 mmol), H2O (0.5 mmol), catalyst (7.5 mol %), additive 1 (0.60 mmol), and additive 2 (0.20 mmol) at 90 oC for 12 h
in 2.0 mL solvent. NCPI = N-chlorophthalimide. NBS = N-bromosuccinimide. NHPI = N-hydroxyphthalimide. The value in parentheses is the isolated yield. N.D. =
Not detected. [b] The ratio of Z/E of 4 was 8.5:1, which was determined by 1H NMR. [c] Reaction conditions: 1 (0.75 mmol), 2 (0.50 mmol), H2O (1.5 mmol), NCPI
(1.0 mmol), and additive (0.50 mmol) at 105 oC for 12 h in 2.0 mL solvent. [d] The ratio was 15:1 in 1.6 mL of mixed solvent. [e] Reaction conditions: 1 (0.75 mmol),
2’ (0.50 mmol), NCPI (1.0 mmol), and 36% HCl (0.50 mmol) at 105 oC for 12 h in 3.0 mL of solvent (MeNO2: HFIP = 2:1).
Shift (NICS) index for each compound on their optimized
geometry was calculated with density functional theory (DFT)
NICS(1) index, and the computational details are provided in the
Supporting Information. The NICS(1) values of 4 and 5 are small
(-2.66 and -0.09), indicating the non-aromaticity of both five-
membered sulfur heterocycles.
substituted diphenylenes, such as 4-CH3-phenyl (36 and 44), 4-
COOCH3-phenyl (37), and 4-NO2-phenyl (38 and 45) were found
to be suitable reaction substrates. In addition, 1-phenyl-1-
propyne, 1-phenyl-1-hexyne or ethyl phenylpropiolate were also
tolerated under the standard conditions (39-41 and 46). To our
delight, the reactions of 1,4-bis(phenylethynyl)benzene and 1,4-
diphenylbuta-1,3-diyne under the optimal conditions gave the
desired products in 51% and 23% yields, respectively (42 and
43). It should be mentioned that this method has the advantages
of high regioselectivity. The crystal structure analysis of 36
indicated that oxygen was adjacent to the rich electron
aromatics. Moreover, some terminal alkynes with an aryl group
worked well in the process and converted to the target products
in moderate yields (47-53, 33-68%). The structures of 7, 36 and
49 were clarified by X-ray crystallography analysis, clearly
suggesting that the Z-configuration was the stable state and the
plane of 1,3-oxathiol was twisted to some extent. It was worthily
noted that there was Z/E configuration transformation between
alkyl-substituted groups and lone pair electrons attached to the
nitrogen atom by 1H NMR analysis, which was the nature of
imine itself.
With the optimized conditions in hand, the substrate scope for
the synthesis of 1,3-oxathiol-2-imines was investigated. As
shown in Scheme 3, the linear alkyl-substituted isothiocyanate,
such as n-hexyl (6, 68%), was found to be suitable substrate.
The desired product containing sterically substituents, including
isopropyl (7, 78%) and t-butyl (8, 47%), could be obtained in
moderate yields. However, the transformation of the substrate
with electron-withdrawing group gave a low yield (9, 37%).
Benzyl-, cyclopropyl-, cyclohexyl, and tetrahydrofurfuryl-
substituted isothiocyanates also proceeded smoothly under the
standard conditions (10-13, 75-77%). A series of isothiocyanate
derivatives with various functional groups on the phenyl ring
were also viable partners, though sterically hindered and
electronic effects resulted in a slight decrease (14-24, 37-77%).
The reaction could also tolerate a range of functionalized
alkynes, including various alkyls (25-29, 77-86%), halides (30-32,
66-71%) and thiophene (34, 38%). However, the substrates with
strong electron-withdrawing substitution or alkyl groups on both
sides showed no reactivities (33 and 35). It is found that
unsymmetrical alkynes could be also successfully applied in this
transformation, maintaining moderate to good yields. Mono-
Gratifyingly, a series of thiazol-2(3H)-one derivatives could be
successfully obtained through slightly switch of reaction
conditions in Scheme 4. Using phenyl isothiocyanate instead of
ethyl isothiocyanate with 1.0 equivalent of HCl led to a modest
increase in yield (75%, 54) (Table S2). This method displayed
good functional group tolerance for various phenyl
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10.1002/anie.202010889
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RESEARCH ARTICLE
isothiocyanates bearing CH3- (55-57), OCH3- (58), F- (59), Cl-
(60), Br- (61), I- (62), COOCH3- (63), CF3- (64), and CN- (65),
affording the corresponding products in 39-76% yields.
Additionally, isothiocyanates with alkyl chain moieties such as
isopropyl- (66), n-hexyl (67) were also suitable substrates,
transforming to the desired products in 39% and 42% yields,
respectively. However, the t-Bu functional group (68) showed no
reactivities in this system. Interestingly, cyclopropyl- (69, 41%),
cyclohexyl- (70, 43%), ether (71, 49%), ester (72, 31%), and
tetrahydrofurfuryl- (73, 36%) substituted isothiocyanates were
Scheme 3. Substrate scope[a]
a]
[
Reaction Conditions A: alkyne (0.20 mmol), isothiocyanate (0.40 mmol), H2O (0.5 mmol), Fe2(SO4)3·xH2O (7.5 mmol%), N-chlorophthalimide (0.60 mmol), and
HOTf (0.20 mmol) for 12 h in 2.0 mL solvent. Yields of isolated products are given below the products. The ratio of Z/E was determined by 1H NMR. [b] 1 mmol.
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10.1002/anie.202010889
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RESEARCH ARTICLE
well tolerated. In addition, the reaction was amenable to many
different kinds of alkynes. For examples, aromatic inner alkynes
exclusive product was formed in moderate to good yields,
respectively
(84-88,
33-68%).
Furthermore,
terminal
were efficiently transformed to the target products (74-79, 81-83), phenylacetylenes were also compatible with this catalytic system,
however, aliphatic alkyne could not react under the standard
conditions (80). When 1-phenyl-1-propyne, 1-phenyl-1-hexyne,
1,4-bis(phenylethynyl)benzene, 1-bromo-2-phenylacetylene and
1-chloro-2-phenylacetylene were used as substituents, the
albeit in low yields (89 and 90, 30% and 28%). The structures of
5 and 82 were exemplified by a single-crystal X-ray diffraction
study. To highlight the practicality of this method, the reaction
was carried out on a gram scale, affording 54 in 70% yield.
Scheme 4. Substrate scope[a]
[a]
Reaction conditions B: alkyne (0.75 mmol), isothiocyanate (0.50 mmol), N-chlorophthalimide (1.0 mmol), and 36% HCl (0.50 mmol) for 12 h in 3 mL of mixed
solvent (MeNO2: HFIP = 2: 1). [b] Conditions C: alkyne (0.75 mmol), isothiocyanate (0.50 mmol), N-chlorophthalimide (1.0 mmol), HCOOH (0.50 mmol), and H2O
(1.5 mmol) for 12 h in 1.5 mL of mixed solvent (MeNO2: HFIP = 15: 1). [c] 5 mmol. [d] (iodoethynyl)benzene instead of phenylacetylene.
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To gain some insights into the mechanism of this
transformation, a series of control experiments were conducted
(Scheme 5). First, 18O-labeling experiment was performed and
the isotopic labeling studies demonstrated that the origin of the
in 35% GC yield (eqn. 5c), which was further confirmed by NMR,
HRMS and IR.18 When using 92 under the standard conditions
instead of ethyl isothiocyanate and H2O, no product was
obtained (eqn. 5d). Both results indicated that 92 was only the
oxygen sources in the oxathiol molecules derived from H2O (eqn. side product and water was preferred to react with
5a). Next, the employment of 1,2-diphenylethan-1-one (91)
under the standard conditions could not afford the desired
product 4 or 5, suggesting that 91 might not be involved in the
transformation (eqn. 5b). In addition, compound 92 was detected
isothiocyanate rather than alkynes. Meanwhile, control
experiments revealed that HOTf and NCPI were crucial to the
reaction of isothiocyanate with H2O instead of Fe3+ ion (eqns.
5e-5g). Then, the reaction was completely quenched when
Scheme 5. Mechanistic studies
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10.1002/anie.202010889
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RESEARCH ARTICLE
3.0 equivalents of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO)
was added (eqns. 5h and 5i). And the addition of 3.0 equivalents
of 1,1-diphenylethene to the standard conditions afforded the
corresponding adducts 94 and 95 (eqns. 5j and 5k). The results
revealed that this transformation might proceed via a radical
pathway. Moreover, the EPR experiments strengthened the
hypothesis that the radical was involved in the catalytic cycle.18
Finally, the corresponding bifunctional product 97 was detected
by the replacement of H2O with isopropanol 96 as the cation
scavenger, which further demonstrated the process from free
radical to cation (eqn. 5j).
Based on experimental results and previous reports,19-21
a
plausible mechanism is proposed in Scheme 6. Under the
promotion of proton acid, H2O attacked the isothiocyanate and
intermediate A was given, which was then rapidly oxidized to
form free radical B. The isomerization of B would generate the
side product 92 with another isothiocyanate. Meanwhile, the
radical C/C’ could be trapped by alkyne to produce alkene
radical D/D’ in different solvents. The stability of alkene radical
played a key role in the regiochemistry-determining step. The
intermediate D/D’ was then oxidized to a carbocation species
E/E’, followed by the intramolecular attack of oxygen atom to
Scheme 6. Possible mechanism.
Scheme 7. The construction of polycyclic heterocycles
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Figure 1. (A) Absorption spectra and (B) photoluminescence (PL) spectra of compounds 4, 29, 37, 40 and 42 in 10-5 M THF solution. (C and F) The changes in
the PL spectra of 45 and 38 in 10-5 M THF solution upon addition of 10 equiv of the respective ions (as their OAc- salts). (D and G) The changes in the PL spectra
of 45 and 38 upon addition of Pd2+ (from 1 equiv to 300 equiv) in 10-5 M THF solution. (E and H) The changes in the PL spectra of 45 and 38 upon addition of Pd2+
(from 0.05 equiv to 30 equiv) in a mixture (fw = 95%).
give a pentacyclic ion intermediate F/F’. The final deprotonation
provided the desired product. Catalytic Fe3+ ion might stabilize
free intermediate C and facilitate the oxidation process from D to
E via single electron transfer.
Considering the potential of sulfur heterocycles in
photoelectronic fields, the corresponding spectrum
characterzations were also performed. As shown in Figures 1A
and 1B, the UV absorption and PL spectrum of 1,3-oxathiol-2-
imine derivates (4, 29, 37, 40, and 42) were investigated in dilute
THF solution. According to the conjugation expanding effect, the
maximum absorption peak has greater redshift (297-345 nm),
and the corresponding PL spectrum emits stronger yellow
fluorescence. The results indicated that these 1,3-oxathiol-2-
imines derivates showed potential photophysical properties. In
addition, N-ethyl-4-(4-nitrophenyl)-5-phenyl-1,3-oxathiol-2-imine
(38) and (Z)-4-(4-nitrophenyl)-N,5-diphenyl-1,3-oxathiol-2-imine
(45) were selected to further explore the photophysical
To further demonstrate the utilities of this method, the
modification of the multi-cyclics was attempted (Scheme 7).
Under
the
standard
conditions,
1-bromo-2-(p-
tolylethynyl)benzene (98) and phenyl isothiocyanate (2’) were
easily converted to the target products 99/101. Moreover,
[6,6,6,5]polycyclic heterocycles could be obtained with o-
bromodiaryl precursors via Pd-catalyzed intramolecular arylation
in good yields,22 providing
a versatile method for the
construction of polycyclic compounds.
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10.1002/anie.202010889
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RESEARCH ARTICLE
properties. They emit fluorescence intensity at around 560 nm in
both THF solution and water solution, indicating potential
applications in the fields of environmental protection and
biological materials.18
Keywords: non-activated alkynes • isothiocyanates • three
component reactions
• non-aromatic five-membered sulfur
heterocycles • reaction mechanisms.
Achieving the detection of metal ions is of great importance.
As a noble metal with excellent catalytic perfomance, Pd is
widely used in pharmaceutical industry. However, Pd ions
tended to accumulate in organisms. High concentrations of Pd
ions will destroy the central nervous system, leading to the
occurrence of various diseases. Therefore, it is of great
significance to develop a facile method to detect Pd ions. Owing
to obvious fluorescence intensity of compounds 38 and 45,
experiments on the selectivity towards various metal ions were
conducted (Figures 1C-1H). The PL spectra in the presence of
twelve common metal ions [Ag+, Co2+, Cu2+, Fe2+, Fe3+, K+, Li+,
Mg2+, Mn2+, Na+, Zn2+ and Pd2+ (using their OAc- salts)] in THF
solution or aqueous THF/H2O solutions (fw = 95%) are shown in
Schemes 8C-8H. Delightfully, Pd2+ is the only metal ion that
causes an obvious fluorescence quenching. Meanwhile, the
fluorescence intensity at around 560 nm declines gradually with
the increase of Pd2+ ion concentration. On the contrary, the
fluorescence intensity under other metal ions slightly increases.
Therefore, the detection of Pd2+ by the fluorescence quenching
effect of 38 or 45 can be achieved. These results indicated that
the newly formed five-membered sufur heterocycles 1,3-
oxathiol-2-imines could be served as a special fluorescent probe
for Pd2+ ion under certain conditions.
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In summary, a general method for the construction of un-
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Acknowledgements
The authors thank the National Natural Science Foundation of
China (21672072, 22071063), the National Key Research and
Development Program of China (2016YFA0602900), and the
Fundamental Research Funds for the Central Universities
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The authors declare no conflict of interest.
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Entry for the Table of Contents
Wentao Yu, Baiyao Zhu, Fuxing Shi,
Peiqi Zhou, Wanqing Wu,* Huanfeng
Jiang,* Page No. – Page No.
Selective Synthesis of Non-Aromatic
Five-Membered Sufur Heterocycles from
Alkynes
with
a
Proton
Acid/N-
Chlorophthalimide System
Under a proton acid/N-chlorophthalimide system, two classes of important non-
aromatic heterocycles (1,3-oxathiol-2-imine and thiazol-2(3H)-one) are selectively
obtained from alkynes, isothiocyanates and water through slightly switch of reaction
conditions. Readily available starting materials, broad substrate scope, gram-scale
synthesis, late-stage modification and potential metal ion Pd2+ sensor demonstrate
the utility of this method.
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