Insight into the role of the counteranion of an imidazolium salt in organocatalysis: A combined experimental and computational study

Article abstract of DOI:10.1002/chem.201002839

N-Heterocyclic carbenes (NHCs) can serve as very reactive nucleophilic catalysts and exhibit strong basicity. Herein, we initiate a combined experimental and computational investigation of the NHC-catalyzed ring-closing reactions of 4-(2-formylphenoxy)but

Full text of DOI:10.1002/chem.201002839

FULL PAPER
DOI: 10.1002/chem.201002839
Insight into the Role of the Counteranion of an Imidazolium Salt in
Organocatalysis: A Combined Experimental and Computational Study
Siping Wei, Xi-Guang Wei, Xiaoyu Su, Jingsong You,* and Yi Ren*[a]
Abstract: N-Heterocyclic carbenes
(NHCs) can serve as very reactive nu-
cleophilic catalysts and exhibit strong
basicity. Herein, we initiate a combined
experimental and computational inves-
tigation of the NHC-catalyzed ring-
closing reactions of 4-(2-formylphen-
oxy)but-2-enoate derivatives 1 to un-
cover the relationship between the
counteranion of an azolium salt, the
nucleophilicity and basicity of the car-
bene species, and the catalytic perfor-
mance of the carbene species by taking
imidazolium salts IPr·HX (X=counter-
anion, IPr=1,3-bis(2,6-diisopropylphe-
nyl)imidazol-2-ylidene) as the repre-
sentative precatalysts. The plausible
mechanisms of IPr-mediated ring-clos-
ing reactions have been investigated by
using DFT calculations. The hydrogen-
accepting ability, assigned as the basici-
ty of the counteranion of IPr·HX and
evaluated by DFT calculations, is cor-
related with the rate of deprotonation
of C2 in IPr·HX, which could be moni-
tored by the capture of the free car-
bene formed in situ with elemental
sulfur. The deprotonation of C2 in
IPr·HX with a more basic anion gives
rise to a higher concentration of the
free carbene and vice versa. At a rela-
tively low concentration, IPr prefers to
show a nucleophilic character to induce
the intramolecular Stetter reaction. At
a relatively high concentration, IPr pri-
marily acts as a base to afford benzo-
furan derivatives. These data compre-
hensively disclose, for the first time,
that the counteranions of azolium salts
significantly influence not only the cat-
alytic activity, but also possibly the re-
action mechanism.
Keywords: basicity · counteranions ·
N-heterocyclic carbenes · nucleo-
philicity · organocatalysis
Introduction
ionic scaffold to impart specific chemical properties in orga-
nocatalysis,[3] the contribution of the anionic partner is
almost logically ignored, except for sporadic examples prob-
ably because the real catalysts (i.e., NHCs) are easily avail-
able in situ by the deprotonation of C2 in the corresponding
conjugate azolium salts. Is the anion just an appendage to
tune the solubility or to facilitate the purification of the
salts?
Scattered examples have casually mentioned that the
counteranions of salts influence the catalytic activity of the
NHCs generated in situ. In particular, in the case of some
asymmetric transformations, both stereoselectivity and yield
are significantly dependent on the anions.[7] It is well known
that NHCs are not only very reactive nucleophilic catalysts,
but also possess strong basicity.[8] What is the relationship
between the counteranions of the azolium precatalysts, the
nucleophilicity and basicity of the carbene species, and the
catalytic performance? Herein, we wish to reveal the essen-
tial role of the counteranions of the salts through a com-
bined experimental and computational study on the NHC-
catalyzed ring-closing reactions of the 4-(2-formylphenoxy)-
but-2-enoate derivatives 1 depicted in Scheme 1. Thus, a rel-
atively comprehensive investigation demonstrates for the
first time that the counteranions can not only influence the
catalytic activity of NHCs, but also determine the reaction
routes, depending on either a nucleophilic or base-induced
pathway.
Over recent decades, N-heterocyclic carbenes (NHCs) have
grown from being regarded as chemical curiosities[1] to ver-
satile ligands in transition-metal-mediated processes,[2] nu-
cleophilic organic catalysts,[3] and reagents in organic reac-
tions.[4] Recently, the crucial role of the counteranion of an
azolium salt used is starting to attract attention in the coor-
dination mode of a NHC ligand to the metal ion.[5] More-
over, calculation and spectroscopy studies have uncovered
À
the interaction between the C2 H bond of the imidazolium
cation and counteranion in ionic liquids and have demon-
strated that variation of the anion moiety may modify the
physicochemical properties and intermolecular forces be-
tween the salts.[6] However, although much work has been
devoted to the design and development of the azolium cat-
[a] S. Wei, X.-G. Wei, Dr. X. Su, Prof. Dr. J. You, Prof. Dr. Y. Ren
Key Laboratory of Green Chemistry and Technology of Ministry of
Education College of Chemistry, and
State Key Laboratory of Biotherapy
West China Hospital, Sichuan University
29 Wangjiang Road, Chengdu 610064 (PR China)
Fax : (+86)28-85412203
E-mail: jsyou@scu.edu.cn
jsyou@scu.edu.cn
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201002839.
Chem. Eur. J. 2011, 17, 5965 – 5971
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5965

Scheme 1. NHC-catalyzed synthesis of chromene and benzofuran derivatives.
Results and Discussion
Table 1. Ring-closing reactions of 1a promoted by imidazol-2-ylidenes.[a]
Investigation of the ring-closing reactions of (E)-methyl 4-
(2-formylphenoxy)but-2-enoate (1a) promoted by imidazol-
À
2-ylidenes: As an extensively studied C C bond-forming an-
nelation through umpolung reactivity of carbonyl com-
pounds, the intramolecular Stetter reaction has been pro-
moted by numbers of structurally simple and commercially
available thiazole-,[9] triazole-,[10] or imidazoline-based carbe-
nes.[7c] However, to the best of our knowledge, successful ex-
amples of the intramolecular Stetter reaction mediated by
imidazole-based carbenes are unknown so far.[11] In this con-
text, we initially employed a typical catalytic system gener-
ated in situ to carry out the intramolecular Stetter reaction
of 1a in the presence of well-established imidazolium salts
(i.e., IAd·HX, IMes·HX, and IPr·HX; X=counteranion,
Entry
Precatalyst/catalyst
Yield [%][b]
3+4
2
5
[c]
1
2
3
4
5
6
7
8
9
10
11
12
13
IPr·HPF6
43
IPr·HBF4
IPr·HCl
IMes·HPF6
IMes·HBF4
IMes·HCl
IAd·HPF6
IAd·HBF4
Iad·HCl
94
21
72
88
17
66
62
19
79 (90)[d]
12
81
IAd=1,3-bis(adamantyl)imidazol-2-ylidene,
bis(2,4,6-trimethylphenyl)imidazol-2-ylidene,
IMes=1,3-
IPr=1,3-
35
80
bis(2,6-diisopropylphenyl)imidazol-2-ylidene). Surprisingly,
IPr (0.1 mol%)[e]
IPr (0.5 mol%)[e]
IPr (1 mol%)[e]
IPr (5 mol%)[e]
24
9
5
65
73
54
45
[a] Reactions were performed on a 1.0 mmol scale with 5 mol% of imida-
zolium salt and 5 mol% of K2CO3 in THF (4 mL) under N2 at room tem-
perature for 15 h. [b] Yield of isolated product based on 1a. [c] Traces of
benzofuran derivatives could be observed within 20 h. [d] Reaction
time=28 h. [e] Yield of isolated free carbene (IPr) as the catalyst.
we found that the counteranions of the salts greatly influ-
enced the efficiency of substrate conversion and the catalyt-
ic mechanism of the ring-closing reaction of 1a (Table 1).
Among the salts investigated, the catalytic activity of the
hexafluorophosphate salts appeared to be inferior to those
of the corresponding chloride and tetrafluoroborate salts.
By taking IPr·HX as a representative example, IPr·HPF6 af-
forded 3,4-dihydro-2H-chromene (2a) through an umploung
nucleophilic pathway in a moderate yield of 43%, which
demonstrated the first imidazol-2-ylidene-catalyzed intramo-
lecular Stetter reaction (Table 1, entry 1). In sharp contrast,
both IPr·HBF4 and IPr·HCl gave excellent yields of the ben-
We next investigated this type of intramolecular coupling
in the presence of the isolated free carbene IPr. In general,
the catalyst concentration (loading) is correlated with the ef-
ficiency of substrate conversion. Herein, we did surprisingly
find that the catalyst concentration impacted not only the
conversion of substrate, but also the pathway of the ring-
closing reaction. The Stetter reaction was carried out in
24% yield at a lower loading of IPr (0.1 mol%, 2.5ꢁ
10À4 molLÀ1; Table 1, entry 10). As the concentration of IPr
went up, the Stetter reaction was suppressed in concomi-
tance with an increasing yield of benzofuran derivatives 3a,
4a, and 5a (Table 1, entries 10–13). By using 5 mol% of IPr
(5ꢁ10À2 molLÀ1), the umploung nucleophilic pathway was
restrained completely. Thus, we concluded that IPr preferred
to exhibit nucleophilicity at lower concentration and basicity
at higher concentration. Provided that the concentration of
the carbene is related with the rate of the deprotonation of
C2 in its conjugate salt, we rationalized that the concentra-
tion of the carbene might be taken as a medium to elucidate
the relationship between the counteranion of imidazolium
salt and the catalytic performance.
zofuran derivatives through
a base-mediated pathway
(Table 1, entries 2 and 3). More interestingly, IPr·HCl could
further provoke dehydration of 3a to provide benzofuran
derivative 5a in 90% yield (Table 1, entry 3). The imidazoli-
um salts IAd·HX and IMes·HX did not afford 2a, but the
benzofuran derivatives (Table 1, entries 4–9). The ratios of
3a, 4a, and 5a obtained were also dramatically dependent
on the anions of the salts. These findings stimulated us to in-
itiate an investigation of the role of the counteranions of the
imidazolium salts by taking IPr·HX as the representative
precatalyst.
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Effect of the Anion of Azolium Precatalysts on Catalytic Performance
FULL PAPER
Exploration of the plausible pathways for the ring-closing
reactions: The reaction pathways of the IPr-mediated ring-
closing reactions of 1a were proposed on the basis of both
experimental inspection and molecular modeling validation.
The mechanism of the Stetter reaction has been well-estab-
lished by experimental and computational research.[12] As il-
lustrated in Scheme 2 (the left cycle), IPr initiated a nucleo-
ACHTUNGTRENNUNG
the Supporting Information).
These results showed that 5a is
a thermodynamically controlled
product, whereas 4a is a prod-
uct of kinetic control.
Computational investigation of
the basicity of the counteran-
ions of imidazolium salts: Imi-
dazolium salts are composed of
cations and anions. The electro-
static interactions and hydro-
gen-bonding interactions be-
À
tween the C2 H unit of the
imidazolium ring and the anion-
ic partner are two essential fea-
tures. The effects of the interac-
Scheme 2. The concise, plausible mechanisms of IPr-mediated ring-closing reactions of 1a.
tions of the ion pairs on physi-
philic attack on the aldehyde moiety of 1a to generate the
well-known Breslow intermediate I, which further under-
went the intramolecular ring-closing reaction between the
enolamine and the Michael acceptor to provide the Stetter
product 2a. On the other hand, IPr acted as a base to ab-
stract the C4 proton of 1a with an overall barrier of DG=
116.5 kJmolÀ1 to form the intermediate III, which subse-
quently went through a ring-closing process to afford methyl
3-(3-hydroxy-2,3-dihydrobenzofuran-2-yl)acrylate
(3a),
which might be assigned as a mixture of two diastereoiso-
mers (see Figure S1 and Table S1 in the Supporting Infor-
mation).
Further dehydroxylation of benzofuran derivative 3a with
the aid of basic IPr led to the formation of (E)-methyl 3-
(benzofuran-2-yl)acrylate (5a) at room temperature
(Scheme 3), which afforded a new simple route to a valuable
substrate for the synthesis of the major inhibitory neuro-
transmitter (g-aminobutyric acid) in the central nervous
system.[13] The structure of 5a was confirmed by X-ray crys-
tallographic analysis (Figure 1, right).[14] In addition, benzo-
furan derivative 3a could also partially isomerize to form a
mixture of (E)- and (Z)-methyl 3-(3-hydroxybenzofuran-2-
Figure 1. ORTEP drawing of the molecular structures of 4c (top) and 5a
(bottom). Thermal ellipsoids are set at the 50% probability level.
cal properties, such as thermal stability, solubility, electrolyt-
ic conductivity, and spectroscopic analysis, have drawn in-
creasing attention in the study
of imidazolium ionic liquids.[6,15]
However, to our knowledge, in-
depth investigations of the ef-
fects of the counteranion on
chemical properties in organo-
Scheme 3. The IPr-induced isomerization and elimination of 3a.
catalysis are scarce hitherto. It
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5967

J. You, Y. Ren et al.
is well known that in a typical catalytic system a free car-
bene is formed in situ through deprotonation of the imida-
zolium salt with a base, and the loss of the counterion and
the corresponding 3a,b, 4a,b, and/or 5a,b derivatives were
promoted, except by IPr·HPF6. This exception hinted that
the deprotonation of C2 in IPr·HPF6 in situ led to a low con-
centration of IPr, which was beneficial for the intramolecu-
lar Stetter mechanism.
À
fission of the labile acidic C2 H unit is involved. Recent
studies have indicated that the acidity of the 2-position in
imidazolium ionic liquids is dependent not only on the cat-
ionic moiety, but also on the nature of the counteranion.[16]
Thus, the basicity of the counteranion in concordance with
its hydrogen-accepting ability may significantly influence the
rate of deprotonation. The hydrogen-accepting ability of the
counteranion could be estimated through investigation of
the activation energy for the hydrogen-abstraction reaction
by using DFT calculations with the 6-31++G** basis sets.
The huge substituent group (2,6-diisopropylphenyl) on the
nitrogen atom of IPr·HX was simplified as a methyl group
(see Equation S1 and Table S3 in the Supporting Informa-
tion). The basicity of the counteranions could then be re-
To further inspect the role of the counteranions, 1d was
taken as a model substrate in the ring-closing reactions. Nat-
ural population analysis (NPA) of C2–C4 in 1a and 1d
showed that the charges on the carbon atoms in 1d were
less negative than those in 1a, thus predicting that the reac-
tivity of C4 in 1d is lower than that of 1a (see Table S4 in
the Supporting Information). Thus, 1d might be unfavorable
for the base-mediated ring-closing reaction, which signifi-
cantly clarified the distinctness of the catalytic performance
of IPr·HX. Indeed, the smooth conversion of 1d required
20 mol% of IPr·HX, whereas 1a was converted into the cor-
responding benzofuran derivatives with a loading of less
than 5 mol% precatalyst. In the presence of IPr·HCl, 1d
quantitatively afforded the benzofuran derivatives involving
82 and 18% of 3d and 5d, respectively (Table 3, entry 4). In
addition, the isomerization of 3d to 4d could be hardly ob-
À
flected by evaluating the ability to abstract C2 H from the
imidazolium cation. The estimated DG values for hydrogen
abstraction are shown in Table 2. The Gibbs free energy of
1
served from the H NMR spectroscopic analysis carried out
Table 2. Calculated relative energies for hydrogen abstraction reactions.
in situ. These results were attributed to the methyl substitute
at the C3 position. More interestingly, IPr·HO3SCH3,
IPr·HNO3, IPr·HOTs, IPr·HBF4, and IPr·HO2CCF3 exhibit-
ed a similar catalytic performance and gave rise to 3d in a
good yield (81–96%; Table 3, entries 8, 12, 16, 20, and 24).
Although these imidazolium salts encountered the base-
Counteranion
DG
[kJmolÀ1
Counteranion
DG
[kJmolÀ1
]
G
]
E
À
ClÀ
452.1
495.2
501.2
509.1
529.8
CF3SO3
580.7
583.8
607.5
662.9
À
À
CH3SO3À
ClO4
À
CF3CO2
OTSÀ
BF4À
PF6
À
À
À
NO3
mediated route, surprisingly, the salts with ClO4 , CF3SO3 ,
À
and PF6 counterions afforded the Stetter product, although
in low yield (Table 3, entries 28, 32, and 36). Therefore, the
counteranions did determine the catalytic route.
IPr·HCl is DG=452.1 kJmolÀ1, which is 43.1 kJmolÀ1 lower
than that of IPr·HO3SCH3. While the DG values of IPr·-
HO3SCF3 and IPr·HClO4 are close, IPr·HO3SCH3, IPr·-
HO2CCF3, IPr·HOTs (OTsÀ =para-toluenesulfonate), and
IPr·HNO3 exhibit slightly different values in a range from
DG=495.2 to 529.8 kJmolÀ1. The Gibbs free energy value
Correlation between the counteranion and the catalytic per-
formance of IPr·HX: As described above, the basicity of the
counteranions could determine the rate of forming free IPr.
The deprotonation of C2 in IPr·HX with a more basic
anion, such as ClÀ, produced a high concentration of IPr,
which led to the base-mediated ring-closing reaction to
afford the benzofuran derivatives (Tables 2 and 3). In con-
trast, the deprotonation of C2 in IPr·HX with a less basic
–1
of IPr·HPF6 is DG=662.9 kJmolÀ1, which is 210.8 kJmol
higher than that of IPr·HCl. Thus, the basicity (hydrogen-ac-
cepting ability) of the counteranions decrease in the follow-
À
ing
order:
ClÀ >CH3SO3À >CF3CO2À >OTsÀ >NO3
>
À
À
CF3SO3À >ClO4À >BF4À >PF6 .
anion, such as PF6 , gave rise to a low concentration of IPr,
which induced the Stetter reaction.
Experimental study of the catalytic performance of IPr pre-
pared in situ: To investigate the role of the counteranions of
imidazolium salts, the IPr-catalyzed ring-closing reactions of
1 were carried out through the deprotonation of IPr·HX in
situ with the weak base K2CO3 in THF. A control experi-
ment indicated that 20 mol% of K2CO3 was incapable of
promoting these ring-closing reactions, thus elucidating that
IPr served as a main promoter. Table 3 clearly illustrated
that the counteranions of IPr·HX showed a correlation not
only with the catalytic activity, but also with alternative re-
action pathways depending on either a nucleophilic or base-
driven mechanism. When 1c was induced to convert into
three benzofuran derivatives, including 3c, 4c, and 5c, by all
of IPr·HX salts investigated, the conversions of 1a,b into
To advance the understanding of relationship between the
counteranion and the rate of the deprotonation of C2 in
IPr·HX, 1H NMR spectroscopic analysis was employed to
monitor the concentration of IPr formed in situ by the de-
protonation of C2 in IPr·HX with different counteranions in
the presence of K2CO3. However, all attempts were unsuc-
cessful due to a partial overlap of the peaks of IPr·HX and
IPr. Fortunately, IPr could almost be completely captured
by elemental sulfur both at high and low concentrations
(0.05 and 2.5ꢁ10À4 m, respectively) to form thione 6 in excel-
lent yields (>99 and 95%, respectively; Table 4, entries 1
and 2), which provided an alternative opportunity to detect
the rate of deprotonation of C2 in IPr·HX. Thus, IPr·HX
was treated with an equivalent amount of K2CO3 in THF
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Effect of the Anion of Azolium Precatalysts on Catalytic Performance
Table 3. Synthesis of chromane and benzofuran derivatives catalyzed by IPr·HX.[a]
FULL PAPER
C2 in IPr·HX and further influ-
enced the catalytic perfor-
mance.
The experimental results, in-
cluding the observations of the
catalytic experiments and the
detection of the concentration
of IPr formed in situ, were
nearly in accordance with the
computational
investigation,
except for IPr·HBF4. It is
known that electronic effects
(e.g., electron distribution and
79 electrostatic interaction) and
Entry
Precatalyst
IPr·HCl
Substrate
Yield [%][b]
2
3+4 (3/4)[c]
5
1
2
3
4
5
6
7
8
9
1a
1b
3a+4a
21 (1:1)
28 (1:2.8)
28 (1:2.4)
82
5a
5b
5c
5d
5a
5b
5c
3b+4b
3c+4c
3d
72
steric factors (e.g., the presence
of wing-tip groups on the heter-
ocyclic moiety and the size and
1c
71
18
12
1d[d]
1a
3a+4a
3b+4b
3c+4c
3d
85 (1.9:1)
79 (1.5:1)
41 (1:2.4)
96
position of the anion units) may
affect the interactions between
the imidazolium cation and
counteranion.[5,6] Therefore, it is
reasonable to assume that the
1b
20
59
IPr·HO3SCH3
IPr·HNO3
1c
1d[d]
1a
3a+4a
3b+4b
3c+4c
3d
93 (4:1)
89 (2.6:1)
40 (1:2.1)
95
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
1b
5b
5c
9
59
1c
À
1d[d]
1a
deviation of the BF4 ion might
3a+4a
3b+4b
3c+4c
3d
95 (10.5:1)
96 (3.6:1)
52 (1:1.5)
88
be mainly attributed to the
simplification of the 2,6-diiso-
propylphenyl units with methyl
groups at the two nitrogen
atoms of the imidazolium ring
in the DFT calculation with the
6-31++G** basis sets.
1b
IPr·HOTs
1c
5c
5c
5c
5c
5c
5c
48
51
47
51
40
37
1d[d]
1a
3a+4a
3b+4b
3c+4c
3d
94 (5:1)
96 (3.3:1)
49 (1:2.1)
85
1b
IPr·HBF4
1c
1d[d]
1a
3a+4a
3b+4b
3c+4c
3d
82 (44:1)
85 (10:1)
52 (1:1.6)
81
1b
IPr·HO2CCF3
IPr·HClO4
IPr·HO3SCF3
IPr·HPF6
1c
1d[d]
1a
Conclusion
3a+4a
3b+4b
3c+4c
95 (14.9:1)
94 (4.6:1)
48 (1:1.2)
1b
We have comprehensively in-
vestigated the role of the coun-
teranion of the imidazolium salt
in NHC-catalyzed ring-closing
reactions of 4-(2-formylphenox-
1c
1d[d,e]
1a
2d
48
3a+4a
3b+4b
3c+4c
83 (27.3:1)
90 (19:1)
58 (1:1)
1b
1c
1d[d,e]
1a
2d
2a
2b
42
43
40
y)but-2-enoate derivatives
through combined experimental
and computational means.
1
1b
1c
3c+4c
41 (2.1:1)
1d[d]
2d
17
These results disclose that the
counteranions significantly in-
fluence not only the catalytic
activity, but also possibly the re-
action mechanism. The basicity
of the counteranion of IPr·HX,
[a] Reactions were performed on a 1.0 mmol scale with 5 mol% of ligand and 5 mol% of K2CO3 in THF
(4 mL) under N2 at room temperature for 15 h. [b] Yield of isolated product based on 1. [c] The ratio of 3/4
was determined by 1H NMR spectroscopic analysis of the reaction mixture. [d] IPr·HX=20 mol%, K2CO3 =
20 mol%. [e] Traces of benzofuran derivatives were observed.
for 2 hours, and the resulting filtrate containing IPr·HX and
IPr was transferred into a solution of sulfur in THF to give
thione 6. The yields of 6 illustrated the following order of
the rate of deprotonation of C2 in IPr·HX: IPr·HCl>
IPr·HO3SCH3 >IPr·HO2CCF3 >IPr·HBF4 >IPr·HOTs=
which has been evaluated by calculating the Gibbs free
energy change at the B3LYP/6-31++G** level for hydro-
gen abstraction from the imidazolium cation is indeed corre-
lated with the rate of the deprotonation of C2 in IPr·HX.
The more basic counteranion results in a faster rate of for-
mation of the free carbene. The rate of the deprotonation of
C2 in IPr·HX can be monitored by the capture of the free
carbene generated in situ with elemental sulfur. At a rela-
tively high concentration, IPr mainly acts as a base to medi-
IPr·HNO3 >IPr·HO3SCF3 >IPr·HClO4 >IPr·HPF6,
which
was in accordance with the observations of the catalytic ex-
periments (Table 4). These results clearly demonstrated that
the counteranions determined the rate of deprotonation of
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5969

J. You, Y. Ren et al.
Table 4. Detection of the concentration of IPr by the reaction with ele-
mental sulfur.[a]
THF (4 mL) at room temperature. The reaction mixture was stirred at
the same temperature for 15 h, poured into water, and extracted twice
with ethyl acetate. The combined organic layers were evaporated and the
resulting residue was purified cautiously by column chromatography on
silica gel with ethyl acetate/petroleum ether (1:7) as the eluent to provide
the corresponding product.[17]
General procedure for detection of the amount of IPr by the reaction
with sulfur: A flame-dried Schlenk tube with a magnetic stirring bar was
charged with dry K2CO3 (27.6 mg, 0.2 mmol) and imidazolium salt
IPr·HX (0.2 mmol) in dry THF (4 mL) at room temperature. After the
mixture was stirred for 2 h, the resulting filtrate was transferred through
a double-ended needle to a solution of sulfur in THF (2 equiv, 1 mL).
The reaction mixture was stirred for 24 h, the solvent was removed by
evaporation, and the resulting residue was purified by column chroma-
tography on silica gel with ethyl acetate/petroleum ether (1:10) as the
eluent to provide thione 6.
Entry
Reactant
Yield of 6 [%][b]
1
2
3
4
5
6
7
8
9
IPr (5ꢁ10À2 m)[c]
IPr (2.5ꢁ10À4 m)[c]
IPr·HCl
IPr·HO3SCH3
IPr·HO2CCF3
IPr·HBF4
IPr·HOTs
IPr·HNO3
IPr·HO3SCF3
IPr·HClO4
IPr·HPF6
>99
95
54
45
32
30
29
29
20
15
5
10
11
Acknowledgements
[a] Reagents and conditions: IPr·HX (0.2 mmol) and K2CO3 (0.2 mmol)
in THF (4 mL) were stirred at room temperature for 2 h. The resulting
filtrate was transferred to a solution of sulfur (2 equiv) in THF, and the
reaction mixture was stirred at room temperature for another 24 h.
[b] Yield of isolated product. [c] Isolated IPr was used.
This work was supported by grants from the National NSF of China
(Nos. 21025205, 20972102, 20772086, 21021001 and 20702035), Doctoral
Foundation of Education Ministry of China (20090181110045), PCSIRT
(No. IRT0846), and the National Basic Research Program of China (973
Program, 2011CB808600). We thank the Centre of Testing & Analysis
(Sichuan University) for the NMR spectroscopic, mass-spectrometric,
and elemental analyses and X-ray measurements.
ate a ring-closing reaction to afford benzofuran derivatives.
In the case of a relatively low concentration, IPr primarily
exhibits the nucleophilic character of a classic carbene spe-
cies to catalyze the Stetter reaction. The experimental obser-
vations are closely in accordance with the computational in-
vestigations. Thus, the counteranions of the imidaolium salts
are not just for decoration, but significantly influence cata-
lytic performance in organocatalysis. These findings give us
inspiration to not only take into account the azolium frame-
work, but also pay attention to the effect of the anionic part-
ner in the design of azolium-mediated organocatalysis.
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General procedure for the preparation of IPr·HX by anion exchange:
Method A: A tube with a magnetic stirring bar was charged with
IPr·HCl (425 mg, 1 mmol) and water (20 mL) at room temperature, fol-
lowed by the addition of an aqueous solution of NH4·BF4 (1.0m, 2 mL,
2 mmol). After the reaction mixture was stirred for 10 min, the solid was
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IPr·HBF4 was obtained as colorless crystals in 95% yield after purifica-
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NH4·BF4 for the preparation of IPr·HPF6.
Method B: A tube with a magnetic stirring bar was charged with IPr·HCl
(425 mg, 1 mmol) in water (20 mL) at room temperature, followed by the
addition of AgClO4 in water (1.0m, 2 mL, 2 mmol). After the mixture
was stirred for 10 min, the solid was removed by filtration, washed with
acetone, and the filtrate was concentrated. The obtained white solid was
dried in vacuo. IPr·HClO4 was obtained as colorless crystals in 93% yield
after purification by crystallization from acetone. The corresponding
silver salts were used instead of AgClO4 for the preparation of IPr·
HO3SCH3, IPr·HO2CCF3, IPr·HOTs, IPr·HNO3, and IPr·HO3SCF3.
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Chem. Eur. J. 2011, 17, 5965 – 5971

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Received: October 2, 2010
Published online: April 19, 2011
Chem. Eur. J. 2011, 17, 5965 – 5971
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5971