The dual role of ionic liquid BmimBF4, precursor of N-heterocyclic carbene and solvent, in the oxidative esterification of aldehydes

Article abstract of DOI:10.1016/j.tet.2013.06.014

Room temperature ionic liquid BmimBF₄ (1-butyl-3- methylimidazolium tetrafluoroborate) has been utilized in the N-heterocyclic carbene-catalyzed oxidation of aldehydes to yield esters. In the presence of MnO₂ as oxidant and of DBU and caesium carbonate as bases, aromatic, heteroaromatic and aliphatic esters have been isolated in good to excellent yields. The recyclability of the used ionic liquid along with the excess of inorganic reagents has been proved. The simple and cheap BmimBF₄ ionic liquid played the dual role of precatalyst and solvent. This is the first time that such a reaction has been carried out with an ionic liquid as solvent.

Full text of DOI:10.1016/j.tet.2013.06.014

Tetrahedron 69 (2013) 8088e8095
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
The dual role of ionic liquid BmimBF4, precursor of N-heterocyclic
carbene and solvent, in the oxidative esterification of aldehydes
,
a
b
c,
Isabella Chiarotto a , Marta Feroci , Giovanni Sotgiu , Achille Inesi
*
*
a Dept. Scienze di Base e Applicate per l’Ingegneria (SBAI), Sapienza University of Rome, via Castro Laurenziano, 7, I-00161 Rome, Italy
b Dept. Ingegneria, University of Roma Tre, via Vasca Navale, 84 I-00146 Rome, Italy
c Via Antelao, 9, I-00141 Rome, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Room temperature ionic liquid BmimBF4 (1-butyl-3-methylimidazolium tetrafluoroborate) has been
utilized in the N-heterocyclic carbene-catalyzed oxidation of aldehydes to yield esters. In the presence of
MnO2 as oxidant and of DBU and caesium carbonate as bases, aromatic, heteroaromatic and aliphatic
esters have been isolated in good to excellent yields. The recyclability of the used ionic liquid along with
the excess of inorganic reagents has been proved. The simple and cheap BmimBF4 ionic liquid played the
dual role of precatalyst and solvent. This is the first time that such a reaction has been carried out with an
ionic liquid as solvent.
Received 15 March 2013
Received in revised form 23 May 2013
Accepted 3 June 2013
Available online 29 June 2013
Keywords:
Esters
N-Heterocyclic carbene
Aldehydes
Ó 2013 Elsevier Ltd. All rights reserved.
Umpolung
Room temperature ionic liquid
Oxidations
1. Introduction
recent years, as it allows the oxidation and CeO bond formation in
one-pot.8
In the last decade, an increasing demand for ecofriendly and
economical strategies for organic synthesis, performed without
stoichiometric reagents, has spurred an extensive study directed to
the design of new organocatalysts.
Procedures based on the NHC-catalyzed oxidation of aldehydic
substrates to esters have been developed recently. The syntheses
are performed in solution (THF, CH2Cl2, CH3CN, DMSO, DMF, etc. as
solvents) containing an aldehyde in the presence of a hetero-
azolium salt (as precatalyst), a base (DBU or NEt3, able to deprot-
onate the heteroazolium salt in the C2 position), an oxidant (MnO2,
azobenzene, O2, quinones, etc.) and an alcohol or an alkyl halide.9
The NHC-catalyzed anodic oxidation of aldehydes to yield esters
has been recently reported.10 The possible utilization of suitable
additives (K2CO3, Cs2CO3, NaHCO3) has been reported by some
authors.11
Accordingly, N-heterocyclic carbenes (NHCs)1 have attracted
enormous interest in organocatalysis2 as well as in organometallic
chemistry.3 These NHCs, initially regarded as laboratory curiosi-
ties,4 are easily obtainable via deprotonation of several hetero-
azolium salts under mild conditions.
NHCs are able to induce the umpolung (i.e., the inversion of the
polarity) in the structure of aldehydes, opening up new synthetic
routes. The reaction between an NHC and an aldehyde gives rise to
the formation of the ‘Breslow intermediate’,5 an acylation equiva-
lent in which a nucleophilic carbonyl carbon atom (umpolung) is
present. Many synthetic procedures have been reported based on
the functionalization of this acyl anion equivalent; representative
examples include: the benzoin condensation, the Stetter reaction,
cross-condensation of enals and aldehydes.6
In the same way, functionalized aldehydes (a,b-unsaturated- or
a-halo-aldehydes) have been converted to esters via internal redox
reaction catalyzed by NHC in the absence of an exogenous oxi-
dant.12 This last methodology unfortunately limits the range of
useful aldehydes to a-functionalized ones and precludes the use,
for example, of benzaldehydes.
In any case, the yields of the isolated products are strongly
affected by pKb of the base, the presence of additives as well as by
the nature of the solvent and the oxidant and the structure of the
NHC (and of the precatalyst), the latter being the main influencing
factor. In fact, it seems that each different reaction requires a par-
ticular NHC, often purposely synthesized, rendering the use of
NHCs impractical in general.
Along with the classical synthesis of esters,7 the oxidative es-
terification of aldehydes has received increasing attention during
* Corresponding author. E-mail addresses: isabella.chiarotto@uniroma1.it
(I. Chiarotto), achille.inesi@uniroma1.it (A. Inesi).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.06.014

I. Chiarotto et al. / Tetrahedron 69 (2013) 8088e8095
8089
The systematic utilization of volatile and/or toxic organic sol-
vents (VOCs) should be avoided and synthetic procedures, which
reduce the use of VOCs should be considered a priority in modern
organic synthesis.13 The use of room temperature ionic liquids
(RTILs), in place of VOCs, has been reported by many authors as an
alternative.14
Following these results, we evaluated the influence of the molar
ratio base/aldehyde on the efficiency of the reaction. By increasing
the value of this ratio, significant improvements have been
observed in the yields of the ester (Table 1, entriy 3 vs 1 and entry
5 vs 2).
In order to understand the role of the base, inorganic bases
(Cs2CO3, K2CO3), instead of the organic base DBU, were added to the
BmimBF4 solution, which showed that the efficiency of the reaction
is strongly affected by the nature of the counter-ion (Csþ or Kþ). In
fact, ester 3aa was isolated in good yields using Cs2CO3, but no
product was formed in the presence of K2CO3 (Table 1, entries 6 and
7 vs 8).
When DBU and Cs2CO3 were used together, the efficiency of the
procedure appeared better than when using only DBU (Table 1,
entry 9 vs 5), showing a synergy of the two bases. The yield of
isolated ester was strongly influenced by the molar ratio oxidant/
aldehyde (Table 1, entries 10e13 vs 4 and 9). However, when
a smaller amount of oxidant was used with both DBU and Cs2CO3,
the reaction proceeded with an excellent yield (Table 1, entry 12).
This synthesis of esters via the oxidation of aldehydes is, in any
case, related to the deprotonation of the heteroazolium cation to
NHC, to the coupling of NHC with the aldehyde yielding the Breslow
intermediate and, finally, to the ability of the NHC to activate the
structure of the aldehyde, present in the Breslow intermediate,
versus the oxidative process.11 Moreover, the efficiency of the
synthesis is affected by the competition between the reaction of the
Breslow intermediate with the oxidant (yielding the ester) and
with a further molecule of aldehyde (yielding benzoin) (Scheme 2).
Our preliminary results suggest that the organic base DBU is
strong enough to deprotonate the ionic liquid BminBF4 yielding the
corresponding NHC, while the reactivity (and solubility) of the
anionic inorganic base CO23ꢁ is influenced by the counter-ion. In
addition, the NHC thus generated leads to the Breslow in-
termediate, in which the aldehyde is activated enough to be oxi-
dated by MnO2. Azobenzene, under the same conditions, proved to
be ineffective.
The exceptionally low vapour pressure of the ionic liquids en-
courage their use as solvents, which are not air-pollutant and in the
majority of the cases they can be recycled in the same reaction and
reused many times, thus abating their costs. Moreover, the use of
ionic liquids as solvents can drastically change the outcome of
a reaction due to their ionic nature, which can accelerate the rate
of reactions with ionic or dipolar intermediates and retard re-
actions with intermediates, which do not present a charge sepa-
ration. Concerning this, we have considered the easily available and
cheap imidazolium room temperature ionic liquid BmimBF4
(1-butyl-3-methylimidazolium tetrafluoroborate) and studied the
synthesis of esters via NHC-catalyzed oxidation of aldehydes, based
on the double role of BmimBF4 as precatalyst (in the presence of
a suitable base) and solvent (in place of VOCs). Moreover, we have
evaluated the reaction medium recyclability.
2. Results and discussion
Initially, to verify the efficiency of BmimBF4 in the dual role of
precatalyst and solvent, we have investigated the reactivity of
benzaldehyde 1a and an alcohol, with base and either MnO2 or
azobenzene (classical oxidants, previously utilized by other authors
in the procedures carried out in organic solvents, Scheme 1).9,11
O
O
BmimBF4, base
R'
R
H
R
O
oxidant, R'OH 2
1
3
Therefore, a solution of DBU or a mixture DBU/Cs2CO3 (as base)
and MnO2 (as oxidant) in BmimBF4 (as solvent and precatalyst)
could be regarded as suitable conditions for the synthesis of esters
via oxidation of aldehydes in environmental friendly conditions
(i.e., in the absence of volatile and/or toxic organic solvent, except
during work up/recycling).
Scheme 1. NHC-catalyzed oxidation of aldehyde 1 to ester 3.
Accordingly, 0.5 mL of BmimBF4, containing an organic base
(DBU, 0.2 mmol) was added to a mixture of benzaldehyde 1a
(0.5 mmol), MnO2 or azobenzene (2.5 mmol) and methanol
(1.5 mmol). The workup of the resulting solution, stirred under
a nitrogen atmosphere (25 ꢀC, 24 h), provides methylbenzoate
3aa (12% or 46% isolated yield utilizing azobenzene or MnO2,
respectively, Table 1, entries 1 and 2).15
To test the efficiency and the generality of this procedure for the
synthesis of esters in BmimBF4, the investigation, carried out in the
optimized condition (Table 1, entry 12), has been extended to ar-
omatic 1bel, heteroaromatic 1mep and aliphatic 1q aldehydes
with several alcohols 2aee. The procedure is successful (in addition
to benzaldehyde 1a) with aromatic aldehydes incorporating elec-
tron withdrawing or donating groups, with 1- or 2-napthaldehydes
(1h, i) and it does not seem to be sensitive to steric effects (see
substituted benzaldehydes 1deg, jel). Heteroaromatic (1mep)
and aliphatic aldehydes (1q) gave modest results except for ethyl
3-pyridinecarboxyaldehyde (giving 3ob, 70% yield). Among the
aliphatic alcohols, ethanol 2b gave better yields than methanol 2a
and dodecanol 2d whereas a high yield was obtained using benzyl
alcohol 2c and diethylamino ethanol 2e (Table 2 entries 14 and 16).
In any case, esters 3 have been isolated in good to elevated yields
(Table 2).
Room temperature ionic liquids, due to their remarkable phys-
ico-chemical properties, have received attention as possible re-
cyclable solvents. The recyclability is a significant feature of this
reaction medium to abate their costs. The used ionic liquid was
recovered and recycled using two different methodologies. The first
one was the most obvious, being the purification of the used ionic
liquid carried out by flash chromatography on silica gel increasing
the polarity of the mobile phase to pure acetonitrile after the
Table 1
Optimization of the conditions for the NHC-catalyzed oxidation of benzaldehyde 1a
to methylbenzoate 3aa in ionic liquid BmimBF4 as solvent and precatalysta
Entry
Oxidant (mmol)
Organic base
(mmol)
Inorganic base
(mmol)
Yield of
3aab (%)
1
2
3
4
5
6
7
8
PheN]NePh (2.5)
MnO2 (2.5)
PheN]NePh (2.5)
MnO2 (2.5)
MnO2 (2.5)
MnO2 (2.5)
DBU (0.2)
DBU (0.2)
DBU (1.0)
DBU (1.0)
DBU (2.5)
d
d
12
46
21
70
85
50
52
d
d
d
d
d
Cs2CO3 (1.5)
Cs2CO3 (3.0)
K2CO3 (1.5)
Cs2CO3 (1.5)
d
MnO2 (2.5)
MnO2 (2.5)
MnO2 (2.5)
MnO2 (0.75)
MnO2 (1.5)
d
d
9
DBU (0.5)
DBU (1.0)
DBU (1.0)
DBU (0.5)
DBU (0.5)
89
38
40
86
68
10
11
12
13
d
MnO2 (1.5)
MnO2 (1.0)
Cs2CO3 (1.5)
Cs2CO3 (1.5)
a
Reaction conditions: a mixture of 1a (0.5 mmol), oxidant agent and methanol 2a
(1.5 mmol) was added to 0.5 mL of BmimBF4 containing the base (T¼25 ꢀC; t¼24 h).
b
Reported yields of the isolated 3aa are based upon the starting aldehyde 1a.

8090
I. Chiarotto et al. / Tetrahedron 69 (2013) 8088e8095
Me
Bu
Me
Me
RCHO
BF4
N
N
N
OH
R
+ base
- (H+; BF4 )
-
N
N
N
NHC
Breslow
intermediate
Bu
Bu
BmimBF4
O
R
+ Oxidant
+ R'OH
OR'
ester
O
R
HO
+ RCHO
R
benzoin
Scheme 2. Reaction scheme.
Table 2
Oxidative esterification of aldehydes. Synthesis of esters 3 from aldehydes 1aeq and alcohols 2aee. Room temperature ionic liquid BmimBF4 as precatalyst and green solventa
Entry
Substrate
Alcohols
Product
Yieldb (%)
1
CH3OH (2a)
86
1a
3aa
2
3
2a
2a
45
70
1b
3ba
1c
3ca
4
2a
43
1d
1e
1f
3da
5
6
2a
2a
71
63
3ea
3fa

I. Chiarotto et al. / Tetrahedron 69 (2013) 8088e8095
8091
Table 2 (continued )
Entry
Substrate
Alcohols
Product
Yieldb (%)
7
8
9
2a
2a
2a
79
53
66
1g
1h
3ga
3ha
1i
1j
3ia
3ja
10
2a
64
11
12
13
2a
73
85
85
1k
3ka
C2H5OH (2b)
1k
3kb
2b
1e
3eb
14
90
2c
1k
3kc
15
16
2b
80
91
1l
3lb
2d
1l
3ld
(continued on next page)

8092
I. Chiarotto et al. / Tetrahedron 69 (2013) 8088e8095
Table 2 (continued )
Entry
Substrate
Alcohols
Product
Yieldb (%)
17
18
19
2b
25
1m
1a
3mb
30
42
2e
3ae
2b
3nb
1n
20
21
2b
70
1o
1p
3ob
3pb
2b
2b
30
30
22
1q
3qb
a
Experimental conditions: see Table 1, entry 12.
Reported yields of isolated esters are based upon the starting aldehydes.
b
elution of the desired products. In this case, it was reused in
a successive run obtaining the same yield in ester (as expected for
pure BmimBF4), according to the experimental condition of Table 1,
entry 12. The second method of recycling the used ionic liquid was
more challenging, as we have studied the possibility to reuse the
reaction mixture with the excess of the inorganic components
(not extracted by diethyl ether in the procedure for the isolation of
the ester). Accordingly, after ethereal extraction of the product, new
substrates were added to the reaction mixture (aldehyde and al-
cohol), and the other reagents (DBU, Cs2CO3 MnO2) were merely
integrated (adding 30% of the initial amounts). In this way the ionic
liquid was recycled for five times and each time the yield of ester
remains about 80% yield (Fig.1). It is preferable to follow the second
procedure, which allows to recycle both IL and inorganic reactants,
avoiding the use of VOCs (except for the extraction).
3. Conclusions
The oxidative esterification of aldehydes has been performed
using room temperature ionic liquid BmimBF4 as solvent and pre-
catalyst. Accordingly, a simple green procedure of synthesis of es-
ters in ionic liquid has been set-up by reaction of an aldehyde with
a suitable base, an oxidant and methanol in BmimBF4. The effi-
ciency of the methodology is strongly affected by the nature of the
base and of the oxidizing agent. The best results were obtained
Fig. 1. Recycling of the reaction mixture (RTIL, DBU, Cs2CO3, MnO2) using aldehyde 1k
and alcohol 2b and yields of isolated ester 3kb with subsequent runs. In every run, 30%
of DBU, Cs2CO3 and MnO2 have been integrated with respect to the initial amount.

I. Chiarotto et al. / Tetrahedron 69 (2013) 8088e8095
8093
using MnO2 and DBU (or a mixture DBU/Cs2CO3); esters 3 were
isolated in good to excellent yields. To the best of our knowledge,
this is the first time that such a reaction has been carried out in an
ionic liquid. The IL was recycled by reusing the reaction mixture five
times, with no significant loss in the yields, or by purifying the used
ionic liquid by flash chromatography. Further explorations along
this reaction are currently underway in our laboratory.
temperature for 24 h. This procedure has been repeated for five
times (yields: 85, 83, 85, 83, 83%).
4.4. Characterization of esters
4.4.1. Methyl benzoate 3aa.16 Yield: 86% as yellow oil obtained in
pure form. 1H NMR (CDCl3, 200 MHz):
d 3.93 (s, 3H), 7.41e7.58
(m, 3H), 8.03e8.08 (m, 2H); 13C NMR (CDCl3, 50.3 MHz):
d 52.1,
4. Experimental section
4.1. General
128.3, 129.6, 130.2, 132.9, 167.1.
4.4.2. Methyl 4-chlorobenzoate 3ba.17 Yield: 45% as white solid; mp
42e43 ꢀC (lit.17b mp 42e44 ꢀC), obtained in pure form. 1H NMR
All reagents were purchased from suppliers and were used
without any further purification. Ionic liquid BmimBF4 (Iolitec) was
used after having heated it under vacuum at 45 ꢀC for 2 h. Yields
refer to chromatographically and spectroscopically homogeneous
materials, unless otherwise stated. Reactions were monitored by
thin-layer chromatography (TLC) carried out on 0.25 mm E. Merck
silica gel plates (60F-254) using UV light (254 nm and 365 nm) as
the visualizing agent and an ethanolic solution of phosphomolyb-
dic acid and heat as developing agents. NMR spectra were recorded
on a Bruker AC200 (200 and 50.3 MHz) instrument and calibrated
using residual undeuterated solvent as internal reference (peak at
7.26 ppm in 1H NMR and peak at 77.0 ppm in 13C NMR in the case of
CDCl3). Chemical shifts were expressed in parts per million (ppm)
and coupling constants (J) in hertz (Hz). Melting point apparatus
SMP2 (Stuart Scientific).
(CDCl3, 200 MHz):
d
3.93 (s, 3H), 7.42 (d, 2H, J¼9.0 Hz), 7.98 (d, 2H,
J¼9.0 Hz). 13C NMR (CDCl3, 50.3 MHz):
d 52.2, 128.6, 128.7, 130.9,
139.3, 166.2.
4.4.3. Methyl 4-methoxybenzoate 3ca.18 Yield: 70% as white solid;
mp 48e49 ꢀC (lit.17b mp 46e47 ꢀC), obtained in pure form. 1H NMR
(CDCl3, 200 MHz):
d
3.86 (s, 3H), 3.89 (s, 3H), 6.92 (d, 2H, J¼9.0 Hz),
7.99 (d, 2H, J¼9.0 Hz). 13C NMR (CDCl3, 50.3 MHz):
d 51.8, 55.3,113.6,
122.6, 131.5, 163.3, 166.8.
4.4.4. Methyl 2-methoxybenzoate 3da.19 Yield: 43% as brownish oil
obtained in pure form. 1H NMR (CDCl3, 200 MHz):
3.90 (s, 3H),
d
3.92 (s, 3H), 6.97e7.03 (m, 2H), 7.44e7.52 (m, 1H), 7.78e7.83
(m, 1H). 13C NMR (CDCl3, 50.3 MHz):
131.6, 133.5, 159.1, 166.7.
d52.0, 56.0, 112.0, 120.0, 120.1,
4.4.5. Methyl 2-methylbenzoate 3ea.18 Yield: 71% as brown oil ob-
tained in pure form. 1H NMR (CDCl3, 200 MHz):
2.61 (s, 3H), 3.90
(s, 3H), 7.21e7.28 (m, 2H), 7.37e7.45 (m, 1H), 7.90e7.94 (m, 1H). 13C
4.2. General procedure for oxidative esterification of
aldehydes
d
NMR (CDCl3, 50.3 MHz):
140.1, 168.1.
d 21.7, 51.8, 125.7, 129.6, 130.5, 131.7, 131.9,
In a typical procedure, a capped vessel was charged with ionic
liquid BmimBF4 (0.5 mL) and put under positive pressure of nitrogen.
DBU (0.5 mmol) and Cs2CO3 (1.5 mmol) were added followed by the
aldehyde (0.5 mmol) and MnO2 (1.5 mmol). The reaction mixture
was stirred for a few minutes and alcohol (1.5 mmol) was added. The
reaction mixture was stirred at ambient temperature for 24 h. The
mixture was then filtered through a thin pad of silica, which was
washed with ethyl acetate (30 mL). The filtrate was analyzed by TLC
and 1H NMR and then concentrated under vacuum. The resulting
residue was purified by flash chromatography on silica gel where
needed.
4.4.6. Methyl 2-chlorobenzoate 3fa.17 Yield: 63% as brown oil ob-
tained in pure form. 1H NMR (CDCl3, 200 MHz):
3.94 (s, 3H),
7.28e7.46 (m, 3H), 7.81e7.85 (m, 1H). 13C NMR (CDCl3, 50.3 MHz):
52.3, 126.5, 130.1, 131.0, 131.3, 132.5, 133.6, 166.1.
d
d
4.4.7. Methyl 2,6-dichlorobenzoate 3ga.17 Yield: 79% as brownish
oil obtained in pure form. 1H NMR (CDCl3, 200 MHz):
d
3.99 (s, 3H),
7.24e7.35 (m, 3H). 13C NMR (CDCl3, 50.3 MHz):
d 53.0, 127.8, 131.0,
All esters are known compounds and their 1H and 13C NMR
spectral data were consistent with those available in the literature.
131.8, 133.5, 165.2.
4.4.8. Methyl 1-naphthoate 3ha.4 Yield: 53% as brownish oil ob-
tained in pure form. 1H NMR (CDCl3, 200 MHz):
4.02 (s, 3H),
7.50e7.64 (m, 3H), 7.87e7.91 (m, 1H), 8.01e8.05 (m, 1H), 8.19e8.22
(m, 1H), 8.92e8.97 (m, 1H). 13C NMR (CDCl3, 50.3 MHz):
52.1,
d
4.3. Recycle of IL
d
4.3.1. Procedure 1. A neat ionic liquid has been obtained by flash
chromatography purification on silica gel. The reaction mixture
from the reaction reported in Table 1, entry 12, was purified by
eluting with hexane/ethyl acetate 1:1. After the isolation of product
(86%), the change of eluent mixture with CH3CN (75.0 mL for 2.0 mL
of IL) led to obtain the pure ionic liquid. Inorganic compounds were
not eluted and remained on the silica gel. The neat ionic liquid, thus
obtained, was reused in a subsequent run, obtaining nearly the
same yield (83%).
124.5, 125.8, 126.2, 127.1, 127.8, 128.5, 130.2, 131.4, 133.4, 133.9,
168.0 ppm.
4.4.9. Methyl 2-naphthoate 3ia.19 Yield: 66% as white solid; mp
75e76 ꢀC (lit.17b mp 74e75 ꢀC), Rf (10% ethyl acetate in n-hexane)
0.67. 1H NMR (CDCl3, 200 MHz):
d
3.99 (s, 3H), 7.51e7.64 (m, 2H),
7.87e7.99 (m, 4H), 8.62 (s, 1H). 13C NMR (CDCl3, 50.3 MHz):
d
52.2,
125.2, 126.6, 127.4, 127.7, 128.1, 128.2, 129.3, 131.1, 132.5, 135.5, 167.2.
4.4.10. Methyl 4-(iso-propyl)benzoate 3ja.20 Yield: 64% as yellow oil
4.3.2. Procedure 2. After the extraction with Et2O (about 5.0 mL
three times) of the product 3kb (85%) and reagents 1k and 2b, the
reaction mixture was kept under vacuum at room temperature for
1 h to eliminate Et2O residues. The reaction mixture was then used,
with the addition of DBU (0.5 mmol), Cs2CO3 (0.5 mmol), followed
by the aldehyde (0.5 mmol), MnO2 (0.5 mmol) and alcohol
(1.5 mmol). The reaction mixture was stirred at ambient
obtained in pure form. 1H NMR (200 MHz, CDCl3)
d: 1.27 (d, 6H,
J¼6.8 Hz), 2.97 (m, 1H), 3.91 (s, 3H), 7.29 (d, 2H, J¼8.2 Hz), 7.97
(d, 2H, J¼8.2 Hz). 13C NMR (CDCl3, 50.3 MHz)
d: 23.7, 34.2, 52.0,
126.4, 127.8, 129.7, 154.3, 167.1.
4.4.11. Methyl 4-methylbenzoate 3ka.21 Yield: 73% as colourless oil
obtained in pure form. 1H NMR (200 MHz, CDCl3)
2.40 (s, 3H), 3.90
d

8094
I. Chiarotto et al. / Tetrahedron 69 (2013) 8088e8095
(s, 3H), 7.22e7.24 (m, 2H), 7.91e7.96 (m, 2H). 13C NMR (CDCl3,
50.3 MHz): 21.6, 51.9, 127.4, 129.0, 129.6, 143.5, 167.1.
J¼7.2 Hz), 4.43 (q, 2H, J¼7.2 Hz), 7.87e7.90 (m, 2H), 8.78e8.80 (m,
2H). 13C NMR (CDCl3, 50.3 MHz):
14.2, 61.8, 122.9, 137.6, 150.6, 165.1.
d
d
4.4.12. Ethyl 4-methylbenzoate 3kb.21 Yield: 85% as brownish oil
obtained in pure form. 1H NMR (200 MHz, CDCl3):
1.40 (t, 3H,
4.4.22. Ethyl octanoate 3qb.12a Yield: 30% as yellow oil obtained in
pure form. 1H NMR (200 MHz, CDCl3):
0.91e0.87 (m, 3H),
d
d
J¼7.2 Hz), 2.42 (s, 3H), 4.36 (q, 2H, J¼7.2 Hz), 7.24 (d, 2H, J¼8.2 Hz),
1.35e1.21 (m, 11H), 1.64e1.60 (m, 2H), 2.29 (t, 2H, J¼7.2 Hz), 4.13 (q,
7.94 (d, 2H, J¼8.2 Hz). 13C NMR (CDCl3, 50.3 MHz):
d
14.3, 21.6, 60.7,
2H, J¼7.2 Hz). 13C NMR (CDCl3, 50.3 MHz):
d 14.1, 14.2, 22.6, 25.0,
127.7, 129.0, 129.5, 143.4, 166.7.
29.0, 28.9, 31.7, 34.4, 60.1, 173.9 BFꢁ4 .
4.4.13. Ethyl 2-methylbenzoate 3eb.22 Yield: 85% as yellow oil, Rf
(10% ethyl acetate in n-hexane) 0.66. 1H NMR (200 MHz, CDCl3):
Acknowledgements
d
1.40 (t, 3H, J¼7.2 Hz), 2.61 (s, 3H), 4.36 (q, 2H, J¼7.2 Hz), 7.21e7.24
We thank Mr. Marco Di Pilato for his contribution to the ex-
perimental part of this work and Miur (Italy) for financial support.
(m, 2H), 7.36e7.45 (m, 1H), 7.89e7.94 (m, 1H). 13C NMR (CDCl3,
50.3 MHz):
167.7.
d 14.3, 21.7, 60.7, 125.7, 130.0, 130.5, 131.6, 131.8, 140.0,
References and notes
4.4.14. Benzyl 4-methylbenzoate 3kc.9a,23 Yield: 90% as white solid;
mp 45e46 ꢀC (lit.9a mp 45e46 ꢀC), Rf (10% ethyl acetate in n-hex-
1. (a) Bourissou, D.; Guerret, O.; Gabbai, F. P.;Bertrand, G. Chem. Rev. 2000,100, 39e91;
(b) Diez-Gonzalez, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109, 3612e3676.
2. (a) Moore, J. L.; Rovis, T. Top. Curr. Chem. 2009, 291, 77e144; (b) Nair, V.; Val-
lalath, S.; Babu, B. P. Chem. Soc. Rev. 2008, 37, 2691e2698; (c) Enders, D.; Nie-
meier, O.; Henseler, A. Chem. Rev. 2007, 107, 5606e5655; (d) Marion, N.; Dìez-
ane) 0.48. 1H NMR (200 MHz, CDCl3):
d 2.42 (s, 3H), 5.36 (s, 2H), 7.25
(d, 2H, J¼8.2 Hz), 7.38e7.40 (m, 5H), 7.98 (d, 2H, J¼8.2 Hz). 13C NMR
ꢀ
(CDCl3, 50.3 MHz):
136.2, 143.7, 166.5.
d 21.7, 66.5, 127.4, 128.1, 128.2, 128.6, 129.1, 129.7,
Gonzalez, S.; Nolan, S. N. Angew. Chem., Int. Ed. 2007, 46, 2988e3000.
3. (a) Topics in Organometallic Chemistry; Glorius, F., Ed.; Springer: Berlin, Ger-
many, 2007; Vol. 48; (b) N-Heterocyclic Carbenes in Synthesis; Nolan, S. N., Ed.;
Wiley-VCH: Weinheim, Germany, 2006.
4. Biju, A. T.; Kuhl, N.; Glorius, F. Acc. Chem. Res. 2011, 44, 1182e1195.
5. Breslow, R. J. Am. Chem. Soc. 1958, 80, 3719e3726.
6. (a) Chiang, P.-C.; Bode, J. W. N-Heterocyclic Carbenes; The Royal Society of
Chemistry: Cambridge, UK, 2011; pp 399e435; (b) Cohen, D. T.; Scheidt, K. A.
Chem. Sci. 2012, 53e57; (c) Asymmetric Organocatalysis; Chiang, P.-C., Bode, J. W.
, Eds.; Georg Thieme: Stuttgart, Germany, 2012; Vol. 1, pp 636e672; (d) Vora,
H. U.; Wheeler, P.; Rovis, T. Adv. Synth. Catal. 2012, 354, 1617e1639; (e) Bugaut,
X.; Glorius, F. Chem. Soc. Rev. 2012, 41, 3511e3522.
4.4.15. Ethyl 4-dimethylamino benzoate 3lb.22 Yield: 80% as yellow
oil, Rf (10% ethyl acetate in n-hexane) 0.37. 1H NMR (200 MHz,
CDCl3):
d
1.37 (t, 3H, J¼7.2 Hz), 3.04 (s, 6H), 4.32 (q, 2H, J¼7.2 Hz),
6.65 (d, 2H, J¼9.2 Hz), 7.92 (d, 2H, J¼9.2 Hz). 13C NMR (CDCl3,
50.3 MHz):
d 14.5, 40.0, 60.1, 110.7, 117.3, 131.2, 153.2, 167.0.
4.4.16. 2-Diethylamino
3ld.24 Yield: 91% as yellow oil, Rf (20% ethyl acetate in n-hexane)
0.31. 1H NMR (200 MHz, CDCl3):
ethyl
4-dimethylamino
benzoate
7. Ishihara, K. Tetrahedron 2009, 65, 1085e1109 and references therein.
8. Ekoue-Kovi, K.; Wolf, C. Chem.dEur. J. 2008, 14, 6302e6315.
9. (a) Li, Y.; Du, W.; Deng, W.-P. Tetrahedron 2012, 68, 3611e3615; (b) Kuwano, S.;
Harada, S.; Oriez, R.; Yamada, K.-I. Chem. Commun. 2012, 145e147; (c) Arde, P.;
Ramanjaneyulu, R. T.; Reddy, V.; Saxena, A.; Anand, R. V. Org. Biomol. Chem.
2012, 10, 848e851; (d) Yoshida, M.; Katagiri, Y.; Zhu, W.-B.; Shishido, K. Org.
Biomol. Chem. 2009, 7, 4062e4066; (e) Maki, B. E.; Chan, A.; Phillips, E. M.;
Scheidt, K. A. Tetrahedron 2009, 65, 3102e3109; (f) Noonan, C.; Baragwanath, L.;
Connon, S. J. Tetrahedron Lett. 2008, 49, 4003e4006; (g) Maki, B. E.; Scheidt, K.
A. Org. Lett. 2008, 10, 4331e4334; (h) De Sarkar, S.; Grimme, S.; Studer, A. J. Am.
Chem. Soc. 2010, 132, 1190e1191.
d
1.08 (t, 6H, J¼7.2 Hz), 2.65 (q, 4H,
J¼7.2 Hz), 2.85 (t, 2H, J¼6.2 Hz), 3.05 (s, 6H), 4.35 (t, 2H, J¼6.2 Hz),
6.65 (d, 2H, J¼9.2 Hz), 7.92 (d, 2H, J¼9.2 Hz). 13C NMR (CDCl3,
50.3 MHz):
166.9.
d 12.1, 39.9, 47.8, 51.1, 62.6, 110.6, 116.9, 131.2, 153.2,
4.4.17. Ethyl 2-furoate 3mb.25 Yield: 25% as white solid; mp
34e35 ꢀC (lit.25b mp 35e36 ꢀC), Rf (20% ethyl acetate in n-hexane)
10. Finney, E. E.; Ogawa, K. A.; Boydston, A. J. J. Am. Chem. Soc. 2012, 134,
12374e12377.
0.29. 1H NMR (200 MHz, CDCl3):
d
1.39 (t, 3H, J¼7.0 Hz), 4.37 (q, 2H,
11. (a) Maji, B.; Vedachalan, S.; Ge, X.; Cai, S.; Liu, X.-W. J. Org. Chem. 2011, 76,
3016e3023; (b) Xin, Y.-C.; Shi, S.-H.; Xie, D.-D.; Hui, X.-P.; Xu, P.-F. Eur. J. Org.
Chem. 2011, 32, 6527e6531.
12. (a) Sohn, S. S.; Bode, J. W. Org. Lett. 2005, 7, 3873e3876; (b) Chan, A.; Scheidt, K.
A. Org. Lett. 2005, 7, 905e908; (c) Reynolds, N. T.; Read de Alaniz, J.; Rovis, T. J.
Am. Chem. Soc. 2004, 126, 9518e9519; (d) Reynolds, N. T.; Rovis, T. J. Am. Chem.
Soc. 2005, 127, 16406e16407; (e) Zeitler, K. Org. Lett. 2006, 8, 637e640; (f)
Feroci, M.; Chiarotto, I.; Orsini, M.; Pelagalli, R.; Inesi, A. Chem. Commun. 2012,
5361e5363.
J¼7.0 Hz), 6.51 (dd, 1H, J¼3.4, J¼1.6 Hz), 7.19 (dd, 1H, J¼3.4,
J¼1.0 Hz), 7.58 (m, 1H). 13C NMR (CDCl3, 50.3 MHz):
d 14.3, 61.0,
111.8, 117.7, 144.9, 146.2, 158.8.
4.4.18. Dodecyl benzoate 3ae.26 Yield: 30% as colourless oil, Rf (2%
ethyl acetate in n-hexane) 0.36. 1H NMR (200 MHz, CDCl3):
0.89 (t,
d
13. (a) Sheldon, R. A. Chem. Soc. Rev. 2012, 41, 1437e1451; (b) Sheldon, R. A. Green
Chem. 2008, 10, 359e360; (c) Tucker, J. L. Org. Process Res. Dev. 2010, 14,
328e331; (d) Anastas, P.; Eghbali, N. Chem. Soc. Rev. 2010, 39, 301e312; (e)
Sheldon, R. A. Chem. Commun. 2008, 3352e3365; (f) Green Chemistry and Ca-
talysis; Sheldon, R. A., Arends, I. W. C. E., Hanefeld, U., Eds.; Wiley-VCH:
Weinheim, Germany, 2007; (g) Li, C. J.; Trost, B. M. Proc. Natl. Acad. Sci. U.S.A.
2008, 105, 13197e13202; (h) Horvath, I. T.; Anastas, P. T. Chem. Rev. 2007, 107,
2169e2173.
14. (a) Hallett, J. P.; Welton, T. Chem. Rev. 2011, 111, 3508e3576; (b) Wasserscheid, P.;
Welton, T. In Ionic Liquid in Synthesis; Wiley-VCH: Weinheim, 2002; Vols. 1e2; (c)
Chowdhury, S.; Mohan, R. S.; Scott, J. L. Tetrahedron 2007, 63, 2363e2389; (d) Jain,
N.; Chauhan, A.; Chauhan, S. M. S. Tetrahedron 2005, 61, 1015e1060; (e) Olivier-
Bourbigou, H.; Magna, L.; Morvan, D. Appl. Catal., A: Gen. 2010, 373, 1e56; (f) Par-
vulescu, V. I.; Hardacre, C. Chem. Rev. 2007, 107, 2615e2665; (g) Matrinez- Palou, R.
Mol. Divers. 2010, 14, 3e25; (h) Bellina, F.; Chiappe, C. Molecules 2010, 15,
2211e2245; (i) Feroci, M.; Chiarotto, I.; Inesi, A. Curr. Org. Chem. 2013, 17, 204e219.
15. Although it has been reported (Reger, D. L.; Watson, R. P.; Gardinier, J. R.; Smith,
M. D.; Pellechia, P. J. Inorg. Chem. 2006, 45, 10088e10097 and references
therein) that the anion BF4 is not stable in the presence of strong metallic
electrophilic cations, yielding MF and BF3, we have not observed this kind of
decomposition in our experimental conditions. In fact, we have tested the
stability of this anion carrying out the following reaction: 1 mL of BmimBF4, 1.
5 mmol of Cs2CO3, 0.5 mmol of DBU and 0.5 mmol of styrene oxide were stirred
under a positive pressure of nitrogen at room temperature for 24 h. The mix-
ture was extracted with diethyl ether and after the usual workup, analyzed by
1H NMR. Only styrene oxide in quantitative yield was obtained, and phenyl
3H, J¼6.6 Hz), 1.22e1.39 (m, 18H), 1.70e1.84 (m, 2H), 4.32 (t, 2H,
J¼6.6 Hz), 7.41e7.60 (m, 3H), 8.03e8.08 (m, 2H). 13C NMR (CDCl3,
50.3 MHz):
d 14.1, 22.7, 26.1, 28.7, 29.3, 29.4, 29.6, 29.6, 29.7, 32.0,
65.1, 128.3, 129.5, 130.5, 132.8, 166.6.
4.4.19. Ethyl 2-pyridinecarboxylate 3nb.27 Yield: 42% as yellow oil
obtained in pure form. 1H NMR (200 MHz, CDCl3):
d 1.46 (t, 3H,
J¼7.0 Hz), 4.50 (m, 2H, J¼7.0 Hz), 7.45e7.53 (m, 1H), 7.87 (t, 1H,
J¼7.8 Hz), 8.14 (d, 1H, J¼7.8 Hz), 8.78 (d, 1H, J¼4.8 Hz). 13C NMR
(CDCl3, 50.3 MHz):
165.2.
d 14.3, 61.9, 125.1, 126.8, 137.0, 148.2, 149.8,
4.4.20. Ethyl 3-pyridinecarboxylate 3ob.27 Yield: 70% as brownish
oil obtained in pure form. 1H NMR (200 MHz, CDCl3):
1.40 (t, 3H,
d
J¼7.2 Hz), 4.40 (q, 2H, J¼7.2 Hz), 7.35e7.42 (m, 1H), 8.30e8.32 (m,
1H), 8.76 (d, 1H, J¼3.6 Hz), 9.22 (s, 1H). 13C NMR (CDCl3, 50.3 MHz):
d
14.2, 61.4, 123.2, 126.3, 137.0, 150.8, 153.3, 165.2.
4.4.21. Ethyl 4-pyridinecarboxylate 3pb.27 Yield: 30% as brownish
oil obtained in pure form. 1H NMR (200 MHz, CDCl3):
1.42 (t, 3H,
d

I. Chiarotto et al. / Tetrahedron 69 (2013) 8088e8095
8095
acetaldehyde was not observed. The isomerization of styrene oxide to phenyl
acetaldehyde is a well-known reaction (Parker, R. E.; Isaacs, N. S. Chem. Rev.
1959, 59, 737e799) that is catalyzed by BF3.
22. Schmidt, A.; Habeck, T.; Snovydovych, B.; Eisfeld, W. Org. Lett. 2007, 9,
3515e3518.
23. Liu, C.; Tang, S.; Zheng, L.; Liu, D.; Zhang, H.; Lei, A. Angew. Chem., Int. Ed. 2012,
15, 5662e5666.
24. Loccufier, J.; Roland, C. PCT Int. Appl. WO 2008061954 A120080529, 2008.
25. (a) Yin, G.; Gao, M.; Wang, Z.; Wu, Y.; Wu, A. Bull. Chem. Soc. Jpn. 2008, 81,
369e372; (b) Calvo, K. C.; Weisenberger, C. R.; Anderson, L. B.; Klapper, M. H.
Anal. Chem. 1981, 53, 981e982.
26. Nguyen, H.-P.; Znifeche, S.; Baboulene, M. Synth. Commun. 2004, 34,
2085e2093.
16. Dawar, P.; Bhagavan Raju, M.; Ramakrishna, R. A. Tetrahedron Lett. 2011, 52,
4262e4265.
17. (a) Gassmann, J.; Voss, J. Z. Naturforsch. 2008, 63b, 1291e1299; (b) Ma, L.; Yuan, L.;
Xu, C.; Li, G.; Tao, M.; Zhang, W. Synthesis 2013, 45, 45e52.
18. Keck, G. E.; McLaws, M. D.; Wager, T. T. Tetrahedron 2000, 56, 9875e9883.
19. Ushijima, S.; Moriyama, K.; Togo, H. Tetrahedron 2012, 68, 4701e4709.
20. Cahiez, G.; Foulgoc, L.; Moyeux, A. Angew. Chem., Int. Ed. 2009, 48, 2969e2972.
21. Shang, R.; Fu, Y.; Li, J.-B.; Zhang, S.-L.; Guo, Q.-X.; Liu, L. J. Am. Chem. Soc. 2009,
131, 5738e5739.
27. Al-Awadi, N. A.; El-Dusouqui, O. M. E.; Mathew, T. Int. J. Chem. Kinet. 1997, 29,
289e293.