Synthesis of novel room temperature chiral ionic liquids. Application as reaction media for the Heck arylation of aza-endocyclic acrylates

Article abstract of DOI:10.1590/S0103-50532010000500009

New achiral and chiral RTILs were prepared using novel and/or optimized synthetic routes. These new series of imidazolinium, imidazolium, pyridinium and nicotine-derived ionic liquids were fully characterized including differential scanning calorimetry (D

Full text of DOI:10.1590/S0103-50532010000500009

J. Braz. Chem. Soc., Vol. 21, No. 5, 821-836, 2010.
Printed in Brazil - ©2010 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Synthesis of Novel Room Temperature Chiral Ionic Liquids. Application as Reaction
Media for the Heck Arylation of Aza-endocyclic Acrylates
Julio C. Pastre,a Yves Génisson,*,b Nathalie Saffon,c Jany Dandurandd and
Carlos R. D. Correia*,a
aInstituto de Química, Universidade Estadual de Campinas, CP 6154,
13083-970 Campinas-SP, Brazil
bLaboratoire de Synthèse et Physicochimie des Molécules d’Intérêt Biologique UMR-CNRS 5068,
Université Paul Sabatier, 118 route de Narbonne, 31062, Toulouse Cedex 9, France
cSFTCM, FR2599, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse Cedex 9, France
dLaboratoire de Physique des Polymères, Université Paul Sabatier, 118 route de Narbonne,
31062 Toulouse Cedex 9, France
Novos líquidos iônicos aquirais e quirais foram preparados utilizando-se rotas sintéticas
inéditas e/ou otimizadas. Estas séries de líquidos iônicos do tipo imidazolínico, imidazólico e
piridínico foram totalmente caracterizadas, incluindo-se análises por calorimetria diferencial de
varredura (DSC). O desempenho desses líquidos iônicos (LIs) foi demonstrado empregando-se a
arilação de Heck de aza-acrilato endocíclicos com sais de arenodiazônio ou iodetos de arila. As
arilações de Heck realizadas na presença destas entidades iônicas quirais, seja como um solvente
ou um aditivo, foram eficazes levando à completa conversão do substrato, em bons a excelentes
rendimentos do aduto de Heck na maioria dos casos, apesar de não ser observada indução
assimétrica em nenhum dos casos estudados. Dois novos complexos quirais de paládio do tipo
carbeno N-heterocíclico foram preparados em bons rendimentos a partir de um sal imidazólico
quiral e suas estruturas caracterizadas por difração de raios-X. De modo geral, a arilação de Heck
empregando tetrafluoroboratos de arenodiazônio em líquidos iônicos demonstrou ser mais eficiente
do que os protocolos tradicionais em termos de reatividade e rendimentos de reação.
New achiral and chiral RTILs were prepared using novel and/or optimized synthetic routes.
These new series of imidazolinium, imidazolium, pyridinium and nicotine-derived ionic liquids were
fully characterized including differential scanning calorimetry (DSC) analysis. The performance
of these achiral and chiral room temperature ionic liquids (RTILs) was demonstrated by means
of the Heck arylation of endocyclic acrylates employing arenediazonium salts and aryl iodides.
The Heck arylations performed in the presence of these ionic entities, either as a solvent or as an
additive, were effective leading to complete conversion of the substrate and good to excellent yield
of the Heck adduct. In spite of the good performances, no asymmetric induction was observed in
any of the cases studied. Two new diastereoisomeric NHC-palladium complexes were prepared in
good yields from a chiral imidazolium salt and their structure characterized by X-ray diffraction.
Overall, the Heck arylations employing arenediazonium tetrafluoroborates in RTILs were more
effective than the traditional protocols employing aryl iodides in terms of reactivity and yields.
Keywords: ionic liquids, chiral ionic liquids, Heck arylation, arenediazonium salts, aryl iodides
Introduction
to classical organic solvents.1 In addition, they can
offer unique opportunities to modulate the course of a
reaction, which combined with their highly adaptable
structure opens up almost unlimited prospects in
synthesis.2 In the context of homogenous catalysis, in
particular with Pd(0), RTILs have also proven to be
Room temperature ionic liquids (RTILs) have been
proposed as a safer and more eco-friendly alternative
*e-mail: genisson@chimie.ups-tlse.fr; roque@iqm.unicamp.br

822
Synthesis of Novel Room Temperature Chiral Ionic Liquids
J. Braz. Chem. Soc.
highly beneficial, contributing to catalyst stabilization,
immobilization and recovery.3
was described by Leitner and co-workers.12 Using a
specifically designed ionic liquid with a chiral anion,
enantioselectivities of up to 84% ee were obtained in the
aza-Baylis-Hillman reaction. These results are comparable
with the values obtained with the best catalysts for
the enantioselective aza-Baylis-Hillman reaction in
conventional solvents (94% ee,13 83% ee14).
These results indicate that the key to effective chirality
transfer lies in strong intermolecular interactions such as
electrostatic attraction and hydrogen bonding between the
solvent molecules and the intermediates or the transition
states of the enantioselective reaction step.
In view of their intrinsic structural flexibility, RTILs
also offer wide prospects for potential chirality transfer in
organometallic catalysis. This includes in situ generation of
the active catalyst through carbene palladium complexes.
Indeed, the participation of 1,3-dialkylimidazolium-type
ionic liquids in the stabilization of catalytic Pd species,
related to the so-called “non-innocent” nature of these
cations, has been proposed in several cases.15 In particular,
in the course of Heck arylation16 and Suzuki cross-
coupling,17 1,2-diaminocarbenes formed in situ from an
imidazolium-based ionic liquid have been suggested to be
involved as Pd ligands.
However, examples of asymmetric versions of
this approach based on the use of chiral ionic reaction
medium remain scarce. Kiss et al.18 have notably studied
the influence of a 1-((S)-2-methylbutyl)imidazolium
hexafluorophosphateonthestereochemicalcourseofaHeck
oxyarylation reaction. Although the enantioselectivities
observed were very modest (4-5% ee), this interesting
precedent validated the concept.
The eventuality of creating a stereogenic center in a
stereocontrolled manner in the course of the Heck reaction
would certainly contribute to strengthen its synthetic
potential. In line with our continuous efforts to widen the
scope and demonstrate the potential of the Heck arylation
with arenediazonium in multi-step synthesis of bioactive
compounds,19 we recently reported a new synthesis of the
antidepressant drug ( )-paroxetine (4) (Scheme 1).20
Our synthetic route was based on a fast, clean and simple
palladium-catalyzed arylation of a substituted acrylate in
CH3CN/H2O (2:1) with Pd(OAc)2 as catalyst. Application
of this protocol to the aza-endocyclic acrylate 1 afforded
an efficient access to an arylated tetrahydropyridine 2.
We wish to report herein the synthesis of several chiral
ionic liquids, as well as our initial results concerning the
performance of these new ionic species as reaction media
and additive for the Heck arylation of aza-endocyclic
acrylates employing either arenediazonium salts or aryl
iodides as electrophiles.
Among the Pd(0)-catalyzed C-C coupling reactions
employed in multi-step synthesis, the Heck reaction
plays a preponderant role. However, Heck arylations
employing arenediazonium salts as electrophiles have
received relatively less attention in comparison to the more
traditional aryl halide- or triflate-based arylation protocols.4
Yet, arenediazonium salts offer several economical,
environmental and practical advantages over aryl halides.
Arenediazonium salts are easily prepared, are often less
expensive than the aryl halides, provide faster palladium-
catalyzed arylation reactions, are used under phosphine-
free conditions and allow more user-friendly open-air
experimental conditions. Surprisingly, the Heck arylation
employing arenediazonium salts have been scarcely studied
in RTILs.5
In view of the increasing importance of RTILs as
reaction media in organic synthesis, several groups have
recently focused on the synthesis of chiral ionic liquids
(CILs), particularly for their potential applications to chiral
discrimination and to optical resolution of racemates.6
Main advantages of using water-immiscible CILs
as solvents include the following: (i) the CILs are
inexpensively, easily made, and can be recycled;
(ii) enantiomers of the ionic liquids can be synthesized;
(iii) they are easily removed from the reaction mixture,
and as a result the analyses are usually simpler and more
accurate. Additionally, because of their high degree of
organization and ionic properties there is also a potential for
a more effective solvent-solute interaction and ion-paring
formation.The impact of the latter effect on chirality transfer
has been illustrated by Wasserscheid and co-workers7 who
reported the asymmetric hydrogenation of a prochiral
imidazolium salt embedding a chiral camphorsulfonate
anion with the enantioselectivity reaching 94%.
However, despite the large variety of CILs reported
so far, their use as reaction media in asymmetric
transformations has met with limited success in term of
chiral induction.8 For example, Armstrong et al.9 reported
on an enantioselective photoisomerisation induced
by a chiral ionic liquid (12% ee), and Vo-Thanh and
co-workers10 demonstrated that asymmetric inductions of
up to 44% ee could be achieved using CILs as reaction
media for the Baylis-Hillman reaction. More recently,
Afonso et al.11 disclosed the application of CILs as
an asymmetric inducing agent in the catalytic Rh(II)
carbenoid C-H insertion (27% ee) and in the Sharpless
dihydroxylation (85% ee). Finally, the highest level of
induced enantioselectivity reported to date by a solvent
as the only source of chirality in an asymmetric reaction

Vol. 21, No. 5, 2010
Pastre et al.
823
F
the palladium catalyzed process was found to be highly
dependent on the nature of the imidazolium counter-ion.21
These observations paralleled Kabalka’s study.5 Heck
arylations were sluggish in [BMIM][Br] and [BMIM]
[BF4], providing low conversion and decomposition under
forced conditions (Table 1, entries 1 and 2). On the other
hand, the reaction proceeded smoothly in the hydrophobic
RTILs embedding an hexafluorophosphate (PF6–) as well
F
O
O
OCH3
OCH3
N2BF4
N
N
Pd(OAc)2
CH3CN/H2O (2 : 1)
(87%)
CO2CH3
CO2CH3
1
2
3 steps
(52%)
–
as a bis(trifluoromethanesulfonyl)imide (NTf2 ) anion.22
F
F
Completeandcleanconversionswereobservedafteronlyone
hour at 65 °C, thus allowing isolation of the expected adduct
in good yields (Table 1, entries 3 to 5). Interestingly, the
reaction worked equally well in [BDIM][NTf2] (1-n-butyl-
2,3-dimethylimidazolium bis(trifluoromethanesulfonyl)
imide) where the critical C-2 position of the imidazolium
cation is substituted with a methyl group (Table 1, entries
5 and 6). The use of Pd(OAc)2 or Pd2(dba)3 as pre-catalyst
gave comparable results (compare entries 3 and 4 or entries
6 and 7). Several bases were also tested in [BMIM][NTf2]
in order to neutralize the HBF4 produced in the course of the
reaction. Remarkably, the presence of 2 equivalents of either
DIPEA, K2CO3 or NaOAc totally precluded the reaction.
The same trend has previously been observed in protic
solvents and might be imputed to the relative instability of
the arenediazonium salt in basic media.
In order to better evaluate the performance of
arenediazonium salts in RTILs, the reactivity of other
electrophiles was also assessed. A first set of experiments
was run at 100 °C. Phenyl triflate revealed ineffective in the
presence of NaOAc in [BMIM][NTf2] (Table 1, entry 8) and
the same outcome was observed using iodobenzene with
NaOAc in [BMIM][Br] (Table 1, entry 9).An encouraging
result was obtained with the iodobenzene thanks to the
use of Ag2CO3 in [BMIM][NTf2] (Table 1, entry 10).
Since a comparable result was obtained with 1-fluoro-4-
iodobenzene (Table 1, entry 11) we briefly optimized these
conditions (Table 1, entries 12 to 15). Running the reaction
at 120 °C for 5 h with Pd(OAc)2 in [BDIM][NTf2] gave rise
to a reasonably efficient process (Table 1, entries 14) while
the use of Pd2(dba)3 proved much less efficient.Altogether,
these observations confirmed the higher reactivity of
arenediazonium salts as compared to other electrophilic
reagents, even in ionic media.
O
O
2 steps
(41%)
O
OH
N
H
N
CO2CH3
( )-Paroxetine (4)
3
Scheme 1. The Heck arylation with an arenediazonium salt as a key step
of the synthesis of ( )-paroxetine (4).7
Results and Discussion
The aza-endocyclic acrylate 1 was employed in our
previous total synthesis of ( )-paroxetine (4). However,
in the context of the present study, it was found more
advantageous to employ the N-phenoxycarbonyl starting
tetrahydropyridine 6, since it can be prepared in one step
from arecoline hydrobromide (5), in 76% yield (Scheme 2).
O
O
1. NaHCO3
OCH3
OCH3
HBr
2. PhOCOCl, CH2Cl2
0 ºC - rt, 24 h
N
N
.
CO2Ph
CH3
(76%)
6
Arecoline hydrobromide (5)
Scheme 2. Preparation of the tetrahydropyridine precursor.
Use of achiral ionic media for the key Heck arylation
We first screened a series of 1-n-butyl-3-
methylimidazolium (BMIM) salts as a reaction media for
the Heck arylation reaction (Table 1). A standard protocol
was established as follows: the arenediazonium salt and
the Pd(OAc)2 were simultaneously added to a solution of
the olefin in the RTIL and the reaction mixture was rapidly
heated to 65-70 °C. Alternatively, complete solubilization
of the palladium acetate could be first ensured by a brief
sonication before addition of the arenediazonium salt, giving
essentially the same results. The expected Heck product was
accompanied by a side product which revealed to be the
carboxylic acid derivative generated by acidic hydrolysis
of the a,β-unsaturated methyl ester. The feasibility of
With the feasibility of the key Heck arylation step of
our synthesis of paroxetine in RTILs ensured, we then
turned our attention toward the use of chiral media.A chiral
environment surrounding the metal might indeed lead to
some asymmetric induction in the course of the migratory
insertion step during which the stereogenic center is created.
Ordinary asymmetric induction in the course of the Heck
coupling with arenediazonium salts is a challenging task

824
Synthesis of Novel Room Temperature Chiral Ionic Liquids
J. Braz. Chem. Soc.
Table 1. The key Heck arylation reaction in various RTILs
R
R
R
Pd pre-catalyst
RTIL, ∆
X
O
O
O
OCH3
OCH3
OH
+
N
N
N
CO2Ph
CO2Ph
CO2Ph
6
7a, R = F
7b, R = H
8a, R = F
8b, R = H
Yield (%)d
ester/acid
Entry
Ra
X
RTIL
Pre-catalystb
Base
T (°C)
t (h)
Conv. (%)c
1
F
F
F
F
F
F
F
H
H
H
F
F
F
F
F
N2BF4
N2BF4
N2BF4
N2BF4
N2BF4
N2BF4
N2BF4
OTf f
I f
I f
I i
I i
I i
[BMIM][Br]
[BMIM][BF4]
[BMIM][PF6]
[BMIM][PF6]
[BMIM][NTf2]
[BDIM][NTf2] e
[BDIM][NTf2]e
[BMIM][NTf2]
[BMIM][Br]
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd2(dba)3
Pd(OAc)2
Pd(OAc)2
Pd2(dba)3
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd2(dba)3
Pd(OAc)2
Pd2(dba)3
/
70
65
48
72
1
11
66
59/11
35/12
75/16
77/5
71/18
72/17
70/18
/
2
/
3
/
65
100
100
100
100
100
0
4
/
65
1
5
/
65
1
6
/
65
1
7
/
65
1
8
NaOAc g
NaOAc g
100
100
100
100
120
120
120
120
24
24
24
22
5
9
0
/
h
10
11
12
13
14
15
[BMIM][NTf2]
[BMIM][NTf2]
[BMIM][NTf2]
[BMIM][NTf2]
[BDIM][NTf2]e
[BDIM][NTf2]e
Ag2CO3
46
56/0
30/0
82/0
9/0
h
Ag2CO3
45
h
Ag2CO3
55
h
Ag2CO3
24
5
45
I i
I i
Ag2CO3
100
68/0
h
h
Ag2CO3
24
63
35/0
a Unless otherwise stated, 1.5 equiv. of electrophile were used; b Pd(OAc)2 10 mol%; Pd2(dba)3 5 mol%; c Conversion calculated on the basis of the recovered
starting material; d Isolated yields, based on starting material recovering, when appropriate; e [BDIM] = 1-n-butyl-2,3-dimethylimidazolium; f 2.0 equiv. of
halide were used; g 1.5 equiv. of base were used; h 1.1 equiv. of base were used; i 3.0 equiv. of halide were used.
though, partly because of the arenediazonium instability
in the presence of the phosphine ligands. Moreover, the
use of chiral RTILs as medium for the more traditional
Heck reactions employing aryl halides and aryl triflates as
arylating agents were also evaluated.
The imidazolinic precursors were prepared according to
our previously described route based on the condensation
between an orthoester and the chiral diamine 9.23 Preparation
of the latter was carefully optimized: slow addition
(2 mL h-1) of a concentrated (5.4 mol L-1) aqueous solution
of 2-chloroethylamine to neat chiral amine (2 equiv.) at
80 °C provided, after workup, a crude mixture from
which the excess of chiral amine was distilled off
(40-50 °C/3 × 10-2 mbar). A bulb to bulb distillation
(90-100 °C/3 × 10-2 mbar) allowed isolation of the pure chiral
diamine9in60%yield.Theuseoftriethylorthoformateasthe
orthoester gave access to C-2 unsubstituted imidazoline 10.
Aromatisingdehydrogenationthenproducedthecorresponding
imidazole 14.23 We found that this transformation can be
accomplishedinafewminutesbytheuseofthecommercially
available NiO2 (8 equiv.) in acetonitrile under microwave
activation (200W irradiation while cooling with compressed
air so as to maintain the temperature at 90 °C). The imidazole
14 was thus obtained in 50% yield after a simple filtration
over grade III alumina. Alternatively, this compound can
be prepared by means of a cyclocondensation reaction24
Use of C-2 unsubstituted imidazolinium and imidazolium
chiral ionic liquid
In the first part of this study we focused on the possible
interaction between the palladium-based catalytic species
and the chiral imidazolium cation of the ionic liquid through
the C-2 position, bearing in mind the opportunities for the
in situ formation of imidazol-2-ylidene metal complexes.
Preparation of the chiral ionic liquids
Access to C-2 unsubstituted chiral imidazolinium/
imidazolium salts was envisioned from the corresponding
imidazoline/imidazole through a straightforward
quaternarisation/anion metathesis sequence (Scheme 3).

Vol. 21, No. 5, 2010
Pastre et al.
825
Ph
The preparation of the targeted ionic liquids required
NH
NH2
9
a final anion metathesis step, which was performed
using known procedures (Scheme 3). The imidazolinium
hexafluorophosphate salt 12 was prepared from the
corresponding acid (64% yield) as a solid melting at
86-87 °C. The bis(trifluoromethanesulfonyl)imide was
introduced by mean of the corresponding lithium salt
yielding imidazolinium 13 (80% yield), and imidazolium
Me
ref. 23
NiO2, CH3CN
MW, 90 °C
Ph
Me
Ph
Me
N
N
N
N
14 (50%)
10 (48% over 2 steps )
MeI, MeCN
n-PentBr,
Cl3CCH3
or
n-PentBr,
Cl3CCH3
or
Cl(CH2)3CN,
MeCN
1
18-20 (79-88% yield). Interestingly, H NMR analysis
_
_
X
Br
Me
of the imidazolium 20 revealed that the H-2 proton
had become highly exchangeable with deuterium, thus
indicating an increased acidity.
+
+
Ph
N
Ph
N
N
N
R
n
4
Me
Me
11 (96%)
15, n = 4, R = Me, X = Br (100%)
16, n = 0, R = Me, X = I (100%)
17, n = 3, R = CN, X = Cl (100%)
All these salts are liquid at room temperature and
differential scanning calorimetry (DSC) analyses were
recorded in order to characterize the thermal behaviour
of these new chiral ionic liquids. In sharp contrast with
its hexafluorophosphate counterpart (mp 86-87 °C), the
imidazolinium bis(trifluoromethanesulfonyl)imide 13
displayed glass transition (Tg) at –59 °C. A comparable
Tg of –57 °C was found for the corresponding n-pentyl
imidazolium salt 18. This behaviour parallels, yet to a lesser
extent, what we previously observed in the C-2-substituted
series in which the aromatic imidazolium salts displayed
Tg values 7 to 11 °C higher than the corresponding
imidazolinium derivatives. Overall, the lack of substituent
at C-2 lowered the Tg values which were of –55 °C and
–48 °C for the corresponding 2-ethyl derivatives. Finally
the side chain was also found to exert a certain influence on
the thermal behaviour of these salts since a slightly higher
Tg of –50 °C was observed for the methyl imidazolium
bis(trifluoromethanesulfonyl)imide 19, whereas the nitrile
substituted derivative 20 displayed a glass transition at
–46 °C.
HPF6, H2O
or
LiNTf2, H2O
LiNTf2,
H2O
_
X
_
Ph
N
+
N
Me
4
NTf2
Ph
Me
R
n
N
N
Me
12, X = PF6 ( 64%)
13, X = NTf2 (80%)
18, n = 4, R = Me (88%)
19, n = 0, R = Me (79%)
20, n = 3, R = CN (81%)
Scheme 3. Preparation of the imidazolinium and imidazolium chiral
RTILs.
from glyceraldehyde, a-methylbenzylamine, formaldehyde
and ammonium acetate using the Saigo’s procedure (70%
yield).25 Prolonged reflux of the imidazoline 10 or imidazole
14 in 1,1,1-trichloroethane in the presence of an excess of
1-bromopentane furnished the expected 3-pentyl derivatives
11 and 15, respectively. Treatment of the imidazole 14 with
methyl iodide at room temperature in acetonitrile smoothly
delivered the 3-methylimidazolium 16. In order to enhance
chances of interactions between the catalytic palladium
species and the imidazolium nucleus of the ionic solvent
we also prepared the imidazolium salt 17 in which the alkyl
chain bears a coordinating nitrile functionality.26 Indeed,
mechanistic studies from our laboratories have shown the
role of the solvent acetonitrile in stabilizing catalytic species
generated from Pd2(dba)3 in the course of the Heck arylation
with arenediazonium salts.27
Evaluation of the chiral ionic liquids
In order to evaluate the asymmetric induction
effectively, analytical conditions were sought for the key
arylated product. The enantiomers of 7a were readily
resolved by HPLC using a Chiralcel OD column (Hexane/
i-PrOH 70:30 (v:v), Rt = 6.6 min and 11.5 min). Separation
was sufficient to allow isolation of an enantiomerically
pure sample of each enantiomers on a semi-preparative
column. Characterization of the arylated compound 7a in an
enantiopure form allowed assessment of its configurational
stability. Importantly, no racemisation was observed, as
judged by chiral HPLC analysis, after prolonged heating of
7a in basic media (Ag2CO3, [BMIM][NTf2], 120 °C, 24 h).
On a strictly chemical standpoint, the nature of
the RTIL was found to have a certain influence on the
course of the reaction. In the imidazolinium series the
Atthisstage,itappearedcriticaltocontroltheenantiomeric
purity of our derivatives. This was realized by H NMR
1
analysis of the representative imidazolium bromide 15. The
chiralshiftreagenttris[3-trifluoromethylhydroxymethylene)-
D-camphorato]europiumIIIallowedsplitting(Δδ=0.1ppm)
of the H-2 signal of the racemate at 12.78 ppm in CDCl3.
Analysis of the enantiopure material under the same
conditionsclearlydemonstratedtheabsenceofanydetectable
racemization. This high degree of enantiomeric purity was
independent of the procedure used to prepare the chiral
imidazole precursor.

826
Synthesis of Novel Room Temperature Chiral Ionic Liquids
J. Braz. Chem. Soc.
bis(trifluoromethanesulfonyl)imide salt 13 revealed less
favourable, even under more vigourous conditions, than
the hexafluorophosphate salt 12 which allowed smooth
and clean conversion of the starting acrylate (Table 2,
entries 1, 2 and 3). As far as the imidazolium salts were
concerned, the 3-pentyl derivative 18 gave the best result.
Unexpectedly, the reaction proved rather sluggish when
the less hindered 3-methyl imidazolium salt 19 was used,
which might be correlated to an increase in viscosity
(Table 2, entry 6).A complete conversion was achieved with
the nitrile-functionalized salt 20 after prolonged heating
with Pd2(dba)3 as a pre-catalyst which presented a marked
contrast with Pd(OAc)2 (Table 2, entries 7 and 8).
Several of these chiral RTILs gave rise to an efficient
transformation, although the enantiomeric excess of the
isolated product was found negligible, independently of the
chiral ionic liquid used. In order to ensure that this behavior
was not due to a mechanistic particularity of the Heck
arylation employing arenediazonium salts, we performed
the Heck arylation with the corresponding aryl iodide.
When the olefin 6 was treated with 1-fluoro-4-iodobenzene
in the chiral imidazolium 18 a satisfactory transformation
was obtained (Table 2, entry 5), but unfortunately no
asymmetric induction was evidenced in the Heck adduct.
Preparationanduseofimidazolium-deriveddiaminocarbene
Pd complexes
Aiming at increasing the interaction between the
imidazolium nucleus of the RTIL and the palladium
catalyst, we also studied the use of imidazolium-derived
pre-formed diaminocarbene palladium complexes.28
Thus, we first prepared the 1-n-butyl-3-
methylimidazolium bromide-derived N-heterocyclic
carbene palladium complex 22 described by Xiao
(Scheme 4).16 The latter was generated from Pd(OAc)2 in
refluxing THF in 77% isolated yield as the sole trans isomer
(anti/syn, 1:1). When evaluated in our model reaction of
6 with 4-fluorobenzenediazonium tetrafluoroborate, this
entity proved poorly active in [BMIM][Br] (20 mol%,
80 °C, 48 h, 9% yield bsmr at 60% of conversion) and
totally inefficient in [BMIM][PF6] (20 mol%, 65 °C, 24 h).
Table 2. The Heck arylation in various imidazolinium and imidazolium chiral RTILs
F
F
F
X
O
O
O
Pd pre-catalyst
RTIL, ∆
OCH3
OCH3
OH
+
N
N
N
CO2Ph
CO2Ph
CO2Ph
6
7a
8a
_
_
RTILs:
NTf2
PF6
+
+
Ph
Me
Ph
N
N
N
Me
N
Me
4
4
Me
12
13
_
_
_
NTf2
NTf2
NTf2
+
+
+
Ph
Me
Ph
Me
Ph
Me
Me
4
CN
3
N
N
N
N
N
N
Me
18
19
20
Yield (%) d
ester/acid
Entrya
X
RTIL
Pre-catalystb
T (°C)
t (h)
Conv. (%) c
1
2
3
4
5e
6
7
8
N2BF4
N2BF4
N2BF4
N2BF4
If
12
13
13
18
18
19
20
20
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd2(dba)3
90
65
90
65
90
65
65
65
6
27
7
100
26
72/0
50/0
53/0
66/24
74/0
47/0
79/0
53/10
39
6
100
50
4
N2BF4
N2BF4
N2BF4
11
5
23
27
24
100
a 1.5 equiv. of the arenediazonium salt was used; b Pd(OAc)2 10 mol%; Pd2(dba)3 5 mol%; c Conversion calculated on the basis of the recovered starting
material; d Isolated yields, based on starting material recovering; e 1.1 equiv. of the base Ag2CO3 were used; f 2.0 equiv. of iodide were used.

Vol. 21, No. 5, 2010
Pastre et al.
827
_
Br
to induce any transformation. The same behavior
was observed when 1-fluoro-4-iodobenzene was used
(3.0 equiv. Ag2CO3, DMF, 130 °C, 24 h). The intrinsic
stability of these bis-diaminocarbene palladium complexes
might be responsible for their lack of catalytic activity.
+
N
N
Me
n
R
21, R = Me, n = 3
15, R = (S)-Ph(Me)CH, n = 4
Pd(OAc)2 (0.5 equiv.)
THF, reflux
Me
Use of an hydroxylated chiral ionic liquid
n
N
PdBr2
In the course of the development of our synthetic
methodology we found out that the key Heck reaction
could be run efficiently in MeOH. The beneficial effect
of protic solvents prompted us to explore the influence
of hydroxyl-containing chiral ionic liquids for this
transformation.
2
N
R
22, R = Me, n = 3 (trans-syn/trans-anti 1:1) (77%)
23, R = (S)-Ph(Me)CH, n = 4 (cis-syn/trans-anti 1:1) (54%)
Scheme 4. Preparation of palladium complexes from imidazolium salts.
In parallel, the behaviour of our chiral imidazolium
cation in the presence of Pd(OAc)2 was also explored by
means of the reaction of the bromide 15 with 0.5 equiv.
of the palladium salt in refluxing THF (Scheme 3). A
smooth transformation occurred after heating 15 with
Pd(OAc)2 for 6 h, allowing isolation of the expected
palladium complex 23 in 54% yield as a 1:1 mixture of
We took advantage here of the preparation of the
phenylglycinol derivative 26 we reported recently.30
This ionic liquid was synthesized from pyridinium 25
employing a route previously described by us based
on the use of the Zincke reaction (Scheme 5).31 The
bis(trifluoromethanesulfonyl)imide anion was selected
on the basis of previous studies.32 To our satisfaction, it
was found that this hydroxylated derivative displayed a
Tg of –45 °C measured by DSC analysis as compared to
–30 °C for the its non-hydroxylated counterpart 24.32 The
latter was also considered for the matter of comparison.
1
isomers according to H and 13C NMR. Assignment of
the stereochemical identity of these diaminocarbenes
complexes was not trivial. Gratifyingly, a single crystal
suitable for X-ray diffraction analysis could be obtained
for each isomer thus allowing to identify the two
products as the trans-anti isomer 23a along with the
quite unexpected cis-syn derivative 23b (Figure 1).29 A
π-stacking interaction between the phenyl groups of each
diaminocarbene moieties might account for the formation
of this strained isomer.
_
Cl
+
N
_
ref. 30
ref. 32
+
NO2
+
_
NTf2
N
N
NTf2
OH
Ph
Me
Ph
26 (61%)
NO2
24 (74%)
25
Scheme 5. Preparation of the pyridinium chiral RTILs.
The unsubstituted a-methylbenzylamine-derived
salt 24 gave rise to a smooth transformation with
4-fluorobenzenediazonium tetrafluoroborate (Table 3,
entry 1). Despite the high tolerance of the key Heck
coupling for alcoholic media, the reaction in the
hydroxylated derivative 26 proved much less efficient,
irrespectively to the pre-catalyst (Table 3, entries 2 and 3).
The conversions were not altered, but the yields were
strongly affected. For the sake of comparison, the iodide
was also evaluated as under the reaction conditions
determined previously (Table 3, entries 4 and 5). As
observed before, Pd(OAc)2 was more efficient than
Pd2(dba)3. Notably, in this case the halide gave rise
to a better transformation than the corresponding
arenediazonium salt. Unfortunately, no enantiomeric
excess was detected from the analysis of the isolated
products.
Figure 1. X-ray structure of the trans-anti 23a (left) and cis-syn 23b (right)
diaminocarbene Pd complexes obtained from the chiral imidazolium 15
and Pd(OAc)2.19
The mixture of isomers 23a, b was evaluated in our
key Heck arylation with 4-fluorobenzenediazonium
tetrafluoroborate. However, the use of 10-20 mol% of
these complexes in either THF (reflux, 24 h), CH3CN
(reflux, 24 h), or [BMIM][PF6] (100 °C, 24 h) failed

828
Synthesis of Novel Room Temperature Chiral Ionic Liquids
J. Braz. Chem. Soc.
Table 3. The Heck arylation in hydroxylated and non-hydroxylated chiral pyridinium RTILs
F
F
F
X
O
O
O
Pd pre-catalyst
OCH3
OCH3
OH
+
RTIL, ∆
N
N
N
CO2Ph
CO2Ph
CO2Ph
6
7a
8a
RTILs:
_
+
_
NTf2
+
NTf2
N
N
OH
Ph
Me
Ph
24
26
Yield (%) d
ester/acid
Entry
Xa
RTIL
Catalystb
T (°C)
t (h)
Conv. (%) c
1
N2BF4
24
26
26
26
26
Pd(OAc)2
Pd(OAc)2
Pd2(dba)3
Pd(OAc)2
Pd2(dba)3
65
65
1
1.5
1.5
1
100
100
100
100
100
53/18
34/4
21/3
80/0
51/0
2
N2BF4
3
N2BF4
65
4 e
5 e
I
I
120
120
2
a 1.5 equiv. of arenediazonium salt and 3.0 equiv. of iodide were used; b Pd(OAc)2 10 mol%; Pd2(dba)3 5 mol%; c Conversion calculated on the basis of the
recovered starting material; d Isolated yields, based on starting material recovering; e 1.1 equiv. of the base Ag2CO3 was used.
The use of chiral ionic liquid bearing a basic functionality
as a potential coordination site
the access to the required pyridinium salt. In this regard,
the use of microwave activation proved highly efficient.
Indeed, treatment of the nicotine (27) with i-propyl iodide
in CH3CN at 100 °C under microwave irradiation led to the
clean and efficient formation of the expected pyridinium
iodide 28 in only 2 h (Scheme 6). Anion metathesis
proceeded uneventfully for this iodide salt to afford the
desired chiral pyridinium bis(trifluoromethanesulfonyl)
imide 29. The latter displayed a glass transition at –56 °C
measured by DSC.
In the last part of this study we adopted an alternative
strategy. In order to drive the interaction between the ionic
liquid and the catalytic species we opted for the use of
chiral ionic entities bearing a N-heterocycle susceptible to
coordination to the metal centre. Indeed, several studies
by Shreeve and co-workers33 have recently described
catalytically active entities based on the complex between
a palladium salt and an ionic liquid bearing a basic
functionality. To the best of our knowledge, no examples
of chiral derivative of that kind were reported so far. We
reasoned that such electron-rich entities might interact
significantly with the cationic palladium species involved in
the catalytic cycle operating in the case of arenediazonium
salts.
N
N
i-PrI
LiNTf2
H2O
Me
N
+
Me
NTf2
Me
29 (66%)
+
_
_
N
MeCN
MW, 100 °C
N
Me
I
N
Me
Me
Me
Nicotine (27)
28 (92%)
Scheme 6. Preparation of the nicotine-derived chiral RTIL 29.
We first focused on the readily accessible nicotine
derivative. Albrecht has recently used such a pyridinium
halide as a carbene precursor to prepare a catalytically active
palladium complex.34 The quaternarization of nicotine had
already been described earlier by Shibagaki et al.35 who
showed that it was possible to chemoselectively N-alkylate
the pyridine nucleus versus the pyrrolidine ring on the
basis of steric considerations. However, as the yields and
conversion reported were not satisfactory we first optimized
We then evaluated the influence of this chiral pyridinium
as an additive in the course of our model arylation (Table 4).
Since HBF4 is formed during thetransformation, 1.2 equiv. of
the basic ionic liquid were used. On the other hand, the C-2
methylderivative[BDIM][NTf2]wasselectedasapotentially
“innocent” ionic media, although carbene formation at C-4
and C-5 of the imdazolium ring has also been reported.36 The
presence of the additive strongly changed the conversion in

Vol. 21, No. 5, 2010
Pastre et al.
829
the case of 4-fluorobenzenediazonium tetrafluoroborate and
of the aryl iodide counterpart. In spite of lower conversions,
yields were higher using the aryl halide (Table 4, entries
3 and 4). This observation might be related with some
decomposition of the arenediazonium salt in the reaction
media.
The impact of the chiral pyridinium ionic liquid 32 on
the outcome of the Heck reaction is similar that observed
previously for the ionic liquid 29 (Table 4). The basic nature
of the additive seems to hamper the transformation, although
to a lesser extent than that observed with the nicotine-
Another pyridinium ionic liquid bearing a chiral
pyrrolidine moiety was prepared by the Zincke reaction
(Scheme 7). Thus, treatment of the so-called Zincke salt
by the commercially available chiral primary amine 30
afforded the desired pyridinium chloride 31, which upon
anion metathesis provided the bis(trifluoromethanesulfonyl)
imide salt 32 in 35% overall yield. A Tg of –52 °C was
measured by DSC for this chiral ionic liquid.
NH2
+
Cl
NO2
N
+
+
N
N
N
Et 30
LiNTf2
H2O
Cl
NTf2
n-BuOH
reflux
N
N
Et
Et
NO2
25
31 (51%)
32 (67%)
Scheme 7. Synthesis of the chiral pyridinium RTIL 33 by means of the
Zincke reaction.
Table 4. The Heck arylation in an achiral ionic media in the presence of different chiral ionic additives
F
F
O
O
O
F
X
OH
OCH3
OCH3
Pd pre-catalyst
+
N
N
N
solvent, ∆
29 or 32 or 35
(1.2 equiv.)
CO2Ph
CO2Ph
CO2Ph
6
7a
8a
Chiral ionic additives:
Ph
N
N
N
n-Bu
NTf2
N
N
NTf2
Me
Me
NTf2
Me
+
_
N
N
Me
Et
29
32
35
Yield (%) d
ester/acid
Entry
Additive
Xa
Solvent
Pre-catalystb
T (°C)
t (h)
Conv. (%) c
1
29
29
29
29
32
32
32
32
32
32
35
35
35
35
35
35
N2BF4
N2BF4
I
[BDMIM][NTf2]
[BDMIM][NTf2]
[BDMIM][NTf2]
[BDMIM][NTf2]
[BDIM][NTf2]
[BDIM][NTf2]
THF
Pd(OAc)2
Pd2(dba)3
Pd(OAc)2
Pd2(dba)3
Pd(OAc)2
Pd2(dba)3
Pd(OAc)2
Pd2(dba)3
Pd(OAc)2
Pd2(dba)3
Pd(OAc)2
Pd2(dba)3
Pd(OAc)2
Pd2(dba)3
Pd(OAc)2
Pd2(dba)3
65
65
24
24
24
24
24
24
24
24
24
24
24
24
3
31
23
9
47/0
52/0
80/0
92/0
57/0
47/0
100/0
31/0
91/0
70/0
90/0
96/0
84/0
86/0
58/0
55/0
2
3e
4e
120
120
65
I
12
47
32
19
11
29
14
100
100
54
31
100
45
5
N2BF4
N2BF4
N2BF4
N2BF4
I
6
65
7
65
8
THF
65
9 e
10 e
11
12
13
14
15 e
16 e
[BDIM][NTf2]
[BDIM][NTf2]
[BDIM][NTf2]
[BDIM][NTf2]
THF
120
120
65
I
N2BF4
N2BF4
N2BF4
N2BF4
I
65
65
THF
65
3
[BDIM][NTf2]
[BDIM][NTf2]
120
120
7
I
24
a 1.5 equiv. of arenediazonium salt and 3.0 equiv. of iodide were used; b Pd(OAc)2 10 mol%; Pd2(dba)3 5 mol%; c Conversion calculated on the basis of the
recovered starting material; d Isolated yields, based on starting material recovering; e 1.1 equiv. of the base Ag2CO3 was used.

830
Synthesis of Novel Room Temperature Chiral Ionic Liquids
J. Braz. Chem. Soc.
derived pyridinium salt. For comparison, the reaction
with the 4-fluorobenzenediazonium tetrafluoroborate was
also carried out in THF instead of [BDIM][NTf2] and the
conversions were even lower in this molecular solvent
(Table 4, entries 7 and 8).
also observed in THF (Table 4, entries 13 and 14). The aryl
iodide also gave a reasonably efficient reaction thanks to
the use of Pd(OAc)2 (Table 4, entries 15 and 16).
Conclusions
Finally, in an attempt to reduce the basicity of the
chiral additive, we turned our attention to the possibility
of introducing a heteroaromatic appendage into the
structure of the ionic liquid. Shreeve has described a
series of achiral 2-imidazolyl or 2-pyridylimidazolium
salt useful for the preparation of palladium complexes.33
In line with this work we envisioned the synthesis of such
compounds from a chiral primary amine by means of a
one-pot multi-component reaction. Although application
of this route to the preparation of chiral 2,2’-bisimidazole
did not appear viable,37 we succeeded in preparing a
2-pyrydylimidazole. Indeed, after careful optimization
it was found that treatment of a-methylbenzylamine
with glyoxal, ammonium hydroxide and pyridine-2-
carboxaldehyde furnished imidazole 33 in 18% yield
(Scheme 8).
Eight new chiral RTILs were prepared using novel
and/or carefully optimized synthetic routes. This series
of imidazolinium, imidazolium and pyridinium ionic
liquids were fully characterized, including differential
scanning calorimetry (DSC) analysis. The Heck reaction of
substituted aza-endocyclic acrylates using arenediazonium
tetrafluoroborates and aryl iodides as electrophiles were
investigated in these new RTILs. A strong influence of
the counter-ion was observed, with the lipophilic RTILs
providing the best results. The Heck arylations performed
in these chiral ionic entities, either as a solvent or an
additive, were effective leading to complete conversion of
the substrate and good to excellent yield of the Heck adduct.
In spite of the overall performance of the Heck arylations in
all the cases studied no asymmetric induction was detected.
Two new diastereoisomeric NHC-palladium complexes
were prepared in moderate yields and their structure
characterized by X-ray diffraction analysis thus allowing
the identification of the unusual cis-syn stereoisomer 23b.
Overall, the Heck arylations employing arenediazonium
tetrafluoroborates in RTILs were more effective than the
traditional protocols employing aryl iodides in terms of
reactivity and yields. Applications of the new chiral RTILs
described herein to other synthetic transformations are in
progress and the results concerning these studies will be
reported in due course.
H
H
Ph
Me
N
N
N
O
O
i-PrOH
Ph
NH2
+
NH4OH
80 ºC
CHO
N
Me
33 (18%)
n-BuI, CH3CN,
MW, 100 ºC
Ph
Me
Ph
N
N
N
N
N
N
n-Bu
NTf2
n-Bu
I
LiNTf2
H2O
Me
35 (92%)
34 (83%)
Experimental
Scheme 8. Preparation of the chiral imidazolium ionic liquid 35.
General
Quaternarization of the more basic imidazole nucleus
was then carried out in a highly convenient and efficient
manner. Microwave activation and anion metathesis step
provided the expected chiral ionic liquid 35 in 76% overall
yield (Scheme 8). Despite the presence of the aromatic
substituent at C-2, this bis(trifluoromethanesulfonyl)imide
salt displayed a Tg of –40 °C as measured by DSC.
The less basic additive 35 was found to be fully
compatible with the use of 4-fluorobenzenediazonium
tetrafluoroborate in our key palladium-catalyzed arylation
(Table 4). The expected product was isolated in high yield,
although the transformation appeared to be slower in
[BDIM][NTf2] (Table 4, entries 11 and 12). Remarkably, in
this particular case the pre-catalyst Pd2(dba)3 gave a better
result than Pd(OAc)2. A sluggish, yet clean, reaction was
Reagents and solvents are commercial grade and were
used as supplied, except when specified in the experimental
procedure. CH2Cl2 was distilled from calcium hydride and
THF was distilled from Na. Reactions were monitored by
TLC analysis using Merck Silica Gel 60 F-254 thin layer
plates.FlashcolumnchromatographywasperformedonAcros
silica gel 60, 0.040-0.063 mm. 1H NMR and 13C NMR data
were recorded on aVarian Gemini 2000 (300 MHz for 1H and
75 MHz for 13C NMR), Varian Inova (500 MHz for 1H and
125 MHz for 13C NMR) or Bruker Avance (250 MHz for 1H
and63MHzfor13CNMRor300MHzfor 1Hand75MHzfor
13CNMR)spectrometerusingasinternalstandardtheresidual
nondeuteratedsolvent(CHCl3,CH3OH,acetoneorDMSO)or
TMS (1H NMR). Data are reported as follows: chemical shift

Vol. 21, No. 5, 2010
Pastre et al.
831
in ppm (d), multiplicity (s = singlet, d = doublet, t = triplet, q
= quartet, m = multiplet, br = broad signal), coupling constant
(Hz), integration. High-resolutionmassspectra(HRMS)were
measured on a VG Auto-spec-Micromass spectrometer (EI)
or in a Waters Q-Tof Ultima API (ESI). Infrared spectra (IR)
were obtained on aThermo-Nicolet IR-200 spectrometer and
absorptions are reported in reciprocal centimeters. Melting
points were recorded on an Electrothermal 9100 melting
point apparatus and are uncorrected. Differential scanning
calorimetry(DSC)analyseswererecordedonaDSCDiamond
Perkin Elmer.
by flash column chromatography over silica gel (petroleum
ether/ethyl acetate, 4:1) to furnish the desired Heck adduct 7a
and, in some cases, the corresponding acid 8a.
General procedure for the Heck coupling with aryl iodides
in ionic liquids
To a solution of olefin 6 (1 equiv., 0.25 mmol) in ionic
liquid (4.0 mL mmol-1) was added the aryl iodide (3 equiv.),
Ag2CO3 (1.1 equiv.) and Pd pre-catalyst (5-10 mol%). The
reactionmixturewasimmersedinanoilbathandheatedunder
stirring(seetablesforthetemperatureandreactiontime).After
cooling, the mixture was extracted with Et2O (6 × 10 mL) and
with1,1,1-trichloroethane(3×10mL).Thecombinedorganic
layerswerethenconcentratedtodrynessandpurifiedbyflash
columnchromatographyoversilicagel(petroleumether/ethyl
acetate, 4:1) to furnish the arylated product 7a,b.
General procedures for the quaternarization
A solution of imidazoline 10 or imidazole 14 (1 equiv.)
and alkyl halide (3.0-5.0 equiv.) in 1,1,1-trichloroethane
or acetonitrile (0.6 mL mmol-1) was refluxed until TLC
monitoring showed complete consumption of the starting
material (2-3 days). For the reaction in 1,1,1-trichloroethane,
the insoluble oily material was separated by decantation
and washed several times with 1,1,1-trichloroethane to give
the expected halide salt. For the reaction in acetonitrile, the
mixture was concentrated to dryness and partitioned between
Et2O and water. After two additional extractions with Et2O,
the aqueous phase was concentrated to dryness to give the
expected halide salt.
Specific procedures and compounds data
3-Pentyl-1-((1S)-1-phenylethyl)-4,5-dihydro-1H-imidazolium
bromide (11)
Prepared from imidazoline 10 (1.0 g, 5.75 mmol)
according to the general procedure for quaternarization
in 1,1,1-trichloroethane. Bromide 11 (1.80 g, 96%) was
obtained as light brown liquid. [a]25D –6.8 (c 1.20, CHCl3);
IRnmax/cm-1:2933,2872,1646,1495,1455,1382,1255,1201,
1142, 703 (thin film); 1H NMR (300 MHz, CDCl3) d 9.76 (s,
1H), 7.28-7.42 (m, 5H), 5.06 (q, J 7.0 Hz, 1H), 3.95-3.84 (m,
2H), 3.79-3.64 (m, 4H), 1.79 (d, J 7.0 Hz, 3H), 1.71-1.60 (m,
2H), 1.35-1.23 (m, 4H), 0.87 (t, J 7.0 Hz, 3H);13C NMR (75
MHz, CDCl3) d 156.6 (CH), 137.3 (C0), 129.0 (CH), 128.6
(CH), 126.7 (CH), 57.6 (CH), 48.2 (CH2), 48.0 (CH2), 46.3
(CH2), 28.1 (CH2), 26.8 (CH2), 21.9 (CH2), 19.5 (CH3), 13.6
(CH3); MS (ESI +) m/z: 245 [M+]; MS (ESI–) m/z: 79, 81
[Br–];HRMS(ESI+)m/z:CalcdforC16H25N2 [M+]245.2018,
Found 245.2021.
General procedure for the anion metathesis with lithium
bis(trifluoromethanesulfonyl)imide
Asolutionofhalidesalt(1.0equiv.)inwater(6.5mLmmol-1)
containing lithium bis(trifluoromethanesulfonyl)imide
(1.1 equiv.) was heated with stirring at 70 °C for 2 h and
allowedtostandatroomtemperatureovernight.Theinsoluble
oily material was extracted with dichloromethane and the
organiclayerwasseparatedandwashedwithwaterandbrine,
driedoverNa2SO4, filteredandconcentratedtodrynesstogive
the expected bis(trifluoromethanesulfonyl)imide salt.
3-Pentyl-1-((1S)-1-phenylethyl)-4,5-dihydro-1H-imidazolium
hexafluorophosphate (12)
GeneralprocedurefortheHeckcouplingwitharenediazonium
salts in ionic liquids
To a stirred solution of imidazolinium bromide 11
(1.97 g, 6.04 mmol) in water (12 mL) at 0 °C was added
hexafluorophosphoricacid(1.16mLofa60%solutioninH2O,
7.85 mmol, 1.3 equiv.). The stirring was continued at 0 °C for
2 h and the solution was allowed to stand at room temperature
overnight. The reaction mixture was then extracted with
CH2Cl2 and the combined organic layers were washed with
water, driedoverNa2SO4, filteredandconcentratedtodryness
to give 12 (1.52 g, 64%), obtained as a light yellow solid.
[a]25D –4.0 (c 1.50, CHCl3); mp 86-87 °C; IR nmax/cm-1: 2935,
1659, 1451, 1383, 1344, 1297, 1258, 1200, 1144, 827, 764,
To a solution of olefin 6 (1 equiv., typically 0.25 mmol) in
ionic liquid (4.0 mL mmol-1) was added, at once, a mixture of
the 4-fluorobenzenediazonium tetrafluoroborate (1.5 equiv.)
and Pd pre-catalyst (5-10 mol%). The reaction mixture was
immersed in an oil bath and heated under stirring (see tables
for the temperature and reaction time). After cooling, the
mixture was extracted (6 × 40 mL mmol-1) with Et2O and
with1,1,1-trichloroethane(3×40mLmmol-1).Thecombined
organic layers were then concentrated to dryness and purified

832
Synthesis of Novel Room Temperature Chiral Ionic Liquids
J. Braz. Chem. Soc.
705 (thin film); 1H NMR (300 MHz, CDCl3) d 7.98 (s, 1H),
7.46-7.26 (m, 5H), 4.76 (q, J 6.8 Hz, 1H), 3.96-3.81 (m, 2H),
3.80-3.68 (m, 2H), 3.50 (t, J 7.6 Hz, 2H), 1.72 (d, J 6.9 Hz,
3H), 1.69-1.59 (m, 2H), 1.40-1.21 (m, 4H), 0.89 (t, J 6.9 Hz,
3H);13C NMR (75 MHz, CDCl3) d 155.2 (CH), 137.4 (C0),
129.3 (CH), 128.9 (CH), 126.7 (CH), 58.2 (CH), 48.5 (CH2),
47.9 (CH2), 46.8 (CH2), 28.3 (CH2), 26.7 (CH2), 22.0 (CH2),
19.1 (CH3), 13.7 (CH3); MS (ESI +) m/z: 245 [M+]; MS
(ESI–)m/z:145[PF6–];HRMS(ESI+)m/z:CalcdforC16H25N2
[M+] 245.2018, found 245.2028; HRMS (ESI +) m/z: Calcd
for PF6 [PF6–] 144.9642, found 144.9635.
iodomethane (120 μL, 1.30 mmol, 1.35 equiv.) in acetonitrile
(2.0mL)wasstirredatroomtemperaturefor20h.Thesolution
was concentrated to dryness to give 16 (300 mg, quant.) as
a light yellow oil. [a]25 +4.3 (c 5.3, CHCl3); IR nmax/cm-1:
D
3120, 2934, 1604, 1572, 1496, 1330, 1156, 721 (thin film);
1H NMR (300 MHz, CDCl3) d 10.19 (s, 1H), 7.57 (t, J 1.7
Hz, 1H), 7.51-7.37 (m, 5H), 7.34 (t, J 1.8 Hz, 1H), 5.89 (q,
J 7.0 Hz, 1H), 4.14 (s, 3H), 2.06 (d, J 7.0 Hz, 3H);13C NMR
(75 MHz, CDCl3) d 137.5 (CH), 135.9 (C0), 129.3 (CH),
126.9 (CH), 123.8 (CH), 120.8 (CH), 59.9 (CH), 37.1 (CH3),
21.4 (CH3); MS (ESI +) m/z: 187 [M+]; MS (ESI –) m/z: 127
[I–]; HRMS (ESI +) m/z: Calcd for C12H15N2 [M+] 187.1235,
found 187.1237.
3-Pentyl-1-((1S)-1-phenylethyl)-4,5-dihydro-1H-imidazolium
bis(trifluoromethanesulfonyl)imide (13)
Prepared from imidazolinium bromide 11 (1.80 g,
5.54 mmol) according to the general procedure for the anion
metathesis with lithium bis(trifluoromethanesulfonyl)imide.
Salt 13 (2.32 g, 80%) was obtained as a light yellow liquid.
3-(3-cyanopropyl)-1-((1S)-1-phenylethyl)-1H-imidazolium
chloride (17)
Preparedfromimidazole14(1.04g,6.03mmol)according
to the general procedure for quaternarization in acetonitrile.
Chloride 17 (1.66 g, quant.) was obtained as light yellow oil.
[a]25D –1.2 (c 1.07, CHCl3); IR nmax/cm-1: 3057, 2938, 2467,
2247, 1558, 1496, 1456, 1258, 1158, 1014, 878, 853, 753,
706, 660 (thin film); 1H NMR (300 MHz, CDCl3) d 10.68 (s,
1H), 7.82 (s, 1H), 7.27-7.21 (m, 5H), 7.15 (s, 1H), 5.68 (q,
J 6.9 Hz, 1H), 4.57 (t, J 6.7 Hz, 2H), 2.58 (t, J 6.9 Hz, 2H),
2.28 (quintet, J 6.7 Hz, 2H), 1.89 (d, J 6.9 Hz, 3H);13C NMR
(75 MHz, CDCl3) d 137.7 (CH), 129.3 (CH), 126.7 (CH),
123.0 (CH), 120.7 (CH), 118.6 (C0), 60.0 (CH), 48.3 (CH2),
26.1 (CH2), 21.1 (CH3), 14.4 (CH2); MS (ESI +) m/z: 240
[M+]; HRMS (ESI +)m/z: Calcd for C15H18N3 [M+] 240.1501,
found 240.1481.
[a]25 –2.7 (c 1.49, CHCl3); Tg –59 °C; IR nmax/cm-1: 2961,
D
1649, 1456, 1350, 1186, 1136, 1056, 788, 739, 703 (thin film);
1HNMR(300MHz, CDCl3)d8.05(s, 1H), 7.46-7.34(m, 3H),
7.32-7.27 (m, 2H), 4.80 (q, J 7.0 Hz, 1H), 3.96-3.84 (m, 2H),
3.82-3.70(m,2H),3.48(t,J7.6Hz,2H),1.71(d,J6.9Hz,3H),
1.68-1.58(m,2H),1.39-1.20(m,4H),0.89(t,J7.0Hz,3H);13C
NMR(75MHz, CDCl3)d155.3(CH), 137.1(C0), 129.4(CH),
129.1(CH),126.7(CH),119.8(q,JC-F 321.3Hz,SO2CF3),58.2
(CH3), 48.6 (CH2), 48.0 (CH2), 46.7 (CH2), 28.3 (CH2), 26.8
(CH2),22.0(CH2),19.1(CH3),13.7(CH3);MSESI+)m/z:245
[M+]; MS (ESI –) m/z: 280 [NTf2–]; HRMS (ESI +) m/z: Calcd
for C16H25N2 245.2018 [M+], found 245.2029; HRMS (ESI –)
m/z: Calcd for C2NO4F6S2 279.9173 [NTf2–], found 279.9190.
3-Pentyl-1-((1S)-1-phenylethyl)-1H-imidazolium
bis(trifluoromethanesulfonyl)imide (18)
3-Pentyl-1-((1S)-1-phenylethyl)-1H-imidazoliumbromide(15)
Prepared from imidazole 14 (284 mg, 1.65 mmol)
according to the general procedure for quaternarization in
1,1,1-trichloroethane. Imidazolium 15 (530 mg, quant.) was
obtained as light brown liquid. [a]25D –13.2 (c 1.80, CHCl3);
IR nmax/cm-1: 3056, 2957, 2871, 1672, 1561, 1456, 1382,
1162, 732(thin film); 1H NMR (300 MHz, CDCl3) d 10.77
(s, 1H), 7.47-7.41 (m, 2H), 7.40-7.32 (m, 4H), 7.28-7.25 (m,
1H), 5.99 (q, J 7.0 Hz, 1H), 4.35 (t, J 7.4 Hz, 2H), 2.00 (d, J
7.4 Hz, 3H), 1.92 (quintet, J 7.4 Hz, 2H), 1.37-1.24 (m, 4H),
0.85 (t, J 7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 137.5
(CH), 135.1 (C0), 128.5 (CH), 128.4 (CH), 126.2 (CH), 121.9
(CH), 120.4 (CH), 58.9 (CH), 49.2 (CH2), 29.2 (CH2), 27.5
(CH2), 21.3 (CH2), 20.5 (CH3), 13.1 (CH3); MS (ESI +) m/z:
243 [M+]; MS (ESI –) m/z: 79, 81 [Br–]; HRMS (ESI +)m/z:
Calcd for C16H23N2 [M+] 243.1861, found 243.1865.
Prepared from imidazolium bromide 15 (909 mg,
2.81 mmol) according to the general procedure for the anion
metathesis with lithium bis(trifluoromethanesulfonyl)imide.
Salt 18 (1.30 g, 88%) was obtained as a light yellow liquid.
[a]25D –8.1 (c 1.73, CHCl3); Tg –57 °C; IR nmax/cm-1: 3146,
2962, 1557, 1557, 1457, 1349, 1186, 1136, 1055, 789, 704
1
(thin film); H NMR (300 MHz, CDCl3) d 8.87 (s, 1H),
7.46-7.37 (m, 3H), 7.36-7.32 (m, 2H), 7.31-7.28 (m, 1H),
7.25-7.22 (m, 1H), 5.67 (q, J 7.0 Hz, 1H), 4.18 (t, J 7.5 Hz,
2H), 1.95 (d, J 7.0 Hz, 3H), 1.86 (quintet, J 7.5 Hz, 2H),
1.42-1.22 (m, 4H), 0.88 (t, J 7.0 Hz, 3H);13C NMR (75 MHz,
CDCl3) d 137.5 (CH), 134.3 (C0), 129.5 (CH), 126.7 (CH),
122.5 (CH), 121.0 (CH), 119.8 (q, JC-F 321.4 Hz, SO2CF3),
60.1 (CH), 50.2 (CH2), 29.7 (CH2), 28.0 (CH2), 21.8 (CH2),
20.6 (CH3), 13.6 (CH3); MS (ESI +) m/z: 243 [M+]; MS
(ESI –) m/z: 280 [NTf2–]; HRMS (ESI +) m/z: Calcd for
C16H23N2 [M+] 243.1861, found 243.1865; HRMS (ESI –)
m/z:CalcdforC2NO4F6S2 [NTf2–]279.9173, found279.9170.
3-Methyl-1-((1S)-1-phenylethyl)-1H-imidazoliumiodide(16)
A solution of imidazole 14 (166 mg, 0.96 mmol) and

Vol. 21, No. 5, 2010
Pastre et al.
833
3-Methyl-1-((1S)-1-phenylethyl)-1H-imidazolium
bis(trifluoromethanesulfonyl)imide (19)
(300 MHz, CDCl3) d 7.67 (d, J 7.1 Hz, 2H), 7.57 (d, J 6.8 Hz,
2H), 7.43-7.28 (m, 6H), 6.86 (q, J 7.2 Hz, 1H), 6.80 (d, J 1.8
Hz, 1H), 6.78 (d, J 1.8 Hz, 1H), 6.76 (q, J 7.2 Hz, 1H), 6.57
(apparent d, J 7.1 Hz, 1H), 6.55 (apparent d, J 1.9 Hz, 1H),
4.61-4.35 (m, 4H), 2.19-2.04 (m, 4H), 2.01 (d, J 7.1 Hz, 3H),
1.89 (d, J 7.1 Hz, 3H), 1.50-1.40 (m, 4H), 1.37-1.27 (m, 4H),
0.96(apparentt, J6.9Hz, 3H), 0.80(apparentt, J6.8Hz, 3H);
13C NMR (75 MHz, CDCl3) d 168.9 (C0), 168.8 (C0), 140.2
(C0), 139.9 (C0), 128.6 (CH), 128.6 (CH), 128.0 (CH), 127.9
(CH), 127.8 (CH), 127.7 (CH), 58.3 (2 CH), 51.2 (CH2), 51.1
(CH2), 30.6 (CH2), 30.5 (CH2), 29.2 (CH2), 29.0 (CH2), 22.4
(CH2), 22.3 (CH2), 20.3 (CH3), 20.2 (CH3), 14.0 (CH3), 13.9
(CH3); MS (ESI +) m/z: 671 [M-Br] (most abundant isotopic
distribution); HRMS (ESI +) m/z: Calc. for C32H44N4BrPd
[M-Br] 671.1783, found 671.1818 (most abundant isotopic
distribution).
Preparedfromimidazoliumiodide16(300mg,0.95mmol)
according to the general procedure for the anion metathesis
with lithium bis(trifluoromethanesulfonyl)imide. Salt 19
(350 mg, 79%) was obtained as a light yellow liquid. [a]25
D
–4.3 (c 2.8, CHCl3); Tg –50 °C; IR nmax/cm-1: 3154, 2989,
1621, 1572, 1457, 1345, 1194, 1137, 1055, 707 (thin film);
1H NMR (300 MHz, CDCl3) d 8.73 (s, 1H), 7.45-7.36 (m,
3H), 7.35-7.30 (m, 2H), 7.28 (t, J 1.8 Hz, 1H), 7.21 (t, J 1.8
Hz, 1H), 5.60 (q, J 7.0 Hz, 1H), 3.91 (s, 3H), 1.93 (d, J 7.0
Hz, 3H); 13C NMR (75 MHz, CDCl3) d 137.3 (CH), 135.0
(C0), 129.6 (CH), 129.5 (CH), 126.7 (CH), 123.8 (CH),
121.0 (CH), 119.8 (q, JC-F 318.7 Hz, SO2CF3), 60.2 (CH),
36.4 (CH3), 20.6 (CH3); MS (ESI +) m/z: 187 [M+]; MS
(ESI –) m/z: 280 [NTf2–]; HRMS (ESI +) m/z: Calcd for
C12H15N2 [M+] 187.1235, found 187.1235; HRMS (ESI –)
m/z:CalcdforC2NO4F6S2 [NTf2–]279.9173, found279.9164.
1-isopropyl-3-((S)-1-methylpyrrolidin-2-yl)pyridiniumiodide
(28)
3-(3-cyanopropyl)-1-((1S)-1-phenylethyl)-1H-imidazolium
bis(trifluoromethanesulfonyl)imide (20)
A solution of (–)-nicotine (27) (406 mg, 2.50 mmol) and
2-iodopropane (250 μL, 2.55 mmol) in acetonitrile (2.5 mL)
was heated at 100 °C in a sealed tube under microwave
irradiation (150 W) for 2 h. Next, the volatiles were removed
underreducedpressureandtheresidueobtainedwasdissolved
in water (50 mL). The resulting solution was extracted
with diethyl ether (2 × 60 mL) and the aqueous layer was
concentrated to dryness under reduced pressure to give the
desiredpyridiniumiodide28(1.49g, 92%),obtainedasadark
red viscous oil. [a]25D –65.3 (c 1.68, CH3OH); IR nmax/cm-1:
3023, 2971, 2789, 1497, 1462, 1269, 1149, 731, 691 (thin
film); 1H NMR (300 MHz, CD3OD) d 9.18 (s, 1H), 9.07 (d,
J 6.1 Hz, 1H), 8.67 (d, J 8.0 Hz, 1H), 8.14 (apparent t,
J 7.4 Hz, 1H), 5.12 (septet, J 6.7 Hz, 1H), 4.00-3.75 (m,
1H), 3.42 (apparent t, J 9.6 Hz, 1H), 2.67 (apparent q,
J8.6Hz,1H),2.58-2.30(superposedmultiplet,1Handasinglet
centered at 2.40, 3H), 2.19-1.85 (m, 3H), 1.75 (d, J 6.7 Hz,
6H); 13C NMR (75 MHz, CD3OD) d 146.2 (CH), 145.2 (C0),
143.5 (CH), 143.1 (CH), 129.7 (CH), 68.8 (CH), 66.7 (CH),
57.8 (CH2), 40.6 (CH), 35.5 (CH2), 23.8 (CH2), 23.3 (CH3),
23.2 (CH3); MS (ESI +) m/z: 205 [M+]; HRMS (ESI +) m/z:
Calcd for C13H21N2 [M+] 205.1705, found 205.1713.
Prepared from imidazolium chloride 17 (1.66 g,
6.03 mmol) according to the general procedure for the anion
metathesis with lithium bis(trifluoromethanesulfonyl)imide.
Salt 20 (2.54 g, 81%) was obtained as a light yellow liquid.
[a]25D –4.5 (c 1.78, CH3OH); Tg –46 °C; IR nmax/cm-1: 3153,
2251, 1561, 1457, 1351, 1180, 1141, 1054, 740, 704, 614,
570 (thin film); 1H NMR (300 MHz, acetone-d6) d 9.23 (t,
J 1.6 Hz, 1H), 7.82 (t, J 1.9 Hz, 1H), 7.76 (t, J 1.9 Hz, 1H),
7.44-7.34 (m, 5H), 5.84 (q, J 7.0 Hz, 1H), 4.48 (t, J 7.1 Hz,
2H), 2.59 (t, J 7.4 Hz, 2H), 2.32 (quintet, J 7.2 Hz, 2H), 1.96
(d, J 7.0 Hz, 3H);13C NMR (75 MHz, CD3OD) d 140.0 (CH),
130.5(CH),130.3(CH),127.9(CH),124.1(CH),123.1(CH),
121.2 (q, JCF 320.5 Hz, SO2CF3), 119.8 (C0), 61.4 (CH), 49.7
(CH2), 26.8 (CH2), 21.2 (CH3), 14.7 (CH2); MS (ESI +) m/z:
240 [M+]; MS (ESI –) m/z: 280 [NTf2–]; HRMS (ESI +) m/z:
Calcd for C15H18N3 [M+] 240.1501, found 240.1481.
Diaminocarbene palladium complexes 23a,b
Pd(OAc)2 (47 mg, 0.21 mmol) and 3-pentyl-1-[(1S)-1-
phenylethyl]-1H-imidazolium bromide 15 (135 mg, 0.42
mmol) were dissolved in 7.0 mL of dry THF. After refluxing
for 6 h under argon and cooling to room temperature, the
mixture was filtered through a pad of silica gel. The solvent
wasremovedundervacuumandthecrudeproductwaspurified
by flash column chromatography (petroleum ether/ethyl
acetate, 4:1) to furnish a 1:1 mixture of compound 23a,b (85
1-isopropyl-3-((S)-1-methylpyrrolidin-2-yl)pyridinium
bis(trifluoromethanesulfonyl)imide (29)
Prepared from pyridinium iodide 28 (1.07 g, 3.23 mmol)
according to the general procedure for the anion metathesis
with lithium bis(trifluoromethanesulfonyl)imide. Pyridinium
mg, 54%), obtained as a pale yellow amorphous solid. [a]25
29 (1.04 g, 66%) was obtained as a light brown oil. [a]25
D
D
–190.0 (c 1.17, CHCl3); mp: 114-116 °C; IR nmax/cm-1: 3156,
3124, 3094, 3060, 2957, 2929, 2867, 1602, 1560, 1497, 1453,
1425, 1378, 1216, 1184, 770, 734, 703 (thin film); 1H NMR
–69.2 (c 1.59, CHCl3); Tg –56 °C; IR nmax/cm-1: 3073, 2977,
2948, 2791, 1499, 1465, 1352, 1268, 1196, 1138, 1059, 739
(thin film); 1H NMR (300 MHz, CDCl3) d 8.79-8.76 (m, 2H),

834
Synthesis of Novel Room Temperature Chiral Ionic Liquids
J. Braz. Chem. Soc.
8.46 (apparent d, J 8.0 Hz, 1H), 8.02 (dd, J 6.2 and 7.9 Hz,
2H), 5.02 (septet, J 6.7 Hz, 1H), 3.55 (t, J 8.1 Hz, 1H), 3.27
(ddd, J 2.8, 7.2 and 9.6 Hz, 3H), 2.48 (q, J 8.3 Hz, 1H), 2.41
(tdd, J 6.5, 8.8 and 12.9 Hz, 1H), 2.24 (s, 3H), 2.03-1.82 (m,
2H), 1.80-1.59 (doublet centered at 1.71, J 6.7 Hz, 6H, and
a superposed multiplet, 1H); 13C NMR (75 MHz, CDCl3) d
147.2 (C0), 144.6 (CH), 141.1 (CH), 140.7 (CH), 128.7 (CH),
119.8 (q, JC-F 319.5 Hz, SO2CF3), 67.0 (CH), 65.5 (CH), 56.6
(CH2), 40.2 (CH), 35.7 (CH2), 23.1 (CH2), 23.1 (CH3), 23.0
(CH3);MS(ESI+)m/z:205[M+];MS(ESI–)m/z:280[NTf2–];
HRMS (ESI +) m/z: calcd for C13H21N2 [M+] 205.1705, found
205.1710.
1H),3.00-2.58(m,3H),2.18-2.01(m,1H),2.00-1.82(m,1H),
1.81-1.56 (m, 2H), 1.14 (t, J 7.2 Hz, 3H);13C NMR (75 MHz,
CD3OD) d 147.6 (CH), 146.8 (CH), 129.2 (CH), 121.2 (q,
JC-F 320.3 Hz, SO2CF3), 65.6 (CH), 63.7 (CH2), 54.6 (CH2),
50.7 (CH2), 28.9 (CH2), 23.9 (CH2), 13.0 (CH3); MS (ESI +)
m/z: 191 [M+]; MS (ESI –) m/z: 280 [NTf2–]; HRMS (ESI +)
m/z: Calcd for C12H19N2 [M+] 191.1548, found 191.1582.
(S)-2-(1-(1-phenylethyl)-1H-imidazol-2-yl)pyridine (33)
To a solution of (S)-a-methylbenzylamine (2.25 g,
18.6 mmol) and aqueous ammonia (2.0 mL, 37.2 mmol) in
propan-1-ol (10.0 mL) at 0 °C was added dropwise a solution
ofglyoxal(2.34mL,20mmol)and2-pyridinecarboxaldehyde
(1.9 mL, 20 mmol) in propan-1-ol (20 mL).After 1 h at 0 °C,
the solution was heated to 80 °C and left stirring for 4 h. It
was then cooled to room temperature and water was added.
Subsequently,themixturewasextractedwithdichloromethane
(3 × 100 mL) and the combined extracts were washed with
water (2 × 100 mL), dried over anhydrous Na2SO4, filtered
and the dichloromethane removed under reduced pressure.
The brown oil obtained was purified by flash column
chromatography(petroleumether/ethylacetate,1:1)tofurnish
imidazole 33 (0.84 g, 18%), obtained as a light brown oil.
[a]25D –244.4(c1.00, CHCl3);IRnmax/cm-1:3108, 3046, 2981,
2936, 1589, 1566, 1484, 1451, 1404, 1265, 1149, 1093, 1023,
792, 738, 700 (thin film); 1H NMR (300 MHz, CDCl3) d 8.59
(dt, J 0.8 and 4.8 Hz, 1H), 8.19 (dd, J 0.5 and 8.0 Hz, 2H),
7.75 (tdd, J 0.5, 1.8 and 8.0 Hz, 1H), 7.36-7.16 (m, 7H and a
superposed bs centered at 7.18, 1H), 7.10 (bs, 1H), 1.88 (d, J
7.1 Hz, 3H);13C NMR (75 MHz, CDCl3) d 151.0 (C0), 148.1
(CH), 144.6 (C0), 142.2 (C0), 136.5 (CH), 128.6 (CH), 128.4
(CH),127.3(CH),126.4(CH),123.2(CH),122.4(CH),119.7
(CH), 54.8 (CH), 21.6 (CH3); MS (ESI +) m/z: 250 [M+H+];
HRMS (ESI +) m/z: Calcd for C16H16N3 [M+H+] 250.1344,
found 250.1346.
(S)-1-((1-ethylpyrrolidin-2-yl)methyl)pyridiniumchloride(31)
To a suspension of 1-(2,4-dinitrophenyl)pyridinium
chloride (25) (2.30 g, 8.17 mmol) in n-butanol (80.0 mL)
was added (S)-2-(aminomethyl)-1-ethylpyrrolidine (1.01 g,
7.96 mmol) and the resulting mixture was refluxed for 20 h.
After cooling to room temperature, the solvent was removed
under reduced pressure and water (60.0 mL) was added to
the residue obtained. The aqueous solution was washed with
dichloromethane (3 × 80 mL) and concentrated to dryness
under reduced pressure. The brown oil obtained was purified
byflashcolumnchromatography(dichloromethane/methanol,
9:1 to 1:1 + 3 drops of NH4OH/10 mL of eluent) to furnish
the pyridinium chloride 31 (1.88 g, 51%), obtained as a light
yellowviscousoil. [a]25D +1.3(c1.17, CH3OH);IRnmax/cm-1:
3044, 2974, 2612, 2505, 1581, 1490, 1455, 1187, 1055, 777,
729 (thin film); 1H NMR (300 MHz, CD3OD) d 9.30 (d, J
5.8 Hz, 2H), 8.74 (apparent t, J 7.9 Hz, 1H), 8.24 (dd, J 6.8
and 7.4 Hz, 2H), 5.27 (AB of an ABX, Δδ = 0.36, J 5.6, 8.7
and 13.7 Hz, 2H), 4.26 (quintet, J 7.3 Hz, 1H), 3.90-3.82 (m,
1H), 3.53-3.19 (m, 3H), 2.31-1.99 (m, 4H), 1.40 (t, J 7.2 Hz,
3H);13C NMR (75 MHz, CD3OD) d 148.5 (CH), 146.9 (CH),
130.1 (CH), 67.6 (CH), 61.0 (CH2), 55.2 (CH2), 51.5 (CH2),
29.3 (CH2), 22.8 (CH2), 11.1 (CH3); MS (ESI +) m/z: 191
[M+];HRMS(ESI+)m/z:CalcdforC12H19N2 [M+]191.1548,
found 191.1562.
(S)-3-butyl-1-(1-phenylethyl)-2-(pyridin-2-yl)-1H-imidazol-
3-ium iodide (34)
A solution of imidazole 33 (500 mg, 2.00 mmol) and
1-iodobutane (1.14 mL, 10.0 mmol) in acetonitrile (4.0 mL)
was heated at 100 °C in a sealed tube under microwave
irradiation (150 W) for 2 h. Next, the volatiles were removed
underreducedpressure,andtheresidueobtainedwasdissolved
in water (70.0 mL). A saturated NaCl solution (30.0 mL) was
added and the resulting solution was extracted with diethyl
ether (2 × 80 mL) and dichloromethane (3 × 90 mL). The
combineddichloromethaneextractsweredriedoveranhydrous
Na2SO4, filtered and concentrated under reduced pressure
to give the desired imidazolium iodide 34 (0.72 g, 83%),
obtained as a light yellow oil. [a]25D –109.4 (c 1.56, CHCl3);
IR nmax/cm-1: 3089, 3054, 2960, 2934, 2873, 2190, 1594, 1571,
(S)-1-((1-ethylpyrrolidin-2-yl)methyl)pyridinium
bis(trifluoromethanesulfonyl)imide (32)
Preparedfrompyridiniumchloride31(1.66g,5.90mmol)
according to the general procedure for the anion metathesis
with lithium bis(trifluoromethanesulfonyl)imide. Pyridinium
32 (1.85 g, 67%) was obtained as a light brown viscous oil.
[a]25D +5.6 (c 1.05, CH3OH); Tg –52 °C; IR nmax/cm-1: 3138,
3095, 3072, 2976, 2872, 2812, 1490, 1456, 1353, 1196, 1137,
1
1059, 790, 740 (thin film); H NMR (300 MHz, CD3OD)
d 8.98 (apparent d, J 5.6 Hz, 2H), 8.65 (apparent t, J 7.9 Hz,
1H), 8.14 (apparent t , J 7.4 Hz, 2H), 4.79-4.66 (m, 2H), 3.58-
3.44 (m, 1H), 3.42-3.29 (m superposed with the solvent peak,

Vol. 21, No. 5, 2010
Pastre et al.
835
1499, 1455, 1427, 1221, 1190, 920, 800, 727, 702 (thin film);
1HNMR(300MHz,CDCl3)d8.82(ddd,J1.0,1.7and4.8Hz,
1H),8.32-8.19(m,1H),8.07(apparenttd,J1.7and7.8Hz,1H),
7.95 (s, 1H), 7.66-7.60 (m, 2H), 7,33-7,24 (m, 3H), 7.21-7.12
(m, 2H), 5.70 (q, J 6.9 Hz, 1H), 4.23 (quintet of d, J 2.4 and
7.4 Hz, 2H), 1.96 (d, J 7.7 Hz, 3H), 1.76 (quintet, J 7.5 Hz,
2H), 1.24 (quintet, J 7.4 Hz, 2H), 0.80 (t, J 7.3 Hz, 3H); 13C
NMR (75 MHz, CDCl3) d 150.9 (CH), 142.0 (C0), 141.1 (C0),
138.3 (CH), 137.5 (C0), 129.1 (CH), 128.9 (CH), 128.3 (CH),
126.8 (CH), 126.4 (CH), 123.0 (CH), 119.9 (CH), 58.4 (CH),
49.4 (CH2), 31.6 (CH2), 21.1 (CH3), 19.3 (CH2), 13.2 (CH3);
MS (ESI +) m/z: 306 [M+]; MS (ESI –) m/z: 127 [I–]; HRMS
(ESI+)m/z:CalcdforC20H24N3 [M+]306.1970,found306.2000.
Affaires Étrangères et Européennes”) for an one year “Eiffel”
doctoral grant to J.C.P., as well as to CAPES and COFECUB
forpartialfinancialsupportoftheproject(process635/09).We
are also thankful to C. Zedde for chiral HPLC analysis and to
the “Service des Relations Internationales” of the “Université
Paul Sabatier” (Toulouse, France) for their assistance.
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1H), 7.54 (d, J 2.1 Hz, 1H), 7.43 (d, J 2.1 Hz, 1H), 7.35-7.29
(m, 3H), 7.11 (ddd, J 0.5, 2.2 and 5.2 Hz, 1H), 5.63 (q, J
7.0 Hz, 1H), 4.09 (t, J 7.6 Hz, 2H), 1.89 (d, J 7.0 Hz, 3H),
1.72 (apparent quintet, J 7.5 Hz, 2H), 1.22 (septet, J 7.5 Hz,
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m/z: 280 [NTf2–]; HRMS (ESI +) m/z: Calcd for C20H24N3
[M+] 306.1970, found 306.1982.
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17, 18, 19, 20, 23, 28, 29, 31, 32, 33, 34 and 35, and selected
crystallographicdataforcompounds23aand23bareavailable
free of charge at http://jbcs.sbq.org.br, as PDF file.
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Acknowledgments
We thank CNPq and FAPESP for fellowships and
financial support. We also thank EGIDE (“Centre Français
pour l’Accueil et les Échanges Intenationaux, Ministère des

836
Synthesis of Novel Room Temperature Chiral Ionic Liquids
J. Braz. Chem. Soc.
16. Xu, L.; Chen, W.; Xiao, J.; Organometallics 2000, 19, 1123.
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D. J.; Organometallics. 2001, 20, 3848; McLachlan, F.; Mathews,
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23a,b. CCDC 724261 (23a) and CCDC 724262 (23b) contain
the supplementary crystallographic data for this paper. These data
can be obtained free of charge via www.ccdc.cam.ac.uk/conts/
retrieving.html (or from the CCDC, 12 Union Road, Cambridge
CB21EZ, UK;fax:+441223336033;e-mail:deposit@ccdc.cam.
ac.uk).
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22. The sensitivity of the arenediazonium salt to nucleophilic species
such as the RTIL counter-anion might be invoked as a possible
explanation. However, the presence of remaining diazonium
reagent has been checked at the end of each run. For evidence of
the participation of the ”non-nucleophilic” [Tf2N]- anion in the
dediazoniation reaction performed in ionic liquid, see: Bini, R.;
Chaippe, C.; Marmugi, E.; Pieraccini, D.; Chem. Commun. 2006,
897; Laali, K. K.; Okazaki, T.; Bunge, S. D.; J. Org. Chem. 2007,
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Kaneko, H.; Heterocycles 1982, 19, 1641.
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2,2’-bisimidazole from a-methylbenzylamine, a source of
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and 2 equivalents of glyoxal invariably led to the known C-2
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process.
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Received: October 2, 2009
Web Release Date: February 8, 2010
26. Foraprecedentonthedevelopmentofachiralnitrile-functionalized
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C.; Dyson P. J.; Organometallics 2007, 26, 1588.
FAPESP helped in meeting the publication costs of this article.

J. Braz. Chem. Soc., Vol. 21, No. 5, S1-S19, 2010.
Printed in Brazil - ©2010 Sociedade Brasileira de Química
0103 - 5053 $6.00+0.00
Synthesis of Novel Room Temperature Chiral Ionic Liquids. Application as Reaction
Media for the Heck Arylation of Aza-endocyclic Acrylates
Julio C. Pastre,a Yves Génisson,*, b Nathalie Saffon,c Jany Dandurand d
and Carlos R. D. Correia*,a
aInstituto de Química, Universidade Estadual de Campinas, CP 6154,
13083-970 Campinas-SP, Brazil
bLaboratoire de Synthèse et Physicochimie des Molécules d’Intérêt Biologique UMR-CNRS 5068,
Université Paul Sabatier, 118 route de Narbonne, 31062, Toulouse Cedex 9, France
cSFTCM, FR2599, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse Cedex 9, France
dLaboratoire de Physique des Polymères, Université Paul Sabatier, 118 route de Narbonne,
31062 Toulouse Cedex 9, France
Crystal Structure Determination
The structures of two compounds were determined. The selected crystals were mounted on a glass fibber using
perfluoropolyether oil and cooled rapidly in a stream of cold N2. For all the structures data collection were collected at low
temperature (213 K for compounds 23a and 173 K for compounds 23b) and using a graphite-monochromated MoKa radiation
(l = 0.71073Å). The structure were solved by direct methods (SHELXS-97, G. M. Sheldrick, Acta Crystallogr. 1990, A46,
467-473) and all non hydrogen atoms were refined anisotropically using the least-squares method on F2 (SHELXL-97,
Program for Crystal Structure Refinement, G. M. Sheldrick, University of Göttingen 1997). CCDC 724261 (23a) and CCDC
724262 (23b) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via
www.ccdc.cam.ac.uk/conts/retrieving.html (or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223
336033; e-mail: deposit@ccdc.cam.ac.uk).
Selected crystallographic data for compound 23a
*e-mail: genisson@chimie.ups-tlse.fr; roque@iqm.unicamp.br

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Synthesis of Novel Room Temperature Chiral Ionic Liquids
J. Braz. Chem. Soc.
Selected data for trans-anti Pd complex 23a: C32 H44 Br2 N4 Pd, M = 750.93, orthorhombic, space group P2(1)2(1)2(1),
a = 8.7609(2) Å, b = 12.0766(3) Å, c = 31.6211(9) Å, a = b = g = 90°, V =3345.57(15) Å3, Z = 4, crystal size 0.35 x 0.15 x
0.05 mm3, 32050 reflections collected (6787 independent, Rint = 0.0821), 383 parameters, R1 [I>2s(I)] = 0.0423, wR2 [all
data] = 0.0804, largest diff. peak and hole: 0.422 and -0.392 eÅ-3.
Selected crystallographic data for compound 23b
Selected data for cis-syn Pd complex 23b: C33 H46 Br2 Cl2 N4 Pd, M = 835.86, orthorhombic, space group P2(1)2(1)2(1),
a = 7.7314(8) Å, b = 17.6948(17) Å, c = 27.018(3) Å, a = b = g = 90°, V = 3696.3(6) Å3, Z = 4, crystal size 0.40 x 0.20 x
0.05 mm3, 33902 reflections collected (9117 independent, Rint = 0.0759), 447 parameters, R1 [I>2s(I)] = 0.0544, wR2 [all
data] = 0.1145, largest diff. peak and hole: 0.624 and -0.727 eÅ-3.
1H NMR and 13C NMR spectra for compounds 11, 12, 13, 15, 16, 17, 18, 19, 20, 23, 28, 29, 31, 32, 33, 34 and 35
Figura S1. 1H NMR spectrum (300 MHz, CDCl3) of compound 11.

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Figura S2. 13C NMR spectrum (75 MHz, CDCl3) of compound 11.
Figura S3. 1H NMR spectrum (300 MHz, CDCl3) of compound 12.

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Synthesis of Novel Room Temperature Chiral Ionic Liquids
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Figura S4. 13C NMR spectrum (75 MHz, CDCl3) of compound 12.
Figura S5. 1H NMR spectrum (300 MHz, CDCl3) of compound 13.

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Figura S6. 13C NMR spectrum (75 MHz, CDCl3) of compound 13.
Figura S7. 1H NMR spectrum (300 MHz, CDCl3) of compound 15.

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Synthesis of Novel Room Temperature Chiral Ionic Liquids
J. Braz. Chem. Soc.
Figura S8. 13C NMR spectrum (75 MHz, CDCl3) of compound 15.
Figura S9. 1H NMR spectrum (300 MHz, CDCl3) of compound 16.

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Figura S10. 13C NMR spectrum (75 MHz, CDCl3) of compound 16.
Figura S11. 1H NMR spectrum (300 MHz, CDCl3) of compound 17.

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Synthesis of Novel Room Temperature Chiral Ionic Liquids
J. Braz. Chem. Soc.
Figura S12. 13C NMR spectrum (75 MHz, CDCl3) of compound 17.
Figura S13. 1H NMR spectrum (300 MHz, CDCl3) of compound 18.

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Figura S14. 13C NMR spectrum (75 MHz, CDCl3) of compound 18.
Figura S15. 1H NMR spectrum (300 MHz, CDCl3) of compound 19.

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Synthesis of Novel Room Temperature Chiral Ionic Liquids
J. Braz. Chem. Soc.
Figura S16. 13C NMR spectrum (75 MHz, CDCl3) of compound 19.
Figura S17. 1H NMR spectrum (300 MHz, acetone-d6) of compound 20.

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Figura S18. 13C NMR spectrum (75 MHz, CD3OD) of compound 20.
Figura S19. 1H NMR spectrum (300 MHz, CDCl3) of compound 23a,b.

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Synthesis of Novel Room Temperature Chiral Ionic Liquids
J. Braz. Chem. Soc.
Figura S20. 13C NMR spectrum (75 MHz, CDCl3) of compound 23a,b.
Figura S21. 1H NMR spectrum (300 MHz, CD3OD) of compound 28.

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Figura S22. 13C NMR spectrum (75 MHz, CD3OD) of compound 28.
Figura S23. 1H NMR spectrum (300 MHz, CDCl3) of compound 29.

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Synthesis of Novel Room Temperature Chiral Ionic Liquids
J. Braz. Chem. Soc.
Figura S24. 13C NMR spectrum (75 MHz, CDCl3) of compound 29.
Figura S25. 1H NMR spectrum (300 MHz, CD3OD) of compound 31.