Chirality transfer in imidazolium camphorsulfonate ionic liquids through ion pairing effects

Article abstract of DOI:10.1002/adsc.200800569

The paper describes our studies on ion pair interactions in ionic liquids (IL) using an asymmetric hydrogenation reaction as probe. Three different ionic liquids carrying prochiral keto-functionalized cations were hydrogenated in the presence of their chiral, enantiomerically pure counter-ion using an achiral heterogeneous ruthenium catalyst. For the hydrogenation of N-(3′-oxobutyl) -N-methylimidazolium camphorsulfonate (2), N-(3′-oxobutyl)imidazolium camphorsulfonate (4) and N-(5′-oxohexyl)-N-methylimidazolium camphorsulfonate (6) we found a strong dependency of the enantiomeric excess (ee in the cation) on the polarity of the solvent, the concentration of the IL and the structure of the IL. The highest ee values of up to 94% were found for the hydrogenation of 2 in ethanol. Interestingly, we observed that the ee (and consequently the strength of ion pair interaction) had a pronounced maximum for a certain concentration of the IL in the solvent depending on the nature of the solvent and on the substrate. Remarkably, the concentration leading to the maximum ee could be rationalized by independent determination of the degree of dissociation which was obtained by a combination of diffusion-ordered NMR spectroscopy and conductivity measurements.

Full text of DOI:10.1002/adsc.200800569

FULL PAPERS
DOI: 10.1002/adsc.200800569
Chirality Transfer in Imidazolium Camphorsulfonate Ionic
Liquids through Ion Pairing Effects
a
a
a,
Karola Schneiders, Andreas Bçsmann, Peter S. Schulz, *
a,
and Peter Wasserscheid *
Department of Chemical and Bioengineering, Friedrich-Alexander-Universitꢀt Erlangen-Nꢁrnberg, Egerlandstrasse 3,
a
91058 Erlangen, Germany
Fax : (+49)-9131-852-7421; e-mail: peter.schulz@crt.cbi.uni-erlangen.de or peter.wasserscheid@crt.cbi.uni-erlangen.de
Received: September 15, 2008; Revised: December 4, 2008; Published online: February 13, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800569.
Abstract: The paper describes our studies on ion hydrogenation of 2 in ethanol. Interestingly, we ob-
pair interactions in ionic liquids (IL) using an asym- served that the ee (and consequently the strength of
metric hydrogenation reaction as probe. Three differ- ion pair interaction) had a pronounced maximum for
ent ionic liquids carrying prochiral keto-functional- a certain concentration of the IL in the solvent de-
ized cations were hydrogenated in the presence of pending on the nature of the solvent and on the sub-
their chiral, enantiomerically pure counter-ion using strate. Remarkably, the concentration leading to the
an achiral heterogeneous ruthenium catalyst. For the maximum ee could be rationalized by independent
hydrogenation of N-(3’-oxobutyl)-N-methylimidazoli- determination of the degree of dissociation which
um camphorsulfonate (2), N-(3’-oxobutyl)imidazoli- was obtained by a combination of diffusion-ordered
um camphorsulfonate (4) and N-(5’-oxohexyl)-N- NMR spectroscopy and conductivity measurements.
methylimidazolium camphorsulfonate (6) we found a
strong dependency of the enantiomeric excess (ee in
the cation) on the polarity of the solvent, the concen- Keywords: chirality transfer; diffusion-ordered spec-
tration of the IL and the structure of the IL. The troscopy; hydrogenation; ion pairing; ionic liquids;
highest ee values of up to 94% were found for the NMR spectroscopy
Introduction
ture of the ionic liquid under investigation had a
strong influence on the transition state, the reaction
Understanding the nature of cation–anion interactions order and therefore the rate of syn- and anti-addition
in ionic liquids is a topic of high relevance to explain products. Similar findings concerning the ionic liquidꢂs
ionic liquid properties as well as their interaction with influence on the reaction selectivity were made for
dissolved substances. Among reported studies dealing the C- vs. O-alkylation of sodium b-naphthoxide with
[
29]
[30]
with this topic, most are theoretical studies in which benzyl halides and for Diels–Alder reactions. So
the ion pair interactions are calculated by molecular far – to the best of our knowledge – only two publica-
[
1–16]
modelling.
Experimental investigations have been tion describe the degree of ion pair interaction in
[
17,18]
published on mass spectrometric analyses
and the camphorsulfonate ionic liquids and both link this in-
investigation of physico-chemical properties of either teraction to the endo/exo stereoselectivity of a Diels–
[
19]
[31,32]
ionic liquid mixtures or solutions of polar molecules Alder reaction.
[20]
in ionic liquids.
Most recent publications on the
topic have focussed on NMR spectroscopy,
and Raman spectroscopy.
The interest in chiral ionic liquids (CILs) has in-
FT-IR creased significantly in recent years. The first example
of an ionic liquid with a chiral anion was reported in
[
21–25]
[
26,27]
A few examples are known in which cation–anion 1999 by Seddonꢂs group in a study dealing with lactate
[
33]
interactions and ionic liquid transition state interac- ionic liquids.
tions have been studied by monitoring the selectivity anions were prepared later by the groups of Ohno,
Further ionic liquids with chiral
[34]
[
35]
[36]
of reactions. Chiappe et al. studied, for example, the Machado,
and Leitner,
derived from 19 natural
[
28]
bromination of alkynes and revealed that the struc- amino acids, (S)-10-camphorsulfonate and (R)-1,10-bi-
432
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 432 – 440

Chirality Transfer in Imidazolium Camphorsulfonate Ionic Liquids
FULL PAPERS
While chirality transfer in ionic liquids is a very
young field of research, reports on chiral recognition
have been published already many years ago. In 1931
it was reported that diastereoselective interactions be-
tween a configurationally labile charged metal com-
plex and a chiral counter ion can induce stereoselec-
Figure 1. “Doubly chiral” ionic liquid as published 2005 by
Machadoꢂs group.
[
45]
tivity at the metal center (Pfeiffer effect).
naphthylphosphate, and borate anions based on l- past years a number of papers have been published in
À)-malic acid, respectively. Chiral cations are also high-ranked journals that have applied chiral recogni-
In the
(
[
46]
accessible from the chiral pool. However, usually tion effects successfully in organocatalysis, Brønsted
[
47]
multi-step syntheses are necessary. For example, our acid-catalyzed reactions,
homogeneous metal-cata-
[
48]
group has introduced in 2002 oxazolinium cations pre- lyzed reactions, and especially phase-transfer catal-
pared from amino acids in a four-step synthesis as ysis. Chiral recognition has been proven by 1D- and
well as hydroxyammonium salts derived from the cor- 2D-NMR studies with chiral ions and racemic coun-
[
49]
[
50]
responding amino alcohol by the Leuckart–Wallach ter-ions. In most of these studies it was found that
[37]
reaction. Besides amino acids and amino alcohols, chiral recognition is stronger in less polar solvents
chiral cations have been also synthesized by alkyla- with low dielectric constants.
tion of imidazole or imidazoline with chiral alkylation
agents.
In this paper, we expand on our previous communi-
cation describing the hydrogenation of [N-(3’-oxo-
[38]
[51]
Examples of ionic liquids with chirality in both ions butyl)-N-methylimidazolium] [(+)-camphorsulfonate],
are very rare to date. The first examples of this kind an ionic liquid consisting of a pro-chiral, keto-func-
of a “doubly chiral” ionic liquid was 1-methyl-3-[(S)- tionalized cation and an enantiomerically pure, chiral
2
’-methylbutyl]imidazolium
(S)-camphorsulfonate, counter-ion. At the time, it was found that the hydro-
[
39]
(
Figure 1) published by Machadoꢂs group in 2005.
genation with the achiral Ru catalyst led to a signifi-
Only very recently, the groups of Luo and Cheng pub- cant enantiomeric excess of the hydroxy-functional-
lished a new combinatorial approach to doubly chiral ized product cation. The working hypothesis of this
ionic liquids by ring opening of chiral cyclic sulfates previous paper was that this chiral induction is caused
and cyclic sulfamidates and subsequent reaction with by the intimate ion pair interaction in the ionic liquid.
chiral acids like tartric acid, lactic acid or camphorsul- Chiral poisoning effects on the surface of the hetero-
[40]
fonic acid.
geneous Ru catalyst were excluded by control experi-
Asymmetric synthesis in which the solvent is the ments using the same anion but hydrogenating the
[
51]
source of chiral information is possible. However, up neutral substrate acetophenone.
to now few convincing examples have been reported, The focus of this paper is to highlight the effects of
and the enantioselectivities achieved in this way have the reaction medium and the ionic liquid concentra-
[
41]
been small to moderate in most cases. These find- tion on the ion pair formation and thus on the enan-
ings are in very good agreement with our own former tiomeric excess. Furthermore, we report the results
work showing that the strong interaction between the from an independent investigation of the so-called
ionic liquidꢂs cation and anion makes chirality infor- degree of ion dissociation that was derived from the
mation hardly transferable within the system to un- determination of self-diffusion coefficients and elec-
[
42]
charged molecules and transition states.
However, tric conductivities. For different concentrations the
we and others realized that chiral anions like a-me- degree of ion dissociation is compared to the condi-
thoxy-a-trifluoromethylphenylacetate (deprotonated tions showing the best asymmetric induction in the
Mosherꢂs acid) do strongly interact with the chiral hydrogenation catalysis.
[43]
cation of a CIL. These ion pair interactions could
19
be verified by F NMR spectroscopy using a racemic
mixture of Mosherꢂs acid sodium salt as substrate in Results and Discussion
an enantiomerically pure ephedrinium bis(trifluoro-
methylsulfonyl)imide ionic liquid. In this context it is Synthesis and Properties of Prochiral Ionic Liquids
not surprising that the best results of solvent-induced
chirality transfer reported so far were obtained by In the course of this study we have synthesized three
Leitner and co-workers using a chiral anion-contain- different prochiral ionic liquids. [N-(3’-oxobutyl)-N-
[
36]
ing ionic liquid for an aza-Baylis–Hillman reaction
methylimidazolium] [(+)-camphorsulfonate] 2 was
and for a homogeneous Rh-catalyzed hydrogena- prepared as an example for a N,N’-dialkylated, pro-
[44]
tion. For the aza-Baylis–Hillman reaction an ionic chiral imidazolium salt. [N-(3’-oxobutyl)imidazolium]
transition state was postulated in which the Brønsted [(+)-camphorsulfonate] 4 was synthesized as a repre-
acidic, chiral anion is incorporated as a kind of orga- sentative for an N-protonated, prochiral imidazolium
nocatalyst.
cation. The latter offers the option to liberate a neu-
Adv. Synth. Catal. 2009, 351, 432 – 440
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
433

Karola Schneiders et al.
FULL PAPERS
Scheme 1. Synthesis of [N-(3’-oxobutyl)-N-methylimidazolium] [(+)-camphorsulfonate] 2 via protonation and Michael addi-
tion of methyl vinyl ketone.
tral amino alcohol after a basic work-up of the hydro-
genated ionic liquid. As an example for a different
number of CH -spacers between the carbonyl group
2
and the imidazolium core we synthesized [N-(5’-oxo-
hexyl)-N-methylimidazolium] [(+)-camphorsulfonate]
6.
In the first step of the preparation of ionic liquid 2,
1-methylimidazole was protonated with stoichiometric
amounts of the enantiomeric pure (+)-camphor-10-
sulfonic acid to form the imidazolium salt 1. Salt 1
was reacted under reflux with methyl vinyl ketone in
a Michael-type addition according to our own previ-
ous work to the prochiral ionic liquid [N-(3’-oxobu-
tyl)-N-methylimidazolium]
(
[(+)-camphorsulfonate] Scheme 2. Synthesis of [N-(3’-oxobutyl)imidazolium] [(+)-
2). Compound 2 is a highly viscous oil which is air-
and temperature-stable over months (Scheme 1).
Some important physico-chemical properties of 2
and 6 have been determined and are summarized in
Table 1.
[51]
camphorsulfonate] 4 via Michael addition of methyl vinyl
ketone and subsequent protonation with camphorsulfonic
acid.
In a similar manner, we synthesized [N-(3’-oxobu-
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
tyl)imidazolium]
[(+)-camphorsulfonate]
(4) tral imidazole intermediate 3 by rapid column chro-
(
Scheme 2). In this case the Michael addition of the matography. Once converted into an ionic liquid, pu-
side chain was performed prior to the introduction of rification is usually much more difficult. While the
the chiral camphorsulfonic acid anion. This approach amine 3 is temperature-labile and decomposes readily
offers the advantage of easier purification of the neu- at room temperature (storage at 08C is recommend-
Table 1. Selected physico-chemical properties of [N-(3’-oxobutyl)-N-methylimidazolium] [(+)-camphorsulfonate] 2 and [N-
[a]
(
3’-oxobutyl)imidazolium camphorsulfonate] 4.
[b]
[c]
À1
[d]
[e]
Vicosity [mPas]
Density [gmL ]
TGA Onset
Tg Onset
2
6
1600
390
1.217
1.182
1628C, 2918C
317.58C
À418C
À37.48C, 13.68C
[
[
[
[
a]
All data for 2, 6 have been obtained for samples containing 0.61% and 1.51% of water, respectively.
08C, shear rate: 1–1000 s .
b]
c]
d]
À1
4
408C.
À1
Heating rate: 10 Kmin , sample was kept at 808C for 30 min prior to heating, first value for 2 reflects retro-Michael re-
action, second value further decomposition.
Onset was determined from the heating scan, heating rate: 2 Kmin , first value for 6 reflects the glass transition temper-
[
e]
À1
ature, second value the melting point.
434
asc.wiley-vch.de
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 432 – 440

Chirality Transfer in Imidazolium Camphorsulfonate Ionic Liquids
FULL PAPERS
Scheme 3. Synthesis of N-(5’-oxohexyl)-N-methylimidazolium camphorsulfonate 6 via alkylation followed by anion ex-
change.
ed), the ionic liquid 4 is stable at room temperature tion of the products with enantiomerically pure Mosh-
for days if dry.
erꢂs acid chloride [a-methoxy-a-(trifluoromethyl)-
For the synthesis of 6 a different approach was phenylacetyl chloride, MTPACl]. As reported in our
chosen. First, 1-methylimidazole was alkylated with 1- previous communication this determination method
chlorohexan-5-one to the corresponding chloride IL has been validated by experiments with both enantio-
5
. Then, the anion was exchanged for the camphorsul- mers of Mosherꢂs acid. Moreover, a chiral poisoning
fonate anion using an anion exchange resin of the catalyst surface has been excluded by experi-
(
Scheme 3).
ments with sodium camphorsulfonate as potential
chiral poisoning agent and acetophenone as substrate.
No enantiomeric excess was found in this case as al-
[51]
Hydrogenation Reactions
ready reported in our previous communication
To further investigate the interplay between the
.
For the hydrogenation of the prochiral keto groups of chiral induction and the strength of ion pairing we in-
the prochiral cations in 2, 4, and 6 the ionic liquid was vestigated the hydrogenation of ionic liquids 2, 4, and
dissolved in the respective solvent and ruthenium on 6 over a wide concentration range in water and etha-
charcoal was applied as achiral, heterogeneous cata- nol. As our results indicated that ethanol is a particu-
lyst (Scheme 4). Under the reaction conditions ap- lar interesting solvent for our specific concept, the hy-
plied here, the carbonyl group of the anion is stable. drogenation of 6 was only performed in this solvent.
Clearly harsher conditions are necessary to reduce The ionic liquid concentration was varied from 0.05
the anionꢂs keto group to the corresponding alco- to 0.5 mol/L, the results are summarized in Table 2.
[52]
hol.
Assuming that the enantiomeric excess is a probe
The enantiomeric excess in the respective cations for the intimacy of the ionic liquidꢂs ion pair interac-
of the hydrogenated ionic liquids 7, 8, and 9 was de- tions these results imply that ethanol as a quite polar
19
termined by F NMR spectroscopy after anion ex- solvent separates most of the ions of the ionic liquid
À
change of camphorsulfonate vs. [NTf ] and esterifica- at low concentrations forming separated ions in a way
2
that the contact is not close enough for a very effec-
tive transfer of the chiral information to the transition
state of the reaction. When increasing the concentra-
tion of IL 2, a strong increase in chiral induction is
observed indicating the formation of much closer ion
pairs. At a concentration of 0.3 mol/L, an enantiomer-
ic excess of 94% was found in the cation of IL 7,
which represents an unprecedentedly high value for
this kind of ion pair induced, chiral hydrogenation.
The increase of chiral induction with higher ionic
liquid concentration is attributed to the formation of
solvated contact ion pairs under these reaction condi-
tions. We explain the decrease of chiral induction
with an even higher ionic liquid concentration with
the formation of higher ionic liquid aggregates and
functionalized cations of the ionic liquids 2, 4, and 6 using a ion clusters in which the chirality transfer is less effec-
Scheme 4. Asymmetric hydrogenation of the prochiral keto-
[
53,54]
heterogeneous, achiral Ru-catalyst.
tive.
Adv. Synth. Catal. 2009, 351, 432 – 440
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
435

Karola Schneiders et al.
FULL PAPERS
Table 2. Asymmetric hydrogenation of keto-functionalized imidazolium ionic liquids 2, 4, and 6 – concentration variation in
[a]
water and EtOH vs. ee in the cations of 7, 8, and 9 after hydrogenation.
[b]
À3
À3
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
[mol/L]
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
[mol/mol]
ꢄ10
A
H
U
G
R
N
U
G
ꢄ10
water
ee (EtOH)
ee (water)
EtOH
2
4
6
2
4
0
0
0
0
0
0
.05
.1
.15
.2
.3
.5
2.92
5.83
8.75
11.66
17.49
29.16
0.90
1.81
2.71
3.61
5.42
9.03
18%
55%
72%
64%
94%
80%
n.d
28%
n.d
44%
54%
44%
35%
40%
82%
67%
45%
14%
8%
n.d
27%
54%
42%
4%
36%
41%
50%
38%
36%
4
9
3%
[
a]
Conditions: T=608C, p(H )=60 bar, catalyst: Ru/C (5% Ru, 10 wt% Ru/C with respect to 2 or 4, 10 wt% with respect
2
to 6), t=15 h, conversion X>95% in all cases.
IL/solvent.
[
b]
In order to study the role of the solvent polarity in reveal that the protonation equilibrium is shifted to
more detail, another set of hydrogenation experi- its neutral form in ethanol as we found more decom-
ments was carried out using water as a more polar position products from the temperature-labile imida-
solvent. Again, the enantiomeric excess of the reac- zole derivative 3 if the hydrogenation was carried out
tion was monitored as a function of the ionic liquid in ethanol compared to the same reaction in water.
concentration. As expected, the product ionic liquid 7
It is very remarkable that for all ionic liquid/solvent
showed generally lower ee values when prepared in systems under investigation the maximum chiral in-
water. This can be understood from the fact that duction has not been observed for the highest ionic
water shows in principal a higher ability to dissociate liquid concentration. We account this finding to the
ions. For such a comparison the difference between fact that with higher concentrations larger ion clusters
the molar fraction (mol/mol) of the ionic liquid in the are formed, which prevent the optimum arrangement
solvent and the molar concentration (mol/L) of the of the anion, the cation and the catalytic surface
ionic liquid in the solvent has to be considered. The during hydrogenation for optimum chirality transfer.
molar fraction of the ionic liquid in water is about a Moreover, it is also highly noteworthy that the con-
factor of 3 lower than in ethanol at the same molar centration at which a maximum ee is observed was
concentration, meaning three times more solvating found to be similar for the transformations of 2 and 4
molecules per ion pair. Nevertheless, if comparing the in the same solvent, but different for the two different
ee values in ethanol and water at 0.1 mol/L and solvents. While the hydrogenation of 2 and 4 pro-
0.3 mol/L, respectively, which have rather similar duced the highest ee in the cation at an ionic liquid
molar fractions of ionic liquid in the solvent, the ee in concentration of 0.3 mol/L in EtOH, the same sub-
water is still significantly lower. The maximum ee was strate ionic liquids were transformed with the highest
reached at a concentration of 0.15 mol/L in water and chiral induction at an ionic liquid concentration of
at a concentration of 0.3 mol/L in ethanol.
0.15 to 0.2 mol/L in water.
We were also interested to study the chiral induc-
In order to expand our concept to other cation
tion in the case of the protonated salt 4 as the latter structures and to reveal the structural sensitivity of
offers access to neutral amino alcohols after basic our concept we finally investigated the same hydroge-
work-up. As one can see from Table 1 the enantio- nation using IL 6 as the substrate. As shown above, 6
meric excess of the cation of IL 8 is generally lower is characterized by a longer alkyl spacer between the
compared to the N,N’-dialkylated cation of ionic center of positive charge and the pro-chiral keto func-
liquid 7 when obtained from the hydrogenation in tionality. Table 2 shows the results of the hydrogena-
ethanol. We attribute this effect to the protonation tion of 6 in ethanol. Again, a pronounced dependency
equilibrium of the starting material 4 that should of the product cation ee with the ionic liquid concen-
weaken in average the strength of ion pair interac- tration was observed. The ee reached a maximum
tions (Scheme 5). In addition to that, our experiments value of 82% at an ionic liquid concentration of
Scheme 5. Protonation equilibrium between the ionic liquid and the neutral oxobutylimidazole and camphorsulfonic acid.
436
asc.wiley-vch.de
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 432 – 440

Chirality Transfer in Imidazolium Camphorsulfonate Ionic Liquids
FULL PAPERS
0
.15 mol/L, lower and higher IL concentrations led to where s =conductivity, N=cations per volume, e=
D
significant reduction in chirality transfer.
electric charge, D /D =self-diffusion coefficients and
À
+
a =degree of dissociation.
A very similar approach to determine the degree of
dissociation of non-functionalized ionic liquids was re-
cently proposed by Watanabe.
Figure 2, Figure 3, and Figure 4 display graphs in
Determination of the Degree of Ion Dissociation a
[
56]
Encouraged by this interesting correlation of solvent
and concentration range on the one hand and degree which the degree of dissociation (a) calculated ac-
of chiral induction on the other hand, we aimed to de- cording to Eq. (1) is plotted against the IL concentra-
termine the degree of ion dissociation in our reaction tion.
system by an independent analytical method. For this
From a comparison of Figure 2 and Figure 3 one
purpose, a combination of diffusion ordered NMR can find that the degree of dissociation of 2 in water
spectroscopy (DOSY-NMR) and electric conductivity is significantly higher than in ethanol. This corre-
measurements has been applied. DOSY-NMR is a sponds nicely to our findings from the hydrogenation
very powerful tool to determine the self-diffusion co- experiments and can be taken as a proof that the con-
efficients of the ionic liquidꢂs cation and anion (D+
and D ) independently and was applied for several
À
[
55–60]
ionic liquids in recent years.
In our experiments
the bpp-led sequence (bipolar pulsed pairs longitudi-
nal echo current delay) has been applied. The pulse
sequence has been optimized by adjusting the dura-
tion of the field gradient d/2, the intervals between
the gradient pulses D and the magnitude of the field
gradient g (for details see Experimental Section and
Supporting Information).
From the fact that anion and cation have self-diffu-
sion coefficients in the same order of magnitude one
can conclude that they either diffuse independently
from each other but with the same velocity (which is
rather unlikely due to their different size and shape)
or that they form an ion pair. For the cation as well as
for the anion, the diffusion coefficient stays constant
with rising temperature (within the error of the mea-
surement) up to a temperature limit between 20 and
Figure 2. Degree of dissociation a as a function of the con-
centration of 2 in ethanol at 408C.
308C. When reaching this temperature a remarkable
rise of the values is observed which is strongly de-
pendant on the ionic liquidꢂs concentration. In a simi-
lar manner we have determined the diffusion coeffi-
cients for anion and cation of ionic liquid 2 in D O
2
and for ionic liquid 6 in EtOH.
Besides the self-diffusion coefficients, we also deter-
mined the electric conductivities of ionic liquid 2 at
Figure 3. Degree of dissociation a as a function of the con-
4
08C at different concentrations in ethanol and water
centration of 2 in D O at 408C.
2
and of IL 6 in ethanol (for details of the measurement
and results see Supporting Information). From the
self-diffusion coefficients and the conductivity data
we calculated the degree of dissociation a using a
[
55]
modified Stokes–Einstein equation [Eq. (1)].
It
should be mentioned here that the so-called degree of
dissociation is not a measure for the number of ion
pairs in solution, but reflects the order of cations and
anions. The smaller the value of a, the better ordered
are
the
ions
of
the
whole
system.
Figure 4. Degree of dissociation a as a function of the con-
centration of 6 in ethanol at 408C.
Adv. Synth. Catal. 2009, 351, 432 – 440
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
437

Karola Schneiders et al.
FULL PAPERS
tact of the ionic liquid ions in water is not close were used as received. Ruthenium on charcoal (5% Ru) was
purchased from Fluka. Hydrogenations were carried out in
enough to transfer the chiral information very effec-
a glas liner in a 300-mL Parr autoclave equipped with a gas
tively.
entrainment stirrer, a thermocouple, hydrogen inlet, and
Very remarkably, in every example investigated, a
heating mantle. The conductivity was determined using a
minimum for the degree of dissociation was found in
conductivity cell (LTA 1, WTW, cell constant K=1, plati-
the concentration range between 0.15 and 0.5 mol/L
nized platinum electrode). The differential scanning calorim-
for exactly the concentration where also the highest
enantiomeric excess was found in the hydrogenation
etry (DSC) was carried out using a Netzsch DSC 204 under
N atmosphere in sealed aluminum pans. The temperature
2
experiments. This finding strongly supports the inter- stability was measured by thermogravimetric analysis
pretation that intense ion pair association is indeed a (TGA) using a Netzsch TG 209. The sample was kept at
necessary condition for effective chiral induction in 808C for 30 min and heated to 4508C with a heating rate of
À1
1
0 Kmin . The water content was determined by Karl–
this special type of asymmetric hydrogenation.
Moreover, these results open a new and very prom-
ising way to predict the concentration range of most
intense ion pair interaction also for other systems by
a combination of DOSY-NMR and conductivity
measurements.
Fischer titration using a Metrohm 756 KF Titrator. Electro-
spray mass spectrometry was carried out on a Bruker Es-
quire 6000.
The viscosity was measured under inert gas atmosphere
applying an Anton Paar Physica MCR 100 rheometer at 40,
5
0, 60, 80 and 908C. The density determination was carried
out using an Anton Paar DMA 4500 density meter. NMR
experiments were carried out with a Jeol ECX 400 MHz
spectrometer with a 2-chanel (HF, LF)-probe. Spectra were
referenced to the solvent. The procedure of bpp-led-DOSY-
Conclusions
[53,54,59–62]
NMR followed published procedures.
We have shown that in the asymmetric hydrogenation
of prochiral ionic liquids high enantiomeric excesses
can be realized by transferring the chiral information
from the enantiopure anion to the prochiral cation by
intimate ion pair interactions. Although the formation
of a close contact ion pair in solution is not the only
[
N-(3’-Oxobutyl)-N-methylimidazolium] [(+)-Cam-
phorsulfonate] (2)
A flask was charged with methylimidazole (35.35 g, 0.43
prerequisite it has shown to be crucial for successful mol). Dichloromethane (250 mL) and (+)-camphor-10-sul-
chirality transfer.
fonic acid (100 g, 0.43 mol, 1.0 equiv.) were slowly added.
In addition, we have determined the degree of dis- After 2 h, the solvent was removed and the product was ob-
tained as a white solid. This was dissolved in ethanol
sociation of the ionic liquid in ethanolic and aqueous
(
400 mL) and methyl vinyl ketone (71.67 mL, 60.34 g, 0.861
solutions for different concentrations using DOSY-
NMR and conductivity measurements. With these
measurements we have expanded the scope of ion
pair dissociation studies for the first time to highly
functionalized ionic liquids. Very remarkably, the
lowest value for the degree of dissociation has been
found for the concentration 0.3 mol/L, where also the
highest degree of chiral induction in the hydrogena-
tion experiments was obtained. Our results may serve
to predict the conditions of effective chiral induction
by ion pairing in ionic liquids. In further developing
chiral induction among ion pairs to a potential ionic
auxiliary chemistry, this methodology may save in the
future tedious screening experiments to identify the
mol, 2.0 equiv.) was slowly added. The mixture was refluxed
for 3 d. After removal of the solvent the product was ob-
tained as light brown, highly viscous oil; yield: 157.64 g
(
0.41 mol, 95%).
[
N-(3’-Oxobutyl)imidazolium] [(+)-Camphor-
sulfonate] (4)
A flask equipped with a dropping funnel was charged with
imidazole (29.31 g, 0.43 mol), 1-butyl-2,3-dimethylimidazoli-
um chloride (11.27 g, 0.06 mol, 0.15 equiv.), and water
(
3
300 mL) and cooled to 58C. Methyl vinyl ketone (46.5 mL,
9.18 g, 0.56 mol, 1.3 equiv.) was slowly added. The mixture
was stirred for 12 h while slowly heating up to room temper-
best solvents and concentration ranges for a given ature. The resulting solution was extracted four times with
ionic liquid of interest.
dichloromethane in order to separate the product from
BMMIM Cl, which remains in the water phase. The organic
phase was dried over MgSO and the solvent was removed
4
in vacuo. The brown oil was purified by column chromatog-
raphy (silica, dichloromethane/ethanol, 8/1, v/v) giving the
Experimental Section
1
-methyl-3-(2-oxobutyl)imidazol as colorless viscous liquid;
yield: 38.90 g (0.28 mol, 65%).
General Remarks
The liquid was dissolved in dichloromethane (300 mL)
and (+)-camphor-10-sulfonic acid (65.04 g, 0.28 mol, 1.0
equiv.) was added portion wise. After 2 h the solvent was re-
moved and the ionic liquid was obtained as a light brown
oil; yield: 104.02 g (0.28 mol, 100%).
All syntheses were carried out under argon unless otherwise
specified. Solvents for the hydrogenation reactions were of
spectroscopic grade. Methylimidazole was distilled und kept
under argon at À188C prior to use. All other chemicals
438
asc.wiley-vch.de
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 432 – 440

Chirality Transfer in Imidazolium Camphorsulfonate Ionic Liquids
FULL PAPERS
[
N-(5’-Oxohexyl)-N-methylimidazolium] [(+)-Cam-
References
phorsulfonate] (6)
[
[
[
[
[
[
1] S. I. Lukyanov, Z. S. Zidi, S. V. Shevkunov, Fluid Phase
Equilib. 2005, 233, 34.
2] K. Liu, M. Pu, H. Li, B. Chen, Huaxue Wuli Xuebao
A flask was charged with methylimidazole (8.22 g, 0.10 mol)
and 1-chlorohexan-5-one (14.7 mL, 0.11 mol, 1.1 equiv.) and
heated to 808C for three days. Remaining 1-chlorohexan-5-
one was distilled out of the product under reduced pressure.
A 0.1M aqueous solution of the product ionic liquid was
slowly percolated through a strong base anion exchange
resin charged with (+)-camphorsulfonate. Water was re-
moved under reduced pressure. The resulting yellow ionic
liquid was chloride free according to silver nitrate test;
yield: 37.92 g (0.09 mol, 91%).
2
005, 18, 331.
3] T. Kato, N. Nanbu, Y. Sasaki, T. Ohsaka, F. Kitamura,
Electrochemistry (Tokyo, Japan) 2005, 73, 589.
4] Z. Liu, S. Huang, W. Wang, J. Phys. Chem. B 2004, 108,
1
2978.
5] T. I. Morrow, E. J. Maginn, ACS Symp. Ser. 2003, 856,
62.
1
6] W. R. Carper, Z. Meng, P. Wasserscheid, A. Doelle,
À
Column preparation: A Dowex 1-X8 column (Cl form,
Proceedings – Electrochemical Society 2002, 2002–2019,
capacity=1.2 mmol/mL, r=2.25 cm, h=11 cm) was washed
with 2M NaOH until no chloride could be detected when
adding silver nitrate solution. After washing to neutral pH
with water the column was charged with 0.1M camphorsul-
fonic acid solution and washed to neutrality again.
9
73.
[
[
[
7] S. Tsuzuki, H. Tokuda, K. Hayamizu, M. Watanabe, J.
Phys. Chem. B 2005, 109, 16474.
8] Y. Wang, H. Li, S. Han, J. Chem. Phys. 2005, 123,
1
74501/1.
9] P. A. Hunt, J. Phys. Chem. B 2007, 111, 4844.
Hydrogenation
[
[
[
[
[
10] M. G. Del Popolo, J. Kohanoff, R. M. Lynden-Bell, C.
Pinilla, Acc. Chem. Res. 2007, 40, 1156.
11] P. A. Hunt, I. R. Gould, B. Kirchner, Austr. J. Chem.
007, 60, 9.
12] P. A. Hunt, B. Kirchner, T. Welton, Chem. Eur J. 2006,
2, 6762.
13] T. Koddermann, D. Paschek, R. Ludwig, ChemPhys-
Chem 2007, 8, 2464.
Prior to every hydrogenation, the hygroscopic ionic liquid
was thoroughly dried at 458C and under reduced pressure
to guarantee minimal water content. The ionic liquid was
dissolved in 75 mL of the solvent and ruthenium on activat-
ed charcoal was added (5% Ru/C, 10 wt% with respect to
IL 2 and 4, 5% Ru/C, 50 wt% with respect to IL 6). The
mixture was hydrogenated in an autoclave at 608C, 60 bar
hydrogen pressure for 16 h. After filtration of the catalyst
and removal of the solvent the product was obtained as
highly viscous brown oil.
2
1
14] S. Nguyen Vinh, H. Matus Myrna, J. Grant Daniel, T.
Nguyen Minh, A. Dixon David, J. Phys. Chem. A 2007,
1
11, 8844.
15] W. Jiang, Y. Wang, G. A. Voth, J Phys Chem. B 2007,
11, 4812.
16] K. Fujii, Y. Soejima, Y. Kyoshoin, S. Fukuda, R. Kanza-
ki, Y. Umebayashi, T. Yamaguchi, S.-I. Ishiguro, T. Ta-
kamuku, J. Phys. Chem. B 2008, 112, 1359.
[
[
1
Anion Exchange
The ionic liquid was dissolved in dichloromethane and an
aqueous solution of 1.2 equivalents Li
ACHTUNGTNERNU[GN NTf ] was added.
2
After 30 min half of the water phase was replaced. The pro-
[17] M. Kanakubo, Y. Hiejima, T. Aizawa, Y. Kurata, A.
cedure was repeated twice. Drying over MgSO and removal
4
Wakisaka, Chem. Lett. 2005, 34, 706.
of the solvent led to a viscous light brown oil in up to 60%
yield.
[
[
18] S. Dorbritz, W. Ruth, U. Kragl, Adv. Synth. Catal. 2005,
47, 1273.
3
19] L. P. N. Rebelo, V. Najdanovic-Visak, Z. P. Visak, M.
Nunes da Ponte, J. Szydlowski, C. A. Cerdeirina, J.
Troncoso, L. Romani, J. M. S. S. Esperanca, H. J. R.
Guedes, H. C. de Sousa, Green Chem. 2004, 6, 369.
20] K. A. Fletcher, S. N. Baker, G. A. Baker, S. Pandey,
New J. Chem. 2003, 27, 1706.
21] H. Tokuda, S. Tsuzuki, M. A. B. H. Susan, K. Hayami-
zu, M. Watanabe, J. Phys. Chem. B 2006, 110, 19593.
22] A. Wulf, K. Fumino, D. Michalik, R. Ludwig, Chem-
PhysChem 2007, 8, 2265.
19
F NMR
The ionic liquid was dissolved in dry dichloromethane and re-
acted with enantiopure Mosherꢂs acid chloride [a-methoxy-a-
[
[
[
[
(
trifluormethyl)-phenylacetyl chloride, MTPACl] and tripro-
pylamine to drive the reaction to completion. The diastereo-
1
9
meric esters were analyzed by F NMR spectroscopy.
Supporting Information
23] A. Mele, G. Romanꢅ, M. Giannone, E. Ragg, G.
The analytical data of the products and selected examples of
19
Fronza, G. Raos, V. Marcon, Angew. Chem. 2006, 118,
F NMR spectra for the determination of the ee and
1
141; Angew. Chem. Int. Ed. 2006, 45, 1123.
DOSY-NMR spectra are given in the Supporting Informa-
tion.
[
24] C. S. Consorti, P. A. Z. Suarez, R. F. de Souza, R. A.
Burrow, D. H. Farrar, A. J. Lough, W. Loh, L. H. M. da
Silva, J. Dupont, J. Phys. Chem. B 2005, 109, 4341.
25] Y. Zhao, S. Gao, J. Wang, J. Tang, J. Phys. Chem. B
2008, 112, 2031.
[
[
Acknowledgements
26] B. Fazio, A. Triolo, G. D. Marco, J. Raman Spectr. 2008,
39, 233.
The authors wish to thank the German Science Foundation
(
DFG) for funding this work within its priority program
[27] T. Koeddermann, C. Wertz, A. Heintz, R. Ludwig,
SPP1191 “ionic liquids”.
ChemPhysChem 2006, 7, 1944.
Adv. Synth. Catal. 2009, 351, 432 – 440
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
439

Karola Schneiders et al.
FULL PAPERS
[
[
[
[
28] C. Chiappe, V. Conte, D. Pieraccini, Eur. J. Org. Chem.
[47] a) M. Rꢁping, B. J. Nachtsheim, S. A. Moreth, M.
Bolte, Angew. Chem. 2008, 120, 603; Angew. Chem. Int.
Ed. 2008, 47, 593; b) M. Rꢁping, W. Leawsuwan, A. P.
Antonchick, B. J. Nachtsheim, Angew. Chem. 2007, 119,
2143; Angew. Chem. Int. Ed. 2007, 46, 2097.
2
002, 2831.
29] M. Badri, J.-J. Brunet, R. Perron, Tetrahedron Lett.
992, 33, 4435.
1
30] M. J. Earle, P. B. McCormac, K. R. Seddon, Chem.
Commun. 1998, 2245.
31] K. Nobuoka, S. Kitaoka, K. Kunimitsu, M. Iio, T.
Harran, A. Wakisaka, Y. Ishikawa, J. Org. Chem. 2005,
[48] G. Hamilton, E. J. Kang, M. Mba, F. D. Toste, Science
2
007, 317, 496.
[
49] a) T. Ooi, K. Maruoka Angew. Chem. 2007, 119, 4300;
Angew. Chem. Int. Ed. 2007, 46, 4222; b) C. Carter, S.
Fletcher, A. Nelson, Tetrahedron: Asymmetry 2003, 14,
7
0, 10106.
[
32] K. Nobuoka, S. Kitaoka, M. Iio, T. Harran, Y. Ishikawa,
Phys. Chem. Chem. Phys. 2007, 9, 5891.
33] M. J. Earle, P. B. McCormac, K. R. Seddon, Green
1
995.
50] S. Yu, S. Lindeman, C. D. Tran, J. Org. Chem. 2008, 73,
576.
[
[
[
Chem. 1999, 1, 23.
2
[
[
[
34] K. Fukumoto, H. Ohno Chem. Commun. 2006, 3081.
35] M. Y. Machado, R. Dorta, Synthesis 2005, 2473.
36] R. Gausepohl, P. Buskens, J. Kleinen, A. Bruckmann,
C. W. Lehmann, J. Klankermayer, W. Leitner Angew.
Chem. 2006, 118, 3772; Angew. Chem. Int. Ed. 2006, 45,
51] P. S. Schulz, N. Mꢁller, A. Bçsmann, P. Wasserscheid,
Angew. Chem. 2007, 119, 1315; Angew. Chem. Int. Ed.
2
007, 46, 1293.
[
52] a) N. Furukawa, Y. Sugihara, H. Fujihara, J. Org.
Chem. 1989, 54, 4222; b) J.-L. Hsu, J.-M. Fang, J. Org.
Chem. 2001, 66, 8573.
3
689.
[
[
37] P. Wasserscheid, A. Bçsmann, C. Bolm, Chem.
Commun. 2002, 200.
38] C. Baudequin, D. Bregeon, J. Levillain, F. Guillen, J.-C.
[
[
[
[
53] F. C. Gozzo, L. S. Santos, R. Augusti, C. S. Consorti, J.
Dupont, M. N. Eberlin, Chem. Eur. J. 2004, 10, 6187.
54] R. Bini, O. Bortolini, C. Chiappe, D. Pieraccini, T. Sici-
liano, J. Phys. Chem. B 2007, 111, 598.
Plaquevent, A.-C. Gaumont, Tetrahedron: Asymmetry
2
005, 16, 3921.
55] K. Hayamizu, Y. Aihara, S. Arai, C. Garcia Martinez,
[
[
39] M. Y. Machado, R. Dorta, Synthesis 2005, 2473.
40] L. Zhang, S. Luo, X. Mi, S. Liu, Y. Qiao, H. Xu, J.-P.
Cheng Org. Biomol. Chem. 2008, 6, 567.
J. Phys. Chem. B 1999, 103, 519.
56] A. Noda, K. Hayamizu, M. Watanabe, J. Phys. Chem.
B 2001, 105, 4603.
[
41] C. Reichardt, Solvents and Solvent Effects in Organic
nd
[57] R. Giernoth, D. Bankmann, Eur. J. Org. Chem. 2005,
Chemistry Wiley-VCH, Weinheim, 1988 (2 edn.), 2003
rd
4529.
(3
edn.).
[
[
58] D. Nama, P. G. A. Kumar, P. S. Pregosin, T. J. Geldbach,
P. J. Dyson, Inorg. Chim. Acta 2006, 359, 1907.
59] Y. Saito, T. Umecky, J. Niwa, T. Sakai, S. Maeda, J.
Phys. Chem. B 2007, 111, 11794.
[42] A. Bçsmann, Dissertation, University Erlangen-Nꢁrn-
berg, in preparation.
[
43] a) P. Wasserscheid, A. Bçsmann, C. Bolm, Chem.
Commun. 2002, 200; b) M. L. Patil, C. V. L. Rao, K.
Yonezawa, S. Takizawa, K. Onitsuka, H. Sasai, Org.
Lett. 2006, 8, 227; c) J. Levillain, G. Dubant, I. Abrun-
hosa, M. Gulea, A.-C. Gaumont, Chem. Commun.
[60] G. Annat, D. F. MacFarlane, M. Forsyth, J. Phys. Chem.
B 2007, 111, 9018.
[61] a) P. Stilbs, Prog. Nucl. Magn. Reson. Spectrosc. 1987,
19, 1; b) C. S. Johnson Jr. , Prog. Nucl. Magn. Reson.
Spectrosc. 1999, 34, 203.
2
003, 2914.
[
[
44] M. Schmitkamp, D. Chen, W. Leitner, J. Klankermeyer,
G. Franciꢅ; Chem. Commun. 2007, 39, 4012.
[62] a) S. Berger, S. Braun, 200 and more NMR Experi-
nd
45] a) P. Pfeiffer, K. Quehl, Ber. Dtsch. Chem. Ges. 1931,
ments, Wiley-VCH, Weinheim, 1998, 2 edn., p 467;
6
4, 2667; b) S. Bergman, R. Franz, D. Gut, M. Kol, J.
b) H. Weingꢀrtner, Z. Phys. Chem. (Neue Folgen) 1982,
132, 129; c) M. Holz, H. Weingꢀrtner, J. Magn. Reson.
1991, 92, 115.
Lacour, Chem. Commun. 2006, 850.
[
46] Y. Chi, S. H. Gellman J. Am. Chem. Soc. 2006, 128,
6
804.
440
asc.wiley-vch.de
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 432 – 440