Coordinating chiral ionic liquids: Design, synthesis, and application in asymmetric transfer hydrogenation under aqueous conditions

Article abstract of DOI:10.1002/ejoc.201403555

Hydrophilic coordinating chiral ionic liquids with an amino alcohol substructure were developed and efficiently applied to the asymmetric reduction of ketones. Their careful design and adaptability to the desired reaction conditions allow for these chiral ionic liquids to be used as the sole source of chirality in a ruthenium-catalyzed transfer hydrogenation reaction of aromatic ketones. When used in this reaction system, these chiral ionic liquids afforded excellent yields and high enantioselectivities.

Full text of DOI:10.1002/ejoc.201403555

Job/Unit: O43555
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Date: 18-02-15 16:52:54
Pages: 9
FULL PAPER
DOI: 10.1002/ejoc.201403555
Coordinating Chiral Ionic Liquids: Design, Synthesis, and Application in
Asymmetric Transfer Hydrogenation under Aqueous Conditions
[a]
[a]
[b]
[a]
Maria Vasiloiu, Peter Gaertner, Ronald Zirbs, and Katharina Bica*
Keywords: Ionic liquids / Self-assembly / Asymmetric catalysis / Hydrogenation / Ruthenium / Ketones
Hydrophilic coordinating chiral ionic liquids with an amino
alcohol substructure were developed and efficiently applied
to the asymmetric reduction of ketones. Their careful design
and adaptability to the desired reaction conditions allow for
these chiral ionic liquids to be used as the sole source of
chirality in a ruthenium-catalyzed transfer hydrogenation
reaction of aromatic ketones. When used in this reaction
system, these chiral ionic liquids afforded excellent yields
and high enantioselectivities.
Introduction
siderable effort has been put into the development of new
water-soluble catalysts and ligands for ATH reactions.[
Still, many known asymmetric reactions have drawbacks
such as the comparatively high price of the chiral ligands
as well as catalyst leaching, and, therefore, the optimization
and improvement of these methods is a constant matter of
3,6]
Because of the significant role that enantiopure com-
pounds have in biological applications, there is tremendous
interest in research with regard to their stereospecific syn-
thesis. The stereoselective reduction of carbonyls and imines
are among the most important transformations in asym-
metric synthesis, as chiral alcohols can be widely used as
[7]
investigation. Chiral ionic liquids (CILs) represent an
innovative approach to deal with some of the drawbacks, as
they can be used as a sole source of chirality in asymmetric
[
1]
starting materials for further synthetic transformations.
Consequently, a variety of options for this reaction have
been investigated in search of the best conditions with
respect to conversion, enantioselectivity, atom efficiency,
and sustainability.
[8]
reactions. Their unique structures allow for the activity of
the ligand or catalyst in hand to be fine-tuned to the given
[9]
reaction conditions.
The adaptation of properties,
especially solvation behavior, is difficult with conventional
catalysts, which makes chiral ionic liquids particularly
attractive in this field of study. With the employment of
chiral ionic liquids, there is also the possibility of recycling
the catalyst (Figure 1).
Among catalytic procedures that have emerged in recent
years, asymmetric transfer hydrogenations (ATH) are a par-
ticularly attractive strategy, as they provide efficient access
to chiral alcohols by using small and nonhazardous organic
molecules as the hydrogen donor.[ The use of water-
soluble sodium formate as a hydrogen donor is particularly
attractive, as it provides not only an inexpensive and non-
reversible hydrogen source but also the opportunity to run
the reaction in aqueous medium.[ Driven by the trend of
modifying organic reaction procedures to have greener con-
ditions, the replacement of volatile organic solvents with
2]
In addition, the ionic structure, high degree of organiza-
tion, and hydrogen-bonded supramolecular network
inherent to ionic liquids have already been proposed as
features of chiral solvents that might allow for a significant
transfer of chirality in an asymmetric synthesis as well as
3]
[10]
for its ease of separation from the reaction mixture.
Hence, it was the wide field of asymmetric organocatalysis
that gave access to these highly enantioselective reactions
[
4]
water is presently a rapidly growing area of research. In
addition to the environmental benefits, water has been
that were catalyzed by chiral ionic liquids, along with the
shown to influence reaction rates and the selectivity of
[11]
extra benefit of recycling the chiral catalyst.
Soon
many organic transformations.[
5]
Consequently, con-
applications in other asymmetric reactions followed, and
successful examples for the use of chiral ionic liquids as a
catalyst, solvent, or ligand included reactions as diverse as
[
[
a] Institute of Applied Synthetic Chemistry, Vienna University of
Technology,
[
12]
asymmetric hydrogenations,
aza-Baylis–Hillman reac-
Getreidemarkt 9/163, 1060 Vienna, Austria
E-mail: katharina.bica@tuwien.ac.at
http://www.ias.tuwien.ac.at/home/
b] Laboratory for Bioinspired Materials, Department of
[
13]
[14]
[15]
tions, sulfoxide oxidations, and alkylation reactions.
Inspired by the outstanding progress with ruthenium-cat-
NanoBiotechnology, BOKU – University of Natural Resources alyzed asymmetric transfer hydrogenation reactions in the
and Life Sciences Vienna,
past years, a new approach that featured hydrophilic chiral
ionic liquids was explored. The modular design of chiral
ionic liquids with variable anions is a clear advantage, as
Muthgasse 11, 1190 Vienna, Austria
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201403555.
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M. Vasiloiu, P. Gaertner, R. Zirbs, K. Bica
FULL PAPER
Figure 1. Concept and benefits of coordinating chiral ionic liquids with tunable properties (IL-pre = ionic liquid precursor).
chiral ligands with adaptable solubility can be designed for alkylation to form an ionic liquid (Scheme 1). We selected
the desired reaction conditions in aqueous asymmetric three different chiral primary amino alcohols as starting
transfer hydrogenations that use sodium formate as the materials. Norephedrine (1), 2-amino-1,2-diphenylethanol
hydrogen source. Herein, we present the design, synthesis, (6), and 2-amino-1-indanol (9) were treated with pyridine-
and application of the highly coordinating amino alcohol 2-carbaldehyde in the presence of activated molecular sieves
derived chiral ionic liquids that, on the basis of their and subsequently reduced with sodium borohydride to ob-
tunable properties, can be applied as the sole chirality tain the chiral ionic liquid precursors. As already shown in
source in asymmetric transfer hydrogenations under the case of chiral ionic liquid mediated asymmetric alkyl-
[
16]
aqueous conditions.
ations, we chose a pyridinium system as the ionic liquid
head group, as it avoids the presence of acidic protons that
are found in common imidazolium cations, which have an
unpredictable influence on transition-metal catalysis be-
cause of carbene formation. The enantiopure N,N,O-tri-
dentate ligands were further converted into the ionic liquid
through quarternization with n-butyl bromide at 50 °C
under solvent-free conditions. The obtained halide ionic li-
quids are highly hydrophilic and provide water solubility
for the active ruthenium complex.
Results and Discussion
[
19]
As demonstrated in the literature, chiral amino alcohols
are increasingly considered for asymmetric transfer hyd-
[
17]
rogenations.
In contrast to chiral diamines, which are
[2]
preferably used as ligands in this reaction, amino alcohols
can often be directly obtained from the chiral pool, and,
hence, they provide an inexpensive and attractive alternative
for the often expensive chiral diamine ligands. Furthermore,
II
amino alcohol based ligands in ligand-accelerated Ru -cat-
alyzed ATH reactions have result in higher reaction rates
than those that have used other chiral ligands such as
diamines,
2,2Ј-bis(diphenylphosphino)-1,1Ј-binaphthyl
(
BINAP), or phosphorus-based ligands. Excellent selectivi-
[17c,18]
ties were also observed.
Previously, we reported the
design of highly coordinating chiral ionic liquids with a ter-
tiary amino alcohol substructure to be applied as recyclable
Figure 2. Design of chiral ionic liquid-supported complex vs con-
ventional complex (IL = ionic liquid).
ligands in asymmetric diethylzinc additions.[
15]
Conse-
quently, the concept of coordinating chiral ionic liquids
with an amino alcohol structure was further adapted and
Additionally, to investigate the influence of the self-
expanded to provide hydrophilic chiral ligands grafted onto assembly of the catalyst complex in water, different alkyl
a cationic head group for future applications in transfer chain lengths were installed at the pyridinium moiety in the
hydrogenations under aqueous conditions.
case of norephedrine-derived chiral ionic liquids 3–5. The
However, the application in asymmetric transfer hydro- different alkyl chain lengths might further influence their
genations requires a secondary amine functionality to form catalytic performance as ligands in the ATH reaction. We
a six-membered transition state with the carbonyl substrate have already shown that the self-assembly of ionic liquids
[
20]
(Figure 2). A small set of chiral ionic liquids with the sec- in water can result in increased reaction rates.
ondary amino alcohol substructure were therefore devel-
The successful selective alkylation of the pyridine nitro-
oped, which relied on grafting an ionic liquid precursor to gen atom is the key step in the preparation of these highly
an already established chiral ligand followed by a selective coordinating chiral ionic liquids. In contrast to the alkyl-
2
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Coordinating Chiral Ionic Liquids
Scheme 1. Synthesis of amino alcohol derived chiral ionic liquids for asymmetric transfer hydrogenation.
ation of tertiary N,N,O-ligands such as the methylated
ephedrine derivative, the alkylation of secondary amino
alcohols 1, 6, and 9 with n-butyl bromide did not occur
selectively at the pyridine nitrogen atom. The quaterni-
zation of 2, 7, and 10 with n-butyl bromide at 50 °C gave a
mixture of the mono- and dialkylated derivatives. However,
the pyridinium cation was still formed preferentially, and
the ratio of the mono-/dialkylated species was approxi-
1
mately 2:1, as calculated by H NMR analysis (Figure 3).
When the amount of n-butyl bromide was decreased to
1
equiv. and the reaction temperature was lowered to 40 °C,
a double alkylation was still observed. The mono- and di-
alkylated species in the mixture were eventually separated
by preparative HPLC, and the isolated yields of the desired
final chiral ionic liquids were still in an acceptable range of
45–64%. Preparative HPLC was performed under reversed-
phase conditions by using methanol and water as the
mobile phase on a C18 column.
To evaluate these new hydrophilic chiral ionic liquids in
an asymmetric transfer hydrogenation reaction, the re-
duction of acetophenone 12 by using 5 mol-% [Ru(p-
cymene)Cl ] as the catalyst with sodium formate as the
2
2
hydrogen source was chosen as the model system. Initially,
we evaluated the reaction for the ideal conditions with re-
spect to temperature and concentration of acetophenone in
water (Scheme 2).
Varying the concentration of chiral ionic liquid 3 re-
vealed that a range from 0.5 to 2 m was suitable to observe
the complete conversion of acetophenone 12 after 48 h with
good enantioselectivities of 68–75%ee (enantiomeric ex-
cess). More dilute conditions resulted in a significant
decrease in the reaction rate (Table 1, Entries 1–6).
1
Figure 3. H NMR spectra after alkylation of substrate 7, which
afforded a mixture of mono- and dialkylated species (top). Purifica-
tion by preparative HPLC afforded the monoalkylated species
(bottom).
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M. Vasiloiu, P. Gaertner, R. Zirbs, K. Bica
FULL PAPER
chiral ionic liquid 11 gave a lower conversion and selecti-
vity.
In a further experiment, the reaction with the chiral ionic
liquid supported Ru catalyst 3 was compared to that with
the neutral ephedrine ligand 2, that is, the product prior to
the quaternization step. Although there was no difference
in the enantioselectivity of the two systems, the reaction did
proceed significantly faster with the salt form of the ligand.
In the case of ephedrine-derived ionic liquid 3, the reaction
reached complete conversion after 7 h, whereas the same
reaction with neutral ephedrine ligand 2 only reached 60%
conversion after this period of time, thereby emphasizing
the merit of a hydrophilic chiral ionic liquid. The influence
of different chain lengths however seems to have a limited
effect in the reaction, as ephedrine-derived chiral ionic
liquids 3, 4, and 5 with different alkyl chain lengths gave
similar results (Table 2, Entries 1–3). This is surprising,
given the fact that dynamic light scattering (DLS) experi-
ments clearly indicate the presence of ruthenium metallo-
micelles for N-dodecylpyridinium bromide 5, which were
not observed with the CILs of shorter alkyl chain length
Scheme 2. Asymmetric transfer hydrogenation reaction of aceto-
phenone in the presence of a chiral ionic liquid.
Table 1. Optimization of reaction conditions.[a]
[b]
[c]
% ee[d,e]
Entry T [°C] Conc. of 3 [m] % Conversion /isol. yield
1
2
3
4
5
6
7
8
9
50
50
50
50
50
50
30
40
60
70
2
1
97
Ͼ99/99
98/97
86
51
27
73 (R)
68 (R)
71 (R)
68 (R)
46 (R)
66 (R)
75 (R)
75 (R)
63 (R)
40 (R)
0.5
0.25
0.1
0.05
0.5
0.5
0.5
0.5
85
Ͼ99/97
Ͼ99/96
76
12
[
(
(
a] Performed with acetophenone (2 mmol), sodium formate
10 mmol), chiral ionic liquid 3 (12 mol-%), and Ru catalyst
5 mol-%) for 48 h. [b] Conversion determined by GC analysis.
II
(Figure 4).
[
c] Isolated yields after flash column chromatography. [d] Deter-
mined by HPLC analysis using a DAICEL Chiralcel IB column.
e] Absolute configuration determined by optical rotation data and
[
comparing with literature values.
Changing the reaction temperature was observed to have
a strong influence on the enantioselectivity, as a higher re-
action temperature gave lower enantiomeric excess values.
Because the reaction reached completion after 24 h in most
of the cases, an increase in the temperature to over 50 °C
was not necessary. Eventually, the ideal reaction conditions
were identified as a 0.5 m solution of acetophenone 12 in
degassed water at 50 °C, and these conditions were em-
ployed to investigate the influence of different hydrophilic
chiral ionic liquids. As can be seen from Table 2, the best Figure 4. Dynamic light scattering of chiral ionic liquid 5 and chiral
results were obtained with the ephedrine-derived hydro- ionic liquid based ruthenium metallomicelles. Reagents and condi-
tions: chiral ionic liquid 5 (0.02 mmol) with and without [Ru(p-
cymene)Cl ] (0.01 mmol) in H O (4 mL).
2 2 2
philic chiral ionic liquids. Aminodiphenylethanol-derived
system 8 also performed quite well, whereas indanol-based
In principle, the concept of hydrophilic ionic liquids also
holds potential for recycling the precious chiral ruthenium
species, as the ionic liquid bound catalyst is immobilized in
the bulk aqueous layer. We consequently investigated recy-
cling of the active catalyst in asymmetric transfer hydrogen-
ation and extracted the obtained chiral alcohol derivative
from the aqueous layer containing the chiral ionic liquid
with small amounts of degassed n-hexane. After phase sepa-
ration, the ruthenium-containing aqueous layer could in-
deed be recycled for use in a consecutive asymmetric trans-
fer hydrogenation reaction (Table 2, Entries 6 and 7). How-
Table 2. Variation of chiral ionic liquids for asymmetric transfer
hydrogenation reaction.[
a]
[b]
[c]
% ee[d,e]
Entry CIL Core structure
% Conv. /isol. yield
1
2
3
4
5
3
4
5
8
ephedrine, n = 4
ephedrine, n = 8
ephedrine, n = 12
94/93
98/98
Ͼ99/98
71 (R)
72 (R)
71 (R)
47 (S)
28 (R)
63 (R)
38 (R)
aminodiphenylethanol 83/80
11 indanol
3
3
28/22
61
25
[
f]
6
7
ephedrine, n = 4
ephedrine, n = 4
[
f]
[
(
a] Performed with acetophenone (2 mmol), sodium formate
II
10 mmol), chiral ionic liquid (12 mol-%), and Ru catalyst (5 mol- ever, losses to both the conversion and enantioselectivity
%
) for 24 h. [b] Conversion determined by GC analysis. [c] Isolated occurred in the third run, which indicates that the recycling
yields after flash column chromatography. [d] Determined by
HPLC analysis using a DAICEL Chiralcel IB column. [e] Absolute
configuration determined by optical rotation data and comparing
with literature values. [f] Reaction was carried out at 60 °C with
recycled catalyst (1 and 2ϫ).
protocol under these conditions suffers from catalyst leach-
ing and still needs to be optimized.
To investigate the substrate scope, a series of prochiral
ketones were chosen that contained both electron-with-
4
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Coordinating Chiral Ionic Liquids
drawing and electron-rich substituents. With the exception as the eluents. Preparative HPLC was performed on a Shimazu
preparative HPLC that was equipped with a SDP20A PDA detec-
of propiophenone, moderate to good conversions and good
selectivities of Ͼ60%ee were obtained by using chiral ionic
liquid 3 (Table 3).
2
tor by using a C18(2) column (250ϫ21.20 cm ID) and MeOH/H O
–
1
as the eluent at a flow rate of 20 mLmin . TLC analysis was
carried out with precoated aluminum-backed plates that were pur-
1
13
Table 3. Investigation of substrate scope.[a]
chased from Merck (silica gel 60 F254). The H and C NMR
spectroscopic data were recorded with a Bruker AC 200 (200 MHz)
or a Bruker Advance UltraShield 400 (400 MHz) spectrometer, and
[b]
[c]
% ee[d,e]
Entry Substrate
% Conv. /isol. yield
1
2
3
4
5
6
7
8
9
propiophenone
34/30
90/86
93/89
89/87
77/76
98/95
64/62
76/71
86/85
65 (R)
26 (R)
70 (R)
68 (R)
73 (R)
67 (R)
60 (R)
85 (S)
71 (S)
3 3
CDCl or CD OD was used as the NMR solvent. The chemical
shifts (δ) are reported in ppm by using tetramethylsilane as the
internal standard, and coupling constants (J) are reported in Hertz
2-nitroacetophenone
3-nitroacetophenone
4-nitroacetophenone
4-bromoacetophenone
4-chloroacetophenone
4-methoxyacetophenone
1-indanone
[
Hz]. The following abbreviations are used to explain the signal
multiplicities: s (singlet), d (doublet), t (triplet), q (quartet), quin
quintet), sext (sextet), m (multiplet), br. s (broad singlet). Infrared
(
spectra were recorded on a Perkin–Elmer Spectrum 65 FT IR spec-
trometer that was equipped with a Specac MK II Golden Gate
Single Reflection ATR (attenuated total reflectance) unit. Optical
rotations were measured on an Anton Paar MCP500 polarimeter
at the specified conditions. Thermal stabilities were determined on
a Netzsch TGA in a range of 25 to 500 °C with a heating rate of
1-acetonaphthone
[
(
(
a] Performed with acetophenone (2 mmol), sodium formate
10 mmol), chiral ionic liquid 3 (12 mol-%), and Ru catalyst
5 mol-%) for 24 h. [b] Conversion determined by GC analysis.
II
[
c] Isolated yields after flash column chromatography. [d] Deter-
mined by HPLC analysis using a DAICEL Chiralcel IB column.
e] Absolute configuration determined by optical rotation data and
–
1
1
0 °Cmin . Decomposition temperatures (T5%onset) were reported
[
from the onset to a 5 wt.-% loss of mass. Melting points above
room temperature were measured on a Kofler hot-stage microscope
or on an automated melting point system OPTI MELT of Stanford
Research Systems. Elemental analysis was performed at Vienna
University, Department of Physicochemistry - Laboratory for Mi-
croanalysis, Währingerstraße 42, 1090 Vienna. GC analysis was
conducted with a Thermo Finnigan Focus GC/DSQ II that was
equipped with a flame ionization detector (FID) detector and used
comparing with literature values.
Conclusions
Chiral ionic liquids can be efficiently synthesized from
naturally occurring enantiopure starting materials and can a standard capillary column BGB5 (30 mϫ0.32 mm ID) at a flow
–
1
demonstrate strong chiral interactions. This characteristic rate of 2.0 mLmin and a split ratio of 20 with helium as the
in combination with the tunable nature of ionic liquids carrier gas. The enantiomeric excess values were determined by
HPLC analysis on a DAIONEX UPLC that was equipped with a
reveals new solutions for asymmetric synthesis. Herein, we
photodiode array (PDA) plus detector (190–360 nm) and by using
a DAICEL IB column (250ϫ4.60 mm) as the stationary phase,
showed that amino alcohol derived chiral ionic liquids
provide an attractive alternative to conventional ligands in
asymmetric ruthenium-catalyzed transfer hydrogenations.
mixtures of n-heptane/iPrOH as the solvent, and flow rates of 0.5–
–
1
1
.0 mLmin .
The modular design based on the chiral pool derived amino
alcohol norephedrine allowed the formation of highly coor-
dinating chiral ionic liquids, and the adaptation of its solu-
bility to the given reaction conditions could be obtained by
the choice of anion. When employed as a sole source of
chirality in asymmetric transfer hydrogenation reactions,
the chiral ionic liquids provided excellent enantioselecti-
(
1R,2S)-1-Phenyl-2-[(pyridin-3-ylmethyl)amino]propan-1-ol
(2):
Freshly distilled pyridine-3-carbaldehyde (0.31 mL, 3.31 mmol) was
added to a mixture of (1R,2S)-norephedrine (1, 0.50 g, 3.31 mmol)
and activated molecular sieves (3 Å, 1.50 g) in anhydrous methanol
(
50 mL), and the resulting mixture was heated at reflux for 14 h
until TLC analysis showed full conversion of the starting material.
Sodium borohydride (0.14 g, 3.64 mmol) was then added in small
vities and yields. Our current research focuses on the devel- portions, and the mixture was stirred at room temperature until the
opment of improved recycling strategies for ionic liquid TLC plate showed complete conversion of the starting material.
bound transition-metal catalysts that are immobilized in the The reaction mixture was filtered through silica and diluted with
distilled H
the aqueous layer was extracted with CH
further purified by MPLC (100 g silica, CH
product 2 (0.65 g, 2.1 mmol, 80% yield) as a colorless solid. Data
2
O. Methanol was removed under reduced pressure, and
Cl . The product was
Cl /MeOH, 6:1) to give
aqueous layer as well as on more detailed investigations
towards the merit of surface-active chiral ionic liquids,
which is an active area of research for our group.
2
2
2
2
was in accordance with the literature.[
CD OD): δ = 8.46–8.40 (m, 2 H, H-pyridine), 7.78–7.73 (m, 1 H,
H-pyridine), 7.41–7.25 (m, 5 H, H-Ar), 4.70 (d, J = 5.00 Hz, CH-
OH), 3.82 (dd, J = 5.28 Hz, J = 32.50 Hz, 2 H, CH -NH), 2.92–
.79 (m, 1 H, CH-CH ), 1.04 (d, J = 6.46 Hz, 3 H, CH ) ppm.
15] 1
H NMR (400 MHz,
3
H
Experimental Section
1
2
2
General Methods: All reagents were purchased from commercial
suppliers and used without further purification unless otherwise
2
3
3
noted. CH
free reactions were predistilled and dried on Al
PURESOLV, Innovative Technology). Column chromatography
was performed on a Büchi Sepacore Flash System (2ϫ Büchi
Pump Module C-605, Büchi Pump Manager C-615, Büchi UV
Photometer C-635, Büchi Fraction Collector C-660) with mixtures
2 2 2
Cl , Et O, and MeOH that were intended for water- 1-Butyl-3-({[(1R,2S)-1-hydroxy-1-phenylpropan-2-yl]amino}methyl)-
2
O
3
columns
pyridin-1-ium Bromide (3): Compound 2 (1.14 g, 4.71 mmol) and
freshly distilled n-butyl bromide (0.51 mL, 4.71 mmol) were mixed
in a round-bottom flask, which was sealed, and the resulting mix-
ture was stirred at 60 °C for 24 h. The excess amount of n-butyl
bromide was evaporated, and the brown oil was washed (2ϫ) with
anhydrous ethyl acetate. The remaining volatile materials were re-
(
2 2
of petroleum ether (PE)/ethyl acetate (EtOAc) or MeOH/CH Cl
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M. Vasiloiu, P. Gaertner, R. Zirbs, K. Bica
FULL PAPER
moved under reduced pressure at 60 °C to give the crude product,
which was purified by preparative HPLC (MeOH/H O, 50:50) to
give compound 3 (0.89 g, 2.58 mmol, 55% yield) as a light yellow
d, C-Ar), 146.1 (d, C-Ar), 144.9 (d, C-Ar), 140.2 (s, C-Ar), 128.2
(2 d, C-Ar), 128.0 (s, C-Ar), 127.5 (d, C-Ar), 125.7 (2 d, C-Ar),
2
70.4 (d, CH-OH), 62.2 (t, CH
2
-NH), 62.1 (d, CH-CH
11-CH ], 31.5 [t, (CH -CH
], 28.8/28.7 [2 t, (CH -CH , (CH
], 22.3 [t, (CH -CH ], 13.0 [t, (CH
], 7.8 [q, (CH 12-CH ], 6.3 (q, CH-CH
3
), 52.2 (t,
1
+
oil. H NMR (400 MHz, CD
.85 (d, J = 6.00 Hz, 1 H, H-pyridine), 8.46 (d, J = 8.05 Hz, 1 H,
H-pyridine), 8.03–7.96 (m, 1 H, H-pyridine), 7.40–7.25 (m, 5 H, H-
Ar), 4.72 (d, J = 4.80 Hz, CH-OH), 4.60 (t, J = 7.54 Hz, 2 H, CH
N), 4.08 (dd, J = 6.60 Hz, J = 37.28 Hz, 2 H, CH
.86 (m, 1 H, CH-CH ), 2.07–1.91 (m, 2 H, CH -CH
sext, J = 7.44 Hz, 2 H, CH -CH -CH -N), 1.08–0.98 (m, 6 H, 702 (C–H-Ar) cm . C27
CH , CH -CH -CH -CH -N) ppm. C NMR (100 MHz, N 5.70; found C 65.89, H 8.52, N 6.01.
CD OD): δ = 143.4 (2 d, C-Ar), 142.5 (d, C-Ar), 141.3 (d, C-Ar),
41.2 (s, C-Ar), 126.6 (s, C-Ar), 126.5 (2 d, C-Ar), 126.0 (d, C-Ar),
24.9 (2 d, C-Ar), 73.4 (d, CH-OH), 60.0 (t, CH -NH), 57.2 (d,
-CH ), 17.6 (t,
), 11.0 (q, CH-
= +3.52 (c = 0.79, MeOH). T5%onset: 213 °C. IR:
3
OD): δ
H
= 8.92 (s, 1 H, H-pyridine), CH
2
-N ), 45.5 [2 t, (CH
2
)
2
2
)
9
2
], 31.2 [t,
], 25.9 [t,
8
(CH
2
)
8
-CH
2
2
)
6
2
2
)
7
-CH
2
(CH
(CH
2
)
5
-CH
-CH
2
2
)
4
2
2 3 2
) -CH ], 9.08 [t,
2
0
2
-
2
)
2
2
2
)
3
3
). [α]
D
= +0.58
1
2
2
-NH), 2.98– (c = 0.97, MeOH). T5%onset: 225 °C. IR: ν˜ max = 3305 (N–H), 2922
-N), 1.42 (O–H), 1632 (C–C), 1634 (C–C), 1498 (C=C), 1198 (NH–CH ),
O (491.56): calcd. C 65.97, H 8.82,
2
(
3
2
2
3
–
1
2
2
2
H43BrN
2
1
3
3
3
2
2
2
3
C
(
1S,2R)-1,2-Diphenyl-2-[(pyridin-3-ylmethyl)amino]ethanol (7): By
1
1
following the procedure for compound 2, (1S,2R)-2-amino-1,2-di-
phenylethanol (6, 2.00 g, 9.33 mmol), freshly distilled pyridine-3-
carbaldehyde (0.88 mL, 9.33 mmol), activated molecular sieves
(3 Å, 5.00 g), and sodium borohydride (0.35 g, 9.33 mmol) in anhy-
drous methanol (100 mL) were employed to give the product, which
2
+
CH-CH
CH
CH
3
), 45.4 (t, CH
2
-N ), 31.6 (t, CH
-CH
2
-CH
-CH
2
-CH
-CH
2
3
2
-CH
) ppm. [α]
2
-CH -CH ), 12.2 (q, CH
2
3
2
2
2
3
2
0
3
D
ν˜ max = 3276 (O–H), 1633 (C–C), 1593 (C–C), 1449 (C=C), 1116
–1
was further purified by MPLC (200 g silica, CH
Et N) to give 7 (2.52 g, 8.28 mmol, 89% yield) as a colorless
solid. Crystallization from toluene gave colorless crystals. Data was
2 2
Cl /MeOH, 40:1
(
6
7
NH–CH
3
), 702 (C–H-Ar) cm . C19
0.16, H 7.17, N 7.38; calcd. (including 0.69ϫH
.30, N 7.15; found C 58.27, H 6.99, N 7.38.
H
27BrN
2
O (379.34): calcd. C
+
3
2
O) C 58.25, H
in accordance with the literature.[
= 8.38 (d, J = 4.78 Hz, 1 H, H-pyridine), 8.28 (s, 1 H, H-pyr-
idine), 7.42–7.38 (m, 1 H, H-pyridine), 7.18–7.10 (m, 11 H, H-Ar),
.71 (d, J = 6.06 Hz, 1 H, CH-OH), 3.81 (d, J = 6.06 Hz, 1 H, CH-
NH), 3.60 (d, J = 13.67 Hz, 1 H, CH -NH), 3.43 (d, J = 13.69 Hz,
H, CH ), 2.80 (br. s, 1 H, OH), 1.68 (br. s, 2 H, NH ) ppm.
15] 1
3
H NMR (400 MHz, CD OD):
3-({[(1R,2S)-1-Hydroxy-1-phenylpropan-2-yl]amino}methyl)-1-octyl-
δ
H
pyridin-1-ium Bromide (4): By following the procedure for com-
pound 3, compound 2 (0.46 g, 1.89 mmol) and n-octyl bromide
4
(
0.33 mL, 1.89 mmol) afforded the crude product as a viscous
brown oil, which was purified by preparative HPLC (MeOH/H O,
0:50) to give 4 (0.35 g, 0.92 mmol, 49% yield) as a light yellow
2
2
1
2
2
5
1
1-Butyl-3-({[(1S,2R)-2-hydroxy-1,2-diphenylethyl]amino}methyl)pyr-
idin-1-ium Bromide (8): By following the procedure for compound
oil. H NMR (400 MHz, CD
3 H
OD): δ = 8.94 (s, 1 H, H-pyridine),
8.86 (d, J = 5.98 Hz, 1 H, H-pyridine), 8.48 (d, J = 8.05 Hz, 1 H,
3, compound 7 (0.40 g, 1.31 mmol) and n-butyl bromide (0.14 mL,
H-pyridine), 8.03–7.96 (m, 1 H, H-pyridine), 7.40–7.25 (m, 5 H, H-
Ar), 4.89 (d, J = 4.89 Hz, 1 H, CH-OH), 4.59 (t, J = 7.54 Hz, 2 H,
1.31 mmol) gave the crude product as a viscous yellow oil, which
was was purified by preparative HPLC (MeOH/H
yield product 8 (0.31 g, 0.79 mmol) as a light yellow liquid.
NMR (200 MHz, CD OD): δ = 9.33 (s, 1 H, H-pyridine), 9.06
2
O, 80:20) to
CH
2
-N), 4.09 (dd, J
.00–2.88 (m, 1 H, CH-CH
.38–1.30 (m, 10 H, CH -CH
.60 Hz, 3 H, CH ), 0.93–0.86 (m, 3 H, CH
OD): δ
1
= 6.10 Hz, J
2
= 36.82 Hz, 2 H, CH
-CH
-N), 1.06 (d, J =
2
-NH),
1
H
3
1
6
3
), 2.04–2.01 (m, 2 H, CH
2
2
-N),
-CH
2
-CH
2
-CH
2
3
H
2
2
1
3
(d, J = 5.76 Hz, 1 H, H-pyridine), 8.11 (d, J = 7.89 Hz, 1 H, H-
pyridine), 7.86–7.79 (m, 1 H, H-pyridine), 7.17–7.06 (m, 5 H, H-
3
3
-alkyl-N) ppm.
C
NMR (100 MHz, CD
3
C
= 148.6 (2 d, C-Ar), 147.7 (d, C-
Ar), 5.09 (d, J = 3.91 Hz, CH-OH), 4.74 (t, J = 7.25 Hz, 2 H, CH
N), 3.97 (d, J = 4.00 Hz, CH-NH), 3.86 (s, 2 H, CH -NH), 2.91
(br. s, 1 H, NH), 2.98–2.86 (m, 1 H, CH-CH ), 2.00–1.85 (m, 2 H,
2
-
Ar), 146.5 (d, C-Ar), 141.4 (s, C-Ar), 134.5 (s, C-Ar), 129.6 (2 d,
C-Ar), 129.0 (d, C-Ar), 127.0 (2 d, C-Ar), 71.5 (d, CH-OH), 63.6
2
+
(
(
(
(
t, CH
2
-NH), 61.6 (d, CH-CH
], 32.4 [t, (CH -CH
], 27.7 [t, (CH -CH ], 20.5 [t, (CH
-CH ], 14.4 [q, (CH
= = +6.75 (c = 0.77, MeOH). T5%onset: 200 °C.
3
), 43.3 (t, CH
], 30.2/30.1 [2 t, (CH
-CH ], 20.1 [t,
12-CH ], 10.1 (q,
2
-N ), 33.9 [t,
3
CH
.33 Hz, 3 H, CH
CD OD): δ = 146.5 (d, C-Ar), 144.4 (d, C-Ar), 143.5 (s, C-Ar),
140.9 (d, C-Ar), 130.0 (s, C-Ar), 129.2 (s, C-Ar), 129.0 (d, C-Ar),
28.8 (d, C-Ar), 128.7 (d, C-Ar), 128.3 (d, C-Ar), 78.3 (d, CH-OH),
2
-CH
2
-N), 1.40–1.29 (m, 2 H, CH
2 2 2
-CH -CH -N), 0.92 (t, J =
CH 10-CH
2
)
2
2
)
9
2
2
)
7
-CH ,
2
1
3
7
3
-CH -CH -CH -N) ppm. C NMR (50 MHz,
2
2
2
CH
CH
2
2
)
)
8
-CH
-CH
2
2
2
)
6
2
2
)
5
2
], 15.6 [t, (CH
2
)
3
2
2
)
3
3
C
4
) ppm. [α]2
0
CH-CH
3
D
1
IR: ν˜ max = 3294 (N–H), 2925 (O–H), 1632 (C–C), 1535 (C–C),
–1
69.9 (d, CH-N), 62.8 (t, CH -CH -CH ), 55.7 (t, CH ), 34.4 (t,
1498 (C=C), 1197 (NH–CH
3
), 702 (C–H-Ar) cm . C23
H
35BrN
2
O
2
2
2
2
CH
CH
2
-CH
) ppm. [α]
2
-CH
2
0
), 20.5 (t, CH
= +9.66 (c = 1.02, MeOH). T5%onset: 218 °C. IR:
2
-CH
2
-CH
2
3 2
), 13.8 (q, CH -CH -
(
435.45): calcd. C 63.44, H 8.30, N 6.43; calcd. (including
2
2
4.71ϫH O) C 53.95, H 8.76, N 5.24; found C 53.97, H 8.53, N
2
D
ν˜ max = 3250 (N–H), 2707 (O–H), 1598 (C–C), 1357 (C=C), 1191
4.97.
–
1
(
6
6
NH–CH
3
), 702 (C–H-Ar) cm . C24
5.31, H 6.62, N 6.35; calcd. (including 2.62ϫH
.91, N 5.95; found C 61.29, H 7.07, N 5.81.
H
29BrN
2
O (441.41): calcd. C
1
-Dodecyl-3-({[(1R,2S)-1-hydroxy-1-phenylpropan-2-yl]amino}-
2
O) C 61.25, H
methyl)pyridin-1-ium Bromide (5): By following the procedure for
compound 3, compound 2 (1.14 g, 4.70 mmol) and n-dodecyl
bromide (1.13 mL, 4.70 mmol) afforded the crude product as a vis-
cous brown oil, which was purified by preparative HPLC (MeOH/
(1S,2R)-2-[(Pyridin-3-ylmethyl)amino]-2,3-dihydro-1H-inden-1-ol
(10): By following the procedure for compound 2, (1S,2R)-amino-
indanol (9, 0.51 g, 3.41 mmol), pyridine-3-carbaldehyde (0.32 mL,
2
H O, 50:50) to give 5 (1.05 g, 2.77 mmol, 59% yield) as a light
1
yellow oil. H NMR (400 MHz, CD
3
OD): δ
H
= 8.89 (s, 1 H, H- 3.41 mmol), activated molecular sieves (3 Å, 2.00 g), and sodium
borohydride (0.13 g, 3.41 mmol) were employed to give the crude
product, which was purified by MPLC (CH Cl /MeOH, 6:1) to af-
.25 (m, 5 H, H-Ar), 4.69 (d, J = 4.89 Hz, CH-OH), 4.58 (t, J = ford 10 (0.74 g, 3.08 mmol, 59% yield) as colorless crystals; m.p.
pyridine), 8.84 (d, J = 6.06 Hz, 1 H, H-pyridine), 8.45 (d, J =
.15 Hz, 1 H, H-pyridine), 8.02–7.95 (m, 1 H, H-pyridine), 7.40–
8
7
7
2
2
1
.53 Hz, 2 H, CH
2
-N), 4.05 (dd, J
-NH), 2.94–2.81 (m, 1 H, CH-CH
-N), 1.38–1.30 (m, 18 H, CH -CH
-CH
-alkyl-N) ppm. C NMR (100 MHz, CD
1
= 6.90 Hz, J
2
= 37.66 Hz, 2 H, 90–93 °C. H NMR (200 MHz, CD
3
OD): δ
= 1.59 Hz, J
= 1.84 Hz, J = 7.45 Hz, 1 H, H-pyr-
H
= 8.64 (d, J =
CH
CH
CH
CH
2
2
2
3
3
), 2.04–1.97 (m, 2 H, CH
-CH -CH -CH -CH -CH
2
-
-
2.00 Hz, 1 H, H-pyridine), 8.55 (dd, J
H, H-pyridine), 7.78 (td, J
1
2
= 4.81 Hz, 1
2
2
2
2
2
2
2
1
2
2
-N), 1.06 (d, J = 6.65 Hz, 3 H, CH
3
), 0.93–0.87 (m, 3 H, idine), 7.34–7.25 (m, 5 H, H-Ar), 4.48–4-42 (m, 1 H, CH-NH), 4.14
OD): δ = 147.0 (2 (d, J = 5.28 Hz, CH-OH), 4.04 (s, 2 H, CH -NH), 3.15–2.92 (m, 2
13
3
C
2
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O43555
/KAP1
Date: 18-02-15 16:52:54
Pages: 9
Coordinating Chiral Ionic Liquids
H, CH
CD OD): δ
s, C-Ar), 140.9 (s, C-pyridine), 136.0 (d, C-pyridine), 135.2 (s, C- 7.62 (m, 1 H, H-Ar), 7.46 (t, J = 7.92 Hz, 1 H, H-Ar), 4.97–4.93
2
-indol), 2.85 (br. s, 1 H, NH) ppm. 13C NMR (50 MHz,
= 149.6 (d, C-pyridine), 148.8 (d, C-pyridine), 142.0
(R)-1-(3-Nitrophenyl)-1-ethanol:[24] 1H NMR (200 MHz, CDCl
δ = 8.07–8.06 (m, 1 H, H-Ar), 8.06–8.02 (m, 1 H, H-Ar), 7.66–
H
3
):
3
C
(
Ar), 128.2 (C-pyridine), 126.8 (d, C-Ar), 125.7 (d, C-Ar), 123.9 (d,
(m, 1 H, CH-OH), 2.11 (br. s, 1 H, OH), 1.47 (d, J = 6.45 Hz,
CH -CH) ppm.
C-Ar), 123.6 (d, C-Ar), 71.0 (d, CH-OH), 65.3 (d, CH-NH), 49.8
3
0
(t, CH
2
-NH), 39.7 (t, CH
2
-indanol) ppm. [α]2
D
= –9.84 (c = 0.89,
(
δ
R)-1-(4-Nitrophenyl)-1-ethanol:[24] 1H NMR (200 MHz, CDCl
3
):
H
= 8.11 (d, J = 8.70 Hz, 2 H, H-Ar), 7.46 (d, J = 8.70 Hz, 2 H,
MeOH). T5%onset: 255 °C. IR: ν˜ max = 3300 (N–H), 2916 (O–H),
–1
1
737 (C–C), 1456 (C=C), 729 (C–H-Ar) cm . C15
16 2
H N O (240.31):
H-Ar), 5.00–4.88 (m, 1 H, CH-OH), 2.18 (br. s, 1 H, OH), 1.43 (d,
J = 6.46 Hz, CH -CH) ppm.
calcd. C 74.97, H 6.71, N 11.66; found C 75.00, H 6.55, N 11.66.
3
1
-Butyl-3-({[(1S,2R)-1-hydroxy-2,3-dihydro-1H-inden-2-yl]amino}-
(
δ
R)-1-(4-Bromophenyl)-1-ethanol:[23] 1H NMR (200 MHz, CDCl
3
):
H
= 7.38 (d, J = 8.49 Hz, 2 H, H-Ar), 7.15 (d, J = 8.39 Hz, 2 H,
methyl)pyridin-1-ium Bromide (11): By following the procedure for
compound 3, compound 10 (0.81 g, 3.35 mmol) and n-butyl brom-
ide (0.36 mL, 3.35 mmol) gave 11 (0.78 g, 2.06 mmol, 61% yield)
H-Ar), 4.78 (q, J = 6.39 Hz, 1 H, CH-OH), 2.04 (br. s, 1 H, OH),
.38 (d, J = 6.46 Hz, CH -CH) ppm.
1
3
1
as a viscous brown oil. H NMR (200 MHz, CD
3
OD): δ
H
= 9.17
s, 1 H, 8.64, H-pyridine), 8.94 (d, J = 6.06 Hz, 1 H, H-pyridine), (R)-1-(4-Chlorophenyl)-1-ethanol:[23] 1H NMR (200 MHz, CDCl
.70 (d, J = 8.03 Hz, 1 H, H-pyridine), 8.11–8.08 (m, 1 H, H-pyr-
= 7.22 (s, 4 H, H-Ar), 4.76 (q, J = 6.43 Hz, 1 H, CH-OH), 1.97
(br. s, 1 H, OH), 1.38 (d, J = 6.46 Hz, CH -CH) ppm.
(
8
3
):
δ
H
+
idine), 7.53–7.25 (m, 5 H, H-Ar), 4.70–4.63 (m, 3 H, CH
CH2a-NH), 4.38–4.30 (m, 3 H, CH-OH, CH2b-NH, CH-NH),
.10–2.92 (m, 2 H, CH -indanol), 2.03 (m, J = 7.58 Hz, 2 H, CH
CH -CH -CH ), 1.50–1.38 (m, 2 H, CH -CH -CH -CH ), 1.02 (t,
J = 7.23 Hz, 3 H, CH -CH -CH -CH
) ppm. 13C NMR (50 MHz,
CD OD): δ = 149.6 (d, C-pyridine), 148.8 (d, C-pyridine), 142.0
2
-N ,
3
(
R)-1-(4-Methoxyphenyl)-1-ethanol:[25] 1H NMR (200 MHz,
CDCl ): δ = 7.21 (d, J = 8.63 Hz, 2 H, H-Ar), 6.79 (d, J =
.74 Hz, 2 H, H-Ar), 4.76 (q, J = 6.39 Hz, 1 H, CH-OH), 1.88 (br.
s, 1 H, OH), 1.39 (d, J = 6.46 Hz, CH -CH) ppm.
3
2
2
-
3
H
2
2
3
2
2
2
3
8
2
2
2
3
3
3
C
s, C-Ar), 140.9 (s, C-pyridine), 136.0 (d, C-pyridine), 135.2 (s, C- (S)-1-Indanol:[26] 1H NMR (200 MHz, CDCl
): δ = 7.36–7.32 (m,
(
3
H
Ar), 129.4 (C-pyridine), 128.9 (d, C-Ar), 127.8 (d, C-Ar), 126.4 (d,
C-Ar), 126.0 (d, C-Ar), 72.8 (d, CH-OH), 66.8 (d, CH-NH), 62.9
1 H, H-Ar), 7.22–7.15 (m, 3 H, H-Ar), 5.17 (t, J = 6.19 Hz, 1 H,
CH-OH), 3.07–3.01 (m, 1 H, H-cyclopent), 2.82–2.66 (m, 1 H, H-
cyclopent), 2.50–2.33 (m, 1 H, H-cyclopent), 2.01–1.89 (m, 1 H, H-
cyclopent), 1.92 (s, 1 H, H-cyclopent) ppm.
+
(
t, CH
CH -CH
5%onset: 231 °C. IR: ν˜ max = 3264 (N–H), 2929 (O–H), 1637 (C–
2
-N ), 40.5 (t, CH
2
-NH), 34.4 (t, CH
2
-indanol), 20.5 (t, CH
2
-
) ppm. [α]2
0
= –2.04 (c = 0.47, MeOH).
2
3
), 13.8 (q, CH
3
D
T
(
S)-1-(2Ј-Naphthyl)ethanol:[25] 1H NMR (200 MHz, CDCl
3
): δ
H
=
–1
C), 1634 (C–C), 1456 (C=C), 729 (C–H-Ar) cm . C19
2
H25BrN O
8
3
1
.07–8.04 (m, 1 H, H-Ar), 7.83–7.59 (m, 3 H, H-Ar), 7.46–7.37 (m,
H, H-Ar), 5.63–5.60 (m, 1 H, CH-OH), 1.84 (br. s, 1 H, OH),
.57 (d, J = 6.54 Hz, 3 H) ppm.
(377.33): calcd. C 60.48, H 6.68, N 7.42; calcd. (including
2
1.47ϫH O) C 56.54, H 6.97, N 6.94; found C 56.48, H 6.45, N
6.90.
Supporting Information (see footnote on the first page of this arti-
General Procedure for the Enantioselective Transfer Hydrogenation
of Ketones. Application of Amino Alcohol Chiral Ionic Liquids: In-
side a glove box, the chiral ionic liquid (0.02 mmol) and the Ru
catalyst (0.01 mmol) were weighed, added to a predried Schlenk
flask, and then dissolved in water (4 mL), which was freeze-dried
prior to use. The active catalyst complex was stirred at 40 °C for
1
13
cle): Copies of the H and C NMR spectra for all new chiral ionic
1
liquids and their precursors and copies of the H NMR spectra for
the enantioenriched alcohols.
Acknowledgments
30 min, and then the ketone (2.00 mmol) and sodium formate
(
10.00 mmol) were added under an inert atmosphere. The reaction
Financial support from the Austrian Science Fund (FWF) (project
number P25504-N28) is gratefully acknowledged.
mixture was stirred under the given conditions for 24 h. Upon com-
pletion of the reaction, the mixture was extracted with n-hexane,
2 4
and the combined extracts were dried with Na SO and filtered
[
1] a) M. J. Palmer, M. Wills, Tetrahedron: Asymmetry 1999, 10,
045–2061; b) E. N. Jacobsen, A. Pfaltz, H. Yamamoto (Eds.),
through a short plug of silica to remove the excess ruthenium par-
ticles. The filtrate was concentrated to yield the product as a color-
less liquid. The alcohols were purified by column chromatography
2
Comprehensive Asymmetric Catalysis I–III, Springer, New
York, 1999, vol. 3; c) P. G. Anderson, I. J. Munslow (Eds.),
Modern Reduction Methods, Wiley-VCH, Weinheim, Germany,
[
PE with diethyl ether (EE) as a gradient), and the product was
1
analyzed by H NMR, GC, and HPLC. The analytical data were
in accordance with the literature.
2008.
[2] S. Hashiguchi, A. Fujii, J. Takehara, T. Ikariya, R. Noyori, J.
Am. Chem. Soc. 1995, 117, 7562–7563.
(
R)-1-Phenyl-1-ethanol:[21] 1H NMR (200 MHz, CDCl
3
): δ
H
=
[
[
3] X. Wu, J. Xiao, Chem. Commun. 2007, 2449–2466.
4] B. Cornils, W. A. Herrmann (Eds.), Applied Homogeneous Ca-
talysis with Organometallic Compounds, vol. 3: Developments,
7.30–7.18 (m, 5 H, H-Ar), 4.83 (q, J = 6.45 Hz, 1 H, CH-OH), 1.70
(
br. s, 1 H, OH), 1.42 (d, J = 6.45 Hz, CH
R)-1-Phenyl-1-propanol:[22] 1H NMR (200 MHz, CDCl
): δ
3 H
3
-CH) ppm.
2
nd ed., Wiley-VCH, Weinheim, Germany, 2002.
5] a) T. Dwars, E. Paetzold, G. Oehme, Angew. Chem. Int. Ed.
005, 44, 7174–7199; Angew. Chem. 2005, 117, 7338; b)
(
=
[
7.7–7.17 (m, 5 H, H-Ar), 4.50 (t, J = 6.50 Hz, 1 H, CH-OH), 1.91
2
(
br. s, 1 H, OH), 1.75–1.61 (m, 2 H, CH
2
-CH ), 0.83 (t, J = 7.43 Hz,
3
J. B. F. N. Engberts, in: Methods and Reagents for Green Chem-
istry: An Introduction (Eds.: P. Tundo, A. Perosa, F. Zecchini),
John Wiley & Sons, Inc., Hoboken, 2007, p. 159–170.
3
CH -CH) ppm.
(
δ
=
5
R)-1-(2-Nitrophenyl)-1-ethanol:[23] 1H NMR (200 MHz, CDCl
= 7.65 (td, J = 5.39 Hz, J = 1.27 Hz, 2 H, H-Ar), 7.57 (td, J
3.87, J = 1.18 Hz, 1 H, H-Ar), 7.31 (t, J = 7.73 Hz, 1 H, H-Ar),
.37 (q, J = 6.26 Hz, 1 H, CH-OH), 2.41 (br. s, 1 H, OH), 1.49 (d,
J = 6.46 Hz, CH -CH) ppm.
3
):
[6] a) H. Y. Rhyoo, H.-J. Park, Y. K. Chung, Chem. Commun.
H
1
2
1
2
001, 2064–2065; b) L. Li, J. Wu, F. Wang, J. Liao, H. Zhang,
2
C. Lian, J. Zhu, J. Deng, Green Chem. 2007, 9, 23–25.
[7] M. Yoshimura, S. Tanaka, M. Kitamura, Tetrahedron Lett.
2014, 55, 3635–3640.
3
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O43555
/KAP1
Date: 18-02-15 16:52:54
Pages: 9
M. Vasiloiu, P. Gaertner, R. Zirbs, K. Bica
FULL PAPER
[
8] a) K. Bica, P. Gaertner, Eur. J. Org. Chem. 2008, 3235–3250;
b) J. Ding, D. W. Armstrong, Chirality 2005, 17, 281–292; c) C.
Baudequin, D. Bregeon, J. Levillain, F. Guillen, J.-C. Plaquev-
ent, A.-C. Gaumont, Tetrahedron: Asymmetry 2005, 16, 3921–
[16] L. Gonzalez, B. Altava, M. Bolte, M. I. Burguete, E. Garcia-
Verdugo, S. V. Luis, Eur. J. Org. Chem. 2012, 4996–5009.
[17] a) P. Brandt, P. Roth, P. G. Andersson, J. Org. Chem. 2004, 69,
4885–4890; b) M.-L. Han, X.-P. Hu, J.-D. Huang, L.-G. Chen,
Z. Zheng, Tetrahedron: Asymmetry 2011, 22, 222–225; c) D. A.
Alonso, S. J. M. Nordin, P. Roth, T. Tarnai, P. G. Andersson,
M. Thommen, U. Pittelkow, J. Org. Chem. 2000, 65, 3116–
3122; d) G. D. Williams, R. A. Pike, C. E. Wade, M. Wills, Org.
Lett. 2003, 5, 4227–4230.
[18] a) J. Takehara, S. Hashiguchi, A. Fujii, S.-i. Inoue, T. Ikariya,
R. Noyori, Chem. Commun. 1996, 233–234; b) A. Fujii, S.
Hashiguchi, N. Uematsu, T. Ikariya, R. Noyori, J. Am. Chem.
Soc. 1996, 118, 2521–2522.
3945; d) A. Winkel, P. V. G. Reddy, R. Wilhelm, Synthesis 2008,
999–1016.
[
9] N. Rios-Lombardia, E. Busto, V. Gotor-Fernandez, V. Gotor,
R. Porcar, E. Garcia-Verdugo, S. V. Luis, I. Alfonso, S. Garcia-
Granda, A. Menendez-Velazquez, Chem. Eur. J. 2010, 16, 836–
847.
[
10] S. Chen, S. Zhang, X. Liu, J. Wang, J. Wang, K. Dong, J. Sun,
B. Xu, Phys. Chem. Chem. Phys. 2014, 16, 5893–5906.
[
11] a) S.-P. Luo, D.-Q. Xu, H.-D. Yue, L.-P. Wang, W.-L. Yang,
Z.-Y. Xu, Tetrahedron: Asymmetry 2006, 17, 2028–2033; b) M.
Vasiloiu, D. Rainer, P. Gaertner, C. Reichel, C. Schroeder, K.
Bica, Catal. Today 2013, 200, 80–86; c) S. Luo, X. Mi, L.
[19] a) L. Ta, A. Axelsson, J. Bijl, M. Haukka, H. Sunden, Chem.
Eur. J. 2014, 20, 13889–13893; b) D. Enders, O. Niemeier, A.
Henseler, Chem. Rev. 2007, 107, 5606–5655.
Zhang, S. Liu, H. Xu, J.-P. Cheng, Tetrahedron 2007, 63, 1923– [20] a) K. Bica, P. Gaertner, P. J. Gritsch, A. K. Ressmann, C.
1
930; d) S. Luo, L. Zhang, X. Mi, Y. Qiao, J.-P. Cheng, J. Org.
Schroeder, R. Zirbs, Chem. Commun. 2012, 48, 5013–5015; b)
J. Li, Y. Tang, Q. Wang, X. Li, L. Cun, X. Zhang, J. Zhu, L.
Li, J. Deng, J. Am. Chem. Soc. 2012, 134, 18522–18525.
[21] X. Wu, X. Li, M. McConville, O. Saidi, J. Xiao, J. Mol. Catal.
A 2006, 247, 153–158.
[22] M. Rachwalski, S. Jarzy n´ ski, S. Le s´ niak, Tetrahedron: Asym-
metry 2013, 24, 421–425.
[23] P. Vitale, C. D’Introno, F. M. Perna, M. G. Perrone, A. Scilim-
ati, Tetrahedron: Asymmetry 2013, 24, 389–394.
[24] B. A. Barros-Filho, F. M. Nunes, M. d. C. F. de Oliveira,
T. L. G. Lemos, M. C. de Mattos, G. de Gonzalo, V. Gotor-
Fernández, V. Gotor, J. Mol. Catal. B 2010, 65, 37–40.
Chem. 2007, 72, 9350–9352; e) S. Luo, L. Zhang, J.-P. Cheng,
Chem. Asian J. 2009, 4, 1184–1195.
[
[
12] a) P. S. Schulz, N. Mueller, A. Boesmann, P. Wasserscheid, An-
gew. Chem. Int. Ed. 2007, 46, 1293–1295; Angew. Chem. 2007,
119, 1315; b) V. Wagner, P. S. Schulz, P. Wasserscheid, J. Mol.
Liq. 2014, 192, 177–184; c) K. Schneiders, A. Boesmann, P. S.
Schulz, P. Wasserscheid, Adv. Synth. Catal. 2009, 351, 432–440;
d) N. Ferlin, M. Courty, A. N. Van Nhien, S. Gatard, M. Pour,
B. Quilty, M. Ghavre, A. Haiss, K. Kuemmerer, N. Gath-
ergood, S. Bouquillon, RSC Adv. 2013, 3, 26241–26251.
13] R. Gausepohl, P. Buskens, J. Kleinen, A. Bruckmann, C. W.
Lehmann, J. Klankermayer, W. Leitner, Angew. Chem. Int. Ed. [25] J.-i. Ito, T. Teshima, H. Nishiyama, Chem. Commun. 2012, 48,
2006, 45, 3689–3692; Angew. Chem. 2006, 118, 3772–3775.
1105–1107.
[
[
14] F. Bigi, H. Q. Nimal Gunaratne, C. Quarantelli, K. R. Seddon,
C. R. Chim. 2011, 14, 685–687.
15] M. Vasiloiu, S. Leder, P. Gaertner, K. Mereiter, K. Bica, Org.
Biomol. Chem. 2013, 11, 8092–8102.
[26] T. Suzuki, K. Ghozati, T. Katoh, H. Sasai, Org. Lett. 2009, 11,
4286–4288.
Received: December 1, 2014
Published Online: ᭿
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O43555
/KAP1
Date: 18-02-15 16:52:54
Pages: 9
Coordinating Chiral Ionic Liquids
Chiral Ionic Liquids
The
ruthenium-catalyzed
asymmetric
M. Vasiloiu, P. Gaertner, R. Zirbs,
transfer hydrogenation of aromatic ketones
was carried out under aqueous conditions
by using a hydrophilic chiral ionic liquids
with an amino alcohol substructure as the
sole source of chirality. When used in the
reaction system, these chiral ionic liquids
provided high yields and excellent selec-
tivities.
K. Bica* ............................................ 1–9
Coordinating Chiral Ionic Liquids: Design,
Synthesis, and Application in Asymmetric
Transfer Hydrogenation under Aqueous
Conditions
Keywords: Ionic liquids / Self-assembly /
Asymmetric catalysis / Hydrogenation /
Ruthenium / Ketones
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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