β-Cyclodextrins grafted with chiral amino acids: A promising supramolecular stabilizer of nanoparticles for asymmetric hydrogenation?

Article abstract of DOI:10.1016/j.apcata.2013.08.011

Water-soluble ruthenium nanoparticles stabilized by randomly methylated β-cyclodextrins (RaMeCDs) grafted with chiral amino-acid moieties like l-alanine (Ala) and l-leucine (Leu) were prepared in aqueous solution by two approaches: (i) a one-step hydrogen reduction of ruthenium trichloride as metal source in the presence of appropriate cyclodextrins (one-pot method) or (ii) a NaBH₄ reduction of the metal salts, followed by the stabilization of ruthenium hydrosol by the addition of chirally modified RaMeCDs (cascade method). The influence of the ligand's nature and the synthesis methodologies on the size, dispersion and surface properties of the obtained ruthenium colloids were studied by TEM and NMR analyses. The spherical ruthenium suspensions contain very small particles (0.82-1.00 nm) with narrow size distributions. Their catalytic properties were evaluated in biphasic hydrogenation of various prochiral compounds (olefins, ketones and disubstituted arenes) showing promising results in terms of activity and selectivity. Nevertheless, no significant enantiomeric excesses were observed.

Full text of DOI:10.1016/j.apcata.2013.08.011

Applied Catalysis A: General 467 (2013) 497–503
Contents lists available at ScienceDirect
Applied Catalysis A: General
journal homepage: www.elsevier.com/locate/apcata
␤-Cyclodextrins grafted with chiral amino acids: A promising
supramolecular stabilizer of nanoparticles for asymmetric
hydrogenation?
Nguyet Trang Thanh Chaua,b, Jean-Paul Guégana,b, Stéphane Menuelc,
Miguel Guerrerod,e, Frédéric Hapiotc, Eric Monflierc, Karine Philippotd,e
,
Audrey Denicourt-Nowickia,b,∗, Alain Roucouxa,b,∗
a Ecole Nationale Supérieure de Chimie de Rennes, CNRS UMR 6226, 11, allée de Beaulieu, CS 50837, 35708 Rennes cedex 7, France
b Université Européenne de Bretagne, France
c Université d’Artois, CNRS UMR 8181, Faculté des Sciences Jean Perrin, Rue Jean Souvraz, SP 18, F-62307 Lens Cedex, France
d CNRS, LCC (Laboratoire de Chimie de Coordination), 205 Route de Narbonne, F-31077 Toulouse, France
e Université de Toulouse, UPS, INPT, LCC, F-31077 Toulouse, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 May 2013
Received in revised form 6 August 2013
Accepted 8 August 2013
Available online 18 August 2013
Water-soluble ruthenium nanoparticles stabilized by randomly methylated ␤-cyclodextrins (RaMeCDs)
grafted with chiral amino-acid moieties like l-alanine (Ala) and l-leucine (Leu) were prepared in aqueous
solution by two approaches: (i) a one-step hydrogen reduction of ruthenium trichloride as metal source
in the presence of appropriate cyclodextrins (one-pot method) or (ii) a NaBH4 reduction of the metal
salts, followed by the stabilization of ruthenium hydrosol by the addition of chirally modified RaMeCDs
(cascade method). The influence of the ligand’s nature and the synthesis methodologies on the size,
dispersion and surface properties of the obtained ruthenium colloids were studied by TEM and NMR
analyses. The spherical ruthenium suspensions contain very small particles (0.82–1.00 nm) with narrow
size distributions. Their catalytic properties were evaluated in biphasic hydrogenation of various prochiral
compounds (olefins, ketones and disubstituted arenes) showing promising results in terms of activity and
selectivity. Nevertheless, no significant enantiomeric excesses were observed.
Keywords:
Ruthenium nanoparticles
Aqueous suspension
Grafted cyclodextrins
Biphasic catalysis
© 2013 Elsevier B.V. All rights reserved.
1. Introduction
ligands, etc. . . [14–16]. Towards the increasing demand in opti-
cally enriched intermediates, various chiral compounds have been
Optically active cyclohexyl moieties play a key role in the syn-
thesis of various biologically active molecules or auxiliaries [1].
Among the various strategies, enzymatic or chemical resolution
approaches [2] or chiral auxiliary-bound substrates [3–6] were
used to produce these optically enriched intermediates. An ele-
gant alternative method will rely on the catalytic diastereoselective
hydrogenation of monocyclic polysubstituted benzenes. Recently,
metal nanoparticles (NPs) have emerged as a pertinent class of
catalysts for various reactions [7,8], and especially for arene hydro-
genation under mild conditions [9,10], owing to their original
surface reactivities [11–13]. Their preparation usually requires the
presence of protective agents such as surfactants, polymers, or
investigated as protective agents of colloidal species for the devel-
opment of asymmetric catalytic reactions. In this case, the coating
agents should be able to transmit their chiral information to the
substrate and thus control the enantiodiscrimination in reduction
processes [17,18]. According to our knowledge, only a few chirally
modified metal nanocatalysts have been described in the hydro-
genation of prochiral aromatic molecules within organic media
[10]. First studies were performed in the hydrogenation of o-cresol
derivatives using colloidal rhodium protected by a chiral lipophilic
amine(R)-(−)-dioctylcyclohexyl-1-ethylamine(DOCEA), leading to
very low asymmetric induction [19]. Metal NPs stabilized by chi-
ral N-donor ligands [20] or carbohydrate -derived 1,3-diphosphite
ligands [21,22] also revealed poor enantiomeric excess (ee) values
in the hydrogenation of methylanisole isomers.
Besides, in order to fit in with green chemistry principles
[23], the use of finely dispersed nanoparticles in water, a readily
available and environmentally benign solvent, has gained grow-
ing attention due to their recovery ability and easy work-up
[24–28]. In this aqueous medium, the problematic undissolved
∗
Corresponding authors at: Ecole Nationale Supérieure de Chimie de Rennes,
CNRS UMR 6226, 11, allée de Beaulieu, CS 50837, 35708 Rennes cedex 7, France.
Tel.: +33 02 2323 8037; fax: +33 02 2323 8199.
E-mail addresses: audrey.denicourt@ensc-rennes.fr (A. Denicourt-Nowicki),
alain.roucoux@ensc-rennes.fr (A. Roucoux).
0926-860X/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.apcata.2013.08.011

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N.T.T. Chau et al. / Applied Catalysis A: General 467 (2013) 497–503
2. Experimental
2.1. Reagents and chemicals
Randomly methylated ␤-cyclodextrin (RaMeCD (1.8)) was
purchased from Sigma-Aldrich. This cyclodextrin was partially
methylated. Methylation occurred at positions C2, C3 or C6 and
1.8 OH groups per glucopyranose unit were statistically modi-
fied. l-Alanine-N-[(1-randomly methylated-␤-cyclodextrinyl-1H-
1,2,3-triazol-4-yl)methyl amide] (RaMeCD-trz-Ala) and l-leucine-
N-[(1-randomly methylated-␤-cyclodextrinyl-1H-1,2,3-triazol-4-
yl)methylamide] (RaMeCD-trz-Leu) were prepared according to a
previously described procedure [49].
Ruthenium chloride hydrate was obtained from Strem Chemi-
cals. Sodium borohydride and all substrates were purchased from
Sigma–Alrich, Acro¯s Organics or Alfa Aesar and were used without
further purification. Water was purified using Millipore Elix 5 (type
MSP 100) system.
Fig. 1. Structure of grafted ␤-cyclodextrins with chiral amino-acid moieties like
l-alanine (Ala) and l-leucine (Leu).
substrates can be circumvented by the use of micellar systems
[29,30], like surfactants [31–34]. In this context, our group has
described a series of optically amphiphilic compounds, derived
from N-methylephedrine, N-methylprolinol or cinchona deriva-
tives possessing various counter-ions as efficient stabilizers of
rhodium NPs in water [35,36]. These nanocatalysts proved to be
highly active in the asymmetric hydrogenation of ethyl pyruvate
or prochiral disubstituted benzenes, with modest enantiodiscrim-
ination.
2.2. Analytical procedures
2.2.1. TEM analysis
An alternative approach to improve biphasic catalytic pro-
cesses consists on the use of inverse phase-transfer catalysts,
such as cyclodextrins (CDs) or calixarenes [37–39]. In case of CDs,
physico-chemical properties could be easily modulated through
the choice of the cavity’s size, the nature of the substituents and
the substitution degree [40,41]. Among them, randomly meth-
ylated ␤-cyclodextrins (RaMeCD) have proved to be particularly
efficient [37,42,43] and have demonstrated to be promising can-
didates as stabilizers for metallic nanospecies in water [44]. Based
on these physico-chemical properties, our group has investigated
RaMeCD-protected ruthenium NPs (Ru0 NPs) as nanocatalysts in
the hydrogenation of olefins [45], ketones [46] and arenes [45,47].
Recently, the influence of the preparation method on NPs size as
well as on their reactivity has particularly been studied [46]. Both
synthesis methodologies (one-pot and cascade) led to very small
NPs with narrow size distributions, which proved to be very active
in the reduction of model substrates.
Although the use of CDs-based structures in chiral discrimina-
tion is well-documented [48], the use of CDs modified by chiral
substituents for the stabilization of NPs and their application in
enantioselective hydrogenations has not been described to our
knowledge. Here, we report the synthesis of novel ruthenium NPs
capped by methylated CDs grafted with chiral moieties, such as
l-alanine (RaMeCD-trz-Ala) or l-leucine (RaMeCD-trz-Leu) (Fig. 1)
in order to induce asymmetry during supramolecular recognition
processes. These supramolecules [49] were synthesized in 5 steps
from mono-6-azido RaMeCD precursor using click synthesis [50]
with good yields and were subsequently used to avoid aggregation
of Ru0 NPs during their preparation. Two easy and reproducible
routes (one-pot and cascade methods) were applied for the syn-
thesis of Ru0 colloids and their comparison. Their characterizations
have been performed by Transmission Electron Microscopy (TEM)
and Diffusion Ordered SpectroscopY (DOSY) experiments while
their catalytic reactivity was compared in the biphasic asymmet-
ric hydrogenation of various prochiral substrates. In a first set of
experiments, methyl 2-acetamidoacrylate and ethyl pyruvate were
studied as model substrates of a prochiral functionalized olefin and
ketone, respectively. Acetophenone was also investigated as a per-
tinent substrate in terms of chemoselectivity (carbonyl group vs.
aromatic ring) and stereoselectivity through the asymmetric reduc-
tion of the ketone function. Finally, the obtained nanocatalysts
were evaluated in the stereoselective reduction of a prochiral arene
(m-methylanisole), which remains a real challenge in asymmetric
catalysis field.
Transmission electron microscopy (TEM) images were per-
formed at “Service Commun de Microscopie Electronique de
l’Université Paul Sabatier” (UPS-TEMSCAN) in Toulouse or at “Uni-
versité Pierre et Marie Curie”. They were recorded with a JEOL 1011
electron microscope operating at 100 kV with resolution point of
˚
4.5 A or with a JEOL TEM 100CXII electron microscope operated at
an acceleration voltage of 100 kV, respectively. A drop of Ru0-NPs
in water was deposited on a carbon-coated copper grid and dried in
air. The size distributions were determined through a manual anal-
ysis of enlarged micrographs with Image J software using Microsoft
Excel to generate histograms of the statistical size distribution and
a mean diameter. At least 200 particles on a given grid were mea-
sured in order to obtain a statistical size distribution and a mean
diameter.
2.2.2. NMR analysis
DOSY NMR was recorded on a Bruker Avance III 400 spec-
trometer at 400.13 MHz for 1H and equipped with a BBFO probe
and Z-gradient coil and a GREAT 1/10 gradient unit. All experi-
ments were recorded using the 2D-PGSE sequence for diffusion
measurement using stimulated echo with bipolar gradient with-
out spinning. The relaxation delay was adjusted to 3 s while the big
DELTA and the little DELTA were set at 50 ms and 3200 ␮s, respec-
tively. A series of 16 experiments of 64 or 80 scans was recorded.
The shape of the gradient was rectangular and its duration was 5 ms.
The strength of the gradient was varied during the experiments
and calibrated by measuring the self-diffusion of the residual HDO
signal at 298 K of a doped water tube containing 1% H2O in D2O,
with 0.1 mg GdCl3/mL D2O and 0.1% CH3OH (1.87 × 10−9 m2 s−1).
All the spectra were acquired using 65 K points and 5600 Hz and
processed with the Bruker Topspin software package DOSY using
a line broadening of 1 Hz. All of samples (RaMeCD-trz-Ala, mixture
of RuCl3·3H2O and RaMeCD-trz-Ala or Ru0@RaMeCD-trz-Ala NPs
synthesized by one-pot method) were prepared in D2O solution
at a concentration of 7.2 mM of RaMeCD-trz-Ala and analyzed at
298 K.
2.2.3. Gas chromatography
For hydrogenation of prochiral substrates, the conversion
and the enantiomeric excess were determined by gas chro-
matography using Fisons Instruments GC 9000 series with
FID detector equipped with a chiral Varian Chiralsil-Dex CB
capillary column (30 m, 0.25 mm i.d.). Parameters were as fol-
lows: isotherm programme with oven temperature, 90 ◦C (ethyl

N.T.T. Chau et al. / Applied Catalysis A: General 467 (2013) 497–503
499
pyruvate and m-methylanisole) or 130 ◦C (acetophenone and
methyl 2-acetamidoacrylate); carrier gas pressure, 50 kPa.
2.3. Synthesis of aqueous ruthenium(0) suspension
2.3.1. One-pot method
To an aqueous solution (6 mL) of RuCl3·3H2O (3.8 mg,
1.44 × 10−2 mmol) was added at once cyclodextrin (RaMeCD-trz-
Ala or RaMeCD-trz-Leu) (7.2 × 10−2 mmol) dissolved in 4 mL of
water. The mixture was vigorously stirred at room temperature
under H2 atmosphere (PH2 = 1 bar) until the reaction’s colour turned
from dark brown to green brown (about 5–7 h). The colloidal ruthe-
nium solution was then stirred overnight at room temperature
before used in catalytic test.
Scheme 1. Two methodologies for Ru0@RaMeCD-trz-Ala and Ru0@RaMeCD-trz-Leu
NPs synthesis.
(rt) and stabilized in water in the presence of appropriate chi-
ral cyclodextrins (RaMeCD-trz-Ala or RaMeCD-trz-Leu) (5 eq). The
higher steric hindrance of grafted CDs and/or the coordination of
the metal precursor with triazole moieties [51,52] rendered the
reduction more difficult than previously observed for the prepara-
tion of Ru0@RaMeCD NPs, thus requiring a longer reaction time.
The cascade method consists on the preparation of Ru0 sus-
pensions in two steps: (i) chemical reduction of RuCl3,·3H2O by
a dropwise addition of an aqueous NaBH4 solution [53]; (ii) post-
stabilization of obtained Ru0 hydrosol by addition of 5 eq of suitable
chiral CDs. Therefore, this strategy offers a great advantage, allow-
ing the modulation of the cyclodextrin’s amount.
2.3.2. Cascade method
To an aqueous solution (50 mL) of RuCl3·3H2O (26.1 mg,
0.1 mmol) was added dropwise and under vigorous stirring a
freshly prepared aqueous solution (about 1.8 mL) of NaBH4 0.1 M at
room temperature. The reduction occurred quickly and was char-
acterized by a progressive colour change from dark brown to light
brown then green brown. The addition of NaBH4 was stopped
when an additional drop made all of reaction solution turn dark
brown while the pH value was kept lower 4.9. The colloidal solution
was then stirred overnight at room temperature before addition of
the aqueous solution (48.2 mL) of cyclodextrin (RaMeCD-trz-Ala or
RaMeCD-trz-Leu) (0.5 mmol). The obtained ruthenium nanoparti-
cles were stirred for 24 h before used in catalytic test.
3.2. Characterization of ruthenium(0) nanoparticles
2.4. General procedure for high pressure hydrogenation reactions
The water-soluble Ru0@RaMeCD-trz-Ala or Ru0@RaMeCD-trz-
Leu colloids obtained by both methods were characterized by TEM
analysis [54], in order to correlate the influence of the ligands and
the preparation approaches on the size, morphology and disper-
sion of the metallic cores of the NPs. The micrographs and the size
distributions are presented in Figs. 2 and 3.
The stainless steel autoclave was charged with the aque-
ous colloidal ruthenium suspension (10 mL, 1.44 × 10−2 mmol
or 1.00 × 10−2 mmol for the catalyst prepared by one-pot
or cascade methods, respectively) and appropriate substrate
([substrate]/[Ru0] ratio = 100/1). The autoclave was degassed three
times and hydrogen gas was admitted to the system at a constant
pressure (20 bars). The mixture was stirred vigorously at room tem-
perature for time (h). Samples were removed from time to time to
monitor the reaction by gas chromatography in previously men-
tioned conditions.
In all cases, the colloids were well-dispersed on the grid, with
spherical morphologies and narrow standard deviations. The Ru0
NPs displayed a mean size in the range 0.82–1.00 nm, depending
on the ligand nature and the preparation methods. The more ste-
rically hindered ligand, l-leucine-grafted cyclodextrin, appeared
to be more effective than its alanine analogue in the stabiliza-
tion of Ru0 suspensions, leading to the formation of smaller NPs
(0.96 and 0.82 nm vs. 1.00 and 0.98 nm, respectively). In addition,
while similar sizes were observed with RaMeCD-trz-Ala-protected
Ru0 NPs synthesized by both approaches (Fig. 2), the Ru0 NPs pre-
pared by the cascade strategy were slightly smaller than those
obtained by the one-pot method in the case of RaMeCD-trz-Leu
as stabilizing agent (Fig. 3a vs Fig. 3b). This better control of the
NPs growth could result from the pre-stabilization of Ru0 hydrosol
with hydronium ions or other hydrated ions (H5O2+, H7O3+, etc.)
generated during the NaBH4 reduction of the RuCl3·3H2O [53].
Moreover, in comparison with Ru0@RaMeCD systems [46], these
NPs exhibited smaller diameters. As previously mentioned [53,54],
this phenomenon could be explained by the protonation of Ala or
Leu moieties at pH of medium (∼4.9), thus producing ammonium
forms that may reinforce the NPs stability within aqueous solu-
tion thanks to coulombic interactions [55,56] while the RaMeCD
backbone provides only a steric stabilization.
2.5. General procedure for catalytic lifetime tests
The stainless steel autoclave was charged with the aque-
ous colloidal ruthenium suspension (10 mL, 1.44 × 10−2 mmol or
1.00 × 10−2 mmol for the NPs produced by the one-pot or cas-
cade methods, respectively) and ethyl pyruvate ([substrate]/[Ru0]
ratio = 100/1). The autoclave was degassed three times and hydro-
gen gas was admitted to the system at a constant pressure (20 bar
H2). The mixture was stirred vigorously at room temperature until
total conversion of ethyl pyruvate (18 h and 6 h depending on the
catalyst system). The aqueous phase was washed successively with
EtOAc (4 mL × 10 mL) then stirred overnight before reuse in the
next run.
3. Results and discussion
3.1. Synthesis of ruthenium(0) nanoparticles
As comparable size and morphology of NPs were observed,
Ru0@RaMeCD-trz-Ala produced from the one-pot method was cho-
sen among these nanocatalysts for NMR investigation in order to
study the nature of the interactions between the protective agent
and the metallic core. 1H NMR measurements in D2O solution of the
CDs and the corresponding Ru0 NPs showed no significant differ-
ence in the chemical shifts of the chirally modified CDs. Moreover,
Based on results previously obtained in our group with
Ru0@RaMeCD systems [46], ruthenium nanoparticles were pre-
pared through two approaches, one-pot (H2 gas reduction) and
cascade (NaBH4 chemical reduction) routes (Scheme 1).
In the one-pot method, ruthenium(III) chloride was simulta-
neously reduced under hydrogen pressure at room temperature

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N.T.T. Chau et al. / Applied Catalysis A: General 467 (2013) 497–503
Fig. 2. TEM images of Ru0@RaMeCD-trz-Ala NPs prepared by (a) one-pot method (scale bar = 20 nm) and (b) cascade method (scale bar = 20 nm).
Table 1
3.3. Biphasic catalytic hydrogenation of prochiral substrates
using ruthenium(0) nanoparticles
D values and rH values determined by DOSY NMR.a
Entry
Sample
D (10−10 m2 s−1
)
rH (nm)
The Ru0@RaMeCD-trz-Ala and Ru0@RaMeCD-trz-Leu NPs have
been investigated in the reduction of various prochiral substrates,
such as an activated olefin (methyl 2-acetamidoacrylate), a lin-
ear ketone (ethyl pyruvate), an aromatic ketone (acetophenone)
and a disubstituted arene (m-methylanisole). The hydrogenation
of these model compounds was carried out under biphasic con-
ditions (water/substrate) at room temperature and monitored by
gas chromatography analysis. In addition, these reactions have
been performed at 20 bar H2 since no conversion was observed
at atmospheric hydrogen conditions as shown in previous stud-
ies [46,60]. Moreover, the stability of the triazole ring under
reduction conditions of the synthesis and the catalysis was also
demonstrated [51,52,61]. The catalytic performances of these sys-
tems are reported in Tables 2 and 3. First, whatever the chiral
ligand (RaMeCD-trz-Ala or RaMeCD-trz-Leu) and the prepara-
tion methods (one-pot or cascade), the reduction of methyl
1
2
3
4
RaMeCD-trz-Ala
Ru0@RaMeCD-trz-Alab
RaMeCD [46]
2.267
2.290
2.460
2.463
0.851
0.842
0.784
0.783
Ru0@RaMeCD [46]
a
NMR analysis performed at 298 K in D2O.
NPs were prepared by one-pot method.
b
DOSY analysis [57] indicated quite similar values of diffusion coef-
ficient (D) of these samples at the given concentration (7.2 mM)
(Table 1, entries 1 and 2). These results evidenced the very weak
interactions between the CDs and the metallic core in opposition
to the coordination induced by strong ligands, such as 1,3,5-triaza-
7-phosphaadamantane (PTA) [58].Compared to Ru0@RaMeCD NPs,
chirally modified CDs-stabilized Ru0 colloids displayed compara-
ble D values (2.463 × 10−10 and 2.290 × 10−10 m2 s−1, respectively)
(Table 1, entries 4 and 2). This slightly slower diffusion in D2O
solution could be attributed to the higher steric hindrance and
the potential electrostatic stabilization of the RaMeCD-trz-Ala. The
hydrodynamic radius rH [59] of these self-diffusing species were
calculated from D using the Stokes–Einstein equation. These val-
ues revealed that the aggregation state of CDs near the particle is
very low. Finally, these DOSY NMR experiments suggest the pres-
ence of non-aggregated but mobile CDs acting as a dispersive agent
around the particle surface.
2-acetamidoacrylate occurred exclusively on the activated C
C
double bond with complete conversion in 6 h (Table 2, entries
1–4). However, the carbonyl group of ethyl pyruvate was selec-
tively and totally reduced into the corresponding alcohol only with
Ru0@RaMeCD-trz-Leu (Table 2, entries 6 and 8), while RaMeCD-
trz-Ala-capped Ru0 NPs synthesized by both methods displayed
lower reactivity towards this compound (61 and 54%, respectively)
(Table 2, entries 5 and 7). In all cases, no significant enantiomeric
Fig. 3. TEM images of Ru0@RaMeCD-trz-Leu NPs prepared by (a) one-pot method (scale bar = 20 nm) and (b) cascade method (scale bar = 50 nm).

N.T.T. Chau et al. / Applied Catalysis A: General 467 (2013) 497–503
501
Table 2
Hydrogenation of methyl 2-acetamidoacrylate and ethyl pyruvate using Ru0@RaMeCD-trz-Ala and Ru0@RaMeCD-trz-Leu.a
Entry
Substrate
Chiral moiety
Method
t (h)
Products
Yields (%)b
1
2
3
4
Ala
Leu
Ala
Leu
One-pot
One-pot
Cascade
Cascade
6
6
6
6
100
100
100
100
Methyl 2-acetamidoacrylate
Methyl 2-acetamidopropanoate
5
6
7
8
9
Ala
Leu
Ala
One-pot
One-pot
Cascade
Cascade
Cascade
6c
6
6
61
100
54
100
12
Ethyl pyruvate
Ethyl 2-hydroxypropanoate
Leu
6
Leud
6c
a
Conditions: Ru0@RaMeCD-trz-Ala or Ru0@RaMeCD-trz-Leu ([Substrate]/[Ru0] molar ratio = 100/1), 10 mL H2O, 20 bar H2, rt.
Determined by GC analysis.
100% yield after 18 h of reaction.
10 eq of RaMeCD-trz-Leu were used.
b
c
d
excess was recorded (<5%). To improve the enantiodiscrimation
clearly confirmed. Effectively, the conversion of this disubstituted
arene was approximately two times greater in case of NPs pre-
pared by cascade method than those obtained from one-pot system
(Table 3, entries 7 and 8 vs. 5 and 6), probably owing to the NPs sizes.
Here, the nature of the ligands provided a comparable effect on the
reactivity and the selectivity of the m-methylanisole hydrogena-
tion. In all cases the thermodynamically less stable cis compound
was the major product providing a diastereoisomeric excess (de) of
50% (Table3, entries 5–8). This selectivity hasusually beenobserved
with heterogeneous catalytic systems,[62] and is explained by ␲-
interactions between the substrate and the catalyst’s surface during
the process, favouring the addition of hydrogen to only one “face” of
the arene.[19,63] For reactivity and selectivity comparisons, 100%
of 1-methoxy-3-methyl-cyclohexane were obtained in higher de
values (70–100% in cis-isomer) with water-soluble Ru0@RaMeCDs
NPs [46]because of the less steric hindrance of non-grafted CDs.
Increase of the reaction time until 18 h could simultaneously
improve the conversion (up to 100%) and the diastereoisomeric
selectivity (up to 70%) of the m-methylanisole’s reduction (Table 3,
entry 5, footnote c). However, addition of five additional equiva-
lents of ligands (Table 3, entry 9, footnote d) affected neither the
rate nor the selectivity of hydrogenation reaction. Finally, these
adjusted conditions did not afford a better value of ee (<5%). As
observed by DOSY NMR, the high mobility of the CDs at the parti-
cles’ surface probably limits the chiral induction.
during the catalytic process, higher amounts of CDs grafted with
chiral amino acids (up to 10 eq.) were introduced, but unfortunately
with no enhancement of the asymmetric induction and a dramatic
decrease in the initial hydrogenation rate of ethyl pyruvate (12%
after 6 h) (Table 2, entry 9, footnote d). Extra amount of added
RaMeCD-trz-Leu probably hampered the substrate’s approach dur-
ing the catalytic process, thus lowering the reaction rate. Finally, the
complete conversion was achieved in 18 h of reaction time (Table 2,
entries 5 and 9, footnote c). In a second set of experiments, the influ-
ence of the nanocatalyst on the chemoselectivity (carbonyl group
vs. aromatic ring) was studied, using acetophenone as substrate.
Under the standard reduction conditions, only Ru0@RaMeCD-trz-
Ala NPs prepared by cascade method led to the quantitative for-
mation of the totally hydrogenated product (1-cyclohexylethanol)
in 8 h (Table 3, entry 3). Other nanocatalysts gave a mixture
of 1-cyclohexylethanol and 1-phenylethanol as the intermediate
obtained from the reduction of the carbonyl group (Table 2, entries
1, 2 and 4). No 1-cyclohexylethanone intermediate, produced from
the reductionof thearomaticring, was detected, suggestingthatthe
carbonyl group is easily reducible, compared to the aromatic ring.
Besides, for both methodologies, Ru0@RaMeCD-trz-Ala nanocata-
lysts were found slightly more active than RaMeCD-trz-Leu-capped
Ru0 NPs (Table 3, entries 1 and 3 vs. 2 and 4). Furthermore, the
nanospecies synthesized by the cascade method (Table 3, entries 3
and 4) also revealed faster kinetics than those formed by the one-
pot pathway (Table 3, entries 1 and 2). In a third set experiments,
considering the original efficiency of nanoparticles-based catalysts
towards the reduction of aromatic rings, the challenging stereos-
elective hydrogenation of m-methylanisole was investigated. The
different reactivity of the NPs prepared by both approaches was
3.4. Catalytic lifetime of ruthenium(0) nanoparticles
The catalytic lifetime of Ru0 NPs capped by chirally modified
CDs was checked in the hydrogenation of ethyl pyruvate (20 bar H2
at rt) to justify their stability (Scheme 2).
Table 3
Hydrogenation of acetophenone and m-methylanisole using Ru0@RaMeCD-trz-Ala and Ru0@RaMeCD-trz-Leu.a
Entry
Substrate
Chiral moiety
Method
t (h)
Products
Yields (%)b
1
2
3
4
Ala
Leu
Ala
Leu
One-pot
One-pot
Cascade
Cascade
8
8
8
8
1-Phenylethanol/1-Cyclohexylethanol (2/98)
1-Phenylethanol/1-Cyclohexylethanol (10/90)
1-Phenylethanol/1-Cyclohexylethanol (0/100)
1-Phenylethanol/1-Cyclohexylethanol (16/84)
94
87
100
92
Acetophenone
5
6
7
8
9
Ala
Leu
Ala
One-pot
One-pot
Cascade
Cascade
Cascade
6c
6
6
6
6
1-Methoxy-3-methylcyclohexane (cis/trans:75/25)
1-Methoxy-3-methylcyclohexane (cis/trans:74/26)
1-Methoxy-3-methylcyclohexane (cis/trans:75/25)
1-Methoxy-3-methylcyclohexane (cis/trans: 76/24)
1-Methoxy-3-methylcyclohexane (cis/trans:76/24)
22
21
42
47
41
m-Methylanisole
Leu
Leud
a
Conditions: Ru0@RaMeCD-trz-Ala or Ru0@RaMeCD-trz-Leu ([subtrate]/[Ru0] molar ratio = 100/1), 10 mL H2O, 20 bar H2, rt.
Determined by GC analysis.
100% yield of 1-methoxy-3-methylcyclohexane (cis/trans:85/15) was obtained after 18 h of reaction.
10 eq of RaMeCD-trz-Leu were used.
b
c
d

502
N.T.T. Chau et al. / Applied Catalysis A: General 467 (2013) 497–503
[5] M. Besson, P. Gallezot, S. Neto, C. Pinel, Tetrahedron Asymmetry 11 (2000)
1809–1818.
[6] P. Kukula, R. Prins, Top. Catal. 25 (2003) 29–42.
[7] V. Polshettiwar, T. Asefa (Eds.), Nanocatalysis: Synthesis and Applications,
Wiley-VCH, Weinheim, 2013.
[8] Y. Yuan, N. Yan, P.J. Dyson, ACS Catal. 2 (2012) 1057–1069.
[9] A. Roucoux, A. Nowicki, K. Philippot, in: D. Astruc (Ed.), Nanoparticles and
Catalysis, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 2008, pp. 349–388.
[10] A. Gual, C. Godard, S. Castillon, C. Claver, Dalton Trans. 39 (2010) 11499–11512.
[11] J.P. Wilcoxon, B.L. Abrams, Chem. Soc. Rev. 35 (2006) 1162–1194.
[12] R. Narayanan, M. El-Sayed, Top. Catal. 47 (2008) 15–21.
[13] D. Astruc, Nanoparticles and Catalysis, Weinheim,Wiley-VCH Verlag GmbH &
Co. KGaA, 2008, pp. 1–48.
[14] B. Chaudret, K. Philippot, in: R.H. Crabtree, D.M.P. Mingos (Eds.), Comprehensive
Organometallic Chemistry III, Elsevier, Oxford, 2007, pp. 71–99.
[15] L.D. Pachón, G. Rothenberg, Appl. Organomet. Chem. 22 (2008) 288–299.
[16] A. Roucoux, J. Schulz, H. Patin, Chem. Rev. 102 (2002) 3757–3778.
[17] V. Mévellec, C. Mattioda, J. Schulz, J.-P. Rolland, A. Roucoux, J. Catal. 225 (2004)
1–6.
[18] S. Roy, M.A. Pericas, Org. Biomol. Chem. 7 (2009) 2669–2677.
[19] K. Nasar, F. Fache, M. Lemaire, J.-C. Béziat, M. Besson, P. Gallezot, J. Mol. Catal.
87 (1994) 107–115.
[20] S. Jansat, D. Picurelli, K. Pelzer, K. Philippot, M. Gomez, G. Muller, P. Lecante, B.
Chaudret, New J. Chem. 30 (2006) 115–122.
[21] A. Gual, M.R. Axet, K. Philippot, B. Chaudret, A. Denicourt-Nowicki, A. Roucoux,
S. Castillon, C. Claver, Chem. Commun. (2008) 2759–2761.
[22] A. Gual, C. Godard, K. Philippot, B. Chaudret, A. Denicourt-Nowicki, A. Roucoux,
S. Castillón, C. Claver, ChemSusChem 2 (2009) 769–779.
[23] P.T. Anastas, J.C. Warner (Eds.), Green Chemistry: Theory and Practice, Oxford
University Press, New York, 1998.
Scheme 2. Catalytic lifetime study of Ru0@Chiral CDs nanoparticles in the hydro-
genation of ethyl pyruvate.
After a first run, the aqueous phase containing the nanocatalysts
was separated from the hydrogenated product by extraction with
ethyl acetate (EtOAc) and then reused in a second run after addi-
tion of a new quantity of substrate. All catalytic systems kept both
their reactivity and stability since total conversion was achieved
and no agglomerates were visually observed during the recycling
tests. Consequently, as well as methylated CDs [46], the RaMeCDs
grafted with optically active moieties (Ala or Leu) proved to be effi-
cient supramolecular edifices in the nanoparticle environment to
maintain the colloidal solutions within the aqueous phase during
the catalytic process in the studied conditions.
[24] T. Mallat, E. Orglmeister, A. Baiker, Chem. Rev. 107 (2007) 4863–4890.
[25] F.-X. Felpin, E. Fouquet, ChemSusChem 1 (2008) 718–724.
[26] K.D.M. Harris, S.J.M. Thomas, ChemCatChem 1 (2009) 223–231.
[27] V. Polshettiwar, R.S. Varma, Green Chem. 12 (2010) 743–754.
[28] A. Denicourt-Nowicki, A. Roucoux, in: P. Serp, K. Philippot (Eds.), Nanomaterials
in Catalysis, Wiley-VCH, Weinheim, 2013, pp. 55–96.
[29] T. Dwars, E. Paetzold, G. Oehme, Angew. Chem. 117 (2005) 7338–7364.
[30] T. Dwars, E. Paetzold, G. Oehme, Angew. Chem. Int. Ed. 44 (2005) 7174–7199.
[31] E. Paetzold, G. Oehme, J. Mol. Catal. A: Chem. 152 (2000) 69–76.
[32] A. Roucoux, J. Schulz, H. Patin, Adv. Synth. Catal. 345 (2003) 222–229.
[33] C. Hubert, A. Denicourt-Nowicki, J.P. Guégan, A. Roucoux, Dalton Trans. 36
(2009) 7356–7358.
[34] E. Guyonnet Bilé, R. Sassine, A. Denicourt-Nowicki, F. Launay, A. Roucoux, Dal-
ton Trans. 40 (2011) 6524–6531.
[35] E. Guyonnet Bilé, A. Denicourt-Nowicki, R. Sassine, P. Beaunier, F. Launay, A.
Roucoux, ChemSusChem 3 (2010) 1276–1279.
[36] E. Guyonnet Bilé, E. Cortelazzo-Polisini, A. Denicourt-Nowicki, R. Sassine, F.
Launay, A. Roucoux, ChemSusChem 5 (2012) 91–101.
[37] F. Hapiot, J. Lyskawa, H. Bricout, S. Tilloy, E. Monflier, Adv. Synth. Catal. 346
(2004) 83–89.
[38] M. Baur, M. Frank, J. Schatz, F. Schildbach, Tetrahedron 57 (2001) 6985–6991.
[39] S.C. Mhadgut, K. Palaniappan, M. Thimmaiah, S.A. Hackney, B. Torok, J. Liu,
Chem. Commun. (2005) 3207–3209.
[40] E. Monflier, S. Tilloy, Y. Castanet, A. Mortreux, Tetrahedron Lett. 39 (1998)
2959–2960.
[41] A.R. Khan, P. Forgo, K.J. Stine, V.T. D‘Souza, Chem. Rev. (Washington, DC, USA)
98 (1998) 1977–1996.
[42] S. Tilloy, H. Bricout, E. Monflier, Green Chem. 4 (2002) 188–193.
[43] T. Mathivet, C. Méliet, Y. Castanet, A. Mortreux, L. Caron, S. Tilloy, E. Monflier,
J. Mol. Catal. A: Chem. 176 (2001) 105–116.
[44] A. Denicourt-Nowicki, A. Roucoux, Curr. Org. Chem. 14 (2010) 1266–1283.
[45] A. Denicourt-Nowicki, A. Ponchel, E. Monflier, A. Roucoux, Dalton Trans. (2007)
5714–5719.
[46] N.T.T. Chau, S. Handjani, J.-P. Guegan, M. Guerrero, E. Monflier, K. Philippot, A.
Denicourt-Nowicki, A. Roucoux, ChemCatChem 5 (2013) 1497–1503.
[47] A. Nowicki, Y. Zhang, B. Leger, J.-P. Rolland, H. Bricout, E. Monflier, A. Roucoux,
Chem. Commun. (2006) 296–298.
4. Conclusions
In summary, ruthenium nanoparticles stabilized by 5 equiv-
alents of randomly methylated ␤-cyclodextrins grafted with
optically active skeletons (l-alanine or l-leucine) were easily and
reproducibly prepared by two pertinent methods. Among both
approaches, the cascade method offers more flexibility in adjus-
ting the CDs quantities. The nanospecies have been compared in
terms of structure, stability and catalytic performances. TEM anal-
yses showed very small (<1.0 nm) and well-dispersed NPs and
DOSY NMR experiments revealed the presence of mobile CD edi-
fices around the particle surface. These observations confirmed an
efficient dispersing role of the CDs to prevent NPs from aggre-
gate formation in water. The obtained Ru0 NPs revealed efficient
catalytic activities and selectivities in the biphasic hydrogenation
of various prochiral substrates at room temperature under 20 bar
H2. Generally, Ru nanocatalysts containing l-leucine moiety were
more active than NPs capped by RaMeCD-trz-Ala and those pre-
pared by the cascade method seem to be more efficient than those
synthesized from one-pot method. Finally, the stability of the Ru0
NPs was also investigated through recycling tests of ethyl pyruvate
hydrogenation. Regarding the results, methylated cyclodextrins
are relevant candidates for supramolecular catalysis in terms of
selectivity. The functionalization of their secondary face by chiral
synthons could modify the interactions with the particle’s surface
as well as with the substrate, and thus may be promising in terms
of the (expected) enantiodiscrimination.
[48] J. Szejtli, T. Osa, in: J. Szejtli, T. Osa (Eds.), Comprehensive Supramolecular
Chemistry, Pergamon, Oxford, 1996, pp. 185–204.
[49] D.N. Tran, C. Blaszkiewicz, S. Menuel, A. Roucoux, K. Philippot, F. Hapiot, E.
Monflier, Carbohydr. Res. 346 (2011) 210–218.
Acknowledgements
[50] H.-Y. Kim, J. Sohn, G.T. Wijewickrama, P. Edirisinghe, T. Gherezghiher, M.
Hemachandra, P.-Y. Lu, R.E. Chandrasena, M.E. Molloy, D.A. Tonetti, G.R.J.
Thatcher, Bioorg. Med. Chem. 18 (2010) 809–821.
[51] D. Astruc, C. Ornelas, A.K. Diallo, J. Ruiz, Molecules 15 (2010) 4947–4960.
[52] E. Boisselier, A.K. Diallo, L. Salmon, C. Ornelas, J. Ruiz, D. Astruc, J. Am. Chem.
Soc. 132 (2010) 2729–2742.
The authors are grateful to CNRS and the Agence Nationale de
la Recherche (ANR-09-BLAN-0194) for the financial support of the
SUPRANANO program. We are also indebted to Patricia Beaunier
from Université Pierre et Marie Curie for obtaining the TEM images.
[53] J. Yang, J.Y. Lee, T.C. Deivaraj, H.-P. Too, J. Colloid Interface Sci. 271 (2004)
308–312.
[54] N. Yao, Z.L. Wang, Handbook of Microscopy for Nanotechnology, 1st ed.,
Springer, New York, 2005.
References
[55] S. Mandal, P. Selvakannan, S. Phadtare, R. Pasricha, M. Sastry, Proc. Indian Acad.
Sci. Chem. Sci. 114 (2002) 513–520.
[56] O. Horovitz, A. Mocanu, G. Tomoaia, L. Bobos, D. Dubert, I. Daian, T. Yusanis, M.
Tomoaia-Cotisel, Stud. Univ. Babes-Bolyai Chem. 52 (2007) 97–108.
[57] K.F. Morris, C.S. Johnson, J. Am. Chem. Soc. 114 (1992) 3139–3141.
[1] J.K. Whitesell, Chem. Rev. 92 (1992) 953–964.
[2] R.-L. Gu, C.J. Sih, Tetrahedron Lett. 31 (1990) 3287–3290.
[3] M. Besson, B. Blanc, M. Champelet, P. Gallezot, K. Nasar, C. Pinel, J. Catal. 170
(1997) 254–264.
[4] M. Besson, S. Neto, C. Pinel, Chem. Commun. (1998) 1431–1432.

N.T.T. Chau et al. / Applied Catalysis A: General 467 (2013) 497–503
503
[58] P.-J. Debouttière, Y. Coppel, A. Denicourt-Nowicki, A. Roucoux, B. Chaudret, K.
Philippot, Eur. J. Inorg. Chem. 2012 (2012) 1229–1236.
[61] S. Gatard, L. Liang, L. Salmon, J. Ruiz, D. Astruc, S. Bouquillon, Tetrahedron Lett.
52 (2011) 1842–1846.
[59] A. Macchioni, G. Ciancaleoni, C. Zuccaccia, D. Zuccaccia, Chem. Soc. Rev. 37
(2008) 479–489.
[62] H. Nagahara, M. Ono, M. Konishi, Y. Fukuoka, Appl. Surf. Sci. 121–122 (1997)
448–451.
[60] A. Nowicki, V. Le Boulaire, A. Roucoux, Adv. Synth. Catal. 349 (2007) 2326–2330.
[63] T.Q. Hu, C.-L. Lee, B.R. James, S.J. Rettig, Can. J. Chem. 75 (1997) 1234–1239.