Aqueous asymmetric transfer hydrogenation using modular hydrophobic aminoalcohols

Article abstract of DOI:10.1016/j.tetasy.2008.01.001

A series of new modular Ru/aminoalcohol systems were used as enantioselective catalysts in the asymmetric transfer hydrogenation reaction in both water and 2-propanol. The catalytic behavior exhibited in these two media follows different tendencies regard

Full text of DOI:10.1016/j.tetasy.2008.01.001

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 374–378
Aqueous asymmetric transfer hydrogenation using modular
hydrophobic aminoalcohols
a
a
a
a,b,
*
`
Esther Alza, Amaia Bastero, Susanna Jansat and Miquel A. Pericas
aInstitute of Chemical Research of Catalonia (ICIQ), Av. Paı¨sos Catalans 16, 43007 Tarragona, Spain
b
`
Departament de Quı´mica Organica, Universitat de Barcelona (UB), 08028 Barcelona, Spain
Received 4 December 2007; accepted 3 January 2008
Available online 30 January 2008
Abstract—A series of new modular Ru/aminoalcohol systems were used as enantioselective catalysts in the asymmetric transfer hydro-
genation reaction in both water and 2-propanol. The catalytic behavior exhibited in these two media follows different tendencies regard-
ing the tunable ligand structure. While the bulkiness of the R1 group has a positive effect on the activity for reactions in 2-propanol,
ligands with bulky R1 groups are generally less active in water. Additionally, cationic, anionic, and neutral surfactants do not improve
the catalytic behavior in water.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
ous phase and the substrate and product/s in the organic
one. These systems present the possibility of catalyst recy-
cling by simple phase separation. However, the application
of most of these catalysts is limited by the rather long syn-
theses needed to introduce water-solubilizing groups in the
catalyst structure. A way to overcome this difficulty is the
use of stable hydrophobic catalysts directly on water,4 an
approach of interest for reactions taking place at the inter-
phase between an organic substrate and water.
Sustainability concerns have led in recent times to in-
creased research efforts aimed to decrease the environmen-
tal impact of chemical processes. For this reason, the atom
economy1 provided by catalytic reactions becomes crucial.
To minimize the catalyst loading or to avoid treatments re-
quired for separation or removal from reaction products,
different approaches to enantioselective catalysis have fo-
cused on the heterogenization of the catalytic system.2
Enantioselective reduction of prochiral ketones to yield
enantiopure secondary alcohols is of interest because of
the importance of these alcohols as intermediates in the
production of pharmaceuticals and advanced materials.
Among the different catalytic methods reported to this
end, the Asymmetric Transfer Hydrogenation (ATH) is
of importance since it avoids the use of flammable hydro-
gen as a reducing agent.5 The first successful examples were
reported by Noyori et al., with ruthenium-based catalysts
bearing monotosylated diamines or 1,2-aminoalcohols as
chiral ligands. The most popular solvents for this catalytic
reaction are either 2-propanol or the formic acid/triethyl-
amine mixture, which act at the same time as hydrogen do-
nors for the reduction process. Nevertheless, aqueous
formate, which is used in nature by enzymes for reduction
reactions, has been rarely used until quite recent reports by
Xiao and co-workers6a,b and by Wills,6c who have shown
the possibility of performing ATH in water using sodium
formate as a hydrogenation agent. Most of the catalytic
On the other hand, the use of water as a solvent or even sol-
vent-free methodologies is the strategy commonly used to-
ward greener chemistry.3 Water as a reaction medium is
highly desirable since it is safe, non-toxic, environmentally
friendly, and inexpensive. However, many transition metal
catalysts are moisture sensitive, making aqueous catalysis
only possible in extremely careful conditions. In addition,
the insolubility of many organic compounds in water limits
its application in various chemical transformations.
An interesting approach to aqueous catalysis is the use of
water-soluble catalysts, which are assembled through the
use of water-soluble ligands. Generally, water-soluble cata-
lysts act in biphasic systems, the catalysts being in the aque-
*
Corresponding author. Tel.: +34 977 920 211; fax: +34 977 920 222;
e-mail: mapericas@iciq.es
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.01.001

E. Alza et al. / Tetrahedron: Asymmetry 19 (2008) 374–378
375
systems reported for the aqueous ATH bear N,N type
ligands (amino-amide,7 monotosylated8 or sulfonated9 dia-
mine ligands, and imino-pyridines10). The use of aminoal-
cohols, which are also important ligands in this reaction,
has been only quite recently reported.11
for the synthesis of aminoalcohols 1–6 is based on the lith-
ium perchlorate catalyzed,13a regioselective and stereospe-
cific ring opening of a protected Sharpless enantiopure
epoxide with a primary amine (Scheme 1).13b All new li-
gands are air stable, orange-yellowish oils, which have been
1
characterized by H and 13C NMR spectroscopy, high res-
Given the interest in conducting this reaction in water, the
search for new catalysts, which are active and stable in an
aqueous medium, is a significant challenge. We report here
on the use of a family of readily accessible chiral 1,2-
aminoalcohols (1–6) as enantioselective ligands for the
catalytic aqueous ATH reaction. Their tunable backbone
allows for a programmed variation of their hydrophobic
nature, and results on their catalytic activity show that
reaction occurring at the surface of the organic substrate
droplets dispersed in water is faster in some cases than
homogeneous reactions in isopropanol mediated by the
same catalytic systems (Fig. 1).
olution mass spectrometry, and specific rotation.
i) NaH; THF
ii) R1X
O
O
OR1
OH
1 R1 = Me; R2 = Ph (83%)
2 R1 = Me; R2 = 4-Ph-C6H4 (23%)
3 R1 = CPh3; R2 = Ph (87%)
iii) LiClO4 (15 equiv)
R2NH2 (10 equiv)
4 R1 = CPh3; R2 = 4-Ph-C6H4 (83%)
5 R1 = CPh3; R2 = 4-CF3-C6H4 (82%)
6 R1 = CPh3; R2 = 4-F-C6H4 (80%)
R2
NH
2. Results and discussion
OR1
OH
It has been recently reported that the asymmetric transfer
hydrogenation of aromatic ketones using Noyori’s catalyst
(Ru-(R,R)-TsDPEN) can be performed in an open atmo-
sphere using water as a solvent with very good results.3
Chiral aminoalcohols can in general be readily prepared,
while some of them are even commercially available. How-
ever, to the best of our knowledge, there are only two re-
ports using commercially available aminoalcohols as
ligands for the ATH in water. Among them, (ꢀ)-ephed-
rine11 gave the best activities, with enantioselectivities up
to 78% for the reduction of acetophenone.
Scheme 1. Synthesis of ligands 1–6.
A preliminary screening of the transfer hydrogenation of
acetophenone in 2-propanol was conducted with amino-
alcohols 1–4 (Scheme 2 and Table 1). These ligands showed
that the bulkiness of the primary alcohol protecting group
R1 increases dramatically the activity of the catalyst
(entries 1 and 2 vs 3 and 4 in Table 1), while enantioselec-
tivity is mainly influenced by the R2 substituent on the
amino group (entries 1 and 3 vs 2 and 4). It is important
to note the use of a 4-phenylbenzyl group as an amine sub-
stituent (R2) that improved the selectivity of the process up
to 90%. This ee is substantially higher than the previously
reported with similar ligands bearing alkyl R2 substituents
as Me or Bu (ee: 76%; 0 °C; R2: Bu).12b
We reported some time ago the preparation of a family of
modular aminoalcohols from enantiopure Sharpless epox-
yalcohols. The steric and electronic properties of these li-
gands were conveniently tuned for the application in
several catalytic processes12 including ATH in 2-propa-
nol.12b For the asymmetric transfer hydrogenation in an
aqueous medium, we decided to test related ligands, bear-
ing some structural changes. The general route followed
The ATH in aqueous medium was conducted similarly, al-
beit under air. Formate was chosen as a hydrogen source
CO2
O
H
O-
CO2
CO2
H
Ru
OH
O
Figure 1. Cartoon representation of the use of hydrophobic catalysts in aqueous medium.

376
E. Alza et al. / Tetrahedron: Asymmetry 19 (2008) 374–378
Table 2. Aqueous asymmetric transfer hydrogenation using chiral ami-
noalcohols 1–6
O
OH
cat: Ru(II) or Rh(III) /L*
HCO2Na / H2O
Entry
Ligand
Temp (°C)
Time (h)
Conv.a (%)
eea (%)
1
2b
3
1
1
1
1
1
1
1
1
2
3
3
3
4
4
5
6
25
25
25
40
25
40
25
25
25
25
25
25
25
25
25
25
12
12
24
24
12
12
24
24
24
24
24
24
24
24
24
24
35
41
60
47
58
94
14
13
25
52
60
72
60
33
49
52
81 (S)
79 (S)
82 (S)
81 (S)
53 (S)
48 (S)
67 (S)
84 (S)
83 (S)
70 (S)
60 (S)
60 (S)
68 (S)
61 (S)
67 (S)
68 (S)
R2
HN
4
OR1
OH
5c
L*:
6c
7d
8e
Scheme 2. ATH reaction in water using ligands 1–6.
9
10
11b,f
12b
13
14g
15
16
Table 1. Transfer hydrogenation in 2-propanol using aminoalcohols 1–4
Entry
Ligand
Time (h)
Conversiona (%)
eea (%)
1
2
3
4
1
2
3
4
6
24
4
22
13
>99
51
80 (S)
86 (S)
82 (S)
90 (S)
Reaction conditions: [RuCl2(p-cymene)2]2 (0.0125 mmol); ligand
(0.05 mmol); water (2 mL); NaHCOO (6.25 mmol); acetophenone
(1.25 mmol); acetophenone/Ru: 50.
6
Reaction
conditions:
[RuCl(p-cymene)]2
(0.004 mmol);
ligand
(0.016 mmol); 2-propanol (6.8 mL); KOH (0.029 mmol; 0.08 M in 2-pro-
panol); acetophenone (0.4 mmol; 0.5 M in 2-propanol); temperature:
25 °C (see Section 4).
a Determined by GC with a b-DEX 120 column at 120 °C isotherm.
b Shaker.
c [RhCl2Cp*]2 used as the catalyst precursor.
a Determined by GC, with a b-DEX 120 column.
d CTAB added as cationic surfactant (1.25 mmol, 100%).
e SDS added as anionic surfactant (1.25 mmol, 100%).
f DiMePEG added as neutral surfactant (0.125 mmol, 10%).
g SDS added as anionic surfactant (0.025 mmol, 2%).
because for Ru/aminoalcohol systems reaction rates are
faster in basic media (HCOONa, initial pH 7.3;
HCOOH–NEt3–H2O with HCOOH/NEt3 = 1/1.7, initial
pH 5.7).11b As a representative procedure, a suspension
of the ruthenium precursor and the ligand was stirred in
water for 2 h at room temperature. The solution became
yellow in color although part of the precursor remained
as a solid. Then, formate and acetophenone were directly
added and the solution was vigorously stirred or shaken,
ensuring a homogeneous emulsion with no phase separa-
tion during the whole process. The solution was stirred
for 12 or 24 h at room temperature, while the progress of
the reaction was followed by GC.
According to this result, the rest of the experiments in this
study were performed using as optimized conditions: 25 °C,
[RuCl2(p-cymene)]2 as the ruthenium source and sodium
formate as hydrogen donor in neat water as the only
solvent.
Amino alcohols 2–6 showed moderate activities (up to 60%
of conversion) after 24 h (entries 9–13 in Table 2) working
at a 1/50 Ru/substrate ratio, thus suggesting possible mass
transfer limitations at the organic-aqueous interphase. An-
ionic, cationic, and neutral surfactants as SDS, CTAB, and
DiMePEG, respectively, were added to increase the misci-
bility of reactants in the water phase and/or interphase (en-
tries 7 and 8) and, hence, to improve the catalytic behavior
of the system.15 Surprisingly, a negative effect in conversion
was observed with both the ionic surfactants. This could be
due to the existence of interactions between the surfactant
molecules and the ruthenium species at the droplet surface,
with the consequence of the catalytic sites being partially
blocked. The enantioselectivity did not change when using
SDS, indicating that the catalytically active species is the
same. With CTAB, in turn, a slight decrease in enantio-
selectivity is observed. Effect of the neutral agent DiMe-
PEG was limited to a small decrease of catalytic activity.
To find the best conditions for the aqueous ATH, we ini-
tially studied the reaction performed with the catalytic sys-
tem containing ligand 1 (Table 2). At 25 °C, conversions of
35% and 60% after 12 h and 24 h, respectively, were re-
corded. This shows that although less active in water, the
catalyst Ru/1 is stable for hours in this medium. Interest-
ingly, the enantioselectivity was maintained as high as in
the reaction performed in 2-propanol (82% ee versus 80%
ee). 1-Phenylethanol with the same absolute configuration
(S) was obtained in water and in isopropanol.
When the temperature was increased to 40 °C, which is the
temperature at which other reported systems have been tes-
ted,11b a decrease in conversion was observed, albeit the ee
kept constant, probably indicating a decomposition of the
14
catalyst. The use of [RhClCp*]2 as the catalyst precursor
Additionally, electronic effects on the ligand backbone
were analyzed by placing electron-withdrawing groups
(fluoride and trifluoromethyl) in the para-position of the
aromatic ring in the R2 substituent in the structure of
ligand 3 (ligands 5 and 6). This had no effect on the cata-
lytic activity or the enantioselectivity (entries 10 vs 15
and 16 in Table 2).
led to a more active catalyst, as reported for diamine-
containing systems,6a but the enantioselectivity was only
moderate (entry 4, 53% ee). An increase in temperature
up to 40 °C with the Rh/1 system led to an important
increase in reaction rate but enantioselectivity deteriorated
slightly.

E. Alza et al. / Tetrahedron: Asymmetry 19 (2008) 374–378
377
3. Conclusion
CH2–OMe), 3.29 (br dd, 1H, CH2–OMe), 3.29 (s, 3H,
CH3). 13C NMR (100 MHz, CDCl3) d 139.8 (C), 135.9
(C), 134.0 (C), 132.1 (C), 128.8–124.0 (CHarom), 73.8
(CH2–OMe), 72.7 (CH–OH), 65.2 (CH–NH), 59.1 (CH3),
49.5 (CH2–NH). ESI +ve for C23H26NO2 [M+H]
348.1964; found 348.1978.
In summary, a series of new modular aminoalcohols 1–6
have been prepared in good yields from enantiopure phen-
ylglycidol and used as ligands in the ruthenium-catalyzed
ATH both in water and in 2-propanol as reacting media.
The tunable structure of 1–6 allows for a programmed var-
iation of their hydrophobic nature. Results on ATH show
that, for some of the ligands studied, reaction in aqueous
media is faster than in isopropanol. In isopropanol, aceto-
phenone is reduced with enantioselectivities up to 90%.
Quite significantly, the catalytic behaviors of these systems
in water and in isopropanol follow different trends regard-
ing the structure of the chiral ligand (bulkiness of the R1
substituent) which has different effects in isopropanol ver-
sus water: while bulky R1 substituents dramatically acceler-
ate reductions in isopropyl alcohol, an opposite effect is
observed in water. This fact suggests that bulky groups pre-
vent proper access of the substrate to the metallic specie at
the substrate/water interphase. The enantioselectivity re-
corded under aqueous conditions in the ATH of acetophe-
none reaches 83%, only slightly below than in isopropanol.
This result opens the possibility of using hydrophobic sys-
tems in catalytic reactions performed in water as the only
solvent.
4.3. Ligand 3: (1R,2R)-1-(Benzylamino)-1-phenyl-3-(trityl-
oxy)propan-2-ol
23
See ligand 1 for synthesis. Yield: 87%, ½aꢁD ¼ ꢀ193:7 (c
0.99, CHCl3); 1H NMR; (400 MHz, CDCl3) 7.45–7.15
(m, 25H, CHarom), 4.03 (d, J = 5.3 Hz, 1H, CH–NH),
3.95-3.89 (m, 1H, CH–OH), 3.76 (d, J = 12.9 Hz, 1H,
CH2–NH), 3.58 (d, J = 12.9 Hz, 1H, CH2–NH), 3.19 (dd,
J = 9.7 Hz, J = 4.4 Hz, 1H, CH2–OCPh3), 2.96 (dd, J =
9.7 Hz, J = 4.4 Hz, 1H, CH2–OCPh3). 13C NMR
(100 MHz, CDCl3): d 143.9 (C), 139.9 (C), 139.1 (C),
128.7–127.1 (CHarom), 87.1 (C), 72.7 (CH–OH), 65.2
(CH–NH), 64.6 (CH2–OCPh3), 51.6 (CH2–NH). ESI +ve
for C35H34NO2 [M+H] 500.2590; found 500.2576.
4.4. Ligand 4: (1R,2R)-1-(Biphenyl-4-ylmethylamino)-1-
phenyl-3-(trityloxy)propan-2-ol
22
See ligand 1 for synthesis. Yield: 83%, ½aꢁD ¼ þ34:9 (c 1.09,
CHCl3); 1H NMR; (400 MHz, CDCl3) d 7.96–7.14 (m,
29H, CHarom), 4.01 (d, J = 5.3 Hz, 1H, CH–NH), 3.91–
3.87 (m, 1H, CH–OH), 3.75 (d, J = 12.9 Hz, 1H, CH2–
NH), 3.58 (d, J = 12.9 Hz, 1H, CH2–NH), 3.19 (dd, J =
9.9 Hz, J = 4.1 Hz, 1H, CH2–OCPh3), 2.95 (dd, J =
9.9 Hz, J = 4.1 Hz, 1H, CH2–OCPh3). 13C NMR
(100 MHz, CDCl3): d 143.9 (C), 141.2 (C), 140.1 (C),
139.4 (C), 128.9–127.1 (CHarom), 87.1 (C), 73.0 (CH–
OH), 65.5 (CH–NH), 64.8 (CH2–OCPh3), 51.3 (CH2–
NH). ESI +ve for C41H38NO2 [M+H] 576.2903; found
576.2910.
4. Experimental
4.1. Ligand 1: (1R,2R)-1-(Benzylamino)-3-methoxy-1-phen-
ylpropan-2-ol
A mixture of (2S,3S)-2-(methoxymethyl)-3-phenyloxiran
(250 mg, 1.52 mmol), lithium perchlorate (2.4 g, 22.8
mmol) and benzylamine (1.6 mL, 15.2 mmol) in 4 mL of
acetonitrile was reacted under nitrogen at 80 °C overnight.
After that time, reaction was analyzed by TLC and deter-
mined to be complete. Work-up included the addition of
water (10 mL) and the aqueous layer was extracted with
CH2Cl2. The combined organic extracts were dried and
concentrated under reduced pressure. The residual oil
was purified by flash chromatography on deactivated silica
4.5. Ligand 5: (1R,2R)-1-(4-Fluorobenzylamino)-1-phenyl-3-
(trityloxy)propan-2-ol
23
See ligand 1 for synthesis. Yield: 82%. ½aꢁD ¼ ꢀ221:7 (c
1
(2.5% Et3N v/v) eluting with hexane-ethyl acetate 80:20 to
0.99, CHCl3); H NMR (400 MHz, CDCl3) d 7.39–6.97
24
afford the desired aminoalcohol (340.6 mg, 83%), ½aꢁD
¼
(m, 24 H, CHarom), 3.95 (d, J = 5.3 Hz, 1H, CH–NH),
3.88–3.84 (m, 1H, CH–OH), 3.68 (d, J = 13.2 Hz, 1H,
CH2–NH), 3.50 (d, J = 13.2 Hz, 1H, CH2–NH), 3.18 (dd,
J = 9.7 Hz, J = 4.4 Hz, 1H, CH2–OCPh3), 2.94 (dd, J =
9.8 Hz, J = 4.2 Hz, 1H, CH2–OCPh3). 13C NMR
(100 MHz, CDCl3) d 143.8 (C), 139.2 (C), 136.0 (C),
129.9–115.2 (CHarom), 72.8 (CH–OH), 65.2 (CH–NH),
64.4 (CH2–OCPh3), 50.9 (CH2–NH). ESI +ve for
C35H33NO2F [M+H] 518.2495; found 518.2484.
1
ꢀ466:3 (c 1.03, CHCl3); H NMR (400 MHz, CDCl3) d
7.40–7.28 (m, 10H, CHarom), 3.98–3.94 (m, 1H, CH–NH),
3.91 (d, J = 4.9 Hz, 1H, CH–OH), 3.87 (br, 2H, CH2–
NH), 3.76 (d, J = 13.2 Hz, 1H, CH2–OMe), 3.57 (d,
J = 13.2 Hz, 1H, CH2–OMe), 3.29 (s, 3H, CH3). 13C
NMR (100 MHz, CDCl3) d 128.8–127.2 (CHarom), 73.9
(CH2–OMe), 72.6 (CH–OH), 64.6 (CH–NH), 59.2 (CH3),
51.5 (CH2–NH). ESI +ve for C17H22NO2 [M+H]
272.1651; found 272.1656.
4.6. Ligand 6: (1R,2R)-1-Phenyl-1-(4-(trifluoromethyl)-
benzylamino)-3-(trityloxy)propan-2-ol
4.2. Ligand 2: (1R,2R)-1-(Biphenyl-4-ylmethylamino)-3-
methoxy-1-phenylpropan-2-ol
23
See ligand 1 for synthesis. Yield: 80%, ½aꢁD ¼ ꢀ193:7 (c
24
1
See ligand 1 for synthesis. Yield: 23%, ½aꢁD ¼ ꢀ4:1 (c 0.96,
0.99, CHCl3); H NMR; (400 MHz, CDCl3): d 7.62–7.10
CH2Cl2); 1H NMR (400 MHz, CDCl3) d 7.92–7.42 (m,
14H, CHarom), 4.22 (d, J = 13 Hz, 1H, CH2–NH), 4.06
(d, J = 13 Hz, 1H, CH2–NH), 4.04 (d, J = 5.0 Hz, 1H,
CH–NH), 4.01–3.98 (m, 1H, CH–OH), 3.32 (br dd, 1H,
(m, 24H, CHarom), 3.94 (d, J = 5.0 Hz, 1H, CH–NH),
3.88–3.84 (m, 1H, CH–OH), 3.75 (d, J = 13.5 Hz, 1H,
CH2–NH), 3.56 (d, J = 13.5 Hz, 1H, CH2–NH), 3.20 (dd,
J = 9.8 Hz, J = 4.5 Hz, 1H, CH2–OCPh3), 2.96 (dd,

378
E. Alza et al. / Tetrahedron: Asymmetry 19 (2008) 374–378
J = 9.9 Hz, J = 4.4 Hz, 1H, CH2–OCPh3). 13C NMR
(100 MHz, CDCl3) d 143.9 (C), 128.7–125.5 (CHarom),
73.1 (CH–OH), 65.6 (CH–NH), 64.8 (CH2–OCPh3), 51.4
(CH2–NH). ESI +ve for C36H33NO2F3 [M+H] 568.2463;
found 568.2455.
2003; (c) Benaglia, M.; Puglisi, A.; Cozzi, A. Chem. Rev.
2003, 103, 3401–3429.
3. (a) Breslow, R. Acc. Chem. Res. 1991, 24, 159–164; (b) Walsh,
J. P.; Li, H.; de Parrodi, C. A. Chem. Rev. 2007, 107, 2503–
2545; (c) Sheldon, R. A. In Methods and Reagents for Green
Chemistry: An Introduction; Tundo, P., Perosa, A., Zecchini,
F., Eds.; John Wiley & Sons: Hoboken, 2007; pp 191–199; (d)
Engberts, J. B. F. N. In Methods and Reagents for Green
Chemistry: An Introduction; Tundo, P., Perosa, A., Zecchini,
F., Eds.; John Wiley & Sons: Hoboken, 2007; pp 159–170; (e)
Herrerias, C. I.; Yao, X.; Li, Z.; Chao-Jun, L. Chem. Rev.
2007, 107, 2546–2562; For solvent-free examples: Walsh, P.
J.; Li, H.; Anaya de Parrodi, C. Chem. Rev. 2007, 107, 2503–
2545.
4.7. Asymmetric transfer hydrogenation in 2-propanol
The reactions in Table 1 were performed under argon.
[RuCl2(p-cymene)]2 (0.004 mmol) and the aminoalcohol
(0.016 mmol) were placed in 2-propanol (6.84 mL) at
80 °C and reacted for 30 min giving a yellow solution. Then
the mixture is allowed to reach 25 °C and a solution of
KOH (0.029 mmol; 0.08 M in 2-propanol) and of aceto-
phenone (0.4 mmol; 0.5 M in 2-propanol) were added.
The reaction proceeded for the reported times at room tem-
perature. After reaction time, the reaction mixture was
passed through a silica plug to eliminate metal traces and
analyzed by GC with a b-DEX 120 column.
4. Narayan, S.; Muldoon, J.; Finn, M. G.; Fokin, V. V.; Kolb,
H. C.; Sharpless, K. B. Angew. Chem., Int. Ed. 2005, 44,
3275–3279.
5. (a) Hashiguchi, S.; Fujii, A.; Takehara, J.; Ikariya, T.;
Noyori, R. J. Am. Chem. Soc. 1995, 117, 7562–7563; (b)
Takehara, J.; Hashiguchi, S.; Fujii, A.; Inoue, A.; Ikariya, T.;
Noyori, R. Chem. Commun. 1996, 233–234; (c) Fujii, A.;
Inoue, S.; Hishiguchi, S.; Uemastu, N.; Ikariya, T.; Noyori,
R. J. Am. Chem. Soc. 1996, 118, 2521–2522; (d) Uematsu, N.;
Fujii, A.; Hashiguchi, S.; Ikariya, T.; Noyori, R. J. Am.
Chem. Soc. 1996, 118, 4916–4917.
6. (a) Wu, X.; Vinci, D.; Ikariya, T.; Xiao, J. Chem. Commun.
2005, 4447–4449; (b) Wu, X.; Xiao, J. Chem. Commun. 2007,
24, 2449–2466; (c) Matharu, D. S.; Morris, D. J.; Clarkson,
G. J.; Wills, M. Chem. Commun. 2006, 3232–3234.
7. Rhyo, H. Y.; Park, H-J.; Chung, Y. K. Chem. Commun. 2001,
2064–2065.
4.8. Aqueous asymmetric transfer hydrogenation
The metal precursor (0.0125 mmol) and the aminoalcohol
(0.05 mmol) were placed in 2 mL of distilled water and stir-
red for 2 h at the corresponding temperature. Then sodium
formate (6.25 mmol) and acetophenone (1.25 mmol) were
added and the reaction was vigorously stirred (see Table
2 for times and type of agitation). After a suitable reaction
time, diethyl ether was added and the organic phase was
extracted (3 ꢂ 5 mL). The combined organic phases were
dried with MgSO4 and passed through a short silica plug
to eliminate metal traces. The sample was analyzed by
GC with a b-DEX 120 column.
8. Wu, X. F.; Li, G. X.; Hems, W.; King, F.; Xiao, J. L. Org.
Biomol. Chem. 2004, 2, 1818–1821.
9. Canivet, J.; Suss-Fink, G. Green Chem. 2007, 9, 391–397.
¨
10. Himeda, Y.; Onozawa-Komatsuzaki, N.; Sugihara, H.;
Arakawa, H.; Kasuga, K. J. Mol. Catal. A: Chem. 2003,
195, 95–100.
11. (a) Mao, J.; Wan, B.; Wu, F.; Lu, S. Tetrahedron Lett. 2005,
46, 7341–7344; (b) Wu, X.; Li, X.; McConville, M.; Saisdi, O.;
Xiao, J. J. Mol. Catal. A: Chem. 2006, 247, 153–158.
12. Selected examples (a) Jimeno, C.; Pasto, M.; Riera, A.;
Acknowledgments
We thank MEC (Grant CTQ2005-02193/BQU), DURSI
(Grant 2005SGR225), Consolider Ingenio 2010 (Grant
CSD2006-0003), and ICIQ Foundation for financial sup-
port. A.B. is grateful to MEC for a ‘Juan de la Cierva’ re-
search contract. E.A. thanks ICIQ Foundation for a
predoctoral fellowship.
`
´
Pericas, M. A. J. Org. Chem. 2003, 68, 3130–3138; (b) Pasto,
`
M.; Riera, A.; Pericas, M. A. Eur. J. Org. Chem. 2002, 2337–
2341; (c) Puigjaner, C.; Vidal-Ferran, A.; Moyano, A.;
`
Pericas, M. A.; Riera, A. J. Org. Chem. 1999, 64, 7902–
`
7911; (d) Vidal-Ferran, A.; Moyano, A.; Pericas, M. A.;
Riera, A. Tetrahedron Lett. 1997, 38, 8773–8776; (e) Vidal-
`
Ferran, A.; Moyano, A.; Pericas, M. A.; Riera, A. J. Org.
Chem. 1997, 62, 4970–4982.
References
13. (a) Chini, M.; Crotti, P.; Flippin, L. A.; Gardelli, C.; Giovani,
E.; Macchia, F.; Pineschi, M. J. Org. Chem. 1993, 58, 1221–
1227; (b) Canas, M.; Poch, M.; Verdaguer, X.; Moyano, A.;
Pericas, M. A.; Riera, A. Tetrahedron Lett. 1991, 32, 6931–
6934.
14. Booth, B. L.; Haszeldine, I. N.; Hill, M. J. Chem. Soc. (A)
1969, 1299–1303.
15. Rhyoo, H. Y.; Park, H-J.; Suh, W. H.; Chung, Y. K.
Tetrahedron Lett. 2002, 43, 269–272.
1. Trost, B. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 259–281.
2. (a) Chiral Catalyst Immobilization and Recycling; De Vos, D.
E., Vankelecom, I. F. J., Jacobs, P. A., Eds.; Wiley-VCH:
Weinheim, 2000; (b) Frenzel, T.; Solodenko, W.; Kirsching,
A. Solid-Phase Bound Catalysts: Properties and Applica-
tions. In Polymeric Materials in Organic Synthesis and
Catalysis; Buchmeiser, M. R., Ed.; Wiley-VCH: Weinheim,