Synthesis and studies of 6,6′-BINAP derivatives for the heterogeneous asymmetric hydrogenation of methyl acetoacetate

Article abstract of DOI:10.1016/S0957-4166(02)00264-1

New BINAP derivatives (polyamide, polyureas or ureas) were synthesized and employed in the ruthenium-catalyzed asymmetric heterogeneous hydrogenation of methyl acetoacetate. Enantiomeric excesses in the range 48-100% were observed. Furthermore, the most efficient have been recovered and the recycled catalysts were shown to maintain their efficiency in subsequent reactions.

Full text of DOI:10.1016/S0957-4166(02)00264-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 1141–1146
Synthesis and studies of 6,6%-BINAP derivatives for the
heterogeneous asymmetric hydrogenation of methyl acetoacetate
a
a
b
a,
Christine Saluzzo, Thierry Lamouille, Fr e´ d e´ ric Le Guyader and Marc Lemaire *
a
Laboratoire de Catalyse et Synth e` se Organique, UMR 5622, Universit e´ Claude Bernard, CPE, 43 Bd. du 11 Novembre 1918,
6
9622 Villeurbanne Cedex, France
b
Rhodia, CR de Lyon, 85 av. des Fr e` res Perret, 69192 Saint-Fons Cedex, France
Received 12 March 2002; accepted 31 May 2002
Abstract—New BINAP derivatives (polyamide, polyureas or ureas) were synthesized and employed in the ruthenium-catalyzed
asymmetric heterogeneous hydrogenation of methyl acetoacetate. Enantiomeric excesses in the range 48–100% were observed.
Furthermore, the most efficient have been recovered and the recycled catalysts were shown to maintain their efficiency in
subsequent reactions. © 2002 Elsevier Science Ltd. All rights reserved.
1
. Introduction
phosphines still remain rare, which is probably a result
of problems with separation and recovery of the expen-
sive chiral catalyst.
Pharmaceuticals, agrochemicals, flavors and fragrances
are the principal areas that require the synthesis of
enantiomerically pure chiral compounds. Most of these
compounds are still synthesized starting from the chiral
pool or else they are prepared in racemic form and the
desired enantiomer is subsequently obtained by resolu-
tion. However, they can be obtained from prochiral
substrates by enantioselective catalysis, mainly through
asymmetric catalytic hydrogenation. Chiral diphosphi-
nes have been known to be catalytic ligands for this
To overcome these drawbacks, heterogeneous catalysts
can be employed, as can support homogeneous cata-
lysts, a methodology that has been widely studied over
the last few years. This latter approach consists of the
‘heterogenization’ of an efficient homogeneous catalyst
by anchoring it to a solid support, i.e. an inorganic
8
9
material or an organic polymer in order to perform
the separation of the catalyst from the reaction mixture
by filtration. Another possibility is to use soluble poly-
mer-supported catalysts, which combine the advantages
of homogeneous (mobility and accessibility of the
active sites) and heterogeneous catalysis (easy separa-
tion and recovery). After the reaction the catalyst is
recovered by simple precipitation upon addition of an
appropriate solvent, followed by filtration. In the case
of BINAP, the first concept was developed in 1998 by
1
,2
reaction for more than 30 years.
having C -symmetry, lead to high activity and selectiv-
ity. Among them, BINAP, developed by Noyori et al
Many of them,
2
3
is a very active and selective ligand for which the
chirality is induced by binaphthyl skeleton atropoiso-
merism. The BINAP, rhodium or ruthenium complexes
are able to reduce a wide range of substrates such as
a-ketoesters, b-ketoesters, alkenes and ketones giv-
ing from 70 to 99% e.e. It is noteworthy that the best
activity has been observed in the case of the hydrogena-
tion of acetophenone in the presence of 1,2-
4
4
5
5
10
Bayston et al., who described their heterogeneous
version by grafting a monofunctionalized BINAP
derivative onto a polystyrene resin via an amide bond.
This polymer-supported catalyst afforded high selectiv-
ity (from 70 to 100% e.e.) and activity (from 70 to 100%
yield) with relatively low substrate/catalyst ratio
diphenylethylene
diamine
(DPEN)
with
a
6
substrate/catalyst ratio (S/C) as high as 2,400,000;
nevertheless, in most of the practical cases, such high
turnover numbers could not be reached. However,
(
ꢀ200) in the Ru-catalyzed hydrogen reduction of b-
7
industrial applications of BINAP and other chiral
ketoesters and functionalized olefins. Nevertheless,
attempts to re-use the catalyst led to lower selectivity
and activity. Noyori et al have shown that this ruthe-
11
*
Corresponding author. Tel.: 33-(0)4 72 43 14 07; fax: 33-(0)4 72 43
4 08; e-mail: marc.lemaire@univ-lyon1.fr
1
nium (R)-polymer supported catalyst in the presence of
0
957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00264-1

1
142
C. Saluzzo et al. / Tetrahedron: Asymmetry 13 (2002) 1141–1146
1
8
(
R,R)-1,2-diphenylethylene diamine was able to reduce
a five step synthesis) with diisocyanatotoluene. This
approach incorporated the chiral BINAP structure in
the polymer backbone as a result of the careful step by
step design of the material.
some ketones and particularly acetonaphthone under
H (8 atm) at 25°C in a mixture of i-PrOH/DMF (1/1)
with a substrate/catalyst ratio of 2470 with 99% e.e.
and 98% of conversion. The product e.e. remained
consistently high (97–98%), even after the 14th experi-
ment, but the catalytic activity gradually decreased
after the 10th experiment (total TON: 33000).
2
In order to obtain an insoluble, easily separable and
recyclable catalyst, we have studied several structural
parameters. The use of crosslinked polymer was shown
to give rise to an inefficient and non-selective catalytic
system. Therefore, the concept we have developed is the
use of polymer chain of molecular weight sufficiently
high to avoid solubilization but without crosslinking to
allow swelling and chain mobility. Low accessibility of
the catalytic site is obviously the main limitation of
heterogeneous supported catalysis, therefore we chose
to use low molecular weight non-crosslinked material.
Limitation of the molecular weight was obtained by
using non-polar poorly solubilizing solvent during the
polymerization. On the other hand and contrary to the
approach of Bayston, we have focused our efforts on
heterogeneization of BINAP with the conservation of a
pseudo-C - or C -symmetry. Urea and amide functional
groups are known as potential ligands for transition
metals and could interfere with the formation of the
active species. So the two types of linker were tested.
Various types (flexible or rigid) of spacer were also
evaluated. In addition well-defined BINAP derivatives
with high molecular weight and low solubility in
methanol were also synthesized. Their subsequent use
as Ru-ligands in the asymmetric heterogeneous cata-
lytic hydrogenation of methyl acetoacetate was
evaluated.
On the other hand, Pu et al. have prepared a poly(BI-
1
2
NAP), an optically active copolymer formed by poly-
merization of BINAP derivative with
,4-dibromo-2,5-dialkylbenzene. They used a rhodium
1
precursor and obtained >99% conversion with enan-
tiomeric excesses from 40 to 75% in the asymmetric
hydrogenation of dehydroamino acid derivatives (sub-
strate/catalyst ratio: 50). However, the reduction of
methylarylketones performed by means of poly-
(
BINAP) catalyst in the presence of (R,R)-1,2-
10
diphenylethylene diamine under H (200 psi) exhibited
good enantioselectivities from about 90% and conver-
sions up to 99%. The authors also obtained an optically
active poly(BINOL-BINAP) copolymer Ru-catalyst
which was involved in the asymmetric hydrogenation of
acetophenone with a conversion up to 99 and 84% e.e.
with BINAP unit to substrate ratio of 1/4900.
2
2
2
1
3
19
The second concept was improved by Chan et al. who
15
1
4
synthesized soluble chiral polyester and dendritic
BINAP derivatives as Ru-ligands in order to study the
hydrogenation of acrylic acid derivatives. Conversions
from 65 to 100% with a substrate/catalyst ratio of 200
and enantiomeric excess values from 88 to 95% were
obtained in the case of Ru-polyester supported catalyst.
For the Ru-dendrimer catalyst, with a substrate/cata-
lyst ratio of 125, total conversion and similar enan-
tiomeric excesses were observed.
2
. Results and discussion
The polyamide 2 (Scheme 2) was obtained with 60%
yield by polycondensation of (S)-diam-BINAP 1 with
terephthaloyl chloride in dimethylacetamide (DMA).
The polymer (S)-2 is soluble in aprotic solvents such as
DMF, DMSO, DMA, but insoluble in dichloro-
2
0
In 1999, we heterogenized BINAP by copolymerization
of diam-BINAP (6,6%-diaminomethyl-BINAP) 1
(
16,17
Scheme 1), (accessible starting from BINOL unit using
1
methane, methanol and toluene. H NMR spectroscopy
provides a means of evaluating the average degree of
polymerization (DP), which is about 20 in comparison
H N
2
with the integrals of the signals at 4.39 ppm (CH ) and
2
PPh2
PPh2
1
.22 ppm (CH3).
Ureas and polyureas were prepared by addition of
diam-BINAP with mono or diisocyanate in dichloro-
methane. Diureas 3 and 4 were obtained in 80 and 61%
yields, respectively, by addition of 2 equiv. of octa-
decylisocyanate or 2-naphthylisocyanate (Scheme 3).
H N
2
diam-BINAP (1)
Scheme 1.
Scheme 2.

C. Saluzzo et al. / Tetrahedron: Asymmetry 13 (2002) 1141–1146
1143
O
1
7 N
H
N
H
CH (CH ) NCO, CH Cl
2
3
2 17
2
PPh2
PPh2
H
N
H
N
H N
2
1
7
3
PPh2
PPh2
O
O
80%
H N
2
HN
HN
N
H
NCO
PPh2
PPh2
CH Cl
2
2
H
N
4
61%
O
Scheme 3.
For polyurea, the addition of diisocyanatohexane led to
expected polyurea 5 in 96% yield. Other less flexible
diisocyanates such as di(4-isocyanatophenyl)methane
and 2,6-diisocyanatotoluene were involved. They
afforded polymers 6 and 7a in 76 and 93% yield,
respectively (Scheme 4). The crosslinked polymer 7b
was prepared by addition of a 7:3 w/w mixture of di-
and tri-isocyanatotoluene in 84% yield.
A DP of about 15 for polymer 6 and of about 13–14 for
polymer 7 was determined in the same way as for
21
polymer 2. Attempts to use MALDI-TOF analysis
have failed, probably due to the poor solubility of such
polymers in the a-cyano hydroxycinnamic acid matrix.
In order to validate the NMR results, we performed gel
permeation chromatography analysis (GPC) for poly-
mer 7. An average molecular weight of 8400 g/mol and
Scheme 4.

1
144
C. Saluzzo et al. / Tetrahedron: Asymmetry 13 (2002) 1141–1146
6
a degree of polymerization of 10 were found although
the index of polydispersity was rather large (7.5). Nev-
ertheless, we can consider that the degree of polymer-
ization is quite similar to that obtained by NMR
spectroscopy.
Table 3. Diurea ruthenium cationic complexes ([RuCl(h -
benzene)L*]Cl)-catalyzed asymmetric hydrogenation of
methyl acetoacetate
Run Ligand
Use Conversion (%)a
E.e. (%)a
1
2
3
4
5
6
BINAPb
100
100
100
100
99
\99
\99
100
100
97
Unlike diurea 3, which is soluble in all organic solvents,
diurea 4 and polymers 5, 6 and 7 are insoluble in
dichloromethane, toluene and methanol, but soluble in
dipolar non-protic solvents such as dimethylformamide
or dimethylsulfoxide.
b,c
diam-BINAP
b
3
4
1st
2nd
3rd
54
33
a
Conversion and e.e. were determined by chiral GC analysis on a
The neutral ruthenium complexes of polyamide 2 and
ureas 3, 5, 6 and 7 and the cationic ruthenium com-
plexes of compounds 2, 3, 4, 5, 6 and 7 were synthe-
sized from the [Ru (benzene)] precursor according to
Lipodex A column.
Homogeneous catalysis.
S/C=2000.
b
c
2
2
2
2,23
the procedures presented by Noyori et al.
The cata-
lytic activities of these ruthenium complexes in the
hydrogenation of ethyl acetoacetate were tested in
methanol with a substrate/catalyst ratio of 1000
down sharply, probably due to leaching (run 2). We
then concentrated our efforts on diureas and polyureas
as ligands (Tables 2–4) using both neutral and cationic
complexes.
(
Scheme 5). The results are summarized in Tables 1–3.
Ruthenium complexes of 2, 4, 5, 6 and 7, insoluble in
methanol, have been used for heterogeneous reduction.
In contrast, the Ru-3 complex is soluble in methanol
and was used as a homogeneous catalyst.
For neutral ruthenium complexes (Table 2), the rigid
polymeric systems 6 and 7 are more efficient; leading to
1
00% conversion with 97 and 99% e.e., respectively
Our first attempts were realized with ruthenium
polyamide 2 neutral complex (Table 1), which led to
interesting results 100% conversion and 78% e.e. (run
(
runs 3 and 5) than diurea 3 or polymer 5 with a
flexible spacer chain showing conversions of less than
0, 48 and 88% e.e. (runs 1 and 2). For the best ligand
5
1
). Unfortunately, after removing the catalyst from the
(
6), we investigated its re-use and observed poor con-
reaction mixture and recycling it, the conversion fell
version with low e.e. (run 4).
It is noteworthy that in their first use ligands 6 and 7
gave similar results to BINAP (run 6).
Of the diurea ruthenium cationic complexes, (Table 3)
Ru-4 is the most active in heterogeneous conditions
leading to complete conversion and product with 100%
e.e. It has been shown to be as efficient as BINAP,
diam-BINAP or diurea 3 (runs 1, 2 and 3), in homoge-
neous conditions. Attempts to re-use catalyst Ru-4 were
performed after centrifugation and filtration in order to
remove the catalyst from the reaction mixture. During the
second use, the product e.e. remains high and the catalyst
Scheme 5.
Table 1. Ruthenium neutral complexes with polyamide
backbone (RuCl -2 DMF) )-catalyzed asymmetric hydro-
genation of methyl acetoacetate
2
n
Run
Ligand
Use
Conversion (%)a
E.e. (%)a
1
2
2
2
1st
2nd
100
4
78
99
a
Conversion and e.e. were determined by chiral GC analysis on a
Lipodex A column.
Table 4. Polyurea ruthenium cationic complexes
6
Table 2. Ruthenium neutral complexes (RuCl L*(DMF) )-
([RuCl(h -benzene)L*]Cl)-catalyzed asymmetric hydrogena-
2
n
catalyzed asymmetric hydrogenation of methyl acetoac-
tion of methyl acetoacetate
etate
Run
Ligand
Use
Conversion (%)a
E.e. (%)a
Run
Ligand
Use
Conversion (%)a
E.e. (%)a
1
2
3
4
5
6
7
8
5
1st
2nd
1st
2nd
1st
2nd
3rd
52
3
97
53
100
100
100
25
88
30
99
99
99
99
99
9
b
1
2
3
4
5
6
3
5
6
36
46
100
17
100
100
48
88
97
7
99
99
6
1st
2nd
7a
7a
BINAP
b
7b
a
Conversion and e.e. were determined by chiral GC analysis on a
Lipodex A column.
Homogeneous catalysis.
a
Conversion and e.e. were determined by chiral GC analysis on a
Lipodex A column.
b

C. Saluzzo et al. / Tetrahedron: Asymmetry 13 (2002) 1141–1146
1145
shows excellent activity, but for the third recycle, both
3. Experimental
the activity and enantioselectivity decrease. These last
results are probably due to partial solubilization of the
ruthenium complex in methanol.
3.1. General
All dried solvents used were of p.a. quality and are
commercially available from Acros. Acid chloride and
isocyanates were used without purification. Diam-
BINAP was prepared according to the literature
Of the polymeric ligands (Table 4) the most effective
are those formed with polymers 6 and 7a, which present
from 97% (run 3) to total conversion (run 5). Neverthe-
less, polymer 5 having a flexible spacer (run 1) is less
selective (88% e.e.) than ligands 6 and 7 (99% e.e., runs
16
procedure.
1
13
31
H, C and P NMR spectra were recorded on a
3
and 5). It is worth noting that for polyureas 5, 6 and
a, the more rigid the polymer, the better the conver-
1
13
Br u¨ ker AM 200 spectrometer ( H: 200 MHz, C: 50
7
31
MHz, P: 81 MHz) unless otherwise stated. Chemical
shifts (l) are reported in parts per million. Coupling
constants are reported in Hz, using TMS as external
standard. Uncorrected melting points were determined
on a Kofler apparatus. Polarimetric measurements were
performed on a Perkin–Elmer 241 instrument at room
temperature at 589 nm (concentration in g/100 mL
solution). Conversion and e.e. were determined by chi-
ral GC analysis on a Macherey–Nagel lipodex A
column (25 m×0.25 mm), using a Shimadzu GC-14A
apparatus equipped with a flame ionization detector
connected to a Shimadzu C-R6A integrator. MALDI-
TOF spectra have been performed on a Perkin–Elmer
sion and e.e. are (runs 1, 3 and 5).
The re-use of the catalysts was performed with the same
method as for the Ru-4 catalyst; for ligand 5, marked
decreases in conversion from 52 to 3% and also in
enantioselectivity from 88 to 30% (runs 1 and 2) were
observed during the second use. Concerning the re-use
of polymer 6 and 7a, no change in selectivity (runs 4, 6
and 7, respectively) was observed, but a drop in conver-
sion from 97 to 53% was noticed for 6 (runs 3 and 4).
There was no change in conversion observed for 7a.
Subsequent re-use of polymer 7a showed no drop in
either selectivity or activity after three runs. It is note-
worthy that diurea 4 (Table 3, runs 4 and 5) is almost
as efficient as polyurea 7a (Table 4, runs 6 and 7). In
contrast to polymer 7a, the crosslinked ligand 7b led to
poor results both in conversion and activity (run 8).
–
Voyager-DE STR apparatus, 20 kV, N laser: 2350
2
nm with an extraction delay of 250 ns. Matrix: a-cyano-
4
-hydroxycinnamic acid. GPC was carried out at the
RHODIA research center. Elemental analyses were car-
ried out by the CNRS (Service Central d’Analyse-
D e´ partement Analyse El e´ mentaire), Solaize, France.
Compared to neutral complexes, the corresponding
cationic complexes have been shown to give higher
conversion and e.e. For ligand 3, an important increase
of conversion from 36 to 100% and e.e. from 48 to up
to 99% has been observed (Tables 1 and 2, runs 3). For
ligand 6, the difference appeared only during the re-use.
With the neutral complex, a significant decrease in
conversion is observed (from 100 to 17%, Table 1, runs
3
3
.2. General procedures
.2.1. Synthesis of polyamide 2. Under argon, a solution
of
(S)-6,6%-diamino-2,2%-bis(diphenylphosphino)-1,1%-
binaphthyl (100 mg, 0.147 mmol) in dimethylacetamide
4 mL) was treated with terephthaloyl chloride (29.8
(
mg, 0.147 mmol). The mixture was stirred overnight at
room temperature and then isopropanol (1 mL) was
added dropwise. After 1 h of stirring, the solvent was
5
and 6) and for the cationic complex a smaller
decrease in conversion with no change in enantioselec-
tivity was observed (from 97 to 53% conversion, Table
removed leading to oligomer 2 (70 mg, 60%). [h] =
D
3, runs 3 and 4).
1
+
66.1 (c 1, DMF); H NMR (DMSO) (l): 1.22 (m,
CH ), 4.39 (m, CH ), 6.7–8.1 (m, CH). P { H} NMR
31
1
3
2
This paper demonstrates that chiral chain, non-
(DMSO) (l): −15.82 (s); mp >260°C.
crosslinked polymers such as polyurea 7a presenting
pseudo C -symmetry or diurea 4 with C -symmetry are
2
2
3.2.2. Synthesis of (S)-diam-BINAP dioctadecylurea 3.
Under argon, to a solution of 100 mg (0.147 mmol) of
suitable as catalytic ligands for the asymmetric hetero-
geneous catalytic hydrogenation of ethyl acetoacetate.
We have found that ruthenium cationic complexes are
generally more efficient than the corresponding neutral
(
S)-diam-BINAP (1) in dichloromethane (4 mL) was
added dropwise 0.087 mg (0.294 mmol) of octadecyliso-
cyanate. The solution was stirred overnight and the
resulting solid was filtered under argon and dried. 0.187
mg (0.145 mmol) of diurea 3 was obtained. Yield:
12,13
complexes. As previously described in the literature,
we have shown that the rigidity of the spacer is one of
the most influential factors upon the reaction. The less
flexible the ligand, the better the conversion and enan-
tioselectivity are. From a synthetic point of view, the
use of such a heterogeneous cationic ruthenium catalyst
in the reduction of CꢀO bonds is interesting because of
high conversions and enantioselectivities. Moreover,
they offer ready separation of the catalyst from the
reaction products by filtration and their re-use is also
effective, without loss either in conversion or
enantioselectivity.
100%; [h] =+62.0 (c 1, DMF).
D
1
3
H NMR (CDCl ) (l): 0.88 (t, JHH=6 Hz, 3H, CH3);
3
1.1–1.6 (m, 32H, CH ); 1.6–1.7 (m, 2H, CH ); 3.1–3.2
2
2
(m, 2H, CH ); 6.7–6.9 (m, 1H, CH); 7.0–7.3 (m, 11H,
2
3
CH); 7.40 (d, J =9 Hz, 1H, CH); 7.63 (s, 1H, CH);
HH
3
31
1
7.78 (d, JHH=9 Hz, 1H, CH); P { H} NMR(CDCl )
3
(l): −15.07 (s); mp 69°C; elemental analysis: calcd: C,
79.33; H, 8.88; N, 4.41; O, 2.52; P, 4.87. Found: C,
79.47; H, 8.95; N, 4.52; P, 4.61%.

1
146
C. Saluzzo et al. / Tetrahedron: Asymmetry 13 (2002) 1141–1146
3
.2.3. Synthesis of (S)-diam-BINAP-dinaphthylurea 4.
washing the catalyst with methanol, the reduction was
performed according the above procedure.
1
D 3
[
h] =+59.0 (c 1, DMF); H NMR (CDCl ) (l): 3.32 (s,
2
5
H); 4.3–4.5 (bs, NH); 6.9–7.8 (m, 14H); 7.8–8.2 (m,
3 31 1
H); 8.10 (d, JHH=4 Hz, 2H); 9.21 (s, 1H); P { H}
NMR(CDCl ) (l): −15.71 (s); elemental analysis: calcd:
C: 80.14, H: 5.14, N: 5.50, O: 3.14, P: 6.08. Found: C:
References
3
8
0.31, H: 5.23, N: 5.70, P: 5.75%.
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equiv. di- and tri-isocyanate for crosslinked 7b) was
added. The suspension was then stirred overnight and
isopropanol (1 mL) was added. After stirring the mixture
for 1 h, the solid was filtered under argon and washed
twice with isopropanol (2 mL) and twice with
dichloromethane (2 mL). The polyurea was dried under
vacuum.
1
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Polyurea 5: [h] =−87.0 (c 0.041, DMF); H NMR
D
(
DMSO-d ) (l): 1.0–1.3 (m, CH ); 3.2–3.7 (m, CH );
6
3
2
2
01–210.
3
1
1
4
.2–4.3 (m, CH, NH); 6.5–8.0 (m, CH); P { H} NMR
8
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(
DMSO-d ) (l): −15.75 (s); mp >260°C.
6
1
Polyurea 6: [h] =−91.0 (c 0.086, DMF); H NMR
D
1
1
0. Bayston, D. J.; Fraser, J. L.; Ashton, M. R.; Baxter, A. D.;
(
DMSO-d ) (l): 1.05(d, CH ); (s, CH ); 4.2–4.3 (m, CH ,
6 3 2 2
31 1
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1681–1685.
NH); 6.4–8.0 (m, CH); 8.51 (s, CH); P { H} NMR
DMSO-d ) (l): −15.71 (s); mp >260°C.
137–3140.
(
6
1
Polyurea 7a: [h] =−96.0 (c 0.345, DMF); H NMR
D
(
DMSO-d ), 1.21 (d, CH ); 2.04 (s, CH ); 4.3–4.4 (m,
CH2, NH); 6.66 (d, JHH=6.2, CH); 7–7.6 (m, CH);
.7–8.0 (m, CH). P { H} NMR (DMSO-d ), −15.75 (s);
6
3
3
3
3
1
1
1
3. Yu, H.-B.; Hu, Q.-S.; Pu, L. J. Am. Chem. Soc. 2000, 122,
500–6501.
7
6
6
mp >260°C.
1
4. Fan, Q.-H.; Ren, C.-Y.; Yeung, C.-H.; Hu, W.-H.; Chan,
A. S. C. J. Chem. Soc. 1999, 121, 7407–7408.
15. Fan, Q.-H.; Chen, Y.-M.; Chan, X.-M.; Jiang, D.-Z.; Xi,
1
Polyurea 7b: H NMR (DMSO-d ), 0.9–1.1 (CH ); 2.04
6
3
(
s, CH ); 4.3 (bs, NH); 4.6–4.7 (m, CH ); 6.5–8.1 (m, CH);
P { H} NMR (DMSO-d ), −15.02 (s); mp >260°C.
3
2
3
1
1
F.; Chan, A. C. S. Chem. Commun. 2000, 789–790.
6
1
6. Lemaire, M.; ter Halle, R.; Schulz, E.; Colasson, B.;
3
.4. Typical procedure for the preparation of the Ru
Spagnol, M.; (Rhodia/CNRS) French patent FR2789992,
1
8
19
neutral catalyst and Ru-cationic catalyst
1999, PCT: WO0049028, 2000.
1
7. ter Halle, R.; Colasson, B.; Schulz, E.; Spagnol, M.;
The polymer (0.006 mmol) and [RuCl (benzene)] (1.3
2
2
Lemaire, M. Tetrahedron Lett. 2000, 643–646.
mg, 0.003 mmol) were stirred at room temperature for 3
1
8. Lemaire, M.; ter Halle, R.; Schulz, E.; Colasson, B.;
Spagnol, M.; (Rhodia/CNRS) French patent FR 2790477,
Lemaire, M.; ter Halle, R.; Schulz, E.; Colasson, B.;
Spagnol, M.; Saluzzo, C.; Lamouille, T.; PCT WO
1
8
19
h in DMF (1 mL) or in ethanol/benzene (8/1). The
solvent was removed under reduced pressure to yield a
brown solid.
0
052081, 2000.
3
.5. Typical procedure for the reduction of methyl
1
9. Fache, F.; Schulz, E.; Tommasino, M. L.; Lemaire, M.
Chem. Rev. 2000, 100, 2159–2231 and references cited
therein.
acetoacetate
To a suspension of the catalyst in methanol (1.5 mL), the
substrate (5.8 mmol) was added and hydrogen intro-
duced into the autoclave to a pressure of 40 atm (S/C:
2
2
0. Gamez, P. Ph.D. Thesis, University Claude Bernard Lyon
1, 1995.
1. MALDI-TOF (matrix-assisted laser desorption ionization
time of flight): Barbacci, D. C.; Edmondson, R. D.;
Russell, D. H. Int. J. Mass Spectrom. Ion Process. 1987,
1
000). The mixture was rigorously stirred at 50°C for 18
h. After carefully venting the hydrogen, the sample was
centrifuged and the liquid phase was removed by syringe
to determine the activity and selectivity by GC.
165/166, 221–235 and references cited therein.
2
2. Kitamura, M.; Tokunaga, T.; Takaya, H.; Noyori, R.
In order to recycle the catalyst, the product solution was
separated from the catalyst by centrifugation then trans-
ferred via cannula or by filtration under argon. After
Tetrahedron Lett. 1991, 32, 4163–4166.
23. Mashima, K.; Kusano, K.; Ohta, T.; Noyori, R.; Takaya,
H. J. Chem. Soc., Chem. Commun. 1989, 1208–1210.