Acceleration of enantioselective hydrogenation of olefins over Pd/C by cinchonidine as a chiral modifier. Comparison with cinchonine, pseudoenantiomer

Article abstract of DOI:10.1246/cl.2010.232

The performance of cinchonidine (CD) and cinchonine (CN) as chiral modifiers in enantioselective hydrogenation over Pd/C were compared in different concentrations. The catalytic hydrogenation with CD always occurred in better ee and at faster rate than that with CN. The difference is not attributable to the adsorption properties of the modifiers, but to the intrinsic enantio differentiation that accompanies the reaction acceleration.

Full text of DOI:10.1246/cl.2010.232

doi:10.1246/cl.2010.232
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32
Published on the web February 6, 2010
Acceleration of Enantioselective Hydrogenation of Olefins over Pd/C by Cinchonidine
as a Chiral Modifier. Comparison with Cinchonine, Pseudoenantiomer
Takashi Sugimura* and Hiroyuki Ogawa
Graduate School of Material Science, University of Hyogo, 3-2-1 Kohto, Kamigori, Ako-gun, Hyogo 678-1297
(
Received November 27, 2009; CL-091058; E-mail: sugimura@sci.u-hyogo.ac.jp)
The performance of cinchonidine (CD) and cinchonine (CN)
type, N.E. Chemcat) is pretreated at 353 K under H , and then
2
as chiral modifiers in enantioselective hydrogenation over Pd/C
were compared in different concentrations. The catalytic hydro-
genation with CD always occurred in better ee and at faster rate
than that with CN. The difference is not attributable to the
adsorption properties of the modifiers, but to the intrinsic enantio
differentiation that accompanies the reaction acceleration.
mixed with CD (20 ¯mol) in dioxane containing 2.5% water at
296 K. With this modified catalyst, PCA (0.5 mmol) in the
6
solvent (10 mL) is fully converted to the saturated acid within 2­
3 h under atmospheric hydrogen. The CN modification was
performed just by replacing CD with CN. The catalytic activity
was estimated by the hydrogen consumption at around 25%
conversion and the stereoselectivity was evaluated by product
enantiomer excess (ee) determined by chiral HPLC.
Cinchonidine (CD) and cinchonine (CN) are enantiomeric at
the 8 and 9 positions, but have the same configurations at the 3
and 4 positions (Figure 1). They are popular in asymmetric
syntheses as chiral ligands or chiral organocatalysts, and usually
give antipodes of the product since the 3-vinyl group does not
The difference between CD and CN was investigated by
systematically changing solvent, temperature, Pd support, and
pressure. The ee values with CD varied, but the ee with CN was
always lower than CD to give the ee ratio in a range of 1.5­2.1.
The CD-modified catalysts are more active than the correspond-
1
11
play a major role during the chiral recognition of the substrate.
ing CN-modified catalysts (see Supporting Information ).
Both CD and CN could be also used for chiral surface
modification of supported metal catalysts,2 and asymmetric
catalyses have been developed with Pt, Rh, Ru, Ir, and Pd
catalysts. When the modified Pd catalyst is used for the
Selected results are given in Table 1. The results indicated that
the optimized conditions with CD were also suitable for the
reaction with CN, suggesting a common stereocontrol mecha-
nism among the modifiers.
3
hydrogenation of phenylcinnamic acid (PCA), CD gives higher
Important phenomena were observed in the modifier-
concentration dependence. The ee values obtained with the
product ee than CN, while CN provides better selectivity in the
4
¹5
¹2
¹3
hydrogenation of substituted ¡-pyrones. Although the CD/CN-
modifier in a concentration from 10 to 10 mol dm are
given in Figure 2a. The observed initial rates are converted to
modified Pd catalysts have been intensively studied from a
variety of viewpoints, no systematic study comparing CD and
CN has been reported. Comparison of these chiral modifiers in
hydrogenation of PCA revealed an acceleration effect by the
7
the relative rates standardized by the unmodified catalysis, and
are given in Figure 2b. The ee profiles for the modified reactions
8
with CD and CN are very similar, largely constant above
5
modifier (ligand-acceleration effect) as an apparent and essen-
0.5 mM, while decreasing below 0.5 mM maintaining a differ-
ence of 26­29% until the ee induced by CN reaches zero. The
ee decrease occurring at the same concentration of modifier
suggests that the adsorption constants governing concentration
of the ee saturation are comparable with each other. The main
factor governing the ee difference between the two modifiers
tial difference between the two modifiers.
The optimized procedure for the hydrogenation of PCA with
CD modifier is as follows. A commercial 5% Pd/C (23 mg, STD
COOH
must be the intrinsic stereocontrollability of the adsorbed
+
H2
¹4
modifier. However, the ee at the low concentration (<10
)
are not proportional indicating that the difference is not simply
due to the intrinsic stereocontrollability, but CD has an extra
advantage under insufficient surface modification.
PCA
H
H
N
N
H
3
8
Table 1. Enantiomer excess (%ee) of the product and initial hydro-
HO
HO
4
¹1 ¹1
Pd/C
genation rate (r /mmol g
h )
Pd/C
9
0
H
CD
CN
Entry
Conditions
%ee
r0
%ee
r0
N
N
Optimized for CDa
5% Pd/Al2O3
1% Pd/C
1
2
3
4
5
82.6
72.7
61.7
52.9
74.4
90.2
51.4
102
73
23
51
19
53.9
33.9
30.7
36.8
48.4
72.8
24.0
45
31
11
45
13
27
72
cinchonidine (CD)
cinchonine (CN)
COOH
COOH
in MeOH
in MeOH at 273 K
b
6
7
DMPCA
MCA
51
108
c
a
The hydrogenation of PCA was carried out with 5% Pd/C in dioxane
b
Figure 1. Configurations of cinchona alkaloids and the hydrogenation
using Pd/C modified with them.
containing 2.5% water at 296 K. Substrate: p,p¤-dimethoxylphenyl-
cinnamic acid. Substrate: methylcinnamic acid.
c
Chem. Lett. 2010, 39, 232­233
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

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33
(
a)
the reaction conditions, and the catalytic activity of the chiral
modified area is the same. Line B is drawn under the same
assumption except for the catalytic activity, which is 2 times
faster with CD than with CN. The experimental results
reasonably fit the latter presumption.
In this report, the acceleration effect by the modifier was
observed for the first time in the Pd-catalyzed reactions. The
acceleration effectively maintains ee when chiral surface
modification is incomplete and the nonenantioselective hydro-
genation over the unmodified surface competes. Since both the
intrinsic stereocontrollability and the activity of the chiral
modified area are better with CD than with CN, the CD
modification results in better ee than CN irrespective of the
catalysis conditions. It is concluded that the difference between
CD and CN is not due to the adsorption properties, but due to the
intrinsic stereocontrollability and the acceleration effect, both of
which originate from the interaction between the modifier and
substrate.
2
mM
(
b)
11
This work was supported by Grant-in-Aid for Scientific
Research on Priority Areas (No. 20037058, “Chemistry of
Concerto Catalysis”) from MEXT, Japan.
0
.1 mM 0.3 mM
References and Notes
1
Chiral Reagents for Asymmetric Synthesis, ed. by L. A. Paquette,
Wiley, Chichester, 2003.
(
c)
2
D. Y. Murzin, P. Mäki-Arvela, E. Toukoniitty, T. Salmi, Catal.
Rev. 2005, 47, 175; E. Klabunovskii, G. V. Smith, A. Zsigmond,
.
.
Line A = 1/2 ee(CD) − 1/2 ee(CN)
.
Line B = 2/3 ee(CD) − 1/3ee(CN)
Heterogeneous
Enantioselective
Hydrogenation,
Springer,
Dordrecht, 2006, Chapters 4 and 5; M. Heitbaum, F. Glorius, I.
Escher, Angew. Chem., Int. Ed. 2006, 45, 4732; T. Mallat, E.
Orglmeister, A. Baiker, Chem. Rev. 2007, 107, 4863; T. Sugimura, in
Handbook of Asymmetric Heterogeneous Catalysis, ed. by K. Ding,
Y. Uozumi, Wiley-VCH, Verlagsgesellschaft, 2008.
3
J. R. G. Perez, J. Malthête, J. Jacques, C. R. Acad. Sci. Paris, Ser. II
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Huck, T. Bürgi, T. Mallat, A. Baiker, J. Catal. 2003, 219, 41; N. J.
Colston, R. P. K. Wells, P. B. Wells, G. J. Hutchings, Catal. Lett.
Figure 2. Hydrogenation of PCA over Pd/C modified with different
concentration of CD or CN. (a) Product ee after 100% conversion.
2005, 103, 117; G. Szöllösi, B. Hermán, F. Fülöp, M. Bartók, React.
Kinet. Catal. Lett. 2006, 88, 391.
W.-R. Huck, T. Mallat, A. Baiker, Catal. Lett. 2002, 80, 87; W.-R.
Huck, T. Mallat, A. Baiker, Catal. Lett. 2003, 87, 241.
The ligand acceleration is known in the CD-modified Pt-catalyzed
hydrogenation of ketones. M. Garland, H.-U. Blaser, J. Am. Chem.
Soc. 1990, 112, 7048; H.-U. Blaser, H.-P. Jalett, M. Garland, M.
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Misaki, T. Okuyama, J. Catal. 2009, 262, 57.
(
b) Hydrogenation rate at ca. 25% conversion given as the relative rate (%)
4
5
standardized by the rate with the unmodified catalyst. (c) Observed and
expected ee with the CD/CN comodified catalyst.
Activity of the Pd catalyst for hydrogenation is known to be
suppressed by CD-modification.8 As expected, hydrogenations
are slower at the standard or higher modifier concentrations
,9
6
7
(
²2 mM), where the degree of suppression is smaller with CD
The initial rate observed without the modification process was
than CN. Since the adsorption constants of CD and CN should
be similar to each other, the rate difference is attributable to the
difference in kinetic effects of the chiral modifier. In this
context, the rate ratio of the chiral modified specific area should
be CD/CN = 2.1­2.4. It should be noted that the rates modified
with CD at 0.1­0.3 mM are even faster than the unmodified
catalysis. The observed rate increment is ca. 30%, and this is the
first observation of the acceleration by the CD-modification of
Pd catalyst. The rate acceleration should originate from the
substrate interaction with the modifier.10
The observed properties were confirmed with a comodified
catalyst prepared with a 1/1 mixture of CD and CN. Figure 2c
shows the ee dependency on the total modifier concentration.
Dotted line A is an expected curve using the data in Figure 2a
assuming that CD and CN modified the Pd surface evenly under
¹
1
¹1
¹1 ¹1
190 mmol g
h
. However, we adopted 140 mmol g
h , which
was obtained for the catalyst after the modification process with no
modifier (30 min at 296 K under H2).
¹3
¹3
8
The ee decrease around 10 mol dm was also observed with 5%
Pd/TiO2 and 40% Pd/TiO2. Y. Nitta, K. Kobiro, Chem. Lett. 1996,
897; T. Kubota, H. Kubota, T. Kubota, E. Moriyasu, T. Uchida, Y.
Nitta, T. Sugimura, Y. Okamoto, Catal. Lett. 2009, 129, 387.
T. Tarnai, A. Tungler, T. Máthé, J. Petró, R. A. Sheldon, G. Tóth, J.
Mol. Catal. A: Chem. 1995, 102, 41.
9
1
0 The rate acceleration should occur with other substrates, but the
appearances largely depend on their adsorption properties. For
example, DMPCA is known to show smaller deceleration effect
by the CD modification (Ref. 6), and the rate with 2 mM CD
¹1 ¹1
(
51 mmol g
under the present definition (26 mmol g
1 Supporting Information is available electronically on the CSJ-
h ) is already faster than the unmodified catalysis
¹1 ¹1
h
).
1
Journal Web site, http://www.csj.jp/journals/chem-lett/index.html.
Chem. Lett. 2010, 39, 232­233
© 2010 The Chemical Society of Japan www.csj.jp/journals/chem-lett/