Angewandte
Chemie
DOI: 10.1002/anie.200801995
Asymmetric Catalysis
Enantioselective Hydrogenation with Racemic and Enantiopure Binap
in the Presence of a Chiral Ionic Liquid**
Dianjun Chen, Mike Schmitkamp, Giancarlo Franciò, Jürgen Klankermayer,* and
Walter Leitner*
There is growing interest in the use of chiral ionic liquids
[
1,2]
(
cILs)
in asymmetric catalysis as the reaction media or as
an additive. Whereas chiral solvents have shown limited
[
3,4]
success in enantioselective synthesis,
the use of cILs have
recently resulted in generating significant enantioselectivity
[
5,6]
[7]
in organocatalysis,
heterogeneous catalysis, and transi-
[
8,9]
tion-metal-catalyzed reactions.
As part of our interest in
this area, we investigated the Rh-catalyzed homogeneous
hydrogenation in amino-acid-derived cILs. Product enantio-
selectivities up to 69% ee were obtained by using rhodium
catalysts derived from tropoisomeric phosphine ligands in
[9]
combination with cILs as the only source of fixed chirality.
Herein we report for the first time that cILs can be used to
induce high levels of enantioselectivity when combined with
racemic catalysts; the product enantioselectivites obtained
are as high as those obtained with the corresponding
enantiomerically pure ligand. We provide experimental
evidence that the key role of the cIL is to effectively block
the catalytic cycle for one of the two enantiomers of the
Scheme 1. Homogeneous rhodium-catalyzed hydrogenation of bench-
mark substrates with binap-derived catalysts in the presence of a cIL
(
[MeProl][NTf ]).
2
The hydrogenation of S1 was carried out under a set of
standard reaction conditions employing a 5:1 mixture of
CH Cl and [MeProl][NTf ] as the reaction medium. By using
2
2
2
[
10]
catalyst (chiral poisoning ). In addition, the cIL can amplify
and even reverse the enantioselectivity of a given enantiopure
ligand in comparison to the reaction in organic solvents.
Binap (2,2’-bis(diphenylphosphanyl)-1,1’-binaphthyl) was
selected as a prototypical ligand as it has a broad range of
possible applications. The rhodium-catalyzed hydrogenation
of dimethyl itaconate (S1) and methyl N-acetamido acrylate
a rhodium catalyst, formed in situ from [Rh(acac)(cod)] (A;
acac = acetylacetonate, cod = 1,5-cyclooctadiene) and race-
mic binap, (S)-2-methyl-succinic acid dimethyl ester ((S)-P1)
was obtained quantitatively with an enantioselectivity of
67% ee (Table 1, entry 1). Almost the same enantioselectivity
was achieved with complex B as the rhodium source (Table 1,
entry 2). These results demonstrate that an identical level of
enantiodifferentiation can be achieved with the combination
(S2) were chosen as benchmark reactions (Scheme 1). Under
conventional conditions, enantiomerically pure (S)-binap
leads to only moderate enantioselectivities (P1: 67% ee,
of racemic binap and [MeProl][NTf ], compared to that
2
obtained with a single enantiomer of the chiral ligand.
In the case of substrate S1, the presence of the cIL does
not affect the principle mode of enantiodifferentiation of the
chiral ligand. This is demonstrated by the observation that the
use of enantiomerically pure (R)-binap leads to enantiose-
lectivities of 66–71% for (R)-P1 in the presence of [MeProl]-
[11]
[12]
(S); P2: 21–25% ee, (R) ) in these transformations, thus
providing a sensitive diagnostic tool for the effectiveness of
the cIL. The methyl ester of (S)-proline was used as the source
of chirality in the cIL ([MeProl][NTf ]), which has already
2
[
9]
proved successful in case of the tropoiosmeric ligands.
[
NTf ] (Table 1, entry 3 and 4). The use of (S)-binap results in
2
(S)-P1 having almost identical enantioselectivities of 64–70%
[
*] D. Chen, M. Schmitkamp, Dr. G. Franciò, Dr. J. Klankermayer,
Prof. Dr. W. Leitner
Table 1: Rhodium-catalyzed hydrogenation of dimethyl itaconate (S1) in
[
a]
the presence of [MeProl][NTf ] as the cIL.
2
Institut für Technische und Makromolekulare Chemie, RWTH
Aachen University
Entry
Ligand
[Rh]
ee [%]
Worringerweg 1, 52074 Aachen (Germany)
E-mail: jklankermayer@itmc.rwth-aachen.de
rac-binap
rac-binap
(R)-binap
(R)-binap
(S)-binap
(S)-binap
A
B
A
B
A
B
67 (S)
65 (S)
71 (R)
66 (R)
64 (S)
70 (S)
Prof. Dr. W. Leitner
Max-Planck-Institut für Kohlenforschung
Mülheim an der Ruhr (Germany)
[
**] We gratefully acknowledge the Deutsche Forschungsgemeinschaft
[a] Reaction conditions: [Rh]=0.01 mmol, binap/[Rh]=1:1, substrate/
[Rh]=300:1, p(H )=40 bar, [MeProl][NTf ] (0.2 mL), CH Cl (1 mL),
(
DFG-SPP1191) and the Fonds der Chemischen Industrie for
2
2
2
2
financial support, and Umicore for a generous gift of precious
metals. Binap=2,2’-bis(diphenylphosphanyl)-1,1’-binaphthyl.
16 h, RT; conversion and enantioselectivity determined by GC analysis
(Lipodex E); full conversion in all entries.
Angew. Chem. Int. Ed. 2008, 47, 7339 –7341
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7339