Solvent dependent asymmetric hydrogenation with self-assembled catalysts: A combined catalytic, NMR- and IR-study

Article abstract of DOI:10.1039/b820730e

For the first time the hydrogen bond based structure of self-aggregated Rh-phosphine complexes in fluorinated alcohols was directly determined, which gives a rationale for the high enantioselectivity observed in the asymmetric hydrogenation.

Full text of DOI:10.1039/b820730e

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Solvent dependent asymmetric hydrogenation with self-assembled
catalysts: a combined catalytic, NMR- and IR-studyw
Ivan A. Shuklov,a Natalia V. Dubrovina,*b Enrico Barsch,ac Ralf Ludwig,ac Dirk Michalika
ab
¨
and Armin Borner*
Received (in Cambridge, UK) 19th November 2008, Accepted 8th January 2009
First published as an Advance Article on the web 26th January 2009
DOI: 10.1039/b820730e
For the first time the hydrogen bond based structure of
self-aggregated Rh–phosphine complexes in fluorinated alcohols
was directly determined, which gives a rationale for the high
enantioselectivity observed in the asymmetric hydrogenation.
based chelating structure of the ligands, where one phosphorus
atom is connected to a 2-pyridinol unit and the other is part of a
2-pyridone backbone. In order to support this indirect evidence,
herein we will report on a combined catalytic and spectroscopic
study, including IR-investigations, which will give unambiguous
proof for the chelating nature of ligands in these catalysts.7
We have chosen phospholane 1 and phosphepine 2, previously
described,5d as ligands for the Rh-catalyzed asymmetric hydro-
genation capable of self-assembly. Precatalysts were prepared by
reaction of [Rh(COD)2]BF4 (COD = 1,5-cyclooctadiene) with
two equivalents of ligand. The hydrogenations were conducted in
methanol, CH2Cl2 or trifluoroethanol or mixtures thereof
under isobaric (1 bar) conditions. Results of the catalytic
transformation using the benchmark substrates methyl
Z-a-N-acetamidocinnamate (3a) and dimethyl itaconate (3b)
are detailed in Table 1. In general ee-values obtained with the
bulky phosphepine ligand 2 are higher than those induced
with phospholane 1. Highest enantioselectivity of 99% was
observed with dimethyl itaconate as substrate in CH2Cl2
(run 21). As clearly shown irrespective of the ligand used in
methanol low ee-values were yielded (runs 1, 7, 13 and 16).
Moreover, long reaction times were required to achieve com-
plete conversion. In contrast, in CH2Cl2 high activities and
ee-values are noted (runs 3, 9 and 21). Similarly superior
ee-values and very fast reactions were measured in pure
CF3CH2OH (runs 2, 8, 14, 17). Interestingly also in mixtures
of fluorinated alcohol and methanol the catalysts displayed
The effect of monodentate versus bidentate phosphorus ligands
in metal-catalyzed asymmetric hydrogenation is a matter of
controversial discussions in the literature.1 In general chelating
ligands are reputed to display higher stereodiscriminating pro-
perties. However, catalysts bearing bulky monodentate ligands
have also been shown as highly stereoselective.2 Unfortunately,
the comparison of ligands differing strongly in steric and/or
electronic properties does not really contribute to the final
clarification of this issue. Some more clarity can be expected
from the comparison of similar ligands under similar reaction
conditions. In this connection we are interested in the solvent
dependent structure of self-assembling catalysts.3,4 Due to their
particular construction originally monodentate phosphorus
ligands are able to aggregate through hydrogen bonds in the
coordination sphere of a metal and thus ‘‘pseudo’’-chelating
ligands are formed.5 Clearly, the formation of the desired self-
assembling architecture is dependent on the solvent.5d,f Polar
solvents with strong hydrogen bonding accepting properties
should interrupt the formation of the weak intramolecular
interactions, whereas nonpolar solvents have a stabilizing effect.
In a recent study on the enantioselective hydrogenation with
cationic Rh-complexes based on chiral 2-pyridone-phosphino
ligands we noted high enantioselectivity in CH2Cl2 as solvent.5d
In contrast, in methanol the catalysts induced poor ee-values. In
general slow conversion took place. Superior effects on activity
and stereoselectivity were found in 2,2,2-trifluoroethanol
(TFE), 2-fluoroethanol and 1,1,1,3,3,3-hexafluoro-2-propanol
(HFIP)6a illustrating the unique features of fluorinated
alcohols, in particular high polarity, but low hydrogen bond
acceptor properties.6 31P-NMR spectroscopic investigations
showed two resonances in the nonpolar solvent and in fluori-
nated alcohols, indicating the presence of two different phos-
phorus nuclei. This feature gave us a hint for the hydrogen bond
high activity and enantioselectivity. Even
a ratio of
CH3OH–CF3CH2OH 1 : 1 was sufficient to maintain the
beneficial effect of the fluorinated alcohol (ee up to 94%,
runs 11, 19). Further dilution with methanol led to a lowering
of the enantioselectivity (runs 4, 10, 15, 18). It is worthy of note
that the addition of CF3CH2OH to CH2Cl2 accelerated the
reaction, but did not affect the high enantioselectivity (run 22).
Our hypothesis was that in CH2Cl2 and in the fluorinated
alcohol, hydrogen bonds within the catalyst generate a
‘‘pseudo’’-chelating structure, whereas in methanol this architec-
ture is destroyed. Due to the similar catalytic results the hydrogen
bonding assembly should be maintained also in mixtures of
CF3CH2OH–CH3OH. In order to confirm this assumption, a
sample of the precatalyst [Rh(COD)(1)2]BF4 dissolved in mixtures
of CF3CD2OD and CD3OD was investigated by 31P{1H}-NMR
spectroscopy.
a Leibniz-Institut fur Katalyse an der Universitat Rostock e.V.,
A.-Einstein-Str., 29a, 18059 Rostock, Germany.
¨
¨
E-mail: armin.boerner@catalysis.de; Fax: +49 (0)381 1281 5202
b Institut fur Chemie der Universitat Rostock, A.-Einstein-Str. 3a,
18059 Rostock, Germany. E-mail: natalia.dubrovina@uni-rostock.de
¨
¨
Indeed, the spectra in CF3CD2OD–CD3OD mixtures
showed a similar signal pattern characterized by a doublet of
c Institut fur Chemie der Universitat Rostock, Dr.-Lorenz-Weg 1,
¨
18059 Rostock, Germany
¨
5d
doublets as found in CDCl3 and pure CF3CD2OD6a [d 52.0
w Electronic supplementary information (ESI) available: Details on the
IR investigations and ab initio calculations. See DOI: 10.1039/b820730e
(dd, J(31P–103Rh) = 147 Hz, J(31P–31P) = 36 Hz) and d 50.4
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Table 1 Results of the enantioselective hydrogenation in different solvents
Run
Ligand
Substrate
Solvent
Conversion (%)
t/minÀ1
ee (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
1a
1a
1a
1a
1a
1a
2b
2b
2b
2b
2b
2b
1a
1a
1a
2b
2b
2b
2b
2b
2b
2b
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3b
3b
3b
3b
3b
3b
3b
3b
3b
CH3OH
CF3CH2OH
CH2Cl2
CH3OH–CF3CH2OH (3 : 1)
CH3OH–CF3CH2OH (1 : 1)
CH3OH–CF3CH2OH (1 : 3)
CH3OH
CF3CH2OH
CH2Cl2
CH3OH–CF3CH2OH (3 : 1)
CH3OH–CF3CH2OH (1 : 1)
CH3OH–CF3CH2OH (1 : 3)
CH3OH
20
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
100
1300e
1200e
1200e
1300
1300
1300
60e
13 (R)c,e
68 (R)c,e
69 (R)c,e
49 (R)c
57 (R)c
63 (R)c
64 (R)c,e
95 (R)c,e
94 (R)c,e
87 (R)c
94 (R)c
95 (R)c
racd,e
10e
10e
10
10
10
1300e
1300e
1300
60e
CF3CH2OH
68 (S)d,e
31 (S)d
64 (S)d,e
97 (S)d,e
78 (S)d
94 (S)d
96 (S)d
99 (S)d,e
98 (S)d
CH3OH–CF3CH2OH (3 : 1)
CH3OH
CF3CH2OH
CH3OH–CF3CH2OH (3 : 1)
CH3OH–CF3CH2OH (1 : 1)
CH3OH–CF3CH2OH (1 : 3)
CH2Cl2
10e
60
15
10
20e
12
CH2Cl2–CF3CH2OH (1 : 1)
a
b
c
Substrate–catalyst = 50 : 1, 7.5 ml solvent. Substrate–catalyst = 100 : 1, 7.5 ml solvent. Determined by GC, 25 m g-cyclodextrin, Lipodex E
d
e
(Machery and Nagel), fused silica, 130 1C. Determined by GC, 25 m g-cyclodextrin, Lipodex E (Machery and Nagel), fused silica, 70 1C. Values
derived from ref. 5d.
(J(31P–103Rh) = 140 Hz, J(31P–31P) = 36 Hz], indicating that
the chelating species is still present, but the amount is reduced
depending on the concentration of methanol (Fig. 1).
In order to get information on the hydrogen bonds
IR-investigations were performed. For comparison the tauto-
meric model system 2-hydroxypyridine–2-pyridone (5a,b) was
also studied.7 The measured IR-spectra together with the
relevant calculated spectrum are shown in Fig. 2.
Ab initio calculations at the B3LYP level8 on the model
system 5a,b reveal that only the pyridine form 5a contributes
to the CO-stretching vibration nCO whereas the tautomeric
Fig. 2 IR-spectra of the free ligand 1 and [Rh(COD)(1)2]BF4 in
CH2Cl2 at 25 1C. The dotted line gives the B3LYP 6-31+G*
calculated IR-spectrum for the tautomeric equilibrium 5a–b for
comparison.
pyridinol (5b) gives large contributions at slightly different
wavenumbers to nring
. By inspection of the measured
IR-spectrum of the free ligand 1 in CH2Cl2 it can be therefore
concluded that the pyridone structure of IB (Scheme 1) is the
dominant species. When the complex [Rh(COD)(1)2]BF4 is
formed, both tautomers of the ligand are present in solution
(Scheme 1, IIA). This can be concluded from the reduced
Fig. 1 31P{1H}-NMR (202.4 MHz) spectrum of [Rh(COD)(1)2]BF4 in
mixtures of CF3CD2OD–CD3OD at 0 1C. (a) CF3CD2OD–CD3OD =
1 : 3; (b) CF3CD2OD–CD3OD = 1 : 1; (c) CF3CD2OD–CD3OD = 3 : 1,
(d) CF3CD2OD.
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on this result the usually assumed bis-pyridone structure of the
Rh-complex in methanol has to be revised.
The Rh-complex in mixtures of MeOH–TFE is dominated
by the self-assembled structure of complex IIA, which is typical
for the pure TFE solution. This fact gives an explanation
why the high enantioselectivities observed in the asymmetric
hydrogenation remains approximately constant in solvent
mixtures.
Scheme
1 Self-assembly of two monodentate 6-phosphino-2-
In summary, the asymmetric hydrogenation of model sub-
strates in mixtures of trifluoroethanol and methanol as solvent
was investigated. The results of the catalytic reaction, of IR- and
NMR-investigations as well as of chemical calculations show
that a self-assembling hydrogen bond based architecture exists.
This ‘‘pseudo’’-chelate is apparently responsible for the superior
catalytic activities in nonpolar solvents and fluorinated alcohols.
Moreover, our results show that the amount of the precious
fluorinated alcohol, necessary for the achievement of high rates
and enantioselectivities, can easily be halved without losing the
advantageous self-assembling properties of the catalyst.
We are grateful to Dr H. Jendralla (Sanofi Aventis)
for helpful discussions. We thank Dr C. Fischer and
Mrs S. Buchholz for the analysis of the chiral hydrogenation
products. We deeply appreciate financial support from the
pyridone ligands with rhodium in dependence on the solvent.
intensity of the band of nCO and the broadening of the band
for nring. Also the increasing band at 1455 cmÀ1 is due to the
presence of the pyridinol form.
Because of the strong solvent absorption from 1500 cmÀ1
down to lower wavenumbers it was not possible to examine
the same spectral range for the alcoholic solutions. Therefore
it is advantageous to focus on nCO and the ring mode nring
around 1590 cmÀ1. The free ligand 1 exists in both tautomeric
forms IB in methanol as well as in TFE (Fig. 3, Scheme 1). In
TFE in comparison with methanol nCO is shifted to lower
wavenumbers. This observation illustrates the excellent
hydrogen bond donor properties of this solvent. When the
Rh-complex is formed in TFE nCO is shifted to nearly the same
wavenumber as in CH2Cl2 (Fig. 3), which is in agreement with
results of the 31P-NMR study and the hydrogenation and
therefore a proof for a comparable structure. Because TFE
molecules are poor hydrogen bond acceptors, they do not
disturb the self-assembly of the catalyst.
Leibniz-Gemeinschaft (Pakt fur Innovation und Forschung).
¨
Notes and references
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¨
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2 C. Bruneau and J.-L. Renaud, Monophosphines with Chiral
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Fig.
3 IR-spectra of the free ligand and the Rh-complex in
CF3CH2OH (TFE) and CH3OH, respectively, to the right. IR-spectra
of the Rh-complex in CF3CH2OH (TFE), CH3OH and their mixtures
to the left.
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Chem. Commun., 2009, 1535–1537 | 1537