Ionic liquid-phase asymmetric catalytic hydrogenation: Hydrogen concentration effects on enantioselectivity

Article abstract of DOI:10.1016/S0957-4166(01)00341-X

Molecular hydrogen is almost four times more soluble in the ionic liquid 1-n-butyl-3-methylimidazolium tetrafluoroborate (BMI·BF₄) than in its hexafluorophosphate (BMI·PF₆) analogue at the same pressure. The Henry coefficient solubility constant for the solution BMI·BF₄/H₂ is K = 3.0 × 10^-3 mol L^-1 atm^-1 and 8.8 × 10^-4 mol L^-1 atm^-1 for BMI·PF₆/H₂, at room temperature. The asymmetric hydrogenation of (Z)-α-acetamido cinnamic acid and kinetic resolution of (±)-methyl-3-hydroxy-2-methylenebutanoate by (-)-1,2-bis((2R,5R)-2,5-diethylphospholano)benzene(cyclooctadiene)rhodium(I) trifluoromethanesulfonate and ichloro[(S)-(-)-2,2′-bis(di-p-tolylphosphino)-1,1′- binaphthyl]ruthenium(II) complexes immobilised in BMI·PF₆ and BMI·BF₄ were investigated. Remarkable effects in the conversion and enantioselectivity of these reactions were observed as a function of molecular hydrogen concentration in the ionic phase rather than pressure in the gas phase.

Full text of DOI:10.1016/S0957-4166(01)00341-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 1825–1828
Ionic liquid-phase asymmetric catalytic hydrogenation: hydrogen
concentration effects on enantioselectivity
Alexsandro Berger, Roberto F. de Souza, Marcelo R. Delgado and Jairton Dupont*
Laboratory of Molecular Catalysis, Institute of Chemistry, UFRGS, Av. Bento Gon c¸ alves,
9500 Porto Alegre 91501-970 RS, Brazil
Received 19 March 2001; accepted 23 July 2001
Abstract—Molecular hydrogen is almost four times more soluble in the ionic liquid 1-n-butyl-3-methylimidazolium tetra-
fluoroborate (BMI·BF ) than in its hexafluorophosphate (BMI·PF ) analogue at the same pressure. The Henry coefficient
4
6
−
3
−1
−1
−4
−1
−1
solubility constant for the solution BMI·BF /H is K=3.0×10 mol L atm and 8.8×10 mol L atm for BMI·PF /H , at
4
2
6
2
room temperature. The asymmetric hydrogenation of (Z)-a-acetamido cinnamic acid and kinetic resolution of (±)-methyl-3-
hydroxy-2-methylenebutanoate by (−)-1,2-bis((2R,5R)-2,5-diethylphospholano)benzene(cyclooctadiene)rhodium(I) trifluoro-
methanesulfonate and dichloro[(S)-(−)-2,2%-bis(di-p-tolylphosphino)-1,1%-binaphthyl]ruthenium(II) complexes immobilised in
BMI·PF and BMI·BF were investigated. Remarkable effects in the conversion and enantioselectivity of these reactions were
6
4
observed as a function of molecular hydrogen concentration in the ionic phase rather than pressure in the gas phase. © 2001
Elsevier Science Ltd. All rights reserved.
1
. Introduction
neous asymmetric hydrogenations the solution concen-
tration of hydrogen, rather than the pressure in the
gas phase, is the kinetic variable that must be consid-
ered when evaluating the enantioselectivity data
obtained under different gas–liquid mass transfer con-
Molten salts based on the 1-alkyl-3-methylimidazolium
cation exhibit a relatively wide electrochemically stable
window, a broad range of room temperature liquid
compositions, negligible vapour pressure, and excellent
chemical and thermal stabilities. These materials have
been used as the mobile phase in organometallic
biphasic catalytic reactions ranging from Ziegler–
Natta-type processes to hydroformylations.
ever, in only a few cases, asymmetric organometallic
catalytic reactions have been carried out in ionic liq-
10
ditions.
Herein, we report our results for the determination of
the solubilities of molecular hydrogen in these imida-
zolium ionic liquids and the influence of the hydrogen
concentration over the asymmetric hydrogenation of
1
–3
How-
(
Z)-a-acetamido cinnamic acid as well as the asym-
4
–9
metric kinetic resolution of (±)-methyl-3-hydroxy-2-
methylenebutanoate by Rh(I)- and Ru(II)-catalyst
uids.
tion processes.
hydrogenation of atropic acid by Ru-BINAP
BINAP=2,2%-bis(diphenylphosphino)-1,1%-binaphthyl)
These studies essentially comprise hydrogena-
4,5,9
In this respect, it was found that the
precursors immobilised in BMI·PF and BMI·BF4
6
11
ionic liquids.
(
complex immobilised in 1-n-butyl-3-methylimida-
zolium tetrafluoroborate (BMI·BF4) furnishes 5e.e.
essentially independent of the hydrogen-pressure. In
contrast, in the reduction of tiglic acid by the same
catalyst dissolved in 1-n-butyl-3-methylimidazolium
2. Results and discussion
2
.1. Hydrogen solubility in 1-n-butyl-3-methylimida-
zolium ionic liquids
hexafluorophosphate (BMI·PF ) ionic liquid, the e.e. is
6
9
hydrogen-pressure dependent. These apparently confl-
icting results are probably related to a different hydro-
gen solubility in the two ionic liquids. Moreover, it is
well known that in various homogenous and heteroge-
The gas–liquid mass transfer coefficients and molecu-
lar hydrogen solubilities in the ionic liquids have been
determined using a known procedure (see Section 4).
12
The Henry coefficient solubility constant for the solu-
−
3
−1
−1
tion BMI·BF /H is K=3.0×10 mol L atm and
4
2
−1
−
4
−1
*
0
Corresponding author.
8.8×10 mol L atm for BMI·PF /H , at room tem-
6 2
957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00341-X

1
826
A. Berger et al. / Tetrahedron: Asymmetry 12 (2001) 1825–1828
perature. Thus, the hydrogen solubility in these ionic
liquids at different pressures can easily be determined,
assuming ideal-gas behaviour, by the Henry equation:
BMI·PF6 as compared to the other two liquids
(BMI·BF and iso-propanol) indicates that at 50 atm
4
pressure there is not sufficient hydrogen in the ionic
phase. Indeed, hydrogenation reactions performed at
higher hydrogen pressures (100 atm) gave e.e. values
similar to those observed in iso-propanol. These results
demonstrate that the hydrogen concentration in solu-
tion determines the enantioselectivity in this system.
−
1
M=K×P, where M is the gas solubility in mol L , K
−
1
−1
the Henry constant in mol L atm and P is the gas
partial pressure in atm. The K values indicate that
molecular hydrogen is almost four times more soluble
in BMI·BF than in BMI·PF under the same pressure.
4
6
It is important to note that recovered ionic catalyst
solutions could be re-used for further hydrogenations
maintained the enantioselectivity, but after the fourth
recycle a significant drop in the conversion was
observed (from 73 to 35%). This loss of efficiency
results from catalyst leaching from the ionic phase to
the product/iso-propanol solution as verified by atomic
absorption analysis.
2
.2. Hydrogen pressure effects in Rh-catalysed asym-
metric hydrogenation
The effect of the hydrogen concentration in the liquid
phase was investigated in the asymmetric reduction of
(
Z)-a-acetamido cinnamic acid catalysed by (−)-1,2-
bis((2R,5R)-2,5-diethylphospholano)benzene(cycloocta-
diene)rhodium(I) trifluoromethanesulfonate dissolved
in iso-propanol, BMI·BF and BMI·PF (Scheme 1 and
4
6
Table 1).
2.3. Kinetic resolution catalysed by Ru-(tolyl-BINAP)
It is apparent that the conversion increases when the
solubility of molecular hydrogen increases in the liquid
phase (Table 1). This is most probably related to the
availability of the hydrogen at the catalyst site. The
relatively lower enantioselectivity in the case of
We also tested the influence of hydrogen pressure by
investigating the kinetic resolution of (±)-methyl-3-
hydroxy-2-methylenebutanoate by [RuCl
binap] ·NEt /BMI·BF -catalysed hydrogenation under
-(S)-tolyl-
2
2
3
4
various reaction conditions (Scheme 2 and Table 2).
The best kinetic resolution was obtained at a reaction
pressure of 40 atm where the unreacted substrate was
recovered in 29% yield with 98% e.e. (entry 6, Table 2).
Note that under homogeneous conditions, but at 50
atm, the yield and e.e of recovered substrate are of the
same order of the magnitude as those observed in ionic
liquid media, (Table 2, entry 9). Moreover, the sense of
the diastereoselection was the same for the reactions
performed either in methanol or in ionic liquid.
The degree of enantiomer differentiation (k /k ) is con-
f
s
siderably influenced by hydrogen pressure. Higher k /ks
f
values were obtained up to 40 atm hydrogen pressures
(
entries 1–6, Table 2). A significant drop was observed
Scheme 1.
at higher pressure (entries 7 and 8). This trend is
Table 1. The asymmetric hydrogenation of (Z)-a-acetamido cinnamic acid: the effect of hydrogen concentration in the liquid
a
phase on the conversion and the enantioselectivity
Entry
Catalyst phase
P (atm)
Sol. H2 (mol L−1)
Conversion (%)
E.e.b (%)
−
−
−
−
3
2
1
1
1
2
3
4
5
BMI·PF6
BMI·PF6
BMI·PF6
5
50
100
50
4.4×10
4.4×10
8.9×10
1.5×10
7
26
41
73
99
66
81
90
93
94
BMI·BF
4
i
c
PrOH
50
129.3
a
Reactions performed at room temperature, 24 h, 950 rpm, 3 mL of the ionic liquid and 9 mL of iso-propanol, substrate/[Rh]=100.
b
c
Determined by chiral GC.
13
Calculated from the data reported by Frolich.
Scheme 2.

A. Berger et al. / Tetrahedron: Asymmetry 12 (2001) 1825–1828
1827
Table 2. Kinetic resolution of methyl-3-hydroxy-2-methylenebutanoate by Ru(tol-BINAP)/BMI·BF catalysed asymmetric
4
a
hydrogenation
Entry
P (atm)
Sol. H2 (mol L−1)
Time (min)
(%) recovery
E.e. (%)b
kf/ksc
−
−
−
−
−
−
−
−
2
2
2
2
1
1
1
1
1
2
3
4
5
6
7
8
20
20
30
30
40
40
50
50
50
4
6.0×10
6.0×10
9.0×10
9.0×10
1.2×10
1.2×10
1.5×10
1.5×10
30
145
30
145
30
145
30
145
150
660
53
47
43
39
36
29
31
27
37
24
59
75
83
87
91
98
85
89
97
99
9
11
11
10
10
10
6
5
14
16
d
e
9
144.2
0d
11.54
e
1
a
The reactions were carried out with 0.5 mL (4.1 mmol) of the substrate in 3 mL of the ionic liquid and 5 mL of iso-propanol at room
temperature.
b
c
E.e. of the unreacted substrate determined by GC.
14
k /k (enantiomeric selection) calculated by Kagan’s equation.
f
s
d
e
15
In ‘homogeneous’ conditions (methanol).
Calculated from the data reported by Frolich.
13
consistent with other enantio-face discriminating
homogenous hydrogenations where high e.e.s were
obtained at lower pressures.
FID detector; H was the carrier (2.3 mL/min); the
temperature program was: 30°C (40 min) to 70°C (10
min) at a heating rate of 4°C/min. The products of
2
1
6
(
Z)-a-acetamido cinnamic acid were analysed using a
Chirasil-Val III column 25 m long, id 0.32 mm, H was
2
the carrier (2.0 mL/min); the temperature program was:
3. Conclusions
9
0°C (20 min) to 110°C (30 min) at a heating rate of
°C/min.
4
In summary, our results show that classical homoge-
neous Rh(I)- and Ru(II)-catalysed asymmetric hydro-
genations can be transposed to liquid–liquid two-phase
systems using imidazolium based ionic liquids as the
mobile phase. It is evident that the hydrogen concentra-
tion in the ionic phase rather than the hydrogen pres-
sure in the gas phase, is the important kinetic
parameter to be considered when comparing studies
performed under different gas–liquid mass transfer con-
ditions. This is particularly true for the 1-n-butyl-3-
methylimidazolium ionic liquids, where the hydrogen
solubility is almost four times larger in the hydrophilic
1
1
The ionic liquids were prepared as described earlier
and all other reagents were obtained from commercial
sources (Strem or Aldrich).
4
.2. Catalytic hydrogenation
−
3
The [RuCl -(S)-tolyl-binap] ·NEt (6.8×10 mmol) or
Rh(cod)(2R,5R)-EtDuphos]CF SO (1.22×10 mmol)
catalyst precursors were dissolved in dichloromethane
2–3 mL) and then added to the ionic liquid (3 mL).
After 15–30 min under agitation the volatiles were
2
2
3
−
2
[
3 3
(
tetrafluoroborate (BMI·BF ) than in the hydrophobic
4
−
3
removed under reduced pressure (10 atm) at room
temperature until the residue had constant weight. The
ionic liquid catalyst solution was charged in the reactor
and then a solution of the substrates ((±)-methyl-3-
hydroxy-2-methylenebutanoate 4.1 mmol, or (Z)-a-
acetamido cinnamic acid, 1.2 mmol) in iso-propanol (5
and 9 mL, respectively) were added and the reactor was
pressurised with molecular hydrogen.
hexafluorophosphate (BMI·PF ) analogue, under the
same pressure.
6
4. Experimental
4.1. General
All manipulations have been performed under dry,
oxygen-free argon using standard techniques. All sol-
vents were dried and distilled under argon prior to use.
Hydrogenation reactions were carried out in a Parr 50
mL reactor with agitation speeds of 900–990 rpm and
at room temperature. The hydrogen pressure was mea-
sured with electronic flow mass controller at 1 Hz. The
kinetic resolution reaction product was analysed by gas
chromatography on a Varian 3400 chromatograph
equipped with a Beta Dex 120 column 30 m long, id
4.3. Gas–liquid mass transfer coefficients
Gas–liquid mass transfer coefficients and hydrogen sol-
ubilities in the ionic liquids were measured using a
12
known procedure. The ionic liquid (10 mL) was
charged to the reactor and degassed, and the reactor
was pressurised and isolated under hydrogen (20–50
atm). Agitation (990 rpm) was then initiated and pres-
sure drop in the reactor was measured at the rate of 1
Hz, until constant pressure. The data was treated
10,12
0.25 mm and 0.25 mm film thickness, equipped with a
according to established methods.

1
828
A. Berger et al. / Tetrahedron: Asymmetry 12 (2001) 1825–1828
8. Comyns, C.; Karodia, N.; Zeler, S.; Andersen, J.-A.
Acknowledgements
Catal. Lett. 2000, 67, 113.
9
. Brown, R. A.; Pollet, P.; McKonn, E.; Eckert, C. A.;
Liotta, C. L.; Jessop, P. G. J. Am. Chem. Soc. 2001, 123,
We thank the FAPERGS and the CNPq for partial
financial support and CAPES for a fellowship (A.B.).
1254.
1
0. Sun, Y.; Landau, R. N.; Wang, J.; LeBlond, C.; Black-
mond, D. G. J. Am. Chem. Soc. 1996, 118, 1348 and
references cited therein.
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