Propylene carbonate as a solvent for asymmetric hydrogenations

Article abstract of DOI:10.1002/anie.200700990

(Figure Presented) A penny saved is a penny earned: The use of propylene carbonate as the solvent in iridium-catalyzed hydrogenations of non-functionalized olefins allows efficient catalyst recycling through the formation of two-phase mixtures with nonpolar solvents such as n-hexane. In the picture, the hydrogenated tetrahydronaphthalene derivative is extracted into the hydrocarbon phase.

Full text of DOI:10.1002/anie.200700990

Angewandte
Chemie
DOI: 10.1002/anie.200700990
Asymmetric Catalysis
Propylene Carbonate as a Solvent for Asymmetric Hydrogenations**
Jerome Bayardon, Jens Holz, Benjamin Schäffner, Vasyl Andrushko, Sergej Verevkin,
Angelika Preetz, and Armin Börner*
Dedicated to Professor Rüdiger Selke
The correct choice of solvent is one of the central problems in
synthetic chemistry, for in many cases the physical and
toxicological properties of a solvent have a pivotal influence
on its use on both the laboratory and industrial scale.
Multiphase methods with immiscible solvents allow repeated
recycling of the catalyst in homogeneous catalysis.[1] Prom-
inent examples of this ecologically and economically sensible
approach include catalyzed reactions in multiphase systems
containing water,[2] fluorinated hydrocarbons,[3] supercritical
CO2,[4] and ionic liquids (ILs).[5]
For comparison the hydrogenations were carried out in
parallel in MeOH, THF, and CH2Cl2. The results for methyl
a-acetylaminocinnamate and dimethyl itaconate are listed in
Table 1 and Table 2. It is clear from these measurements that
PC is ideally suited for asymmetric hydrogenation, since
similar or even higher enantioselectivities are achieved with
comparable reactivity.[17]
Table 1: Rhodium-catalyzed asymmetric hydrogenation of methyl
a-acetylaminocinnamate with different phosphane ligands.[a]
Up to now organic cyclic carbonates, in particular
propylene carbonate (PC), have not played a role as solvents
for asymmetric hydrogenations. The few exceptions in
homogeneous catalysis include the platinum-catalyzed hydro-
silylation of unsaturated fatty acids investigated by Behr
et al.[6] and regioselective, rhodium-catalyzed hydroformyla-
tion in PC as solvent.[7] Reetzet al. were successful in
stabilizing palladium colloids with PC.[8]
Propylene carbonate is a dipolar aprotic solvent that has
previously found application mainly in extractions, electro-
chemistry, cosmetics, and medicine. In addition to its excellent
solvation properties, PC has valuable physical properties such
as low viscosity, and it is essentially odorless. Like other
organic carbonates PC is usually anhydrous, noncorrosive,
nontoxic, and biodegradable.[9] Based on these properties
organic carbonates offer a “safe” and environmentally
friendly alternative to standard solvents such as CH2Cl2 and
THF, as well as aromatic and toxic solvents.[10] Many alkyl
carbonates are available commercially.[11]
ee [%][b]
Ligand
PC
MeOH
THF
CH2Cl2
catASium M
Me-duphos
binap
tol-binap
josiphos
97
99
43
50
79
94
98
14
4
99
97
45
47
86
98
98
32
35
–
77
[a] Complexes of the type [Rh(cod)2]BF4 (L=ligand) were used as
catalysts; catASium M=2,3-bis[(2R,5R)-2,5-dimethylphospholanyl]ma-
leic acid anhydride, Me-duphos=1,2-bis[(2R,5R)-2,5-dimethylphospho-
lanyl]benzene, binap=(R)-2,2’-bis(diphenylphosphanyl)-1,1’-binaphthyl,
tol-binap=(R)-2,2’-bis(di-p-tolylphosphanyl)-1,1’-binaphthyl, josiphos=
(R)-1-[(S)-2-diphenylphosphanyl)ferrocenyl]ethyldicyclohexylphosphane.
Substrate/cat. 100:1, 7.5 mL solvent, p(H2)=1 bar (isobar), 258C.
[b] Determined by GC, 25 m g-cyclodextrin, lipodex E (Machery und
Nagel), silica, 1308C, complete conversion after 3 h.
Table 2: Rhodium-catalyzed asymmetric hydrogenation of dimethyl
itaconate with different phosphane ligands.[a]
In order to investigate the suitability of PC for asymmetric
hydrogenations, rhodium-catalyzed asymmetric hydrogena-
tions were initially carried out with a set of common olefins.
The commercially available diphosphanes catASiumM,[12]
Me-duphos,[13] binap,[14] tol-binap,[15] and josiphos[16] were
used as ligands. The precatalysts were prepared by reaction
of the ligands with [Rh(cod)2]BF4 in PC in situ (cod = 1,5-
cyclooctadiene).
ee [%][b]
Ligand
PC
MeOH
THF
CH2Cl2
catASiumM
Me-duphos
binap
tol-binap
josiphos
95
97
73
78
99
60
95
4
0
88
86
97
19
5
98
80
77
75
–
92
[a] Complexes of the type [Rh(cod)2]BF4 (L=ligand) were used as
catalysts; substrate/cat. 100:1, 7.5 mL solvent, p(H2)=1 bar (isobar),
258C. [b] Determined by GC, 25 m g-cyclodextrin, lipodex E (Machery
und Nagel), silica, 1308C, complete conversion after 3 h.
[*] Dr. J. Bayardon, Dr. J. Holz, Dipl.-Chem. B. Schäffner,
Dr. V. Andrushko, Priv.-Doz. Dr. S. Verevkin, Dipl.-Chem. A. Preetz,
Prof. Dr. A. Börner
Leibniz-Institut für Katalyse e.V.
Universität Rostock
Albert-Einstein-Strasse 29a, 18059 Rostock (Germany)
Fax: (+49)381-1281-5202
E-mail: armin.boerner@catalysis.de
Since PC is not miscible with nonpolar solvents, a two-
phase reaction would allow catalyst recycling. The require-
ment is that the catalyst is soluble in PC and the product is
more soluble in the nonpolar solvent than in PC. This is not
the case for the amino acid and dicarboxylate in Tables 1 and
2. In contrast, in the hydrogenation of nonfunctionalized
[**] We thank the Graduiertenkolleg 1213 of the DFG for financial
support.
Angew. Chem. Int. Ed. 2007, 46, 5971 –5974
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5971

Communications
Table 4: Iridium-catalyzed asymmetric hydrogenation of 5 in PC and
olefins, the alkanes formed are highly soluble in hexane.
CH2Cl2.[a]
Iridium complexes with the oxazoline phosphites 3 and 4 as
ligands were used as catalysts (Scheme 1);[18] these ligands are
known to be suitable for the hydrogenation of styrene
Lig.
Solv.
H2 [atm]
t [h]
Conv. [%][b]
6/7[b]
ee [%][c]
3
3
3
3
4
PC
CH2Cl2
PC
CH2Cl2
PC
50
50
1
1
50
4
3
20
3
4
8
4
4
3
100
100
85
7:93
8.3 (R)
25.7 (S)
3.5 (R)
0:100
62:38
50:50
13:87
4:96
5:95
3:97
0:100
63:37
71:29
85
28.6 (S)
81.3 (R)
82.1 (R)
82.1 (R)
82.4 (R)
16.9 (R)
73.2 (R)
46.3 (R)
100
100
100
100
100
74
4
4
4
4
4
PC
PC
CH2Cl2
PC
CH2Cl2
85
100
50
1
20
3
1
100
[a] Conditions: 0.4 mmol substrate, 0.004 mmol [Ir(cod)L]BArF , 2 or
4
8 mL LM, 258C. [b] Determined by NMR spectroscopy and GC on chiral
phase. [c] Determined by GC on chiral phase.
Scheme 1. Asymmetric hydrogenation of p-substituted a-ethylstyrene.
[19]
derivatives such as 1a–d based on the work of Pfaltzet al.
As can be seen from Table 3, similar enantioselectivity values
were obtained in PC, although reaction times were signifi-
cantly greater in PC than in CH2Cl2. Most results show the
known dependency of enantioselectivity on hydrogen pres-
sure.[19]
Scheme 2. Asymmetric hydrogenation of 1-methylene-1,2,3,4-tetrahy-
dronaphthalene (5).
Table 3: Iridium-catalyzed asymmetric hydrogenation of styrene deriva-
of the hydrogenation product 7 is usually higher for reactions
in CH2Cl2 than those in PC.
tives in PC and CH2Cl2.[a]
Substr. Solv.
H2 [atm]
[Ir(cod)(3)]BArF
[Ir(cod)(4)]BArF
4
4
Only very low enantioselectivities were obtained with the
t [h][b]
ee [%][c]
t [h][b]
ee [%][c]
use of [Ir(cod)(3)]BArF (BArF4 = B(C6H3(CF3)2)4); the best
4
1a
1a
1a
1a
1b
1b
1b
1b
1c
1c
1c
1c
1d
1d
1d
1d
PC
50
4
3
6
0.1
4
1
7
0.5
4
1
6
0.5
4
1
7
61 (S)
64 (S)
46 (S)
78 (S)
62 (S)
73 (S)[d]
47 (S)
88 (S)[d]
61 (S)
71 (S)[d]
54 (S)
90 (S)[d]
30 (S)
46 (S)[d]
5 (S)
4
3
4
0.1
4
2
2
0.5
4
2
2
0.5
4
2
6
76 (S)
52 (S)
83 (S)
86 (S)
78 (S)
56 (S)[d]
85 (S)
91 (S)[d]
74 (S)
58 (S)[d]
82 (S)
94 (S)[d]
74 (S)
54 (S)[d]
66 (S)
88 (S)[d]
value in CH2Cl2 was about 28.6% ee. For the hydrogenation
with iridium catalysts with the ligand 4 the results in PC were
significantly better than those in CH2Cl2 (increase by about
60% ee). Further improvement to 82.4% ee was obtained
with an increase in pressure.
To explain these differences, the isomerization of the
external olefin 5 to the internal olefin 6 was investigated
initially in the presence of the iridium catalyst but without
hydrogen atmosphere (Scheme 3). DFT calculations confirm
that 6 is significantly more stable than 5 with its exocyclic
double bond.[20] NMR spectroscopic investigations show that
the isomerization proceeds more slowly in PC than in
CH2Cl2.[21]
CH2Cl2 50
PC
CH2Cl2
PC
CH2Cl2 50
PC
CH2Cl2
PC
CH2Cl2 50
PC
CH2Cl2
PC
CH2Cl2 50
PC
CH2Cl2
1
1
50
1
1
50
1
1
50
1
1
0.5
59 (S)[d]
0.5
[a] Conditions: 0.4 mmol substrate, 0.004 mmol [Ir(cod)L]BArF4 , 2 or
8 mL solvent (Solv.), 258C. [b] Time for complete conversion. [c] Deter-
mined by GC or HPLC. [d] Data from Ref. [19].
In Table 4 the results of a detailed study of the hydro-
genation of 1-methylene-1,2,3,4-tetrahydronaphthalene (5;
Scheme 2) at different hydrogen pressures and temperatures
are compared with the results obtained in CH2Cl2. The chiral
product 7 is formed in this reaction as well as the isomerized
olefin 6 as an intermediate, which can also be hydrogenated.
The hydrogenation of 5 under normal pressure leads to a
mixture of 6 and 7 with conversions of 74–100%. The fraction
Scheme 3. Studies on the isomerization and hydrogenation of olefins.
5972
www.angewandte.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2007, 46, 5971 –5974

Angewandte
Chemie
By use of the same catalyst, products with opposite
configurations are obtained in the hydrogenation of 5 and 6.
The exocyclic olefin is almost exclusively stereoselectively
hydrogenated in PC. In contrast, the parallel hydrogenation
of 5 and 6 in CH2Cl2 leads to a mixture of R and S products
and thus to a lower enantioselectivity.[22]
obtained in standard solvents. The asymmetric hydrogenation
of nonfunctionalized olefins appears particularly interesting,
since then a nonpolar product is formed which can be
removed by extraction and the catalyst can be used repeat-
edly. Further asymmetric catalysis in PC and other organic
carbonates is currently under investigation.
The use of PC would be especially beneficial if the
separation of the expensive catalyst in a two-phase mixture
Received: March 6, 2007
Published online: July 3, 2007
were possible. The yellow iridium complex [Ir(cod)(4)]BArF
4
(Figure 1) is located exclusively in the PC phase.
Keywords: asymmetric catalysis · green chemistry ·
hydrogenations · iridium · solvent effects
.
[1] a) Chemistry in Alternative Reaction Media, Wiley, Chichester,
2004; b) Multiphase Homogeneous Catalysis (Eds.: B. Cornils,
W. A. Herrmann, I. T. Horvath, W. Leitner, S. Mecking, H.
Olivier-Bourbigou, D. Vogt), Wiley-VCH, Weinheim, 2005.
[2] Aqueous-Phase Organometallic Catalysis (Eds.: B. Cornils,
W. A. Herrmann), Wiley-VCH, 1998.
[3] “Fluorous Catalyst”: I. Horvath in Multiphase Homogeneous
Catalysis (Eds.: B. Cornils, W. A. Herrmann, I. T. Horvath, W.
Leitner, S. Mecking, H. Olivier-Bourbigou, D. Vogt), Wiley-
VCH, Weinheim, 2005, p. 339 – 404.
[4] “Catalysis Using Supercritical Solvents”: W. Leitner, A. M.
Scurto, C. M. Gordon, P. G. Jessop, D. J. Cole-Hamilton, T.
Kunene, P. B. Webb, K. Burgemeister, M. Poliakoff in Multi-
phase Homogeneous Catalysis (Eds.: B. Cornils, W. A. Herr-
mann, I. T. Horvath, W. Leitner, S. Mecking, H. Olivier-
Bourbigou, D. Vogt), Wiley-VCH, Weinheim, 2005, p. 605 – 750.
[5] Ionic Liquids in Synthesis (Eds.: P. Wasserscheid, T. Welton),
Wiley-VCH, Weinheim, 2003.
[6] a) A. Behr, F. Naendrup, D. Obst, Eur. J. Lipid Sci. Technol.
2002, 104, 161 – 166; b) A. Behr, N. Tosly, Chem. Eng. Technol.
2000, 23, 122 – 125; c) A. Behr, F. Naendrup, D. Obst, Adv. Synth.
Catal. 2002, 344, 1142 – 1145.
Figure 1. Two-phase system composed of n-hexane and PC with
[Ir(cod)(4)]BArF .
4
In a typical experiment olefin 5 was hydrogenated in PC
and the product was removed by extraction with n-hexane.
The catalyst can be used up to five times without significant
loss in enantioselectivity or an increase in the formation of
isomer 6 (Table 5), although an increase in reaction time was
[7] a) A. Behr, D. Obst, C. Schulte, T. Schosser, J. Mol. Catal. A
2003, 197, 115 – 126; b) A. Behr, D. Obst, B. Turkowski, J. Mol.
Catal. A 2005, 226, 215 – 219.
Table 5: Recycling experiments with the catalyst [Ir(cod)(4)]BArF and
4
olefin 5 as substrate in PC.[a]
[8] M. T. Reetz, G. Lohner, Chem. Commun. 1996, 1921 – 1922.
[9] Selected properties of PC: m.p. À488C; b.p. 2428C; vapor
pressure: 0.045 mm Hg at 258C; solubility in water:
175.00 mgLÀ1 at 258C; stable in water at pH 4, decomposition
begins at higher pH values and at higher temperatures; UV
stable; totally biodegradable; LC50 = 480 mgLÀ1 (fish, butylene
Cycle[b]
t [h]
Conv. [%]
6/7[c]
ee [%]
1
2
3
4
5
6
7
8
4
6
100
100
100
100
100
100
85
1.5:98.5
3:97
2:98
1.5:98.5
1.5:98.5
2:98
4.5:95.5
5:95
83.1 (R)
84.6 (R)
83.7 (R)
83.4 (R)
83.4 (R)
79.2 (R)
58.8 (R)
50.5 (R)
20
20
20
20
20
20
carbonate); EC50 = > 5000 mgkgÀ1 (invertebrates); EC50
=
> 929 mgkgÀ1 (aquatic plants); EC50 = > 5000 mgkgÀ1 (acute
toxicity, oral); EC50 = > 3000 mgkgÀ1 (acute toxicity, dermal); no
gentotoxicity; repeated administration to rats (male/female):
> 5000 mgkgÀ1 (oral); repeated administration to rats (male/
female): > 100 mgmÀ3 (inhalation.
63
[a] Conditions: 0.4 mmol substrate, 0.004 mmol [Ir(cod)(4)]BArF
p(H2)=85 bar, 2 mL LM, 258C. [b] The catalyst was reused after
liquid–liquid extraction with n-hexane. [c] Determined by NMR spectros-
copy and GC on chiral phase.
,
4
[10] BASF recently presented a study in which PC and cresol were
compared as solvents in the covering of copper wire from both
economic and ecological standpoints. For most of the properties
investigated PC was clearly superior. http://www.corporate.basf.
com/en/sustainability.
[11] For example, the Huntsman Corporation produces roughly
32000 t alkyl carbonates per annum by ring-opening of the
respective epoxide. http://www.huntsman.com.
[12] J. Holz, O. Zayas, H. Jiao, W. Baumann, A. Spannenberg, A.
Monsees, T. H. Riermeier, J. Almena, R. Kadyrov, A. Börner,
Chem. Eur. J. 2006, 12, 5001 – 5013.
[13] M. J. Burk, J. Am. Chem. Soc. 1991, 113, 8518 – 8519.
[14] A. Miyashita, A. Yasuda, H. Takaya, K. Toriumi, T. Ito, T.
Souchi, R. Noyori, J. Am. Chem. Soc. 1980, 102, 7932 – 7934.
observed. The iridium complex probably passes in part into
the hexane phase, which could explain the loss in reactivity on
repeated use. Modification of the ligand to improve catalyst
solubility in PC could be of help.
The results illustrate the considerable potential of PC in
asymmetric hydrogenation. In the reaction of functionalized
olefins, the results obtained are similar to or better than those
Angew. Chem. Int. Ed. 2007, 46, 5971 –5974
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5973

Communications
[15] K. Mashima, K. Kusano, N. Sato, Y. Matsumura, K. Nozaki, H.
foot, P. Schnider, A. Pfaltz, Angew. Chem. 1998, 110, 3047 – 3050;
Angew. Chem. Int. Ed. 1998, 37, 2897 – 2899.
[19] a) F. Menges, A. Pfaltz, Adv. Synth. Catal. 2002, 344, 40 – 44; b) S.
McIntyre, E. Hörmann, F. Menges, S. P. Smidt, A. Pfaltz, Adv.
Synth. Catal. 2005, 347, 2 – 3, 282 – 288.
Kumobayshi, N. Sayo, Y. Hori, T. Ishizaki, S. Akutagawa, H.
Takaya, J. Org. Chem. 1994, 59, 3064 – 3075.
[16] A. Togni, C. Breutel, A. Schnyder, F. Spindler, H. Landert, A.
Tijani, J. Am. Chem. Soc. 1994, 116, 4062 – 4066.
[17] Comparative measurements on the hydrogenation of cyclo-
octadiene– and norbornadiene–rhodium complexes provided
first indications that the catalytically active complex was formed
at about the same rate in PC as in other solvents; “Catalyst
Inhibition and Deactivation in Homogeneous Hydrogenation”:
D. Heller, A. H. M. de Vries, J. G. de Vries in Handbook of
Homogeneous Hydrogenation (Eds.: J. G. de Vries, C. J. Elsev-
ier), Wiley-VCH, Weinheim, 2007, chap. 44.
[18] a) S. Nanchen, A. Pfaltz, Chem. Eur. J. 2006, 12, 4550 – 4558;
b) C. Hedberg, K. Kallstrom, P. Brandt, L. K. Hansen, P. G.
Andersson, J. Am. Chem. Soc. 2006, 128, 2995 – 3001; c) X. Cui,
K. Burgess, Chem. Rev. 2005, 105, 3272 – 3296; d) S. P. Smidt, F.
Menges, A. Pfaltz, Org. Lett. 2004, 6, 2023 – 2026; e) A. Light-
[20] S. Verevkin, B. Schꢀffner, V. Andrushko, A. Börner, unpublished
results .
[21] To study the isomerization, samples of the substrate were stirred
under argon in the presence of the prehydrogenated precatalyst
and then analyzed: PC: 39% (10 min), 83% (1 h); CH2Cl2:
100% (10 min).
[22] Comparable isomerizations have been observed previously in
the ruthenium-catalyzed hydrogenation of geraniol: a) Y. Sun,
C. LeBlond, J. Wang, D. G. Blackmond, J. Am. Chem. Soc. 1995,
117, 12647 – 12648; b) Y. Sun, J. Wang, C. LeBlond, R. N.
Landau, J. Laquidona, J. R. Sowa Jr, D. G. Blackmond, J. Mol.
Catal. A 1997, 115, 495 – 502.
5974
www.angewandte.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2007, 46, 5971 –5974