Enantioselective hydrogenation catalyzed by highly active rhodium complexes of chiral phosphites with atropisomeric moieties

Article abstract of DOI:10.1016/S0957-4166(03)00131-9

Excellent ee's and extremely high activities are obtained in the rhodium-catalyzed hydrogenation of dimethyl itaconate using simple and readily available H₈-BINOL based monodentate phosphites. The hydrogenation proceeds efficiently even at a substrate concentration of 5.263 mol L^-1 and at a substrate to catalyst ratio (S/C) of 40,000 to give the product in 95.1% yield with up to 96.9% ee.

Full text of DOI:10.1016/S0957-4166(03)00131-9

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 1087–1090
Enantioselective hydrogenation catalyzed by highly active
rhodium complexes of chiral phosphites with atropisomeric
moieties
a
b
b
´
c
d
Ildik o´ Gergely, Csaba Heged u¨ s, Henrik Guly a´ s, Aron Sz o¨ llo3 sy, Axel Monsees,
d
a,
Thomas Riermeier and J o´ zsef Bakos *
a
Department of Organic Chemistry, University of Veszpr e´ m, H-8201 Veszpr e´ m, Hungary
Research Group for Petrochemistry, Hungarian Academy of Science, PO Box 158, H-8201 Veszpr e´ m, Hungary
b
c
Department of General and Analytical Chemistry, Technical University of Budapest, H-1521 Budapest, Hungary
d
Degussa AG, Projecthause Catalyse, Industriepark H o¨ chst, Building G830, D-65926 Frankfurt a. M., Germany
Received 20 December 2002; accepted 4 February 2003
Abstract—Excellent ee’s and extremely high activities are obtained in the rhodium-catalyzed hydrogenation of dimethyl itaconate
using simple and readily available H -BINOL based monodentate phosphites. The hydrogenation proceeds efficiently even at a
8
−
1
substrate concentration of 5.263 mol L and at a substrate to catalyst ratio (S/C) of 40,000 to give the product in 95.1% yield
with up to 96.9% ee. © 2003 Elsevier Science Ltd. All rights reserved.
Asymmetric catalytic hydrogenation is one of the most
efficient and convenient methods for preparing a wide
range of enantiomerically pure compounds. The precise
The novel ligands 4a and 4b were prepared by the
reaction of enantiomerically pure (S)-2-chloro-5,5%,
6,6%,7,7%,8,8% - octahydrodinaphtho[2,1 - d:1%,2% - f ][1,3,2]-
1
control of molecular chirality plays an increasingly
important role in chemistry, life science and materials
science. High activity, selectivity and stability, readily
accessible ligands and enzyme-like stereocontrol are
among the characteristic features of an ideal catalyst for
dioxaphosphepine based on (S)-H -BINOL (H -
8 8
BINOL=5,5%,6,6%,7,7%,8,8%-octahydro-1,1%-bi-2-naphthol)
8
with the corresponding alcohol. (S)-H -BINOL can be
8
readily derived from BINOL using the protocol of
9
Cram. For a comparative study, the (S)-BINOL (1,1%-
1
6
practical asymmetric synthesis.
bi-2-naphthol) based mono (3a, 3b) and chelating
diphosphite analogues ((2S,4S)-bis-(S)-5 and (2S,4S)-
2
10
With the reports of Horner and two Monsanto chemists,
bis-(S)-6) have also been synthesized.
3
Knowles and Sabacky, chiral monophosphanes began
The precatalysts were prepared in the usual way by the
to be used as chiral modifiers for asymmetric enantiose-
lective hydrogenation. However, shortly thereafter
reaction of phosphites with [Rh(cod) ]BF in CH Cl
2
4
2
2
4
5
(
ligand to Rh molar ratio is generally 2:1). NMR
Kagan’s group (DIOP) and Knowles et al. (DIPAMP)
demonstrated that in the hydrogenation reaction the
rhodium complexes of chelating diphosphanes (ee 90%)
are superior compared to the corresponding monophos-
spectroscopic analysis showed that complexes with two
coordinated ligands in cis positions were formed. The
1
1
conditions used for the hydrogenation are given in Table
12
1
.
phanes (ee=3–15%). In view of recent successes with
6
monodentate ligands and with H -BINOL based
8
7
To see if combining H -BINOL with chiral and achiral
ligands we decided to design new phosphites incorporat-
8
alcohols leads to efficient ligands, the two phosphites 4a,
ing these advantageous features. Herein, we report
monodentate phosphites as new ligands for the enan-
tioselective hydrogenation of itaconic acid dimethyl ester
4
b, prepared from racemic 1-phenylethanol and iso-
propanol, respectively, were tested in the Rh-catalyzed
hydrogenation of 1. Reetz and Mehler demonstrated that
the chiral binaphthyl unit of monodentate binaph-
tholphosphites (3a and 3b) determines the enantioselec-
(
Scheme 1) with exceptionally high activity.
6
tivity of the reduction, the configuration of the
*
Corresponding author. Tel.: 36-88-422022; fax: 36-88-427492;
e-mail: bakos@almos.vein.hu
stereogenic carbon of the sec-phenethyloxy residue of
0
957-4166/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00131-9

1
088
I. Gergely et al. / Tetrahedron: Asymmetry 14 (2003) 1087–1090
Scheme 1. Asymmetric catalytic hydrogenation. cod=cycloocta-1,5-diene, L*=chiral ligand.
a
Table 1. Enantioselective Rh-catalyzed hydrogenation of itaconic acid dimethyl ester 1
Entry
Ligand
Time (min)
p(H ) (bar)
P/Rh ratio
Eeb (%)
2
1
2
3
4
5
6
7
8
9
3a
3a
4a
4a
4a
3b
3b
4b
4b
4b
5
180
15
165
5
1
20
1
20
60
1
20
1
20
20
20
20
2
2
2
2
2
2
1.2
2
1
98.1 (S)
97.6 (S)
98.3 (S)
97.6 (S)
94.2 (S)
98.9 (S)
96.3 (S)
98.7 (S)
96.2 (S)
96.9 (S)
59.7 (R)
88.5 (R)
4
135
20
120
15
15
30
10
1
1
1
0
1
2
2
2.2
2.2
6
a
Reaction conditions: solvent CH Cl ; 23°C; c (substrate)=0.467 mol L−1; S/C=1000; catalyst preparation see text; 100% conversion was
2 2
observed.
b
The enantiomeric excess of the product was determined by GC analysis of the distilled product (Hewlett–Packard HP 4890 gas chromatograph,
split/splitless injector, b-DEX 225, 30 m, internal diameter 0.25 mm, film thickness 0.25 mm, carrier gas: 100 kPa nitrogen, FID detector; the
retention times of the enantiomers are 33.3 min (S), 36.9 min (R)). Absolute configuration was determined by comparison with the known sign
of specific rotation.
3
a does not play any role, we therefore chose to use
tivity of the reaction, but a profound effect on the
reaction rate. The ee’s of 98.1–98.9% (entries 1, 3, 6,
racemic alcohols. Under otherwise identical condi-
tions, both catalytic systems give excellent ee values.
and 8) were obtained at 1 bar of H , but the values
2
The H -BINOL-based catalysts have higher catalytic
activity than the BINOL-based systems. Hydrogen
pressure had only a slight effect on the enantioselec-
decrease to 97.6% (compound 3a), 97.6% (compound
4a), 96.3% (compound 3b), 96.9% (compound 4b) at
20 bar.
8

I. Gergely et al. / Tetrahedron: Asymmetry 14 (2003) 1087–1090
1089
−
1
Table 2. Enantioselective Rh-catalyzed hydrogenation of
strate concentrations of 4.166 and 5.263 mol L to give
the product in 94.9 and 95.1% conversions, respectively,
with up to 96.9% ee.
a
itaconic acid dimethyl ester 1 at low catalyst loading
Entry
Ligand
S/C
Conv. (%)
Ee (%)
The effectiveness of these catalysts is manifested by the
high turnover frequencies (TOF). For example, with a
substrate:catalyst ratio of 40,000:1 a turnover frequency
1
2
3
4
5
6
4a
4a
4a
4b
4b
4b
10,000
20,000
40,000
10,000
20,000
40,000
100
97.7 (S)
98.5 (S)
95.9 (S)
96.8 (S)
96.2 (S)
95.5 (S)
91.9
58.9
98.2
98.2
72.9
(
calculated for the whole reaction) of higher than
100,000 h was obtained (Table 3, entry 3). Finally, 4b
−1
in solvent free conditions at a substrate:catalyst ratio
(
S/C) of 20,000 catalyzes the hydrogenation of itaconic
a
Reaction conditions: solvent CH Cl ; 23°C; p(H )=20 bar, P/Rh
ratio is 2, c (substrate)=0.467 mol L ; reaction time is 15 min; for
other experimental conditions, see footnotes to Table 1.
2
2
−
2
acid dimethyl ester under 20 bar of H and 23°C to
afford the hydrogenated product in 95.4 ee and 91%
conversion.
2
1
It was reported that Ir(I)- and Ru(II)-complexes of
An interesting point to note is that high selectivity for
the (S)-product might be favored by conditions in
which the system is starved of hydrogen, and hence
working in a diffusion limited system could be
H -BINAP served as more effective catalyst precursors
8
for the asymmetric hydrogenation of some substrates
1
5
than did the analogous complexes of BINAP. Fur-
thermore, the Pd(II) complex of (R,S)-H -BINAPHOS
8
1
3
is
a
more active catalyst compared to (R,S)-
beneficial.
BINAPHOS in the copolymerization of propene with
16
carbon monoxide. The dihedral angles in these struc-
When 6, a partially hydrogenated analogue of 5 was
used as a bisphosphite ligand for the catalyst precursor,
the enantioselectivity was distinctly higher with 6 than
with 5 (Table 1, entries 11 and 12). The lower enan-
tiomeric purities and inverse (R) configuration of the
product induced by bidentate ligands demonstrate that
the mono- and diphosphite systems differ considerably.
tures suggest that ligands having an H -BINOL-based
8
backbone possess quite different axial flexibility, how-
ever, in our case the seven-membered dioxaphosphepine
ring hinders this flexibility. Unfortunately, suitable
crystals of the free ligands or their rhodium complexes
for X-ray analysis could not be obtained.
In conclusion, our catalytic system provides attractive
features: (i) the chemicals are cheap and easily avail-
able; (ii) unusually high activity is maintained when the
amount of catalyst is reduced; (iii) the reaction is
environmentally benign and energy-saving because of
the high substrate concentration or solvent free condi-
tions; and (iv) exceptionally low catalyst loading (0.1–
While most of the hydrogenation reactions are per-
formed in the presence of 1 mol% of catalyst, use of 4a
and 4b allows hydrogenation to be carried out at low
catalyst loading (0.005 mol%) without observing a neg-
ative effect on the yield and selectivity (Table 2). Partic-
ularly noteworthy is that, 4a and 4b with
a
substrate:rhodium ratio of 20,000, still afford almost
complete conversions (91.9 and 98.2%) and 98.5 and
0
.0025 mol%) is sufficient to achieve high yield and
enantiomeric purity of the product. We anticipate that
this catalyst system will find use in an extensive array of
applications.
96.2% ee, respectively, in 15 min under 20 bar pressure.
For practical synthesis, a solvent free system is the ideal
process in terms of productivity, reaction volume and
1
4
environmental safety. However, asymmetric catalytic
processes are usually highly sensitive to both solvent
and substrate concentration effects. Our previous
findings prompted us to further optimize our catalytic
system by decreasing the amount of solvent, i.e. by
increasing the concentration of the substrate (Table 3).
The hydrogenation proceeded efficiently even at sub-
Acknowledgements
Support from Hungarian National Science Foundation
(OTKA T 032 004) is gratefully acknowledged. We
´
thank Mr. B e´ la Edes for skilful assistance in the syn-
thetic and catalytic experiments.
Table 3. Enantioselective Rh-catalyzed hydrogenation of itaconic acid dimethyl ester 1 with low catalyst loading and with
a
high concentration of substrate
Entry
Ligand
S/C
c (S) (mol L−1)
Time (min)
Conv. (%)
Ee (%)
1
2
3
4
4b
4b
4b
4b
20,000
20,000
40,000
80,000
0.877
4.166
5.263
6.060
20
20
20
60
100
96.5 (S)
96.0 (S)
96.9 (S)
83.1 (S)
94.9
95.1
20.9
a
Reaction conditions: solvent CH Cl ; 23°C; p(H )=20 bar, P/Rh ratio is 2; for other experimental conditions, see footnotes to Table 1.
2
2
2

1
090
I. Gergely et al. / Tetrahedron: Asymmetry 14 (2003) 1087–1090
overlapped), 28.23 (s, CH ), 29.60 (s, 2 CH overlapped),
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31
2
2
2
1
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phosphite 4b (3.8 mg, 0.01 mmol) with [Rh(cod) ]BF4
2
(
2.0 mg, 0.005 mmol) in CH Cl (10 mL) under argon.
2 2
The solution was stirred for 15 min and then the sub-
strate (0.7 mL, 5 mmol) was added. The mixture was
transferred into the autoclave under an argon atmo-
sphere. The autoclave was pressurized with H and then
2
8
shaken at a frequency of 180/min, 75° from the upright
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31
1
ture of two diastereomers): P{ H} NMR (202.45 MHz,
1
CDCl ): l 139.30 (s), 143.10 (s). H NMR (500.13 MHz,
3
1
1
3
CDCl ): l 1.62 (m, 4H; CH ), 1.64 (d, J(H,H)=6.3 Hz,
3
2
3
3 3
3
H; CH ), 1.65 (d, J(H,H)=6.3 Hz, 3H; CH ), 1.83 (m,
1
2H; CH ), 2.34 (m, 4H; CH ), 2.71 (m, 4H; CH ), 2.86
2
2
2
3
(
m, 8H; CH ), 5.37 (m, 2H; CH), 6.37 (d, J(H,H)=8.1
2
3
Hz, 1H; aromatic proton), 6.76 (d, J(H,H)=8.1 Hz, 1H;
aromatic proton), 6.95 (d, J(H,H)=8.1 Hz, 1H; aro-
matic proton), 7.01 (d, J(H,H)=8.1 Hz, 1H; aromatic
proton), 7.05 (d, J(H,H)=6.9 Hz, 1H; aromatic proton),
3
3
3
3
7
.06 (d, J(H,H)=6.9 Hz, 1H; aromatic proton), 7.12 (d,
3
J(H,H)=8.1 Hz, 2H; aromatic protons), 7.25–7.45 (m,
13
1
1
0H; Ph-protons). C{ H} NMR (125.75 MHz, CDCl ):
3
3318–3319.
l 22.91 (s, 2 CH overlapped), 22.99 (s, CH ), 23.02 (s,
2
2
1
6. (a) Nozaki, K.; Yasutomi, M.; Nakamoto, K.; Hiyama,
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CH ), 23.09 (s, 2 CH overlapped), 23.18 (s, CH ), 23.20
2
2
2
3
2 3
(
s, CH ), 25.44 (d, J(P,C)=3.6 Hz, CH ), 26.13 (d,
3
J(P,C)=3.6 Hz, CH ), 28.17 (s, CH ), 28.20 (s, CH
2
3
2