Electronic and steric effects of ligands as control elements for rhodium-catalyzed asymmetric hydrogenation

Article abstract of DOI:10.1016/j.tetlet.2003.09.217

Electronic and steric effects in the rhodium diphosphinite catalyzed asymmetric hydrogenation were investigated. A series of electronically and sterically modified (S)-BINOL and (S)-H₈-BINOL ligands was synthesized and effects on the catalytic

Full text of DOI:10.1016/j.tetlet.2003.09.217

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 9025–9028
Electronic and steric effects of ligands as control elements for
rhodium-catalyzed asymmetric hydrogenation
a
b
Ildiko´ Gergely, Csaba Hegedu¨s, Aron Szo¨llo3
sy,c Axel Monsees,d Thomas Riermeierd and
´
Jo´zsef Bakosa,*
aDepartment of Organic Chemistry, University of Veszpre´m, H-8201 Veszpre´m, PO Box 158, Hungary
bResearch Group for Petrochemistry, Hungarian Academy of Sciences, H-8201 Veszpre´m, PO Box 158, Hungary
cDepartment of General and Analytical Chemistry, Technical University of Budapest, H-1521 Budapest, Hungary
dDegussa AG, Projecthause Catalyse, Industriepark Ho¨chst, Building G830, D-65926 Frankfurt a. M., Germany
Received 28 August 2003; revised 29 September 2003; accepted 29 September 2003
Abstract—Electronic and steric effects in the rhodium diphosphinite catalyzed asymmetric hydrogenation were investigated. A
series of electronically and sterically modified (S)-BINOL and (S)-H8-BINOL ligands was synthesized and effects on the catalytic
performance were studied. Phosphinite basicity was varied by using p-CH3O, p-CH3, p-H, p-CF3, 3,5-(CH3)2, 3,5-(CF3)2
substituents on the diphenylphosphine moieties. In the hydrogenation of dimethyl itaconate and methyl (Z)-a-acetamido
cinnamate an increase in enantioselectivity and activity was observed with increasing phosphine basicity.
© 2003 Elsevier Ltd. All rights reserved.
Rhodium-catalyzed asymmetric hydrogenation is one
of the most important applications of homogeneous
catalysis in industry.1 While a rational understanding of
how ligand structure can steer the selectivity in the
hydrogenation is now unfolding,2 only limited attention
has been paid to the electronic properties of phosphine3
and phosphinite ligands4 and their influence on cata-
lytic performance.
from these modified systems can have different reaction
rates and selectivities when compared to the parent
ligand system. To study the exact nature of the elec-
tronic effect in rhodium diphosphinite catalyzed asym-
metric hydrogenation,7 we synthesized a series of
(S)-BINOL and (S)-H8-BINOL based diphosphinite
ligands with varying basicities.
The novel ligands (3a, 3b, 3d, 4a, 4b, 4d, 4f) were
prepared by reacting (S)-BINOL (1,1%-bi-2-naphthol) or
(S)-H8-BINOL (H8-BINOL=5,5%,6,6%,7,7%,8,8%-octahy-
dro-1,1%-bi-2-naphthol) with the corresponding chloro-
diarylphosphine in the presence of dry triethylamine in
diethyl ether under an argon atmosphere at room tem-
perature.8,9 (S)-H8-BINOL can be readily derived from
BINOL using the protocol of Cram.10 For a compara-
tive study, the diphosphinites8 (3c, 3e, 4e) already
described have also been synthesized.
Very recent research has shown that the chiral catalysts
derived from 5,5%,6,6%,7,7%,8,8%-octahydro-1,1%-binaph-
thyl ligands exhibit higher activities and enantioselectiv-
ities for asymmetric reactions5 than those prepared
from their parent ligands due to the steric and elec-
tronic modulation in binaphthyl backbone.6 A simple
modification, namely the reduction of the unsubstituted
rings of the BINOL, provides a superior catalyst for the
enantioselective hydrogenation.
In addition to the binaphthyl moieties, the phosphorus
groups can be modified through the phenyl groups. The
introduction of substituents can modify the electron
density of the aromatic rings, and this, in turn, alters
the electron density at phosphorus. Catalysts prepared
The precatalysts were prepared as usual by the reaction
of diphosphinites with [Rh(cod)2]BF4 in CH2Cl2. For
all diphosphinite ligands, the formation of the [(diphos-
phinite)Rh(COD)]BF4 complexes was evidenced by the
appearance of a doublet in their 31P NMR spectra.
NMR spectroscopic analysis showed that complexes
with two coordinated phosphorus in the cis positions
were formed.11 We have found that decreasing the
phosphine basicity gave increasing rhodium/phospho-
Keywords: asymmetric hydrogenation; diphosphinites; rhodium;
dimethyl itaconate; methyl(Z)-a-acetamido cinnamate.
* Corresponding author. E-mail: bakos@almos.vein.hu
1
rus J(Rh,P) coupling constants and increasing coordi-
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.09.217

9026
I. Gergely et al. / Tetrahedron Letters 44 (2003) 9025–9028
indicated that the electron-withdrawing para sub-
stituent on the phenyl rings decreases enantioselectivity,
while electron-donating substituents were found to
increase the enantioselectivities of the desired product
and the activities of the catalysts. The highest ee,
93.9%, was achieved at atmospheric pressure (entry 7).
Increased hydrogen pressure accelerated the reaction
but played a minor role in enantioselectivity.
nation shifts (lP for complex – lP for free ligand).
Unlike the other parameters, the chemical shift values
for the [(diphosphinite)Rh(COD)]BF4 complexes are
very similar.
We carried out asymmetric hydrogenation of electron-
deficient olefins, dimethyl itaconate 1 (Scheme 1), and
methyl (Z)-a-acetamido cinnamate 5, using the Rh-
complexes of the series of electronically modified (S)-
BINOL and (S)-H8-BINOL diphosphinite ligands.
These complexes are useful in terms of quantifying the
electronic as well as steric influences of the ligands. The
conditions used for the hydrogenation are given in
Table 1.12
Other interesting features can be noted from Table 1.
While the (S)-BINOL based system provided hydro-
genated products with moderate to good ee values, the
partially hydrogenated BINOL based catalysts gave
higher activities and ee values for all ligands studied in
the hydrogenation of dimethyl itaconate 1, giving fur-
ther support to the beneficial effect of the
5,5%,6,6%,7,7%,8,8%-octahydro-1,1%-binaphthyl backbone.5
A comparison of the experimental results from entries
1, 2 and 4, 5 (Table 1) revealed the detrimental effect on
enantioselectivity and catalytic activity caused by elec-
tron-withdrawing substituents. These results are not
consistent with the expectation that the electronic effect
is less significant when compared to the steric hindrance
effect in influencing the enantioselectivity of the reac-
tion. An analysis of the results from entries 2, and 4, 6
The catalytic hydrogenation can be applied successfully
to methyl (Z)-a-acetamido cinnamate 5 (Scheme 2).
The experimental results revealed that rhodium cata-
lysts bearing these diarylphosphinite ligands gave very
different enantioselectivities and activities (Table 2).
Scheme 1.
Table 1. Asymmetric hydrogenation of 1a
Entry
Ligand
Ar
React. time (min)
Conv (%)
87.7 (82.3)
100 (100)
(100)
100 (100)
100
100
ee (%)
Config.
1
2
3
4
5
6
7
4a (3a)
4b (3b)
(3c)
4d (3d)
4e
3,5-(CF3)2C6H3
4-CF3C6H4
C6H5
90 (90)
20 (30)
(17)
7 (10)
9
51.6 (50.9)
72.9 (65.6)
(81.3)
89.5 (81.0)
91.5
(R)
(R)
(R)
(R)
(R)
(R)
(R)
4-MeC6H4
3,5-(CH3)2C6H3
4-MeOC6H4
4-MeOC6H4
4f
4f
5
25
92.2
100
93.9b
a General conditions:12 substrate:catalyst (s:c)=500, pH2=20 atm, room temperature.
b pH2=1 bar.

I. Gergely et al. / Tetrahedron Letters 44 (2003) 9025–9028
9027
Scheme 2.
Table 2. Asymmetric hydrogenation of 5a: influence of the structure of the ligand
Entry
Ligand
Ar
React. time (min)
Conv (%)
ee (%)
Config.
1
2
3
4
5
6
4a
4b
4d
4e (3e)
4f
3,5-(CF3)2C6H3
4-CF3C6H4
4-MeC6H4
3,5-(CH3)2C6H3
4-MeOC6H4
4-MeOC6H4
105
50
25
13 (25)
6
25
29.3
81.8
100
100 (100)
100
97.5
30.9
48.7
92.5
(S)
(S)
(S)
(S)
(S)
(S)
95.4 (93.9)
96.8
4f
98.6b
a General conditions:12 substrate:catalyst (s:c)=500, pH2=7 bar, room temperature, 2 mmol of 5 was used.
b pH2=1 bar.
When the aryl groups on the phosphorus of the phos-
phinite ligand having an electron-withdrawing group
were replaced by aryl groups with electron-donating
groups the enantioselectivity and the activity of the
catalyst enhanced greatly. For example, 48.7% ee was
obtained with 4b. On replacing CF3 in 4b by an Me
group in 4d the enantioselectivity increased to 92.5%.
The enantioselectivity was further increased to 96.8%
with the methoxy-substituent in the para position 4f.
The highest ee, 98.6%, was achieved at atmospheric
pressure. Comparison of the sense of asymmetric induc-
tion by 3b, 3c, and 3d or 4b, 4d, and 4f suggested that
the electronic effect is one of the key elements that
controls enantioselectivity. The electronic nature of the
para substituents in phosphinites has a significant effect
not only on the enantioselectivity but also on the
activity of the catalysts. Phosphinites with electron-
donating substituents (4d–f, entries 3–6 in Table 2) gave
higher catalytic activities than those with electron-with-
drawing substituents (4a–b, entries 1–2).
remarkable improvement in the activity and selectivity
of the hydrogenation of electron-deficient olefins (1, 5).
Since the BINOL and H8-BINOL based ligands have
been widely used in catalytic reactions, the substantial
improvements of enantioselectivities and catalytic activ-
ities by simply changing the basicity of the ligands
clearly indicate the high potential of this new strategy,
which, we believe, can be applied to other catalytic
reactions. A more detailed study of this new approach
with different kinds of catalysts is underway.
Acknowledgements
Support from Hungarian National Science Foundation
(OTKA T 032 004) is gratefully acknowledged. We
´
thank Mr. Be´la Edes for skillful assistance in the syn-
thetic and catalytic experiments.
(S)-H8-BINOL based diphosphinites, 4 possessing more
electron-rich and bulkier backbone uniformly gave
higher ee values than the analogous (S)-BINOL based
diphosphinites; however, the effect is small. The effect
is particularly impressive when the electronic nature of
the substituents is changed, enantioselectivities range
from 30.9% with 4a to 95.4% with 4e. The special
‘3,5-dialkyl meta effect’ is well demonstrated in the
literature.8c,13 The (S)-BINOL and (S)-H8-BINOL
diphosphinite ligands 3d, 4d–f bearing both para elec-
tron-donating groups and meta-methyl groups proved
to be more efficient than those bearing electron-with-
drawing groups in the para or meta positions 3a–b,
4a–b.
References
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In summary, we have developed a highly efficient
method for improving the enantiomer discriminating
power of the catalytic system. Electronic effects
employed as a control element for enantioselectivity
and the electronically modified ligands produced a
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4a 129.7 (d, 1J(P,Rh) =175.9 Hz), 4b 127.1 (d, 1J(P,Rh)=
170.2 Hz), 4d 129.1 ppm (1J(P,Rh)=167.6 Hz), 4e 130.4
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autoclave. The catalysts were made in situ by mixing
phosphinite (0.011 mmol) with [Rh(cod)2]BF4 (4.1 mg, 0.01
mmol) in 10 mL of CH2Cl2 under argon. The solution was
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autoclave under argon atmosphere. The autoclave was
pressurized with H2 and then shaken at a frequency of
180/min, 75° from the upright position, with horizontal
amplitude of 3 centimeters. The reaction was monitored by
the change in pressure. The reaction mixture and the
distilled products were analyzed by gas chromatography.
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by GC analysis of the distilled product (Hewlett-Packard
HP 4890 gas chromatograph, split/spitless injector, b-DEX
225, 30 m, internal diameter 0.25 mm, film thickness 0.25
mm, carrier gas: 100 kPa nitrogen, F.I.D. detector; the
retention times of the enantiomers are 30.5 min (R), 32.1
min (S)). In the case of 6 the reaction mixture was passed
through a short silicagel column to remove the catalyst.
The enantiomeric excess was determined on CP-CHI-
RASIL-L-VAL column (25 m, internal diameter 0.25 mm,
film thickness 0.12 mm, carrier gas: 100 kPa nitrogen,
F.I.D. detector; the retention times of the enantiomers are
32.5 min (R), 34.2 min (S)). The configuration of the
prevailing enantiomer in the products was determined by
the sign of optical rotation of the hydrogenated product.
Conversions were determined by GC (SPB-1).
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