New soluble bifunctional polymeric chiral ligands for enantioselectively catalytic reactions

Article abstract of DOI:10.1016/S0040-4039(01)02004-4

Two new soluble bifunctional polymeric ligands (R,R)-4 and (R,R)-5 have been prepared via the direct condensation reaction of (R)-3,3′-diformyl-1,1′-bi-2-naphthol (R)-1 with (R)-5,5′-diamino BINAP (R)-2 and with (R)-5,5′-diamino BINAPO (R)-3, respectively. The different types of catalytic centers, BINOL and BINAP or BINAPO, were alternatively organized in a regular chiral polymer chain. Both polymeric ligands were found to be effective in the addition of diethylzinc to benzaldehyde either in the presence or in the absence of Ti(OPrⁱ)₄ with different enantioselectivities. (R,R)-4/Ti(IV) catalyst, which showed similar efficiency to the parent catalyst BINOL/Ti(IV), was more enantioselective than (R,R)-5/Ti(IV). (R,R)-4 was also found to be highly effective in the Ru(II)-catalyzed asymmetric hydrogenation of 2-arylacrylic acids. The results demonstrated that the use of the co-polymer catalyst rather than a mixture of monomer catalysts not only simplified the recycling of the catalyst, but also improved the enantioselectivity and/or the activity in some cases.

Full text of DOI:10.1016/S0040-4039(01)02004-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 9047–9050
New soluble bifunctional polymeric chiral ligands for
enantioselectively catalytic reactions
a,
a
a
a
b,
Qing-Hua Fan, * Guo-Hua Liu, Guo-Jun Deng, Xiao-Min Chen and Albert S. C. Chan *
a
LMRSS, Center for Molecular Science, Institute of Chemistry, The Chinese Academy of Sciences, Beijing 100080, PR China
b
Open Laboratory of Chirotechnology and Department of Applied Biology and Chemical Technology,
The Hong Kong Polytechnic University, Hong Kong, PR China
Received 29 June 2001; revised 1 October 2001; accepted 19 October 2001
Abstract—Two new soluble bifunctional polymeric ligands (R,R)-4 and (R,R)-5 have been prepared via the direct condensation
reaction of (R)-3,3%-diformyl-1,1%-bi-2-naphthol (R)-1 with (R)-5,5%-diamino BINAP (R)-2 and with (R)-5,5%-diamino BINAPO
(
R)-3, respectively. The different types of catalytic centers, BINOL and BINAP or BINAPO, were alternatively organized in a
regular chiral polymer chain. Both polymeric ligands were found to be effective in the addition of diethylzinc to benzaldehyde
either in the presence or in the absence of Ti(OPr ) with different enantioselectivities. (R,R)-4/Ti(IV) catalyst, which showed
i
4
similar efficiency to the parent catalyst BINOL/Ti(IV), was more enantioselective than (R,R)-5/Ti(IV). (R,R)-4 was also found to
be highly effective in the Ru(II)-catalyzed asymmetric hydrogenation of 2-arylacrylic acids. The results demonstrated that the use
of the co-polymer catalyst rather than a mixture of monomer catalysts not only simplified the recycling of the catalyst, but also
improved the enantioselectivity and/or the activity in some cases. © 2001 Elsevier Science Ltd. All rights reserved.
Bifunctional ligands and multifunctional asymmetric
catalysis have been attracting much attention in recent
The development of soluble polymer-supported chiral
ligands for asymmetric catalysis combines the advan-
tages of homogeneous and heterogeneous catalysis.
1
,2
5
years. The joining of two different types of catalytic
centers together provides some unique advantages over
their mono functional counterparts. Recently, Pu and
co-workers extended this approach to bifunctional
Recently, we have developed several kinds of soluble
6
polymer or dendrimer-supported chiral ligands.
Herein, we report the synthesis and applications of two
new soluble polymer-supported bifunctional chiral cata-
lysts based on the BINOL and BINAP ligands. The key
feature of this kind of bifunctional ligand is that two
different types of chiral ligands, BINOL and BINAP or
BINAPO, were alternatively organized in a regular
chiral polymer chain, which provided an opportunity
for the study of interactions between the two types of
catalytic centers. Furthermore, the two chiral binaph-
thyl moieties were linked together with an imine bond.
Recently, imine and other nitrogen-containing ligands
have attracted much attention in asymmetric catalytic
3
polymeric catalysts. They reported the first optically
active bifunctional BINOL–BINAP copolymer catalyst,
in which the two catalytically different units, BINOL
and BINAP, were distributed randomly along the poly-
mer chain. This finding was highly interesting because it
not only demonstrated two different asymmetric trans-
formations in a one-pot protocol, but also established
the combination of two concepts of ‘bifunctional cataly-
sis’ and ‘soluble polymer-supported ligand for cataly-
4
sis’. Because of the possible facilitation of and the
potential positive influence of the polymer support on
the rate and/or stereoselectivity of the bifunctional cat-
alyst, the successful use of soluble bifunctional poly-
meric ligands for asymmetric catalysis may open a new
front for active research.
7
reactions.
The commercially available (R)-BINOL and (R)-
BINAP were chosen as model ligands for this study due
to their very extensive applications in asymmetric cataly-
8
,9
10
sis. (R)-3,3%-Diformyl-1,1%-bi-2-naphthol (R)-1 was
synthesized and used as a monomer for this study.
(
R)-5,5%-Diamino BINAP (R)-2 and its phosphine
Keywords: bifunctional catalyst; soluble polymeric ligand; asymmetric
oxide, (R)-5,5%-Diamino BINAPO (R)-3, were used as
the co-monomer. In contrast to BINAP, its phosphine
oxide may be used to coordinate with a hard metal
catalysis; BINAP; BINOL.
*
Corresponding authors. Tel.: ++86-10-62554472; fax: ++86-10-
2559373; e-mail: fanqh@infoc3.icas.ac.cn
6
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02004-4

9
048
Q.-H. Fan et al. / Tetrahedron Letters 42 (2001) 9047–9050
1
1
center to generate a Lewis acid catalyst. Both (R)-2
and (R)-3 were synthesized directly from (R)-BINAP
tive addition of diethylzinc to benzaldehyde was chosen
14
as a model reaction. Our previous study showed that
toluene was a suitable solvent for this type of reaction.
We also found that toluene dissolved these polymeric
ligands and thus used it as a solvent for this study. The
preliminary results are summarized in Table 1. Both
polymeric ligands were found to be active in the addi-
1
2
according to published methods.
With these
monomers in hand, two optically active bifunctional
polymeric ligands, BINOL–BINAP copolymer (R,R)-4
and BINOL–BINAPO copolymer (R,R)-5, were pre-
pared by direct condensation reactions using glacial
acetic acid as solvent. The synthetic routes to chiral
polymer (R,R)-4 and (R,R)-5 are outlined in Scheme 1.
Since the two types of catalytic centers were linked
together at the 3,3%-positons of (R)-1 and 5,5%-positions
of (R)-2 or (R)-3 via an imine bond, alternative major
groove and minor groove structures along the chiral
polymer chain were expected to be formed.
1
3
tion of diethylzinc to benzaldehyde 6 in the presence of
i
Ti(OPr ) , while they showed notably different enan-
4
tioselectivities. The (R,R)-4/Ti(IV) catalyst was found
to have similar efficiency to the parent catalyst (entries
15
1
and 2), which gave 1-phenyl-2-propanol 7 in 84%
Table 1. Asymmetric addition of diethylzinc to 6 catalyzed
by (R)-BINOL and the bifunctional polymeric ligands in
i
a
the presence or absence of Ti(OPr )4
Both polymer (R,R)-4 and (R,R)-5 can be dissolved in
O
OH
common organic solvents such as CH Cl , THF and
2
2
chiral catalyst
*
Et
H
+
ZnEt2
toluene, but quantitatively precipitated upon the addi-
tion of methanol. This different solubility provided a
convenient and reliable method for the characterization
and recycling of these polymeric ligands. The molecular
6
7
Entry
Catalyst
E.e. (%)b
Conv. (%)b
weights of (R,R)-4 and (R,R)-5 were M =4251 (PDI=
w
2
.7) and 5083 (PDI=3.7), respectively, which were
l
1
2
3
(R)-BINOL+Ti(OPr )
(R,R)-4+Ti(OPr )
(R,R)-4+Ti(OPr )
(R,R)-5+Ti(OPr )
BINAPO+Ti(OPr )
BINOL+BINAPO
+Ti(OPr )
(R)-BINOL
(R,R)-4
85
84
84
48
5
98
95
99
100
86
99
4
measured by gel permeation chromatography relative
I
4
to polystyrene standards. The specific optical rotation
c
i
4
of (R,R)-4 and (R,R)-5 were found to be [h] =−14
I
D
4
5
6
4
I
(
c=0.1, CHCl ) and [h] =138 (c=1.0, CHCl ), respec-
3
D
3
4
3
1
tively. The P NMR spectra of (R,R)-4 and (R,R)-5
displayed singlet signals at l −14.2 and 30.0, respec-
tively, which were consistent with the BINAP and
14
I
4
7
8
9
5
38
16
19
100
98
1
BINAPO ligands. A singlet at l 8.93 in the H NMR
−
1
(R,R)-5
spectra and a strong absorption at 1612 w/cm in the
IR spectra of these copolymers indicated the existence
of the CꢀN bond.
a
i
6
:ligand:Ti(OPr ) :ZnEt =1.0:0.2:0.8:3 (molar ratio); reaction tem-
4
2
perature=0°C; solvent=toluene; reaction time=24 h.
Determined by chiral GLC analyses. The absolute configuration of
the product is R.
b
c
In order to evaluate the efficiency of these soluble
bifunctional polymeric chiral ligands, the enantioselec-
Recovered ligand of entry 2 was used.
NH2
CHO
acetic acid
OH
PPh2
PPh2
OH OH
HC
OH OH
CH
HC
+
CH
OH
83%
N
N
N
N
CHO
NH2
PPh2PPh2
PPh2PPh2
(R)-2
(R)-1
(R, R)-4
NH2
CHO
OH
O
acetic acid
PPh2
OH OH
HC
OH OH
CH
HC
+
CH
OH
PPh2
7
8%
N
N
N
N
O
CHO
NH2
Ph2P
PPh2
Ph2P
PPh2
O
O
O
O
(R)-3
(R)-1
(R, R)-5
Scheme 1. The synthesis of bifunctional BINOL–BINAP and BINOL–BINAPO copolymers.

Q.-H. Fan et al. / Tetrahedron Letters 42 (2001) 9047–9050
9049
a
Table 2. Asymmetric hydrogenation of 8 and 9 catalyzed by Ru[(R,R)-4] and Ru(BINAP)
CH3
Cat.
H2
*
COOH
COOH
R
R
8
9
: R = H;
: R = Bui
Entry
Ligand
Sub.
Solvent
Time (h)
Conv. (%)b
E.e. (%)b
1
2
3
4
5
6
7
(R,R)-4
(R,R)-4
(R,R)-4
(R,R)-4
BINAP
BINAP
BINAP
8
8
9
9
8
9
9
Toluene/MeOH (1:1)
CH Cl /MeOH (1:1)
16
16
14
14
18
18
18
70
100
76
58
99
88
84
84
85
92
88
87
2
2
Toluene/MeOH (1:1)
CH Cl /MeOH (1:1)
2
2
Toluene/MeOH (1:1)
Toluene/MeOH (1:1)
CH Cl /MeOH (1:1)
100
100
2
2
a
The hydrogenation was carried out in 0.032 M of 8 and 9 under the following conditions: H2 pressure=50 atm; substrate/ruthenium (molar
ratio)=100:1; substrate/NEt3 (molar ratio)=1.5:1.
Based on GLC analysis with a Chrompack Chirasil-dex (25 m×0.25 mm). The absolute configuration of the product is R.
b
ee (entry 2) while (R,R)-5/Ti(IV) gave the correspond-
In addition to the use in the asymmetric addition of
diethylzinc to benzaldehyde, the bifunctional polymer
(R,R)-4 can also be used as a ligand for asymmetric
hydrogenation. In order to test the asymmetric induc-
tion of (R,R)-4, we chose the asymmetric hydrogena-
tion of 2-arylacrylic acid as a model reaction. The
catalyst, which was conveniently prepared in situ
ing alcohol in 48% ee only (entry 4). This was proba-
bly due to the different enantioselectivity of the two
types of catalytically active centers on (R,R)-5. In
order to further explain this phenomenon, two control
experiments were carried out under similar reaction
conditions using (R)-BINAPO and the 1:1 (mole ratio)
mixture of (R)-BINOL and (R)-BINAPO as ligands,
respectively. The results showed that much lower ee’s
were obtained (entries 5 and 6). Most interestingly,
however, enhancement of the enantioselectivity (14 to
from (R,R)-4 and [RuCl (cymene)] in a methanol–
2 2
toluene (3:2, v/v) mixed solvent system, was com-
pletely homogeneous. The preliminary results are
summarized in Table 2. It was seen that the
Ru[(R,R)-4] catalyst gave high enantioselectivity and
high catalytic activity. In comparison with the parent
Ru(BINAP) catalyst, only slight decreases in enan-
tioselectivity and activity were observed.
4
8% ee) was achieved by organizing these two types of
catalytically active units in a regular polymer chain
entries 4 and 6). We also investigated this addition
(
reaction under the same conditions in the absence of
i
Ti(OPr ) . It was found that the polymeric ligands
4
performed very differently from BINOL. Polymer
In summary, two new soluble bifunctional polymeric
ligands were prepared via the direct condensation
reaction of (R)-3,3%-diformyl-1,1%-bi-2-naphthol (R)-1
with (R)-5,5%-diamino BINAP (R)-2 and with (R)-
(
R,R)-4 gave 7 in 100% conversion and 38% ee, while
BINOL gave the corresponding alcohol only in 19%
conversion and 5% ee (entries 7 and 8). The higher
efficiency of polymer (R,R)-4 might be due to the
existence of the imine groups at the 3,3%-position of
BINOL. Demonstration of the role of the imine
groups on the catalytic reaction required further
experimental evidence. Polymer (R,R)-5 also showed
lower enantioselectivity than polymer (R,R)-4, which
was probably due to the different enantioselectivity of
the catalytically active centers, BINOL and BINAPO,
on the polymer chain, as described above (entries 8
and 9). An important feature of the design of soluble
polymeric catalyst is the easy and reliable separation
of the chiral ligand based on its different solubilities in
various organic solvents. For example, upon comple-
tion of the reaction, polymer (R,R)-4 was quantita-
tively precipitated by the addition of methanol and
was recovered via filtration. The recovered ligand
showed similar enantioselectivity and reactivity (entry
5
,5%-diamino BINAPO (R)-3, respectively. The differ-
ent types of catalytic centers, BINOL/BINAP or
BINOL/BINAPO, were alternatively organized in a
regular chiral polymer chain. Both polymer ligands
were found to be active in the addition of diethylzinc
i-
to benzaldehyde in the presence or absence of Ti(O
Pr)4 with different enantioselectivities. The polymer
(R,R)-4/Ti(IV) catalyst, which showed similar
efficiency to the parent catalyst BINOL/Ti(IV), was
more enantioselective than (R,R)-5/Ti(IV). (R,R)-4
was also found to be effective in the Ru(II)-catalyzed
asymmetric hydrogenation of 2-arylacrylic acid. The
results demonstrated that the use of the copolymer
catalyst rather than a mixture of monomer catalysts
not only simplified the recycling of the catalyst, but
also improved the enantioselectivity and/or the activ-
ity in some cases. The use of these bifunctional poly-
meric ligands in other transformations is in progress.
3).

9
050
Q.-H. Fan et al. / Tetrahedron Letters 42 (2001) 9047–9050
Acknowledgements
Fan, Q. H.; Deng, G. J.; Chen, X. M.; Xie, W. C.; Jiang,
D. Z.; Liu, D. S.; Chan, A. S. C. J. Mol. Cat. A: Chem.
000, 159, 37–43; (c) Fan, Q. H.; Deng, G. J.; Lin, C. C.;
2
We are grateful to The Chinese Academy of Sciences,
and National Natural Science Foundation for Youth of
China (projects 29904009) and The Hong Kong Poly-
technic University ASD Fund for financial support.
Chan, A. S. C. Tetrahedron: Asymmetry 2001, 12, 1241–
1247; (d) Fan, Q. H.; Liu, G. H.; Chen, X. M.; Deng, G.
J.; Chan, A. S. C. Tetrahedron: Asymmetry 2001, 12,
1559–1565.
7
8
. For a comprehensive and excellent recent review, see:
Fache, F.; Schulz, E.; Tommasino, M. L.; Lemaire, M.
Chem. Rev. 2000, 100, 2159–2231.
. For reviews on asymmetric catalysis with BINOL, see: (a)
Rosini, C.; Franzini, L.; Raffaelli, A.; Salvadori, P. Syn-
thesis 1992, 503–517; (b) Brunner, H.; Zettlmeier, W.
Handbook of Enantioselective Catalysis; VCH: Weinheim,
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1
3. Synthesis of polymer ligand (R,R)-4: To a solution of 50
mg of (R)-1 (0.146 mmol) in 2 mL of tetrahydrofuran
and 8 mL of glacial acetic acid was added a warm
solution of 95.3 mg of (R)-2 (0.146 mmol) in 4 mL glacial
acetic acid. Then the temperature was slowly raised to
5
(
7
40°C and the mixture was stirred for 2 h. After cooling to
room temperature, a yellow precipitate was formed. The
precipitate was filtered, washed with water, alcohol, THF
and ether, and dried to give (R,R)-4 (116.4 mg, yield
(
83%).
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