A dendrimer-supported heterobimetallic asymmetric catalyst

Article abstract of DOI:10.1016/S0957-4166(02)00573-6

Plural ligands consisting of catalysts such as AlLibis(binaphthoxide) complex (ALB) and GaNabis(binaphthoxide) complex (GaSB) are effectively introduced onto the periphery of a dendrimer. The resulting dendrimer-supported heterobimetallic catalysts promot

Full text of DOI:10.1016/S0957-4166(02)00573-6

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 2083–2087
A dendrimer-supported heterobimetallic asymmetric catalyst
a
a
a
a
b
Takayoshi Arai, Tetuya Sekiguti, Yoshimasa Iizuka, Shinobu Takizawa, Shigeru Sakamoto,
b
a,
Kentaro Yamaguchi and Hiroaki Sasai *
a
The Institute of Scientific and Industrial Research (ISIR), Osaka University, Mihogaoka, Ibaraki, Osaka 567-0047, Japan
b
Chemical Analysis Center, Chiba University, Yayoicho, Inage-ku, Chiba 263-8522, Japan
Received 26 August 2002; accepted 9 September 2002
Abstract—Plural ligands consisting of catalysts such as AlLibis(binaphthoxide) complex (ALB) and GaNabis(binaphthoxide)
complex (GaSB) are effectively introduced onto the periphery of a dendrimer. The resulting dendrimer-supported heterobimetallic
catalysts promoted the asymmetric Michael reaction of 2-cyclohexenone with dibenzyl malonate to give the adduct with up to 97%
ee. © 2002 Elsevier Science Ltd. All rights reserved.
Dendrimers are defined as a class of polymers with
hyper-branched chains, typically having a spherical
structure, and possessing a central core with a number
of branching dendron units attached. Because the struc-
ture, size, shape and solubility of the dendrimers are
tunable, these polymers have attracted considerable
attention as a new class of well-defined nanometer-scale
three molecules of BINOLs construct one catalyst
through a self-assembly process. For heterobimetallic
catalysts, the conventional method of catalyst immobi-
lization using a sterically disordered polymer backbone
(e.g. polystyrene resin) was resulted in the inefficient
construction of polymer-supported catalyst due to the
random orientation of the ligands. In the case of den-
drimers, the highly defined branches can serve as an
ideal structure for arranging two BINOL molecules to
the suitable positions in the construction of an efficient
1
material. Among the large number of various applica-
tions, the development of dendrimer-supported cata-
lysts is one attractive area of research into dendritic
2
6
materials. Using the nanometer-scale branching den-
heterobimetallic multifunctional catalytic site. Herein,
drimer scaffold, these well-defined dendrimers could
combine the advantages of homogeneous and heteroge-
neous catalysis. Despite the potential of these systems,
positive reports on dendritic effects in catalysis have
we report on the first synthesis of dendritic hetero-
bimetallic multifunctional asymmetric catalysts, and
their application as catalysts in asymmetric Michael
reactions. The substitution at the 6-position of BINOL
was not expected to affect the asymmetric environment
generated by the BINOL derived catalyst. The length of
the alkyl side chain as a spacer was determined based
3
been rather limited. Recently, Jacobsen et al. reported
on an example in which two catalytic sites at the
terminal positions of a dendrimer assisted the ring-
4
7
opening reaction of epoxides. We have also assumed
on computational calculations. Molecular dynamics
that a dendritic framework would be useful for enforc-
ing and controlling cooperative interactions between
two ligands attached to the periphery of the dendrimer,
as represented in Fig. 1.
simulation of the dendrimer-supported ALB catalyst
Starting from BINOL as a chiral ligand we have devel-
oped heterobimetallic catalysts such as LaNa tris-
3
(
binaphthoxide) complex (LSB) and AlLibis(binaph-
thoxide) complex (ALB), which promote asymmetric
reactions with synergistic cooperations of metals in the
catalysts to give the products with high regio- and
5
stereoselectivities. In heterobimetallic catalysts, two or
Figure 1. Efficient construction of plural ligands consisting
*
Corresponding author. Tel.: +81-6-6879-8465; fax: +81-6-6879-8469;
e-mail: sasai@sanken.osaka-u.ac.jp
catalyst on the periphery of the dendrimer.
0
957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00573-6

2
084
T. Arai et al. / Tetrahedron: Asymmetry 13 (2002) 2083–2087
Scheme 1. Synthesis of dendrimer supported BINOL.

T. Arai et al. / Tetrahedron: Asymmetry 13 (2002) 2083–2087
2085
with various spacer lengths suggested a C to C alkyl
An insoluble catalyst of G1 dendritic ALB was formed
4
6
side chain would be optimal for the formation of ALB
on the dendrimer periphery. Since a longer spacer may
result in the unwanted formation of the ALB type
catalyst in an inter-dendron manner, the synthesis of
by the treatment of G1 DSB 8 with AlMe and n-BuLi.
3
As expected, chiral dendritic ALB exhibited moderate
catalytic activity in the asymmetric Michael reaction of
2-cyclohexenone 11 with dibenzyl malonate 12. After 48
h, the Michael adduct 13 was obtained in 63% yield
with 91% ee (Table 1, entry 1). In a similar procedure,
G2 dendritic ALB gave 13 in 59% yield with 91% ee
8
the terminal dendron 2 was initiated using 1, which has
a C alkyl chain. As shown in Scheme 1, two molecules
4
of BINOL derivative 1 were incorporated with methyl
3
,5-dihydroxybenzoate using the Mitsunobu coupling
(
Table 1, entry 4). Because the ALB derived from
9
reaction to give the dendrimer terminal unit 2 in 66%
yield, which was reduced with LiAlH to afford com-
randomly introduced BINOLs on polystyrene resin
4
gave 13 with almost racemic form, this is an apparent
15–17
pound 3 in 98% yield. The resulting benzyl alcohol 3
advantage of the use of dendrimers.
The chiral
1
0
was combined with core unit 6 under Mitsunobu
conditions to give the chiral generation 1 (G1) den-
drimer 7 in 63% yield, which contains six BINOL units
at the terminal positions. Subsequent deprotection of 7
using TBAF afforded the corresponding G1 dendrimer
dendritic BINOLs 8 and 10 were quantitatively recov-
18
ered using silica gel column chromatography.
Since G1 dendritic ALB was efficient as a solid catalyst,
we examined the re-use of the catalyst in asymmetric
Michael reactions. Because it has been reported that
moisture sensitive aluminum Lewis acid catalysts are
difficult to re-use, recovery of the dendritic ALB was
carried out simply by removing the clear supernatant
via syringe under a stream of argon. THF, 11, and 12
were successively added to the residue to carry out the
next Michael reaction. As shown in Table 1, the recy-
cled catalyst gave comparable results with that of entry
1
1
ligand 8 (G1 DSB) in 92% yield. The G1 DSB was
characterized by spectroscopic analyses including
12
coldspray ionization (CSI) mass spectrometry by the
+
observation of an ion peak [M+Na] at m/z=2786 (Fig.
2
). Similarly, as shown in Scheme 1, the second genera-
13
tion dendrimer 10 (G2 DSB), which consists of 12
BINOL units at its terminal positions, was prepared
using the improved Mitsunobu reagent. The molecu-
lar weight of G2 dendrimer 10 (G2 DSB) up to 5538
was also confirmed by CSI mass spectrometry by the
detection of the peaks corresponding to [M+Na] (m/
z=5561) and [M+2Na] (m/z=2792).
14
19
1
(entries 2 and 3).
+
These preliminary results prompted us to conduct fur-
2+
2
0
ther studies using the activated ALB (ALB-II). Addi-
tion of an equivalent quantity of a basic reagent to the
parent ALB catalyst enhances the catalytic activity
while maintaining high enantiomeric excess of the
Michael adducts. Although the dendritic ALB cata-
21
lyzed reactions in the presence of 0.9 equiv. of n-BuLi
or NaO-t-Bu reduced the enantiomeric excess values of
2
1
1
7
3, the use of 0.3 equiv. of NaO-t-Bu gave the 13 in
9% yield with 89% ee (Table 1, entry 5).
Table 1. Asymmetric Michael reaction catalyzed by den-
dritic heterobimetallic catalysts
Entry
Dendritic catalyst
Time
h)
Yield
(%)
Ee
(%)
(
1
2
3
4
5
6
7
G1 Dendritic ALB
48
48
48
72
48
22
72
63
63
57
59
79
40
83
91
93
94
91
89
92
97
G1 Dendritic ALB (2nd use)
G1 Dendritic ALB (3rd use)
G2 Dendritic ALB
G1 Dendritic ALB II
G1 Dendritic GaSB
b
c
G1 Dendritic GaSB II
a
Based on a single catalytic site on the dendrimer.
b
0
.3 equiv. of NaO-t-Bu to Al was added.
Figure 2. CSI mass spectra of 8 and 10.
c0.5 equiv. of NaO-t-Bu to Ga was added.

2
086
T. Arai et al. / Tetrahedron: Asymmetry 13 (2002) 2083–2087
Furthermore, we examined another type of hetero-
bimetallic multifunctional catalyst, which consisted of
gallium, sodium and two BINOL moieties (GaNabis(bi-
T.; Ohtake, K.; Kodaka, R.; Hirokawa, Y.; Shirai, N.;
Soai, K. Tetrahedron Lett. 2000, 41, 3123–3126; (h) Mar-
aval, V.; Laurent, R.; Caminade, A.-M.; Majoral, J.-P.
Organometallics 2000, 19, 4025–4029; (i) Fan, Q.-H.;
Chen, Y.-M.; Chen, X.-M.; Jiang, D.-Z.; Xi, F.; Chan, A.
S. C. Chem. Commun. 2000, 789–790; (j) Ropartz, L.;
Morris, R. E.; Foster, D. F.; Cole-Hamilton, D. J. Chem.
Commun. 2001, 361–362.
. Breinbauer, R.; Jacobsen, E. N. Angew. Chem., Int. Ed.
Engl. 2000, 39, 3604–3607.
. (a) Sasai, H.; Arai, T.; Satow, Y.; Houk, K. N.;
Shibasaki, M. J. Am. Chem. Soc. 1995, 117, 6194–6198;
2
0
naphthoxide) complex) (GaSB). A solution of 8 (G1
DSB) was treated with GaCl and NaO-t-Bu to form
3
G1 dendritic GaSB as an insoluble catalyst, which was
shown to have moderate catalytic activity in the asym-
metric Michael reactions. Moreover, the combined use
2
1
of 0.5 equiv. of NaO-t-Bu and 10 mol% dendritic
GaSB showed enhanced catalyst activity, affording the
Michael adduct 13 in 83% yield with up to 97% ee
4
5
22
(
Table 1, entry 7).
(
b) Shibasaki, M.; Sasai, H.; Arai, T. Angew. Chem., Int.
In conclusion, dendrimer-supported heterobimetallic
catalysts such as ALB and GaSB promoted the Michael
reaction with excellent enantiomeric excess. These reac-
tions are the first examples of the immobilization of a
heterobimetallic multifunctional catalyst on the periph-
ery of a dendrimer surface. Further applications toward
the immobilization of other heterobimetallic catalysts,
consisting of plural ligands, are the focus of our contin-
uing efforts.
Ed. Engl. 1997, 36, 1236–1256.
6
. Recent progress with re-usable heterobimetallic multi-
functional asymmetric catalysts, see: (a) Arai, T.; Hu,
Q.-S.; Zheng, X.-F.; Pu, L.; Sasai, H. Org. Lett. 2000, 2,
4
261–4263; (b) Kim, Y. S.; Matsunaga, S.; Das, J.;
Sekine, A.; Ohshima, T.; Shibasaki, M. J. Am. Chem.
Soc. 2000, 122, 6506–6507; (c) Matsunaga, S.; Ohshima,
T.; Shibasaki, M. Tetrahedron Lett. 2000, 41, 8473–8478;
(
2
d) Jayaprakash, D.; Sasai, H. Tetrahedron: Asymmetry
001, 12, 2589–2595.
7
8
9
. Molecular dynamics simulations using polymer specific
consistent forcefield (PCFF) were performed on Cerius 2
Acknowledgements
(
Accelrys Inc.).
. Bayston, D. J.; Fraser, J. L.; Ashton, M. R.; Baxter, A.
D.; Polywka, M. E. C.; Moses, E. J. Org. Chem. 1998, 63,
This work was supported by a Grant-in-Aid for Scien-
tific Research from the Ministry of Education, Science,
Sports, and Culture, Japan. We thank the technical
staff in the Materials Analysis Center of ISIR, Osaka
University.
3137–3140.
. Freeman, A. W.; Chrisstoffels, L. A. J.; Fr e´ chet, J. M. J.
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1
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1. Selected physical properties of G1 DSB 8: IR (neat)
091.6, 1220.9, 1359.7, 1419.5, 1635.5, 1705.0, 3510.0
1
1
1
−
1 13
cm ; C NMR (67.7 MHz, acetone-D ): l 28.58, 30.38,
6
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13. Selected physical properties of G2 DSB 10: IR (neat)
8
2
2
1
1
1
1
19.7, 1126.4, 1145.6, 1458.1, 1508.2, 1596.9, 1701.1,
−
1
13
923.9, 3410.0 cm ; C NMR (67.7 MHz, CDCl ): l
3
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(catalog No. 038-09524, Wako Pure Chemical Industries,

T. Arai et al. / Tetrahedron: Asymmetry 13 (2002) 2083–2087
2087
Ltd.), followed by the removal of the TBS group and
18. The recovered 8 was able to re-use as a ligand giving the
Michael adduct in 63% yield with 91% ee.
catalyst formation with AlMe and n-BuLi. The polymer
3
supported ALB gave 13 in 27% yield with 0% ee after 72
h.
6. Under high dilution conditions (0.03 M G1 dendritic
ALB), the Michael adduct was obtained with 94% ee,
which strongly suggests that the ALB complex forms on
a single independent dendrimer molecule.
19. In the 4th use, 13 was obtained in 57% yield with 79% ee.
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1
1
2
2
1. Equivalency to the single catalytic site.
2. Typical procedure for asymmetric Michael reaction: To
the insoluble dendritic heterobimetallic catalyst (0.1
equiv. as the single catalytic site) in THF (0.03 M) was
added a solution of NaO-t-Bu (0.03 equiv. to Al, 0.05
equiv. to Ga) in THF at 0°C. After stirring for 2 h at
room temperature, 11 (0.031 mL, 0.317 mmol, 1.1 equiv.)
and 12 (0.072 mL, 0.289 mmol, 1.0 equiv.) were added.
After completion of the reaction, the reaction mixture
was quenched with 1N HCl aq. at 0°C and then extracted
with AcOEt. The combined organic extract was washed
with brine, dried (Na SO ), and concentrated to give an
7. The ALB catalyst derived from the peripheral dendron
unit i gave 13 in 72% yield with 97% ee after 48 h.
2
4
oily residue. Purification by flash chromatography (SiO2,
acetone/hexane=1/10) gave 13. The enantiomeric purity
of the product was determined by chiral HPLC analysis
(
Daicel CHIRALPAK AS, i-PrOH/hexane=1/4, 1.0 mL/
min, 254 nm).