Metal-Bridged Polymers as Insoluble Multicomponent Asymmetric Catalysts with High Enantiocontrol: An Approach for the Immobilization of Catalysts without Using any Support

Article abstract of DOI:10.1002/anie.200352354

Immobile without support: The first synthesis of chiral Al-bridged and Ti-bridged polymers by a metal-mediated self-assembly of (R,R)-6,6′ -bi(binol) (binol = 1,1′-bi-2-naphthol), which bears two pairs of phenolic hydroxy groups at the opposite sides in t

Full text of DOI:10.1002/anie.200352354

Angewandte
Chemie
Figure 1. Schematic representation of multicomponent asymmetric
catalysts.
tional units onto a sterically irregular polymer backbone,
resulted in less effective catalysts. Multidentate ligands with
attached sites for metals at the opposite sides in the molecular
skeleton readily form insoluble metal-bridged polymers
(Figure 2). If chiral metal-bridged regions on the generated
Multicomponent Asymmetric Catalysis
Figure 2. A concept of metal-bridged polymers as enantioselective cat-
alysts.
Metal-Bridged Polymers as Insoluble
Multicomponent Asymmetric Catalysts with High
Enantiocontrol: An Approach for the
Immobilization of Catalysts without Using any
Support**
polymer function as asymmetric catalysts, a simple and
efficient approach for the immobilization of multicomponent
asymmetric catalysts without the need for a polymer support
would be realized. While metal–organic coordination net-
works, including metal-bridged polymers, have been utilized
for catalytic asymmetric reactions, the enantioselectivity of
Shinobu Takizawa, Hidenori Somei, Doss Jayaprakash,
and Hiroaki Sasai*
[
4]
the products obtained has been very low.
Herein, the synthesis of insoluble multicomponent asym-
metric catalysts by the self-assembly of multidentate ligands
Immobilization, as a methodology to effectively recover and
reuse asymmetric catalysts, has attracted the interest of many
research groups resulting in a large number of catalysts being
[
5]
containing binol (binol = 1,1’-bi-2-naphthol) with metal ions
3
+
4+
such as Al or Ti is described. To obtain the metal-bridged
[
1]
subjected to investigation. Multicomponent asymmetric
polymers, (R,R)-6,6’-bis(binol) derivatives (2a–c) and (R,R)-
[
2,3]
[6]
catalysts,
composed of plural ligands, metals, and func-
6,6’-bi(binol) (2d) were synthesized by linking the binol
[
7]
tional moieties, have proved to be challenging systems in this
regard (Figure 1). Multicomponent asymmetric catalysts
function like enzymes in facilitating a wide range of regio-
and stereoselective reactions that make use of the synergistic
cooperation between the active sites; it is important to
maintain the structural motif during immobilization if high
reactivities are to be realized. The conventional approach,
which involves the random introduction of ligand and func-
units at 6-position (Figure 3).
We have reported the ready preparation of AlÀLi–
bis(binaphthoxide) complex (ALB) as a multicomponent
asymmetric catalyst by the reaction of LiAlH with two molar
4
[
2b]
equivalents of binol (Figure 4). ALB was revealed to have
[
*]Prof. Dr. H. Sasai, Dr. S. Takizawa, Dr. H. Somei, Dr. D. Jayaprakash
The Institute of Scientific and Industrial Research (ISIR)
Osaka University
Mihogaoka, Ibaraki, Osaka 567-0047 (Japan)
Fax: (+81)6-6879-8469
E-mail: sasai@sanken.osaka-u.ac.jp
[
**]This work was supported by a Grant-in-Aid for Scientific Research
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan. We thank the technical staff in the Materials
Analysis Center of ISIR, Osaka University.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
Figure 3. (R,R)-6,6’-bis(binol) derivatives (2a–c) and (R,R)-6,6’-bi(bi-
nol) (2d).
Angew. Chem. Int. Ed. 2003, 42, 5711 –5714
DOI: 10.1002/anie.200352354
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5711

Communications
solution removed with a syringe under argon. The super-
natant solution exhibited no catalyst activity in the Michael
reaction, whereas the precipitate afforded 5 with ee value of
9
1%. In addition two reactions were carried out with 3 and 4
under optimized conditions. One reaction was quenched after
8 h during which 5 was obtained in 22% yield with an ee value
of 94%. The supernatant solution of the other reaction was
separated from the heterogeneous catalyst and stirred further
for 40 h. This reaction afforded 5 in 19% yield with an ee
value of 90%. In addition ligand 2d was not observed in the
supernatant solution. These results confirm the absence of
catalyst activity in the solution phase. The heterogeneous
catalyst as Al-bridged polymer, derived from 2d and LiAlH4,
was characterized by elemental analysis and by a comparison
of its IR spectrum with that of the ALB complex. Character-
istic absorptions for Al-bridged polymer are similar to ALB
Figure 4. Al-Li-bis(binaphthoxide) complex (ALB).
high enantioselectivity in the asymmetric Michael reaction
e.g., 2-cyclohexenone (3) with dibenzyl malonate (4)). The
(
catalyst activity of ALB can be increased by the addition of
about one equivalent of a basic reagent such as BuLi to form
ALB II catalyst while maintaining high enantiocontrol.
Ligands 2a–d were examined in the first attempt at creating
a chiral metal-bridged polymer that could function as ALB II-
type catalyst in the enantioselective Michael reaction of 3
[
2c]
[
9]
with 4. The addition of LiAlH (1 equivalent) to a homoge-
complex.
4
neous solution of 2 (1 equivalent) in THF at 08C sponta-
neously gave a white precipitate. After the reaction mixture
was stirred for 0.5 h, BuLi (0.5 equivalents) was added to the
obtained white solid. ALB II (20 mol%) was used as the
heterogeneous catalyst in the enantioselective Michael reac-
tion. The results with ligands 2a–d are summarized in Table 1.
Having been encouraged by the success with Al-bridged
polymer as an insoluble asymmetric catalyst, we examined the
reuse of the catalyst in asymmetric Michael reaction
(Table 2). The reuse experiments were performed by removal
of the clear supernatant solution containing the product with
a syringe under argon followed by the addition of substrates.
The metal-bridged polymer maintained its activity even after
being reused three times, albeit with a slight decrease in
enantioselectivity (yield: 74%, ee value of 85%).
Table 1: Enantioselective Michael reaction catalyzed by Al-bridged
polymer.
Table 2: Reuse of Al-bridged polymer in enantioselective Michael
[
a]
reaction of 3 with 4.
[
b]
[c]
Cycle
t [h]Yield [%]
ee [%]
[
a]
[b]
Entry
2a–d
t [h]Yield [%]
ee [%]
1
2
3
4
5
72
98
98
98
98
88
86
74
60
59
96
87
85
77
77
1
2
3
4
5
6
2a
2b
2c
2d
48
48
48
48
72
12
94
69
89
86
88
Quant
6
17
88
96
99
97
[
c]
ALB
ALB II
[a]Al-bridged polymer generated from 2d (1 mol equiv), LiAlH4 (1
mol equiv) and BuLi (0.5 mol equiv) in the presence of MS 4A was used.
[
c]
[b]Isolated yield. [c]Determined by HPLC (Daicel Chiralpak AS).
[
[
a]Isolated yield. [b]Determined by HPLC (Daicel Chiralpak AS).
c]10 mol% of catalyst was used. See reference [2c].
The generality of the concept of chiral metal-bridged
Heterogeneous catalysts derived from 2a and 2b afforded the
Michael adduct 5 with ee values of 6% and 17%, respectively
polymer catalysis was also demonstrated through asymmetric
[
2i]
carbonyl–ene reaction by using a Ti–binol complex.
A
(
entries 1 and 2). The low ee values are attributable to the
solution of Ti(O-iPr) (2 equivalents) in toluene and H O
4
2
bent shape of the ligands that facilitate the formation of
(four molar equivalents) were added to a solution of 2d in
[
2d]
unsuitable aggregates. In contrast, heterogeneous catalysts
derived from 2c and 2d, in which each pair of the phenolic
hydroxy groups is situated at the opposite sides in the
multidentate ligands, gave the Michael adduct 5 with high
enantioselectivity. As we have previously reported that
polystyrene-supported ALB derived from randomly intro-
duced binol derivatives on polystyrene resin afforded 5 with
CH Cl . The solution was stirred at room temperature for 24 h
2
2
to afford the precipitate. After removal of the solvents at
808C under reduced pressure, the residue was dried in vacuo
at 808C for 19 h. The resulting red solid was characterized by
elemental analysis and by comparison of its IR spectrum with
[
2i]
hitherto known titanium complex, and found to be a
titanium-bridged polymer. The characteristic absorptions for
titanium-bridged polymer are similar to the parent titanium
[
8]
no enatiomeric excess, there is obviously an advantage in
the present method that uses a metal-bridged polymer for
immobilizing ALB. The ability of the insoluble polymer to act
as an asymmetric catalyst was confirmed by the following
experiments: The heterogeneous catalyst derived from 2d
[
10]
complex.
As shown in Scheme 1, the titanium-bridged
polymer catalyzed the reaction of aldehyde 6 and olefin 7 to
give the product 8 in 81% yield with an ee value of 90%. In
contrast to the Al-bridged polymer, Ti-bridged polymer could
be recovered in air. After being reused four times the Ti-
and LiAlH was allowed to settle and the clear supernatant
4
5
712
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Angew. Chem. Int. Ed. 2003, 42, 5711 –5714

Angewandte
Chemie
[
2] Representative examples of multicomponent
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2
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[
Table 3: Reuse of Ti-bridged polymer in enantioselective carbonyl–ene
reaction of 6 with 7.
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binol was chosen to be modified as chiral multidentate ligands
because binol as a ligand is used in various chiral metal catalysts.
a) C. Roshini, L. Franzini, A. Raffaelli, P. Salvadori, Synthesis
[
a]
[b]
Cycle
t [h]Yield [%]
ee [%]
[
1
2
3
4
5
98
98
98
147
147
88
72
71
88
66
88
92
89
88
88
1992, 503; b) R. Noyori, I. Tomino, Y. Tanimoto, J. Am. Chem.
Soc. 1979, 101, 3129; c) H. Yamamoto, A. Yanagisawa, K.
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C. Zhu, T. Huang, J. Chem. Soc. Perkin Trans. 1 1998, 2131; e) H.
Sasai, T. Arai, S. Watanabe, M. Shibasaki, Catal. Today 2000, 62,
[a]Yield of isolated product. [b]Determined by HPLC (Daicel Chiralpak
AS).
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Ishitani, Chem. Rev. 1999, 99, 1069; h) J. Inanaga, H. Furuno, T.
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bridged polymer exhibited consistent catalytic selectivity
affording 8 with an ee value of 88% (Table 3).
[
6] Starting from known (R)-6-Br-2,2’-bis(methoxymethyloxy)-1,1’-
binaphthalene, novel chiral multidentate ligands 2a-c were
prepared in four steps by using the Suzuki–Miyaura coupling
reaction as the key step (See the Supporting Information). The
ligand 2d was also prepared in four steps by using the Suzuki–
Miyaura coupling reaction and was identical in all the respects
with spectra reported by Lin and co-workers. (See Supporting
Information). L. Ma, P. S. White, W. Lin, J. Org. Chem. 2002, 67,
The results presented herein is the first example of a chiral
metal-bridged polymer, formed by a metal-mediated self-
assembly of chiral multidentate ligands, that functions as an
asymmetric catalyst with high enantioselectivity. This novel
method offers the possibility of immobilization of multi-
component asymmetric catalysts without using any sup-
[
8,11]
port.
The design of other types of chiral multidentate
7577.
ligands is currently being pursued.
[
7] Shibasaki and co-workers reported an efficient enantioselective
reaction by linking binol at C3. Y. S. Kim, S. Matsunaga, J. Das,
A. Sekine, T. Ohshima, M. Shibasaki, J. Am. Chem. Soc. 2000,
Received: July 11, 2003
Revised: August 18, 2003 [Z52354]
122, 6506.
[
[
8] T. Arai, T. Sekiguti, Y. Iizuka, S. Takizawa, S. Sakamoto, K.
Keywords: asymmetric catalysis · heterogeneous catalysis ·
immobilization · self-assembly · synthetic methods
.
Yamaguchi, H. Sasai, Tetrahedron: Asymmetry 2002, 13, 2083.
9] Al-bridged polymer (generated from ligand 2d with LiAlH in
4
the ratio of 1:1): Elemental analysis calcd (%) for polymeric
C H AlLiO (containing three molecules of THF per active
5
2
46
7
site): C 76.46, H 5.68; found: C 76.26, H 5.75. IR: ALB complex
2
871, 1591, 1502, 1463, 1425, 1340, 1126, 1049, 953, 860, 816,
[
1] For recent reviews, see: a) N. E. Leadbeater, M. Marco, Chem.
Rev. 2002, 102, 3217; b) C. A. McNamara, M. J. Dixon, M.
Bradley, Chem. Rev. 2002, 102, 3275; c) T. J. Dickerson, N. N.
Reed, K. D. Janda, Chem. Rev. 2002, 102, 3325; d) D. E.
Bergbreiter, Chem. Rev. 2002, 102, 3345; e) R. van Heerbeek,
P. C. J. Kamer, P. W. N. M. van Leeuwen, J. N. H. Reek, Chem.
Rev. 2002, 102, 3717.
À1
746 cm , Al-bridged polymer 2862, 1587, 1499, 1458, 1423, 1339,
1126, 1045, 949, 862, 820, 746 cm
À1
.
[10] Ti-bridged polymer: Elemental analysis calcd (%) for polymeric
Ti (containing one molecule of toluene per active site):
C
H
O
6
47
30
2
C 71.78, H 3.84; found: C 71.96, H 4.15. IR: Ti-binol complex
1585, 1499, 1458, 1333, 1234, 1113, 1078, 974, 935, 814, 746 cm
À1
,
Angew. Chem. Int. Ed. 2003, 42, 5711 –5714
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ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
5713

Communications
Ti-bridged polymer 1583, 1499, 1454, 1427, 1333, 1236, 1074, 976,
À1
9
41, 820, 727 cm .
[
11] Recent progress in immobilized multicomponent asymmetric
catalysts: a) T. Arai, Q.-S. Hu, X.-F. Zheng, L. Pu, H. Sasai, Org.
Lett. 2000, 2, 4261; b) D. Jayaprakash, H. Sasai, Tetrahedron:
Asymmetry 2001, 12, 2589; c) T. Arai, T. Sekiguti, K. Otsuki, S.
Takizawa, H. Sasai, Angew. Chem. 2003, 115, 2194; Angew.
Chem. In. Ed. 2003, 42, 2144; d) T. Sekiguti, Y. Iizuka, S.
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2647; e) S. Matsunaga, T. Ohshima, M. Shibasaki, Tetrahedron
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Tetrahedron Lett. 1999, 40, 8011; j) Y. M. A. Yamada, M.
Ichinohe, H. Takahashi, S. Ikegami, Tetrahedron Lett. 2002, 43,
3431.
5
714
ꢀ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2003, 42, 5711 –5714