Immobilization of heterobimetallic multifunctional asymmetric catalyst

Article abstract of DOI:10.1021/ol006837g

(equation presented) Immobilization of an asymmetric AlLibis(binaphthoxide) catalyst (ALB) is described. The immobilized ALBs (poly-ALBs) are readily prepared from polymeric BINOL derivatives and LiAlH₄. The combined use of 9 mol % of BuLi with

Full text of DOI:10.1021/ol006837g

ORGANIC
LETTERS
2000
Vol. 2, No. 26
4261-4263
Immobilization of Heterobimetallic
Multifunctional Asymmetric Catalyst
Takayoshi Arai,† Qiao-Sheng Hu,‡ Xiao-Fan Zheng,‡ Lin Pu,*,‡,§ and
,†
Hiroaki Sasai*
The Institute of Scientific and Industrial Research (ISIR), Osaka UniVersity, Ibaraki,
Osaka 567-0047, Japan, and Department of Chemistry, UniVersity of Virginia,
CharlottesVille, Virginia 22901
sasai@sanken.osaka-u.ac.jp
Received November 8, 2000
ABSTRACT
Immobilization of an asymmetric AlLibis(binaphthoxide) catalyst (ALB) is described. The immobilized ALBs (poly-ALBs) are readily prepared
from polymeric BINOL derivatives and LiAlH . The combined use of 9 mol % of BuLi with ca. 10 mol % (as a monomeric catalyst) of 6,6′-
4
aryl-tethered poly-ALB gave the Michael adducts with up to 93% ee. After completion of the reaction, the insoluble catalyst was recovered in
air and is reusable.
Heterobimetallic multifunctional catalysts1 have been rec-
ognized as new type of catalysts, which realize highly
efficient asymmetric reactions. For example, the AlLibis-
(binaphthoxide) complex (ALB),2 which consists of alumi-
num, lithium, and two molecules of BINOLs, enabled
excellent enantioselective Michael reactions of malonates
with enones in up to 99% ee (Figure 1).
process in which the insoluble catalyst is reusable after
filtration from the reaction mixture. The preparation of
immobilized catalysts has been traditionally studied by
introducing of chiral ligands to a sterically disordered
polymer backbone (e.g., polystyrene). In such a system, the
chiral ligands are randomly oriented along the polymer chain,
making it very difficult to systematically modify the het-
erobimetallic catalysts on a polymer. We envisioned the use
of chiral conjugated and sterically regular polymeric BINOL
derivatives3 for the efficient construction of immobilized
heterobimetallic multifunctional catalysts. These polymers
would have the ability to prepare polymeric catalysts where
the catalytic centers are highly organized along the polymer
chain. Herein, we report the first immobilization of a
heterobimetallic multifunctional asymmetric catalyst using
Figure 1. AlLibis(binaphthoxide) complex (ALB).
(1) Shibasaki, M.; Sasai, H.; Arai, T. Angew. Chem., Int. Ed. Engl. 1997,
36, 1236-1256.
(2) Arai, T.; Sasai, H.; Aoe, K.; Okamura, K.; Date, T.; Shibasaki, M.
Angew. Chem., Int. Ed. Engl. 1996, 35, 104-106.
Immobilization of the heterobimetallic catalysts is fasci-
nating for the development of an environmentally benign
(3) (a) Hu, Q.-S.; Zheng, X.-F.; Pu, L. J. Org. Chem. 1996, 61, 5200-
5201. (b) Hu, Q.-S.; Huang, W.-S.; Vitharana, D.; Zheng, X.-F.; Pu, L. J.
Am. Chem. Soc. 1997, 119, 12454-12464. For reviews, see: (c) Pu, L.
Chem. ReV. 1998, 98, 2405-2494. (d) Pu, L. Chem. Eur. J. 1999, 5, 2227-
2232.
† Osaka University.
‡ University of Virginia.
§ E-mail address: lp6n@virginia.edu.
10.1021/ol006837g CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/29/2000

conjugated polymeric BINOL derivatives. The immobilized
ALB was readily recovered by simple filtration and was
reusable.
Table 1. Asymmetric Michael Reaction Catalyzed by
Poly-ALB
In the creation of practically useful immobilized hetero-
bimetallic multifunctional catalysts, LiAlH4 was reacted with
polymeric BINOL (1a),3a which was directly conjugated at
the 6,6′-position of the BINOLs (Figure 2, top). When
entry
catalyst
time (h)
yield (%)
ee (%)
1
2
3
4
5
6
2a
73
26
49
48
49
52
32
85
69
78
26
66
55
58
85
93
56
11
2a -IIa
2b
2b-IIa
2c
2c-IIa
a The second generation of poly-ALB: 0.9 molar equiv of BuLi was
added to ca. 10 mol % of the parent poly-ALBs.
the enantiomeric excess of 5 to give values up to 85% ee.
This significant improvement may be attributed to the
flexibility of 2b, which should reduce the constraint on the
catalyst formation. The separation of the catalytic sites on
the polymer chain would also allow easy access of substrates
to the catalytic sites. These preliminary results prompted us
to conduct further studies using the second-generation ALB
(ALB-II).6
We have shown that addition of an equivalent quantity of
a basic reagent to the ALB catalyst dramatically enhances
the catalytic activity without reducing the enantiomeric
excesses of the Michael adducts. The combined use of 9 mol
% of BuLi with ca. 10 mol % (as a monomeric catalyst) of
poly-ALB 2b (poly-ALB-II (2b-II)) showed enhancement
of the catalytic activity and produced the adduct in 78% yield
with up to 93% ee (Table 1, entry 4).7 To represent other
types of poly-ALBs, the polymeric BINOL derivative (1c),3b
conjugated at the 3,3′-position on BINOLs, was also
examined. Compared to the 6,6′-tethered polymers (1a, 1b)
1c did not produce the insoluble complex upon reaction with
LiAlH4. In addition, the solution phase reactions using 2c
resulted in poor catalytic activity and was limited to a low
level of asymmetric induction. Starting from the 3,3′-tethered
BINOL derivative, catalyst formation would be sterically
disfavored. As a result, the immobilized second-generation
catalyst of poly-ALB 2b (poly-ALB-II (2b-II)) was revealed
to be the most promising for further studies. After 48 h the
Figure 2. Polymeric BINOL derivatives.
LiAlH4 powder was added to a THF solution of 1a,
spontaneous formation of an insoluble complex was ob-
served, with associated hydrogen gas generation.
(4) Preparation of poly-ALB catalyst (2b): To a stirred solution of
(R)-6,6′-aryl-tethered binaphthol derivative 1b (57.4 mg, 0.1 mmol as a
monomer) in THF (1 mL) was added a powder of LiAlH4 (1.9 mg, 0.05
mmol) at 0 °C. After being stirred for 12 h at room temperature, the resulting
suspension was directly used as a poly-ALB catalyst.
(5) The influence of the ratio of LiAlH4 and 1b on the Michael reaction
of 3 with 4 after 24 h at room temperature is as follows: 1:1 (67% yield,
32% ee), 1:2 (49%, 87% ee), 1:3 (19% yield, 89% ee).
(6) (a) Arai, T.; Yamada, Y. M. A.; Yamamoto, N.; Sasai, H.; Shibasaki,
M. Chem. Eur. J. 1996, 2, 1368-1372. (b) Arai, T.; Sasai, H.; Yamaguchi,
K.; Shibasaki, M. J. Am. Chem. Soc. 1998, 120, 441-442.
(7) Preparation of poly-ALB-II catalyst (2b-II): To a suspension of
poly-ALB catalyst (2b) (0.05 mmol as a monomeric catalyst) in THF was
added a solution of BuLi (28 µL, 0.045 mmol) in hexane at 0 °C. After
being stirred for 1 h at room temperature, the resulting suspension was
directly used as a poly-ALB-II catalyst.
The resulting insoluble polymeric ALB catalyst (poly-
ALB) 2a was revealed to have moderate catalytic activity
in the asymmetric Michael reaction of 2-cyclohexenone (3)
with dibenzyl malonate (4) and produced the target Michael
adduct (5) in 32% yield with 55% ee (Table 1, entry 1). The
reaction of a 6,6′-aryl-tethered polymeric BINOL derivative
(1b)3b with LiAlH4 was also found to form an insoluble
complex (2b) smoothly.4,5 The insoluble catalyst 2b improved
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Org. Lett., Vol. 2, No. 26, 2000

reaction was quenched by addition of 1 N HCl. The chiral
polymeric BINOL derivative (1b) was recovered from the
evaporated mixture by precipitation with methanol. More-
over, it is noteworthy that the immobilized poly-ALB-II (2b-
II) is directly recovered and reusable.
In conclusion, the insoluble AlLibis(binaphthoxide) com-
plex (ALB) was constructed by reaction of chiral polymeric
BINOL derivatives with LiAlH4. The immobilized poly-ALB
catalyst produced the Michael adducts in excellent ee, and
the insoluble catalyst was readily recovered and was reusable.
This is the first example of the immobilization of a
heterobimetallic multifunctional catalyst.9 The observation
that the aluminum-based chiral catalyst can be recovered in
air with retention of most of its catalytic activity and
enantioselectivity is very remarkable. This demonstrates that
the polybinaphthyl structure not only allows easy separation
of the catalysts from the reaction medium but can also lead
to more stable catalysts. The applications of polymeric
BINOLs to the preparation of other heterogeneous catalysts
are in progress.
As shown in Table 2, the catalyst was quantitatively
Table 2. Reuse of Immobilized Poly-ALB-II (2b-II)
run
yield (%)
ee (%)
recovery of catalyst
1
2
3
4
5
6a
78
66
68
56
51
83
93
89
88
76
73
85
quant.
98%
97%
95%
95%
93%
Acknowledgment. This work was supported by CREST
and a Grant-in-Aid for Scientific 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.
a 5 mol % of BuLi was added to the poly-ALB-II (2b-II) recovered from
run 5.
OL006837G
(8) Experimental procedure for 2b-II catalyzed asymmetric Michael
reactions: To a stirred suspension of poly-(R)-ALB-II (2b-II) (0.05 mmol
as a monomeric catalyst) in THF were added cyclohexenone (3) (48 µL,
0.5 mmol) and dibenzyl malonate (4) (125 µL, 0.5 mmol) at room
temperature. After being stirred for 48 h at the same temperature, the reaction
mixture was filtered to separate immobilized catalyst from the reaction
mixture. The organic extracts were concentrated to give an oily residue.
Purification by flash chromatography (SiO2, 25% acetone/hexane) gave the
Michael adduct 5 (165 mg, 87%) in 93% ee. After the residue was dried
under reduced pressure, poly-(R)-ALB-II (2b-II) (60 mg, quant.) was
recovered and reused to the next reaction.
recovered by simple filtration, and the catalyst exhibited
activity even after being used five times.8 In general, an
aluminum Lewis acid catalyst was difficult to reuse because
of the highly moisture-sensitive character. In the case of poly-
ALB-II (2b-II) catalyzed reactions, although the catalytic
activity was gradually reduced after being reused several
times, the addition of basic reagents restored the catalytic
activity (Table 2, entry 6). These results showed that the
immobilized aluminum catalyst in this study resisted deac-
tivation by moisture.
(9) Recently reported immobilized catalysts for asymmetric Michael
reactions: (a) Kim, Y. S.; Matsunaga, S.; Das, J.; Sekine, A.; Ohshima, T.;
Shibasaki, M. J. Am. Chem. Soc. 2000, 122, 6506-6507. (b) Matsunaga,
S.; Ohshima, T.; Shibasaki, M. Tetrahedron Lett. 2000, 41, 8473-8478.
Org. Lett., Vol. 2, No. 26, 2000
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