Polymer-supported bisBINOL ligands for the immobilization of multicomponent asymmetric catalysts

Article abstract of DOI:10.1021/ol034797l

(Matrix presented) Polymer-supported bisBINOL ligands were successfully utilized for the immobilization of multicomponent asymmetric catalysts. The polymer-supported Al-Li-bis(binaphthoxide) (ALB) catalyst was more effective than the dendrimer-supported A

Full text of DOI:10.1021/ol034797l

ORGANIC
LETTERS
2003
Vol. 5, No. 15
2647-2650
Polymer-Supported BisBINOL Ligands
for the Immobilization of
Multicomponent Asymmetric Catalysts
Tetuya Sekiguti, Yoshimasa Iizuka, Shinobu Takizawa, Doss Jayaprakash,
Takayoshi Arai, and Hiroaki Sasai*
The Institute of Scientific and Industrial Research (ISIR), Osaka UniVersity,
Mihogaoka, Ibaraki, Osaka 567-0047, Japan
sasai@sanken.osaka-u.ac.jp
Received May 9, 2003
ABSTRACT
Polymer-supported bisBINOL ligands were successfully utilized for the immobilization of multicomponent asymmetric catalysts. The polymer-
supported Al-Li-bis(binaphthoxide) (ALB) catalyst was more effective than the dendrimer-supported ALB in the Michael reaction of 2-cyclohexen-
1-one with dibenzyl malonate affording the adduct in 91% yield with 96% ee. The polymer was also effective for the immobilization of a
µ-oxodititanium complex that promoted carbonyl-ene reaction of ethyl glyoxalate with r-methyl styrene to provide the adduct with up to 98%
ee.
Synergistic cooperation between two or more functional
groups and/or metals plays an important role in realizing high
reactivity and stereoselectivity in many enzymatic reactions.
Highly organized multicomponent asymmetric catalysts have
recently been designed that utilize this synergistic cooperation
strategy for enantioselective reactions.1,2 In this regard, we
have reported a series of multicomponent asymmetric
catalysts that consist of two or three molecules of BINOL
and two kinds of metals for a range of asymmetric
transformations.3 Immobilization of these catalysts onto
recoverable supports would expand their potential in terms
of economic and operational benefits. However, such an
attempt would require organization of the corresponding
ligands on these supports in a manner observed in the parent
homogeneous catalysts. The conventional approach using
polystyrene resin resulted in less efficient catalysts due to
the random orientation of ligands on the polymer affording
the product in 27% yield with 0% ee. Dendrimers with well-
defined macromolecular structures would construct a pre-
cisely controlled catalyst structure on their periphery.4
Recently, we have developed dendrimer-supported BINOL
ligands (Figure 1) for the immobilization of catalysts such
as Al-Li-bis(binaphthoxide) complex (ALB) and Ga-Na-bis-
(binaphthoxide) complex (GaSB).5 The dendrimer-supported
catalysts were found to promote the asymmetric Michael
(1) (a) Mikami, K.; Korenaga, T.; Terada, M.; Ohkuma, T.; Pham, T.;
Noyori, R. Angew. Chem., Int. Ed. 1999, 38, 495-497. (b) Ishitani, H.;
Ueno, M.; Kobayashi, S. J. Am. Chem. Soc. 2000, 122, 8180-8186. (c)
Furuno, H.; Hanamoto, T.; Sugimoto, Y.; Inanaga, J. Org. Lett. 2000, 2,
49-52. (d) Kobayashi, S.; Ishitani, H. J. Am. Chem. Soc. 1994, 116, 4083-
4084.
(2) For recent reviews, see: (a) Shibasaki, M.; Sasai, H.; Arai, T. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1236-1256. (b) Rowlands, G. J. Tetrahedron
2001, 57, 1865-1882. (c) Shibasaki, M.; Yoshikawa, N. Chem. ReV. 2002,
102, 2187-2209.
(3) (a) Arai, T.; Sasai, H.; Aoe, K.; Okamura, K.; Date, T.; Shibasaki,
M. Angew. Chem., Int. Ed. Engl. 1996, 35, 104-106. (b) Arai, T.; Yamada,
Y. M. A.; Yamamoto, N.; Sasai, H.; Shibasaki, M. Chem. Eur. J. 1996, 2,
1368-1372. (c) Arai, T.; Sasai, H.; Yamaguchi, K.; Shibasaki, M. J. Am.
Chem. Soc. 1998, 120, 441-442.
10.1021/ol034797l CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/24/2003

Scheme 1. Representative Preparation of Polymer Containing
BisBINOL Ligand
Figure 1. Dendrimer-supported multicomponent asymmetric cata-
lyst.
reaction of 2-cyclohexen-1-one with dibenzyl malonate.
While the Michael adduct was obtained with good selectivity,
the chemical yields were moderate. In addition, the synthesis
of the dendrimers involves multiple steps and often results
in low yields, thereby limiting their potential in dendrimer-
supported catalysts. In this regard, dendronized polymers,6
which combine the advantages of dendrimers and linear
polymers, appear to be promising alternatives. Polymerization
of a dendron with a comonomer would readily afford
polymeric ligands (Scheme 1) that could be used for the
efficient construction of asymmetric catalysts.7 Herein, we
report the immobilization of multicomponent asymmetric
catalysts using polymers containing bisBINOL ligands that
closely resemble dendronized polymers.
The polymer-supported ALB catalyst 4a was obtained as
a white precipitate by the addition of AlMe3 and t-BuLi to
polymer 3a in THF.8 The catalyst 4a promoted asymmetric
Michael reaction of 2-cyclohexen-1-one (5) with dibenzyl
malonate (6), affording the Michael adduct 7 in 36% yield
with 96% ee (Table 1, entry 1).9 A possible reason for the
As shown in Scheme 2, monomer 2 consisting of bis-
BINOL moiety was synthesized from 15 by coupling with
acryloyl chloride followed by cleavage of the protecting
groups. Copolymerization of 2 with 1 equiv of methyl
methacrylate (MMA) in the presence of AIBN afforded the
polymer-supported bisBINOL ligand 3a, which was precipi-
tated from MeOH (Mw ) 84 000, PDI ) 10 by GPC
analysis).
Table 1. Asymmetric Michael Reaction Catalyzed by
Polymer-Supported ALB
entry
catalyst
yield (%)
ee (%)
(4) (a) Sato, I.; Shibata, T.; Ohtake, K.; Kodaka, R.; Hirokawa, Y.; Shirai,
N.; Soai, K. Tetrahedron Lett. 2000, 41, 3123-3126. (b) Schneider, R.;
Ko¨llner, C.; Weber, I.; Togni, A. Chem. Commun. 1999, 2415-2416. (c)
Seebach, D.; Marti, R. E.; Hintermann, T. HelV. Chim. Acta 1996, 79, 1710-
1740. (d) Van Heerbeek, R.; Kamer, P. C. J.; Van Leeuwen, P. W. N. M.;
Reek, J. N. H. Chem. ReV. 2002, 102, 3717-3756. (e) Astruc, D.; Chardac,
F. Chem. ReV. 2001, 101, 2991-3023. (f) Reek, J. N. H.; De Groot, D.;
Oosterom, G. E.; Kamer, P. C. J.; Van Leeuwen, P. W. N. M. ReV. Mol.
Biotechnol. 2002, 90, 159-181.
1
2
3
4a
4b
36
91
77
96
93
90
dendrimer-supported catalyst
a As a monomeric catalyst.
low yield could be overcrowding of the catalytic sites
resulting in diminished reaction rates. To enable site separa-
tion between the catalysts, momomer 2 was polymerized with
3 equiv of MMA to obtain polymer 3b (Mw ) 16 000, PDI
) 2.1 by GPC analysis). As expected the catalyst 4b,
(5) Arai, T.; Sekiguti, T.; Iizuka, Y.; Takizawa, S.; Sakamoto, S.;
Yamaguchi, K.; Sasai, H. Tetrahedron: Asymmetry 2002, 13, 2083-2087.
(6) (a) Grayson, S. M.; Fre´chet, J. M. J. Chem. ReV. 2001, 101, 3819-
3867. (b) Hecht, S.; Fre´chet, J. M. J. Angew. Chem., Int. Ed. 2001, 40,
74-91. (c) Schlu¨ter, A. D.; Rabe, J. P. Angew. Chem., Int. Ed. 2000, 39,
864-883. (d) Yin, R.; Zhu, Y.; Tomalia, D. A.; Ibuki, H. J. Am. Chem.
Soc. 1998, 120, 2678-2679. (e) Percec, V.; Ahn, C.-H.; Ungar, G.;
Yeardley, D. J. P.; Mo¨ller, M.; Sheiko, S. S. Nature 1998, 391, 161-164.
(f) Frey, H. Angew. Chem., Int. Ed. 1998, 37, 2193-2197. (g) Schlu¨ter, A.
D. Dendrimers with Polymeric Core: Towards Nanocylinders. In Topics
in Current Chemistry; Vo¨gtle, F., Ed.; Springer: Berlin, 1998; Vol. 197:
Dendrimers, pp 165-191.
(8) Typical Procedure for the Preparation of a Polymer-Supported ALB
Catalyst: Polymer 3a (18.2 mg, 0.04 mmol as a BINOL unit) was dissolved
in 0.4 mL of THF after drying at 45 °C in vacuo for 2 h. To the solution
were added AlMe3 (0.98M, 20.4 µL, 0.02 mmol) and t-BuLi (1.49M, 13.5
µL, 0.02 mmol) at -78 °C. A white precipitate, obtained when the solution
was warmed to room temperature, was directly used as an immobilized
ALB catalyst.
(7) Dendronized polymers as chiral ligands: (a) Hu, Q.-S.; Sun, C.;
Monaghan, C. E. Tetrahedron Lett. 2002, 43, 927-930. (b) Sellner, H.;
Rheiner, P. B.; Seebach, D. HelV. Chim. Acta 2002, 85, 352-387.
2648
Org. Lett., Vol. 5, No. 15, 2003

Scheme 2. Synthesis of Polymer-Supported BisBINOL Ligand and Preparation of Supported ALB Catalyst
prepared from polymer 3b, afforded the Michael adduct in
91% yield with 93% ee (entry 2). The polymers enable easy
site separation, thereby resulting in enhanced reactivity.
While a similar effect could account for lower yields in the
case of dendrimer-supported catalysts (entry 3),5 site separa-
tion on the periphery with higher generation dendrimers is
rather difficult. Thus, by virtue of a simpler synthetic route,
the new polymer-supported catalysts promise to be advanta-
geous over dendrimer-supported counterparts. After the
completion of the reaction, the polymer 3b was quantitatively
recovered by precipitation from MeOH.
To demonstrate the generality of the use of polymer-
supported bisBINOL ligands for the construction of im-
mobilized multicomponent asymmetric catalysts, the study
was extended to µ-oxodititanium catalysts. Nakai et al.
reported that bimetallic titanium BINOL complex promoted
the asymmetric carbonyl-ene reaction of methyl glyoxylate
(9) with R-methyl styrene (10) in high yield with excellent
enantioselectivity.10 The polymer-supported Ti complex was
prepared as shown in Scheme 3.
To a solution of 3b (27 mg, 0.06 mmol as BINOL unit)
in CH2Cl2 (1.5 mL) was added 1 equiv of Ti(O-i-Pr)4 (18
µL, 0.06 mmol) at 0 °C. After the mixture was stirred for 6
h at room temperature, a mixed solution of toluene (0.7 mL),
CH2Cl2 (7 mL), and H2O (0.06 mmol, 1.1 µL) was added.
The solution was stirred for 18 h, and the solvents were
removed azeotropically at 80 °C under reduced pressure. The
reddish brown complex 8 thus obtained promoted the
carbonyl-ene reaction of 9 with 10 in Et2O to give the adduct
11 in 53% yield with 95% ee after 72 h (Table 2, entry 1).
Addition of 4 Å molecular sieves (MS) (100 mg/mmol of
10) dramatically improved the catalytic activity (entry 2).
The enantioselectivities obtained with this system are higher
than those reported with soluble linear polymers and highlight
Scheme 3. Preparation of Polymer-Supported Ti Complex
(9) Typical Procedure for Asymmetric Michael Reaction. To the polymer-
supported ALB catalyst 4 (0.02 mol as a single catalytic site) in THF (0.4
mL) were added 5 (25 µL, 0.22 mmol) and 6 (50 µL, 0.20 mmol) at room
temperature. After completion of the reaction, the reaction was quenched
with aqueous 1 N HCl at room temperature, and the mixture was then
extracted with AcOEt. The combined organic extracts were neutralized with
saturated aqueous NaHCO3, washed with brine, dried over Na2SO4, and
concentrated. Separation of crude Michael product from polymer 3 was
accomplished by precipitation of the residue from hexane. After concentra-
tion of the resulting supernatant, purification by flash chromatography (SiO2,
acetone/hexane ) 1/10) gave 7. The enantiomeric purity of 7 was determined
by chiral HPLC analysis (Daicel CHIRALPAK AS, i-PrOH/hexane ) 1/4,
1.0 mL/min, 254 nm).
(10) Kitamoto, D.; Imma, H.; Nakai, T. Tetrahedron Lett. 1995, 36,
1861-1864.
Org. Lett., Vol. 5, No. 15, 2003
2649

17% decrease in chemical yield was observed between the
first and second use of the catalyst. The decrease in yield
was unavoidable despite the addition of 4 Å MS to the
reaction during the second use of the catalyst. A possible
reason for the decrease in yield could be the conversion of
the polymer-bound complex to a less active form with time.
In conclusion, we have demonstrated a brief preparation
of polymer-supported bisBINOL ligands to immobilize
multicomponent asymmetric catalysts such as ALB and
µ-oxodititanium catalysts. Both immobilized catalysts pro-
moted the target reactions with high enantioselectivities. This
is the first example of the use of polymers containing
bisBINOL ligands to immobilize multicomponent asym-
metric catalysts. Further applications toward the immobiliza-
tion of other catalysts are in progress.13
Table 2. Application and Reuse of Polymer-Supported Ti
Catalyst in Asymmetric Carbonyl-Ene Reaction
entry
mol % catalyst
4 Å MS
yield (%)
ee (%)
1
2
10
10
20
20
-
+
+
+
53
quant
83
95
96
98
92
3 (2nd use)
4 (3rd use)
74
the advantage of these polymers.11 Encouraged by these
results, we tried to reuse 8.12 The catalyst 8 was recovered
by removing the clear supernatant with a syringe under an
Ar atmosphere. The catalyst maintained high enantioselec-
tivity even during the third use (entry 4). Although the ICP-
AES analysis revealed that less than 2% of the immobilized
titanium was lost by way of leaching after the first use, a
Acknowledgment. This work was supported by a Grant-
in-Aid for Scientific Research from the Ministry of Educa-
tion, Culture, Sports, Science and Technology, Japan. We
thank the technical staff in the Materials Analysis Center of
ISIR, Osaka University.
Supporting Information Available: Experimental pro-
cedures and spectral data. This material is available free of
charge via the Internet at http://pubs.acs.org.
(11) Yamada, Y. M. A.; Ichinohe, M.; Takahashi, H.; Ikegami, S.
Tetrahedron Lett. 2002, 43, 3431-3434.
(12) Typical Procedure for Reuse of Polymer-Supported µ-Oxodititanium
Catalyst. To a mixture of activated 4 Å MS (dried in vacuo at 150 °C for
2 h) (30 mg) and the insoluble polymer-supported µ-oxodititanium catalyst
(0.03 mmol as the single catalytic site) in Et2O (2 mL) were added 9 as a
50% toluene solution (92 µL, 0.9 mmol) and 10 (39 µL, 0.3 mmol). After
the mixture was stirred at room temperature for 72 h, the clear supernatant
was removed via syringe. The catalyst was repeatedly washed with fresh
Et2O (1 mL × 2) under an Ar atmosphere. The combined Et2O extract was
concentrated and purified by flash column chromatography (SiO2, AcOEt/
hexane ) 1/7) to give 11. To the catalyst residue were added fresh Et2O (2
mL), 9 (46 µL, 0.45 mmol), and 10 (20 µL, 0.15 mmol). The enantiomeric
purity of 11 was determined by chiral HPLC analysis (Daicel CHIRALPAK
AS, i-PrOH/hexane ) 1/4, 1.0 mL/min, 254 nm).
OL034797L
(13) Recently, we have demonstrated a new and general concept for
constructing multicomponent asymmetric catalysts using a “catalyst ana-
logue”. In this method, after copolymerization of a catalyst analogue having
olefinic moieties with a monomer (e.g., MMA), the resulting polymer was
used to prepare an active catalyst by exchanging the connecting group in
the catalyst analogue with a catalytically active group. Arai, T.; Sekiguti,
T.; Otsuki, K.; Takizawa, S.; Sasai, H. Angew. Chem., Int. Ed. 2003, 42,
2144-2147.
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Org. Lett., Vol. 5, No. 15, 2003