Immobilization of chiral ligands on polymer fibers by electron beam induced grafting and applications in enantioselective catalysis

Article abstract of DOI:10.1021/ol016212y

(Equation presented) Styrenic TADDOL and L-prolinol-derived monomers were immobilized on polyethylene fibers by electron beam induced preirradiation grafting using styrene as comonomer. The polymer-supported chiral ligands were utilized as catalysts in th

Full text of DOI:10.1021/ol016212y

ORGANIC
LETTERS
2001
Vol. 3, No. 16
2551-2554
Immobilization of Chiral Ligands on
Polymer Fibers by Electron Beam
Induced Grafting and Applications in
Enantioselective Catalysis
Sylvestre Degni, Carl-Eric Wile´n, and Reko Leino*
Laboratory of Polymer Technology, A° bo Akademi UniVersity, FIN-20500 A° bo, Finland
reko.leino@abo.fi
Received June 1, 2001
ABSTRACT
Styrenic TADDOL and L-prolinol-derived monomers were immobilized on polyethylene fibers by electron beam induced preirradiation grafting
using styrene as comonomer. The polymer-supported chiral ligands were utilized as catalysts in the asymmetric addition of diethylzinc to
benzaldehyde. Fiber-bound titanium TADDOLate gave a quantitative conversion of benzaldehyde to 1-phenylpropan-1-ol in a 97:3 S/R enantiomeric
ratio. The catalyst was successfully regenerated and employed in subsequent reactions with retention of high enantioselectivities.
Covalent immobilization of homogeneous catalysts to in-
soluble polymer supports has received considerable attention
in recent years.1 Heterogenization facilitates the separation
of the catalyst from reagents and products, simplifies the
efficient recovery of the often expensive or toxic catalysts,
and potentially allows the adaptation of the immobilized
catalysts to continuous flow type processes. While the
heterogenization of achiral catalysts is becoming standard
practice, effective immobilization of asymmetric catalysts
and auxiliaries remains as a particularly challenging target.2
Immobilization of chiral catalysts often results in lower
activities and enantioselectivities than observed for their
homogeneous counterparts.3 Evidently, architecture and
properties of the polymeric support play an important role
in determining the catalytic performance. The most common
type of polymeric supports are cross-linked polystyrene beads
prepared by suspension copolymerization of a polymerizable
ligand together with styrene and a suitable cross-linker such
(2) (a) Vidal-Ferran, A.; Bampos, N.; Moyano, A.; Perica`s, M. A.; Riera,
A.; Sanders, J. K. M. J. Org. Chem. 1998, 63, 6309. (b) Sung, D. W. L.;
Hodge, P.; Stratford, P. J. Chem. Soc., Perkin Trans. 1 1999, 1463. (c)
Altava, B.; Burguete, M. I.; Garc´ıa-Verdugo, E.; Luis, S. V.; Salvador, R.
V.; Vicent, M. J. Tetrahedron 1999, 55, 12987. (d) Angelino, M. D.; Laibnis,
P. E. J. Polym. Sci., Part A: Polym. Chem. 1999, 37, 3888. (e) Canali, L.;
Cowan, E.; Deleuze, H.; Gibson, C. L.; Sherrington, D. C. J. Chem. Soc.,
Perkin Trans. 1 2000, 2055. (f) Hu, J.; Zhao, G.; Yang, G.; Ding, Z. J.
Org. Chem. 2001, 66, 303.
(3) For exceptions, see: (a) Annis, D. A.; Jacobsen, E. N. J. Am. Chem.
Soc. 1999, 121, 4147. (b) ten Holte, P.; Wijgergangs, J.-P.; Thijs, L.;
Zwanenburg, B. Org. Lett. 1999, 1, 1095. (c) Wang, X.-W.; Sheng, J.-H.;
Da, C.-S.; Wang, H.-S.; Su, W.; Wang, R.; Chan, A. S. C. J. Org. Chem.
2000, 65, 295. (d) Sellner, H.; Faber, C.; Rheiner, P. B.; Seebach, D. Chem.
Eur. J. 2000, 6, 3692. (e) Reger, T. S.; Janda, K. D. J. Am. Chem. Soc.
2000, 122, 6929. (f) Hu, J.; Zhao, G.; Ding, Z. Angew. Chem., Int. Ed.
2001, 40, 1109.
(1) For reviews, see: (a) Shuttleworth, S. J.; Allin, S. M.; Sharma, P.
K. Synthesis 1997, 1217. (b) Bolm, C.; Gerlach, A. Eur. J. Org. Chem.
1998, 21. (c) Sherrington, D. C. Chem. Commun. 1998, 2275. (d) de Miguel,
Y. R. J. Chem. Soc., Perkin Trans. 1 2000, 4213. (e) Itsuno, S. In Lewis
Acids in Organic Synthesis; Yamamoto, H., Ed.; Wiley-VCH: Weinheim,
2000; Vol. 2, Chapter 21, p 945. (f) Bergbreiter, D. E. In Chiral Catalyst
Immobilization and Recycling; De Vos, D. E., Vankelecom, I. F. J., Jacobs,
P. A. Eds.; Wiley-VCH: Weinheim, 2000; Chapter 3, p 43. (g) Clapham,
B.; Reger, T. S.; Janda, K. D. Tetrahedron 2001, 57, 4637.
10.1021/ol016212y CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/17/2001

as divinylbenzene.4 Alternatively, the ligands can be grafted
to an existing cross-linked polystyrene resin containing
properly functionalized reactive groups. The degree of cross-
linking and the structure of the cross-linking agent strongly
influence the activity and selectivity of the catalyst.
Practical drawbacks of cross-linked polystyrene supports
are their low mechanical strength and restricted thermo-
oxidative stability. If the spherical beads are not sufficiently
stable to withstand stirring over a long period of time, their
breakdown will result in the formation of a fine powder,
which severely limits their handling during filtration and
recycling of the supported catalyst. Likewise, grafting of
functionalized ligands to chemically modified polystyrene
resins may result in undesired side reactions and incomplete
grafting; also functionalities may remain in the support
material that could reduce the effectiveness of the polymeric
catalyst. Thus, the development of new approaches for facile
anchoring of chiral catalysts to mechanically stable, inert
polymeric supports is of special interest. Fibrous supports
have received very little attention in the present context.5
Also, to our knowledge, radiation-induced grafting has not
been employed previously for immobilization of chiral
catalysts or auxiliaries on polymer supports. Nevertheless,
electron beam accelerators are not only readily available but
also widely used in the polymer processing industry.6
We report here the immobilization of chiral ligands on
chemically inert, mechanically stable polyethylene fibers by
electron beam induced preirradiation grafting using styrene
as a comonomer.7 Application of the resulting materials as
effective and recyclable catalysts in enantioselective organic
transformations is described.
The monomeric ligands selected for the present study
together with the corresponding supported catalysts are
depicted in Figure 1. The styrenic R,R,R′,R′-tetraaryl-1,3-
dioxolane-4,5-dimethanol (TADDOL) derivative 1 was pre-
pared as described previously by Seebach and co-workers.8
The protected L-proline-derived ligand precursor 2 was
prepared in 69% yield by addition of 4-(vinylphenyl)-
magnesium chloride to L-proline N-ethylcarbamate methyl
ester obtained by one-pot N,O-protection of L-proline.9
Refluxing of 2 in KOH/MeOH gave the chiral amino alcohol
3 in 84% yield after purification by flash chromatography.10
Ligand 1 was grafted on preirradiated polyethylene fibers
with styrene comonomer to produce the polymeric catalyst
P1 with a loading of 0.15 mmol/g.11 Reference catalyst P1B
Figure 1. Monomeric ligands and model compounds 1-5 and the
corresponding polymer-supported catalysts P1-P3 of the present
study.
was prepared by supporting ligand 1 on polystyrene beads
with a loading of 0.6 mmol/g by suspension copolymerization
of 1 with styrene using divinylbenzene as a cross-linking
agent.8 The protected prolinol 2 was grafted in a fashion
similar to that described for 1 to produce the fiber-supported
catalyst P2 with a loading of 0.2 mmol/g as confirmed by
nitrogen analysis. The deprotected prolinol functionalized
polymer P3 with similar loading was obtained in quantitative
yield by refluxing P2 in KOH/MeOH followed by drying in
vacuo. The homogeneous reference ligands 4 and 5 were
purchased from commercial sources.
(4) Syntheses and Separations Using Functional Polymers; Sherrington,
D. C., Hodge, P., Eds.; Wiley: Chichester, 1988.
Watanabe, K.; Koizumi, T.; Ito, K. React. Polym. 1995, 24, 219. Polymer-
supported 3 was employed as catalyst in the Diels-Alder reaction of
methacrolein with cyclopentadiene, resulting in high yield and high exo-
selectivity but a low level of asymmetric induction (ee ) 25%).
(5) Grafting of a phenolic TADDOL derivative to a chloromethylated
ethylene-styrene copolymer has been described briefly, see: Altava, B.;
Burguete, M. I.; Escuder, B.; Luis, S. V.; Salvador, R. V.; Fraile, J. M.;
Mayoral, J. A.; Royo, A. J. J. Org. Chem. 1997, 62, 3126.
(6) McGinniss, V. D. In Encyclopedia of Polymer Science and Engineer-
ing, 2nd ed.; Kroschwitz, J. I., Ed.; Wiley: New York, 1986; Vol. 4, p
418.
(7) (a) Stannett, V. T. Radiat. Phys. Chem.1990, 35, 82. (b) Na¨sman, J.
H.; Sundell, M. J.; Ekman, K. B. U.S. Patent 5 326 825, 1994.
(8) Seebach, D.; Marti, R. E.; Hintermann, T. HelV. Chim. Acta 1996,
79, 1710.
(9) Bhaskar Kanth, J. V.; Periasamy, M. Tetrahedron 1993, 49, 5127.
(10) A low-yield synthesis of 3 from TMS-protected L-proline and its
copolymerization with styrene to insoluble polymeric catalyst has been
reported previously, see: (a) Itsuno, S.; Kamahori, K.; Watanabe, K.;
Koizumi, T.; Ito, K. Tetrahedron: Asymmetry 1994, 5, 523. (b) Itsuno, S.;
(11) Loading of P1 was approximated gravimetrically. In a typical
grafting procedure, 10 g of cut PE fibers (0.7 Dtex) were irradiated under
an inert atmosphere to a total dose of 200 kGy using an electron accelerator
operating at an accelerator voltage of 175 kV and beam current of 5 mA.
The irradiated fibers were immersed in a reaction mixture containing 15 g
of styrene, 1.8 g of 1, 40 mL of EtOH, and 20 mL of water. To the reaction
mixture were additionally added 0.03 g of divinyl benzene and 0.155 g of
a 25 wt % solution of dibenzoyl peroxide. The mixture was purged with
N2 before initiating the reaction and the grafting was allowed to continue
to completion for approximately 6 h. The temperature was raised to 80 °C
for 2 h, and the resulting fibers were subsequently filtered and washed with
EtOH and dichloroethane. The weight gain of the recovered fibers was
determined and the conversion of the monomers calculated to 80%.
2552
Org. Lett., Vol. 3, No. 16, 2001

The fiber-supported TADDOL P1 was employed as a
ligand in the titanium-catalyzed addition of diethylzinc to
benzaldehyde12 and its performance compared with those of
previously described P1B and 4. The results are summarized
in Table 1. The enantioselectivity of the fibrous catalyst P1
support morphology was observed in the present work when
P1B was subjected to stirring, especially with longer reaction
times. The fiber-supported TADDOL described here thus
provides an attractive alternative as a mechanically stable,
easily recyclable heterogeneous catalyst resulting in equally
high enantioselectivities.
The fiber-supported chiral amino alcohol P3 was employed
as a catalyst in two types of reactions. The results of
diethylzinc addition to benzaldehyde12 using P3 along with
the homogeneous reference catalysts 3 and 5 are presented
in Table 2. The reduction of benzophenone with NaBH4/
Table 1. Comparison of the Fiber-Supported Titanium
TADDOLate Derived from P1 with P1B and 4 in the Addition
of Et2Zn to PhCHO
Table 2. Comparison of the Fiber-Supported Amino Alcohol
P3 with 3 and 5 as Catalysts in the Addition of Et2Zn to
PhCHO
PhCHO
(mmol/mL)a
loading
(mmol/g)c
convn
(%)d
ligand
pol. (g)b
S/R
4
P 1
P 1e
P 1f
P 1B
P 1Be
0.13
0.06
0.06
0.06
0.15
0.15
quant.
quant.
99
89
quant.
90
99:1
97:3
96:4
97:3
97:3
97:3
1.0
0.8
0.7
0.25
0.23
0.15
0.15
0.15
0.6
PhCHO
(mmol/mL)a
loading
(mmol/g)c
yield
(%)d
ligand
pol. (g)b
R/S
0.6
5
3
P 3
P 3f
P 3g
0.38
0.38
0.52
0.56
0.49
97
70e
36
33
30
84:16
88:12
62:38
60:40
61:39
a Concentration in mmol of PhCHO per mL of toluene. b Amount of
polymer before loading with titanate. c Loading of the polymeric catalyst
in mmol of TADDOL per g of polymer. d Conversion after 19 h by GC.
e First regeneration of the polymeric catalyst. f Second regeneration.
1.0
0.8
0.7
0.21
0.21
0.21
a Concentration in mmol of PhCHO per mL of toluene. b Amount of
polymer. c Loading of the polymeric catalyst in mmol of amino alcohol
per g of polymer. d Yield after 24 h by GC. e Isolated yield by column
chromatography. f First regeneration of the polymeric catalyst. g Second
regeneration.
(es ) 97%) was equally high compared with that of
TADDOL P1B supported on beads and only slightly lower
than that observed for the homogeneous system (es ) 99%).
Both polymer-supported catalysts were successfully recycled
after quenching with HCl, filtration, and subsequent washings
with H2O, THF, and Et2O.8 Conversions decreased slightly
upon regeneration whereas the enantioselectivities remained
high. Performance of P1B was analogous to that reported
earlier by Seebach.8 The main difference between the two
polymer-supported catalysts was the slower rate of reaction
observed with the fibrous TADDOL P1, which may result
from the different swelling characteristics, different loadings,
and different accessibilities of the active sites between the
two types of catalysts. These parameters are, however,
subject to optimization, and studies along these lines are
currently in progress.
TMSCl using P3, 3, and 5 is presented in Table 3.16
In the addition of diethylzinc to benzaldehyde, the
performance of the styryl-substituted homogeneous catalyst
3 was comparable to that of the phenyl analogue 5. Both
catalysts resulted in high yields and moderate enantioselec-
Table 3. Comparison of the Fiber-Supported Amino Alcohol
P3 with 3 and 5 as Catalysts in the Reduction of PhCOMe with
NaBH4/Me3SiCl
Since the seminal work of Seebach and co-workers,
TADDOLs and their closely related derivatives have become
an extraordinarily versatile class of chiral auxiliaries with
applications extending from utilization as stoichiometric
reagents or chiral Lewis acids to catalytic enantioselective
hydrogenations and stereoregular metathesis polymeriza-
tions.13 In previous reports, TADDOLs have been heterog-
enized by incorporation or grafting onto Merrifield resin,
polystyrene, controlled pore glass, dendritic macromolecules,
and monolithic polymer rods.5,8,14,15 Severe degradation of
PhCOMe
(mmol/mL)a
loading
(mmol/g)c
yield
(%)d
ligand
pol. (g)b
0.5
R/S
5
3
P 3
0.5
0.5
0.5
quant.
98
99
98:2
97:3
52:47
0.21
a Concentration in mmol of PhCOMe per mL of THF. b Amount of
polymer. c Loading of the polymeric catalyst in mmol of amino alcohol
per g of polymer. d Quenched 2 min after completed addition.
(12) For a review, see: Pu, L.; Yu, H.-B. Chem. ReV. 2001, 757.
(13) For a review, see: Seebach, D.; Beck, A. K.; Heckel, A. Angew.
Chem., Int. Ed. 2001, 40, 92.
Org. Lett., Vol. 3, No. 16, 2001
2553

tivities (es ) 84-88%), consistent with the literature data
for proline-based ligands.12 The polymer-supported catalyst
P3, however, suffered from a considerable decrease in yield
and a significant drop in enantioselectivity (es ) 60%), as
observed previously for other supported chiral amino al-
chols.12 Recyclability of P3 was, however, successful, and
both enantioselectivity and conversion remained on the same
level upon regeneration of the catalyst. Also the fibrous
morphology of the support was retained.
Table 4. Titanium-Mediated Addition of Et2Zn to PhCHO
Using P2 and 2
PhCHO
(mmol/mL)a
pol.
(g)b
loading
(mmol/g)c
yield
(%)
Supporting of the prolinol ligand from the phenyl sub-
stituents possibly decreases the flexibility of the chiral ligand,
causing steric hindrance at the active site. In earlier reports,
higher enantioselectivities have been obtained by immobi-
lization of similar ligands via a flexible linker connected to
the nitrogen atom.12 A similar approach using the methodol-
ogy described here may provide a feasible access to highly
selective fiber-supported amino alcohols.
ligand
S/R
2
P 2
0.10
0.11
87d
55e
74:26
62:38
2.25
0.21
a Concentration in mmol of PhCHO per mL of toluene. b Amount of
polymer before loading with titanate. c Loading of the polymeric catalyst
in mmol of L-prolinol N-ethylcarbamate per g of polymer. d Yield after 26
h by GC. e Yield after 24 h.
An even more dramatic decrease in enantioselectivity was
observed in the reduction of benzophenone using P3 in
combination with NaBH4 and trimethylchlorosilane (Table
3). Whereas both homogeneous catalysts 3 and 5 produced
the chiral alcohol in high enantioselectivities (es ) 97-98%)
and nearly quantitative yields, the fiber-supported P3 ex-
hibited only marginal enantiocontrol (es ) 52%) despite the
retained yield. The performance of 5 was analogous to that
described in the literature.16
The fiber-supported ethyl carbamate ligand P2 was further
employed as a catalyst in the titanium-catalyzed addition of
diethylzinc to benzaldehyde in the same fashion as described
for the TADDOL-based catalysts P1 and P1B. The results
are presented in Table 4. Both P2 and the homogeneous
reference catalyst 2 displayed moderate but significant
enantioselectivities (es ) 62-74%) with higher yields
obtained under homogeneous conditions. Apparently the
alcohol and/or keto functionalities of this ligand are acces-
sible for coordination to titanium, generating a chiral
environment resulting in enantiocontrol.17
approach for immobilization of chiral catalysts on mechani-
cally stable fibrous polymer supports. This method provides
an attractive alternative to the traditional and predominant
suspension copolymerization and grafting methods for het-
erogenization of chiral ligands and auxiliaries. High yields
and high enantioselectives, as well as simple and efficient
recyclabilities, are accessible with the fibrous catalysts,
especially in combination with the TADDOL-based auxil-
iaries. While the loadings described here are relatively low,
attempts to increase the degrees of functionalization will be
addressed in future work.
Acknowledgment. This work was supported by the
Academy of Finland and Smoptech Ltd. S.D. is grateful to
Svenska Tekniska Vetenskapsakademin for a graduate fel-
lowship. The authors thank Robert Peltonen, Kenneth Ekman,
and Mats Sundell (Smoptech Ltd.) for supplying the polymer
fibers and for carrying out the preirradiation grafting experi-
ments. Pa¨ivi Pennanen, Markku Reunanen, and Mattias
Roslund are thanked for their skillful assistance with MS
and NMR analyses. The authors would also like to thank
Professor Dr. Dieter Seebach and Alexander Heckel for
helpful comments during the preparation of the manuscript.
In summary, we have shown that the combination of
electron beam induced preirradiation grafting using styryl-
substituted chiral ligands provides a facile high yield
(14) (a) Altava, B.; Burguete, I.; Luis, S. V.; Mayoral, J. A. Tetrahedron
1994, 50, 7535. (b) Altava, B.; Burguete, M. I.; Fraile, J. M.; Garc´ıa, J. I.;
Luis, S. V.; Mayoral, J. A.; Vicent, M. J. Angew. Chem., Int. Ed. 2000, 39,
1503.
(15) (a) Rheiner, P. B.; Sellner, H.; Seebach, D. HelV. Chim. Acta 1997,
80, 2027. (b) Comina, P. J.; Beck, A. K.; Seebach, D. Org. Process Res.
DeV. 1998, 2, 18. (c) Rheiner, P. B.; Seebach, D. Chem. Eur. J. 1999, 5,
3221. (d) Heckel, A.; Seebach, D. Angew. Chem., Int. Ed. . 2000, 39, 163.
(16) Jiang, B.; Feng, Y.; Zheng, J. Tetrahedron Lett. 2000, 41, 10281.
(17) See also: Takahashi, H.; Kawabata, A.; Higashiyama, K. Chem.
Pharm. Bull. 1987, 35, 1604.
Supporting Information Available: Experimental pro-
cedures and analytical data for compounds 2 and 3 and
polymeric catalysts P1-P3 and the addition and reduction
reactions. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL016212Y
2554
Org. Lett., Vol. 3, No. 16, 2001