Synthesis of Catalytically Active Polymers by Means of ROMP: An Effective Approach toward Polymeric Homogeneously Soluble Catalysts

Full text of DOI:10.1021/jo990533u

5730
J . Org. Chem. 1999, 64, 5730-5731
Communications
bicyclic olefins. A successful application of this method that
leads to homogeneously soluble catalysts is demonstrated.
Encouraged by the results of Kiessling et al.,7,8 who used
Grubbs’s commercially available ROMP catalyst 19 for the
synthesis of complex carbohydrate-substituted polymers, we
envisaged functionalized bicyclic monomers 2 and 3 as
appropriate starting materials. This approach has the
advantage of being highly modular and thus allows a flexible
process optimization by combining independently selected
bicyclic frameworks, linkers, and catalytically active sub-
units. Furthermore, the polymer structure could easily be
modified by random copolymerization or systematic block-
copolymerization with other olefins10 and by introduction of
backbone chirality, respectively.11
Syn th esis of Ca ta lytica lly Active P olym er s by
Mea n s of ROMP : An Effective Ap p r oa ch
tow a r d P olym er ic Hom ogen eou sly Solu ble
Ca ta lysts
Carsten Bolm,*,† Christian L. Dinter,† Andreas Seger,†
Hartwig Ho¨cker,‡ and J o¨rg Brozio‡
Institut fu¨r Organische Chemie der RWTH Aachen,
Professor-Pirlet-Str. 1, D-52056 Aachen, Germany, and
Deutsches Wollforschungsinstitut an der RWTH Aachen e.V.,
Veltmansplatz 8, D-52062 Aachen, Germany
Received March 29, 1999
Polymeric reagents and catalysts have widely been used
in organic synthesis.1 In large-scale industrial processes the
application of polymer-supported catalysts is also desirable
because it can lead to durable catalytic activity or allow easy
catalyst separation.1,2 A common strategy for the preparation
of such catalysts involves the attachment of a previously
identified catalytically active subunit to a preformed poly-
meric support. For the development of chiral catalysts to be
used in the synthesis of optically active products, this
protocol is particularly difficult because the systematic
optimization of reactivity and enantioselectivity is hindered
due to the fact that the catalytically active subunits are more
or less randomly distributed along an irregular polymer
chain. Recently, another synthetic concept was nicely ex-
amplified by Pu and co-workers,3 who introduced a new type
of polymeric catalysts having a rigid, highly organized
binaphthyl-based chiral backbone. These polymers are
prepared by multiple palladium-catalyzed Suzuki couplings
of appropriately substituted arenes, and they have success-
fully been applied in Mukaiyama aldol reactions,3 diethylzinc
additions to aldehydes,4 and hetero-Diels-Alder reactions.5
Here, we present an alternative approach for the generation
of polymeric multivalent chiral catalysts, which is based on
ring opening metathesis polymerization (ROMP)6 of strained
On the basis of our previous work with 4a ,12 a chiral
hydroxylpyridinyl fragment was selected as the catalytically
active subunit. A two-carbon linker was attached to known
pyridine (R)-4b13 to give (R)-5 in 83% yield. Bicyclic olefin 7
was then obtained by coupling of 2 equiv of (R)-5 with exo-
7-oxanorbornene anhydride (6) under Mukaiyama esterifi-
cation conditions.14 This route provides rapid access to mono-
mers bearing two identical homochiral hydroxylpyridinyl
residues. Preparation of the unsymmetrical bicyclic mono-
mer 9 was achieved by reacting monomethyl ester 815 with
1 equiv of pyridinyl diol (R)-5. Standard DCC coupling gave
9, bearing only a single hydroxylpyridinyl unit, in 94% yield.
ROMP of 7 and 9, respectively, was accomplished by
treatment of their dichloromethane solutions with Grubbs’s
* To whom the correspondence should be addressed. Phone: (int) +49
241 804675. Fax: (int) +49 8888 391. e-mail: Carsten.Bolm@oc.rwth-
aachen.de.
† Institut fu¨r Organische Chemie der RWTH Aachen.
‡ Deutsches Wollforschungsinstitut an der RWTH Aachen e.V.
(1) (a) Pittman, C. U., J r. In Comprehensive Organometallic Chemistry;
Wilkinson, G.; Stone, F. G. A.; Abel, E. W., Eds.; Pergamon Press: Oxford,
1982; Vol. 8, p 553. (b) Shuttleworth, S. J .; Allin, S. M.; Sharma, P. K.
Synthesis 1997, 1217. (c) Sherrington, D. C. Chem. Commun. 1998, 2275.
(d) Hermkens, P. H. H.; Ottenheijm, H. C. J .; Rees, D. Tetrahedron 1996,
52, 4527. (e) Hermkens, P. H. H.; Ottenheijm, H. C. J .; Rees, D. C.
Tetrahedron 1997, 53, 5643. (f) Fru¨chtel, J . S.; J ung, G. Angew. Chem., Int.
Ed. Engl. 1996, 35, 17. (g) Bolm, C.; Gerlach, A. Eur. J . Org. Chem. 1998,
21. (h) Brown, R. C. D. J . Chem. Soc., Perkin Trans. 1 1998, 3293.
(2) (a) Blossey, E. C.; Ford, W. T. In Comprehensive Polymer Science.
The Synthesis, Characterization, Reactions and Applications of Polymers;
Allen, G., Bevington, J . C., Eds.; Pergamon Press: New York, 1989; Vol. 6,
p 81. (b) Cornils, B.; Herrmann, W. A. In Applied Homogeneous Catalysis
with Organometallic Compounds; Cornils, B., Herrmann, W. A., Eds.;
VCH: Weinheim, 1996; Vol. 2, Chapter 3.1.1, p 575.
(7) (a) Mortell, K. H.; Weatherman, R. V.; Kiessling, L. L. J . Am. Chem.
Soc. 1996, 118, 2297. (b) Kanai, M.; Mortell, K. H.; Kiessling, L. L. J . Am.
Chem. Soc. 1997, 119, 9931. (c) Schuster, M. C.; Mortell, K. H.; Hegeman,
A. D.; Kiessling, L. L. J . Mol. Catal. 1997, 116, 209.
(8) For recent contributions see: Kirkland, T. A.; Lynn, D. M.; Grubbs,
R. H. J . Org. Chem. 1998, 63, 9904 and references therein.
(9) Schwab, P.; France, M. B.; Ziller, J . W.; Grubbs, R. H. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 2039.
(10) (a) Kanaoka, S.; Grubbs, R. H. Macromolecules 1995, 28, 4707. (b)
Weck, M.; Schwab, P.; Grubbs, R. H. Macromolecules 1996, 29, 1789.
(11) Optically active bicyclic monoesters can easily be synthesized from
meso-anhydrides. For a recent example see: Bolm, C.; Gerlach, A.; Dinter,
C. L. Synlett 1999, 195.
(12) For the preparation of (R)-4a and its use in dialkylzinc additions to
aldehydes, see: (a) Bolm, C.; Ewald, M.; Felder, M.; Schlingloff, G. Chem.
Ber. 1992, 125, 1169. (b) Bolm, C.; Schlingloff, G.; Harms, K. Chem. Ber.
1992, 125, 1191. (c) (S)-4a and its polymer-attached counterparts afforded
(S)-configured products.
(3) (a) Hu, Q.-S.; Zheng, X.-F.; Pu, L. J . Org. Chem. 1996, 61, 5200. (b)
Pu, L. Tetrahedron: Asymmetry 1998, 9, 1457. (c) Pu, L. Chem. Rev. 1998,
98, 2405.
(4) (a) Huang, W.-S.; Hu, Q.-S.; Zheng, X.-F.; Anderson, J .; Pu, L. J . Am.
Chem. Soc. 1997, 119, 4313. (b) Hu, Q.-S.; Huang, W.-S.; Vitharana, D.;
Zheng, X.-F.; Pu, L. J . Am. Chem. Soc. 1997, 119, 12454.
(13) Bolm, C.; Derrien, N.; Seger, A. Synlett 1996, 387.
(14) (a) Saigo, K.; Usui, M.; Kikuchi, K.; Shimada, E.; Mukaiyama, T.
Bull. Chem. Soc. J pn. 1977, 50, 1863. (b) Mukaiyama, T. Angew. Chem.,
Int. Ed. Engl. 1979, 18, 707.
(5) J ohannsen, M.; J ørgensen, K. A.; Zheng, X.-F.; Hu, Q.-S.; Pu, L. J .
Org. Chem. 1999, 64, 299.
(6) For recent reviews on metathesis reactions, see: (a) Grubbs, R. H.;
Chang, S. Tetrahedron 1998, 54, 4413. (b) Schuster, M.; Blechert, S. Angew.
Chem., Int. Ed. Engl. 1997, 36, 2036. (c) Grubbs, R. H.; Miller, S. J .; Fu, G.
C. Acc. Chem. Res. 1995, 28, 446. (d) Armstrong, S. K. J . Chem. Soc., Perkin
Trans. 1 1998, 371.
(15) In this study racemic 8 was used. See also ref 11.
(16) (a) Kragl, U.; Dreisbach C.; Wandrey, C. in Applied Homogeneous
Catalysis with Organometallic Compounds; Cornils, B., Herrmann, W. A.,
Eds.; VCH: Weinheim, 1996; p 832. (b) Kragl, U.; Dreisbach, C. Angew.
Chem., Int. Ed. Engl. 1996, 35, 642.
10.1021/jo990533u CCC: $18.00 © 1999 American Chemical Society
Published on Web 07/14/1999

Communications
J . Org. Chem., Vol. 64, No. 16, 1999 5731
Ta ble 1. Rea ction of Ben za ld eh yd e (10) a n d Dieth ylzin c Ca ta lyzed by Va r iou s P yr id in yl Alcoh ols
pyridinyl
alcohol/polymer
amount of pyridinyl
Mw/Mn
alcohol (mg/µmola)
time (h)
yield of 11 (%)
ee of 11 (%)d
4a
5
7
-
15.0/62.1
15.0/49.8
16.8/44.6
38.1/79.1
22.6/60.2
23.1/61.5
48.7/130.0
35.3/73.0
b
4b
24c
24b
24c
48b
48b
48b
48c
91
86
72
89
88
83
77
78
87
83
79
80
73
73
73
71
-
-
-
1.2
1.4
1.7
1.1
9
P 1
P 2
P 3
P 4
With respect to catalytically active subunits. Reaction was performed at 0 °C. c Reaction was performed at room temperature.
a
d
Determined by HPLC using a chiral stationary phase.
used as a test reaction.17,18 All catalyses proceeded under
homogeneous conditions in toluene using 5 mol % of catalyst
and an excess of diethylzinc (1.5 equiv). The most significant
results are summarized in Table 1.
All polymers showed catalytic activity, and optically active
1-phenylpropanol (11) was obtained in good yield (Table 1).
Compared to the low-molecular weight pyridinyl alcohols 4a ,
5, 7, and 9, the catalytic activity of the polymers P 1-P 4 is
somewhat decreased. Thus, for achieving high aldehyde
conversion, longer reaction times were required. Fortunately,
we noticed that the enantioselectivity in the product forma-
tion was only slightly reduced even though we were using
functionalized polymers with a high density of potentially
catalytically active sites.19 For example, catalysis with
polymer P 1 gave 11 with 73% ee whereas its monomeric
counterpart afforded the same product with 79% ee. As
expected from our previous results,12 (R)-configured pyridi-
nyl alcohols gave (R)-11 as the major enantiomer. Variation
of the polymer chain length did not influence the enantio-
selectivity. Thus, with all three polymers (P 1-P 3) derived
from 7, 1-phenylpropanol was formed with 73% ee.
catalyst 1, affording the corresponding polymers in good to
excellent yields (up to 99%). These results convincingly
demonstrate the tolerance of the ruthenium catalyst toward
the various functional groups in 7 or 9.8 The polymeric
In conclusion, we have demonstrated that the ROMP
reaction can be used for the synthesis of chiral homogeneous
polymeric catalysts which found first application in enan-
tioselective diethylzinc additions to benzaldehyde.
1
products were analyzed by H NMR spectroscopy (cf. Sup-
Ack n ow led gm en t. This work was supported by Ka-
talyseverbund NRW, Deutsche Forschungsgemeinschaft
(DFG; Graduiertenkolleg), Volkswagenstiftung, and Fonds
der Chemischen Industrie. We are grateful to Witco and
Degussa-Hu¨ls for the generous donation of chemicals.
porting Information) and by gel permeation chromatography.
By comparison of the elution volume of the polymers relative
to polystyrene standards, it was estimated that for poly-
merizations with 2 mol % of 1, the molecular masses of
polymers P 2 and P 4 derived from 7 and 9, respectively, were
about 3 × 104 g/mol. Polymers of this size can be easily
recovered through ultrafiltration techniques and might find
application in continuously operating flow reactors.16 Vary-
ing the monomer-to-catalyst ratio from 50 to 20 and 100 (to
give polymers P 1 and P 3, respectively) allowed the modi-
fication of the molecular weight of the polymer (for details
cf. Supporting Information).
Su p p or tin g In for m a tion Ava ila ble: Detailed experimental
procedures, characterization of all new compounds, and the
analyses of chiral alcohols 4b and 11. This material is available
free of charge via the Internet at http://pubs.acs.org.
J O990533U
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Next, the catalytic activity of each polymer was evaluated.
To allow a comparison with known systems, the well-
established addition of diethylzinc to benzaldehyde (10) was
(19) For a related observation in asymmetric reductions see: Fre´chet,
J . M. J .; Bald, E.; Lecavalier, P. J . Org. Chem. 1986, 51, 3462.