Recover a ble, Reu sa ble, High ly Active, a n d
Su lfu r -Toler a n t P olym er In ca r cer a ted
P a lla d iu m for Hyd r ogen a tion
Kuniaki Okamoto, Ryo Akiyama, and Shuj Kobayashi*
Graduate School of Pharmaceutical Sciences, The University
of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, J apan
skobayas@mol.f.u-tokyo.ac.jp
Received December 21, 2003
Abstr a ct: A new type of immobilized palladium, PI (poly-
mer incarcerated) Pd (2b), from Pd(PPh3)4 and copolymer
(1b) has been developed. The excellent activity of PI Pd has
been demonstrated in hydrogenation of various olefins,
benzyl ethers, and nitro and aromatic compounds. PI Pd is
tolerant under high pressure and high temperature and can
be recovered and reused several times without loss of activity
even under harsh conditions. Moreover, PI Pd is highly
resistant to poisoning by sulfur.
F IGURE 1. Compounds 1-4.
temperature. We decided to modify the structure of PI
Pd (2a ) and now report here a new type of highly active
and versatile PI Pd, which has high resistance to harsh
conditions and poisoning by sulfur in various hydrogena-
tions.
Palladium-catalyzed hydrogenation is frequently used
not only in laboratories but also in industry. While
immobilized palladium catalysts such as Pd/C and Pd/
Al2O3, etc. have been often employed, leaching of the
palladium from the supports, moderate yields of recovery,
contamination of the palladium to products, and poison-
ing by sulfur are sometimes serious problems especially
in the manufacture of pharmaceuticals.1
We have recently developed the polymer-incarcerated
(PI) method2 to immobilize metal catalysts onto poly-
mers.3 The method is based on microencapsulation4 and
cross-linking, and Pd(PPh3)4 was immobilized using this
method to form polymer-incarcerated palladium (PI Pd).
It was revealed that PI Pd (2a ) derived from polymer (1a )
consisted of phosphine-free palladium(0) and effectively
catalyzed hydrogenation of olefins in THF under atmo-
spheric pressure. Moreover, the catalyst was recovered
completely by simple filtration and could be reused
several times without loss of activity. On the other hand,
it was assumed that the benzyl ether moieties of PI Pd
(2a ) would be cleaved in the hydrogenation under harsh
conditions, such as high hydrogen pressure and high
We designed a new copolymer (1b) for higher resistant
PI Pd (2b), which has no benzylic ether moiety. Copoly-
mer (1b) was synthesized by radical copolymerization of
styrene, epoxide monomer (3), and tetraethyleneglycol
monomer (4) (Figure 1).5 PI Pd (2b) was prepared from
Pd(PPh3)4 and polymer (1b) according to the method for
the preparation of 2a .2,5 First, we examined the catalytic
activity and the effect of loading levels5,6 of 2a and 2b in
the hydrogenation of benzalacetone and cholesterol under
atmospheric pressure (Tables 1 and 2). It was revealed
that the activity of 2b was almost the same as that of 2a
in the hydrogenation of benzalacetone, while 2b exhibited
higher activity than 2a in the reduction of cholesterol, a
more hindered substrate. We also confirmed that the
loading level of the palladium did not affect the activity
of either PI Pd catalyst.
Several other substrates were hydrogenated using PI
Pd (2b), and the results are summarized in Table 3. In
addition to normal C-C double and triple bonds, benzyl
ethers, nitrobenzene, and quinoline were easily hydro-
genated under atmospheric pressure at room tempera-
ture. We also applied PI Pd (2b) to the reduction of less
reactive substrate 7, which is the intermediate for the
synthesis of an antidiabetic agent, pioglitazone (8). This
agent is expected to effectively ameliorate the abnormal
glucose and lipid metabolism associated with noninsulin
dependent diabetes mellitus or obesity.7 It is known that
the yields of the hydrogenation of 7 using conventional
(1) (a) Trimm, D. L. Design of Industrial Catalysts; Elsevier:
Amsterdam, 1980. (b) Rylander, P. N. Hydrogenation Methods; Aca-
demic Press: New York, 1985. (c) Satterfield, C. N. Heterogeneous
Catalysis in Industrial Practice, 2nd ed.; McGraw-Hill: New York,
1991.
(2) Akiyama, R.; Kobayashi, S. J . Am. Chem. Soc. 2003, 125, 3412.
(3) For recent reviews of polymer-supported metal catalysts, see:
(a) Corain, B.; Centomo, P.; Lora, S.; Kralik, M. J . Mol. Catal. A: Chem.
2003, 755. (b) Karakhanov, E. A.; Maximov, A. L. Met. Complexes Met.
Macromol. 2003, 457. (c) Leadbeater, N. E.; Marco, M. Chem. Rev.
2002, 102, 3217. (d) Stefan, B.; J ohannes, K.; Nils, G. Handb.
Organopalladium Chem. Org. Synth. 2002, 2, 3031. (e) Kralik, M.;
Biffis, A. J . Mol. Catal. A: Chem. 2001, 177, 113.
(4) (a) Kobayashi, S.; Nagayama, S. J . Am. Chem. Soc. 1998, 120,
2985. (b) Nagayama, S.; Endo, M.; Kobayashi, S. J . Org Chem. 1998,
63, 6094. (c) Kobayashi, S.; Endo, M.; Nagayama, S. J . Am. Chem. Soc.
1999, 121, 11229. (d) Kobayashi, S.; Ishida, T.; Akiyama, R. Org. Lett.
2001, 3, 2649. (e) Akiyama, R.; Kobayashi, S. Angew. Chem., Int. Ed.
2001, 40, 3469. (f) Akiyama, R.; Kobayashi, S. Angew. Chem., Int. Ed.
2002, 41, 2602.
(5) Details are shown in the Supporting Information.
(6) The loading level of the palladium was determined by XRF
analysis.
(7) (a) Sohda, T.; Momose, Y.; Meguro, K.; Kawamatsu, Y.; Sug-
iyama, Y.; Ikeda, H. Arzneim-Forsch. 1990, 40, 37. (b) Sugiyama, Y.;
Taketomi, S.; Shimura, Y.; Sohda, T.; Meguro, K.; Fujita, T. Arzneim-
Forsch. 1990, 40, 253. (c) Sugiyama, Y.; Shimura, Y.; Ikeda, H.
Arzneim-Forsch. 1990, 40, 436.
10.1021/jo0358527 CCC: $27.50 © 2004 American Chemical Society
Published on Web 03/10/2004
J . Org. Chem. 2004, 69, 2871-2873
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