Polymer-supported ruthenium porphyrins: Versatile and robust epoxidation catalysts with unusual selectivity

Article abstract of DOI:10.1021/ja000461k

Carbonyl ruthenium(II) 5,10,15-tris(4-R-phenyl)-20-(4- hydroxyphenyl)porphyrins (R = Cl, Me) covalently attached to Merrifield's peptide resin were prepared. The catalyst with R = Cl was found to efficiently catalyze Cl₂pyNO epoxidation of a wide variety of alkenes, including aromatic and aliphatic terminal alkenes, cis- and trans-stilbene, cyclohexene and cyclooctene, α,β-unsaturated ketones, conjugated enyne, glycal, and protected α-amino alkene. Unusual selectivities were observed for the epoxidations of 1,5-cyclooctadiene, cis-1-phenyl-3-penten-1-yne (9), 3,4,6-tri-O-acetyl-D-glucal (11), and 2-(Boc-amino)-1-phenylbut-3-ene (13), which feature a complete bisepoxide selectivity (1,5-cyclooctadiene), unprecedentedly high cis:trans ratio (9), and complete diastereoselectivity (11 and 13). The new heterogenized metalloporphyrin epoxidation catalysts are of high stability and reusability.

Full text of DOI:10.1021/ja000461k

J. Am. Chem. Soc. 2000, 122, 5337-5342
5337
Polymer-Supported Ruthenium Porphyrins: Versatile and Robust
Epoxidation Catalysts with Unusual Selectivity
Xiao-Qi Yu, Jie-Sheng Huang, Wing-Yiu Yu, and Chi-Ming Che*
Contribution from the Department of Chemistry and the HKU-CAS Joint Laboratory on New Materials,
The UniVersity of Hong Kong, Pokfulam Road, Hong Kong, China
ReceiVed February 7, 2000
Abstract: Carbonyl ruthenium(II) 5,10,15-tris(4-R-phenyl)-20-(4-hydroxyphenyl)porphyrins (R ) Cl, Me)
covalently attached to Merrifield’s peptide resin were prepared. The catalyst with R ) Cl was found to efficiently
catalyze Cl2pyNO epoxidation of a wide variety of alkenes, including aromatic and aliphatic terminal alkenes,
cis- and trans-stilbene, cyclohexene and cyclooctene, R,â-unsaturated ketones, conjugated enyne, glycal, and
protected R-amino alkene. Unusual selectivities were observed for the epoxidations of 1,5-cyclooctadiene,
cis-1-phenyl-3-penten-1-yne (9), 3,4,6-tri-O-acetyl-D-glucal (11), and 2-(Boc-amino)-1-phenylbut-3-ene (13),
which feature a complete bisepoxide selectivity (1,5-cyclooctadiene), unprecedentedly high cis:trans ratio (9),
and complete diastereoselectivity (11 and 13). The new heterogenized metalloporphyrin epoxidation catalysts
are of high stability and reusability.
Introduction
phyrin onto polyisocyanide, mainly to study the effect of site-
isolation. Since then, a number of investigations on hetero-
genized metalloporphyrins as catalysts for alkene epoxidation
have appeared in the literature.4,5 However, almost all these
studies are confined to iron and manganese porphyrins, which
are usually sterically encumbered and/or have strongly electron-
withdrawing groups, and involve only one or a few common
alkenes such as cyclooctene, stilbene, and styrenes.3,4 In no case
have the heterogenized catalysts been reported to be as efficient
as the corresponding homogeneous ones for a wide variety of
alkenes. The partial loss of chemo- or stereoselectivity,4c,l,5b
catalyst leaching,4k,5b and the significant or complete loss of
catalytic activity toward some substrates4e,5b are among the
problems encountered.
Herein we report on the first alkene epoxidation catalyzed
by polymer-supported ruthenium porphyrins, which employ
simple porphyrinato ligands and can readily be prepared yet
exhibit a high versatility and stability, with complete diaste-
reoselectivity in epoxidation of glycal and R-aminoalkyl alkene.
The formation of aminoalkyl epoxides via catalytic oxidation
of their alkene precursors has never been realized before.
Epoxidation of unfunctionalized alkenes catalyzed by met-
alloporphyrins is a subject of tremendous investigations.1 By
tailoring the porphyrin macrocycles with steric hindrance,
sophisticated chiral auxiliaries, or strongly electron-withdrawing
groups, the homogeneous systems involving these catalysts can
exhibit high regio-,2a-d shape-,2c,e and enantioselectivity1b and
extremely high catalyst turnovers.2f,g However, these appealing
features are usually outweighed by the relatively high costs of
the catalysts and their applicability for rather limited types of
alkenes, rendering their application to synthesis so far impracti-
cal. In fact, the majority of the studies are directed to
understanding the mechanism of the catalytic activity of heme-
containing enzymes such as cytochrome P-450.1 Perhaps a
potential approach to commercial metalloporphyrin catalysts is
to immobilize them onto solid supports. Such immobilization
can (i) make the catalysts readily separable from the products
and reusable, (ii) enhance the catalyst stability toward oxidative
degradation through efficient site-isolation, and (iii) allow
preparation of environmentally friendly catalysts. It would
further be beneficial if the heterogenized catalysts with required
selectivity bear simple porphyrinato ligands and are applicable
for a wide variety of alkenes.
(4) (a) Wo¨hrle, D.; Gitzel, J. Makromol. Chem., Rapid Commun. 1988,
9, 229. (b) Wo¨hrle, D.; Gitzel, J.; Krawczyk, G.; Tsuchida, E.; Ohno, H.;
Okura, I.; Nishisaka, T. J. Macromol. Sci., Chem. 1988, A25, 1227. (c)
Leanord, D. R.; Lindsay Smith, J. R. J. Chem. Soc., Perkin Trans. 2 1990,
1917. (d) Leanord, D. R.; Lindsay Smith, J. R. J. Chem. Soc., Perkin Trans.
2 1991, 25. (e) Turk, H.; Ford, W. T. J. Org. Chem. 1991, 56, 1253. (f)
Traylor, T. G.; Byun, Y. S.; Traylor, P. S.; Battioni, P.; Mansuy, D. J. Am.
Chem. Soc. 1991, 113, 7821. (g) Barloy, L.; Lallier, J. P.; Battioni, P.;
Mansuy, D.; Piffard, Y.; Tournoux, M.; Valim, J. B.; Jones, W. New J.
Chem. 1992, 16, 71. (h) Campestrini, S.; Meunier, B. Inorg. Chem. 1992,
31, 1999. (i) Cooke, P. R.; Lindsay Smith, J. R. Tetrahedron Lett. 1992,
33, 2737. (j) Battioni, P.; Bartoli, J. F.; Mansuy, D.; Byun, Y. S.; Traylor,
T. G. J. Chem. Soc., Chem. Commun. 1992, 1051. (k) Cooke, P. R.; Lindsay
Smith, J. R. J. Chem. Soc., Perkin Trans. 1 1994, 1913. (l) Gilmartin, C.;
Lindsay Smith, J. R. J. Chem. Soc., Perkin Trans. 2 1995, 243. (m)
Tangestaninejad, S.; Moghadam, M. J. Chem. Res. (S) 1998, 242. (n) das
Dores Assis, M.; Lindsay Smith, J. R. J. Chem. Soc., Perkin Trans. 2 1998,
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(5) (a) Liu, C.-J.; Li, S.-G.; Pang, W.-Q.; Che, C.-M. Chem. Commun.
1997, 65. (b) Liu, C.-J.; Yu, W.-Y.; Li, S.-G.; Che, C.-M. J. Org. Chem.
1998, 63, 7364.
The first alkene epoxidation employing a heterogenized
metalloporphyrin catalyst was reported in 1983 by Nolte, Drenth,
and co-workers,3 who grafted a manganese meso-tetraarylpor-
(1) (a) Meunier, B. Chem. ReV. 1992, 92, 1411. (b) Collman, J. P.; Zhang,
X. M.; Lee, V. J.; Uffelman, E. S.; Brauman, J. I. Science 1993, 261, 1404.
(c) Mansuy, D. Coord. Chem. ReV. 1993, 125, 129.
(2) Selected examples: (a) Groves, J. T.; Nemo, T. E. J. Am. Chem.
Soc. 1983, 105, 5786. (b) Tabushi, I.; Morimitsu, K. J. Am. Chem. Soc.
1984, 106, 6871. (c) Collman, J. P.; Brauman, J. I.; Meunier, B.; Hayashi,
T.; Kodadek, T.; Raybuck, S. A. J. Am. Chem. Soc. 1985, 107, 2000. (d)
Groves, J. T.; Neumann, R. J. Am. Chem. Soc. 1987, 109, 5045. (e) Collman,
J. P.; Zhang, X.; Hembre, R. T.; Brauman, J. I. J. Am. Chem. Soc. 1990,
112, 5356. (f) Traylor, P. S.; Dolphin, D.; Traylor, T. G. J. Chem. Soc.,
Chem. Commun. 1984, 279. (g) Collman, J. P.; Wang, Z.; Straumanis, A.;
Quelquejeu, M. J. Am. Chem. Soc. 1999, 121, 460.
(3) van der Made, A. W.; Smeets, J. W. H.; Nolte, R. J. M.; Drenth, W.
J. Chem. Soc., Chem. Commun. 1983, 1204.
10.1021/ja000461k CCC: $19.00 © 2000 American Chemical Society
Published on Web 05/20/2000

5338 J. Am. Chem. Soc., Vol. 122, No. 22, 2000
Yu et al.
Figure 1. Schematic structures of ruthenium porphyrins (a) coordi-
natively grafted onto surface modified MCM-41 and (b) covalently
attached to a solid support. 4-Cl-TPP ) meso-tetrakis(4-chlorophenyl)-
porphyrinato dianion; 2,6-Cl-TPP ) meso-tetrakis(2,6-dichlorophenyl)-
porphyrinato dianion.
Results and Discussion
The pioneering work by Groves and co-worker6a on ruthenium
porphyrin-catalyzed alkene epoxidations, combined with the
unique periodic relation of ruthenium to iron and the facile
isolation of dioxoruthenium(VI) porphyrins, stimulated much
recent interest in the utilization of ruthenium porphyrins as
homogeneous catalysts in alkene epoxidation.6b-r However,
heterogenized ruthenium porphyrin catalysts are rare, the first
of which appeared in 1993 and were used to catalyze the
decomposition of cyclohexyl hydroxide rather than alkene
epoxidation.7 We recently immobilized two ruthenium porphy-
rins, via coordinatiVe bonding, onto a surface-modified meso-
porous molecular sieve (MCM-41) to form the heterogenized
catalysts 1- and 2-MCM-41 (Figure 1a), and examined their
catalytic behavior toward alkene epoxidation.5 While catalyst
2-MCM-41, which contains a sterically encumbered porphyri-
nato ligand, has been found to effect highly selective alkene
epoxidations by Cl2pyNO,5b reuse experiments reveal significant
catalyst leaching and/or deactivation. This stimulated our interest
in attaching ruthenium porphyrins to a solid support through a
coValent linkage, forming more stable catalysts as depicted in
Figure 1b. On the other hand, the covalent attachment of
porphyrin ligands to a solid support represents a unique type
of porphyrin modification. By utilizing a simple porphyrin
macrocycle and judiciously choosing the support, it is possible
to obtain a heterogenized catalyst showing high selectivity as
well as high stability.
Figure 2. Synthesis of ruthenium porphyrins covalently immobilized
onto Merrifield’s peptide resin.
functional groups such as hydroxyl. The excellent solvation and
swelling of MPR in certain organic solvents such as dichloro-
methane and N,N-dimethylformamide (DMF)9 may allow met-
alloporphyrins to be attached not only at the surface of the
polymer bead but also within the interior of the cross-linked
polymeric matrix. Consequently, there is a possibility of
achieving a high selectivity by supporting sterically unencum-
bered ruthenium porphyrins onto MPR as a result of the unique
microenvironment constituted by the porphyrin macrocycle and
the polymer matrix. Moreover, owing to the solvation and
swelling, the heterogeneous catalysis involving an MPR-
supported catalyst would proceed rapidly (note that the previ-
ously reported hetereogenized metalloporphyrin catalysts often
operate much more slowly than their homogeneous counter-
parts4c,n).
Preparation of Polymer-Supported Ruthenium Porphy-
rins. The solid support used in the present work is the well-
known Merrifield’s peptide resin (abbreviated here as MPR), a
chloromethylated styrene-divinylbenzene copolymer. This type
of support can be considered as an “insoluble benzyl chloride”,8
and could readily react with compounds bearing appropriate
To obtain ruthenium porphyrins bearing a periphery hydroxyl
group, we started from simple unsymmetrically substituted
meso-tetraarylporphyrin free bases, 5,10,15-tris(4-R-phenyl)-20-
(4-hydroxyphenyl)porphyrins (R ) Cl, Me), which can be
prepared readily via a “one-pot” reaction of the corresponding
aldehydes and pyrrole.10 Reaction of these porphyrins with Ru3-
(CO)12 in refluxing Decalin afforded ruthenium(II) porphyrins
3 and 4 depicted in Figure 2 in ca. 80% isolated yields.
Complexes 3 and 4 exhibit intense IR bands at 1941 and 1942
cm-1, respectively, characteristic of carbonylruthenium(II) meso-
(6) (a) Groves, J. T.; Quinn, R. J. Am. Chem. Soc. 1985, 107, 5790. (b)
Marchon, J.-C.; Ramasseul, R. J. Chem. Soc., Chem. Commun. 1988, 298.
(c) Higuchi, T.; Ohtake, H.; Hirobe, M. Tetrahedron Lett. 1989, 30, 6545.
(d) Higuchi, T.; Ohtake, H.; Hirobe, M. Tetrahedron Lett. 1991, 32, 7435.
(e) Ho, C.; Leung, W.-H.; Che, C.-M. J. Chem. Soc., Dalton Trans. 1991,
2933. (f) Ohtake, H.; Higuchi, T.; Hirobe, M. Tetrahedron Lett. 1992, 33,
2521. (g) Tavares, M.; Ramasseul, R.; Marchon, J.-C.; Bachet, B.; Brassy,
C.; Mornon, J.-P. J. Chem. Soc., Perkin Trans. 2 1992, 1321. (h) Tokita,
Y.; Yamaguchi, K.; Watanabe, Y.; Morishima, I. Inorg. Chem. 1993, 32,
329. (i) Leung, W.-H.; Che, C.-M.; Yeung, C.-H.; Poon, C.-K. Polyhedron
1993, 12, 2331. (j) Scharbert, B.; Zeisberger, E.; Paulus, E. J. Organomet.
Chem. 1995, 493, 143. (k) Gross, Z.; Ini, S.; Kapon, M.; Cohen, S.
Tetrahedron Lett. 1996, 37, 7325. (l) Gross, Z.; Ini, S. J. Org. Chem. 1997,
62, 5514. (m) Lai, T.-S.; Zhang, R.; Cheung, K.-K.; Kwong, H.-L.; Che,
C.-M. Chem. Commun. 1998, 1583. (n) Liu, C.-J.; Yu, W.-Y.; Peng, S.-
M.; Mak, T. C. W.; Che, C.-M. J. Chem. Soc., Dalton Trans. 1998, 1805.
(o) Lai, T.-S.; Kwong, H.-L.; Zhang, R.; Che, C.-M. J. Chem. Soc., Dalton
Trans. 1998, 3559. (p) Zhang, R.; Yu, W.-Y.; Lai, T.-S.; Che, C.-M. Chem.
Commun. 1999, 409. (q) Gross, Z.; Ini, S. Inorg. Chem. 1999, 38, 1446. (r)
Gross, Z.; Ini, S. Org. Lett. 1999, 1, 2077.
1
tetraarylporphyrins.11 Subsequent H NMR, UV/vis, and MS
measurements, together with elemental analyses, further support
their formulations (see Experimental Section).
The covalent attachment of 3 and 4 to MPR was realized by
treating the complexes with MPR in DMF at 80 °C for 4 h in
the presence of anhydrous potassium carbonate (reaction 1 in
Figure 2). This is similar to the reaction between meso-tetrakis-
(4-hydroxyphenyl)porphyrin and butyl bromide, which affords
meso-tetrakis(4-butoxyphenyl)porphyrin in 95% yield.10 The
(8) Loudon, G. M. Organic Chemistry, 2nd ed.; the Benjamin/Cummings
Publishing Company, Inc.: Menlo Park, 1988; p 1164.
(9) Merrifield, B. Science 1986, 232, 341.
(7) Hansen, C. B.; Hoogers, G. J.; Drenth, W. J. Mol. Catal. 1993, 79,
153.
(10) Little, R. G.; Anton, J. A.; Loach, P. A.; Ibers, J. A. J. Heterocycl.
Chem. 1975, 12, 343.

Polymer-Supported Ruthenium Porphyrin
J. Am. Chem. Soc., Vol. 122, No. 22, 2000 5339
Table 1. Epoxidation of a Wide Variety of Alkenes with Cl2pyNO Catalyzed by 3a-MPRa
a Unless otherwise specified, all reactions were carried out in benzene at room temperature for 24 h with a catalyst:oxidant:substrate molar ratio
of 1:1400:1600. b Based on the amount of Cl2py formed. c Trace amounts of the corresponding aldehyde were also detected. d Other products:
cyclohex-2-en-1-one (25%) and cyclohex-2-en-1-ol (7.5%). e Yield of trans epoxide: 7%. f Reaction conditions: 40 °C, 48 h, catalyst:oxidant:
substrate molar ratio of 1:610:600. g Overall isolated yield after epoxidation and methanolysis. h Isolated yield based on the amount of starting
alkene.
Scheme 1
resulting heterogenized catalysts are designated as 3- and
4-MPR, respectively. In the case of 3-MPR, two catalysts with
different 3 loadings (8.6 and 0.17 wt %) designated as 3a- and
3b-MPR, respectively, were prepared by changing the amount
of 3 used for reaction 1. Evidence for the successful hetero-
genization includes the following: (i) The IR spectra of 3- and
4-MPR each show a ν(CO) band at ca. 1945 cm-1, similar to
the corresponding bands of 3 and 4. (ii) The Raman spectrum
of 3a-MPR was examined, which is similar to that of 3 if the
bands belonging to MPR are excluded. (iii) While the support
MPR itself exhibits no activity toward alkene epoxidations, both
3- and 4-MPR are efficient catalysts for these kinds of reactions
in a manner analogous to homogeneous ruthenium porphyrin
catalysts (see below).
Alkene Epoxidation with 2,6-Dichloropyridine N-Oxide
(Cl2pyNO) Catalyzed by 3- and 4-MPR. It has been well
established, first by Hirobe and co-workers,6c that substituted
pyridine N-oxides, such as Cl2pyNO, can efficiently epoxidize
alkenes in the presence of homogeneous ruthenium porphyrin
catalysts.6c,d,f,p-r Preliminary examinations of the catalytic
behavior of 3b-MPR and 4-MPR toward epoxidation of styrene
with Cl2pyNO revealed that the catalyst 3-MPR, which bears
electron-withdrawing Cl groups, was superior to 4-MPR, and
higher yields of epoxides were obtained in benzene than in
dichloromethane, toluene, or acetonitrile. Accordingly, unless
otherwise indicated, all the results described below were
obtained through reactions in benzene by employing the catalyst
3-MPR (reaction 2, Scheme 1).
(i) Versatility. To inspect the applicability of 3-MPR for
various types of alkenes, we first used the catalyst 3a-MPR,
which has a relatively high 3 loading. The results obtained
for this catalyst at a catalyst:oxidant:substrate molar ratio of
1:1400:1600 are shown in Table 1. Evidently, 3a-MPR is an
efficient catalyst for epoxidation of a wide variety of alkenes.
In the cases of styrene, cis-stilbene, norbornene, cyclohexene,
cyclooctene, and 1-octene (entries 1, 5, 9, 10, 11, and 13,
respectively), the epoxide yields and stereoselectivity for cis-
stilbene and norbornene are comparable to those obtained by
employing the catalyst 2-MCM-41 with a sterically encumbered
porphyrin. Surprisingly, 3a-MPR is also efficient in catalyzing
the epoxidation of trans-alkenes. For trans-stilbene and trans-
â-methylstyrene, the yields of the corresponding trans epoxides
were as high as 90 and 86% (entries 6 and 7), respectively, and
no cis epoxides were detected. In contrast, 2-MCM-41 was not
found to be an effective catalyst for epoxidation of trans-alkenes.
For example, 2-MCM-41 is completely ineffective toward the
epoxidation of trans-stilbene.5b
(11) Carbonyl ruthenium(II) meso-tetraarylporphyrins generally exhibit
intense ν(CO) bands in the range of 1918-1965 cm-1, see for examples:
(a) Tsutsui, M.; Ostfeld, D.; Hoffman, L. M. J. Am. Chem. Soc. 1971, 93,
1820. (b) Bonnet, J. J.; Eaton, S. S.; Eaton, G. R.; Holm, R. H.; Ibers, J. A.
J. Am. Chem. Soc. 1973, 95, 2141. (c) Brown, G. M.; Hopf, F. R.; Ferguson,
J. A.; Meyer, T. J.; Whitten, D. G. J. Am. Chem. Soc. 1973, 95, 5939. (d)
Eaton, S. S.; Eaton, G. R. J. Am. Chem. Soc. 1975, 97, 3660. (e) Rillema,
D. P.; Nagle, J. K.; Barringer, L. F., Jr.; Meyer, T. J. J. Am. Chem. Soc.
1981, 103, 56. (f) Collman, J. P.; Barnes, C. E.; Swepston, P. N.; Ibers, J.
A. J. Am. Chem. Soc. 1984, 106, 3500. (g) Collman, J. P.; Barnes, C. E.;
Brothers, P. J.; Collins, T. J.; Ozawa, T.; Gallucci, J. C.; Ibers, J. A. J. Am.
Chem. Soc. 1984, 106, 5151.
The epoxidation of the alkenes in entries 8, 12, 14-16, and
18 has not been catalyzed by any of the previously reported
heterogenized metalloporphyrin catalysts.3-5 The catalytic activ-
ity of 3a-MPR toward epoxidation of electron-deficient alkenes,
namely R,â-unsaturated ketones, is remarkable. For example,
in the cases of alkenes 5 (entry 14) and 7 (entry 15), reaction

5340 J. Am. Chem. Soc., Vol. 122, No. 22, 2000
Yu et al.
2 afforded the corresponding epoxides 6 and 8 in close to 90%
yields. To our knowledge, even in the homogeneous systems,
no metalloporphyrins are reported to be active catalysts for Cl2-
pyNO or PhIO epoxidation of these types of alkenes.12Although
epoxidation of R,â-unsaturated ketones can be efficiently
catalyzed by other metal complexes or polypeptides,13 very few
such reports deal with the epoxidation of alkenes 5 and 7.14
(ii) Unusual Selectivity. Besides the aforementioned versatil-
ity, another remarkable feature of 3a-MPR lies in its unusual
selectivity obtained for the following alkenes.
Scheme 2
Cl2pyNO is completely diastereoselectivesonly R-12 was
obtained (entry 17).
(a) 1,5-Cyclooctadiene. As shown in Table 1 (entry 12),
reaction 2 (Scheme 1) for 1,5-cyclooctadiene afforded the
corresponding bisepoxide in 76% yield. No monoepoxide was
detected. This is contrary to the epoxidation of the same alkene
with H2O2 catalyzed by molybdenum porphyrins15a and epoxi-
dation of 1,3-cyclohexadiene in the NaClO-manganese
porphyrin15b and PhIO-iron porphyrin systems,2a which all
selectively produced the corresponding monoepoxide. Since
excess 1,5-cyclooctadiene was used for reaction 2, and the
monoepoxide of this alkene is a stable compound, the selective
formation of its bisepoxide is very surprising.
(b) cis-1-Phenyl-3-penten-1-yne (9). The monoepoxides of
conjugated enynes are valuable intermediates in organic syn-
thesis16 and, especially, are closely related to bioactive enediyne
antitumor agents.17 The applicability of reaction 2 for 9, a simple
enyne, was examined. Notably, this reaction afforded the
corresponding epoxides cis- and trans-10 in 91 and 7% yields,
respectively (entry 16), with a cis:trans ratio of 13:1, very
different from the cis:trans ratio of 1:2 obtained for the
epoxidation of the same alkene with NaClO catalyzed by a
manganese-salen catalyst.18
(d) Protected r-Amino Alkene. Protected aminoalkyl ep-
oxides have attracted much attention in recent years owing to
their utility in organic synthesis20 and particularly in the
preparation of several dipeptide isosteres for synthesizing the
inhibitors of some key aspartic proteases such as renin21 and
HIV protease.22 Such epoxides can be prepared from stoichio-
metric epoxidation of protected R-amino alkenes with m-
chloroperoxybenzoic acid (m-CPBA), which exclusively affords
a mixture of threo and erythro diastereomers (reaction 3,
Scheme 2) with the threo diastereomer as the major products.22b,e,23
To develop a catalytic epoxidation for these types of alkenes,
we examined the applicability of reaction 2 to 2-(Boc-amino)-
1-phenylbut-3-ene (13, Boc ) tert-butoxycarbonyl), a typical
protected R-amino alkene, whose threo-epoxide is a key
intermediate for the synthesis of HIV-1 protease.22b,d,23g Re-
markably, under the conditions identical with those for 11,
reaction 2 for (R)-13 afforded the corresponding epoxide 14 in
the threo configuration only (88% isolated yield, entry 18). To
our knowledge, this is the first epoxidation of protected R-amino
alkenes catalyzed by a metal complex.
Catalyst Stability and Reuse. The covalent attachment of 3
to the polymer support indeed makes the resulting supported
ruthenium porphyrins 3-MPR a highly stable catalyst for reaction
2. Under the conditions denoted in Table 1, the catalyst 3a-
MPR was consecutively reused four times without detectable
catalyst leaching or a significant loss of epoxide yield.24 In
contrast, the previously reported catalyst 2-MCM-41 lost about
half its original activity after being reused just two times.5b With
a 3 loading as low as 0.17 wt %, the catalyst 3b-MPR is still
(c) Glycal. Glycal epoxides are important intermediates for
the synthesis of carbohydrates.5b,19 We previously observed that,
unlike the dioxirane oxidation of 3,4,6-tri-O-acetyl-D-glucal (11)
which produced a mixture of epoxides R- and â-12,19
a
homogeneous ruthenium porphyrin catalyst, [RuII(2,6-Cl-TPP)-
(CO)(EtOH)], could catalyze the epoxidation of this substrate
with Cl2pyNO to form R-12 only.5b However, immobilization
of the ruthenium porphyrin onto MCM-41 to form 2-MCM-41
resulted in a significant loss of the diastereoselectivity, producing
a mixture of R- and â-12 in a 3:1 ratio.5b Interestingly, by
employing 3a-MPR as catalyst with a catalyst:oxidant:substrate
molar ratio of 1:610:600, the epoxidation of the glycal with
(20) (a) Pegorier, L.; Haddad, M.; Larcheveque, M. Synlett 1996, 585.
(b) Castejo´n, P.; Moyano, A.; Perica`s, M. A.; Riera, A. Tetrahedron 1996,
52, 7063. (c) Aguilar, N.; Moyano, A.; Perica`s, M. A.; Riera, A. Tetrahedron
Lett. 1999, 40, 3913.
(21) Greenlee, W. J. Med. Res. ReV. 1990, 10, 173.
(12) Groves and co-worker first examined the catalytic behavior of an
iron porphyrin toward the epoxidation of a cyclic R,â-unsaturated ketone
(cyclohex-2-en-1-one) with iodosylbenzene, and observed no activity (see
ref 2a). Thereafter, Hirobe and co-workers (ref 6c) demonstrated that the
Cl2pyNO oxidation of l-carvone, a cyclic R,â-unsaturated ketone with an
extra terminal alkene group, catalyzed by a dioxoruthenium(VI) sterically
encumbered porphyrin resulted in epoxidation of only the terminal alkene
group without affecting the R,â-unsaturated ketone moiety.
(13) (a) Julia´, S.; Masana, J.; Vega, J. C. Angew. Chem., Int. Ed. Engl.
1980, 19, 929. (b) Ebrahim, S.; Wills, M. Tetrahedron: Asymmetry 1997,
8, 3163. (c) Pu, L. Tetrahedron: Asymmetry 1998, 9, 1457. (d) Yu, H.-B.;
Zheng, X.-F.; Lin, Z.-M.; Hu, Q.-S.; Huang, W.-S.; Pu, L. J. Org. Chem.
1999, 64, 8149 and references therein.
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H.; Shibasaki, M. J. Am. Chem. Soc. 1997, 119, 2329), the epoxidation of
alkene 5 with tert-butyl hydroperoxide catalyzed by a lanthanoid complex
affords epoxide 6 in 83% yield within 96 h.
(15) (a) Legemaat, G.; Drenth, W.; Schmidt, M.; Prescher, G.; Goor, G.
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(24) The first run gave styrene epoxide in 96% yield (entry 1 in Table
1). After the catalyst had been reused four times, its 3 loading was
determined to be 8.5 wt %. The epoxide yields for the 2nd, 3rd, 4th, and
5th runs were 93, 90, 92, and 91%, respectively.

Polymer-Supported Ruthenium Porphyrin
J. Am. Chem. Soc., Vol. 122, No. 22, 2000 5341
Table 2. Alkene Epoxidation with Cl2pyNO Catalyzed by
3b-MPRa
(iv) The catalysts 3-MPR are robust toward the epoxidation
reactions. With styrene as substrate, consecutively reusing the
catalysts 3a-MPR and 3b-MPR (3 loading: 0.17 wt %) four
and nine times, respectively, results in no detectable catalyst
leaching, and in the former case reveals no significant decrease
in epoxide yield. Turnovers as high as 3.0 × 104 can be obtained
by employing the catalyst 3b-MPR.
Experimental Section
General. Merrifield’s peptide resin (Aldrich, 2% cross-linked, 200-
400 mesh, ∼2 mmol Cl/g), Ru3(CO)12 (Strem), and alkene 11 (Aldrich)
were used as received. 1,2-Dihydronaphthalene and norbornene were
purified by sublimation. Alkene (R)-13 was prepared by a literature
method.23a The other alkenes, all liquid compounds of the highest quality
available from commercial vendors, were purified by passing through
a column of activated alumina before use. 2,6-Dichloropyridine N-oxide
was prepared by Rousseau’s method.26 5,10,15-Tris(4-R-phenyl)-20-
(4-hydroxyphenyl)porphyrins (R ) Cl, Me) were synthesized according
to the reported procedures.10 All solvents were of AR grade. 1H NMR
spectra were measured on a Bruker DPX 300 spectrometer (300 MHz)
by using tetramethylsilane (TMS) as an internal standard, with the
chemical shifts relative to TMS. Infrared spectra (KBr pellets) were
recorded on a Bio-Rad FTS-7 FT-IR spectrometer and Raman spectra
on a Bio-Rad FT-Raman laser spectrometer. UV-visible spectra were
measured on a Milton Roy Spectronic 3000 diode-array spectropho-
tometer. Gas chromatography was performed on a Hewlett-Packard
5890 Series II gas chromatograph equipped with a flame ionization
detector and a 3396 Series II integrator. The ruthenium contents in 3-
and 4-MPR were determined on a Perkin-Elmer 3110 flame atomic
absorption spectrometer. Elemental analyses were performed by the
Institute of Chemistry, the Chinese Academy of Sciences.
Preparation of Ruthenium Porphyrins 3 and 4. A mixture of Ru3-
(CO)12 (200 mg) and the corresponding free base porphyrin (200 mg)
in Decalin (50 mL) was refluxed under nitrogen for 24 h. The resulting
red solution was loaded on an alumina column. Decalin and some other
impurities were removed by using hexane as the eluent. The brick red
band containing the desired product was then eluted with dichlo-
romethane and collected. Removal of the solvent followed by recrys-
tallization of the residual solid from dichloromethane/n-hexane (1:6
v/v) afforded complex 3 or 4 as red purple crystals.
a All reactions were performed in benzene at 50 °C for 48 h with a
catalyst:oxidant:substrate molar ratio of 1:30000:43000. b Determined
1
by GC or H NMR based on the amount of Cl2py formed.
efficient in catalyzing alkene epoxidation with Cl2pyNO, as
shown in Table 2. The catalyst turnovers are very high (up to
1.8 × 104). However, the epoxide yields are lower than those
obtained by employing catalyst 3a-MPR (cf. Table 1). For the
epoxidation of styrene, consecutively reusing 3b-MPR nine
times, under conditions identical with those denoted in Table 2
except for a shorter reaction time (24 h), revealed no detectable
catalyst leaching,25 with total turnovers reaching 3.0 × 104.
Conclusion
(i) Treatments of carbonyl ruthenium(II) 5,10,15-tris(4-R-
phenyl)-20-(4-hydroxyphenyl)porphyrins (R ) Cl, 3; Me, 4)
with Merrifield’s peptide resin (MPR) in DMF at 80 °C for 4
h result in the covalent attachment of 3 and 4 to the polymer
matrix.
(ii) The polymer-supported ruthenium porphyrin 3a-MPR
with 3 loading of 8.6 wt % is an efficient catalyst for epoxidation
of both electron-rich and -deficient alkenes, including 1,5-
cyclooctadiene, trans-stilbene, R,â-unsaturated ketones, conju-
gated enyne, glycal, and protected R-amino alkene, as well as
common unfunctionalized alkenes such as styrenes and nor-
bornene. Prior to this work, no metalloporphyrins have been
reported to be active catalysts for Cl2pyNO or PhIO epoxidation
of R,â-unsaturated ketones.
(iii) Unusual selectivities are observed in the epoxidations
of (a) 1,5-cyclooctadiene: only the corresponding bisepoxide
is detected, contrary to the selective monoepoxide formation
previously reported for epoxidation of the same alkene catalyzed
by a molybdenum porphyrin; (b) cis-1-phenyl-3-penten-1-yne:
the epoxides obtained feature a cis:trans ratio of 13:1, much
higher than the ratio of 1:2 reported for manganese-salen
catalysts; and (c) 3,4,6-tri-O-acetyl-D-glucal, and (R)-2-(Boc-
amino)-1-phenylbut-3-ene: complete diastereoselectivity is
obtained, in contrast to the corresponding epoxidation catalyzed
by a ruthenium porphyrin immobilized onto surface-modified
MCM-41 and stoichiometric epoxidation by m-CPBA, respec-
tively.
3: Yield: 80%. UV/vis (CHCl3): λmax 418 (Soret), 530 nm. IR:
1
ν(CO) 1941 cm-1. FAB-MS: m/z 862 (M+), 834 ([M - CO]+). H
NMR (CDCl3): δ 8.69 (s, 8H), 8.09 (m, 6H), 8.00 (m, 2H), 7.72 (m,
6H), 7.15 (m, 2H). Anal. Calcd for C45H25Cl3N4O2Ru‚2H2O: C, 60.24;
H, 3.26; N, 6.24. Found: C, 60.19; H, 3.38; N, 6.02.
4: Yield: 86%. UV/vis (CHCl3): λmax 416 (Soret), 530 nm. IR:
1
ν(CO) 1942 cm-1. FAB-MS: m/z 800 (M+), 772 ([M - CO] +). H
NMR (CDCl3): δ 8.72 (s, 8H), 8.03 (m, 8H), 7.53 (m, 6H), 7.02 (m,
2H), 2.69 (s, 9H). Anal. Calcd for C48H34N4O2Ru‚2H2O: C, 68.97; H,
4.58; N, 6.70. Found: C, 68.76; H, 4.52; N, 6.30.
Preparation of Polymer-Supported Ruthenium Porphyrin Cata-
lysts 3- and 4-MPR. A Typical Procedure. To a solution of 3 (0.1
mmol) in DMF (30 mL) were added Merrifield’s peptide resin (1.0 g)
and anhydrous potassium carbonate (0.5 g). The mixture was vigorously
stirred at 80 °C for 4 h under a nitrogen atmosphere. After cooling,
the red resin was collected by filtration, washed thoroughly with water,
ethanol, and chloroform, and dried in vacuo at room temperature for
several hours. This procedure gave the catalyst 3a-MPR. The catalysts
3b- and 4-MPR were prepared in a similar manner by using a smaller
amount of 3 and 4 (both 2 µmol), respectively. The contents of 3 or 4
in 3- or 4-MPR were calculated from the ruthenium contents in the
heterogenized catalysts determined by atomic absorption spectroscopy.
3a-MPR: IR: ν(CO) 1944 cm-1. Raman: 1611, 1548, 1366, 1239,
411 cm-1 (bands associated with the attached 3; for comparison, these
bands appear at 1612, 1548, 1368, 1234, 412 cm-1 in the Raman
spectrum of 3). 3b-MPR: IR: ν(CO) 1946 cm-1. 4-MPR: IR: ν(CO)
(25) After each run, the loading of 3 in the recovered 3b-MPR was
determined, which remained unchanged within the experimental error.
However, there was a considerable drop of the epoxide yield in the second
run. For the remaining runs, the epoxide yield became fairly stable.
1947 cm-1
.
(26) Rousseau, R. J.; Robins, R. K. J. Heterocycl. Chem. 1965, 2, 196.

5342 J. Am. Chem. Soc., Vol. 122, No. 22, 2000
Yu et al.
Procedure for Cl2pyNO Epoxidation of Alkenes Catalyzed by
3a-MPR. All the epoxidation reactions were carried out in a sealed
vial or flask under nitrogen. The products were identified by GC in
the cases where the corresponding authentic samples were available,
or by comparison with the previously reported H NMR spectral data
in the other cases. Product quantification was made through GC or
NMR measurements in the presence of appropriate internal standards.
(ii) Other Alkenes. A mixture of alkene (0.80 mmol), Cl2pyNO
(0.70 mmol), and 3a-MPR (5 mg) in benzene (4 mL) was stirred for
24 h at room temperature. After filtration, the filtrate was analyzed by
1
GC or H NMR spectroscopy.
1
Procedure for Cl2pyNO Epoxidation of Alkenes Catalyzed by
3b- or 4-MPR. The procedure is the same as that for the corresponding
alkene epoxidation catalyzed by 3a-MPR, except that a mixture of
alkene (0.86 mmol), Cl2pyNO (0.60 mmol), and 3b- or 4-MPR (10
mg) was used and stirred at 50 °C for 48 h followed by cooling the
mixture to room temperature.
(i) Alkenes 11 and (R)-13. A mixture of alkene (0.60 mmol), Cl2-
pyNO (0.61 mmol), and 3a-MPR (10 mg) in benzene (4 mL) was stirred
at 40 °C. When the reaction was complete, as revealed by TLC analysis,
the mixture was filtered, and the filtrate was evaporated in vacuo to
remove the solvent. The residue was then purified by column
chromatography. In the case of 11, the colorless oil obtained was stirred
with anhydrous methanol at room temperature under nitrogen until the
methanolysis was complete (monitored by TLC). Removal of methanol
followed by chromatography gave a white solid in 56% yield (based
Reuse of Catalyst 3a- or 3b-MPR for Epoxidation of Styrene.
At the end of the epoxidation reaction, the catalyst was recovered by
filtration and briefly dried under reduced pressure. In all cases, the
filtrate was colorless, and the UV/vis spectrum revealed the absence
of porphyrin species. The epoxidation reaction was repeated by
employing the recovered catalyst, fresh styrene, and Cl2pyNO under
the same conditions.
1
on starting alkene 11), whose H NMR spectrum is characteristic of
pure methyl 3,4,6-tri-O-acetyl-â-D-glucopyranoside.27 This revealed that
the epoxidation product of 11 is R-12 (notice that the methanolysis of
R-12 would result in an inversion of configuration5b,19). For alkene (R)-
13, pure epoxide product was obtained as a colorless oil in 88% yield
(TLC, silica gel, n-hexane/ether (2:1 v/v), Rf ) 0.35). The spectral data
of the oil are identical with those of the enantiomer of threo-14 reported
in the literature.28
Acknowledgment. This work was supported by The Uni-
versity of Hong Kong, the Hong Kong University Foundation,
and the Hong Kong Research Grants Council.
JA000461K
(28) The corresponding erythro-epoxide was not detected (for identifica-
tion of the threo- and erythro-epoxide by means of 1H NMR spectroscopy,
see: Evans, B. E.; Rittle, K. E.; Homnick, C. F.; Springer, J. P.; Hirshfield,
J.; Veber, D. F. J. Org. Chem. 1985, 50, 4615).
(27) Methyl 3,4,6-tri-O-acetyl-â-D-glucopyranoside shows its methoxy
proton resonances at δ 3.58 ppm, which is considerably different from the
corresponding resonances (δ 3.44 ppm) of its R counterpart (see ref 5b).