Soluble Polymer-Supported Ruthenium Porphyrin Catalysts for Epoxidation, Cyclopropanation, and Aziridination of Alkenes

Article abstract of DOI:10.1021/ol0259138

(Matrix Presented) Attachment of poly(ethylene glycol) (PEG) to ruthenium porphyrin via a covalent etheric bond gives soluble polymer-supported ruthenium catalysts 3-5. These catalysts exhibit high reactivity and selectivity toward alkene epoxidation with 2,6-dichloropyridine N-oxide and alkene cyclopropanation with diazo compounds. The application of these catalysts in the synthesis of unstable organic compounds has been demonstrated.

Full text of DOI:10.1021/ol0259138

ORGANIC
LETTERS
2
002
Vol. 4, No. 11
911-1914
Soluble Polymer-Supported Ruthenium
Porphyrin Catalysts for Epoxidation,
Cyclopropanation, and Aziridination of
Alkenes
1
Jun-Long Zhang and Chi-Ming Che*
Department of Chemistry and Open Laboratory of Chemical Biology of the Institute of
Molecular Technology for Drug DiscoVery and Synthesis, The UniVersity of Hong
Kong, Pokfulam Road, Hong Kong, China
cmche@hku.hk
Received March 22, 2002
ABSTRACT
Attachment of poly(ethylene glycol) (PEG) to ruthenium porphyrin via a covalent etheric bond gives soluble polymer-supported ruthenium
catalysts 3−5. These catalysts exhibit high reactivity and selectivity toward alkene epoxidation with 2,6-dichloropyridine N-oxide and alkene
cyclopropanation with diazo compounds. The application of these catalysts in the synthesis of unstable organic compounds has been
demonstrated.
There is a growing interest in developing ruthenium por-
studies have demonstrated that ruthenium porphyrins exhibit
high stability and remarkable selectivity in catalyzing organic
oxidations by 2,6-dichloropyridine N-oxide and cyclopro-
panation of alkenes by diazo compounds. However, the
reported catalytic reactions usually proceed in homogeneous
media; this renders recycling of the ruthenium porphyrin
catalyst difficult. In this regard, there are reports on attach-
1a-g
1h-j
phyrin catalysts for carbon-oxygen,
carbon-nitrogen,
and carbon-carbon1k-n bond formation reactions. Extensive
(
1) Selected examples: (a) Groves, J. T.; Quinn, R. J. Am. Chem. Soc.
1
1
985, 107, 5790. (b) Higuchi, T.; Ohtake, H.; Hirobe, M. Tetrahedron Lett.
989, 30, 6545. (c) Ho, C.; Leung, W.-H.; Che, C.-M. J. Chem. Soc., Dalton
Trans. 1991, 2933. (d) Zhang, R.; Yu, W.-Y.; Lai, T.-S.; Che, C.-M. Chem.
Commun. 1999, 409. (e) Gross, Z.; Ini, S. Org. Lett. 1999, 1, 2077. (f) Liu,
C.-J.; Yu, W.-Y.; Che, C.-M.; Yeung, C.-H. J. Org. Chem. 1999, 64, 7365.
2
ment of an insoluble polymer support, including surface-
2a,b
modified mesoporous molecular sieve (MCM-41), Mer-
(
6
g) Zhang, R.; Yu, W.-Y.; Wong, K.-Y.; Che, C.-M. J. Org. Chem. 2001,
6, 8145. (h) Au, S.-M.; Huang, J.-S.; Yu, W.-Y.; Fung, W.-H.; Che, C.-
2
c
rifield’s peptide resin (MPR), and highly cross-linked
M. J. Am. Chem. Soc. 1999, 121, 9120. (i) Yu, X.-Q.; Huang, J.-S.; Zhou,
X.-G.; Che. C.-M. Org. Lett. 2000, 2, 2233. (j) Liang, J.-L.; Huang, J.-S.;
Zhu, L.-Y.; Che, C.-M. Chem. Eur. J. 2002, 8, 1563. (k) Galardon, E.; Le
Maux, P.; Simonneaux, G. Chem. Commun. 1997, 927. (l) Lo, W.-C.; Che,
C.-M.; Cheng, K.-F.; Mak, T. C. W. Chem. Commun. 1997, 1205. (m) Che,
C.-M.; Huang, J.-S.; Lee, F.-W.; Li, Y.; Lai, T.-S.; Kwong, H.-L.; Teng,
P.-F.; Lee, W.-S.; Lo, W.-C.; Peng, S.-M.; Zhou, Z.-Y. J. Am. Chem. Soc.
2001, 123, 4119. (n) Li, Y.; Huang, J.-S.; Zhou, Z.-Y.; Che, C.-M. J. Am.
Chem. Soc. 2001, 123, 4843.
1
0.1021/ol0259138 CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/04/2002

polymer,2d to ruthenium porphyrins to give heterogeneous
catalysts. However, these ruthenium-modified heterogeneous
catalysts suffer from limited mobility as a result of restriction
of the polymer matrix and accessibility of active sites to
organic substrates. To circumvent the problems encountered
in previous homogeneous and heterogeneous ruthenium
porphyrin catalysts, we set forth to develop dendritic
ruthenium porphyrin and investigate its catalytic reactivity
Scheme 1
3
toward epoxidation and cyclopropanation of alkenes. We
were also attracted to the recent works by Janda and co-
workers that metal catalysts containing poly(ethylene glycol)
(
PEG) have broad solubility profiles and are easily character-
4
ized and separated from organic products after reactions.
Anchoring ruthenium porphyrin to the commercially avail-
able PEG via covalent bond linkage provides a unique
opportunity to combine the best features of both homoge-
neous and heterogeneous ruthenium catalysts. Herein we
describe the applications of soluble polymer-supported
ruthenium porphyrins in catalytic epoxidation, aziridination,
and cyclopropanation of alkenes.
ruthenium porphyrin loading. Thus, catalyst 3 was chosen
for subsequent study.
The unsymmetrically substituted meso-tetraaryl-porphy-
rins, 5,10,15-tris(4-R-phenyl)-20-(4-hydroxyphenyl) porphy-
rins (R ) Cl, Me) were readily prepared via “one-pot”
reactions of the corresponding aldehydes and pyrrole;
As depicted in Table 1, 3 is an efficient catalyst for
epoxidation of a wide variety of alkenes by Cl pyNO. In
2
the cases of styrene, cis-stilbene, norbornene, cyclohexene,
cyclooctene, 1,2-dihydronaphthalene, and 1-octene, the yields
and selectivity of the epoxides were comparable to those
obtained with heterogeneous ruthenium porphyrin catalysts.1
For reactions with trans-stilbene and trans-â-methylstyrene,
the trans-epoxides were obtained in high overall yields (88%
and 93%, respectively). Chalcone, an electron-deficient
alkene, was also oxidized to the corresponding epoxide in
moderate yield. To our knowledge, epoxidation of electron-
deficient alkenes using metalloporphyrin catalysts has seldom
subsequent reactions with Ru
afforded ruthenium(II) porphyrins 1 and 2 in high yields.
3
(CO)12 in refluxing decalin
2
c
Attachment of ruthenium porphyrins to methoxypoly(ethyl-
ene glycol) was realized in high yields (R ) Cl, 75%; R )
Me, 82%) by treating 1 or 2 and the polymer mesylate
derivative in DMF in the presence of anhydrous potassium
carbonate at 60 °C for 6 h. Three catalysts 3 (R ) Cl), 4 (R
a-g
)
Cl), and 5 (R ) Me) with different ruthenium porphyrin
loadings were prepared (Scheme 1). UV-vis and IR
spectroscopic measurements revealed that ruthenium por-
phyrins were covalently bonded to PEG. H NMR spectra
5
1
been reported. The applicability of 3 in the synthesis of
organic building blocks has been examined. Using 1-phen-
ethynyl cyclohexene as substrate, the reaction afforded the
corresponding epoxide, a valuable intermediate in the
synthesis for bioactive enedyne antitumor agents, in high
showed the disappearance of the Me signals of MeSO
PEG at 3.07 ppm and appearance of a new peak at 4.06 ppm
attributed to PEGCH CH O-Por. The loading was deter-
2
-
2
2
1
2
mined by H NMR spectroscopy using the PEGCH OMe
6
overall yield (90%). 3,4,6-Tri-O-acetyl-D-glycal was con-
signal at ca. δ ) 3.30 as the internal reference.
To evaluate catalytic properties, we first investigated the
catalytic activities of catalysts 3 and 5 toward oxidation of
verted to the epoxide derivative, which is a useful intermedi-
7
ate for carbohydrate synthesis, in 67% isolated yield with
the R:â ratio being 10:1. This R/â diastereoselectivity is
significantly higher than that with ruthenium porphyrin
styrene in CH
and 2,6-Cl pyNO were used. The best conversion (96%) and
selectivity (epoxide yield, 98%) were obtained with 2,6-Cl
pyNO. For the epoxidation of styrene by 2,6-Cl pyNO,
2 2 2 2
Cl . The terminal oxidants PhIO, TBHP, H O ,
2
2
a,b
immobilized on MCM-41
and comparable to that with
-TPP)(CO)] , dendritic ruthenium porphyrin,
and ruthenium porphyrin immobilized on Merrifield’s peptide
2
-
II
2b
[
Ru (2,6-Cl
2
2
catalyst 3, which bears electron-withdrawing Cl group, is
superior to 5 and is more reactive than 4, which has a lower
2
c
resin . Last, cholesteryl acetate was epoxidized in high
overall yield (90%) and with complete â- selectivity; similar
VI
findings were previously reported using the “[Ru (TMP)-
(
2) (a) Liu, C.-J.; Li, S.-G.; Pang, W.-Q.; Che, C.-M. Chem. Commun.
8
f,g
(
O)
2
] + air” and “dendritic ruthenium porphyrin + 2,6-
1
1
997, 65. (b) Liu, C.-J.; Yu, W.-Y.; Li, S.-G.; Che, C.-M. J. Org. Chem.
998, 63, 7364. (c) Yu, X.-Q.; Huang, J.-S.; Yu, W.-Y.; Che, C.-M. J. Am.
3
8
Cl pyNO” protocols.
2
Chem. Soc. 2000, 122, 5337. (d) Nestler, O.; Severin, K. Org. Lett. 2001,
3
, 3907.
(3) Zhang, J.-L.; Zhou, H.-B.; Huang, J.-S.; Che, C.-M. Chem. Eur. J.
(5) (a) Groves, J. T.; Nemo, T. E. J. Am. Chem. Soc. 1983, 105, 5786.
2
002, 8, 1554.
(b) Selke, M.; Sisemore, M. F.; Valentine, J. S. J. Am. Chem. Soc. 1996,
118, 2008. (c) Higuchi, T.; Ohtake, H.; Hirobe, M. Tetrahedron Lett. 1989,
30, 6545.
(6) Myers, A. G.; Proteau, P. J. J. Am. Chem. Soc. 1989, 111, 1146.
(7) Halcomb, R. L.; Danishefsky, S. J. J. Am. Chem. Soc. 1989, 111,
6661.
(
4) For recent reviews, see: (a) Wentworth, P.; Janda, K. D. Chem.
Commun. 1999, 1917. (b) Clapham, B.; Reger, T. S.; Janda, K. D.
Tertrahedron. 2001, 57, 4637. (c) Toy, P. H.; Janda, K. D. Acc. Chem.
Res. 2000, 33, 546. (d) Gravert, D. J.; Janda, K. D. Chem. ReV. 1997, 97,
4
89.
1912
Org. Lett., Vol. 4, No. 11, 2002

Table 1. Epoxidation of Alkenes with Cl
3
2
pyNO Catalyzed by
Table 2. Cyclopropanation of Styrenes with Ethyl Diazoacetate
Catalyzed by 3a
a
entry
R
conv. %b
yield %c trans/cis ratiod
TON
1
2
3
4
5
6
7
H
65
86
93
56
82
66
47
88
98
80
93
91
88
82
9.7
9.3
9.5
8.8
10
11
9.2
572
843
744
521
746
581
385
CH3
OCH3
F
Cl
Br
CF3
a
All reactions were performed in dichloromethane at room temperature
for 24 h with a 3/EDA/alkene ratio of 1:1200:1000. b Conversion was
determined by GC analysis of the reaction mixture using the internal standard
method (1,4-dichlorobenzene or chlorobenzene); error, (2% of the stated
values. c Isolated yield based on the alkene consumed. d Determined by GC.
meric ruthenium porphyrin catalysts.3
,1k-n
Catalyst 3 displays
high stability in the cyclopropanation reactions; recycling
up to six times has been found not to affect its reactivity.
Intramolecular cyclopropanation is a useful reaction for
9
the synthesis of natural products. First, we used 3 to catalyze
cyclopropanation of primary allylic diazoacetates in CH
2
-
2
Cl at room temperature. The results are listed in Table 3.
a
All reactions were carried out in CH2Cl2 at 40 °C for 24 h with a
Table 3. Intramolecular Cyclopropanation of Primary Allylic
Diazoacetates Catalyzed by 3a
catalyst/Cl2pyNO/alkene molar ratio of 1:1100:1000, unless otherwise noted.
Conversion was determined by GLC analysis of the reaction mixture using
b
the internal standard method (1,4-dichlorobenzene or 1,3,5-tribromoben-
c
zene); error, (2% of the stated values. Based on the amount of olefin
d
e
consumed. TON ) turnover numbers. Other products: cyclo-2-en-1-one
f
(
41%) and cyclo-2-en-1-ol (11%). Conversion and yield were determined
by H NMR (400 MHz). Isolated yield after epoxidation and methanolysis.
1
g
h
1
R1
R2
isolated yield %b
TONc
Isolated yield. The ratio of â/R was determined by H NMR according to
entry
the previous literature. i The reaction was performed in CH2Cl2 at 40 °C
for 48 h with a catalyst/oxidant/substrate molar ratio of 1:17000:15000.
1
2
3
H
Ph
H
H
H
83
85
78
720
620
740
trans-CH3CHdCH
The soluble polymer catalyst 3 is oxidatively robust.
a
All reactions were performed in CH2Cl2 at room temperature for 24 h
3
Product turnovers up to 9.18 × 10 have been attained for
with a catalyst/substrate ratio of 1:1000. b On the basis of consumed
substrates. c TON ) turnover numbers.
styrene epoxidation in a 48 h reaction (entry 14, Table 1).
After being reused five times, its activity decreased only
slightly upon recycling of the catalyst by filtration.
We found that the catalyst exhibited high reactivity and could
be conveniently removed by adding diethyl ether to the
reaction mixture. Upon concentrating the filtrate, the organic
product could be obtained without purification by column
chromatography.
In this work, we also investigated intramolecular cyclo-
propanation of secondary allylic diazoacetates. Using 2-cy-
clohexen-1-yl diazoacetate as substrate, the reaction afforded
tricyclic cyclopropane as the main product in 85% yield
Catalyst 3 is effective for intra- and intermolecular
cyclopropanation of alkenes. The results for the reactions
between styrenes and ethyl diazoacetate (EDA) catalyzed by
3
are listed in Table 2. The para-substituent of styrene has
an effect on the conversion but minimally affects the trans/
cis ratio (∼10:1) of the cyclopropane products. These results
are different from that obtained with dendritic and mono-
(
8) Selected examples: (a) Parish, E. J.; Li, S. J. Org. Chem. 1996, 61,
5
665. (b) Syamala, M. S.; Das, J.; Baskaran, S.; Chandrasekaran, S. J. Org.
(Scheme 2). The side product 2-cyclohexenone was obtained
Chem. 1992, 57, 1928. (c) Salvador, J. A. R.; S a` e Melo, M. L.; Campos
Nevers, A. S. Tetrahedron Lett. 1996, 37, 687. (d) Kesavan, V.; Chan-
drasekaran, S. J. Org. Chem. 1998, 63, 6999. (e) Yang, D.; Jiao, G.-S.
Chem. Eur. J. 2000, 6, 3517. (f) Tavar e` s, M.; Ramasseul, R.; Marchon,
J.-C.; Bachet, B.; Brassy, C.; Mornon, J.-P. J. Chem. Soc., Perkin Trans. 2
(9) For reviews, see: (a) Doyle, M. P.; Forbs, D. C. Chem. ReV. 1998,
98, 911. (b) Doyle, M. P.; Mckervey, M. A.; Ye, T. Modern Catalytic
Methods for Organic Synthesis with Diazo Compounds; Wiley: New York,
1998.
1
992, 1321. (g) Marchon, J.-C.; Ramasseul, R. Synthesis 1989, 389.
Org. Lett., Vol. 4, No. 11, 2002
1913

followed by filtering of the polymer catalyst. No column
chromatography was needed to remove the catalyst from the
products.
Scheme 2
Catalyst 3 was also tested for catalytic aziridination of
alkenes by PhIdNTs. To our knowledge, there has been no
report on metalloporphyrin catalysts immobilized on soluble
or insoluble polymer support for alkene aziridination. The
results are listed in Table 5; moderate reactivity toward
aromatic alkenes was found.
in 10% yield. This is the first example of intramolecular
cyclopropanation of secondary allylic diazoacetates using
ruthenium porphyrin as catalyst, and the result is comparable
to that previously reported by using rhodium or copper
Table 5. Aziridination of Alkenes with PhIdNTs Catalyzed by
a
3
1
0
catalysts.
We have extended the application of catalyst 3 for
cyclization of γ-alkoxy-R-diazo-â-keto esters to (Z)-2-alkyl-
4
-(alkoxycarbonylmethylene)-1,3-dioxolanes.11 The results
are listed in Table 4. Catalyst 3 displayed remarkably high
Table 4. Unusual R-Diazocarbonyl Reaction of
a
γ-Alkoxy-R-diazo-â-keto Esters Catalyzed by 3 and
II
[
Ru ((TTP)CO]
a
All reactions were carried out at 40 °C for 8 h with a catalyst/PhINTs/
alkene molar ratio of 1:150:75, unless otherwise noted. b Conversion was
determined by GLC analysis of the reaction mixture using the internal
c
standard method (1,4-dichlorobenzene or chlorobenzene). Isolated yield
based on the amount of olefin consumed. d TON ) turnover numbers.
yield
entry
R
R′
catalyst
%b TONc
In summary, we prepared soluble polymer-supported
ruthenium porphyrin catalysts by treatment of ruthenium
porphyrins with methoxypoly(ethylene glycol). Catalyst 3
exhibits high reactivity, selectivity, and stability in epoxi-
dation and cyclopropanation of alkenes. It is worthy to note
that catalyst 3 is particularly useful for synthesis of unstable
organic compounds such as (Z)-2-alkyl-4-(alkoxycarbonyl-
methylene)-1,3-dioxolanes that are easily decomposed upon
chromatography on silica gel column.
1
Ph
Ph
Me
Me
3
92
460
22
430
16
2d
[Ru (TTP)CO] 68
3
II
3
4d
2-cyclohexenyl (-)-menthyl
2-cyclohexenyl (-)-menthyl [Ru (TTP)CO] 50
85
II
a
All reactions were performed in refluxed toluene for 6 h with a catalyst/
substrate ratio of 1:500. On the basis of consumed substrates. c TON )
turnover numbers. According to ref 11.
b
d
reactivity (conversions were up to 99%) and turnovers (up
to 460) compared with the monomeric [Ru (TTP)CO] [H
TTP ) meso-tetrakis(p-tolyl) porphyrin] catalyst. For the
latter, the isolated product yields were lower (entries 2 and
II
Acknowledgment. We are grateful to the University of
Hong Kong, Hong Kong University Foundation, and the
Hong Kong Research Grants Council (No. 7077/019) for the
support of this research.
2
-
4
, Table 4); this was attributed to product decomposition
upon chromatography on silica gel column. In this work,
the products were obtained in higher yields (entries 1 and 3,
Table 4) by adding diethyl ether to the reaction mixture
Supporting Information Available: Experimental details
for the synthesis and characterization of 3, 4, and 5; the
effects of oxidants, solvents and catalysts on epoxidation of
styrene in this protocol; and detailed procedures for the
catalytic reactions. This material is available free of charge
via the Internet at http://pubs.acs.org.
(
10) (a) Clive, D. L. J.; Daigneault, S. J. Org. Chem. 1991, 56, 3801.
b) Doyle, M. P.; Dyatkin, A. B.; Kalinin, A. V.; Ruppar, D. A.; Martin, S.
F.; Spaller, M. R.; Liras, S. J. Am. Chem. Soc. 1995, 117, 11021.
11) Zheng, S.-L.; Yu, W.-Y.; Zhu, N.-Y.; Che. C.-M. Org. Lett. 2002,
, 889.
(
(
4
OL0259138
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Org. Lett., Vol. 4, No. 11, 2002