Ruthenium(II) porphyrin catalyzed tandem carbonyl ylide formation and 1,3-dipolar cycloaddition reactions of α-diazo ketones

Article abstract of DOI:10.1021/ol0201254

equation presented The ruthenium porphyrin-catalyzed reactions of diazo ketones with π-unsaturated compounds via carbonyl ylide formation/cycloaddition cascade exhibit product yields and selectivities comparable to the analogous reactions with dirhodium c

Full text of DOI:10.1021/ol0201254

ORGANIC
LETTERS
2002
Vol. 4, No. 19
3235-3238
Ruthenium(II) Porphyrin Catalyzed
Tandem Carbonyl Ylide Formation and
1,3-Dipolar Cycloaddition Reactions of
r-Diazo Ketones
Cong-Ying Zhou, Wing-Yiu Yu, 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
cmche@hku.hk
Received July 3, 2002
ABSTRACT
The ruthenium porphyrin-catalyzed reactions of diazo ketones with π-unsaturated compounds via carbonyl ylide formation/cycloaddition cascade
exhibit product yields and selectivities comparable to the analogous reactions with dirhodium carboxylates as catalysts. By grafting a ruthenium
porphyrin on poly(ethylene glycol) (Zhang, J.-L.; Che, C.-M. Org. Lett. 2002, 4, 1911), a recyclable catalytic system is developed with over 5700
product turnovers attained for the reaction of 1-diazo-2,5-hexanedione with dimethyl acetylenedicarboxylate.
Dipolar cycloaddition of carbonyl ylides to multiple-bonded
dipolarophiles is a powerful strategy for construction of
carbocyclic ring systems in a regio- and stereocontrolled
manner.1 Dirhodium carboxylates are proven to be effective
catalysts for the tandem carbonyl ylide/1,3-dipolar cycload-
dition reactions, and a highly reactive rhodium-carbenoid
intermediate is widely postulated.2 Indeed, Rh-catalyzed
carbonyl ylide formation/cycloaddition cascade reactions
have been successfully employed for stereoselective synthesis
of highly functionalized oxygen heterocycles and natural
products (Figure 1).2a,3 Apart from dirhodium carboxylates,
few transition-metal complexes are known to exhibit similar
activities.4
Extensive studies by us5 and others6 showed that ruthenium
porphyrins are versatile catalysts for C-O and C-N bond
formations. Recently, ruthenium porphyrin-catalyzed car-
(1) (a) Ho, T. L. Tandem Organic Reactions; John Wiley and Sons: New
York, 1992. (b) Moore, W. H.; Decker, O. H. W. Chem. ReV. 1986, 86,
821. (c) 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; Wiley-
Interscience: New York, 1984.
Figure 1. Ruthenium porphyrins.
10.1021/ol0201254 CCC: $22.00 © 2002 American Chemical Society
Published on Web 08/27/2002

benoid transformations using diazo compounds has received
a growing interest.7-8 Our recent study revealed that a D4-
symmetric chiral ruthenium-carbene porphyrin complex,
[RuII(D4-Por*)(CO)] (D4-H2Por* ) 5,10,15,20-tetrakis-
[(1S,4R,5R,8S)-1,2,3,4,5,6,7,8-octahydro-1,4:5,8-dimeth-
anoanthracen-9-yl]porphyrin), is an effective catalyst for
highly regio- and enantioselective intermolecular cyclopro-
panation of styrenes with high product turnovers using ethyl
diazoacetate as carbene source.7b,h Considering the lower cost
of Ru vs Rh, the high structural diversity, and the remarkable
product turnovers of metalloporphyrin catalysts, we anticipate
that ruthenium porphyrins such as the ones depicted in
Figure 1 would be an attractiVe alternatiVe to dirhodium
carboxylates as catalysts for carbenoid-mediated transfor-
mations.
With activated alkenes such as N-phenylmaleimide as
dipolarophile, the Ru-catalyzed decomposition of 1a,b gave
exo-3a,b exclusively in 80-82% yields (Scheme 2). The
stereochemical assignment was made by comparison with
the reported spectral data.11
When an unsymmetrical methyl propiolate was employed
as dipolarophile (Scheme 3), the Ru-catalyzed reaction of
Scheme 3
In view of the synthetic usefulness of the tandem carbonyl
ylide formation/cycloaddition methodology in organic syn-
thesis, we set forth to develop a ruthenium porphyrin-based
catalytic system for this important class of reactions. In this
work, we employed a ruthenium porphyrin supported on
poly(ethylene) glycol (PEG) as recyclable catalyst9 for the
catalytic cycloaddition of 1-diazo-2,5-hexanedione (1a) with
DMAD, and more than 5700 product turnovers have been
achieved through seven successive reactions.
To begin our study, we examined the reaction of o-(meth-
oxycarbonyl)-R-diazoacetophenone.10 When the diazoace-
tophenone was added slowly over 2 h through a syringe
pump to a CH2Cl2 solution containing DMAD (1.2 equiv)
and [RuII(TTP)(CO)] (1 mol %), the desired cycloadduct was
isolated in 84% yield (Scheme 1).
1a gave two regioisomeric cycloadducts 4a and 5a in 80%
overall isolated yield, where 4a was produced preferentially
(4a/5a ) 15:1) on the basis of H NMR analysis of the
1
reaction mixture. In this work, the analogous [Rh2(CH3-
CO2)4]-catalyzed reaction was found to give a slightly lower
regioselectivity (4a/5a ) 8:1). The phenyl-substituted deriva-
tive 1b reacted with methyl propiolate to afford 4b as the
only product (ca. 77%) under the Ru-/Rh-catalyzed condi-
tions (Scheme 3).
Analogous to the Rh-catalyzed reaction,11 the [RuII(TTP)-
(CO)]-catalyzed reaction of 1a with methyl acrylate produced
a mixture of four diastereomeric cycloadducts: exo-/endo-
6a and exo-/endo-7a (Scheme 4), isolated in 85% overall
Scheme 1
Scheme 4
The reactivity of conformationally flexible diazo ketones
1a,b containing a 2,5-pentanedione backbone has been
examined (Scheme 2). The diazo ketones were derived from
yield. Individual compounds were characterized spectro-
scopically with reference to the literature data.11 On the basis
of H NMR analysis of the crude reaction mixture, the
Scheme 2
1
regioselectivity (6a/7a) was determined to be 2.5:1 with exo/
endo ratios of 4:1 (6a) and 5:1 (7a).
Both CH2Cl2 and C6H6 are equally effective as solvent
for the ruthenium porphyrin-catalyzed cycloaddition reac-
levulinic acid and 3-benzoylpropionic acid according to
reported procedures.11 Under the Ru-catalyzed conditions,
1a and 1b were found to undergo facile cycloaddition with
DMAD (1.2 equiv), furnishing 2a,b in ca. 85% isolated
yields (Scheme 2). It is noteworthy that comparable product
yields [90% (2a); 88% (2b)] were obtained using [Rh2(CH3-
CO2)4] as catalyst.
(2) (a) Hodgson, D. M.; Stupple, P. A.; Pierard, F. Y. T. M.; Labande,
A. H.; Johnstone, C. Chem. Eur. J. 2001, 7, 4465. (b) Hodgson, D. M.;
Pierard, F. Y. T. M.; Stupple, P. A. Chem. Soc. ReV. 2001, 30, 50. (c)
Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for
Organic Synthesis with Diazo Compounds; John Wiley and Sons: New
York, 1998; Chapter 7, 397. (d) Kitagaki, S.; Anada, M.; Kataoka, O.;
Matsuno, K.; Umeda, C.; Watanabe, N.; Hashimoto, S.-I. J. Am. Chem.
Soc. 1999, 121, 1417. (e) Padwa, A.; Weingarten, M. D. Chem. ReV. 1996,
96, 223.
3236
Org. Lett., Vol. 4, No. 19, 2002

tions. When the cycloaddition of 1a with methyl acrylate
was performed in C6H6, 6a and 7a were obtained in 73%
overall yield. On the basis of 1H NMR analysis, the
regioselectivity (6a/7a ) 3:1) and stereoselectivities [exo/
endo ratio ) 4:1 (6a) and 5:1 (7a)] were found to be identical
to the corresponding values when CH2Cl2 was used as the
solvent.
was probably formed via 1,4-hydrogen shift of the carbonyl
ylide intermediate.
The CdO bond of benzaldehyde is also an effective
dipolarophile. Treatment of 1a with benzaldehyde (5 equiv)
and [RuII(TTP)(CO)] (1 mol %) in CH2Cl2 at room temper-
ature afforded the 1:1 cycloadduct exo-13 exclusively in 73%
yield (Scheme 6). Unlike the related Rh-catalyzed reaction,11
A similar reaction of 1b with methyl acrylate produced
four diastereomeric cycloadducts exo-/endo-6b and exo-/
endo-7b (Scheme 4), which were isolated in 78% overall
yield. 1H NMR analysis of the reaction mixture revealed the
regioisomeric (6b/7b) ratio ) 5:1 and the exo/endo ratios
being 15:1 (6b) and 5:1 (7b). The observed product yields
and selectivities for the Ru-catalyzed cycloadditions are
similar to that reported for the analogous Rh-catalyzed
reactions.11
Scheme 6
Dropwise addition of 1b to a CH2Cl2 solution of styrene
(5 equiv) and [RuII(TTP)(CO)] (1 mol %) resulted in
cyclopropanation predominantly, and cyclopropane 10 was
isolated in 55% yield with the anti/syn ratio ) 8.5:1. Yet,
cycloadducts 8 and 9 were obtained in 28% overall yield
(Scheme 5) and characterized spectroscopically.11 The re-
formation of the [2:1] cycloadduct was not observed in this
work. With p-quinone as dipolarophile,3d cycloaddition to
the CdO bond occurred preferentially to give 14 in 72%
1
isolated yield. By H NMR analysis, the CdC cycloadduct
was detected in <10% yield. A similar finding was observed
for the analogous [Rh2(CH3CO2)4]-catalyzed reaction (14:
76% isolated yield).
Scheme 5
Employing 1a and methyl acrylate as substrates, the effect
of the porphyrin structure on the Ru-catalyzed cycloaddition
has been examined. As depicted in Table 1, the regio- and
Table 1. Effect of Ruthenium Porphyrin Catalysts on the
Cyclization of Diazo Compound 1a with Methyl Acrylate
gioselectivity of the cycloaddition (8:9) was determined to
be 7:1 with the exo/endo ratios ) 26:1 (8) and 5:1 (9) based
on H NMR analysis of the reaction mixture. The Ru-
catalyzed reaction of 1b with propargylic bromide afforded
the cycloadduct 11 in only 14% yield by the carbonyl ylide
formation/1,3-dipolar cycloaddition cascade. The enol ether
12 was isolated as the major product (56% yield), which
regio-
% yieldb selectivityc
1
exo/endoc
entry
Ru catalysta
(6a + 7a ) (6a /7a )
6a
7a
1
2
3
4
5
6
[RuII(TTP)(CO)]
85
80
82
83
78
87
2.5:1
2.6:1
3:1
4.8:1
4.5:1
2:1
4:1 5:1
3.8:1 7:1
3.9:1 7:1
3.8:1 3.3:1
3.2:1 3.3:1
3:1 3:1
[RuII(4-OMe-TPP)(CO)]
[RuII(4-F-TPP)(CO)]
[RuII(TMP)(CO)]
(3) Recent examples, see: (a) Hodgson, D. M.; Avery, T. D.; Donohue,
A. C. Org. Lett. 2002, 4, 1809. (b) Wood, J. L.; Thompson, B. D.; Yusuff,
N.; Pflum, D. A.; Mattha¨us, M. S. P. J. Am. Chem. Soc. 2001, 123, 2097.
(c) Chiu, P.; Chen, B.; Cheng, K.-F. Org. Lett. 2001, 3, 1721. (d) Pirrung,
M. C.; Kaliappan, K. P. Org. Lett. 2000, 2, 353.
(4) (a) Ibata, T.; Jitsuhiro, K.; Tsubokura, Y. Bull. Chem. Soc. Jpn. 1981,
54, 240. (b) Ibata, T.; Jitsuhiro, K. Bull. Chem. Soc. Jpn. 1979, 52, 3582.
(5) (a) Zhang, R.; Yu, W.-Y.; Sun, H.-Z.; Liu, W.-S.; Che, C.-M. Chem.
Eur. J. 2002, 8, 2495. (b) Liang, J.-L.; Huang, J.-S.; Yu, X.-Q.; Zhu, N.-
Y.; Che, C.-M. Chem. Eur. J. 2002, 8, 1563. (c) Zhang, R.; Yu, W.-Y.;
Wong, K.-Y.; Che, C.-M. J. Org. Chem. 2001, 66, 8145. (d) Yu, X.-Q.;
Huang, J.-S.; Zhou, X.-G.; Che, C.-M. Org. Lett. 2000, 2, 2233. (e) Zhang,
R.; Yu, W.-Y.; Lai, T.-S.; Che, C.-M. Chem. Commun. 1999, 409. (f) Au,
S.-M.; Huang, J.-S.; Yu, W.-Y.; Fung, W.-H.; Che, C.-M. J. Am. Chem.
Soc. 1999, 121, 9120. (g) Lai, T.-S.; Zhang, R.; Cheung, K.-K.; Kwong,
H.-L.; Che, C.-M. Chem. Commun. 1998, 1583.
[RuII(TDCPP)(CO)]
[Rh2(CH3CO2)4]
a [H2TTP] ) meso-tetrakis(4-tolyl)porphyrin; [H2-4-OMe-TPP] ) meso-
tetrakis(4-methoxyphenyl)porphyrin; [H2-4-F-TPP] ) meso-tetrakis(4-fluo-
rophenyl)porphyrin; [H2TMP] ) meso-tetrakis(mesityl)porphyrin; [H2TDCPP]
) meso-tetrakis(2,6-dichlorophenyl)porphyrin. b Isolated yield. c Based on
1H NMR analysis of the reaction mixture.
stereoselectivities show modest variation with the porphyrin
structure. The sterically bulky [RuII(TMP)(CO)] and [RuII-
(TDCPP)(CO)] were found to exhibit comparable activities
to [RuII(TTP)(CO)] and [Rh2(CH3CO2)4].
When 1-diazo-9-decene-2,5-dione (Scheme 7)12 containing
a tethered terminal CdC bond was added slowly to a CH2-
Cl2 solution of [RuII(TTP)(CO)] (1 mol %), hexahydro-1H-
(6) (a) Gross, Z.; Ini, S. Org. Lett. 1999, 1, 2077. (b) Berkessel, A.;
Frauenkron, M. J. Chem. Soc., Perkin Trans. 1 1997, 2265. (c) Groves, J.
T.; Roman, J. S. J. Am. Chem. Soc. 1995, 117, 5594. (d) Higuchi, T.; Ohtake,
H.; Hirobe, M. Tetrahedron Lett. 1989, 30, 6545. (e) Groves, J. T.; Quinn,
R. J. Am. Chem. Soc. 1985, 107, 5790.
Org. Lett., Vol. 4, No. 19, 2002
3237

cyclopropanations, and yet the catalyst is readily recovered
and reused without loss of catalytic activity.9
Scheme 7
In this work, a recyclable catalytic system for the tandem
carbonyl ylide formation/cyclization reaction was developed.
Addition of 1a to CH2Cl2 containing DMAD and the Ru-
PEG catalyst (0.1 mol %) over 30 h at room temperature
afforded 2a in 85% yield with 850 turnovers. The Ru-PEG
catalyst was recovered and subjected to another six consecu-
tive reactions (see the Supporting Information for details);
the results are listed in Table 2. No apparent loss of catalytic
3a,7-epoxyazulen-6(7H)-one was formed presumably via
intramolecular 1,3-dipolar cycloaddition (Scheme 7). The
cycloadduct was isolated in 83% yield after column chro-
matography and was characterized spectroscopically.12
Previously, we13a-c and others13d reported that ruthenium
porphyrin complexes can be grafted onto various insoluble
solid supports such as Merrifield resin,13a mesoporous
molecular sieves (MCM-41)13b-c and some highly cross-
linked polymers13d for heterogeneous organic oxidations.13
Recently, we developed a ruthenium porphyrin catalyst
supported on poly(ethylene glycol) (Figure 2).9 This sup-
Table 2. Recyclable Ru-PEG Catalyst for Tandem Carbonyl
Ylide Formation/Cycloaddition Reaction
reaction run
% yield
turnovers
1
2
3
4
5
6
7
85
83
83
81
82
80
78
850
830
830
810
820
800
780
activity was observed, and a total product turnover of 5720
was attained.
Acknowledgment. This work is supported by the Area
of Excellence Scheme (AoE/P-10-01) established under the
University Grants Council (HKSAR), The University of
Hong Kong (Generic Drugs Research Program), and the
Hong Kong Research Grants Council (HKU7077/01P). Dr.
Pauline Chiu is gratefully acknowledged for helpful discus-
sions.
Figure 2. Soluble polymer-supported ruthenium porphyrin (Ru-
PEG).
ported ruthenium porphyrin catalyst has been shown to
display excellent reactivities toward alkene epoxidations and
Supporting Information Available: Detailed experi-
mental procedures and characterization data. This material
is available free of charge via the Internet at http://pubs.acs.org.
(7) (a) Zheng, S.-L.; Yu, W.-Y.; Che, C.-M. Org. Lett. 2002, 4, 889. (b)
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. (c) Li, Y.; Huang, J.-S.; Zhou, Z.-Y.; Che, C.-M. J.
Am. Chem. Soc. 2001, 123, 4843. (d) Galardon, E.; Le Maux, P.;
Simonneaux, G. Tetrahedron 2000, 56, 615. (e) Gross, Z.; Galili, N.;
Simkhovich, L. Tetrahedron Lett. 1999, 40, 1571. (f) Frauenkron, M.;
Berkessel, A. Tetrahedron Lett. 1997, 38, 7175. (g) Galardon, E.; Le Maux,
P.; Simonneaux, G. J. Chem. Soc., Chem. Commun. 1997, 927. (h) Lo,
W.-C.; Che, C.-M.; Cheng, K.-F.; Mak, T. C.-W. J. Chem. Soc., Chem.
Commun. 1997, 1205.
OL0201254
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(12) Padwa, A.; Hornbuckle, S. F.; Fryxell, G. E.; Stull, P. D. J. Org.
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3238
Org. Lett., Vol. 4, No. 19, 2002