Asymmetric catalysis by a chiral ruthenium porphyrin: Epoxidation, hydroxylation, and partial kinetic resolution of hydrocarbons

Article abstract of DOI:10.1021/ol991131b

matrix presented A new member of our D₂ symmetry ruthenium porphyrins is shown to be a most selective catalyst for asymmetric epoxidation of terminal and trans-disubstituted olefins. The same catalyst displays some selectivity in kinetic resolution of secondary alcohols and in what appears to be the first example of catalytic enantioselective hydroxylation of tertiary alkanes.

Full text of DOI:10.1021/ol991131b

ORGANIC
LETTERS
1999
Vol. 1, No. 13
2077-2080
Asymmetric Catalysis by a Chiral
Ruthenium Porphyrin: Epoxidation,
Hydroxylation, and Partial Kinetic
Resolution of Hydrocarbons
Zeev Gross* and Santiago Ini
Department of Chemistry and Institute of Catalysis Science and Technology,
Technion - Israel Institute of Technology, Haifa 32000, Israel
chr10zg@tx.technion.ac.il
Received October 8, 1999
ABSTRACT
A new member of our D symmetry ruthenium porphyrins is shown to be a most selective catalyst for asymmetric epoxidation of terminal and
2
trans-disubstituted olefins. The same catalyst displays some selectivity in kinetic resolution of secondary alcohols and in what appears to be
the first example of catalytic enantioselective hydroxylation of tertiary alkanes.
The first utilization of a chiral iron porphyrin as catalyst for
catalytic asymmetric epoxidation of nonactivated olefins has
Scheme 1 Structures of the Catalysts
initiated the preparation of many chiral porphyrins.1,2 We
have contributed to this field by reporting the facile synthesis
of double-side protected porphyrins with D2 symmetry (1 in
Scheme 1).3 This led to the first utilization of a chiral
ruthenium porphyrin (1-Ru(O)2, Scheme 1) as oxidation
catalyst, which was found to be outstandingly active in the
epoxidation of olefins by aromatic N-oxides.4 Subsequently,
similar results were obtained with D4 symmetry ruthenium
porphyrin complexes,5,6 and both types of complexes were
also later found to be excellent cyclopropanation catalysts.7
(1) Groves, J. T.; Myers, R. S.J. Am. Chem. Soc. 1983, 105, 5791.
(2) Collman, J. P.; Zhang, X.; Lee, V. J.; Uffelman, E.; Brauman, J. I.
Science 1993, 261, 1404 and references therein.
(3) Ini, S.; Kapon, M.; Cohen, S.; Gross, Z. Tetrahedron: Asymmetry
1996, 7, 659.
(4) Gross, Z.; Ini, S.; Kapon, M.; Cohen S. Tetrahedron Lett. 1996, 37,
7325.
(5) Berkessel, A.; Frauenkron, M. J. Chem. Soc., Perkin Trans. 1 1997,
Most important, in both catalytic processes it was found that
2265.
for identical chiral porphyrins the ruthenium complexes are
10.1021/ol991131b CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/02/1999

much better at inducing asymmetry than the more commonly
used iron, manganese, or rhodium derivatives.4,7-9 For
example, the 1-Ru(O)2- and 2-Ru(O)2-catalyzed epoxida-
tions of olefins proceed with higher enantioselectivities than
the same reactions in the presence of the iron and manganese
complexes of the same porphyrins.4,9 The enantiomeric
enrichments (ee’s) of the epoxides obtained from the
reactions of ring-substituted styrenes with N-oxides under
2-Ru(O)2 catalysis are in the range of 74-80% ee, record
values at that time.10
and 3,3′-dichlorobenzophenone and connected to 5,10,15,-
20-tetrakis(2,6-dihydroxyphenyl)porphyrin via etherfication,
to afford 3-H2.14 The catalytic reactions were performed
with equimolar amounts of olefin and 2,6-dichloropyridine
N-oxide, with as low as 0.1 mol % of catalyst (note that the
standard procedures with metal salen complexes call for 2
mol %, limiting the system to a maximum of 50 catalytic
turnovers). The data in Table 1 show that 3-Ru(O)2 is a
Another intriguing result with both the iron and the
ruthenium complexes of porphyrins 1 and 2 is that the ee’s
obtained from epoxidation of cis-olefins such as cis-â-
methylstryrene and 1,2-dihydronaphthalene are much lower
than those obtained for styrene.9 This is in sharp contrast to
most other chiral metalloporphyrins,2,11 as well as for chiral
manganese salen complexes.12 Furthermore, Che and co-
workers have most recently found a novel trans-selectivity
for 1-Ru(O)2.13 The epoxidation of trans- and cis-â-
methylstryrene displayed a very large difference in enanti-
oselectivity in favor of the trans-isomer (stoichiometric, 67%
vs 40% ee; catalytic, 50% vs 7% ee), which is in sharp
contrast to all other metal complexes.
Table 1. Asymmetric Epoxidation of Olefinsa
Since we found that the enantioselectivities obtained with
2-Ru(O)2 are much larger than with 1-Ru(O)2, we decided
to explore the ruthenium complex of porphyrin 3. This choice
is based on the X-ray crystal structures of 1 and its ruthenium
complex3,4 and on the molecular modeling investigation of
2. This suggested that meta-substitution of the phenyl groups
of porphyrin 2 will be beneficial for the selective recognition
of the re and si faces of the alkene substrates (Figure 1).
a Reactions were performed at -10 °C with 0.165 µmol of catalyst, 165
µmol of oxidant, and 165 µmol of olefin in 1 mL of toluene under Ar for
48 h. Yields were determined by GC analysis relative to an internal standard,
and the enantiomeric excesses were determined by capillary GC, using a
Cyclodex-B column for the ring-substituted styrenes and Chiraldex A-TA
for trans-â-methylstyrene, and by HPLC, using (s,s)-whelk-01 (5 µm), for
trans-stilbene oxide. aThe absolute configuration of the enantiomer in excess
is (R)-(+). bThe cis:trans ratio is 15:1, and the TON and ee are for the
c
cis-olefin. Only the trans-olefin is obtained.
very good catalyst indeed. The epoxidation of styrene and
its m- and p-chloro-substituted derivatives proceed with a
79-83% ee, practically identical to the most recently
(7) (a) Gross, Z.; Galili, N.; Simkhovich, L. Tetrahedron Lett. 1999, 40,
1571. (b) Galardon, E.; Roue, S.; Le Maux, P.; Simonneaux, G. Tetrahedron
Lett. 1998, 39, 2333. (c) Frauenkron, M.; Berkessel, A. Tetrahedron Lett.
1997, 38, 7175. (d) Lo, W.-C.; Che, C.-M.; Cheng, K.-F.; Mak, T. C. W.
J. Chem. Soc., Chem. Commun. 1997, 1205. (e) Galardon, E.; Le Maux,
P.; Simonneaux, G. J. Chem. Soc., Chem. Commun. 1997, 927.
(8) O’Malley, S.; Kodadek, T. Organometallics 1992, 11, 2299.
(9) Gross, Z.; Ini, S. J. Org. Chem. 1997, 62, 5514.
Figure 1. Computer model (MM2) of the new porphyrin.
(10) Gross, Z.; Ini, S. Inorg. Chem. 1999, 38, 1446.
(11) Halterman, R. L.; Jan, S.-T.; Nimmons, H. L.; Standlee, D. J.; Khan,
M. A. Tedrahedron 1997, 53, 11257.
(12) Katsuki, T. J. Mol. Catal. A 1996, 113, 87
(13) Zhang, R.; Yu, W.-Y.; Lai, T.-S.; Che, C.-M. J. Chem. Soc., Chem.
Commun. 1999, 409.
The new porphyrin and its ruthenium complexes were
prepared by analogy to the published procedures for 1 and
2.3,4,9,10 The chiral moiety was prepared from tartaric acid
(6) Lai, T.-S.; Kwong, H.-L.; Zhang, R.; Che, C.-M. J. Chem. Soc.,
Dalton Trans. 1998, 3559.
(14) The full synthetic procedures are provided as Supporting Informa-
tion.
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Org. Lett., Vol. 1, No. 13, 1999

reported best-ever values.15 In addition, much to our (pleas-
ant) surprise, despite the increased steric crowding, 3-Ru-
(O)2 is more reactive than 2-Ru(O)2. This is reflected in
the high turnover numbers (TON) with 3-Ru(O)2, 190-
550 mol of products/mol of catalyst, as compared to TON
) 11, 135, and 150 for the first three alkenes of Table 1
with 2-Ru(O)2 as catalyst.10
Table 2. Kinetic Resolution of Secondary Alcoholsa
The results for epoxidation of the â-substituted styrenes
are also quite intriguing. Similar to the observations of Che
et al. with 1-Ru(O)2,13 the 3-Ru(O)2-catalyzed reaction of
trans-â-methylstyrene was faster, more efficient, and more
enantioselective than that of the cis-isomer. Actually, the 69%
ee of the produced trans-epoxide is much higher than that
obtained by any other chiral metalloporphyrin catalysis (50%
ee with 1-Ru(O)2 and 25% ee with Collman’s catalyst).13,16
To take the system to its extreme, we have also investigated
the epoxidation of trans-stilbene. This olefin is known to be
a very poor substrate for metalloporphyrin catalysis (0% ee
with the D4 symmetry ruthenium porphyrin),5 and its
enantioselective activation is a remarkable challenge for any
system.17 Still, a 38% ee is obtained, together with 242
catalytic turnovers. Taken together, the chiral induction by
3-Ru(O)2 is high for terminal and trans-olefins but signifi-
cantly poorer for cis-olefins.
Encouraged by these results, we decided to explore the
utilization of our new catalyst in processes that were not
previously investigated for chiral metalloporphyrins. Further
motivation came from the work of Hirobe and co-workers,
who have developed a highly efficient system for hydroxy-
lation of alcohols and alkanes, based on catalytic amounts
of (carbonyl)ruthenium porphyrin and HX (X ) Cl, Br), with
pyridine N-oxides as primary oxidants.18 Accordingly, we
investigated the asymmetric version of the Hirobe system
with 3-Ru(CO).
The oxidation of racemic secondary alcohols was allowed
to proceed to about 50% conversion, after which the reaction
mixture was examined for the amount of kinetic resolution.
The results shown in Table 2 show that high conversion is
indeed achievable and that the selectivity is quite sensitive
to the steric aspects of both the alkyl (entries 1-3) and the
aryl groups (entries 4 and 5). The smaller molecules were
oxidized with larger selectivity, suggesting that the chiral
cavity of the catalyst might be too crowded for large
substrates.
a Reactions conditions: 24 h at 20 °C with 0.1 µmol of catalyst, 25 µmol
of oxidant, 50 µmol of alcohol, and 5 µL of a HCl-saturated benzene solution
in 0.5 mL of benzene under Ar. Chemical yields were determined by GC
analysis relative to an internal standard, and the enantiomeric excesses were
determined by using a Cyclodex-B chiral capillary column. aThe GC
separation between the alcohol and the ketone was not perfect in this case.
oxidant:catalyst ratio of 2500:250:1, shows that the reaction
is quite efficient (high turnovers) and that the products are
formed with significant enantiomeric enrichments (Table 3).
The 38% ee in the hydroxylation of 2-phenylbutane is quite
remarkable, considering that the chiral discrimination relies
Table 3. Catalytic Asymmetric Hydroxylation of Tertiary
Alkanesa
Nevertheless, the results obtained were sufficient as a test
of a most demanding reaction, the catalytic asymmetric
hydroxylation of tertiary alkanes. To our knowledge, there
is no system for that transformation, probably because if a
free radical intermediate is involved, it is expected to be
prone to easy racemization. The examination of racemic
2-phenylbutane and 2-phenylhexane, under a substrate:
(15) Collman, J. P.; Wang, Z.; Straumanis, A.; Quelquejeu, M.; Rose,
E. J. Am. Chem. Soc. 1999, 121, 460.
(16) Collman, J. P.; Lee, V. J.; Kellen-Yuen, C. J.; Zhang, X.; Ibers, J.
A.; Brauman, J. I. J. Am. Chem. Soc. 1995, 117, 692.
(17) End, N.; Macko, L.; Zehnder, M.; Pfaltz, A. Chem. Eur. J. 1998, 4,
818 and references therein.
(18) (a) Ohtake, H.; Higuchi, T.; Hirobe, M. J. Am. Chem. Soc. 1992,
114, 10660. (b) Without HX the reaction is much less efficient, a
phenomenon under current investigation in our laboratory.
a Reactions conditions: 0.4 µmol of catalyst were added to a mixture of
100 µmol of oxidant, 1 mmol of alkane, 15 µL of 48% aqueous HBr, and
50 mg of 4A molecular sieves in 1 mL of benzene under Ar. Chemical
yields were determined by GC analysis relative to an internal standard.
Enantiomeric excesses were determined by GC, using a Cyclodex-B chiral
capillary column.
Org. Lett., Vol. 1, No. 13, 1999
2079

solely on the very small differences between the C-H
substituents, methyl vs ethyl.
introduce the first example of catalytic asymmetric hydroxy-
lation of racemic alkanes and their kinetic resolution. We
trust that these preliminary results will open the gate for
investigations of similar processes with other catalysts. In
this respect, we are indeed pleased to note that the previous
discoveries from our work4,9sthe advantages of ruthenium,
2,6-pyridine N-oxide, and benzene, in asymmetric epoxi-
dationshave been successfully introduced into catalysis by
salen complexes.21
In principle, as the reaction proceeds, the unreacted
substrate also becomes enantiomerically enriched. Obviously,
this will only be apparent at high conversions.19 Accordingly,
we tested the hydroxylation of 2-phenylbutane at a substrate:
oxidant:catalyst ratio of 500:250:1. Under these conditions,
the alcohol was obtained in 35% yield and 18% ee, and the
unreacted alkane with 8% ee (Scheme 2).20
Acknowledgment. We thank the S. and N. Grand
Research Fund and the Fund for the Promotion of Sponsored
Research for financial support and Prof. K. B. Sharpless
(Scripps) for a thorough discussion of kinetic resolution
processes.
Scheme 2. Kinetic Resolution of 2-Phenylbutane
Supporting Information Available: Preparation of the
catalysts and their precursors and detailed procedures for the
catalytic oxidations. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL991131B
(19) Martin, V. S.; Woodard, S. S.; Katsuki, T.; Yamada, Y.; Ikeda, M.;
Sharpless, K. B. J. Am. Chem. Soc. 1981, 103, 6237.
In summary, we have introduced an improved version of
our D2 symmetry complexes which is the most selective
porphyrin-based catalyst for the asymmetric epoxidation of
terminal and trans-disubstituted olefins. In the presence of
mineral acids, the same catalyst displays moderate selectivity
in kinetic resolution of secondary alcohols. In addition, we
(20) Reactions conditions: 24 h at 0 °C with 0.1 µmol of catalyst, 25
µmol of oxidant, 50 µmol of alkane, and 5 µL of a HCl-saturated benzene
solution in 0.5 mL of chlorobenzene under Ar. Chemical yields were
determined by GC analysis relative to an internal standard. Enantiomeric
excesses were determined by GC, using a Cyclodex-B chiral capillary
column for the alcohol and Chiraldex A-TA for the alkane.
(21) Takeda, T.; Irie, R.; Katsuki, T. Synlett 1999, 7, 1157.
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