Catalytic asymmetric epoxidation with a chiral ruthenium porphyrin
and N-oxides
Albrecht Berkessel* and Matthias Frauenkron
Institut für Organische Chemie der Universität zu Köln, Greinstraße 4, D-50939 Köln, Germany
The enantiomerically pure ruthenium porphyrin 3 was syn-
thesized in very high yield by refluxing the porphyrin 2 with
Ru3(CO)12 in phenol; its subsequent use in the catalytic
asymmetric epoxidation of olefins with 2,6-dichloro-
pyridine N-oxide as terminal oxidant, to afford epoxides
in good yields and with enantioselectivities up to 77%, is
reported.
as the terminal oxidant. The ratio of substrate:oxidant :cata-
lyst was 1000:1100:1.‡ The reaction proceeded smoothly and
almost complete conversion of the substrates was achieved
within ca. 48 h (see Table 1). The chemical yields of the
epoxides were quite high (up to 88%, Table 1, entry 3), and the
enantiomeric excesses obtained for (1R,2S)-1,2-epoxy-1,2,3,4-
tetrahydronaphthalene (Table 1, entry 2) and (S)-styrene oxide
(Table 1, entry 10) were 77 and 70%, respectively. The latter
value is the highest one obtained in the asymmetric epoxidation
of styrene using a chiral porphyrin system.8 Interestingly, the
enantioselectivities obtained by us with the ruthenium com-
plex 3 were higher than those found by Halterman et al. for
the corresponding manganese complex using hypochlorite as
terminal oxidant.6 As expected, terminal olefins like oct-1-ene
(Table 1, entry 12) showed only moderate reactivity and poor
enantiomeric excesses. No stereoselectivity was observed for
trans-disubstituted alkenes like (E)-stilbene (Table 1, entry 13)
which reacted only sluggishly.
Running the reaction at higher temperatures (125 ЊC, Table 1,
entry 3) resulted in a dramatic increase in the turnover fre-
quency. Nearly full conversion was achieved within 2 h, albeit
at somewhat lower enantioselectivities (55%). Variation of the
solvent revealed that aromatic solvents gave the best results, a
fact also observed by Gross et al.9 The use of other N-oxides
like 2,6-dibromopyridine N-oxide or N-methylmorpholine N-
The development of an efficient catalytic process for the asym-
metric oxygenation of hydrocarbons is still a challenging goal
in organic chemistry.1 Great progress has been made in the
field of enantioselective epoxidation by the development of the
Jacobsen catalyst.2 Nevertheless, metalloporphyrins present the
most promising class of catalysts due to their stability against
oxidative degradation.3 A notable catalyst is the ruthenium
porphyrin–2,6-dichloropyridine N-oxide system introduced by
Hirobe et al. which shows very high turnover numbers for the
catalytic oxygenation of alkanes and alkenes.4 As part of our
work on transition metal catalyzed asymmetric epoxidations,5
we were interested in developing an efficient catalytic system for
the enantioselective epoxidation of unfunctionalized olefins
based on pyridine N-oxides as terminal oxidants. We chose the
D4-symmetric porphyrin 2 as a chiral ligand. It can easily be
prepared in high yields from the readily available enantiopure
aldehyde precursor 1.6 Here we describe the synthesis of the
corresponding ruthenium carbonyl porphyrin 3, using a modi-
fication of the acetylacetonate method 7 with Ru3(CO)12 as the
metal source. Furthermore, we present the first results for the
asymmetric epoxidation of unfunctionalized olefins using the
complex 3 as catalyst.
The porphyrin ligand 2 was synthesized as described.6 The
separation of the starting enantiomeric aldehydes 1 and ent-1
was achieved by preparative HPLC of their respective diastereo-
meric acetals.6 The enantiomeric purity of the aldehyde 1 was
>98% ee (HPLC). Unfortunately, our first attempts to prepare
the ruthenium carbonyl complex 3 from porphyrin 2 using
standard methods, i.e. refluxing the porphyrin 2 with Ru3(CO)12
in an inert solvent (benzene, toluene, decalin or diethylene gly-
col dimethyl ether) failed, or gave only poor yields (<15%), of
the desired metalloporphyrin. Finally, phenol turned out to be
the solvent of choice: refluxing the porphyrin 2 with excess
Ru3(CO)12 gave the metallated porphyrin 3 (Scheme 1) within
30 min in high yields (up to 90% for ent-2).†
The catalytic epoxidations were run using the enantiomer-
ically pure ruthenium carbonyl complex 3 in benzene at room
temperature under argon. 2,6-Dichloropyridine N-oxide served
† FAB-HRMS (NBA): found Mϩ, 1270.5104. C85H76ON4102Ru requires
Mϩ, 1270.5063.
‡ Typical epoxidation experiment: a Schlenk flask was charged under
argon with a solution of 3 (0.4 mg, 315 nmol) in 1 ml benzene, and 1,2-
dihydronaphthalene (40.0 µl, 315 µmol), 2,6-dichloropyridine N-oxide
(55.4 mg, 347 µmol) and 1,2-dibromobenzene (internal standard) (37 µl,
315 µmol) were added. The reaction mixture was stirred at room
temperature. Conversions, yields and ees were determined by capillary
GC. The product epoxides can be isolated by removal of the solvent
and subsequent silica gel chromatography, eluting with pentane–diethyl
ether [40:1 (v/v)].
Scheme 1 Reagents and conditions: i, pyrrole, BF3ؒEt2O, CHCl3; 29%;
ii, Ru3(CO)12, PhOH, 200 ЊC; 84%
J. Chem. Soc., Perkin Trans. 1, 1997
2265