Stereo- and enantioselective alkene epoxidations: A comparative study of D4- and D2-symmetric homochiral trans-dioxoruthenium(VI) porphyrins

Article abstract of DOI:10.1002/1521-3765(20020603)8:11<2495::AID-CHEM2495>3.0.CO;2-G

The mechanism of stoichiometric enantioselective alkene epoxidations by the D₄- and D₂-symmetric homochiral trans-dioxoruthenium(VI) porphyrins, [Ru^VI(D₄-Por*)O₂] (1) and [Ru^VI(D₂-Por*)O₂] (2a), in the presence of pyrazole (Hpz) was studied by UV/ Vis spectrophotometry and analysis of the organic products. The enantioselectivity of styrene oxidations is more susceptible to steric effects than to substituent electronic effects. Up to 72% ee was achieved for epoxidation of 3-substituted and cis-disubstituted styrenes by employing 1 as the oxidant, whereas entantioselectivities of only 20-40 % were obtained in the reactions with 2-substituted and trans-disubstituted styrenes. Complex 2a oxidized 2-substituted styrenes to their epoxides in up to 88% ee. Its reactions with transalkenes are more enantioselective (67 % ee) than with the cis-alkenes (40 % ee). Based on a two-dimensional NOESY NMR study, 2a was found to adopt a more open conformation in benzene than in dichloromethane, which explains the observed solvent-dependent enantioselectivity of its reactions with alkenes. The oxidation of aromatic alkenes by the chiral dioxoruthenium(VI) porphyrins proceeds through the ratelimiting formation of a benzylic radical intermediate; the observed enantioselectivity (ee_obs) depends on both the facial selectivity of the first C-O bond formation step and the diastereoselectivity of the subsequent epoxide ring closure. To account for the observed facial selection, "side-on" and "top-on" approach transition state models are examined (see: B. D. Brandes, E. N. Jacobsen, Tetrahedron Lett. 1995, 36, 5123).

Full text of DOI:10.1002/1521-3765(20020603)8:11<2495::AID-CHEM2495>3.0.CO;2-G

FULL PAPER
Stereo- and Enantioselective Alkene Epoxidations: A Comparative Study
of D4- and D2-Symmetric Homochiral trans-Dioxoruthenium(vi)Porphyrins
Rui Zhang,[a] Wing-Yiu Yu,[a] Hong-Zhe Sun,[a] Wei-Sheng Liu,[a] and
Chi-Ming Che*[a, b]
Abstract: The mechanism of stoichio-
metric enantioselective alkene epoxida-
tions by the D4- and D2-symmetric
with 2-substituted and trans-disubstitut-
ed styrenes. Complex 2a oxidized 2-sub-
stituted styrenes to their epoxides in up
to 88% ee. Its reactions with trans-
alkenes are more enantioselective
(67% ee) than with the cis-alkenes
(40% ee). Based on a two-dimensional
NOESY NMR study, 2a was found to
adopt a more open conformation in
benzene than in dichloromethane, which
explains the observed solvent-depen-
dent enantioselectivity of its reactions
with alkenes. The oxidation of aromatic
alkenes by the chiral dioxoruthenium(vi)
porphyrins proceeds through the rate-
limiting formation of a benzylic radical
intermediate; the observed enantiose-
lectivity (eeobs) depends on both the
homochiral
trans-dioxoruthenium(vi)
porphyrins, [RuVI(D4-Por*)O2] (1) and
[RuVI(D2-Por*)O2] (2a), in the presence
of pyrazole (Hpz) was studied by UV/
Vis spectrophotometry and analysis of
the organic products. The enantioselec-
tivity of styrene oxidations is more
susceptible to steric effects than to
substituent electronic effects. Up to
72% ee was achieved for epoxidation
of 3-substituted and cis-disubstituted
styrenes by employing 1 as the oxidant,
whereas entantioselectivities of only
20 40% were obtained in the reactions
À
facial selectivity of the first C O bond
formation step and the diastereoselec-
tivity of the subsequent epoxide ring
closure. To account for the observed
facial selection, ™side-on∫ and ™top-on∫
approach transition state models are
examined (see: B. D. Brandes, E. N.
Jacobsen, Tetrahedron Lett. 1995, 36,
5123).
Keywords: asymmetric oxidation ¥
epoxidation ¥ kinetics ¥ macrocycles
¥ ruthenium
made with chiral transition-metal complexes[2, 3] and ketones[4]
as catalysts. These reactions involve prochiral face recognition
Introduction
ˆ
Asymmetric epoxidation of unfunctionalized alkenes is an
appealing strategy for the preparation of optically active
epoxides,[1] and significant advances in this area have been
of a C C bond by the chiral catalysts; achievement of a high
degree of enantioselectivity based on weak nonbonded
interactions constitutes the major challenge in this area. In
biomimetic P-450 oxidation chemistry,[5] participation of
ˆ
highly oxidizing M O reactive intermediates is widely
accepted;[6] however, the mechanistic details regarding the
[a] Prof. Dr. C.-M. Che, Dr. R. Zhang, Dr. W.-Y. Yu,
Dr. H.-Z. Sun, Dr. W.-S. Liu
ˆ
ˆ
reaction of a C C bond with the M O moiety in an
enantioselective manner remain elusive.[7] Toward this end,
our approach is to study the stoichiometric alkene epoxida-
tions by reactive chiral metal oxo complexes that have
tunable structural and electronic properties.[3d,f, 8, 9] We have
shown that trans-dioxoruthenium(vi) porphyrins are useful
models for mechanistic elucidation of organic oxidations by
reactive oxometalloporphyrins.[10] These complexes can un-
dergo alkene epoxidation[10a and alkane hydroxylation[10e]
under mild conditions. Importantly, their structures can be
modified by attaching chiral auxiliaries onto the porphyrin
Department of Chemistry
The University of Hong Kong
Pokfulam Road (Hong Kong)
E-mail: cmche@hku.hk
[b] Prof. Dr. C.-M. Che
The Shanghai-Hong Kong Joint Laboratory in Chemical Synthesis
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences, 354 Fengling Lu
Shanghai 200032 (China)
d]
Fax : ‡(852)2851-1586
Supporting information for this article is available on the WWW under
http://www.wiley-vch.de/home/chemistry/ or from the author. The
1
information includes H NMR data of complex 2a in various solvents,
[3]
ˆ
macrocycle leading to reactive chiral M O oxidants.
results of the asymmetric alkene epoxidations in various solvents,
1H NMR spectra of 2a in CDCl3 and C6D6, and molecular modeling
studies of the transition-state models for the side-on and top-on
approach.
In 1996, Gross and co-workers[3a] reported the synthesis of a
homochiral ruthenium complex with a D2-symmetric por-
phyrin bearing four threitol substituents (D2-H2Por*, Fig-
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C.-M. Che et al.
FULL PAPER
lecular structure of [RuVI(D4-
Por*)O2] (1) had been established
by X-ray crystallography.[3d] The
sterically encumbered D4- and
D2-symmetric porphyrin ligands
disfavor dimerization by Ru-O-
Ru formation even in noncoordi-
nating solvents, such as dichloro-
methane; this eliminates the ne-
cessity of alcohol as co-solvent.[10]
The dioxoruthenium(vi) com-
plexes were purified by column
chromatography on alumina with
dichloromethane (1) or chloro-
form (2) as the eluant, and pure
[RuVI(Por*)O2] complexes were
obtained in ꢀ70 90% yield.
These compounds are air-stable
solids and can be stored at À208C
for months.
Figure 1. Structures of the D4- and D2-symmetric trans-dioxoruthenium(vi) porphyrin complexes.
ure 1). Subsequently, both our group and that of Gross found
that [RuVI(D2-Por*)O2] (2a) and [RuII(D2-Por*)(CO)] are
active catalysts for enantioselective alkene epoxidations.[3a,b, 3f]
Berkessel and our group also reported enantioselective
alkene epoxidation[3d,e] and cyclopropanation[11] catalyzed by
ruthenium complexes bearing a D4-symmetric porphyrin [D4-
H2Por* ˆ 5,10,15,20-tetrakis(1,2,3,4,5,6,7,8-octahydro-1,4:5,8-
dimethanoanthracen-9-yl)porphyrin], which was first devel-
oped by Halterman and co-workers.[2f,12] Similar to other
metalloporphyrin-catalyzed asymmetric alkene epoxida-
tions,[2] the stoichiometric epoxidation of cis-b-methylstyrene
by [RuVI(D4-Por*)O2] (1, Figure 1) gave the cis-epoxide with
good enantioselectivity (72% ee), whereas the analogous
trans-b-methylstyrene epoxidation gave only 20% ee under
identical conditions.[3d,e] More importantly, complex 2a and its
derivatives (Figure 1) were found to undergo enantioselective
epoxidation of trans-b-methylstyrene in up to 70% ee; how-
ever, the related reaction with cis-b-methylstyrene achieved
only 40% ee.[3f] Herein we describe a detailed comparative
study on the reactivities of the D4- and D2-symmetric
homochiral dioxoruthenium(vi) porphyrins toward epoxida-
tion of alkenes. To account for the different enantioselectiv-
ities, we propose two transition state models for the oxygen
atom transfer reactions involving a ™side-on∫ and/or ™top-on∫
All the [RuVI(Por*)O2] complexes show a well-resolved
1H NMR spectrum, consistent with a diamagnetic (dxy)2
ˆ
ˆ
electronic ground state (the O Ru O axis is taken as the z
axis). For 1, all the b-pyrrolic protons are equivalent, showing
a singlet absorption at d ˆ 8.96. In the case of D2-symmetric
complexes 2a d, the b-pyrrolic protons are observed as a pair
of doublets in CDCl3 (d ˆ 8.66 and 8.56 for 2a; 8.64 and 8.53
for 2b; 8.67 and 8.56 for 2c; 8.50 and 8.41 for 2d).
This spectral pattern is compatible with a staggered con-
formational structure, which is characterized by four equiv-
alent pyrrole rings each bearing two nonequivalent b-pro-
tons.[2e] Infrared spectra of the [RuVI(Por*)O2] complexes
show an intense absorption at nÄ ˆ 822 818 cmÀ1 that we
ˆ
ˆ
assign to the asymmetric O Ru O stretches. The oxidation
state marker bands are located at ꢀ1018 cmÀ1, in agreement
with a RuVI formulation.[13] The UV/Vis absorption of
[RuVI(Por*)O2] features an intense Soret band and a less
intense Q band.
Stoichiometric enantioselective epoxidation by [RuVI(Por*)-
O2]: In a degassed benzene solution containing 2%w/w
pyrazole (Hpz), complex 2a (15 30 mmol) reacted with
excess styrene (1 mmol) at room temperature to give styrene
oxide in 64% yield and 62% ee (Table 1 entry 1); a slightly
higher ee of 65% was obtained at a lower temperature of
ꢀ08C. As reported previously, treatment of styrene with 1 in
benzene containing 2%w/w Hpz under ambient conditions
produced styrene oxide in 61% yield and 65% ee. In both
cases, a bis(pyrazolato)ruthenium(iv) porphyrin complex,
[RuIV(Por*)(pz)2] (3a,b), was isolated and characterized
spectroscopically (see the Experimental Section). Com-
plexes 3a,b are paramagnetic with effective magnetic mo-
ments (meff) of ꢀ2.9 mB, which is consistent with a triplet
electronic ground state for a RuIV formulation.[14] The
molecular structure of a related [RuIV(dpp)(pz)2] complex
(H2dpp ˆ 2,3,5,7,8,10,12,13,15,17,18,20-dodecaphenylporphy-
rin), prepared in a similar manner, had previously been
established by X-ray crystallography.[10c]
ˆ
approach of alkene to the Ru O moiety.
Results
Preparation and characterization of D4- and D2-symmetric
chiral [RuVI(Por*)O2] complexes: The syntheses and charac-
terization of trans-dioxoruthenium(vi) porphyrins are well-
documented in the literature,[3d,f, 10] and a chiral picket-fence
trans-dioxoruthenium(vi) porphyrin containing optically ac-
tive peptide substituents was first reported by Simonneaux
and co-workers.[8d,e] Subsequently, we communicated the
synthesis of complexes 1 and 2 by oxidation of their
ruthenium(ii) carbonyl precursors with either PhIO or m-
f]
chloroperoxybenzoic acid in dichloromethane.[3d The mo-
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Dioxoruthenium Porphyrins
2495 2507
Table 1. Stoichiometric alkene epoxidations by chiral dioxoruthenium(vi) porphyrins.[a]
1
2a
Entry
1
Substrate
Product
Yield[%][b]
61
ee[%] (abs. config.)[c, d]
Yield[%][b]
ee[%] (abs. config.)[c, d]
65 (R)
64
66 (08C)
62 (R)
65 (R)
2
3
4
5
6
56
82
86
82
32
64 (R)
57 (R)
70 (R)
54 (R)
66 (R)
64
75
80
85
25
62 (R)
60 (R)
68 (R)
50 (R)
70 (R)
7
78
60 (R)
78
49 (R)
8
9
84
82
72 (R)
80
73
54 (R)
35 (n.d.)[e]
14 (R)[e]
10
11
12
70
82
48
44 (R)
54 (R)
47 (R)
52
68
88
88 (R)
84 (R)
80 (R)
13
14
70
64
5
50 (R)
80
75
1
81 (R)
72 (1R,2S)
8 (1R,2R)
40 (1R,2S)
10 (1R,2R)
15
16
17
66
60
20 (1R,2R)
18 (1R,2R)
90
90 (08C)
67 (1R,2R)
70 (1R,2R)
70
88
76 (1R,2R)
20 (1R,2S)
71
72 (1R,2S)
82 (1R,2S)
78 (À158C)
18
78
70 (R)
< 10
n.d.
[a] Reaction conditions: to a degassed benzene solution (2 mL) containing Hpz (2% w/w) and alkenes (1 mmol) was added [RuVI(Por*)O2] (15 30 mmol)
under an argon atmosphere. After stirring for 12 h at RT (unless otherwise noted), the reaction mixture was filtered through an alumina column with a
hexanes/ethyl acetate (9:1, v/v) mixture as the eluant. The organic products were then analyzed and quantified by GC or 1H NMR by means of the internal
standard method. [b] Yields are based on the ruthenium oxidant used. [c] %ee determined by chiral GC or 1H NMR with [Eu(hfc)3] as shift reagent.
[d] Absolute configuration was assigned by comparison with authentic enantiopure samples. [e] n.d. ˆ not determined.
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C.-M. Che et al.
FULL PAPER
Effect of pyrazole: When the stoichiometric styrene epoxida-
tions were undertaken in benzene without Hpz as an additive,
styrene oxide was produced in significantly lower yields (53%
(1) and 62% (2a)) and lower enantioselectivities (6% ee (1)
and 40% ee (2a)), compared to the same reactions performed
in the presence of Hpz (see Table 2). With 1 as the oxidant, the
reactions of 4-methylstyrene (40% ee) and 4-chlorostyrene
propose that the added Hpz reacted spontaneously with the
putative oxo RuIV intermediate, thereby diverting the reac-
tion pathway away from the undesirable formation of RuII
complexes.
Oxidation of substituted styrenes: In general, ortho-, meta- and
para-substituted styrenes are converted by 1 or 2a to their
(R)-epoxides in good-to-moderate yields, while arylbenzalde-
ˆ
hyde (C C bond cleavage) and/or 1-arylacetaldehyde (rear-
Table 2. Effect of pyrazole on the asymmetric alkene epoxidations by
rangement) were detected as minor products. An exception to
this is para-trifluoromethylstyrene, which was found to react
with 1 and 2a to give the epoxide in 32 and 25% yields,
respectively, (Table 1, entry 6); para-trifluoromethylbenzal-
dehyde was formed as the major product (60% yield). Stirring
the organic epoxide with either [RuVI(Por*)O2] or [RuIV-
(Por*)(pz)2] in benzene at room temperature did not result in
any aldehyde formation; this indicates that the latter side-
products should not arise from degradation of the product
epoxides.
[RuVI(D4-Por*)O2] (1).[a]
with Hpz
without Hpz
Entry
Alkenes
Epoxide
ee[%]
Epoxide
ee[%]
yield[%]
yield[%]
1
2
61
65
64
53
6
56
82
78
41
71
70
40
3
4
57
60
41
0
We have also prepared an enantiomeric D2-symmetric
dioxoruthenium(vi) complex 2a' by replacing the (S,S)-
threitol substituent in 2a to give its antipodal (R,R)-deriva-
tive. As anticipated, complex 2a' reacted with styrene to give
the (S)-epoxide with a product yield and enantioselectivity
identical to that of the (R)-epoxide obtained by similar
reaction with complex 2a.
[a] Same reaction conditions as those given in Table 1 were employed,
except with/without Hpz as the additive. For complex 2a, the styrene
oxidation achieved only 40% ee with 62% epoxide yield in the absence of
Hpz, compared with 62% ee when 2% w/w Hpz was added.
(41% ee) gave lower ee values when no Hpz was added.
Notably, without Hpz, 3-nitrostyrene was oxidized to afford
racemic epoxide (0% ee) in 70% yield (Table 2). Moreover,
when enantiopure (R)-styrene oxide (3 mmol; >99% ee) was
stirred in a reaction mixture containing 4-chlorostyrene
(300 mmol) and 1 (30 mmol) in benzene at room temperature
for 12 h, the initial optically active styrene oxide was
recovered (>95% yield) in only 37% ee.
In the absence of Hpz and with a prolonged reaction time
(24 h), 1/2a reacted with an excess of styrene in benzene to
form the corresponding [RuII(Por*)(CO)] complex, which
was isolated (yield >80%) and characterized by IR and
1H NMR spectroscopy and MS. In a previous study by Groves
and co-workers, [RuII(tmp)(CO)] [H2tmp ˆ meso-tetrakis-
(mesityl)porphyrin] was also found during the course of the
reaction between [RuVI(tmp)O2] and styrene.[15] Since ruth-
enium(ii) porphyrin complexes without p-acid axial ligands
are known to racemize chiral epoxides (Scheme 1),[16] we
As shown in Table 1, para-substitution (p-Y-styrene, Yˆ
Me, Cl, F, Br, and CF3) does not have a significant effect upon
the enantioselectivity of styrene epoxidation by 1 or 2a
(ꢀ65% ee). Complex 1 oxidized 3-chloro- and 3-nitrostyrenes
in 72 and 60% ee respectively; however, its reactions with
2-chloro- and 2-bromostyrenes under identical reaction con-
ditions gave the epoxides with much lower enantioselectivities
(44 and 47% ee). It is noteworthy that the epoxidation of
ortho-substituted styrenes by 2a proceeded with enantiose-
lectivities ꢁ80% ee (entries 10 13). The highest ee of 88%
was attained for the 2-chlorostyrene epoxidation, which is
close to some best ee values reported for the epoxidation of
3]
styrenes.[1 On the other hand, meta-substituted styrenes
reacted with 2a to furnish the organic epoxides (ꢀ80% yield)
in ꢀ50% ee (Table 1, entries 7,8). 2-Vinylnaphthalene under-
went facile reaction with 1 to give the corresponding epoxide
in 70% ee and 78% yield (entry 18). However, the analogous
reaction with 2a was ineffective, 2-vinylnaphthalene oxide
was isolated in less than 10%
yield, despite the fact that
[RuIV(D2-Por*)(pz)2] was iso-
lated in 77% yield. Because of
the poor product yield, the
optical purity of the epoxide
was not determined.
Oxidation of 1,2-disubstituted
alkenes: Under the standard
reaction conditions (alkene ˆ
1 mmol, Ru ˆ 30 mmol in ben-
zene containing 2%w/w Hpz),
epoxidation of cis-b-methylsty-
Scheme 1. Racemization of chiral epoxides by ruthenium(ii) porphyrin complexes with and without pyrazole.
rene by 2a afforded predomi-
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Chem. Eur. J. 2002, 8, No. 11

Dioxoruthenium Porphyrins
2495 2507
nantly cis-b-methylstyrene oxide in 40% ee (cis:trans ratio ˆ
75:1; Table 1, entry 14). Yet, the analogous reaction with 1 can
afford cis-b-methylstyrene oxide in up to 72% ee (cis:trans
ratio ˆ 64:5). The optical purity of the trans-b-methylstyrene
oxide produced from the cis-b-methylstyrene epoxidation was
determined to be ꢂ10% ee. Stirring a benzene solution of
pure cis-b-methylstyrene oxide and [RuIV(Por*)(pz)2] at room
temperature for 12 h led to full recovery of the starting cis-
epoxide, and no trans-epoxide was detected. This finding
indicates that the trans-epoxide formation associated with the
cis-alkene epoxidation is not a consequence of [RuIV-
(Por*)(pz)2]-catalyzed epoxide isomerization.[16]
at the threitol units, and the results are listed in Table 3. For
the styrene epoxidation, the enantioselectivity dropped with
increasing bulkiness of the auxiliaries (c.f. 62% ee (2a),
60% ee (2b), 55% ee (2c), and 40% ee (2d)). A similar trend
has also been observed for the trans-b-methylstyrene epox-
idations (c.f. 67% ee (2a), 50% ee (2b), 36% ee (2c), and
20% ee (2d)). Indeed, the reaction of 2d with trans-b-
methylstyrene required 2 days for completion and the epoxide
was obtained in 28% yield with mass balance <40% (Table 3,
entry 1). However, in a related work by Gross and co-workers
it was reported that 2d can catalyze enantioselective trans-b-
methylstyrene epoxidation with 69% ee.[3g]
More importantly, complex 2a reacted with trans-b-meth-
ylstyrene to give trans-b-methylstyrene oxide in 67% ee and
90% yield (Table 1, entry 15), in contrast to the analogous
reaction with 1 in which the trans-epoxide was afforded in
20% ee (Table 1, entry 15). An enantioselectivity of up to
76% ee was achieved for the stoichiometric epoxidation of
cinnamyl chloride by 2a (Table 1, entry 16). It should be noted
that only few metalloporphyrin-catalyzed enantioselective
trans-b-methylstyrene epoxidations are known to attain
enantioselectivities greater than 20% ee.[2] Recently, some
chiral chromium/Schiff base[9] and ruthenium oxalamide/
Schiff base complexes[17] were found to catalyze enantiose-
lective trans-b-methylstyrene epoxidation with high ee values.
As with 2a, complexes 2b,c reacted with trans-b-methylsty-
rene to give the epoxides in higher ee values than similar
reaction with cis-b-methylstyrene, [cis-b-methylstyrene oxi-
dation: 28% ee (2b) and 13% ee (2c)]. However, we found
that the gem-diphenyl-substituted complex 2d oxidized cis-b-
methylstyrene to give the cis-epoxide in 36% ee, which is
slightly higher than 20% ee obtained for the analogous trans-
alkene oxidation (Table 2, entries 4,5).
Kinetic studies: The alkene epoxidations by 1 or 2a feature
isosbestic transformation of [RuVI(Por*)O2] to [RuIV(Por*)-
(pz)2]. Figure 2 depicts the UV/Vis spectral change for the
reaction of styrene with 2a in 1,2-dichloroethane containing
Figure 2. UV/Vis spectral changes during the reaction of 2a (time scan:
1500 s, 60 s interval) with styrene (1.0 moldmÀ3) in 1,2-dichloroethane with
2%w/w Hpz at 298 K.
Hpz (2%w/w). As shown in Figure 2, the conversion of RuVI
to RuIV is manifested by the decay of the Soret band at l ˆ
442 nm with concomitant development of a new absorption
band at 425 nm. Isosbestic points are located at l ˆ 414, 440,
479, 560 nm for 1 and 430, 458, 512, 556 nm for 2a. In the
absence of Hpz, the kinetic profile for the RuVI to RuIV
transformation was influenced by secondary reactions (plau-
Effect of bulky chiral auxiliaries: We have studied the styrene
and trans-b-methylstyrene epoxidations with several D2-
symmetric dioxoruthenium(vi) porphyrins bearing gem-dieth-
yl (2b), gem-cyclopentyl (2c), and gem-diphenyl (2d) groups
Table 3. Effect of bulky auxiliaries on the asymmetric alkene epoxidations by complex 2.[a]
2d
2b
2c
Entry
1
Alkenes
Epoxide yield[%]
64
ee[%]
Epoxide yield[%]
56
ee[%]
Epoxide yield [%]
28
ee[%]
60
55
40
2
78
55
65
46
35
36
3
4
5
80
79
28
50
74
84
90
56
13
36
21
40
34
33
36
20
82 (cis >99%)
90 (trans >99%)
[a] Same reaction conditions as those given in Table 1 were employed. Similar to complex 2a, the oxidation of styrene (entry 1) and its substituted derivatives
(entries 2 and 3) produced (R) epoxides preferentially. Oxidations of cis- (entry 4) and trans-b-methylstyrenes (entry 5) gave (1R,2S) and (1R,2R)-epoxides,
respectively.
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C.-M. Che et al.
FULL PAPER
sibly by the formation of RuII porphyrin) and deviated from
first-order exponential decay.
Solvent effect: The solvent-dependence of the enantioselec-
tivity has been examined. For the reactions with 1, the solvent
shows little influence on the enantioselectivity, and compara-
ble enantioselectivities were obtained with benzene or
dichloromethane as the solvent. However, when 2a was the
oxidant, the styrene epoxidation resulted in 62% ee with
benzene as the solvent (Table 6, entry 2), and dropped to
41% ee when the reaction was conducted in dichloromethane
In this work, all of the kinetic studies were conducted in 1,2-
dichloroethane and in the presence of 2%w/w Hpz under the
condition that [Ru] ꢃ [alkene] ꢂ 2 moldmÀ3. All the reactions
exhibited clean pseudo-first-order kinetics and isosbestic
spectral changes over four half-lives for the substrates
employed. In benzene, toluene, dichloromethane, or 1,2-
dichloroethane, the alkenes were oxidized by 1 or 2a to give
epoxides in good yields and with mass balances >90% (see
below).
Table 6. Effect of solvent on the asymmetric alkene epoxidations by complex
2a.[a]
The pseudo-first-order rate constants, kobs, were determined
by monitoring the disappearance of the Soret band (lmax
ˆ
424 nm for 1 and 442 nm for 2a) of the dioxoruthenium(vi)
complexes; the second-order rate constants, k2, were eval-
uated from the linear plots of kobs versus [alkene] (see
Table 4). Rate saturation was not observed over the alkene
concentrations employed in this work. It should be noted that
the k2 values are unaffected by the Hpz loading (2 10%w/w),
and no appreciable reaction between 1 or 2a with pyrazole
was observed within the timescale of the kinetic studies.
Entry Solvent
ee
k2 Â 104
ee
k2 Â 104
[b]
[b]
[%] [dm3 molÀ1 sÀ1
]
[%] [dm3 molÀ1 sÀ1
]
1
2
3
4
5
6
toluene
benzene
1,2-dichloroethane
dichloromethane
acetonitrile
14.1 Æ 0.2
62
67
9.3 Æ 0.2
9.2 Æ 1.6
8.4 Æ 0.1
4.2 Æ 0.1
1.4 Æ 0.2
62
13.2 Æ 0.1
7.1 Æ 0.2
41
33
3.5 Æ 0.1
32
26
38
0.97 Æ 0.05
ethyl acetate
[a] Same reaction conditions as those given in Table 1 were employed. [b] The
second-order rate constants were determined at 298 K.
Table 4. Second-order rate constants (k2) for the asymmetric alkene
oxidations at 298 K.[a]
k2 Â 104 [dm3 molÀ1 sÀ1
(2a)
]
(Table 6, entry 4). Moreover, employing acetonitrile as the
solvent led to a low epoxide yield of 13% and enantioselec-
tivity of 33% ee (Table 6, entry 5). Similarly, the stoichiomet-
ric epoxidations of 4-chlorostyrene, cis-/trans-b-methylsty-
renes, and 1,2-dihydronaphthalene by 2a afforded the best
enantioselectivities only when benzene was the solvent (see
the Supporting Information). Gross and co-workers[3b] re-
ported similar solvent dependence for the [RuII(D2-Por*)-
(CO)]-catalyzed styrene epoxidation, and that the use of
aromatic solvents, such as benzene and toluene, was found to
give the highest enantioselectivity.
Entry
Alkenes
(1)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
styrene
21.9 Æ 1.2
96.5 Æ 5.5
40.8 Æ 1.5
30.7 Æ 0.6
26.2 Æ 1.0
38.4 Æ 3.5
24.8 Æ 0.2
26.1 Æ 0.1
72.0 Æ 4.0
29.6 Æ 1.5
21.5 Æ 1.6
21.6 Æ 0.6
24.9 Æ 0.6
28.0 Æ 0.5
7.1 Æ 0.2
45.6 Æ 1.6
13.8 Æ 0.1
12.9 Æ 0.2
8.9 Æ 0.2
12.0 Æ 0.4
13.5 Æ 0.7
7.4 Æ 0.4
14.6 Æ 0.4
5.8 Æ 0.2
8.4 Æ 0.1
7.2 Æ 0.5
8.0 Æ 0.3
8.5 Æ 0.5
4-methoxystyrene
4-methylstyrene
2-methylstyrene
4-fluorostyrene
4-chlorostyrene
2-chlorostyrene
3-chlorostyrene
4-bromostyrene
cis-b-methylstyrene
trans-b-methylstyrene
a-deuteriostyrene
b-d2-styrene
The second-order rate constants (k2) of the reaction of
trans-b-methylstyrene with 2a in different solvents were
measured (Table 6); the k2 values decrease in the order:
toluene ꢀ benzene > 1,2-dichloroethane >
a-methylstyrene
[a] All the kinetic data was obtained in 1,2-dichloroethane with 2% w/w
Hpz as additive.
dichloromethane > acetonitrile. Parallel with the descending
k2 values, the enantioselectivity also decreases in a similar
fashion: 67% (benzene), 32% (CH2Cl2), and 26% (CH3CN)
(Table 6). It should be noted that the trans-b-methylstyrene
epoxidations in the above-mentioned solvents exhibited
isosbestic spectral changes and with kinetics conformed to
pseudo-first-order decay profile.
The effect of temperature on the k2 values for the
epoxidation of some representative alkenes has been studied.
The Eyring plots are linear over a temperature range of 293
333 K. The activation enthalpies DH= and entropies DS= for
the 2-chlorostyrene, 2-methylstyrene, 3-chlorostyrene, cis-b-
methylstyrene, and trans-b-methylstyrene epoxidations by 1
and 2a are listed in Table 5.
In this work, a solvent polarizability parameter (ET)[18] was
employed to correlate the k2 and enantioselectivity values of
the trans-b-methylstyrene oxidation in various solvents. The
ET parameter is generally regarded as a better indicator of
solvent polarity than the dielectric constant because it is an
experimental measure of the molecular interaction between
solvent and solute.[18] In this work, we found that the
log[(100‡ee)/(100 À ee)] values obtained in various solvents
do not correlate linearly with the ET parameter, and a logk2
versus ET plot does not establish a linear free-energy
relationship. Given that the enantiomeric ratio is directly
proportional to the difference in free-energy changes of the
diastereomeric transition states (DDG=).[19] This finding
Table 5. Activation parameters for the asymmetric alkene oxidations.[a]
(1)
(2a)
Alkenes
DH=
[kcalmolÀ1
DS=
[e.u.]
DH=
[kcalmolÀ1
DS=
]
]
[e.u.]
2-chlorostyrene
2-methylstyrene
3-chlorostyrene
cis-b-methylstyrene
11.6 Æ 0.4
11.5 Æ 0.4
13.3 Æ 1.0
12.1 Æ 0.6
À (31.6 Æ 1.8) 11.6 Æ 0.4
À (31.5 Æ 1.5) 11.3 Æ 0.5
À (25.0 Æ 2.2) 11.8 Æ 1.0
À (29.4 Æ 2.0) 14.0 Æ 0.6
À (27.8 Æ 1.4) 11.1 Æ 0.6
À (34.8 Æ 2.3)
À (33.9 Æ 2.0)
À (27.6 Æ 2.1)
À (26.7 Æ 2.8)
À (35.6 Æ 2.4)
trans-b-methylstyrene 12.7 Æ 0.6
[a] All the kinetics data were obtained in 1,2-dichloroethane with 2% w/w Hpz as
additive.
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Dioxoruthenium Porphyrins
2495 2507
suggests that the solvent effect on the enantioselectivity
cannot be explained by specific interaction between solvent
and [RuVI(Por*)O2] in the transition state.
Stereoselectivity in oxidation of aromatic alkenes by chiral
trans-dioxoruthenium(vi)porphyrins : cis-Alkenes, such as
stilbene, have been widely employed as a mechanistic probe
for concertedness in alkene oxidations by highly reactive
metal-oxo complexes. cis-Stilbene is particularly prone to
Compared with complex 1, the chiral scaffold of the D2-
symmetric complex 2a, consisting of four staggered chiral
threitol units, would be more conformationally flexible
through rotation of the meso-phenyl groups and the ethereal
linkages. Indeed, for 2a, the use of C6D6 or CD2Cl2 as the
solvent would result in a different 1H NMR spectral pattern at
room temperature; significant chemical shift difference (DdH)
with magnitude from 0.11 0.47 ppm were found for many of
the signals (see Table S1, Supporting Information). Of partic-
ular note is that the signals corresponding to the gem-methyl
groups are shifted considerably downfield from dH ˆ 0.78 and
À0.64 in CD2Cl2 to dH ˆ 0.93 and À0.15, respectively, in C6D6.
In addition, the absorption peaks for the CHb protons are also
shifted downfield from dH ˆ 2.62 in CDCl3 to dH ˆ 3.05 in
C6D6 (see Figure 3 for atom labeling). However, the 1H NMR
À
cis trans isomerization by C C bond rotation to form trans-
stilbene oxide, if the epoxidation involves an acyclic inter-
mediate.[20] In this work, the reaction of cis-stilbene with 1 or
2a produced the cis-epoxide exclusively, and no trans-stilbene
oxide was detected (see reaction given in Table 7). This result
coincides with our previous findings that the cis-stilbene
oxidation by sterically congested dioxoruthenium(vi) por-
phyrins, such as [RuVI(tdcpp)O2] and [RuVI(tmopp)O2] com-
plexes
(H2tdcpp ˆ meso-tetrakis(2,6-dichlorophenyl)por-
phyrin; H2tmopp ˆ meso-tetrakis(2,4,6-trimethoxyphenyl)-
porphyrin), afforded cis-stilbene oxide stereoretentively.[10d]
However, it should be noted that the analogous reaction with
the less hindered [RuVI(oep)O2] (H2oep ˆ 2,3,7,8,12,13,17,18-
octaethylporphyrin) gave trans-stilbene oxide as the major
product with a trans:cis-oxide ratio ˆ 44:16.[10a]
Table 7. Nonstereoselective cis-alkene oxidations.
Entry
R
Solvent Yield[%] ee[%]
Yield[%] ee[%] cis:trans Ratio
1
2
3
4
5
Ph C6H6
CH3 C6H6
CH3 CH2Cl2 68
75
75
0
1
4
6
12
40
18
69
51
10
8
10
9
99:1
95:5
89:11
75:25
D
D
C6H6
CH2Cl2 36
52
The stereoselectivity of the epoxidation reaction was
further examined by means of cis-b-methylstyrene and cis-b-
deuteriostyrene as mechanistic probes. As depicted in the
reaction given in Table 7, the cis-b-methylstyrene epoxida-
tions by 1 and 2a produced the trans-epoxide as a minor
product: cis:trans ratios ˆ 93:7 (1) and 99:1 (2a) in C6H6;
90:10 (1) and 95:5 (2a) in CH2Cl2. Moreover, the reaction of
cis-b-deuteriostyrene with 2a at room temperature in benzene
and dichloromethane are nonstereoselective with cis:trans-
epoxide ratio ˆ 89:11 in C6H6 and 75:25 in CH2Cl2. The
reactions were repeated three times for each ruthenium
oxidant, and the cis/trans selectivities were obtained reprodu-
Figure 3. Two-dimensional NOESY 1H NMR (500 MHz) spectra of 2a in
CD2Cl2 and in C6D6.
1
cibly. The purity of the cis-alkenes was checked by H NMR
spectroscopy, and trans-alkenes were not detected at the end
of the reactions. A control experiment was performed by
stirring a mixture of pure cis-b-deuteriostyrene oxide and
[RuIV(Por*)(pz)2] in dichloromethane at room temperature
for 12 h; the starting cis-epoxides were recovered without
trans-epoxide being detected. This confirms that the forma-
tion of cis- and trans-epoxides did not arise from the
[RuIV(Por*)(pz)2]-catalyzed epoxide isomerization.[16]
The secondary kinetic H/D isotope effect (KIE) for the
reactions of [RuVI(Por*)O2] with a,b-deuteriostyrenes has
been measured. As illustrated in Scheme 2, a clear inverse
secondary isotope effect[21] was observed only at the b-carbon
atom, but not the a-carbon atom. This implies that only the b-
carbon atom changes its hybridization from sp2 to sp3 [kH/kD ˆ
spectra of 1 in C6D6 and CDCl3 are almost identical (i.e., no
change in chemical shifts). Indeed, the two-dimensional
nuclear Overhauser effect (NOESY) NMR spectrum of 2a
recorded in CD2Cl2 at room temperature revealed significant
NOE between the threitol groups (CHb and CH2) and the b-
pyrrolic protons (Figure 3). It is noteworthy that this NOE for
the threitol groups was completely lost when the NOESY
NMR spectrum was recorded in C6D6. These findings strongly
suggest that in C6D6 the threitol substituents of 2a are slightly
displaced from the deshielding porphyrin core, creating a
more open chiral cavity than in CD2Cl2. Accordingly, the
more open chiral cavity for 2a in aromatic solvents, such as
benzene, would result in better resolution of the diastereo-
meric transition states leading to higher enantioselectivity.
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C.-M. Che et al.
FULL PAPER
Scheme 2. Secondary KIE for the styrene oxidation by the chiral
dioxoruthenium(vi) porphyrins.
0.88(1) or 0.89 (2a)] upon advancing to the transition state
while the a-carbon atom remains essentially sp2 hybridized
[kH/kD ˆ 1.01 (1) or 0.99 (2a)]. The inverse secondary KIE
result is in accord with a nonsymmetrical transition state,
À
wherein the C O bond formation is more advanced at the b-
carbon atom than at the a-carbon atom. The loss of stereo-
selectivity and the KIE results are consistent with rate-
limiting formation of an acyclic intermediate for the alkene
epoxidation.
Linear free-energy relationship for epoxidation of styrenes: To
probe the transition state for the asymmetric alkene epox-
idations, we have investigated the effect of para substituents
on the rate of styrene epoxidations. By analogy with previous
studies on some other dioxoruthenium(vi) porphyrins,[10] both
electron-donating and electron-withdrawing groups moder-
ately accelerate the reactions (1.5-fold for 4-methoxystyrene).
Figure 4. Dual-parameter Hammett correlations for the oxidation of para-
substituted styrenes by 1 (top) and 2a (bottom).
‡
For 1 and 2a, a plot of the logkrel versus s [krel ˆ k2(substi-
tuted styrene)/k2(styrene)] produces concave Hammett
curves, which is in contrast to the linear Hammett correla-
by the spin delocalization effect, while the negative 1mb value
‡
tions (1 ˆ À1.9 to À2.1) obtained for the styrene oxida-
is consistent with the electrophilic nature of the oxoruthenium
.
tions by [FeIV(tmp )O] (H2tmp ˆ tetramesitylporphyrin),[22]
‡
.
complexes. The magnitude of the j1JJ/1mb jˆ 2.93 for 1 and
[(Br8tpp)CrV(O)(X)]
(H2Br8tpp ˆ meso-tetrakis(2,6-dibro-
2.10 for 2a indicates that spin delocalization is more
mophenyl)porphyrin)[23] and [RuVI(N4)O2]2‡ (N4 ˆ macrocy-
clic tertiary amines)[24] complexes. The participation of
carbocation or alkene-derived carbocation radical is not
favored, since the rate-limiting formation of carbocation by
important than the polar effects.[10d,f]
ˆ
electrophilic addition to the C C bond is usually associated
Discussion
‡
with large and negative 1 values, as exemplified in the
hydration (1 ˆ À3.5)[25] and bromination (1 ˆ À4.1)[26]
Based on the results discussed in the previous sections
including the secondary kinetic isotope effect (KIE) results,
we conclude that the reactions of aromatic alkenes with
[RuVI(Por*)O2] proceed through the rate-determining forma-
tion of a benzylic radical intermediate. The carboradical
‡
‡
reactions.
If the styrene epoxidation involves rate-limiting formation
of a carboradical intermediate, its transition-state energy
would be influenced by the polar substituent and spin
delocalization effects as spin density is developing at the a-
carbon atom upon progressing to the transition state. Con-
sidering spin delocalization and polar effects, we employed
À
intermediate would undergo ring closure or C C bond
rotation thereby forming cis- and trans-epoxides, respectively
(Scheme 3). There are several literature reports which
propose the participation of carboradical intermediates in
alkene oxidations by highly reactive metal oxo complexes;
some notable examples are those involving the [FeIV(O)-
.
the sJJ and smb parameters,[27] developed by Jiang and Ji, in
.
.
a dual-parameter Hammett correlation (logkrel ˆ 1JJsJJ
‡
1
mbsmb) for the styrene epoxidations. Two straight lines with
.
.
‡
slope ˆ 1.00 and R ˆ 0.99 [logkrel ˆ 1.29sJJ 0.44smb (1) and
(tmp) ],[28b,c] [MnV(O)(salen)X],[28d] and [RuIV(O)(L1)(L2)]2‡
(L1 and L2 ˆ polypyridine ligands) complexes.[8c]
.
logkrel ˆ 1.35sJJ 0.64smb (2a)] were established (Figure 4).
The linear free-energy correlation with spin delocalization
and polar effects is a good indication of radical character
developed at the a-carbon in the transition state. The positive
With regards to the cis-alkene epoxidation, the stereo-
retention is affected by the bulky substituents on the
porphyrin macrocycle. For instance, the cis-stilbene oxida-
tions by 1 and 2a exhibited complete stereoretention, whereas
.
1JJ values suggest that the epoxidation reaction is promoted
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Dioxoruthenium Porphyrins
2495 2507
Figure 5. Molecular models of the homochiral complexes 1 and 2a.
However, with ortho-substituted styrenes, such as 2-chloro-
and 2-bromostyrenes as substrates, the epoxidations proceed-
ed in considerably lower ee of ꢀ50% (see Table 1). Based on
the ™side-on approach∫ model (Scheme 4), it is conceivable
that ortho-substitution of styrene would intensify steric
interaction between the alkene and the chiral auxiliaries in
both the pro-R and -S facial approaches, leading to reduced
enantioselectivity.
Scheme 3. Proposed mechanism for alkene oxidations by dioxoruthe-
nium(vi) porphyrins.
the analogous reaction with cis-b-deuteriostyrene led to
substantial formation of the trans-epoxide. We reason that
À
bulky groups may hinder the C C rotation of the benzylic
radical intermediate, resulting in stereoretention in the cis-
stilbene oxidation.
Facial selectivity of the D4- and D2-symmetric chiral dioxo-
ruthenium(vi)porphyrins
Side-on approach model: In our earlier attempt to bring about
enantioselective styrene epoxidation by chiral metal-oxo
complexes, we employed [RuIV(terpy)(cxhn)(O)](ClO4)2
[terpy ˆ 2,2':6',2''-terpyridine; cxhn ˆ (À)-(1R,2R)-tetrameth-
yl-1,2-diaminocyclohexane] as the oxidant.[8b] However, this
complex failed to effect asymmetric induction upon reaction
with styrene. This negative result is ascribed to the undesir-
able disposition of the terpyridine and chiral diamine ligands,
resulting in the lack of enantiofacial discrimination. Prior to
this study, Halterman and co-workers reported that the
[MnIII(D4-Por*)Cl] complex was an effective catalyst for
asymmetric epoxidation of styrene and cis-b-methylstyrene
with sodium hypochlorite as the oxidant.[2f] We envisioned
and established by X-ray crystal structure analysis that the
dioxoruthenium group of complex 1 is surrounded by four
dinorbanbenzene moieties to create a D4-symmetric chiral
pocket,[3d] which would facilitate prochiral facial recognition
of the alkene (Figure 5).
The facial selection for the 1-mediated asymmetric alkene
epoxidation can be rationalized by the ™side-on∫ approach
model; (R)-styrene oxide in 65% ee was obtained for the
stoichiometric styrene epoxidation. The formation of the (S)-
epoxide is less favored because of the steric interaction
between the phenyl group and the chiral auxiliaries. We found
that complex 1 effectively epoxidized para- and meta-sub-
stituted styrenes with enantioselectivities of 60 70% ee.
Scheme 4. Side-on approach model for the D4-symmetric chiral dioxo-
ruthenium(vi) porphyrin.
Similarly, the reaction of cis-b-methylstyrene and 1,2-
dihydronaphthalene with
1 preferentially afforded the
(1R,2S)-epoxides in 72 and 82% ee, respectively (see Table 1).
Analogous to some reported metalloporphyrin-catalyzed
alkene epoxidations, reaction of trans-b-methylstyrene with
1 gave the trans-epoxide in 20% ee. Based on the ™side-on
approach∫ model, trans-alkene epoxidation would be hin-
dered as a result of unfavorable nonbonding interaction of
trans-alkene with the porphyrin ligand.[2, 3, 5, 29] Indeed, our
kinetics studies revealed that the oxidation of cis-b-methyl-
styrene (k2 ˆ (29.6 Æ 1.5)  10À4 dm3 molÀ1 sÀ1) is ꢀ1.4 times
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C.-M. Che et al.
FULL PAPER
ˆ
faster that of its trans counterpart (k2 ˆ (21.5 Æ 1.6) Â
alkene to the Ru O group would be disfavored by the bulky
ortho-substituents in these complexes. Therefore, if the side-
on approach is an obligatory pathway for alkene epoxidation,
trans-b-methylstyrene should be unreactive toward these two
bulky dioxoruthenium(vi) porphyrins. Yet, both cis- and trans-
b-methylstyrenes were oxidized by [RuVI(tdcpp)O2] and
[RuVI(tmopp)O2] to afford epoxides in good yields. Moreover,
the reactions of styrene and trans-b-methylstyrene with these
two complexes were found to have comparable DS= values. To
account for these findings, we previously proposed a top-on
transition-state model for the trans-b-methylstyrene epoxida-
tion.[10d] Based on the docking studies for the oxidation of
trans-b-methylstyrene and trans-stilbene by [CrV(Br8tpp)-
(O)(X)] (H2Br8tpp ˆ meso-tetrakis(2,6-dibromophenyl)por-
10À4 dm3 molÀ1 sÀ1) at 298 K (Table 4).
Groves and co-workers[29] first proposed a side-on approach
of the alkene to the putative metal oxo species to account for
the stereoselectivity in the cis-alkene oxidation catalyzed by
metalloporphyrin complexes. It was suggested that the side-on
approach would lead to more effective interaction of the filled
ˆ
À
p-orbital of the C C bond with the dp pp M O antibonding
orbital. The side-on approach model has gained widespread
acceptance in the oxidation chemistry of metalloporphyrins
and has been used to explain the enantioselectivity of the
chiral Mn(salen)-catalyzed asymmetric epoxidation of un-
functionalized alkenes.[1b,c]
phyrin), Bruice and co-workers had also suggested that the
Top-on approach model: Based on the molecular structure of
the [RuII(D2-Por*)(CO)(EtOH)] complex reported earlier by
Gross and co-workers,[3a] we have constructed a molecular
model of [RuVI(D2-Por*)O2] (2a), which reveals that the
V
ˆ
ˆ
C C bond is directed preferentially from the top of the Cr
O
group.[31]
As an alternative to the ™side-on approach∫ model, we
propose here the ™top-on approach∫ to rationalize the
apparent trans-preference and facial selectivity of trans-b-
methylstyrene epoxidation by the D2-symmetric dioxoruthe-
nium(vi) porphyrins. As shown in Scheme 5, the pro-R face of
trans-b-methylstyrene can fit into the chiral scaffold confined
ˆ
Ru O moiety is encased within a chiral pocket containing two
C2-symmetry-related threitol units. As depicted in Figure 5,
the model shows that the porphyrin macrocycle exhibits a
saddle-shaped distortion. In accord with theoretical calcula-
tions by Goddard and co-workers,[30c] complex 2a shows
substantially red-shifted Soret and Q bands (lmax (CH2Cl2) ˆ
442, 536 nm), consistent with a smaller HOMO LUMO gap
caused by saddle distortion.[30]
The styrene epoxidation by 2a afforded the (R)-epoxide in
62% ee, and the enantioselectivity is somewhat insensitive to
the para-substituent (ꢀ65% ee). As discussed earlier, similar
results were found for the stoichiometric epoxidation of para-
substituted styrenes by 1. However, 2a reacted with 3-chloro-
styrene to give 3-chlorostyrene oxide in 54% ee, which is well
below the 72% ee value obtained when 1 was used as the
oxidant. Based on the side-on approach model described
above, ortho-substituted styrenes would be expected to react
with 2a with even lower enantioselectivity. However, the
reaction of 2-chlorostyrene with 2a in benzene containing
2%w/w Hpz yielded (R)-2-chlorostyrene oxide with an
exceptionally high enantioselectivity of 88% ee as compared
to 44% ee achieved with 1 as the oxidant. Other ortho-
substituted styrenes are also epoxidized effectively by 2a in
ꢀ80% ee; their analogous reactions with 1 have attained only
ꢀ50% ee (Table 1, entries 11 13).
Apparently, 2a exhibits trans-preference in contrast to most
of the metalloporphyrin-catalyzed alkene epoxidations, and
up to 76% ee was achieved for its reaction with trans-
cinnamyl chloride. Notably, the analogous reaction with 1
led to only 18% ee under identical reaction conditions
(Table 1). Furthermore, the trans-b-methylstyrene epoxida-
tion by 2a proceeded with a larger k2 value [(8.4 Æ 0.1) Â
10À4 dm3 molÀ1 sÀ1 (Table 4)] and higher enantioselectivity
(72% ee), compared to the related values for the cis-b-
methylstyrene (k2 ˆ (5.8 Æ 0.2)  10À4 dm3 molÀ1 sÀ1 (298 K)
and 40% ee). These findings are inconsistent with the side-
on approach model.
Scheme 5. Transition-state models for the D2-symmetric chiral dioxoru-
thenium(vi) porphyrin.
by the two equatorial methyl groups of the threitol substitu-
ents. Consistent with this model, an increase in the size of the
gem-dialkyl groups reduces the enantioselectivity of the trans-
alkene epoxidation, since the bulky geminal substituents
would hinder both prochiral facial approaches of the alkene.
Both the pro-R and -S faces of cis-b-methylstyrene directed
We have previously reported the epoxidation of cis- and
trans-b-methylstyrenes by two sterically congested dioxoru-
thenium(vi) porphyrins, [RuVI(tdcpp)O2] and [RuVI(tmopp)-
O2].[10d] It is expected that the ™side-on∫ approach of the trans-
ˆ
side-on to the Ru O moiety would be disfavored as a result of
steric interaction with the chiral auxiliaries. The ™top-on
approach∫ model was also proposed by Jacobsen and co-
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Chem. Eur. J. 2002, 8, No. 11

Dioxoruthenium Porphyrins
2495 2507
workers for the chiral [Mn(salen)]-catalyzed enantioselective
epoxidation of tetrasubstituted alkenes.[32]
Epoxidation of ortho-substituted styrenes by 2a gave the
epoxides with exceptional enantioselectivity (ꢀ80% ee vs
50% ee with 1 as oxidant), which can also be understood if the
As mentioned earlier, the use of dichloromethane for the
styrene epoxidation by 2a results in lower enantioselectivity
(40% ee) than that obtained with benzene as the solvent. We
found that cis-b-deuteriostyrene was epoxidized by 2a to give
cis- (51% ee) and trans-epoxides (9% ee) with the cis:trans
ratio being 75:25 (Table 7). The reduction in ee values is the
result of lower facial selectivity (69% ee (benzene) vs. 51% ee
(CH2Cl2)) together with the increased cis trans isomerization
in the epoxide ring closure step (cis/trans: 89:11 in C6H6 vs.
75:25 in CH2Cl2).
ˆ
alkene approaches the Ru O moiety from a top-on direction.
Facial selectivity and diastereoselectivity of epoxide ring
closure: The aromatic alkene epoxidations by [RuVI(Por*)O2]
À
proceed via two nonconcerted C O bond formation steps;
ˆ
ˆ
attack of the C C bond by the Ru O generates a benzylic
radical intermediate which undergoes either collapse (cis) or
rotation/collapse (trans) processes to afford a mixture of cis-
and trans-epoxides. Therefore, the observed enantioselectivity
cannot depend solely on the facial selectivity of the initial
For the asymmetric epoxidation of 1,2-disubstituted al-
kenes, such as cis-/trans-b-methylstyrenes, two diastereomeric
À
carboradical intermediates will be formed at the first C O
bond formation step while creating an asymmetric center at
the b-carbon atom. Depending on the ligand asymmetry, the
two carboradical intermediates would undergo different
degrees of collapse and rotation/collapse processes resulting
in their own cis trans oxide composition. This situation has
been meticulously analyzed by Jacobsen and co-workers in
their investigations of asymmetric epoxidation of alkenes;[34]
the facial selectivity (eefac) is given by [(eecis)  (%cis) ‡
(eetrans) Â (%trans)], while the diastereoselectivity of the
epoxide ring closure is {[(1‡eecis)/(1 À eecis)]  [1 À eetrans)/
(1‡eetrans)]}. The diastereoselective ring closure would en-
hance the enantioselectivity of the cis-alkene epoxidation.
À
C O bond formation, but also upon the extent of cis trans
À
isomerization prior to the formation of the second C O bond.
In the case of styrene epoxidation, the a carbon (i.e., the only
asymmetric carbon center to be created) remains epimeric;
the rotation/collapse pathway tends to reduce the enantiose-
lectivity by generating the opposite enantiomeric epoxide
(Scheme 6).
Experimental Section
General: All the 1H NMR spectra were recorded in CDCl3 at 500 MHz and
coupling constants are rounded to 0.5 Hz unless otherwise noted. Gas
chromatography was performed on
a Hewlett-Packard5890 SeriesII
system equipped with HP5890A flame ionization detector and
a
a
HP3395 integrator. The chiral capillary columns for separation of
enantiomers were J&W Scientific Cyclodex-B (30 m), ChiraldexB-PM
(30 m), and G-TA (30 m) columns. The ee×s were reproducible within Æ2%
error of the stated values.
Scheme 6. Nonstereospecific styrene oxidation.
The detrimental effect of the rotation/collapse pathway on
the enantioselectivity can be evaluated by the use of cis-b-
deuteriostyrene as a probe substrate. The epoxidation of cis-b-
deuteriostyrene by 2a under the standard reaction conditions
(alkene ˆ 1 mmol, 2a ˆ 15 mmol in degassed benzene con-
taining Hpz (2%w/w) at room temperature) afforded a
mixture of cis- and trans-b-deuteriostyrene oxides (cis/trans ˆ
Materials: Dichloromethane and 1,2-dichloroethane were refluxed over
calcium chloride followed by distillation over calcium hydride. Benzene
was distilled over sodium/benzophenone under an argon atmosphere
before use. The deuterated solvents, CD2Cl2, CDCl3, and C6D6 (Aldrich),
were used as received. All the alkene substrates were obtained commer-
cially and purified by either vacuum distillation from calcium hydride, or
passing through a dry column of activated alumina prior to use. The purity
of alkenes was checked by gas chromatography or 1H NMR analysis. m-
Chloroperoxybenzoic acid (Merck), dodecacarbonyltriruthenium(0) and
pyrazole (Aldrich) were used as received. cis-b-Methylstyrene,[35] cis-b-
[D1]styrene,[35] b-[D2]styrene,[36a,b] and a-[D1]styrene[36a,c] were prepared
according to the literature procedures. The D4-[12] and D2-symmetric[3a]
porphyrins were prepared by previously reported procedures. The prep-
aration and characterization of [RuII(D4-Por*)(CO)(MeOH)][3d,e] and
[RuII(D2-Por*)(CO)(MeOH)][3f] have been reported elsewhere.
1
89:11, see Table 7). H NMR analysis of the product mixture
in the presence of the chiral shift reagent [Eu(hfc)3] revealed
the enantiomeric composition of the cis- (69% ee) and trans-
epoxides (10% ee). Since all the steps shown in Scheme 6 are
considered to be irreversible, the observed enantioselectivity
(eeobs) can be correlated to the ee values of the cis- and trans-b-
deuteriostyrene oxides as such: eeobs ˆ [(eecis)  (%cis) À
(eetrans) Â (%trans)] according to the work of Jacobsen and
co-workers.[33] Substituting the data into this equation gives
the calculated eeobs value ˆ 63% ee, which closely matches the
experimental value of 62% ee. Because the a-carbon of
styrene is the only epimeric/asymmetric center, the facial
General procedure for the preparation of [RuVI(Por*)O2]: A solution of
[RuII(Por*)(CO)(MeOH)] (0.05 mmol) in dichloromethane (5 mL) was
added to
a well-stirred solution of m-chloroperoxybenzoic acid
(0.06 mmol) in dichloromethane (15 mL). The mixture was stirred for
ꢀ5 min, and the resultant brown solution was separated by chromatog-
raphy on a short alumina column. The product was eluted by dichloro-
methane (for 1) or chloroform (for 2a d). The solution obtained was
evaporated to dryness in vacuum, affording a dark purple solid in 70 80%
yields.
À
selectivity (eefacial) at the initial C O bond formation step
should approach the eecis value when the styrene epoxidation
became fully stereospecific, and the rotation/collapse pathway
should, therefore, account for approximately 7% ee reduc-
tion.
[RuVI(D4-Por*)O2] (1): IR (KBr): nÄ ˆ 1019 (oxidation-state marker band),
822 cmÀ1 (Ru O); UV/Vis (CH2Cl2): lmax (loge) ˆ 424 (5.38), 521 nm
ˆ
(4.35); 1H NMR (300 MHz, C6D6, TMS): d ˆ 9.24 (s, 8H), 7.40 (s, 4H), 3.46
(s, 8H), 2.78 (s, 8H), 2.03 (m, 8H), 1.66 (m, 8H), 1.41 1.11 (m, 24H) and
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C.-M. Che et al.
FULL PAPER
0.96 (m, 8H); 13C NMR (125.7 MHz, CDCl3): d ˆ 27.18, 27.56, 42.42, 44.40,
49.34, 113.99, 118.92, 127.91, 130.78, 141.53, 144.27, 148.06; FAB-MS: m/z:
dronaphthalene oxide were determined by GC with a chiral column
(Cyclodex-B). The enantiopurities of 2-chloro-, 2-fluoro-, 2-bromo-,
2-methyl-, and a-methylstyrene oxide were analyzed by GC with a chiral
ChiraldexB-PM column. The enantiomeric purities of trans-b-methylstyr-
ene oxide, and epoxycinnamyl chloride were determined by chiral GC on a
ChiraldexG-TA column. The enantiopurities of 4-methylstyrene oxide,
3-nitrostyrene oxide, 3-chlorostyrene oxide, and 2-vinylnaphthalene oxide
were determined by 1H NMR spectroscopy in the presence of a chiral shift
reagent [Eu(hfc)3]. The absolute configurations of the epoxides were
determined by chiral GC and comparison with the authentic enantiopure
samples.
‡
‡
‡
1274 [M ], 1258 [M À O], 1242 [M À 2O].
[RuVI(D2-Por*)O2] (2a): IR (KBr): nÄ ˆ 1018 (oxidation-state marker
band), 818 cmÀ1 (Ru O); UV/Vis (CH2Cl2): lmax (loge) ˆ 442 (5.12),
ˆ
1
536 nm (4.07); H NMR (300 MHz, CDCl3, TMS): d ˆ 8.66 (d, J ˆ 4.7 Hz,
4H), 8.56 (d, J ˆ 4.5 Hz, 4H), 7.75 (t, J ˆ 8.5 Hz, 4H), 7.36 (d, J ˆ 8.5 Hz,
4H), 7.29 (d, J ˆ 8.5 Hz, 4H), 4.91 (d, J ˆ 10.4 Hz, 4H), 4.62 (d, J ˆ 9.0 Hz,
4H), 4.43 (t, J ˆ 9.0 Hz, 4H), 4.22 (d, J ˆ 10.1 Hz, 4H), 3.76 (d, J ˆ 9.0 Hz,
4H), 2.60 (t, J ˆ 8.5 Hz, 4H), 0.77 (s, 12H), À0.78 (s, 12H); 13C NMR (125.7
MHz, CDCl3): d ˆ 23.41, 26.53, 65.33, 68.40, 73.65, 74.42, 75.05, 75.38,
108.22, 111.99, 114.18, 114.68, 121.30, 128.02, 128.57, 129.06, 129.92, 130.00,
Molecular modeling studies: The three-dimensional computer model of 1
was established directly from its crystal structure with a Silicon Graphics
(Indigo 2) computer with a Macromodel software (version 4.5). Construc-
tion of the structure of complex 2a was based on the reported X-ray
‡
130.88, 131.17, 144.52, 144.84, 158.99, 160.90; FAB-MS: m/z: 1379 [M ],
‡
‡
1363 [M À O], 1347 [M À 2O].
Complex 2b: IR (KBr): nÄ ˆ 1019 (oxidation-state marker band), 821 cmÀ1
II
À
coordinates for [Ru (D2-Por*)(CO)], and the O Ru bond length was
ˆ
(Ru O); UV/Vis (CH2Cl2): lmax (loge) ˆ 443 (5.15), 534 nm (4.02);
1H NMR (300 MHz, CDCl3, TMS): d ˆ 8.64 (d, J ˆ 4.7 Hz, 4H), 8.53 (d,
J ˆ 4.7 Hz, 4H), 7.74 (t, J ˆ 6.5 Hz, 4H), 7.17 7.30 (m, m-phenyl H
overlapped with solvent peak, 8H), 4.98 (d, J ˆ 10.4 Hz, 4H), 4.60 (d, J ˆ
8.8 Hz, 4H), 4.44 (t, J ˆ 9.0 Hz, 4H), 4.23 (d, J ˆ 10.4 Hz, 4H), 3.74 (d, J ˆ
9.0 Hz, 4H), 2.63 (t, J ˆ 8.5 Hz, 4H), 1.02 (m, 8H), 0.53 (t, J ˆ 7.2 Hz, 12H),
taken to be 1.74 ä, based on the measured distance obtained from the
crystal structure of 1. All alkene structures used in docking experiments
were energy minimized prior to use.
Kinetic studies on the reactions of [RuVI(Por*)O2] with alkenes: Kinetic
measurements were performed on a Hewlett-Packard8453A Diode Array
spectrophotometer interfaced with an IBM-compatible PC and equipped
with a LaudaRM6 circulating water bath; standard 1.0 cm quartz cuvettes
were employed. The temperature of solutions during kinetic experiments
was maintained to within Æ0.28C.
‡
À0.25 (m, 8H), À1.37 (t, J ˆ 7.3 Hz, 12H); FAB-MS: m/z: 1491 [M ], 1475
‡
‡
[M À O], 1459 [M À 2O].
Complex 2c: IR (KBr): nÄ ˆ 1019 (oxidation-state marker band), 819 cmÀ1
ˆ
(Ru O); UV/Vis (CH2Cl2): lmax (loge) ˆ 441 (5.03), 535 nm (4.02);
1H NMR (300 MHz, CDCl3, TMS): d ˆ 8.67 (d, J ˆ 4.7 Hz, 4H), 8.56 (d,
J ˆ 4.7 Hz, 4H), 7.76 (t, J ˆ 6.5 Hz, 4H), 7.20 7.30 (m, m-phenyl H
overlapped with solvent peak, 8H), 4.88 (d, J ˆ 10.4 Hz, 4H), 4.60 (d, J ˆ
9.4 Hz, 4H), 4.44 (t, J ˆ 9.0 Hz, 4H), 4.24 (d, J ˆ 10.1 Hz, 4H), 3.77 (d, J ˆ
8.6 Hz, 4H), 2.57 (t, J ˆ 8.6 Hz, 4H), 0.83 (m, 12H), 0.60 (m, 12H), 0.32 (m,
The pseudo-first-order rate constants (kobs
) of the reaction between
[RuVI(Por*)O2] and alkenes were measured by monitoring the decrease
of the Soret band under the condition that the alkene concentration is at
least 100-fold in excess of [RuVI(Por*)O2]. The kobs values were obtained by
nonlinear least-squares fits of (Af À At) to time (t) according to the
following equation:(Af À At) ˆ (Af À Ai)exp(Àkobst), where Af and Ai are
the final and initial absorbances, respectively, and At is the absorbance
measured at time t. Kinetic data over four half-lives (t1/2) were used for the
least-squares fitting. Second-order rate constants, k2, were obtained from
the linear fit of kobs values to the concentration of alkenes.
‡
‡
4H), À1.16 (m, 4H); FAB-MS: m/z: 1483 [M ], 1467 [M À O], 1451
‡
[M À 2O].
Complex 2d: IR (KBr): nÄ ˆ 1021 (oxidation-state marker band), 818 cmÀ1
ˆ
(Ru O); UV/Vis (CH2Cl2): lmax (loge) ˆ 443 (5.18), 537 nm (4.05);
1H NMR (300 MHz, CDCl3, TMS): d ˆ 8.50 (d, J ˆ 4.7 Hz, 4H), 8.41 (d,
J ˆ 4.7 Hz, 4H), 7.73 (d, J ˆ 8.2 Hz, 16H), 7.19 7.32 (m, m-phenyl H
overlapped with solvent peak, 16H), 7.10 6.90 (m, phenyl-H, 10H), 6.07 (t,
J ˆ 7.5 Hz, 2H), 5.96 (d, J ˆ 7.0 Hz, 4H), 5.46 (t, J ˆ 7.5 Hz, 4H), 4.65 (dd,
J1 ˆ 11.0 Hz, J2 ˆ 3.0 Hz, 2H), 4.46 (d, J ˆ 7.0 Hz, 2H), 4.36 (m, 4H), 4.28
(d, J ˆ 10.5 Hz, 2H), 4.10 (d, unresolved, 8H), 3.98 (t, J ˆ 5.0 Hz, 4H), 3.24
Activation enthalpy (DH=) and entropy (DS=) were obtained from the
slope and the intercept, respectively, of the plot of ln(k2/T) verus (1/T) on
the basis of the Eyring equation: ln(k2/T) ˆ ln(R/Nꢀh) ‡ DS=/R À DH=/RT
where N is Avogadro×s number, R is the universal gas constant, ꢀh is Planck×s
constant, and T is the temperature in Kelvin. The Eyring plots were fitted
by unweighted linear least-squares methods with the software package
Origin (Microcal Software, Inc). The cited errors in the activation
parameters are the errors of the linear fits.
‡
‡
‡
(t, J ˆ 5.0 Hz, 2H); FAB-MS: m/z: 1876 [M ], 1860 [M À O], 1844 [M À
2O).
Stoichiometric oxidation of alkenes by dioxoruthenium(vi)porphyrins : The
dioxoruthenium(vi) complex (15 30 mmol) under an argon atmosphere
was added to a degassed benzene solution (2 mL) containing alkene
(1 mmol) and pyrazole (2% w/w). When the reaction was completed as
indicated by the disappearance of the Soret band of the starting complex,
the reaction mixture was filtered through a short alumina column with
hexane/ethyl acetate (10:1) as the eluant to remove the ruthenium
complex. After addition of internal standard, the organic products were
then analyzed and quantified by either gas chromatography or 1H NMR
spectroscopy.
Acknowledgements
We acknowledge support from The University of Hong Kong (Generic
Drugs Research), the Hong Kong University Foundation, and the Hong
Kong Research Grants Council (HKU7092/98P, ERB003, and PolyU01/
97C). We thank Drs. J.-S. Huang and M.-K. Wong for their assistance in the
computer modeling experiments, and Dr. T.-S. Lai for helpful discussions.
The bis(pyrazolato)ruthenium(iv) products (3) were eluted by dichloro-
methane, and addition of acetonitrile or n-hexanes gave [RuIV(Por*)(pz)2]
as a dark purple solid. Yield: 70 80%.
[1] For leading references on catalytic asymmetric epoxidations, see: a) C.
Bolm, Angew. Chem. 1991, 103, 414; Angew. Chem. Int. Ed. Engl.
1991, 30, 403; b) T. Katsuki in Catalytic Asymmetric Synthesis (Ed.: I.
Ojima), Wiley-VCH, Weinheim, 2000; c) E. N. Jacobsen, M. H. Wu in
Comprehensive Asymmetric Catalysis (Eds.: E. N. Jacobsen, A. Pfaltz,
H. Yamamoto), Springer, Berlin, 1999, pp. 649 675; d) Y. N. Ito, T.
Katsuki, Bull. Chem. Soc. Jpn. 1999, 72, 603; e) S. E. Denmark, Z. C.
Wu, Synlett. 1999, 847.
[2] For leading examples of chiral iron and manganese porphyrin-
catalyzed enantioselective epoxidations, see: a) J. T. Groves, R. S.
Myers, J. Am. Chem. Soc. 1983, 105, 5791; b) D. Mansuy, P. Battoni,
J. P. Renaud, P. Guerin, J. Chem. Soc. Chem. Commun. 1985, 155; c) S.
O×Malley, T. Kodadek, J. Am. Chem. Soc. 1989, 111, 9116; d) J. T.
Grove, P. Viski, J. Org. Chem. 1990, 55, 3628; e) Y. Naruta, F. Tani, N.
Ishihara, K. Maruyama, J. Am. Chem. Soc. 1991, 113, 6865; f) R. L.
Halterman, S.-T. Jan, J. Org. Chem. 1991, 56, 5253; g) K. Konishi, K.-I.
[RuIV(D4-Por*)(pz)2] (3a): Yield: 80%; IR (KBr): nÄ ˆ 1009 cmÀ1 (oxida-
tion-state marker band); UV/Vis (CH2Cl2): lmax (loge) ˆ 408 (5.25), 512 nm
‡
‡
‡
(4.12); FAB-MS: m/z: 1376 [M ], 1309 [M À pz], 1242 [M À 2pz];
elemental analysis calcd (%) for C90H82N8Ru ¥ H2O: C 77.47, H 6.03, N 8.03;
found: C 77.31, H 6.08, N 8.15; meff (Evan×s method) ˆ 2.9 mB (solid, room
temperature).
[RuIV(D2-Por*)(pz)2] (3b): Yield: 70%; IR (KBr): nÄ ˆ 1006 cmÀ1 (oxida-
tion-state marker band); UV/Vis (CH2Cl2): lmax (loge) ˆ 425 (5.09), 517
‡
‡
‡
(4.04), 550 nm (sh); FAB-MS: m/z: 1483 [M ], 1415 [M À pz], 1347 [M À
2pz]; elemental analysis calcd (%) for C78H76N8O19Ru ¥ 3H2O: C 60.89, H
5.33, N 7.28; found: C 60.77, H 5.31, N 7.25; meff (Evan×s method) ˆ 2.9 mB
(solid, room temperature).
Determination of enantiomeric purities and absolute configurations: The
enantiomeric purities of styrene oxide, 4-fluoro-, 4-chloro-, 4-trifluoro-
methyl-, 4-bromo-styrene oxide, cis-b-methylstyrene oxide, and 1,2-dihy-
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Chem. Eur. J. 2002, 8, No. 11

Dioxoruthenium Porphyrins
2495 2507
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ˆ
ˆ
Am. Chem. Soc. 1996, 118, 8961.
[7] The mechanism of the Jacobsen Katsuki asymmetric alkene epox-
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Received: June 21, 2001
Revised: February 12, 2002 [F3358]
Chem. Eur. J. 2002, 8, No. 11
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