MTO and OsO4: An efficient catalytic couple for mild H2O2-based asymmetric dihydroxylation of olefins

Article abstract of DOI:10.1002/chem.200304828

A novel and robust system for osmium-catalyzed asymmetric dihydroxylation of olefins by aqueous H₂O₂ with methyltrioxorhenium (MTO) as electron transfer mediator (ETM) has been developed. The MTO is catalyzing the H₂O₂ oxidation of the chiral ligand to its mono-N-oxide, which in turn reoxidizes Os^VI to Os^VIII. Thus the (DHQD)₂PHAL plays a dual role serving as the chiral inductor as well as the tertiary amine generating the N-oxide required for the recycling of osmium. The present catalytic system gives vicinal diols in good isolated yields and high enantiomeric excess (up to 99 % ee).

Full text of DOI:10.1002/chem.200304828

FULL PAPER
MTO and OsO4: An Efficient Catalytic Couple for Mild H2O2-Based
Asymmetric Dihydroxylation of Olefins
Sandra Y. Jonsson, Hans Adolfsson,* and Jan-E. B‰ckvall*[a]
Abstract: A novel and robust system for osmium-catalyzed asymmetric dihydrox-
ylation of olefins by aqueous H2O2 with methyltrioxorhenium (MTO) as electron
transfer mediator (ETM) has been developed. The MTO is catalyzing the H2O2
oxidation of the chiral ligand to its mono-N-oxide, which in turn reoxidizes OsVI to
OsVIII. Thus the (DHQD)2PHAL plays a dual role serving as the chiral inductor as
well as the tertiary amine generating the N-oxide required for the recycling of
osmium. The present catalytic system gives vicinal diols in good isolated yields and
high enantiomeric excess (up to 99% ee).
Keywords: asymmetric catalysis
dihydroxylation hydrogen
peroxide ¥ osmium ¥ rhenium
¥
¥
applications.[6] Hence, there is a need for the development of
methods employing alternative cheap environmentally benign
and selective oxidants, such as molecular oxygen or hydrogen
peroxide, for the osmium-catalyzed dihydroxylation of ole-
fins. These oxidants are highly attractive since, in contrast to
many commonly employed inorganic oxidants, they do not
produce any toxic waste products.
Introduction
The cis-dihydroxylation of olefins mediated by osmium
tetroxide represents an important method for olefin function-
alization.[1, 2] With respect to its general applicability, this
protocol is probably the most powerful route toward 1,2-diols.
The active reagent, OsO4, being highly chemoselective
although at the same time toxic and expensive, emphasizes
the importance of developing good reoxidation systems for
osmium(vi), rendering the dihydroxylation catalytic in osmi-
um. Several efficient processes for reoxidation of OsVI have
been developed in the past. Tertiary amine oxides, such as N-
methylmorpholine N-oxide (NMO), are commonly used
oxidants introduced by VanRheenen and co-workers at the
Upjohn company in 1976.[2] Sharpless and co-workers used
NMO as the reoxidant in the development of the catalytic
asymmetric dihydroxylation of olefins,[3] which under certain
reaction conditions gave high yields of the diol products in
high enantiomeric excess. Another addition to this list of co-
oxidants is potassium hexacyanoferrate(iii) (K3[Fe(CN)6]),
which was introduced by Tsuji in the early 1990s as a
reoxidant for the osmium(vi) species.[4] This iron salt was
found to be superior to NMO in the asymmetric version of the
reaction, giving diols with higher ee values.[5] Unfortunately,
substantial quantities of salts are produced from the latter
oxidant, which makes the method unpractical for large-scale
The use of hydrogen peroxide as reoxidant for osmium(vi)
was already reported by Milas and co-workers in the 1930s.[7]
Catalytic cis-dihydroxylation using hydrogen peroxide result-
ed in good yields with certain olefins, but over-oxidation and
non-selective reactions constitute serious limitations of this
method. Apart from the Milas method,[7] only a few proce-
dures for reoxidation of osmium(vi) by H2O2 or O2 are known.
Krief et al. have shown that O2 can reoxidize osmium(vi) in
the presence of a selenium oxide under irradiation by visible
light.[8] Beller and co-workers have reported on a procedure
for aerobic osmium-catalyzed dihydroxylation of olefins
under strictly buffered conditions,[9] and our own group has
developed a mild H2O2-based osmium-catalyzed dihydroxy-
lation employing a flavin and N-methyl morpholine (NMM)
as co-catalysts (Scheme 1).[10] In the latter procedure OsVI is
reoxidized by NMO, generated from NMM and H2O2 with the
aid of a flavin.[11] Direct reoxidation of OsVI by H2O2 does not
work very well. In general, direct reoxidation of the reduced
form of a substrate-selective metal catalyst by O2 or H2O2 is
usually not trivial, since the energy barrier for electron
transfer can be high. In many biological oxidation systems,
nature has solved this problem by the introduction of efficient
electron transfer mediators (ETMs) between the substrate-
selective redox catalyst and the terminal oxidant (O2 or
H2O2).[12] The same principle is also used in several syntheti-
cally important non-biological biomimetic oxidation reac-
[a] Dr. H. Adolfsson, Prof. Dr. J.-E. B‰ckvall, Dr. S. Y. Jonsson
Department of Organic Chemistry
Stockholm University
106 91 Stockholm (Sweden)
Fax : (‡46)8-154908
E-mail: hansa@organ.su.se
jeb@organ.su.se
Chem. Eur. J. 2003, 9, 2783 2788
DOI: 10.1002/chem.200304828
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J.-E. B‰ckvall et al.
FULL PAPER
tions,[13] (e.g. the Wacker process[13a]), where the reduced form
of the substrate-selective redox catalyst is reoxidized by the
oxidized form of a suitable ETM (ETMox). The reduced form
of the ETM (ETMred) is recycled by molecular oxygen or
hydrogen peroxide as the terminal oxidant. In the above
mentioned H2O2-based dihydroxylation system the formal
ETMs are NMM and a flavin (Scheme 1).[10]
Scheme 2. Triple catalytic biomimetic dihydroxylation system.
ethanediol in 65% yield and a modest 80% enantiomeric
excess.[14]
Over the past years methyltrioxorhenium (MTO) has been
shown to act as a powerful and versatile oxidation catalyst
24]
with interesting selectivity behavior.[17, 21, 22
MTO readily
reacts with aqueous hydrogen peroxide forming mono- and
bis-peroxo complexes (Scheme 3). The peroxo-complexes
efficiently catalyze a number of oxidation reactions, for
example epoxidation of olefins[17, 22] and N-oxidation of
amines[23] and pyridines.[24]
Scheme 1. Triple catalytic system for osmium-catalyzed dihydroxylation of
olefins using H2O2 as the terminal oxidant.
With the objective to simplify the catalytic system accord-
ing to Scheme 1 and enhance the utility of the H2O2-based
dihydroxylation, attempts were made to replace the flavin by
a more robust and stable hydrogen peroxide activator. Some
[14]
success was achieved with VO(acac)2 but this system gave
lower activity and enantioselectivity compared to the catalytic
system employing flavin. In the flavin-based system shown in
Scheme 1 we recently discovered that the chiral ligand
(DHQD)2PHAL[15] can also serve as the tertiary amine in
the electron transfer system. This dual role simplifies the
oxidation system since no NMM is required.[16]
We have now found conditions that allow the use of
methyltrioxorhenium (MTO) as the hydrogen peroxide
activator in osmium-catalyzed asymmetric dihydroxylation.
MTO has previously been successfully used as a redox catalyst
in hydrogen peroxide oxidations.[17] In our new system we take
advantage of the dual role of the cinchona alkaloid
(DHQD)2PHAL, which leads to an efficient osmium-cata-
lyzed asymmetric dihydroxylation where the oxidant is
aqueous hydrogen peroxide and the only added co-catalyst
is MTO.
Scheme 3. Reaction of MTO with H2O2.
In initial experiments we found that MTO catalyzes the
oxidation of NMM to NMO by hydrogen peroxide.[14]
Attempts to replace the flavin by MTO as ETM in the
H2O2-based dihydroxylation of trans-5-decene led to moder-
ate success and the corresponding diol was obtained in only
50% yield.[14] The MTO catalyst is known to be stable under
acidic reaction conditions; however, in basic reaction media,
under oxidative conditions, it decomposes into methanol and
catalytically inert perrhenate (ReO4 ).[25] A likely explanation
À
for the poor results obtained in the dihydroxylation reaction
using MTO as ETM is therefore that decomposition of the
rhenium catalyst occurs due to the rather high pH of the
reaction medium. A lowering of the NMM concentration,
which would decrease the pH, was therefore desirable.
We have recently observed that NMM can be omitted in the
triple-catalytic asymmetric dihydroxylation by H2O2
(Scheme 1) when a flavin is employed as H2O2 activator.[16]
In this reaction the cinchona alkaloid serves as the tertiary
amine, participating (via the N-oxide) in the oxygen transfer
from the flavin hydroperoxide to osmium(vi). This process
will give a lower pH since there is no added tertiary amine
(NMM). It was therefore of great interest to try these NMM-
free conditions with the use of MTO as ETM in the
asymmetric dihydroxylation.
Osmium-catalyzed asymmetric dihydroxylation by H2O2
with (DHQD)2PHAL as the ligand and employing MTO as
the ETM under NMM-free conditions, led to a highly
effective catalytic process (Table 1). Reaction of styrene with
aqueous H2O2 in tBuOH/H2O in the presence of 2 mol% of
OsO4 and 6 mol% of (DHQD)2PHAL using 2 mol% of MTO
as ETM gave styrene diol in 90% yield and 95% ee (Table 1,
entry 1). The olefin was added over a period of 9 h, since a low
Results and Discussion
Asymmetric dihydroxylation by H2O2 with MeReO3 as ETM:
Several transition metal complexes are known to activate
hydrogen peroxide and have been employed in oxidation
19]
reactions.[17 Vanadium complexes represent one such class
of transition metal complexes that often has been used as
catalysts in hydrogen peroxide oxidations.[19] For example,
vanadyl acetylacetonate, VO(acac)2, was found to catalyze
the hydrogen peroxide oxidation of NMM to NMO.[20] We
have previously shown that VO(acac)2 and NMM can be used
as efficient co-catalysts in the osmium-catalyzed dihydroxy-
lation of olefins with high chemo-selectivity by means of
hydrogen peroxide as the terminal oxidant (Scheme 2,
ETMred ˆ VO(acac)2).[14] However, employing the vanadium-
based system in the presence of (DHQD)2PHAL in the
dihydroxylation of styrene, produced (1R)-1-phenyl-1,2-
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Asymmetric Dihydroxylation
2783 2788
olefin concentration efficiently prevents the reaction from
entering the enantio-detrimental second catalytic cycle.[26]
Thus, for the first time an enantioselective cascade dihydrox-
ylation of alkenes by means of two homogeneously dissolved
transition metal catalysts was realized.[27] This kinetically
controlled protocol efficiently employs the chiral ligand
(DHQD)2PHAL as electron transfer mediator and source of
chirality, and H2O2 as the terminal oxidant (Scheme 4).
with trans-b-methylstyrene (entry 4) an ee of 99% was
obtained, a higher value than that obtained with MTO (see
above) and also than that obtained previously with the
method based on NMM.[10a] The results with the NMM-free
conditions using either MTO (Table 1) or flavin (Table 2) as
hydrogen peroxide activator complements one another.
Table 1. MTO and OsO4 as an efficient couple for asymmetric dihydroxylation
of olefins using H2O2 as the terminal oxidant.[a]
Entry
Olefin
Ligand and
reoxidant[a]
Os:L
Yield
[%][b]
ee [%][c]
1
(DHQD)2PHAL
1:3
90
95
2[d]
(DHQD)2PHAL
1:3
85
97
Scheme 4. Catalytic system with two transition metals using a chiral ligand
as a dual-function catalyst and H2O2 as the terminal oxidant.
Various aromatic olefins were efficiently dihydroxylated
employing this novel catalytic system. The results are
summarized in Table 1. Previous optimization studies have
revealed that a 3:1 ratio of tert-butyl alcohol and water was the
optimum solvent mixture.[6, 10] With the use of the above
conditions, excellent enantioselectivities were obtained in the
oxidation of trans-stilbene (entry 2) and in that of methyl
trans-cinnamate (entry 3). Initial experiments with trans-b-
methylstyrene, using a ligand concentration Os/L 1:3, were
rather disappointing giving an enantioselectivity of 73%.
However, by increasing the ligand concentration to Os/L 1:7.5
an enantioselectivity of 90% (entry 4) was realized. The tri-
substituted olefin 1-phenyl-1-cyclohexene (entry 6) gave a
substantially lower ee, even though the addition times of both
olefin and hydrogen peroxide were increased from 9 to 20 h
(Os/L 1:7.5). Interestingly, a-methylstyrene gave only an ee of
64%, even if the ligand concentration was increased to Os/L
1:7.5 (entry 5). The substantially lower enantioselectivity
(64% ee) observed in the dihydroxylation of a-methylstyrene
using the MTO system compared with that of the flavin-based
system (90% ee), could be explained by a competing epox-
idation by MTO and subsequent ring-opening reaction. This
was not a serious problem with the reaction of styrene, but the
enhanced reactivity of a-methylstyrene could lead some
MTO-catalyzed epoxidation.
3
4
5
(DHQD)2PHAL
(DHQD)2PHAL
(DHQD)2PHAL
1:3
87
87
85
98
90
64
1:7.5
1:7.5
6[e]
(DHQD)2PHAL
1:7.5
68
77
[a] TEAA (2 equiv), (DHQD)2PHAL (0.06 equiv or 0.15 equiv), and MTO
(0.02 equiv) were dissolved in tBuOH (1.88 mL) and H2O (0.62 mL). After
cooling to 08C, OsO4 (0.02 equiv) was added, followed by ³5 of the H2O2
(0.3 equiv, 30% aq). After stirring for 20 minutes, the olefin (0.5 mmol, 1 equiv)
and the remaining H2O2 (1.2 equiv) were added over 9 h. After complete
addition of the oxidant and olefin, the mixture was stirred for an additional 2
7 h. [b] Isolated yields. [c] Enantiomeric excess was determined by HPLC
(Daicel Chiracel OJ or ODH column, iPrOH/Hexane). [d] Acetone/H2O 4.4:1
was employed. [e] The olefin and H2O2 were added over 20 h.
1
Mechanistic considerations: The proposed catalytic cycle of
the reaction is depicted in Scheme 5. We envisage an ETM-
catalyzed formation of the mono-N-oxide of the ligand, which
via its non-oxidized tertiary amine coordinates to osmium
tetroxide (3).
Dihydroxylation by H2O2 with a flavin as ETM: The
analogous asymmetric dihydroxylation in which the cinchona
alkaloid serves as redox catalyst (via its N-oxide) as well as
chiral ligand can also be carried out using a flavin as the
hydrogen peroxide activator. The results from these asym-
metric dihydroxylations are given in Table 2. Performing the
asymmetric dihydroxylation on styrene using 2 mol% of
osmium tetroxide, 5 mol% of flavin 1 and 6 mol% of
(DHQD)2PHAL, the latter as chiral
In the next step, the olefin enters the binding pocket of the
ligand, which results in the enantioselective formation of an
osmium glycolate 4. Reoxidation of osmium(vi) can now take
place, having the active oxidant within the complex 5.
Hydrolysis of the osmium-glycolate liberates the diol and
osmium tetroxide coordinated to the ligand 2, which can re-
enter the catalytic cycle. Thus, the ligand has a dual role in the
reaction, and participates in both enantiodifferentation and
oxygen transfer. The high activity and selectivity obtained
employing this protocol suggests that the system is operating
under strict kinetic control. Thus, MTO (or the flavin)
efficiently reacts with H2O2 forming the peroxo-complexes,
which are responsible for the mono-N-oxidation of the
alkaloid ligand. OsO4 selectively reacts with the olefin
substrate (via its alkaloid complex) and the reduced form of
ligand as well as ETM, gave the styrene
diol in 75% yield and 95% ee (Table 2,
entry 1). Dihydroxylation of trans-stil-
bene (entry 2) and a-methylstyrene (en-
try 3) gave the corresponding diols in 92
and 90% ee, respectively. Interestingly,
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J.-E. B‰ckvall et al.
FULL PAPER
Table 2. Asymmetric dihydroxylation of olefins using a flavin as ETM and
H2O2 as the terminal oxidant.[a]
the major pathway. In fact, performing the dihydroxylation of
styrene under the above optimized conditions, omitting the
alkaloid ligand, resulted in the formation of the styrene glycol
in only 31% yield. Excluding OsO4 from the protocol resulted
in the formation of a complex mixture of products, where only
a small amount of the diol (< 10%) could be detected. The
latter diol is most likely the result of a nucleophilic ring-
opening reaction of the parent epoxide, formed by the MTO-
catalyst and hydrogen peroxide.
Entry Olefin
Ligand and
reoxidant[a]
Yield [%][b] ee [%][c]
1
(DHQD)2PHAL 75
(DHQD)2PHAL 89
95
92
2[d]
In
a
control experiment we demonstrated that
(DHQD)2PHAL is selectively oxidized to the mono-N-oxide
by H2O2 in the presence of catalytic amounts of MTO
[Eq. (1)] The mono-N-oxide was isolated in 89% yield and
3
4
(DHQD)2PHAL 81
(DHQD)2PHAL 61
90
99
5[e]
(DHQD)2PHAL 58
70
fully characterized. The corresponding reaction using the
flavin/H2O2 system also gave the same N-oxide.[28] Further-
more, when the isolated (DHQD)2PHAL-mono-N-oxide was
used as the stoichiometric reoxidant and chirality transfer
agent in the dihydroxylation of styrene, the corresponding
diol was formed in 71% isolated yield and 98% ee [Eq. (2)].
This supports that the major catalytic pathway in the NMM-
free H2O2-based procedure involves the mono-N-oxide.
The high enantioselectivities obtained in this protocol
suggests that the catalytic reaction predominantly proceeds
via the proposed primary cycle.[26] Hence, for mono-substi-
tuted and 1,2-disubstituted olefins there is most likely only a
[a] TEAA (2 equiv), (DHQD)2PHAL (0.06 equiv), and flavin
1
(0.05 equiv) were dissolved in tBuOH (1.88 mL) and H2O (0.62 mL).
Cooled down to 08C and OsO4 (0.02 equiv) was added followed by 1³5 of the
H2O2 (0.3 equiv, 30% aqueous). Stirred for 20 minutes, and then the olefin
(0.5 mmol, 1 equiv) and the remaining H2O2 (1.2 equiv) were added over
9 h. After complete addition of the oxidant and olefin, the mixture was
stirred for an additional 2 7 h. [b] Isolated yields. [c] Enantiomeric excess
was determined by HPLC (Daicel Chiracel OJ or ODH column, iPrOH/
hexane). [d] Acetone/H2O 4.4:1 was employed. [e] The olefin and H2O2
were added over 20 h.
the osmium catalyst is reoxidized by the ligand N-oxide.
Hence, the system brings about a mild kinetically controlled
electron transfer from the olefin to hydrogen peroxide.
Although reoxidation of osmium(vi) by either of the MTO
peroxo-complexes, or directly from hydrogen peroxide can
not be excluded, these background processes are unlikely as
Scheme 5. The proposed catalytic cycle for the enantioselective dihydroxylation of olefins using (DHQD)2PHAL for oxygen transfer to OsVI and as source
of chirality.
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Asymmetric Dihydroxylation
2783 2788
were carried out using a Sage Model 355 syringe pump. Plastic syringes and
a syringe pump Sage Model 365 were used for slow addition of H2O2.
minor involvement of the secondary catalytic cycle, where the
intermediate OsVIII glycolate is reacting with a second
equivalent of olefin prior to hydrolysis.[29] Such a secondary
cycle would lead to significantly lower enantioselectivities, as
the formation of the OsVI bis-glycolate occurs in the absence
of chiral ligand. As outlined above, the observed enantiose-
lectivities with the NMM-free H2O2-based system are com-
parable to the data previously published by Sharpless and co-
workers. On the contrary, the more reactive 1,1-disubstituted
and trisubstituted olefins substrates, that is a-methylstyrene
and 1-phenyl-1-cyclohexene, were obtained in somewhat
lower enantioselectivites. The slow osmate hydrolysis ob-
served with highly functionalized olefins suggests that, in
these specific cases, there is an involvement of the secondary
catalytic cycle. Furthermore, the structural change of the
binding pocket in the alkaloid ligand,[1b] enforced by the
formation of the mono-N-oxide, could efficiently change the
mode of olefin selectivity and thus lower the enantioselectiv-
ity for certain olefins.
The two hydrogen peroxide-based catalytic systems dis-
cussed in this paper, in which the cinchona alkaloid plays a
dual role, utilize either MTO or a flavin as the hydrogen
peroxide activating catalyst. Both systems provide an efficient
and highly selective route for the production of enantiomeri-
cally enriched vicinal diols. The selectivities obtained using
the flavin system, were in some cases slightly higher than
those with the MTO-based protocol. However, the generally
higher chemical yields obtained employing the latter system
combined with the simplicity and stability of all components
are factors favoring the MTO protocol.
All olefins were obtained from commercial suppliers and used without
further purification. Tetraethylammonium acetate tetrahydrate (TEAA,
99%), (DHQD)2PHAL (99%), H2O2 (30% aqueous), OsO4 (as a 2.5 wt%
solution in tBuOH) and methyltrioxorhenium(vii) were purchased from
Aldrich. The flavin was synthesized according to a previously published
procedure.[11]
(1R)-1-Phenyl-1,2-ethanediol–General procedure for asymmetric dihy-
droxylation of styrene using OsO4-(DHQD)2PHAL-MTO: Tetraethylam-
monium acetate (261 mg, 1 mmol), (DHQD)2PHAL (23 mg, 0.03 mmol)
and MTO (2.5 mg, 0.01 mmol) were added to a flask charged with tBuOH
(1.88 mL) and H2O (0.62 mL). The mixture was stirred and cooled to 08C
and OsO4 (125 mL, 0.01 mmol) was added, followed by 1³5 of the H2O2 (1³5 Â
1
77 mL, 30% aqueous, ³5 Â 0.75 mmol). The yellow reaction mixture was
stirred for 20 minutes and then the neat alkene (57 mL, 0.5 mmol) and the
rest of the H2O2 was added over a period of 9 h using separate syringe
pumps. After the addition was complete the resulting clear yellow solution
was stirred at 08C for an additional 2 h and then quenched by addition of
Na2S2O4 (60 mg) and magnesium silicate (120 mg). After 2 h of stirring the
mixture was diluted with ethyl acetate and filtered through a pad of Celite,
and the Celite pad was washed thoroughly with ethyl acetate. The solvent
was removed and the residue was purified by flash chromatography using a
mixture of pentane/EtOAc 80:20 to afford (1R)-1-phenyl-1,2-ethanediol
(0.062 g, 90%). Analysis by HPLC showed that the product was of 95% ee.
1H NMR (400 MHz, CDCl3): d ˆ 7.34 7.29 (m, 5H), 4.83 (dd, J ˆ 3.6,
8.0 Hz, 1H), 3.77 (d, J ˆ 10.8 Hz, 1H), 3.67 (dd, J ˆ 8.4, 11.6 Hz, 1H), 2.56
(s, 2H); 13C NMR (400 MHz, CDCl3): d ˆ 140.5, 128.6, 128.0, 126.0, 74.7,
68.1; HPLC (Daicel Chiralcel OD-H column, hexane/2-propanol 95:5, flow
rate 0.5 mLminÀ1): tR(major) ˆ 30.2 min, tR(minor) ˆ 33.0 min.
(1R)-1-Phenyl-1,2-ethanediol–General procedure for asymmetric dihy-
droxylation of styrene using OsO4-(DHQD)2PHAL-flavin: The reaction
was carried out according to the procedure described above but MTO was
replaced by flavin 1 (6.7 mg, 0.025 mmol). Workup as described above
furnished (1R)-1-phenyl-1,2-ethanediol (0.051 g, 75%). HPLC analysis of
the pure diol showed an enantiomeric excess of 95%.
Oxidation of (DHQD)2PHAL with H2O2-MTO: MTO (2.5 mg, 0.01 mmol)
was added to a stirred solution of (DHQD)2PHAL (389 mg, 0.5 mmol) in
acetone (3.76 mL) and H2O (1.24 mL) at room temperature. This stirred
mixture was cooled to 08C and H2O2 (52 mL, 30% aqueous, 0.25 mmol) was
added dropwise. Stirring continued for 19 h, during which the mixture was
allowed to warm up to room temperature. The mixture was filtered through
Celite and concentrated in vacuo to give the mono-N-oxide (0.35 g, 89%).
1H NMR (400 MHz, CDCl3): d ˆ 8.63 (d, J ˆ 4.4 Hz, 2H), 8.32 (dd, J ˆ 3.6,
6.4 Hz, 2H), 7.97 (d, J ˆ 9.2 Hz, 2H), 7.93 (dd, J ˆ 3.2, 5.6 Hz, 2H), 7.57 (d,
J ˆ 2 Hz, 2H), 7.43 (d, J ˆ 4.4 Hz, 2H), 7.34 (dd, J ˆ 2.8, 9.2 Hz, 2H), 7.05 (d,
J ˆ 5.6 Hz, 2H), 3.90 (s, 6H), 3.41 (q, J ˆ 6.4 Hz, 2H), 2.85 2.64 (m, 9H),
Conclusion
To the best of our knowledge, this is the first example of a
H2O2-based catalytic asymmetric dihydroxylation process,
relying on two homogeneously dissolved transition metal
catalysts, where the chiral ligand plays two such different and
important roles. The catalytic system is simple with a robust
electron transfer mediator (MTO) as the only added co-
catalyst. The realization of an efficient asymmetric dihydrox-
ylation process of alkenes, with a chiral amine-containing
ligand as the source of chirality and ETM, is conceptually new.
The reaction protocol based on MTO employs accessible
reagents, in combination with a simple operational setup, for
the selective dihydroxylation under mild and green conditions.
2.02 (t, J ˆ 11.6 Hz, 2H), 1.71 (s, 2H), 1.55
1
40 (m, 11H), 0.79 (t, J ˆ
6.8 Hz, 6H); 13C NMR (400 MHz, CDCl3): d ˆ 158.4, 157.7, 156.6, 156.3,
155.3, 147.2, 146.9, 144.6, 142.8, 132.2, 131.5, 127.2, 127.0, 126.0, 123.1, 122.7,
122.5, 122.4, 122.2, 121.9, 121.8, 118.4, 116.9, 102.2, 102.0, 75.9, 72.1, 68.5,
65.9, 65.6, 60.0, 59.9, 56.2, 55.7, 50.7, 49.8, 38.4, 37.2, 26.9, 26.6, 26.2, 25.6,
25.3, 25.2, 23.0, 21.1, 11.8, 11.2; mass-spectral analysis showed that the
mono-N-oxide had been generated: MS (MALDI-TOF): m/z: calcd for
‡
C48H55N6O5: 795.4234; found: 795.4261 [M‡H] .
(1R)-1-Phenyl-1,2-ethanediol–Asymmetric dihydroxylation of styrene
using OsO4-(DHQD)2PHAL-mono-N-oxide: Tetraethylammonium ace-
tate (157 mg, 0.6 mmol) and (DHQD)2PHAL-mono-N-oxide (239 mg,
0.3 mmol) were added to a flask charged with tBuOH (1.13 mL) and H2O
(0.37 mL). This stirred mixture was cooled down to 08C and OsO4 (75 mL,
0.006 mmol) was added, and then the neat alkene (34 mL, 0.3 mmol) was
added over a period of 9 h. After the addition was complete the resulting
clear yellow solution was stirred at 08C for an additional 9 h. Quenched by
addition of Na2S2O4 (36 mg) and magnesium silicate (72 mg). After 2 h of
stirring the mixture was diluted with ethyl acetate and filtered through a
pad of Celite, and the Celite bed was washed thoroughly with ethyl acetate.
The solvent was removed and the residue was purified by flash chroma-
tography using pentane/EtOAc (80:20) to afford (1R)-1-phenyl-1,2-etha-
nediol (0.030 g, 71%). Analysis by HPLC showed that the product was of
98% ee.
Experimental Section
General methods: 1H and 13C NMR spectra were recorded on a Varian
Unity 400 (400 MHz 1H, 100 MHz 13C) spectrometer. Chemical shifts (d)
are reported in ppm, using residual solvent as internal standard and
coupling constants (J) are given in hertz. Merck silica gel 60 (240
400 mesh) was used for flash chromatography, and analytical thin-layer
chromatography was performed on Merck precoated silica gel 60-F254
plates. Analytical high-pressure liquid chromatography (HPLC) was
performed on a Waters liquid chromatograph using a Daicel Chiralcel
OD-H column or a Daicel Chiracel OJ column. Mass-spectra were
recorded on a Bruker BIFLEX MALDI-TOF. Slow additions of olefins
Chem. Eur. J. 2003, 9, 2783 2788
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¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2787

J.-E. B‰ckvall et al.
FULL PAPER
(R,R)-1,2-Diphenyl-1,2-ethanediol: 1H NMR (400 MHz, CDCl3): d ˆ
7.24 7.12 (m, 10H), 4.72 (s, 2H), 2.83 (brs, 2H); 13C NMR (400 MHz,
CDCl3): d ˆ 139.8, 128.1, 127.9, 126.9, 79.1; HPLC (Daicel Chiralcel OJ
column, hexane/2-propanol 90:10, flow rate 1.0 mLminÀ1): tR(minor) ˆ
11.3 min, tR(major) ˆ 12.2 min.
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(2R)-2-Phenylpropane-1,2-diol: 1H NMR (400 MHz, CDCl3): d ˆ 7.47
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74.5, 38.5, 29.2, 24.3, 21.1; HPLC (Daicel Chiralcel OJ column, hexane/2-
propanol 90:10, flow rate 1 mLminÀ1): tR(minor) ˆ 8.0 min, tR(major) ˆ
9.8 min.
¬
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Financial support from the Swedish Research Council, the Swedish
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for Strategic Research is gratefully acknowledged. We would like to thank
Dr. Martina Lahmann for recording the MALDI-TOF spectra.
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Received: February 7, 2003 [F4828]
2788
¹ 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2003, 9, 2783 2788