Efficient Osmium/Rhenium-Catalyzed Dihydroxylation of Olefins with Hydrogen Peroxide under Acidic Conditions

Article abstract of DOI:10.1002/adsc.200303043

Simple addition of citric acid confers great stability to the catalytically active osmium and rhenium species involved in a triple catalytic system utilizing aqueous hydrogen peroxide as the terminal oxidant. The resulting system is capable of dihydroxyla

Full text of DOI:10.1002/adsc.200303043

FULL PAPERS
Efficient Osmium/Rhenium-Catalyzed Dihydroxylation of Olefins
with Hydrogen Peroxide under Acidic Conditions
¬
Alida H. Ell, Adam Closson, Hans Adolfsson, Jan-E. B‰ckvall*
Department of Organic Chemistry, Stockholm University, 10691 Stockholm, Sweden
Fax: ( ‡ 46)-8-154908, e-mail: jeb@organ.su.se
Received: February 2, 2003; Accepted: April 17, 2003
Abstract: Simple addition of citric acid confers great ylating traditionally resistant olefins in high yields.
stability to the catalytically active osmium and
rhenium species involved in a triple catalytic system
utilizing aqueous hydrogen peroxide as the terminal Keywords: alkenes; dihydroxylation; homogeneous
oxidant. The resulting system is capable of dihydrox- catalysis; osmium; oxidation
Introduction
NMM[6c], but it is unstable in basic reaction media under
oxidizing conditions, decomposing into methanol and
[
7]
The osmium-catalyzed dihydroxylation of olefins is one catalytically inert perrhenic acid. Unfortunately, this
of the most useful oxidation reactions in organic MTO deactivation may occur in the H O -based dihy-
2
2
synthesis.[ The reaction is highly specific, and easy to droxylation reaction, as the necessary presence of
carry out. In this redox process, osmium(VIII) is tertiary amine makes the reaction mixture basic. Careful
reduced to osmium(VI) through reaction with an olefin control of the amount of tertiary amine used has been
to yield an osmium(VI) glycolate. The latter is then vital to successfully utilize MTO as an ETM in this
hydrolyzed to yield a diol. A catalytic amount of osmium process.[6d]
1]
may be used if an appropriate reoxidant is present, that
Major classes of substrates still pose problems in the
can oxidize osmium(VI) back to the active osmium(VIII). catalytic dihydroxylation reaction. Among these are
Typical reoxidants for osmium used in catalytic reac- a,b-unsaturated esters and amides, as well as sterically
[
8]
tions are N-methylmorpholine N-oxide (Upjohn reac- encumbered or tetrasubstituted olefins. In a recent re-
tion)[ and potassium ferricyanide, commonly used in examination of the Os-catalyzed dihydroxylation reac-
2]
[
3]
the asymmetric dihydroxylation reaction. Work in our tion, Sharpless and co-workers reported that citric acid,
group has focused on allowing the use of H O as the when added to the reaction mixture, greatly improved
2
2
terminal reoxidant in the dihydroxylation reaction. yields of diol from these normally recalcitrant com-
Hydrogen peroxide is attractive as a terminal oxidant
[
4]
because it is inexpensive and environmentally friendly.
Hydrogen peroxide may be used as adirect reoxidant for
[5]
Os(VI) in dihydroxylation reactions, but in most cases
this results in overoxidation and non-selective reactions.
Our solutions to this problem have revolved around the
use of organic or inorganic compounds as electron
[
6]
transfer mediators (ETMs). This biomimetic approach
couples the oxidation of the ETM by hydrogen peroxide
witht he following oxidation of a tertiary amine (for
example, N-methylmorpholine) to its N-oxide. The N- Scheme 1. Triple catalytic system applied to dihydroxylation.
oxide can then reoxidize Os(VI) to Os(VIII)
(
Scheme 1).
Specific ETMs that we have used for the N-oxidation
of NMM in this triple catalytic system include flavin
analogues[
6a, b]
of type 1, vanadyl acetylacetonate[6c]
[
(
VO(acac) , 2], and methyltrioxorhenium (MTO, 3)
2
Figure 1).[
6c, d]
Each of these ETMs has its own advan-
tages and drawbacks. For example, MTO rapidly and
efficiently catalyzes the reaction between H O and Figure 1. Electron transfer mediators (ETMs).
2
2
1012
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI:10.1002/adsc.200303043
Adv. Synth. Catal. 2003, 345, 1012 ± 1016

Os/Re-Catalyzed Dihydroxylation of Olefins
FULL PAPERS
pounds.[9] The authors attribute this effect to low pH Upjohn conditions. Sharpless and co-workers reported
blocking the major OsO4 decomposition pathway. an improvement to 78% in the modified Upjohn
[
9]
Under conditions where reoxidant has access to all the procedure (25 mol % citric acid). In our initial studies
catalytic intermediates, turnover is achieved only a reaction mixture consisting of olefin, 75 mol % citric
[
10]
through the second cycle (Scheme 2). They propose acid, 1 mol % K OsO ¥ 2 H O, 1 mol % MTO, and
2
4
2
that a major loss of catalytic osmium is through the 20 mol % NMM was dissolved in a 1:1 mixture of
deprotonation of bis-glycolate intermediate c, found in water/t-BuOH. Hydrogen peroxide (1.2 equivalents)
the second cycle, which results in the formation of the was then added over a period of four hours via a syringe
inert osmium dianion d. This therefore explains the poor pump. The yield of diol obtained by this method was
reactivity of electron-deficient olefins, for example, as 95% (Table 1, entry 1). Increasing the concentration of
intermediate c would be easier to deprotonate than the reaction mixture from 1 M to 2 M allowed the
usual. The low pH conferred by the presence of citric reduction of osmium present to 0.5 mol %, without a
acid would keep osmium from being trapped via substantial difference in yield (Table 1, entry 5). Control
intermediate d, and lead to increased yield by preserving reactions run without NMM or MTO (entries 2 and 3)
the catalyst. We noted that these reaction conditions resulted in lower yields, indicating that although the
would be beneficial not only for the conservation of direct reoxidation of osmium by H O is possible under
2
2
OsO , but also for MTO, which becomes more stable at a these conditions, it is beneficial to utilize the triple
4
[7]
low pH. We therefore decided to apply this modifica- catalytic system. The conditions used for entry 5 were
tion to the H O /MTO/NMM triple catalytic system. then applied to a number of other substrates which are
2
2
Not only would the MTO be more resistant towards known to be problematic, for example, those bearing
hydrolysis under these reaction conditions, but it would common electron-withdrawing functional groups such
greatly enhance the usefulness of the H O -based as ester and amide moieties. We also included styrene as
2
2
dihydroxylation reaction if a similar improvement in a ™standard∫ substrate. Table 2 shows the results. Yields
the reactivity towards these important substrate classes of diols obtained from the esters and styrene are high
could be obtained.
(82 ± 93%), while the yield of diol from amide 6 was a bit
lower (67% conversion).
Presented with these results, we realized that the
75 mol % of citric acid is optimal for the stoichiometric
NMO reoxidation of osmium because NMM, which
Results
We chose first to examine the dihydroxylation of allyl neutralizes citric acid, slowly accumulates during the
phenyl sulfone 4 witht eh H O /MTO/NMM triple reaction, eventually reaching high concentrations. How-
2
2
catalytic system (Table 1). This olefin is reported in the ever, in our system, only small amounts of NMM are
literature to yield under 40% of diol using standard present. We therefore decided to limit the amount of
Scheme 2. The two possible pathways of dihydroxylation.
Adv. Synth. Catal. 2003, 345, 1012 ± 1016
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¬
FULL PAPERS
Alida H. Ell et al.
Table 1. Reaction conditions for dihydroxylation of 4.[a]
Entry
K OsO ¥ 2
MTO
NMM
Conc.
H O addition time
Yield [%][b]
2
4
2
2
H O [mol %]
2
[mol %]
[mol %]
of 4
‡ stirring [h]
1
2
3
4
5
6
7
1
1
1
0
0.5
0.5
0.5
1
1
0
1
1
1
1
20
0
0
1 M
1 M
1 M
1 M
2 M
2 M
2 M
4 ‡ 1
95
62
65
0
4 ‡ 1
4 ‡ 1
0
4 ‡ 1
20
20
20
4 ‡ 1
91
87[
c]
Addition at once
Addition at once[
d]
[c]
88
[
a]
Reaction conditions: olefin (1 mmol) was dissolved in 1: 1 t-BuOH:H O, other reaction components added as indicated.
2
H O solution (1.2 equiv.) added via syringe pump over 4 hw he n indicated.
Isolated yield.
Percent conversion.
2
2
[
[
[
b]
c]
d]
1
.5 equivalents of H O .
2 2
citric acid to the lowest possible levels. Dihydroxylations Table 2. Yields of diols under various conditions.[a]
were carried out again withamide 6 and 5 mol % of
citric acid (Table 2). Reaction time was lengthened and
one equivalent of tetraethylammonium acetate
[
11]
(
TEAA) was added to facilitate hydrolysis. Under
these conditions the diol could be obtained in 84% yield.
The rest of the substrates were then resubmitted to
dihydroxylation with 5 mol % of citric acid, and the
results were comparable to those obtained with
7
5 mol % (Table 2). Control reactions run without citric
acid with allyl phenyl sulfone and ethyl crotonate as
substrates resulted in yields of 60% and 47% of the diol,
respectively.
As a final test of functional group tolerance of the
optimal conditions, sulfonamide 7 was subjected to
dihydroxylation using 5 mol % citric acid and the longer
reaction time.[ The yield is shown in Table 2. A
possible explanation for the difference in yields for
amides is that with 75% citric acid present, the small
amount of NMM used in our system may become almost
completely protonated. This would result in slower
turnover as the system depends on NMM being oxidized
to NMO in situ, as well as the possibility of direct
oxidation of the substrate by free H O .
12]
[a]
Reaction conditions: olefin (1 mmol) in 0.5 mL 1: 1 t-
BuOH:H O, 0.5 mol % K OsO ¥ 2 H O, 1 mol % MTO,
2
2
4
2
2
2
2
0 mol % NMM, H O added over 1 h, followed by 1 h
2 2
stirring before quenching with 60 mg Na S O and 120 mg
2
2
4
magnesium silicate.
Isolated yields.
Percent conversion; 1 equiv. TEAA, H O added over 4 h,
followed by 1 hstirring before quenc hi ng.
1 equiv. TEAA, H O added over 4 h, followed by 1 h
stirring before quenching.
Reaction carried out at 0.66 M in 2: 1 acetone:H O, H O
added over 4 h, followed by 8 h stirring.
Conclusion
[b]
[
[
[
c]
d]
e]
2
2
The simple addition of citric acid to dihydroxylation
reaction mixtures has several advantages. Under these
conditions MTO is stabilized, which allows its use as an
ETM in conjunction with hydrogen peroxide. Further-
more, the resulting low pH preserves osmium catalyst,
and thus improves the yield of diols from traditionally
difficult substrate classes. The result of the application of
2
2
2
2
2
1014
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Os/Re-Catalyzed Dihydroxylation of Olefins
FULL PAPERS
citric acid to our triple catalytic system is a robust and to quench the reaction. The resulting slurry was stirred for 2 h
to ensure the reduction of all Os species, diluted with ethyl
effective hydrogen-peroxide based system for dihydrox-
acetate, and loaded directly onto a silica gel column. The
ylation of olefins.
product diol was eluted using ethyl acetate, affording a white
1
solid; yield: 210 mg (84%); H NMR (400 MHz, CDCl ): d ˆ
3
7
6
3
2
.42 ± 7.30 (m, 5H), 4.76 ± 4.72 (br s, 2H), 4.67 (d, 1H, J ˆ
.5 Hz), 4.37 (d, 1H, J ˆ 6.5 Hz), 3.65 ± 3.55 (m, 2H), 3.55 ±
.44 (m, 2H), 3.40 ± 3.32 (m, 1H), 3.15 ± 3.05 (m, 1H), 2.98 ±
Experimental Section
1
3
.90 (m, 1H), 2.70 ± 2.61 (m, 1H). C NMR (100 MHz, CDCl ):
3
d ˆ 170.64, 138.97, 128.85, 128.80, 127.06, 76.70, 72.57, 66.55,
General Methods
6
6.04, 45.67, 42.75.
1
13
H and C NMR spectra were recorded on a Varian Unity 400
1
13
(
400 MHz H, 100 MHz C) spectrometer. Chemical shifts (d)
are reported in ppm, using residual solvent as internal stand-
ard. Millipore Matrex silica gel (60 ä pore size, 35 ± 70 mm) was
used for flash chromatography. Potassium osmate and tetra-
ethylammonium acetate (TEAA) were purchased from Al-
Dihydroxylation of Sulfonamide 7
The substrate 7 (101 mg, 0.29 mmol, 0.66 M) was dissolved in
0
.43 mL of 1:2 H O:acetone. Citric acid (3 mg, 5 mol %) was
2
drich. Olefins 6 and 8 were prepared according to published
dissolved in the reaction mixture. Potassium osmate (0.5 mg,
.5 mol %) was then added to the solution. This was followed
by 0.7 mg MTO (1 mol %) and N-methylmorpholine (5.5 mg,
procedures.[
12,13]
All other reagents and olefins were obtained
0
from commercial suppliers and used without further purifica-
tion.
2
0 mol %). To this mixture a H O solution (0.34 mmol,
2 2
0
.036 mL 30.3% solution) was injected over a 4 hperiod via a
syringe pump. After stirring for an additional 8 h, the insoluble
product could be isolated as a white solid by a simple filtration;
yield: 98 mg (88%) as a 2:1 mixture of diastereoisomers; H
Representative Procedure for Dihydroxylation of
Ester-Substituted Olefins (Procedure A), as
Exemplified for Ethyl Crotonate
1
NMR (400 MHz, CDCl ): major diastereoisomer, d ˆ 7.39 (d,
3
J ˆ 8.1 Hz, 2H), 7.14 ± 6.92 (m, 7H), 5.82 (d, J ˆ 10.6 Hz, 1H),
4.69 (d, J ˆ 10.6 Hz, 1H), 3.85 (s, 3H), 3.68 (d, J ˆ 11.6 Hz, 1H),
3.21 (d, J ˆ 11.6 Hz, 1H), 2.27 (s, 3H); minor diastereoisomer,
d ˆ 7.38 (d, J ˆ 9.6 Hz, 2H), 7.14 ± 6.92 (m, 7H), 5.92 (d, J ˆ 10.4
Water (0.25 mL) and t-BuOH (0.25 mL) were combined in a
small round-bottom flask witha small stir bar. Citric acid
(
(
5 mol %, 9.6 mg) was then added, followed by ethyl crotonate
114 mg, 1 mmol), and potassium osmate (1.8 mg, 0.5 mol %).
Hz, 1H), 4.68 (d, J ˆ 10.4 Hz, 1H), 4.097 (d, J ˆ 12 Hz (H of
A
Methyltrioxorhenium (2.4 mg, 1.0 mol %) and N-methylmor-
pholine (20.2 mg, 20 mol %) were then added to the solution.
Hydrogen peroxide solution (1.2 mmol, 0.124 mL 30.3%
solution) was injected into the solution over a period of 1 h
via a syringe pump. The solution was allowed to stir for a
further 1 h after addition was completed. The reaction was then
quenched via the addition of sodium dithionite (60 mg) and
magnesium silicate (120 mg). The resulting slurry was stirred
for 2 h in order to ensure the reduction of all the Os species,
diluted withethyl acetate, and loaded directly onto a silica gel
column. The product diol was eluted using ethyl acetate,
AB system), 1H), 4.030 (d, J ˆ 12 Hz (H of AB system), 1H),
B
1
3
3.61 (s, 3H), 2.26 (s, 3H); C NMR (75 MHz, CDCl ): d ˆ
3
173.65, 142.99, 137.22, 135.39, 129.10, 128.20, 127.99, 127.85,
126.92, 81.18, 65.78, 59.92, 53.78, 21.33. Minor diastereomer
distinguishible at 172.7, 137.13, 128.15, 128.03, 127.4, 126.83,
81.4, 65.84, 59.27, 53.09.
Dihydroxylation of Allyl Phenyl Sulfone
1
See procedure A. Yield: 202 mg (93%) of white solid; H NMR
1
affording a white solid; yield: 133 mg (90%); H NMR
(400 MHz, CDCl ): d ˆ 7.96 ± 7.92 (m, 2H), 7.71 ± 7.66 (m, 1H),
3
(
400 MHz, CDCl ): d ˆ 4.29 (q, 2H, J ˆ 7 Hz), 4.07 (qd, 1H
7.62 ± 7.52 (m, 2H), 4.28 ± 4.22 (m, 1H), 3.70 (dd, 1H, J ˆ 11.8,
4 Hz), 3.55 (dd, 1H, J ˆ 11.4, 4.9 Hz), 3.39 (dd, 1H, J ˆ 14.1,
3
J ˆ 6, 3 Hz), 4.00 (d, 1H, J ˆ 3 Hz), 2.96 ± 2.61 (br s, 2H), 1.31 (d,
[14]
13
3
H, J ˆ 6 Hz), 1.31 (t, 3H, J ˆ 7 Hz).
9 Hz), 3.25 (dd, 1H, J ˆ 14.3, 2.4 Hz); C NMR (100 MHz,
[9]
CDCl ): d ˆ 139.37, 134.37, 129.73, 128.14, 66.83, 65.60, 59.22.
3
Dihydroxylation of Amide 6
Dihydroxylation of Ethyl Cinnamate
Water (0.25 mL) and t-BuOH (0.25 mL) were combined in a
1
small round-bottom flask witha small stir bar. Citric acid
See procedure A. Yield: 176 mg (84%) of white solid; H NMR
(
2
(
5 mol %, 9.6 mg) and tetraethylammonium acetate (1 mmol,
61 mg) were then dissolved in the solvent mixture. Amide 6
217 mg, 1 mmol) was then added to the solution, followed by
(400 MHz, CDCl ): d ˆ 7.4 ± 7.3 (m, 5H), 4.97 (d, 1H, J ˆ 3 Hz),
3
4.33 (d, 1H, J ˆ 3.2 Hz), 4.23 (q, 2H, J ˆ 7.3 Hz), 3.30 ± 3.04 (br
1
3
s, 2H), 1.25 (t, 3H, J ˆ 7.2 Hz); C NMR (100 MHz, CDCl ):
3
potassium osmate (1.8 mg, 0.5 mol %) and methyltrioxorhe-
nium (2.4 mg, 1.0 mol %). N-Methylmorpholine (20.2 mg,
d ˆ 172.97, 140.19, 128.65, 128.26, 126.53, 74.99, 74.82, 62.36,
14.28.[
14]
20 mol %) was then dissolved in the reaction flask. Hydrogen
peroxide (1.2 mmol, 0.124 mL 30.3% solution) was injected
into the solution over a period of 4 h via a syringe pump. The
reaction mixture was allowed to stir a further 1 h after the
addition of peroxide was completed. After this time, sodium
dithionite (60 mg) and magnesium silicate (120 mg) was added
Dihydroxylation of Diethyl Fumarate
1
See procedure A. Yield: 175 mg (85%) of white solid; H NMR
(400 MHz, CDCl ): d ˆ 4.53 (s, 2H), 4.31 (q, 4H, J ˆ 7.1 Hz),
3
Adv. Synth. Catal. 2003, 345, 1012 ± 1016
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¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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¬
FULL PAPERS
Alida H. Ell et al.
3
.7 ± 3.1 (br s, 2H), 1.32 (t, 6H, J ˆ 7 Hz); 13C NMR (100 MHz,
nier, J. T. Nolan, M. I. Iliopulos, J. Am. Chem. Soc. 1959,
81, 4730.
[15]
CDCl ): d ˆ 171.77, 72.21, 62.71, 14.35.
3
[
6] a) K. Bergstad, S. Y. Jonsson, J.-E. B‰ckvall, J. Am.
Chem. Soc. 1999, 121, 10424; b) S. Y. Jonsson, K.
F‰rnegardh, J.-E. B‰ckvall, J Am. Chem. Soc. 2001,
Dihydroxylation of Styrene
¬
1
23, 1365; c) A. H. Ell, S. Y. Jonsson, A. Bˆrje, H.
Adolfsson, J.-E. B‰ckvall, Tetrahedron Lett. 2001, 42,
569; d) S. Y. Jonsson, H. Adolfsson, J.-E. B‰ckvall,
1
See procedure A. Yield: 113 mg (82%) of white solid; H NMR
(
3
400 MHz, CDCl ): d ˆ 7.3 ± 7.2 (m, 5H), 4.8 (dd, 1H, J ˆ 8.4,
3
2
1
3
.6 Hz), 3.7 ± 3.6 (m, 2 h), 3.4 ± 3.0 (br, 2H); C NMR
Chem. Eur. J. 2003, in press; e) S. Y. Jonsson, H.
Adolfsson, J.-E. B‰ckvall, Org. Lett. 2001, 3, 3463.
7] M. M. Abu-Omar, P. J. Hansen, J. H. Espenson, J. Am.
Chem. Soc. 1996, 118, 4966.
(
6
100 MHz, CDCl ): d ˆ 140.46, 128.47, 127.91, 126.04, 74.67,
3
8.04.[16]
[
[
[
8] Y. L. Bennani, K. B. Sharpless, Tetrahedron Lett. 1993,
Acknowledgements
3
4, 2079.
9] P. Dupau, R. Epple, A. A. Thomas, V. V. Fokin, K. B.
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10] a) J. S. M. Wai, I. Marko, J. S. Svendsen, M. G. Finn, E. N.
Financial support from the Swedish Research Council for
Engineering Sciences, the Swedish Research Council, and the
Swedish Foundation for Strategic Research is gratefully ac-
knowledged.
[
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¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2003, 345, 1012 ± 1016