Methyltrioxorhenium-catalysed epoxidation of alkenes: Enhancement of reactivity in hexafluoro-2-propanol

Article abstract of DOI:10.1016/S0040-4039(01)02316-4

Methyltrioxorhenium-catalysed epoxidation of alkenes with hydrogen peroxide can be improved by using hexafluoro-2-propanol as a solvent. Quantitative conversions of cyclic and terminal olefins can be obtained with only 30% H₂O₂ and 0.1 mol% of catalyst.

Full text of DOI:10.1016/S0040-4039(01)02316-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 1001–1003
Methyltrioxorhenium-catalysed epoxidation of alkenes:
enhancement of reactivity in hexafluoro-2-propanol
Jernej Iskra, Danie`le Bonnet-Delpon and Jean-Pierre Be´gue´*
BIOCIS, Faculte´ de Pharmacie, Universite´ Paris-Sud, rue J. B. Cle´ment, Chaˆtenay-Malabry, F-92296 Cedex, France
Received 26 November 2001; revised 3 December 2001; accepted 5 December 2001
Abstract—Methyltrioxorhenium-catalysed epoxidation of alkenes with hydrogen peroxide can be improved by using hexafluoro-2-
propanol as a solvent. Quantitative conversions of cyclic and terminal olefins can be obtained with only 30% H2O2 and 0.1 mol%
of catalyst. © 2002 Elsevier Science Ltd. All rights reserved.
In the course of our study on oxidation reactions in
fluorous phase, we have reported that the activity of
hydrogen peroxide is markedly increased when reac-
tions are performed in fluorous alcohols, in particular
in hexafluoroisopropanol (HFIP).1 Neumann2 and
Sheldon3 took advantage of such an activating effect
for epoxidation reactions with H2O2 in HFIP without
any catalyst. However, the use of 60% H2O2 at reflux is
needed for good conversions, which is evidently a great
drawback for a safe protocol.
of HFIP. After 1 h stirring at room temperature, the
19F NMR spectrum was recorded and only the signal of
HFIP was observed. Further, stability of the peroxo
form of MTO in HFIP and TFE was compared. MTO
(1 mg) was dissolved in 2 mL of solvent, 1 mL of 30%
H2O2 was added and the solution was stirred at room
temperature. The yellow colour of the solution indicates
the presence of the active form of catalyst. In TFE a
colourless solution was obtained within 1 h, while in
HFIP, the catalyst decomposed only after 6 h. A simi-
lar experiment was performed in the presence of pyra-
zole and the catalyst was active for 3 h in TFE and 10
h in HFIP.
Recently, it was published that with the addition of
methyltrioxorhenium (MTO) as catalyst,4 epoxidations
in trifluoroethanol (TFE) could be efficiently performed
at room temperature.5 In comparison to reactions per-
After these verifications, we first investigated the epoxi-
dation of cyclooctene using 2 equivalents of 30% H2O2,
only 0.1 mol% of MTO as catalyst and 10 mol% of
pyrazole as ligand at 0°C in different solvents. The
conversion of the alkene into epoxide was followed by
GC chromatography. As can be seen from Fig. 1, the
epoxidation in CH2Cl2 was not complete after 4 h,
while the reaction in trifluoroethanol (TFE) was easier
and the oxirane was quantitatively formed after 4 h.
When performed in HFIP, epoxidation was even faster
than in TFE and complete conversion was obtained
within 1 h.9 This reaction time was obtained in TFE
only with 60% H2O2.5 In HFIP, a complete conversion
could also be obtained with only 1.2 equivalent of 30%
H2O2. We then explored the influence of added ligand.
When reducing the amount of pyrazole to 5 mol%,
conversion was also complete in 2 h; using only 1 mol%
the epoxidation drastically decreased, confirming the
role of the basic ligand not only on the acidity of the
catalyst but also on its stability.6a
6
formed in CH2Cl2 the amount of catalyst could be
reduced from 0.5 to 0.1 mol%. However, the protocol
still requires the use of 60% hydrogen peroxide (two
equivalents). Since HFIP is a better hydrogen bond
donor (h=1.96) than TFE (h=1.51),7 and a more
dissociative one (Y=3.61 and 1.80, respectively),8 we
tried to find mild conditions for epoxidation by
combining the powerful catalyst MTO and HFIP as a
strong activator of H2O2.
Before investigation of epoxidation reactions, the sta-
bility of HFIP in the MTO/H2O2 oxidative system, and
the stability of the MTO/H2O2 catalyst in HFIP have
been evaluated. In order to see whether HFIP can be
oxidized in this system, we added 0.45 mL of 30% H2O2
into a solution of 10 mg of MTO (0.04 mmol) in 1 mL
* Corresponding author. Tel.: 33 1 46 83 57 38; fax: 33 1 46 83 57 40;
e-mail: jean-pierre.begue@cep.u-psud.fr
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02316-4

1002
J. Iskra et al. / Tetrahedron Letters 43 (2002) 1001–1003
Figure 1. (left) The effect of solvent on epoxidation of cyclooctene: 4 mmol cyclooctene, 0.1 mol% MTO, 10 mol% pyrazole, 8
mmol 30% H2O2, 2 mL solvent, 0°C. (right) Reactions with different amounts of pyrazole in HFIP.
MTO ligand plays an important role in the stability of
the catalyst,6a we used 2,2%-bipyridine as a ligand
instead of pyrazole for this two substrates.10 This
resulted in a quantitative conversion to the oxirane,
again in 1 h at 0°C. The reaction of limonene occurred
only at the cyclic double bond and diastereoisomers
were formed in a 1.3:1 ratio (according to GC analysis).
In the reaction with a-pinene, styrene and indene, all
starting material was consumed; however, resulting
epoxides were not stable during reaction. Despite the
Having established that the use of HFIP as a solvent
for the epoxidation with MTO/30%H2O2 system is very
promising, we have extended its application to various
key alkenes. Cyclic alkenes (cyclooctene, 1-(3-cyclohex-
ene)methanol) were reactive and oxiranes were quanti-
tatively formed within 1 h at 0°C (Table 1). However,
with cyclic trisubstituted alkenes such as 1-methylcyclo-
hexene and limonene, the catalyst decomposed (as indi-
cated by disappearance of the yellow colour) and the
epoxidation was not complete. Since the structure of
Table 1. Epoxidation of alkenes by MTO/30% H2O2 in HFIPa

J. Iskra et al. / Tetrahedron Letters 43 (2002) 1001–1003
1003
low nucleophilicity of HFIP, which can even be used as
Acknowledgements
a solvent in oxirane ring-opening by nucleophiles,11
these three acid-sensitive epoxides underwent the ring-
opening leading to a mixture of compounds, as already
observed in similar reactions.
This research has been supported by a Marie Curie
Fellowship (J.I.) of the European Community program
Human Potential under contract number HPMF-CT-
1999-00097. We thank the European Union (COST-
program ‘Fluorous Medium’ D12/98/0012, Research
Training Network ‘Fluorous Phase’ HPRN CT 2000-
00002). Central Glass Company is acknowledged for a
kind gift of HFIP.
Finally, reactivity of less reactive terminal aliphatic
alkenes was assessed. The methyl ester of 1-undecen-10-
oic acid was quantitatively converted into the corre-
sponding epoxide with 0.1 mol% of MTO and 10 mol%
of pyrazole at room temperature in 1 day. The presence
of the free acid functionality is also compatible with
this epoxidation method (entry 6, 6 h at room
temperature).
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