An efficient and robust fluoroketone catalyst epoxidation

Article abstract of DOI:10.1016/S0040-4039(01)00751-1

The fluoroalkylketone 2 is an efficient catalyst in the epoxidation reaction using Oxone as oxidant. In hexafluoro-2-propanol (HFIP), the ketone can be used in a catalytic amount (1 or 5 mol%) with only 1.5 equiv. of Oxone. The reaction gave good yields o

Full text of DOI:10.1016/S0040-4039(01)00751-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4463–4466
An efficient and robust fluoroketone catalyst epoxidation
Julien Legros, Benoˆıt Crousse,* Jack Bourdon, Danie`le Bonnet-Delpon and Jean-Pierre Be´gue´
BIOCIS, CNRS, Faculte´ de Pharmacie, Rue J.B. Cle´ment, 92296 Chaˆtenay-Malabry, France
Received 12 March 2001; revised 17 April 2001; accepted 6 May 2001
Abstract—The fluoroalkylketone 2 is an efficient catalyst in the epoxidation reaction using Oxone® as oxidant. In hexafluoro-2-
propanol (HFIP), the ketone can be used in a catalytic amount (1 or 5 mol%) with only 1.5 equiv. of Oxone®. The reaction gave
good yields of epoxides for a number of olefin substrates, included low reactive ones. © 2001 Elsevier Science Ltd. All rights
reserved.
Dioxiranes have been shown to be remarkably promis-
ing oxidation reagents for the epoxidation of olefins.1
At first we envisaged using a non volatile ketone bear-
ing a long perfluorochain instead of the CF3 group. We
chose the ketone 1 (C7F15COCH3: bp 120°C) already
described in the literature.7
Dimethyldioxirane2
and
methyl(trifluoromethyl)-
dioxirane3 are the most widely used. They are generated
from the parent ketone with Oxone® and can be used in
situ,4 or isolated.3 Methyl(trifluoromethyl)dioxirane
exhibits the highest reactivity among dioxiranes
reported so far. However, the starting trifluoroacetone
is expensive, volatile (22°C) and until recently it was
used in excess. Consequently, efforts have been focused
to improve the use of trifluoroacetone and other
fluoroalkylketones as catalysts in epoxidation reactions
in the presence of hydrogen peroxide or Oxone®.1g–i,5,6
We present here our results on a new fluoroalkylketone,
which is particularly stable and efficient in the dioxi-
rane-mediated epoxidation reaction.
The potency of the ketone 1 was evaluated in the
epoxidation reaction of cyclooctene and dodecene. The
reaction was conducted using one equivalent of ketone
1 in homogeneous conditions (MeCN/water)8 in the
presence of NaHCO3 and 5 equivalents of Oxone® was
added by syringe pump over 2 h (Table 1).
Under these conditions, and despite the low solubility
of ketone 1 in MeCN/water, conversion to epoxide was
complete. Epoxides were isolated in high yield (:90%).
Table 1. Epoxidation reaction in MeCN–water with ketones 1 or 2
Olefin
Ketone
Time (h)a
Epoxide/olefin
Recovered ketoneb
Yield (%)c
Cyclooctene
Dodecene
Cyclooctene
Dodecene
1
1
2
2
2
4
1
2
100/0
100/0
100/0
100/0
Traces
Traces
\98
96
89
96
90
\98
a After slow addition of Oxone®.
b Determined by GC and 1H NMR of the crude mixture.
c Isolated yield.
* Corresponding author. Fax: 33 1 46 83 57 40; e-mail: benoit.crousse@cep.u-psud.fr
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00751-1

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J. Legros et al. / Tetrahedron Letters 42 (2001) 4463–4466
However, according to GC and 1H NMR analysis,
after completion of the reaction the ketone 1 was
present only in trace amounts. Although the Baeyer–
Villiger oxidation is the likely decomposition path-
way, no ester could be detected in the crude product.
The aqueous phase was then acidified and work-up
afforded the acid C7F15CO2H (mp: 55–56°C). This
clearly shows that as soon as the ketone catalyst
bears a methyl substituent, the Baeyer–Villiger process
largely affects the ketone stability. This is consistent
with earlier observations concerning trifluoroacetone
procedures and the fact explains that accurate and
specific conditions had to be found to decrease the
amount of catalyst.5,6
Under the same conditions as previously described
with ketone 1, cyclooctene and dodecene reacted
quantitatively with one equivalent of ketone 2 in the
presence of 5 equivalents of Oxone®, affording the
corresponding epoxide. After reaction the ketone 2
was totally present in the crude mixture. No decom-
position of the ketone 2 was observed (Table 1).
We could thus explore the reaction using a catalytic
amount of ketone 2. With 10% of ketone 2, the reac-
tion required a greater quantity of Oxone® (10
equiv.), a longer addition time (4 h) and a longer
reaction time. However, all cyclooctene could be con-
verted into epoxide which could be isolated in 94%
yield. Interestingly, this ketone 2 was also efficient in
affording the epoxide of the poor reactive dodecene
in 79% yield (Table 2).
A solution to avoid the catalyst decomposition was to
design a more stable ketone. A ketone bearing both a
CF3 group and an alkyl group deactivated by an elec-
tron-withdrawing substituent (for example a perfluoro
chain) seemed to be a good candidate: the CF3 group
should maintain the high oxidative potency, and the
electron-withdrawing substituent of the alkyl moiety
In a search for improving the reactivity, we took into
account the great advantages of fluorinated alcohols
in oxidation reactions.11 We thus explored the epoxi-
dation of alkenes using hexafluoro-2-propanol (HFIP)
as a solvent instead of acetonitrile.
should deactivate the development of
a positive
charge on a and b carbons, and hence the migratory
aptitude required for the Baeyer–Villiger process.9
Based on these considerations, the ketone 2 was pre-
pared and tested in an epoxidation reaction.
Reactions of a variety of olefins with ketone 2 in the
presence of Oxone® in HFIP are described in Table
3. Only 1.5 equivalents of Oxone® and 6 equivalents
of NaHCO3 were required to obtain 100% of conver-
sion, and the reaction was faster. Cyclic, acyclic,
trans-, cis-, disubstituted, trisubstituted and even ter-
minal olefins could be epoxidized in good yields. For
those more reactive substrates, the epoxidation was
complete using 1 mol% ketone. Only the usually
poorly reactive substrates required 5 mol% ketone to
gain a high conversion. As expected, in the case of
the limonene, the epoxidation occurred selectively on
the trisubstituted double bond with 90% conversion
(entry 2), and a 1:1 mixture of diastereoisomers was
obtained. The use of HFIP as solvent in the dioxi-
The ketone 2 was prepared according to Guerrero’s
conditions,10 by reacting the corresponding iodide
with ethyl trifluoroacetate in the presence of tBuLi
(89%) (Scheme 1).
rane-mediated epoxidation reaction gave
a great
improvement in efficiency, probably due to a better
solubility of ketone 2 in this solvent.
Scheme 1. Preparation of ketone 2.
In summary, we have found an efficient dioxirane-
mediated epoxidation reaction using the new
fluoroketone 2 as promotor, and using HFIP as sol-
vent. This process presents the following advantages:
fluoroketone 2 is easily prepared and handled, it does
not suffer from Baeyer–Villiger oxidation and then it
can be used in 1–5 mol% amount with only 1.5
equiv. of Oxone®.
Table 2. Catalytic epoxidation reaction in MeCN–water
with ketone 2
Olefin
Time (h)a Oxone®
(equiv.)
Epoxide/olefin Yield (%)b
Acknowledgements
Cyclooctene
Dodecene
3
5
10
10
100/0
90/10
94
79
We thank the European contract of Research Train-
ing Network (‘Fluorous Phase’ HPRN CT 2000-
00002) and the European Union (COST-program
‘Fluorous medium’ D12/98/0012). Central Glass Com-
pany is acknowledged for a kind gift of HFIP.
a After 4 h slow addition of Oxone®.
b Isolated yield.

J. Legros et al. / Tetrahedron Letters 42 (2001) 4463–4466
Table 3. Catalytic epoxidation reaction in HFIP/water with the ketone 2a
4465
Entry
1
Olefin
Mol% ketone 2
Time add. (h)
2
Time (h)b
0.3
Yield (%)c
1
8112
2
3
1
1
4
4
0.5
0.5
71d,13
68e,14
4
5
6
5
5
5
4
4
4
0.5
0.5
0.5
9315
9212
9616
a Reactions were performed as follows: substrate (1.8 mmol), ketone 2 (1 or 5% mmol) and NaHCO3 (10.8 mmol) were placed in a 3/1 mL (entries
1–3, 6) or 12/4 mL (entries 4, 5) mixture of HFIP:water (EDTA 10−4 mol/L) under vigorous stirring. A solution of Oxone® (2.7 mmol) dissolved
in 10 mL of water was added via a syringe pump over the time indicated above.
b After addition of Oxone®.
c Yield of isolated product.
d 10% of starting material recovered, 1:1 mixture of diastereoisomers.
e 1.5:1 mixture of diastereoisomers (not determined).
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