Epoxidation of alkenes using dioxygen in the presence of an alcohol catalyzed by N-hydroxyphthalimide and hexafluoroacetone without any metal catalyst

Article abstract of DOI:10.1039/a901615e

A new approach for the epoxidation of alkenes using O₂ without any metal catalyst was developed; a variety of alkenes were epoxidized in a regio- and stereoselective manner with O₂ in the presence of benzhydrol catalyzed by N-hydroxyphthalimide and hexafluoroacetone.

Full text of DOI:10.1039/a901615e

Epoxidation of alkenes using dioxygen in the presence of an alcohol catalyzed
by N-hydroxyphthalimide and hexafluoroacetone without any metal catalyst
Takahiro Iwahama, Satoshi Sakaguchi and Yasutaka Ishii*
Department of Applied Chemistry, Faculty of Engineering & High Technology Research Center, Kansai University,
Suita, Osaka 564-8680, Japan. E-mail: ishii@ipcku.kansai-u.ac.jp
Received (in Cambridge, UK) 1st March 1999, Accepted 12th March 1999
A new approach for the epoxidation of alkenes using O2
without any metal catalyst was developed; a variety of
alkenes were epoxidized in a regio- and stereoselective
manner with O2 in the presence of benzhydrol catalyzed by
N-hydroxyphthalimide and hexafluoroacetone.
under the influence of catalytic amounts of NHPI and HFA
(Table 1).‡
The first variable examined was the alcohol used as the
source of hydroperoxide (entries 1–4). It was proved that
benzhydrol 2b is the best source of hydroperoxide in the present
epoxidation system. The use of propan-2-ol 2c reduced the
conversion and selectivity of 1 to 3. It is believed that
abstraction of the a-hydrogen from 2c by phthalimide-N-oxyl
(PINO), generated from NHPI and O2, takes place in competi-
tion with abstraction of the allylic hydrogen of the olefin 1.§ In
an electrochemical oxidation using NHPI as the mediator,
Masui et al. reported that the allylic oxidation of olefins occurs
more easily than the dehydrogenation of alcohols, such as
propan-2-ol and cyclohexanol, to ketones.6 Hence, in epoxida-
tions using an alcohol whose a-hydrogen is more easily
abstracted than the allylic hydrogen of 1, the epoxidation was
expected to proceed more easily. Thus, the reaction of 1 using
benzyl alcohol 2d led to 3 with higher selectivity and
conversion. HFA was also important to complete the epoxida-
tion (entries 1, 5 and 6). An a-hydroxy hydroperoxide derived
from 1,1,1-trifluoroacetone was inadequate to epoxidize 1 in
satisfactory yield.
From an economic and environmental viewpoint, the epoxida-
tion of olefins with O2 is valuable and particularly attractive.
Therefore, much effort has been made to utilize O2 for the
epoxidation of olefins, especially using transition metals as
catalysts.1 However, few efficient catalytic aerobic oxidation
systems are known that proceed under mild conditions and are
amenable to the production of bulk and fine chemicals.2 We
have recently found a novel aerobic oxidation system of
hydrocarbons via a radical process which employs N-hydroxy-
phthalimide (NHPI) as the catalyst under mild conditions.3,4
Using this method, alcohols are also able to be oxidized with O2
to ketones or carboxylic acids via the formation of a-hydroxy
hydroperoxides.5 To highlight the importance of this radical
catalyst for aerobic oxidation, our efforts are now directed to a
new approach for the epoxidation of alkenes using O2 without
any metal catalyst.
Our epoxidation involves a new strategy consisting of radical
and ionic processes as key reactions, i.e. (i) in situ generation of
H2O2 via a-hydroxy hydroperoxide A from an alcohol and O2
assisted by NHPI, and (ii) the epoxidation of olefins by
2-hydroperoxyhexafluoropropan-2-ol B derived from the
formed H2O2 and hexafluoroacetone (HFA) (Scheme 1).†
To optimize reaction conditions for the epoxidation of
alkenes, oct-2-ene 1 was chosen as a model substrate and
allowed to react under O2 (1 atm) in the presence of alcohol 2
On the basis of these results, the aerobic epoxidation of
various olefins using 2b in the presence of catalytic amounts of
NHPI and HFA was examined under selected reaction condi-
tions (Table 2).
The epoxidation of cis- and trans-oct-2-enes proceeded
smoothly in a stereospecific manner to form cis- and trans-
2,3-epoxyoctanes, respectively, in high yields. It is noteworthy
that the present system provides a stereospecific epoxidation
route with O2, since in the epoxidation of cis olefins using O2 no
such selectivity has been previously observed. Geranyl acetate
and neryl acetate afforded the corresponding epoxides in which
the double bonds remote from their acetoxy groups were
epoxidized with high regioselectivities. Even terminal olefins,
which are difficult to epoxidize compared with internal olefins,
could be epoxidized by the present method. However, the
epoxidation of cyclohexene led to cyclohexene oxide in
First Step
O2
PINO
NHPI
OH
OH
O2
HO
R
OOH
R'
R
R'
R
R'
2a–d
A
Table 1 Epoxidation of oct-2-ene 1 to 2,3-epoxyoctane 3 with O2 in the
presence of alcohols 2a–d by NHPI and HFAa
O
O
O
+
H2O2
N
O
N
OH
PINO =
NHPI =
R
R'
4a–d
Conversion (%)
Yield (%)b
O
O
Run
Alcohol
1
2a–d
3
4a–d
1
MePhCHOH 2a
Ph2CHOH 2b
PriOH 2c
BnOH 2d
2a
90
94
58
84
7
30
36
—
27
34
34
66 (73)
85 (90)
24 (42)
60 (71)
3
29 (97)
33 (92)
—
20 (74)
32 (94)
33 (98)
Second Step
H2O2
2c
3d
4
O
HO
F3C
OH
O
C5H11
or
F3C
CF3
CF3
5e
6f
3
2a
8
4
a 1 (3 mmol) was allowed to react with O2 (1 atm) in the presence of NHPI
(10 mol%), HFA (HFA•3H2O) (10 mol%) and 2 (15 mmol) in PhCN (6 ml)
for 24 h. b Product yields were determined by GC analysis. Selectivity is in
parentheses. c 18 h. d Conversion of 2c and yield of 4c were not determined.
In the absence of HFA. 1,1,1-Trifluoroacetone was used instead of
HFA.
HO
OOH
CF3
C5H11
F3C
e
f
1
B
Scheme 1
Chem. Commun., 1999, 727–728
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Table 2 Epoxidation of various alkenes with O2 catalyzed by NPHI and HFA in the presence of benzhydrol 2ba
Conversion
(%)
Yield
(%)
Selectivity (%)
(trans:cis)
Entry Substrate
t/h
Product
O
(>99:<1)
(>99:<1)
87
72
93
80
1
18
24
93
90
2 b
(98:2)
(99:1)
81
80
86
83
16
16
94
96
3
4
O
O
O
5
6
15
20
90
88
74
71
82
81
O
OAc
OAc
O
74
83
7
20
89
OAc
OAc
O
8 c,d
9 d,e
24
24
80
83
72
70
90
84
O
10 d,f
24
78
O
63
80
C8H17
H
11 d,e
(75:25)
20
72
60
83
H
H
H
Bn
Bn
H
H
O
a Substrate (3 mmol) was allowed to react under dioxygen (1 atm) in the presence of NHPI (0.3 mmol), HFA (0.3 mmol) and 2b (15 mmol) in PhCN (6 ml)
b
c
d
e
at 80 °C. 2a was used in place of 2b. Reaction was carried out at 90 °C. a,a,a-Trifluorotoluene was used as solvent. NHPI (0.6 mmol) was used.
f Cyclohex-2-en-1-one (8%), cyclohex-2-en-1-ol (2%) and cyclohexane-1,2-diol (1%) were obtained. g Ratio a:b.
corresponding to the a-hydroxy hydroperoxide were observed. In addition,
an independent reaction of 2a (5 mmol) with O2 (1 atm) in the presence of
NHPI (10 mol%) at 70 °C in MeCN (5 ml) gave H2O2 (1.6 mmol) and
acetophenone (4a) (1.8 mmol).
somewhat lower yield because of concomitant formation of
allylic oxidation products such as cyclohexenone (8%) and
cyclohexenol (2%). Cholesteryl benzoate produced the 5,6-a-
epoxide in preference to the 5,6-b-epoxide (a:b = 75:25),
which is comparable to epoxidation by MCPBA.7 In contrast,
the same epoxidation using the aldehyde–O2 system with an Ni
complex is reported to give a:b = 31:69.8
1 S. Ito, K. Inoue and M. Matsumoto, J. Am. Chem. Soc., 1982, 104, 6450;
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We believe that the actual epoxidizing reagent B arises from
HFA and H2O2 liberated from a-hydroxy hydroperoxides A.9 In
fact, 1H NMR experiments show that treatment of 2a with O2 in
the presence of NHPI in CD3CN at 70 °C produced H2O2, but
not a-hydroxy hydroperoxide.¶
In conclusion, we have developed the epoxidation of olefins
by in situ generation of H2O2 from alcohols and O2 under the
influence of NHPI and HFA without any metal catalyst. This
method provides an alternative route to the epoxidation of
olefins by molecular oxygen in a stereospecific manner.
This work was partly supported by the Research for the
Future program.
Notes and references
† 2-Hydroperoxyhexafluoropropan-2-ol is reported to be easily derived
from HFA (or HFA hydrate) and H2O2: see R. P. Heggs and B. Ganem,
J. Am. Chem. Soc., 1979, 101, 2484.
4 Y. Ishii, T. Iwahama, S. Sakaguchi, K. Nakayama and Y. Nishiyama,
J. Org. Chem., 1996, 61, 4520.
5 T. Iwahama, S. Sakaguchi, Y. Nishiyama and Y. Ishii, Tetrahedron Lett.,
1995, 36. 6923.
‡ Typical procedure for the epoxidation of 1: A PhCN (6 ml) solution of 1
(3 mmol), NHPI (49 mg, 10 mol%), HFA•3H2O (66 mg, 10 mol%) and 2b
(15 mmol) was placed in a two–necked flask equipped with a balloon filled
with O2. The mixture was stirred at 80 °C for 18 h, and then extracted with
Et2O. The organic layer was dried over MgSO4 and analyzed by GLC with
an internal standard. The products were separated from the solvent under
reduced pressure and purified by column chromatography on silica gel (n-
hexane–AcOEt = 20:1) to give the corresponding epoxides.
§ In a previous paper, we reported that phthalimide-N-oxyl (PINO) is
produced by exposing NHPI to O2 at 80 °C in PhCN, see ref. 4.
¶ 1H NMR analysis of the resulting reaction mixture indicates a broad peak
at d 8.8 attributed to the proton of H2O2 and protons assigned to the methyl
groups of alcohol 2a and ketone at d 1.4 and d 2.6, respectively, but no peaks
6 C. Ueda, M. Nayama, H. Ohmori and M. Masui, Chem. Pharm. Bull.,
1987, 35, 1372.
7 P. Brougham, M. S. Cooper, D. Cummersou, H. Heaney and N.
Thompson, Synthesis, 1987, 1015.
8 T. Yamada, T. Takai, O. Rhode and T. Mukaiyama, Bull. Chem. Soc.
Jpn., 1991, 64, 2109.
9 It is well-known that the a-hydroxy hydroperoxide easily gives H2O2 and
a ketone, see W. T. Hess, Kirk-Othmer Encyclopedia of Industrial
Chemistry, ed. J. I. Kroschwitz and M. Howe-Grant, 4th edn., Wiley,
New York, 1995, vol. 13, pp. 976–977 and references cited therein.
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Chem. Commun., 1999, 727–728