An effective synthesis of acid-sensitive epoxides via oxidation of terpenes and styrenes using hydrogen peroxide under organic solvent-free conditions

Article abstract of DOI:10.1055/s-0030-1258467

An efficient epoxidation process for various terpenes and styrenes using a hydrogen peroxide-tungsten catalytic system with organic solvent-and halide-free conditions was developed. In the presence of the catalytic system, Na ₂WO₄, PhP(O)(OH)₂, and [Me(n-C ₈H₁₇)₃N]HSO₄, and under weak acidic conditions, hydrogen peroxide successfully epoxidized -pinene to -pinene oxide in 95% selectivity at 91% conversion, while the previously published conditions utilizing NH₂CH₂P(O)(OH)₂ as a promoter provided no epoxide. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0030-1258467

1092
PAPER
An Effective Synthesis of Acid-Sensitive Epoxides via Oxidation of Terpenes
and Styrenes Using Hydrogen Peroxide under Organic Solvent-Free
Conditions
E
poxidation of Ter
o
penes and St
s
yrenes hihiro Kon, Houjin Hachiya, Yutaka Ono, Tomohiro Matsumoto, Kazuhiko Sato*
National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba Central 5 Higashi 1-1-1, Tsukuba, Ibaraki 305-8565, Japan
Fax +81(29)8614578; E-mail: k.sato@aist.go.jp
Received 16 December 2010; revised 8 February 2011
during the reaction. For example, in the case of epoxida-
Abstract: An efficient epoxidation process for various terpenes and
tion of a-pinene, isomerization and/or hydrolysis of both
styrenes using a hydrogen peroxide-tungsten catalytic system with
the reactant and the product may lead to a complex mix-
organic solvent- and halide-free conditions was developed. In the
presence of the catalytic system, Na2WO4, PhP(O)(OH)2, and
ture of b-pinene, 3-carene, camphene, campholenic alde-
[Me(n-C8H17)3N]HSO4, and under weak acidic conditions, hydro- hyde, a-terpineol, and so on.14 A few successful examples
gen peroxide successfully epoxidized a-pinene to a-pinene oxide in
95% selectivity at 91% conversion, while the previously published
conditions utilizing NH2CH2P(O)(OH)2 as a promoter provided no
epoxide.
utilizing an immobilized catalyst of polyoxometalates on
mesoporous silica gel and methyltrioxorhenium catalysts
have been shown to effectively catalyze a-pinene epoxi-
dation.15,16 However, these methods are not fully satisfac-
tory for practical syntheses because of the requirement of
hazardous organic solvents and/or the complicated multi-
step preparation of catalysts using organic solvents. Sty-
rene oxides17 also easily undergo rearrangement, overox-
idation, and hydrolysis to give 1-phenylethane-1,2-diol,
benzaldehyde, benzoic acid, etc. through the epoxidation
of styrenes with aqueous H2O2.12 Therefore, the epoxida-
tion of styrenes using H2O2 without organic solvent is also
a challenging task.
Key words: oxidation, catalysis, epoxides, terpenoids, styrenes
Epoxidation is a core technology for the laboratory and in-
dustrial manufacturing of a wide variety of useful chemi-
cals.1 While various oxidants are now being used for both
laboratory and industry,2 they are often hazardous, expen-
sive, and form equimolar amounts of the deoxygenated
compounds as waste. Hydrogen peroxide (H2O2) is an at-
tractive oxidant for liquid-phase reactions. It can oxidize
organic compounds with the generation of water as the
only theoretical co-product.3 H2O2 is probably the termi-
nal oxidant of choice with respect to environmental and
economic considerations.3,4 A number of aqueous H2O2
epoxidations of alkenes with metal catalysts have been re-
ported thus far.5,6 We have also previously reported effi-
cient methods for the tungsten-catalyzed H2O2
epoxidation of various alkenes under organic solvent-free
conditions.7
A catalytic system applicable to nearly neutral conditions
without loss of activity at ambient temperature is neces-
sary for the epoxidation of terpenes and styrenes under or-
ganic solvent-free conditions. We have recently reported
the effective syntheses of terpene oxides with aqueous
H2O2 using a tungsten catalytic system under organic sol-
vent-free conditions as a practical method.18 We therefore
report herein a detailed study of the efficient syntheses of
acid-sensitive epoxides through the selective epoxidation
of terpenes and styrenes with a tungsten-H2O2 catalytic
system under weak acidic conditions.
Although various types of aqueous H2O2 epoxidation of
terpenes and styrenes have been reported,8–12 the reaction
is still a challenging task due to their sensitivity toward
H2O2 acidic media.13 Terpene oxides and styrene oxides
are key raw materials, functioning as some of the most
useful intermediates and/or precursors for chemical pro-
duction, including resins, paints, glues, flavors, and phar-
maceuticals.13 Terpenes and their epoxides easily undergo
ring-opening, rearrangement, double-bond migration, and
hydrolysis by acid catalysis or by application of heating.
These reactions occur due to their isoprene units possess-
ing trisubstituted alkenes; in addition, their epoxides are
prone to generate a stable intermediate, a tertiary carbocat-
ion, through protonation or ring-opening of the epoxides
a-Pinene was selected as the screening substrate because
it is the major component of wood turpentine, which is an
abundant natural compound, and is one of the challenging
terpenes that is easily hydrolyzed under acidic conditions.
It was found that at near-neutral pH screening of phospho-
nic acid, there are large differences in the catalytic reac-
tivity with organic solvent-free conditions. These
additives for improving the selectivity were tested under
the following conditions: using aqueous H2O2 (60% aq,
1.3 equiv) as an oxidant and NaOH (0.06 equiv), which
adjusts the pH to a nearly neutral condition. The solutions
were mixed with a catalytic system consisting of Na2WO4
(0.08 equiv relative to a-pinene) and [Me(n-
C8H17)3N]HSO4 (phase-transfer catalyst, 0.08 equiv)
(Scheme 1).
SYNTHESIS 2011, No. 7, pp 1092–1098
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x
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Advanced online publication: 10.03.2011
DOI: 10.1055/s-0030-1258467; Art ID: F54210SS
© Georg Thieme Verlag Stuttgart · New York
As shown in Table 1, the best choice of additive as a co-
catalyst, which binds with the tungstate center to form a

PAPER
Epoxidation of Terpenes and Styrenes
1093
attributed to its amino group. The product yield was de-
creased to 54% when the epoxidation (under the same
conditions as entry 1) was carried out in the presence of n-
BuNH2 (0.04 equiv). Though the reason for this deteriora-
tion remained unclear, these epoxidation experiments un-
der nearly neutral pH conditions (adjusted by aqueous
NaOH) eliminated the possibility that the amines work
simply as a base to alter the pH. The addition of NaOH to
weaken the Brønsted acid reactivity is important to pro-
tecting the generated epoxide from hydrolysis. When the
addition of NaOH was omitted (the other conditions being
the same as those of entry 1), 80% of the starting a-pinene
was consumed, though the yield and selectivity of a-
pinene oxide were low (13% and 16%, respectively). As
shown in Table 2, the addition of NaOH increased the se-
lectivity of a-pinene oxide (82, 90, and 95% for 0.02,
0.04, and 0.06 equiv, respectively), but decreased the a-
pinene conversion to a small extent (97, 96, and 91% for
0.02, 0.04, and 0.06 equiv, respectively). The best yield
with good selectivity was obtained with the addition of
0.18 mmol of NaOH (Table 2, entry 4).
60% H2O2 (1.3 equiv)
Na2WO4 (0.08 equiv)
PhP(O)(OH)2 (0.04 equiv)
[Me(n-C8H17)3N]HSO4 (0.08 equiv)
NaOH (0.06 equiv)
O
25 °C, 12 h
87% yield
Scheme 1
phosphonate complex,19 was found to be PhP(O)(OH)2
(0.04 equiv). The reaction of a-pinene with these catalytic
conditions successfully gave a-pinene oxide in 87% yield
(on the basis of the starting a-pinene) after stirring at
25 °C for 12 hours. The reaction proceeded with less de-
composition of a-pinene and its epoxide. This tungsten–
H2O2 catalytic system leads to anti-addition of the ep-
oxide oxygen atom to avoid steric repulsion during the nu-
cleophilic attack of a-pinene on an oxygen atom of
tungsten peroxide active species.9a
Table 1 Effects of Additives on the Epoxidation of a-Pinenea
Entry Additive
Conversion Yield
Selectivity
(%)c
(%)b
(%)b
Table 2 Effects of NaOH on the Epoxidation of a-Pinenea
1
2
3
4
5
6
7
PhP(O)(OH)2
91
87
95
70
75
74
83
77
47
Entry
NaOH
(mmol)
Conversion Yield
Selectivity
(%)c
(%)b
(%)b
MeP(O)(OH)2
EtP(O)(OH)2
n-PrP(O)(OH)2
t-BuP(O)(OH)2
H3PO4
87
61
1
2
3
4
5
0.00
0.06
0.12
0.18
0.24
80
13
16
82
91
68
97
80
88
65
96
87
90
84
70
91
87
95
86
66
82
82
100
NH2CH2P(O)(OH)2
74
35
a Reaction conditions: a-pinene (3.0 mmol), 60% H2O2 (3.9 mmol),
Na2WO4 (0.24 mmol), [Me(n-C8H17)3N]HSO4 (0.24 mmol),
PhP(O)(OH)2 (0.12 mmol), 25 °C, 1000 rpm, 12 h.
b Yield on the basis of a-pinene, determined by GC analysis with bi-
phenyl as an internal standard.
a Reaction conditions: a-pinene (3.0 mmol), 60% H2O2 (3.9 mmol),
Na2WO4 (0.24 mmol), [Me(n-C8H17)3N]HSO4 (0.24 mmol), additive
(0.12 mmol), NaOH (0.18 mmol), 25 °C, 1000 rpm, 12 h.
b Yield on the basis of a-pinene, determined by GC analysis with bi-
phenyl as an internal standard.
c Yield/conversion (%).
c Yield/conversion (%).
Although the reaction was carried out most efficiently
with 60% H2O2 as the oxidant, an epoxidation with aque-
ous 30% and 50% H2O2 also gave satisfactory results
(73% and 81% yield of a-pinene oxide for using 30% and
50% aq H2O2, respectively).
The results with the other additives were examined and
are summarized in Table 1. Alkylphosphonic acids also
worked as co-catalysts under the present reaction condi-
tions, although their efficiencies were somewhat lower
than that of PhP(O)(OH)2; the epoxidations using
MeP(O)(OH)2, EtP(O)(OH)2, n-PrP(O)(OH)2, and t-
BuP(O)(OH)2 resulted in the formation of a-pinene oxide
in 61%, 68%, 65%, and 70% yield, respectively (Table 1,
entries 2–5). In addition to the alkylphosphonic acids, a
reaction in the presence of H3PO4 gave a modest yield
(66%, Table 1, entry 6). It is noteworthy that the catalytic
ability of NH2CH2P(O)(OH)2 [previously reported as the
best co-catalyst under acidic conditions7 and as a better
co-catalyst than PhP(O)(OH)27b] was found to be much in-
ferior to that of PhP(O)(OH)2. That is, the epoxidation us-
ing NH2CH2P(O)(OH)2 gave the epoxide with moderate
conversion and less selectivity (74% and 47%, Table 1,
entry 7). The inefficiency of NH2CH2P(O)(OH)2 could be
This epoxidation system using PhP(O)(OH)2 as a co-cata-
lyst can be adopted for the epoxidation of various other
terpenes to generate the corresponding terpene oxides.
The results are shown in Table 3. 1-Methylcyclohex-1-
ene was successfully converted into the epoxide (92%
yield, Table 3, entry 1). A reaction with bicyclic monoter-
pene, 3-carene, which is known to undergo an acid-cata-
lyzed rearrangement upon treatment with peracid,20 also
provided an excellent yield of the corresponding epoxide
(93%, Table 3, entry 4). A reaction with a-terpineol hav-
ing a hydroxy group that causes intramolecular addition
reactions in its product under acidic conditions21 also gave
the corresponding epoxide in high yield (98%, Table 3,
Synthesis 2011, No. 7, 1092–1098 © Thieme Stuttgart · New York

1094
Y. Kon et al.
PAPER
Table 3 H2O2 Epoxidation of Terpenes and Inner Olefina
monoepoxides in high yields (each 82%, Table 3, entries
8 and 9). Epoxidation of carvone having a carbonyl group
and two alkenes (cyclic alkene and exomethylene), also
gave two types of mono epoxides in a total 55% yield with
a specific rate. Carvone 7,8-oxide was obtained in 50%
yield, and carvone 1,6-oxide was formed in 5% yield
(Table 3, entry 10).
Entry Alkene
1
Product
Yield (%)b
92
O
O
O
This catalytic system was also applied to the syntheses of
various styrene oxides. As shown in Scheme 2 and
Table 4, entry 1, epoxidation of styrene effectively gave
styrene oxide in 78% yield with 89% selectivity, while the
reaction without NaOH produced styrene oxide in only
18% yield. The weak acidic conditions created by the ad-
dition of NaOH effectively protected the generated sty-
rene oxide from hydrolysis. Although epoxidation of
electron-deficient styrenes such as 4-fluoro-, 4-chloro-, 4-
bromo-, and 4-nitrostyrene gave the corresponding oxides
2
87
73
3c
4
93
5d
87e
O
6
98
75
Table 4 Epoxidation of Styrene Derivativesa
OH
OH
Entry Substrate
Product
Yield (%)b
78
O
1
7
O
O
O
2
3
61
71
88
8
9
82
O
3
F
F
O
O
82
4
Cl
Cl
O
O
5
O
O
O
10
55 (10:1)
Br
Br
O
O
6
75
57
a Reaction conditions: alkene (3.0 mmol), 60% H2O2 (3.9 mmol),
Na2WO4 (0.24 mmol), [Me(n-C8H17)3N]HSO4 (0.24 mmol),
PhP(O)(OH)2 (0.12 mmol), NaOH (0.18 mmol), 25 °C, 1000 rpm, 12
h.
O2N
O2N
O
7
b Yield on the basis of alkene, determined by GC analysis with biphe-
nyl as an internal standard.
c Aq 30% H2O2 was used instead of 60% H2O2.
d The reaction was run using 3-carene (100 g), 60% H2O2 (1.3 equiv),
Na2WO4 (0.04 equiv), PhP(O)(OH)2 (0.02 equiv), [Me(n-
C8H17)3N]HSO4 (0.04 equiv), and NaOH (0.04 equiv).
e Isolated yield after distillation.
O
O
8
9
63
98
entry 6). A reaction with b-myrcene, with which it was
difficult to achieve regioselective epoxidation by the
former catalyst system,22 gave the 2,3-epoxide in 75%
yield (Table 3, entry 7). Epoxidation of limonene and b-
caryophyllene, which have two alkene moieties in the
molecule, also successfully produced the corresponding
a Reaction conditions: substrate (3.0 mmol), 60% H2O2 (3.9 mmol),
Na2WO4 (0.24 mmol), [Me(n-C8H17)3N]HSO4 (0.24 mmol),
PhP(O)(OH)2 (0.12 mmol), NaOH (0.12 mmol), 35 °C, 1000 rpm, 12
h.
b Determined by GC.
Synthesis 2011, No. 7, 1092–1098 © Thieme Stuttgart · New York

PAPER
Epoxidation of Terpenes and Styrenes
1095
1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were record-
ed on a JEOL ECX-400P spectrometer using CDCl3 as solvent.
Chemical shifts (d) are reported in parts per million relative to inter-
60% H2O2 (1.3 equiv)
Na2WO4 (0.08 equiv)
PhP(O)(OH)2 (0.04 equiv)
[Me(n-C8H17)3N]HSO4 (0.08 equiv)
NaOH (0.04 equiv)
O
1
nal tetramethylsilane at 0.00 ppm for H and relative to residual
CHCl3 at 77.0 ppm for 13C. Gas chromatographic (GC) analyses
were performed on a Shimadzu GC-17A instrument using a TC-1
column (0.25 mm × 30 m, GL Sciences Inc.).
35 °C, 12 h
78% yield
Scheme 2
a-Pinene, 1-methylcyclohexene, 3-carene, a-terpineol, limonene,
b-caryophyllene, carvone, styrene derivatives, and PhP(O)(OH)2
were obtained from Tokyo Chemical Industry Co., Ltd. b-Myrcene
and NaOH were obtained from Wako Pure Chemicals Ind., Ltd.
Aqueous hydrogen peroxide (30%), Na2WO4·2H2O and aqueous
H3PO4 were obtained from Kanto Chemical Co., Inc. Aqueous hy-
drogen peroxide (50%), NH2CH2P(O)(OH)2, MeP(O)(OH)2,
EtP(O)(OH)2, n-PrP(O)(OH)2, and t-BuP(O)(OH)2 were obtained
from Aldrich Chemical Co. Aqueous hydrogen peroxide (60%)
was obtained from Mitsubishi Gas Chemical Co., Inc. All materials
were used as received except for b-myrcene which was distilled pri-
or to use. [Me(n-C8H17)3N]HSO4 was prepared from [Me(n-
in moderate to good yields (61%, 71%, 88%, and
75%, Table 4, entries 3–6, respectively), epoxidation of
4-methylstyrene as an electron-rich substrate gave little
4-methylstyrene oxide (3% yield, Table 4, entry 2). The
4-methylstyrene was efficiently epoxidized in an 87%
conversion, but the generated epoxide underwent hydro-
lytic ring opening. Epoxidation of a-methylstyrene and
trans-b-methylstyrene gave their oxides in moderate
yields (57% and 63% with conversion of 95% and 73%, C8H17)3N]Cl (Tokyo Chemical Industry Co., Ltd) and aqueous
Table 4, entries 7 and 8, respectively). A reaction with cis-
H2SO4 (Kanto Chemical Co., Inc.).
b-methylstyrene gave the corresponding oxide in good
Epoxidation of a-Pinene; Typical Procedure
yield (98%, Table 4, entry 9). The high reactivity of cis-b-
A test tube equipped with a magnetic stirring bar was charged with
a-pinene (409 mg, 3.00 mmol), 60% H2O2 (221 mg, 3.90 mmol),
methylstyrene relative to the trans-b-methylstyrene is ex-
plained by the steric hindrance of the substituent of olefin
with peroxotungsten complex in the spiro-structured
model in the transition state.7c
Na2WO4·2H2O (79.1 mg, 0.24 mmol), [Me(n-C8H17)3N]HSO4 (112
mg, 0.24 mmol), PhP(O)(OH)2 (19.0 mg, 0.12 mmol), and 3 M aq
NaOH (60 mL, 0.18 mmol). The mixture was vigorously stirred at
25 °C for 12 h and extracted with toluene (3 × 6 mL). The conver-
sion and yield were determined by GC analysis of the toluene solu-
tion with ca. 0.2 mmol of biphenyl as an internal standard.
The present method can be carried out on for hectogram-
scale syntheses of acid-sensitive epoxides. That is, with
100 g of 3-carene as a starting material, 97.6 g of the cor-
responding epoxide was obtained after distillation of the Hectogram-Scale Epoxidation of 3-Carene
To 60% H2O2 (54.1 g, 0.953 mol) in a 1 L round-bottomed flask
crude product (87% yield, Scheme 3 and Table 3, entry
5). Because the epoxidation of 3-carene is quite exother-
mic, careful reaction temperature control was found to be
critical for larger-scale preparation.
cooled in an ice-water bath was slowly added Na2WO4·2H2O (9.69
g, 29.4 mmol), PhP(O)(OH)2 (2.32 g, 14.7 mmol), [Me(n-
C8H17)3N]HSO4 (13.7 g, 29.4 mmol), and NaOH (1.17 g, 29.4
mmol). While the mixture was cooled at 0 °C, 3-carene (100 g,
0.734 mol) was added dropwise. The mixture was gradually
warmed to 25 °C with vigorous stirring. After 12 h, the two phases
were separated, and the organic phase was washed with 10% aq
Na2S2O3 (113 mL). Distillation of the organic phase under reduced
pressure gave the corresponding oxide as a colorless oil; yield: 97.6
g (87%).
+
60% H2O2
1.3 equiv
100 g
Epoxidation of a-Pinene under pH-Controlled Conditions
To 60% H2O2 (5.41 g, 95.3 mmol) in a test tube equipped with a
magnetic stirring bar was added Na2WO4·2H2O (1.94 g, 5.88
mmol), PhP(O)(OH)2 (464 mg, 2.94 mmol), or NH2CH2P(O)(OH)2
(326 mg, 2.94 mmol), and 3 M aq NaOH (1.47 mL, 4.41 mmol). The
solution pH was adjusted to 7.0 with additional aq NaOH. Then
[Me(n-C8H17)3N]HSO4 (2.74 g, 5.88 mmol) and a-pinene (10.0 g,
73.4 mmol) were added. The above procedure was then followed.
Conversion and yield were determined by GC analyses (with biphe-
nyl as an internal standard) instead of by isolation of the product.
Na2WO4 (0.04 equiv)
PhP(O)(OH)2 (0.02 equiv)
[Me(n-C8H17)3N]HSO4 (0.04 equiv)
NaOH (0.04 equiv)
O
25 °C, 12 h
97.6 g
87% after distillation
Scheme 3
Epoxidation of a-Pinene with 50% H2O2
A test tube equipped with a magnetic stirring bar was charged with
a-pinene (409 mg, 3.00 mmol), 50% H2O2 (265 mg, 3.90 mmol),
Na2WO4·2H2O (79.3 mg, 0.24 mmol), [Me(n-C8H17)3N]HSO4 (112
mg, 0.24 mmol), PhP(O)(OH)2 (18.4 mg, 0.12 mmol), and 3 M aq
NaOH (60 mL, 0.18 mmol). The mixture was vigorously stirred at
25 °C for 12 h and extracted with toluene (3 × 6 mL). The conver-
sion and yield were 92% and 81%, respectively, as determined by
GC analysis of the toluene solution with ca. 0.2 mmol of biphenyl
as an internal standard.
In summary, we have presented a green and efficient
method for terpene and styrene epoxidation using aqueous
H2O2 as an oxidant under organic solvent-free and halide-
free conditions. The catalytic system, which consists of
Na2WO4, PhP(O)(OH)2, and [Me(n-C8H17)3N]HSO4, hav-
ing high activity under nearly neutral pH conditions at
ambient temperature, achieved an excellent yield and se-
lectivity for the syntheses of acid-sensitive epoxides.
Synthesis 2011, No. 7, 1092–1098 © Thieme Stuttgart · New York

1096
Y. Kon et al.
PAPER
Epoxidation of a-Pinene with 30% H2O2
Limonene 2,3-Oxide27
A test tube equipped with a magnetic stirring bar was charged with
a-pinene (409 mg, 3.00 mmol), 30% H2O2 (442 mg, 3.90 mmol),
Na2WO4·2H2O (78.8 mg, 0.24 mmol), [Me(n-C8H17)3N]HSO4 (112
mg, 0.24 mmol), PhP(O)(OH)2 (18.7 mg, 0.12 mmol), and 3 M aq
NaOH (60 mL, 0.18 mmol). The mixture was vigorously stirred at
25 °C for 12 h and extracted with toluene (3 × 6 mL). The conver-
sion and yield were 93% and 73%, respectively, as determined by
GC analysis of the toluene solution with ca. 0.2 mmol of biphenyl
as an internal standard.
1H NMR (400 MHz, CDCl3): d = 1.13–2.27 (m, 7 H), 1.29 (s, 3 H),
1.71 (s, 3 H), 3.02 (t, J = 5.5 Hz, 1 H), 4.75 (s, 2 H).
13C NMR (100 MHz, CDCl3): d = 20.2, 22.1, 25.8, 28.5, 30.7, 40.7,
57.3, 59.2, 109.0, 148.8.
b-Caryophyllene Oxide28
1H NMR (400 MHz, CDCl3): d = 0.98 (s, 3 H), 1.01 (s, 3 H), 1.20
(m, 3 H), 1.28–1.52 (m, 3 H), 1.58–1.71 (m, 3 H), 1.76 (t, J = 9.8
Hz, 1 H), 2.06–2.14 (m, 2 H), 2.21–2.28 (m, 1 H), 2.31–2.37 (m, 1
H), 2.61 (q, J = 9.5 Hz, 1 H), 2.87 (dd, J = 10.5, 4.1 Hz, 1 H), 4.85
(s, 1 H), 4.97 (s, 1 H).
Epoxidation of Styrene; Typical Procedure
A test tube equipped with a magnetic stirring bar was charged with
styrene (316 mg, 3.00 mmol), 60% H2O2 (221 mg, 3.90 mmol),
Na2WO4·2H2O (80.0 mg, 0.24 mmol), [Me(n-C8H17)3N]HSO4 (112
mg, 0.24 mmol), PhP(O)(OH)2 (19.4 mg, 0.12 mmol), and 3 M aq
NaOH (40 mL, 0.12 mmol). The mixture was vigorously stirred at
35 °C for 12 h and extracted with toluene (3 × 6 mL). The conver-
sion and yield were determined by GC analysis of the toluene solu-
tion with ca. 0.2 mmol of biphenyl as an internal standard.
13C NMR (100 MHz, CDCl3): d = 17.0, 21.6, 27.2, 29.8, 29.9, 30.2,
34.0, 39.1, 39.8, 48.7, 50.7, 59.8, 63.7, 112.7, 151.8.
Carvone 1,6-Oxide29
1H NMR (400 MHz, CDCl3): d = 1.42 (s, 3 H), 1.72 (s, 3 H), 1.91
(dd, J = 15.0, 11.1 Hz, 1 H), 2.03 (dd, J = 17.4, 11.1 Hz, 1 H), 2.38
(dt, J = 15.0, 3.0 Hz, 1 H), 2.59 (dd, J = 17.4, 4.5 Hz, 1 H), 2.67–
2.76 (m, 1 H), 3.46 (d, J = 2.7 Hz, 1 H), 4.72 (s, 1 H), 4.79 (s, 1 H).
a-Pinene Oxide23
13C NMR (100 MHz, CDCl3): d = 15.2, 20.5, 28.6, 34.9, 41.7, 58.7,
1H NMR (400 MHz, CDCl3): d = 0.94 (s, 3 H), 1.29 (s, 3 H), 1.34
(s, 3 H), 1.62 (d, J = 9.6 Hz, 1 H), 1.70–1.75 (br m, 1 H), 1.87–2.03
(m, 4 H), 3.07 (dd, J = 4.1, 1.4 Hz, 1 H).
61.2, 110.4, 146.2, 205.4.
Carvone 7,8-Oxide30
1H NMR (400 MHz, CDCl3): d = 1.32 (d, J = 6.4 Hz, 3 H), 1.78 (s,
3 H), 2.02–2.70 (m, 7 H), 6.74 (m, 1 H).
13C NMR (100 MHz, CDCl3): d = 20.2, 22.4, 25.9, 26.7, 27.6, 39.7,
40.5, 45.1, 56.9, 60.3.
13C NMR (100 MHz, CDCl3): d = 15.7, 18.4, 19.0, 27.7, 27.9, 39.9,
40.4, 40.7, 41.4, 52.4, 52.9, 57.9, 58.0, 135.5, 135.6, 143.9, 144.2,
198.8, 198.9.
1,2-Epoxy-1-methylcyclohexane24
1H NMR (400 MHz, CDCl3): d = 1.13–1.28 (m, 2 H), 1.30 (s, 3 H),
1.36–1.47 (m, 2 H), 1.63–1.70 (m, 1 H), 1.80–1.93 (m, 3 H), 2.95
(d, J = 3.2 Hz, 1 H).
Styrene Oxide31
1H NMR (400 MHz, CDCl3): d = 2.82 (dd, J = 5.5, 2.5 Hz, 1 H),
3.16 (dd, J = 5.5, 4.0 Hz, 1 H), 3.88 (dd, J = 4.0, 2.5 Hz, 1 H), 7.25
(m, 5 H).
13C NMR (100 MHz, CDCl3): d = 19.6, 20.0, 24.0, 24.7, 29.9, 57.5,
59.5.
3-Carene Oxide20,25
Bp 35 °C/4.5 mmHg.
13C NMR (100 MHz, CDCl3): d = 50.8, 51.9, 125.1, 127.7, 128.1,
137.2.
1H NMR (400 MHz, CDCl3): d = 0.44 (td, J = 9.1, 2.3 Hz, 1 H),
0.52 (td, J = 9.1, 2.3 Hz, 1 H), 0.72 (s, 3 H), 1.00 (s, 3 H), 1.25 (s, 3
H), 1.48 (dd, J = 16.5, 2.3 Hz, 1 H), 1.63 (dt, J = 16.5, 2.3 Hz, 1 H),
2.13 (dd, J = 16.5, 9.2 Hz, 1 H), 2.29 (ddd, J = 16.5, 9.2, 1.8 Hz, 1
H), 2.82 (s, 1 H).
13C NMR (100 MHz, CDCl3): d = 13.8, 14.6, 16.0 (2 C), 19.2, 23.1,
23.3, 27.7, 55.9, 58.2.
4-Methylstyrene Oxide12g
1H NMR (400 MHz, CDCl3): d = 2.33 (s, 3 H), 2.77 (dd, J = 5.5, 2.6
Hz, 1 H), 3.09 (dd, J = 5.5, 4.1 Hz, 1 H), 3.79 (dd, J = 4.1, 2.6 Hz,
1 H), 7.06–7.26 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 20.9, 50.9, 52.1, 125.5, 129.2,
134.8, 138.1.
4-Fluorostyrene Oxide12g
a-Terpineol Oxide21
1H NMR (400 MHz, CDCl3): d = 2.67 (dd, J = 5.6, 2.6 Hz, 1 H),
3.04 (dd, J = 5.6, 4.0 Hz, 1 H), 3.75 (dd, J = 4.0, 2.6 Hz, 1 H), 6.91–
6.96 (m, 2 H), 7.12–7.17 (m, 2 H).
Obtained as a 1:1 mixture of cis- and trans-epoxides.
1H NMR (400 MHz, CDCl3): d = 1.01 (qd, J = 12.3, 6.9 Hz, 1 H),
1.13 (s, 3 H), 1.141 (s, 3 H), 1.144 (s, 3 H), 1.16 (s, 3 H), 1.313 (s,
3 H), 1.315 (s, 3 H), 1.43–1.54 (m, 3 H), 1.58–1.69 (m, 3 H), 1.79–
1.94 (m, 2 H), 2.00–2.08 (m, 2 H), 2.19–2.24 (m, 1 H), 3.00 (d,
J = 5.5 Hz, 1 H), 3.07 (br s, 1 H).
13C NMR (100 MHz, CDCl3): d = 20.1, 22.8, 22.9, 24.4, 25.9, 26.2,
26.6, 27.18, 27.22, 27.4, 29.5, 30.8, 40.2, 44.1, 57.5, 57.7, 59.2,
61.2, 72.2, 72.4.
13C NMR (100 MHz, CDCl3): d = 51.6, 52.2, 115.9 (d, J = 20 Hz),
127.6 (d, J = 7 Hz), 133.7 (d, J = 2 Hz), 163.1 (d, J = 24 Hz).
4-Chlorostyrene Oxide31
1H NMR (400 MHz, CDCl3): d = 2.76 (dd, J = 5.5, 2.5 Hz, 1 H),
3.15 (dd, J = 5.5, 4.0 Hz, 1 H), 3.84 (dd, J = 4.0, 2.5 Hz, 1 H), 7.21
(d, J = 8.5 Hz, 2 H), 7.32 (d, J = 8.5 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 50.8, 51.3, 126.4, 128.2, 133.4,
b-Myrcene 6,7-Oxide20,25,26
1H NMR (400 MHz, CDCl3): d = 1.26 (s, 3 H), 1.31 (s, 3 H), 1.71–
1.76 (m, 2 H), 2.28–2.36 (m, 1 H), 2.40–2.48 (m, 1 H), 2.76 (t,
J = 6.2 Hz, 1 H), 5.02 (s, 1 H), 5.05 (s, 1 H), 5.08 (d, J = 11.0 Hz, 1
H), 5.24 (d, J = 17.5 Hz, 1 H), 6.38 (dd, J = 17.5, 11.0 Hz, 1 H).
135.7.
4-Bromostyrene Oxide32
1H NMR (400 MHz, CDCl3): d = 2.74 (dd, J = 5.5, 2.5 Hz, 1 H),
3.14 (dd, J = 5.4, 4.1 Hz, 1 H), 3.83 (dd, J = 4.1, 2.6 Hz, 1 H), 7.13–
7.17 (d, J = 8.4 Hz, 2 H), 7.45–7.48 (d, J = 8.5 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 18.8, 24.8, 27.6, 28.1, 58.4, 64.0,
113.4, 116.1, 138.5, 145.5.
13C NMR (100 MHz, CDCl3): d = 51.2, 51.8, 122.0, 127.1, 131.6,
136.7.
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PAPER
Epoxidation of Terpenes and Styrenes
1097
4-Nitrostyrene Oxide32
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Sato, K. Chem. Commun. 2003, 1977.
1H NMR (400 MHz, CDCl3): d = 2.79 (dd, J = 5.5, 2.4 Hz, 1 H),
3.24 (dd, J = 5.5, 4.2 Hz, l H), 3.97 (dd, J = 4.0, 2.4 Hz, 1 H), 7.45
(d, J = 8.7 Hz, 2 H), 8.22 (d, J = 8.8 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 51.5, 51.7, 123.8, 126.3, 145.3,
147.9.
a-Methylstyrene Oxide33
1H NMR (400 MHz, CDCl3): d = 1.63 (s, 3 H), 2.70 (d, J = 5.4 Hz,
1 H), 2.88 (d, J = 5.4 Hz, 1 H), 7.14–7.30 (m, 5 H).
(8) For recent examples of heterogeneous catalysts, see:
(a) van der Waal, J. C.; Rigutto, M. S.; van Bekkum, H.
Appl. Catal., A 1998, 167, 331. (b) Skrobot, F. C.; Valente,
A. A.; Neves, G.; Rosa, I.; Rocha, J.; Cavaleiro, J. A. S.
J. Mol. Catal. A: Chem. 2003, 201, 211. (c) de S. E. Silva,
J. M.; Vinhado, F. S.; Mandelli, D.; Schuchardt, U.; Rinaldi,
R. J. Mol. Catal. A: Chem. 2006, 252, 186. (d) Eimer, G.
A.; Díaz, I.; Sastre, E.; Casuscelli, S. G.; Crivello, M. E.;
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(g) Bonon, A. J.; Mandelli, D.; Kholdeeva, O. A.;
Barmatova, M. V.; Kozlov, Y. N.; Shul’pin, G. B. Appl.
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13C NMR (100 MHz, CDCl3): d = 22.2, 57.2, 57.5, 125.7, 127.9,
129.0, 141.6.
trans-b-Methylstyrene Oxide34
1H NMR (400 MHz, CDCl3): d = 1.43 (d, J = 6.8 Hz, 3 H), 3.12 (dq,
J = 6.8, 2.6 Hz, 1 H), 3.55 (d, J = 2.5 Hz, 1 H), 7.27 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 17.8, 58.9, 59.4, 125.4, 127.9,
128.3, 137.7.
cis-b-Methylstyrene Oxide34
1H NMR (400 MHz, CDCl3): d = 1.08 (d, J = 7.1 Hz, 3 H), 3.33 (dq,
J = 7.1, 5.8 Hz, 1 H), 4.05 (d, J = 5.6 Hz, 1 H), 7.29 (m, 5 H).
13C NMR (100 MHz, CDCl3): d = 12.5, 55.0, 57.5, 126.5, 127.4,
127.9, 135.5.
(9) For recent examples of polyoxometalate complexes, see:
(a) Villa de P, A. L.; Sels, B. F.; De Vos, D. E.; Jacobs, P. A.
J. Org. Chem. 1999, 64, 7267. (b) Kamata, K.; Kotani, M.;
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Arzumanov, S. S.; Chesalov, Y. A.; Melgunov, M. S.;
Stepanov, A. G.; Fedin, V. P.; Kholdeeva, O. A. Inorg.
Chem. 2010, 49, 2920.
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(a) Sakaguchi, S.; Nishiyama, Y.; Ishii, Y. J. Org. Chem.
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Acknowledgment
This work was partially supported by the New Energy and Industri-
al Technology Development Organization (NEDO), Japan.
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