Selective Oxidation of Monoterpenes with Hydrogen Peroxide Catalyzed by Peroxotungstophosphate (PCWP)

Article abstract of DOI:10.1021/jo960275q

Catalytic epoxidation of monoterpenes with aqueous hydrogen peroxide catalyzed by peroxotungstophosphate (PCWP) under biphase conditions using chloroform as the solvent was examined.A variety of terpenes was oxidized to the corresponding monoepoxides or diepoxides in good yields under mild conditions.For example, limonene (1) was converted into limonene oxide (1a) in which the cyclohexene double bond was selectively epoxidized in almost quantitative yield.The oxidation of γ-terpinene (2) with 2.2 equiv of 35percent H2O2 took place with high stereoselectivity to give cis-diepoxide 2c.In terpenes bearing electron-withdrawing groups such as neryl acetate (3), geranyl acetate (4), citral (5), and geranyl nitrile (6), the double bonds remote from the substituents were epoxidized in preference to the others.The epoxidation of linalool (9) by the present catalyst-oxidant system produced the cyclic products, hydroxy furan 9a and hydroxy pyran 9b, rather than epoxide. tert-Butyl alcohol was successfully employed as the solvent by treating a hydrogen peroxide solution of tert-butyl alcohol with MgSO4 prior to use.The regioselectivities in the epoxidation of monoterpenes can be favorably explained from the electron densities of the double bonds which were estimated using the CAChe system.

Full text of DOI:10.1021/jo960275q

J . Org. Chem. 1996, 61, 5307-5311
5307
Selective Oxid a tion of Mon oter p en es w ith Hyd r ogen P er oxid e
Ca ta lyzed by P er oxotu n gstop h osp h a te (P CWP )
Satoshi Sakaguchi, Yutaka Nishiyama, and Yasutaka Ishii*
Department of Applied Chemistry, Faculty of Engineering, Kansai University, Suita, Osaka 564, J apan
Received February 9, 1996X
Catalytic epoxidation of monoterpenes with aqueous hydrogen peroxide catalyzed by peroxotung-
stophosphate (PCWP) under biphase conditions using chloroform as the solvent was examined. A
variety of terpenes was oxidized to the corresponding monoepoxides or diepoxides in good yields
under mild conditions. For example, limonene (1) was converted into limonene oxide (1a ) in which
the cyclohexene double bond was selectively epoxidized in almost quantitative yield. The oxidation
of γ-terpinene (2) with 2.2 equiv of 35% H2O2 took place with high stereoselectivity to give cis-
diepoxide 2c. In terpenes bearing electron-withdrawing groups such as neryl acetate (3), geranyl
acetate (4), citral (5), and geranyl nitrile (6), the double bonds remote from the substituents were
epoxidized in preference to the others. The epoxidation of linalool (9) by the present catalyst-
oxidant system produced the cyclic products, hydroxy furan 9a and hydroxy pyran 9b, rather than
epoxide. tert-Butyl alcohol was successfully employed as the solvent by treating a hydrogen peroxide
solution of tert-butyl alcohol with MgSO4 prior to use. The regioselectivities in the epoxidation of
monoterpenes can be favorably explained from the electron densities of the double bonds which
were estimated using the CAChe system.
In tr od u ction
with 35% H2O2 in the presence of PCWP in a two-phase
system gives the corresponding epoxides in good yields.2i
The application of the same methodology to alkynes and
allenes, which are difficult to selectively oxidize by
conventional oxidation methods, led to their first suc-
cessful conversion into R,â-unsaturated ketones2b and/
or R,â-epoxy ketones,2g and R-alkoxy ketones and/or
R-hydroxy ketones,2b respectively. We have now exam-
ined the oxidation of monoterpenes by the PCWP-H2O2
system.
In the fine chemicals industry, the development of
clean oxidation processes, in which toxic salts such as
chromium and manganese salts are not utilized, has
become very important in the interest of “no-waste”
technologies. Molecular oxygen and hydrogen peroxide
which ultimately do not generate salts are thus oxidants
of great interest. Recent advances in the phase-transfer
oxidation method using hydrogen peroxide, by which a
wide variety of organic substrates can be oxidized have
occurred as a result. Although many catalysts have been
developed for this purpose, heteropolyoxometalates have
received particular attention as homogeneous liquid-
phase oxidation catalysts.1 We have shown that the
peroxotungstophosphate ([C5H5N+(CH2)15CH3]3{PO4[W(O)-
(O2)2]4}3-) (PCWP), which has both phase-transfer and
good oxidizing capabilities catalyzes the oxidation of a
wide variety of organic substrates using aqueous hydro-
gen peroxide as an oxidant.2 The oxidation of alkenes
In general, the selective oxidation of monoterpenes is
hard to achieve with peracids due to their oxidizing
strength, by which mono- and diepoxides as well as
cleaved products are simultaneously produced. For the
epoxidation of acid-sensitive substrates, the reaction
must be carried out in a buffered aqueous medium.3
Recently, a few reagents such as dioxiranes4 and
HOF‚CH3CN5 have been developed for the selective
epoxidation of monoterpenes. And catalytic oxidation
systems consisting of Mo, V, or Mn complexes and alkyl
hydroperoxides,6 iodosylbenzene,7 or sodium monoxychlo-
ride8 have been also reported. However, there has been
little study so far of terpene oxidation with hydrogen
peroxide as the oxidant.
X Abstract published in Advance ACS Abstracts, J uly 15, 1996.
(1) (a) Bailey, A. J .; Griffith, W. P.; Parkin, B. C. J . Chem. Soc.,
Dalton. Trans. 1995, 1833. (b) Salles, L.; Aubry, C.; Thouvenot, R.;
Robert, F.; D-Morin, C.; Chottard, G.; Ledon, H.; Jeannin, Y.; Bre´geault,
J .-M. Inorg. Chem. 1994, 33, 871. (c) J amsen, R. J . J .; Veldhuizen, H.
M.; Schwegler, M.; Bekkum, H. Recl. Trav. Chim. Pays-Bas 1994, 113,
115. (d) Dengel, A. C.; Griffith, W. P.; Parkin, B. C. J . Chem. Soc.,
Dalton. Trans. 1993, 2683. (e) Neumann, R.; Vega, M. J . Mol. Cat.
1993, 84, 93. (f) Aubry, C.; Chottard, G.; Platzer, N.; Bre´geault, J .-M.;
Thouvenot, R.; Chauveau, F.; Huet, C.; Ledon H. Inorg. Chem. 1991,
30, 4409. (g) Shimizu, M.; Orita, H., Hayakawa, T.; Watanabe, Y.;
Takehira, K. Bull. Chem. Soc. J pn. 1990, 63, 1835. (h) Schwegler, M.;
Floor, M.; Bekkum, H. Tetrahedron Lett. 1988, 29, 823. (i) Furukawa,
H.; Nakamura, T.; Inagaki, H.; Nishikawa, E.; Imai, C. Misono, M.
Chem. Lett. 1988, 877. (j) Trost, B. M.; Masuyama, Y. Tetrahedron
Lett. 1984, 25, 173.
In this paper, we wish to report the selective oxidation
of monoterpenes 1-9 to the corresponding mono- or
diepoxides with aqueous hydrogen peroxide under the
(3) (a) Fringuelli, F.; Germani, R.; Pizzo, F.; Savelli, G. Tetrahedron
Lett. 1989, 30, 1427. (b) Anderson, W. K.; Veysoglu, T. J . Org. Chem.
1973, 38, 2267.
(4) Lluch, A.-M.; Sa´nchez-Baeza F.; Messeguer, A.; Fusco, C.; Curci,
R. Tetrahedron Lett. 1993, 49, 6299.
(2) (a) Iwahama, T.; Sakaguchi, S.; Nishiyama, Y.; Ishii, Y. Tetra-
hedron Lett. 1995, 36, 1523. (b) Sakaguchi, S.; Watase, S.; Katayama,
Y.; Sakata, Y.; Nishiyama, Y.; Ishii, Y. J . Org. Chem. 1994, 59, 5681.
(c) Ishii, Y.; Tanaka, H.; Nishiyama, Y. Chem. Lett. 1994, 1. (d) Sakaue,
S.; Tsubakino, T.; Nishiyama, Y.; Ishii, Y. J . Org. Chem. 1993, 58, 3633.
(e) Sakata, Y.; Katayama, Y.; Ishii, Y. Chem. Lett. 1992, 671. (f) Sakata,
Y.; Ishii, Y. J . Org. Chem. 1991, 56, 2633. (g) Ishii, Y.; Sakata, Y. J .
Org. Chem. 1990, 55, 5545. (h) Ishii, Y.; Yoshida, K.; Yamawaki, K.;
Ogawa, M. J . Org. Chem. 1988, 53, 5549. (i) Ishii, Y.; Yamawaki, K.;
Ura, T.; Yamada, H.; Yoshida, T.; Ogawa, M. J . Org. Chem. 1988, 53,
3587. (j) Yamawaki, K.; Nishihara, H.; Yoshida, K.; Ura, H.; Ishii, Y.;
Ogawa, M. Synth. Commun. 1984, 14, 865.
(5) Rozen, S.; Kol, M. J . Org. Chem. 1990, 55, 5155.
(6) (a) Huang, Q.; Xu, R. Beijing Daxue Xuebao, Ziran Kexueban
1989, 25, 427. (b) Banthorpe, D. V.; Barrow, S. E. Chem. Ind. 1981,
14, 502.
(7) Barret, R.; Pautet, F.; Daudon, M. Sabot, J . F. Pharm. Acta Helv.
1987, 62, 348.
(8) Zhu, X.; Xu, R. Beijing Daxue Xuebao, Ziran Kexueban 1989,
25, 507.
(9) Duncan, D. C.; Chambers, R. C.; Hecht, E.; Hill, C. L. J . Am.
Chem. Soc. 1995, 117, 681.
(10) (a) Neumann, R.; Gara, M. J . Am. Chem. Soc. 1994, 116, 5509.
(b) Neumann, R.; Khenkin, A. M. J . Org. Chem. 1994, 59, 7577.
S0022-3263(96)00275-7 CCC: $12.00 © 1996 American Chemical Society

5308 J . Org. Chem., Vol. 61, No. 16, 1996
Sakaguchi et al.
influence of a catalytic amount of heteropolyoxometa-
lates. The regioselectivity of the present oxidation is
discussed by considering the frontier electron density of
each double bond in the terpenes.
was obtained in high yield and the turnover number of
the catalyst reached 1180 (run 2), although Hill et al.
have stated that heteropolyoxometalates such as PCWP
react with the resulting epoxide to generate an inactive
inorganic species; hence the catalysis of the PCWP stops
after a modest number of turnovers, up to 500, in the
epoxidation of 1-octene.9 Recently, Neumann has re-
ported that a new type of polyoxometalate, [WZnMn2-
(ZnW9O34)2]12-, consisting of multiple components, shows
higher catalytic turnovers, 2300, than the PCWP for the
epoxidation of cyclooctene with 35% H2O2 under phase-
transfer conditions.10
On the basis of these results, several monoterpenes
were oxidized by the PCWP-H2O2 system (Table 1).
Ta ble 1. Ep oxid a tion of Va r iou s Mon oter p en es w ith 35%
H2O2 Ca ta lyzed by P CWP a
H2O2
(equiv)
time conv
selectivity
(%)
run substrate
(h)
(%) products
1
1
1
2
1.1
1.1
1.1
1.5
24
94 1a
89 1a
91 2a +2b
2c
97
89
87c
12
7
2b
3
4
2
5
2
5
4
5
6
7
2
3
3
4
1.1 + 1.1d
0.6 + 0.6a
2.5
100 2a + 2b
2ce
79
56
33
20
58
86
11
85
99
65
61
98
48
22
96 3a
3bf
100 3a
3bf
0.6 + 0.6d
100 4a
4bf
8
9
10
5
6
7
8
8
9
1.1
1.1
6
3
1
1
24
1
84 5a
100 6a
85 7a
83 8a
91 8a
100 9a f
9bf
0.6 + 0.6d
0.6 + 0.6d
1.5
11
12g
13
1.1
a
Substrate (4 mmol) was allowed to react with 35% H2O2 in
the presence of PCWP (0.02 mol, 0.5 mol %) at room temperature
b
c
in CHCl3 (5 mL). 0.05 mol % of PCWP was used. 2a :2b ) 90:
d
e
10. After stirring for 0.5 h, additional 35% H2O2 was used. cis-
2c:trans-2c ) 95:5. 3b, 4b, 9a , and 9b consisted of about 1:1
stereoisomeric mixture. 8 (4 mmol) was allowed to react with
f
g
35% H2O2 in the presence of CMP (0.016 mol, 0.4 mol %) and
MgSO4 (0.08 g) at room temperature in CHCl3 (10 mL).
γ-Terpinene (2) was epoxidized with 1.1 equiv of 35%
H2O2 in 91% conversion to form a 9:1 regioisomeric
mixture of monoepoxides 2a and 2b (87%) together with
a small amout of the diepoxide, 1,2,4,5-diepoxy-p-men-
thane (2c) (12%) (run 3). When an additional 35% H2O2
(1.1 equiv) was added to this oxidation system after 30
min, 2c was formed in preference to 2a and 2b (run 4).
It is noteworthy that the present epoxidation of 2
produced cis-2c with high stereoselectivity (cis-2c/trans-
2c ) 95/5), because the epoxidation of 2 by mCPBA
produces trans-2c rather than cis-2c (cis-2c/trans-2c )
30/70).11 The regioselectivity in the epoxidation of 2 will
be discussed later. The oxidation of neryl acetate (3) gave
6,7-epoxide 3a along with diepoxide 3b (run 5). By the
use of 2.5 equiv of the oxidant with respect to 3, 3b was
obtained as a major product (run 6). Geranyl acetate (4)
was also oxidized to monoxide 4a in good yield (run 7).
It is interesting to note that the oxidation of citral (5)
under these reaction conditions gave 3,7-dimethyl-6,7-
epoxy-2-octen-1-al (5a ) with good selectivity without
transformation of the aldehyde function to a carboxylic
Resu lts
Limonene (1) was chosen as a model substrate and
allowed to react with hydrogen peroxide by PCWP under
various reaction conditions. The oxidation of 1 with 1.1
equiv of 35% H2O2 in the presence of a catalytic amount
of PCWP (0.5 mol % with respect to 1) in chloroform at
room temperature proceeded regioselectively, but not
stereoselectively, to afford a nearly 1:1 mixture of cis-
and trans-limonene oxides (1a ) in almost quantitative
yield (Table 1, run 1). Even when the PCWP was reduced
to 0.05 mol% from 0.5 mol% under these conditions, 1a
(11) (a) Kozhin, S. A.; Sorochinskaya, E. I. Zh. Obshch. Khim. 1974,
44, 944. (b) Sorochinskaya, E. I. Sovrem. Probl. Khim. 1973, 48. (c)
Kozhin, S. A.; Sorochinskaya, E. I. Zh. Obshch. Khim. 1973, 43, 671.

Selective Oxidation of Monoterpenes
J . Org. Chem., Vol. 61, No. 16, 1996 5309
acid (run 8). These results show that the PCWP prefer-
entially promotes the epoxidation of the double bonds
over the oxidation of aldehydes to carboxylic acids. In
fact, the oxidation of an equimolar mixture of 2-octene
(10) and octanal by the PCWP-H2O2 system produced
2,3-epoxyoctane (10a ) rather than octanoic acid (eq 1).
present system. The oxidation of 1 with 35% H2O2 by
PCWP in tert-butyl alcohol resulted in 1a together with
large quantities of cleaved products such as vic-diol.
However, when a hydrogen peroxide solution of tert-butyl
alcohol obtained by removing the water by treating with
MgSO4 prior to use was employed, the epoxidation was
carried out with higher selectivity. Thus, 1 could be
oxidized to 1a in tert-butyl alcohol in 80% yield, and
1-octene (11), much less reactive than 1a , was also found
to be converted into 1,2-epoxyoctane (11a ) under reflux-
ing conditions in 76% yield (eqs 2 and 3).
In the oxidation of geranyl nitrile (6), monoepoxide 6a ,
in which the carbon-carbon double bond remote from a
cyano group was selectively oxidized, was obtained with
complete regioselectivity (run 9).
The oxidation of allylic monoterpenes such as nerol (7)
and geraniol (8) afforded 2,3-epoxides, 7a and 8a as main
products, in which allylic double bonds were preferen-
tially oxidized (runs 10 and 11). The moderate selectivi-
ties in these epoxidations are believed to be due to the
decomposition of the resulting epoxides by further oxida-
tion by the PCWP-H2O2 system. Molybdenum het-
eropolyoxometalate, [C5H5N+(CH2)15CH3]3(PMo12O40)3-
(CMP), which shows high selectivity for the epoxidation
of allylic alcohols,2j was found to be suitable for the
selective epoxidation of the allylic bonds of 7 and 8. Thus,
8 was converted into 8a with 35% H2O2 in the presence
of a catalytic amount of CMP with 98% selectivity (run
12). On the other hand, linalool (9) was transformed to
tetrahydrofuran derivative 9a (48%) and tetrahydropyran
derivative 9b (22%) by the PCWP-H2O2 system (run 13).
9a and 9b are considered to be formed via an intramo-
lecular cyclization of 3,7-dimethyl-6,7-epoxy-1-octen-3-ol
(9c) resulting from the epoxidation of 9 as shown in
Scheme 1. In contrast to the oxidation of 7 and 8 where
Discu ssion
Although several oxidation systems have been devel-
oped for the epoxidation of terpenes, a variety of mono-
terpenes was oxidized with aqueous hydrogen peroxide
by PCWP under biphase conditions to the corresponding
mono- and diepoxide with good regio- and/or stereose-
lectivities. There are some differences in the selectivity
of the terpene oxidation by the PCWP-H2O2 system
compared with those by conventional methods.
γ-Terpinene (2) was converted into the diepoxide 2c
with high stereoselectivity (cis-2c/trans-2c ) 95/5) by the
present oxidation system (Table 1, run 4), while the
epoxidation of 2 by mCPBA produced trans-2c rather
than cis-2c (cis-2c/trans-2c ) 30/70). In the epoxidation
of 2a and 2b by the PCWP-H2O2 system, the peroxo-
tungsten species seems to be favorable for approaching
the double bond from the same plane where the oxirane
ring is located, probably because of the neighboring effect
of the oxygen atom. Similar neighboring effects are
Sch em e 1. A P ossible Rea ction P a th for th e
Oxid a tion of Lin a lool (9) by th e P CWP -H2O2
System
observed in the epoxidation of 8-syn and 8-anti-hydroxy-
dicyclopentadienes by the heteropolyoxometalate-H2O2
system12 and the oxidation of 3-cyclohexen-1-ol with
t-BuOOH by Mo(CO)6 or VO(acac)2, where syn-3,4-ep-
oxycyclohexan-1-ol was produced with high stereoselec-
tivity (syn-epoxide/anti-epoxide ) 98/2).13
Although linalool (9) is reported to be converted into
3,7-dimethyl-1,2-epoxy-6-octen-3-ol (9d ) by VO(acac)213 or
the allylic double bonds were preferentially epoxidized,
the inner double bond of 9 was more easily oxidized than
the allylic one. A detailed consideration of the regio-
selectivity in the oxidation of 7, 8, and 9 will be described
later.
Although satisfactory results in the epoxidation of
monoterpenes by the PCWP-H2O2 system in chloroform
were obtained, the use of a chlorocarbon as the solvent
is undesirable from environmental and industrial points
of view.9 Hence, we attempted to use nontoxic solvents
other than chloroform, and it was found that tert-butyl
alcohol is suitable for the epoxidation of terpenes by the
Ti(OPri)4 with t-BuOOH, the oxidation of 9 by the
14
PCWP-H2O2 system produced about a 2:1 mixture of
hydroxy furan 9a and hydroxy pyran 9b (Table 1, run
13). The vanadium or titanium hydroperoxo complexes
generated by VO(acac)2 or Ti(OPri)4 and alkyl hydroper-
oxide are thought to coordinate to the hydroxy group of
(12) Okabayashi, T.; Nishimura, T.; Matoba, Y.; Yamawaki, K.; Ishii,
Y.; Hamanaka, S.; Ogawa, M. J . J pn. Petrol. Inst. 1986, 29, 419.
(13) Sharpless, K. B.; Michaelson, R. C. J . Am. Chem. Soc. 1973,
95, 6136.
(14) Sharpless, K. B.; Katsuki, T. J . Am. Chem. Soc. 1980, 102, 5976.

5310 J . Org. Chem., Vol. 61, No. 16, 1996
Sakaguchi et al.
9, and then the oxygen transfers to the allylic double bond
to form 9d . In contrast, the oxidation of 9 by the present
system took place at the inner double bond rather than
the allylic double bond. This finding indicates that the
PCWP possesses higher electrophilicity than the vana-
dium and titanium complexes.15
Recently, Tomaselli and co-workers demonstrated the
strong electrophilicity of the PCWP by spectroscopic
studies.16 They suggested that the remarkable electro-
philic reactivity of polyoxoperoxo complexes such as
PCWP, which are effective epoxidizing agents, in contrast
to anionic simple peroxo complexes such as MO(O2)2-
HMPT‚H2O (M ) Mo, W), is due to a more effective
charge delocalization in the former peroxo complexes. We
have shown that the PCWP possesses a strong electro-
philicity which can even epoxidize electron-deficient
alkenes such as R,â-unsaturated ketones.2g
(56%) along with considerable amounts of diepoxide 3b
(33%), whereas geranyl acetate 4, the geometric isomer
of 3, was converted into monoepoxide 4a (86%) and
diepoxide 4b (11%) under the same reaction conditions
(Table 1, runs 5 and 7). The higher regioselectivity for
4 could be reasonably explained by steric effects and by
comparing the large differences in the HOMO coefficients
between 3 and 4. The coefficients of the C2-C3 double
bond of 4 are somewhat smaller than those of the C6-C7
double bond of 4, compared with those of 3. Hence, the
epoxidation of 4 seems to proceed with high selectivity
at the C6-C7 double bond, in contrast to that of 3.
In the case of terpenes 7 and 8, the HOMO coefficients
of the C2-C3 double bonds are much smaller than those
of the C6-C7 positions, but the epoxidations of 7 and 8
took place at the C2-C3 double bonds. This is believed
to be due to the coordination of the PCWP to the primary
hydroxy groups of 7 and 8 taking place more easily than
that to the tertiary hydroxy group of 9. Therefore, the
epoxidation of 7 and 8 proceeds via the coordination of
the PCWP to the hydroxy group to form epoxy alcohols
7a and 8a , respectively.
In order to explain the regioselectivity in the PCWP-
catalyzed epoxidation of monoterpenes 1-9, the HOMO
coefficients of these substrates were calculated using the
CAChe system (Table 2).17 The eigenvectors in the
Ta ble 2. F r on tier Or bita l Coefficien ts of Va r iou s
Mon oter p en es
In summary, a variety of monoterpenes was selectively
oxidized with 35% H2O2 in the presence of a catalytic
amount of PCWP to give the corresponding mono- and
diepoxides in good yields under mild conditions. The
regioselectivity of the present epoxidation of terpenes is
rationally explained with MO calculations of the double
bonds in the terpene molecules.
eigenvectors
(eV)
eigenvectors
(eV)
terpene
coefficients terpene
coefficients
1
-9.299
-8.999
-9.297
-9.423
-9.517
C1 0.58423
C2 0.62090
C8 0.10685
C9 0.12366
C1 0.41516
C2 0.43447
C4 0.40056
C5 0.41897
C2 0.23278
C3 0.24490
C6 0.55871
C7 0.53411
C2 0.09402
C3 0.07805
C6 0.61937
C7 0.58931
C2 0.02670
C3 0.01427
C6 0.63220
C7 0.59366
6
7
8
9
-9.634
-9.099
-9.330
-9.526
C2 0.03007
C3 0.01870
C6 0.63525
C7 0.59314
C2 0.07121
C3 0.06056
C6 0.62700
C7 0.59490
C2 0.14011
C3 0.12343
C6 0.57970
C7 0.60718
C1 0.01294
C2 0.01017
C6 0.63186
C7 0.59592
2
3
4
5
Exp er im en ta l Section
Gen er a l P r oced u r es. All starting materials were com-
mercially available and used without further purification.
PCWP was prepared by the method reported previously.2d GC
analysis was performed with a flame ionization detector using
a 0.2 mm × 25 m capillary column (OV-1). 1H- and 13C-NMR
were measured at 270 and 67.5 MHz, respectively, in CDCl3
with Me4Si as the internal standard. Infrared (IR) spectra
were measured using NaCl pellets. GC-MS spectra were
obtained at an ionization energy of 70 eV. The yields of
products were estimated from the peak areas based on the
internal standard technique.
Gen er a l P r oced u r e for th e Oxid a tion of Ter p en es. To
a stirred solution of PCWP (41 mg, 0.5 mol %) and 35% H2O2
(4.4 mmol) in CHCl3 (5 mL) was added terpene (4 mmol), and
the reaction mixture was stirred at room temperature for
0.5-6 h. The reaction was quenched by adding water to the
reaction mixture, and the products were extracted with
dichloromethane. The extract was dried over anhydrous
MgSO4 and evaporated under reduced pressure. The products
were purified by column chromatography on silica gel (hexane/
ethyl acetate (10-3/1)). The compounds 2a ,9 2b,9 2c,9 3a ,19
3b,20 4a ,19 4b,20 5a ,21 7a ,13 8a ,2i,13 9a ,22 9b,22 and 9c13 were
reported previously.
HOMO of 1-9 were around -9 eV, and so the oxidation
of all these substrates can occur under similar conditions
(i.e., at room temperature for several hours). The regio-
selectivity of the epoxidation of 1-9 by the PCWP-H2O2
system can be correlated with the frontier molecular
orbital calculations. The carbon-carbon double bonds
having the larger HOMO coefficient in 1-9 (except for 7
and 8) were found to be preferentially oxidized, which
indicates that the regioselectivity in the epoxidation of
terpenes is dominated by the electron density of the
double bonds.
For example, in the substrate 2, the C1-C2 double
bond, having larger HOMO coefficients than the C4-C5
bond, was preferentially oxidized to form 2a although
there could be a steric influence (Table 1, run 3). The
oxidation of neryl acetate 3 produced monoepoxide 3a
3,7-Dim eth yl-6,7-ep oxy-2-octen en itr ile (6a ): IR (NaCl)
1
2964, 2217, 1633, 1446, 1379, 1123, 798, 678 cm-1; H-NMR
(CDCl3, 270 MHz) δ 5.19 (s, 1H), 2.76 (t, J ) 6.3 Hz, 1H), 2.69
(dd, J ) 5.0 and 7.6 Hz, 2H), 1.96 (s, 3H), 1.75-1.57 (m, 2H),
1.33 (s, 3H), 1.29 (s, 3H); δ 5.19 (s, 1H), 2.57 (t, J ) 7.6 Hz,
1H), 2.36 (dd, J ) 7.3 and 15.2 Hz, 2H), 2.09 (s, 3H), 1.85-
1.71 (m, 2H), 1.32 (s, 3H), 1.28 (s, 3H); 13C-NMR (CDCl3, 67.8
(19) (a) Barrero, A. F.; Alvarez-M., Enrique J .; Palomino, P. L.
Tetrahedron 1994, 50, 13239. (b) Canonica, L.; Rindone, B.; Santaniello,
E.; Scolastico, C. Tetrahedron 1972, 28, 4395.
(20) (a) Takai, T.; Hata, E.; Yamada, T.; Mukaiyama, T. Bull. Chem.
Soc. J pn. 1991, 64, 2513. (b) Amouroux, R.; Folefoc, G.; Chastrette,
F.; Chastrette, M. Tetrahedron Lett. 1981, 22, 2259.
(21) (a) Murphy, W. S.; Culhane, A.; Duffy, B.; Tuladhar, S. M. J .
Chem. Soc., Perkin Trans. 1 1992, 3397. (b) Dupuy, C.; Luche, J . L.
Tetrahedron 1989, 45, 3437.
(15) Arcoria, A.; Ballistreri, F. P. Tomaselli, G. A.; Furia, F. D.;
Modena, G. J . Org. Chem. 1986, 51, 2374.
(16) Ballistreri, F. P.; Tomaselli, G. A.; Toscano, R. M.; Conte, V.;
Furia, F. D. J . Mol. Cat. 1994, 89, 295.
(17) The geometries of 1-9 were calculated by the PM3 semiem-
pirical method18 as implemented in the MOPAC version 6.10 system.
The calculation was performed twice to localize the two double bonds
of the monoterpenes into the XY plane.
(18) Stewart, J . J . J . J . Comput. Chem. 1989, 10, 209.
(22) Prat, D.; Lett, R. Tetrahedron Lett. 1986, 27, 707.

Selective Oxidation of Monoterpenes
J . Org. Chem., Vol. 61, No. 16, 1996 5311
MHz) δ 164.1, 163.9, 116.7, 116.5, 96.2, 95.6, 62.9, 62.9, 58.3,
58.2, 35.3, 32.9, 26.9, 26.4, 26.2, 24.5, 20.8, 18.5, 18.4.
P r oced u r e for t h e E p oxid a t ion of 1 in ter t-Bu t yl
Alcoh ol. To a stirred solution of 35% H2O2 (9 mmol) in
t-BuOH (15 mL) was added anhydrous MgSO4 (1.5 g), and the
suspended solution was stirred at room temperature for 0.5 h
and filtered. To the filtrate were added PCWP (62 mg, 0.5
mol %) and 1 (6 mmol), and the mixture was stirred at 40 °C
for 2 h. The workup was performed by the same method as
described above.
Ack n ow led gm en t. We thank Okishiran Chemical
Company Ltd. for financial support.
Su p p or tin g In for m a tion Ava ila ble: Copies of NMR
spectra (26 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
J O960275Q