Solid acid-catalysed isomerization of R(+)-limonene diepoxides

Article abstract of DOI:10.1070/MC2005v015n02ABEH001983

The isomerization of diastereomeric R(+)-limonene diepoxides on solid catalysts, such as clays, zeolites, and solid superacids, results in the formation of bicyclic and tricyclic oxygen-containing compounds.

Full text of DOI:10.1070/MC2005v015n02ABEH001983

,
2005, 15(2), 59–61
Solid acid-catalysed isomerization of R(+)-limonene diepoxides
a
b
b
b
Oksana V. Salomatina,* Olga I. Yarovaya, Dina V. Korchagina, Marina P. Polovinka and
Vladimir A. Barkhash
b
a
Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Russian Federation. E-mail: ana@nioch.nsc.ru
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences,
b
6
30090 Novosibirsk, Russian Federation. Fax: +7 3832 34 4752
DOI: 10.1070/MC2005v015n02ABEH001983
The isomerization of diastereomeric R(+)-limonene diepoxides on solid catalysts, such as clays, zeolites, and solid superacids,
results in the formation of bicyclic and tricyclic oxygen-containing compounds.
Epoxides (oxiranes) are versatile intermediates in organic syn-
thesis. Chemical reactions of terpene epoxide compounds are of
considerable interest because various products can be prepared
8,9-epoxide ring with the nucleophilic participation of a hydroxyl
group to form compounds 3 or 4. Cation B also reacts via two
paths. One of the reaction paths of this rearrangement consists
in the intermediate formation of an aldehyde group by hydride
shift followed by the interaction of this group with the epoxide
ring to form two isomeric compounds 6a,b. The other reaction
path, the stabilization of a cation due to the interaction with the
1,2-epoxide ring, leads to two bicyclic ions C and D, which are
formed by rotation about the C(4)–C(8) bond in cation B. Next,
cation C is converted into compound 4 as a result of proton
detachment and the formation of a double bond, whereas cation
1
on this basis. The use of zeolites, clays, and solid superacids
as catalysts in intramolecular and intermolecular reactions of
terpenes and their oxygen-containing derivatives provides an
opportunity not only to lower the activation barriers of well-known
reactions but also to change the reaction paths, as compared
2
with homogeneous chemical reactions. For example, previ-
3
ously, we found that the isomerization of citral and citronellal
6
,7-epoxides on solid acid catalysts resulted in the formation of
bicyclic ethers, which are structural analogues of well-known
pheromones, whereas these products were not formed under
conditions of homogeneous acid catalysis. In the context of the
biological importance of oxygen-containing p-menthane deriva-
tives, we studied the reactions of the diepoxy derivatives of
R(+)-limonene, which is a widespread naturally occurring com-
‡
Limonene diepoxide 1a,b (0.5 g, 3 mmol) was added to a suspension
of K-10 clay (1 g, calcined for 3 h at 100 °C) and CH Cl (20 ml, dried).
The reaction mixture was stirred at room temperature for 20 min and
filtered. The crude product (0.46 g) was chromatographed (SiO , a
hexane/hexane–80% diethyl ether eluent was used) to give 0.05 g (10%)
of compound 2, 0.07 g (14%) of compound 4, 0.085 g (17%) of com-
pound 5 and 0.01 g (2%) of compounds 6a,b.
2
2
2
4
pound. Note that terpene diepoxides are a poorly studied class
of organic compounds. Diepoxides 1a,b† as a mixture of
(1S,2S,5S,6R)-1,5-Dimethyl-3,10-dioxatricyclo[4.2.1.12,5]decane
2:
,
1
11
9an
H NMR (400 MHz, CCl + CDCl ) d: 0.95 (s, 3H ), 1.158 (ddd, H
diastereomers with respect to the C(8) atom were prepared by
4
3
8ex
Jan,syn 11.5 Hz, J9an,6 4 Hz, J9an,2 1.5 Hz), 1.161 (ddd, H , J8ex,8en 11.5 Hz,
J8ex,7ex 11.5 Hz, J8ex,7en 4 Hz), 1.22 (s, 3H ), 1.61 (dddd, H , J7ex,7en
1
H
the action of bromosuccinimide on limonene in an aqueous
1
2
7ex
dioxane solution followed by dibromohydrin decomposition.5
1.5 Hz , J
11.5 Hz, J
5.5 Hz, J7ex,8en 2.5 Hz), 1.80–1.95 (m,
7
ex,8ex
7ex,6
9syn
We found that the isomerization of diastereomeric diepoxides
8en
6
7en
, H , H ), 2.00 (ddd, H , J 11.5 Hz, J
2.5 Hz, J
2.5 Hz),
1.5 Hz).
9syn,6
9syn,7en
1
a,b on either synthetic K-10 clay or natural ascanite-bentonite
4
4'
2
3
.33 (d, H , J 7 Hz), 4.05 (d, H , J 7 Hz), 4.82 (d, H , J
4,4' 2,9an
clay resulted in compounds 2, 4, 5 and 6a,b in a ratio of ~4:3:7:2,
13
C NMR, d: 46.21 (s, C-1), 108.84 (d, C-2), 74.55 (t, C-4), 82.01 (s, C-5),
‡
respectively (GLC data). With the use of wide-pore zeolite β
4
4.09 (d, C-6), 27.75 (t, C-7), 34.13 (t, C-8), 38.91 (t, C-9), 20.04 (q,
2
–
20
or a TiO /SO solid superacid as a catalyst, the qualitative and
C-11), 19.27 (q, C-12). MS, m/z: 168 [M+]. [a] +29.4 (c 1.36, CHCl3).
2
4
580
quantitative composition of the reaction mixture was changed:
{(1R,5R,7R)-4,7-Dimethyl-6-oxabicyclo[3.2.1]oct-3-en-7-yl}methanol
4.6 [a]580 +154.0 (c 0.91, CHCl ).
20
compounds 2, 3 and 5 were formed in a ratio of ~2:2:5 or
3
§
(1R,3S,6S,9R)-3,6-Dimethyl-2,5-dioxatricyclo[4.4.0.03,9]decane 5:
~
3:1:2, respectively (GLC data).
1
12
11
H NMR (400 MHz, CCl + CDCl ) d: 1.17 (s, 3H ), 1.24 (s, 3H ),
We proposed a mechanism for the formation of these com-
4
3
7
10
7'
8
10'
1
1
2
.52 (m, H ), 1.55 (br. d, H , J
11 Hz), 1.62–1.72 (m, H , H , H ),
.82 (m, H , J 14 Hz, J8',7 9 Hz , J8',7' 9 Hz, J8',10' 2 Hz , J8',9 1.5 Hz),
6.5 Hz, J9,8 5 Hz, J 2 Hz, J9,8' 1.5 Hz), 3.47 (dd,
H , J 9.5 Hz, J 1 Hz), 3.94 (d, H , J 9.5 Hz), 4.03 (dd, H , J 3 Hz,
J1,9 2 Hz). C NMR, d: 81.80 (d, C-1), 78.21 (s, C-3), 70.01 (t, C-4),
2.41 (s, C-6), 32.17 (t, C-7), 25.02 (t, C-8), 41.40 (d, C-9), 33.01 (t,
C-10), 23.32 (q, C-11), 27.91 (q, C-12). MS, m/z: 168 [M ]. [a] +3.9
pounds. Initially, an epoxide ring is opened to form cations A or
B. Next, cation A reacts via the following two alternative paths:
10,10'
8
'
8
',8
9
.20 (dddd, H , J
9
,10'
9,1
(
a) the narrowing of a six-membered ring to a five-membered
4
4'
1
4,4'
4,10
1,10'
ring due to the migration of a C–C bond followed by the reac-
tion of the resulting aldehyde group with a second epoxide ring
to form compound 2; (b) proton detachment occurs with the
formation of a double bond followed by the opening of an
1
3
7
+
20
5
80
(c 7.7, CHCl3).
(
1R,3S,6R,8R,10S)-3,10-Dimethyl-2,9-dioxatricyclo[4.3.1.03,8]decane
†
1
12
Limonene diepoxides 1a,b in a 3:2 ratio between isomers were
6a: H NMR (400 MHz, CCl + CDCl ) d: 1.01 (d, 3H , J
1.214 (s, 3H ), 1.31 (dm, H , J 13.5 Hz, J7,8 3 Hz), 1.55 (br. q, H ,
J10,12 7 Hz), 1.98 (dm, H , J 13.5 Hz, J 4 Hz, J7',5' 2 Hz, J 2 Hz),
7',6 7',8
3.82 (m, H , J 3 Hz, J 2 Hz, J 1.5 Hz), 5.01 (br. s, H ), 1.37–1.55
7 Hz),
4
7
3
12,10
1
1
10
obtained from R(+)-limonene (Aldrich, 98% ee), yield 31%.
7,7'
1
7'
Limonene diepoxide 1a: H NMR (400 MHz, CCl + CDCl ) d: 1.01
4
3
4
a
8
1
(
3
dddd, H , J
12 Hz, J
12 Hz, J
6.5 Hz, J
3 Hz), 1.14 (s,
15 Hz), 1.55 (dd,
4
a,3a
4a,5a
4a,3e
4a,5e
8,7
8,7'
5
8,6
13
10
7
5a
5e
6
4
H ), 1.23 (s, 3H ), 1.26 (m, H ), 1.44 (dm, H , J
15.5 Hz, J 12 Hz), 1.57 (ddd, H , J
J6a,5e 5 Hz), 1.86 (dddd, H , J 15.5 Hz, J 6.5 Hz, J
and 1.65–1.93 (m, H , 2H , 2H ). C NMR, d: 105.04 (d, C-1), 78.17 (s,
C-3), 29.70 (t, C-4), 27.79 (t, C-5), 31.57 (d, C-6), 26.10 (t, C-7), 78.58
(d, C-8), 43.41 (d, C-10), 27.07 (q, C-11), 15.76 (q, C-12).
5
e,5a
3
a
6a
H , J
15.5 Hz, J6a,5a 12 Hz,
3
a,3e
6a,6e
3
e
5 Hz, J
2 Hz),
5 Hz).
3e,2e
3e,5e
6e
9
2e
(1R,3S,6R,8R,10R)-3,10-Dimethyl-2,9-dioxatricyclo[4.3.1.03,8]decane
1
.97 (dm, H , J 15.5 Hz), 2.37–2.47 (m, 2H ), 2.85 (br. d, H , J
2e,3e
1
3
1
12
C NMR, d: 57.17 (s, C-1), 58.08 (d, C-2), 26.59 (t, C-3), 39.97 (d, C-4),
1.36 (t, C-5), 30.21 (t, C-6), 22.95 (q, C-7), 58.29 (s, C-8), 52.79 (t, C-9),
7.48 (q, C-10).
6b: H NMR (400 MHz, CCl + CDCl ) d: 0.85 (d, 3H , J
7 Hz),
4
3
12,10
1
1
10
8
1
13
2
1
1.211 (s, 3H ), 1.88 (m, H ), 3.86 (m, H ), 4.94 (m, H ). C NMR, d:
104.96 (d, C-1), 79.34 (s, C-3), 29.18 (t, C-4), 19.49 (t, C-5), 31.02 (d,
C-6), 30.95 (t, C-7), 77.73 (d, C-8), 40.07 (d, C-10), 26.98 (q, C-11),
14.60 (q, C-12).
1
Limonene diepoxide 1b: H NMR (400 MHz, CCl + CDCl ) d: 1.15
4
3
1
0
7
4
5
(
(
(
d, 3H , J
0.8 Hz), 1.23 (s, 3H ), 1.06–1.32 (m, H , 2H ), 1.49–1.61
1
0,9
6
3a
6'
m, H ), 1.66 (dd, H , J
15.5 Hz, J3a,4a 11.5 Hz), 1.94 (m, H ), 2.01
a,3e
Compounds 6a,b in a ratio of ~1:1 between isomers: MS, m/z: 168
3
3
e
9
2e
13
+
20
m, H ), 2.37–2.47 (m, 2H ), 2.88 (br. d, H , J
5 Hz). C NMR, d:
[M ]. [a] +0.35 (c 0.45, CHCl3).
2
e,3e
580
5
7.21 (s, C-1), 58.20 (d, C-2), 26.46 (t, C-3), 39.39 (d, C-4), 21.24 (t,
Limonene diepoxide 1a,b (0.01 g, 0.06 mmol) was added to a suspen-
sion of ascanite-bentonite clay (0.02 g, calcined for 3 h at 100 °C) and
CH Cl (2 ml, dried). The reaction mixture was stirred at room tem-
C-5), 30.33 (t, C-6), 22.93 (q, C-7), 58.61 (s, C-8), 52.41 (t, C-9), 18.06
(
q, C-10).
2
2
Limonene diepoxides 1a,b in a 3:2 ratio between isomers: MS, m/z:
perature for 5 min and filtered. Analysis by gas-liquid chromatography
showed that the reaction mixture contained compounds 2, 4, 5 and 6a,b.
+
20
1
68 [M ]. [a] +35.5 (c 3.5, CHCl3).
5
80
Mendeleev Commun. 2005 59

,
2005, 15(2), 59–61
7
O
O
O
He
O
OH
1
4
6
2
(a)
a
H+
H+
~H
5
3
C~C
– H+
Ha
O
O
O
OH
O
8
10
9
A
1a,b
B
H+ (b)
–
Han
Hex
syn
H
11
H'
H
9
OH
1
1
3
7
O
O
O
8
1
4
3
2
9
Hen
8
4
10O
6
OH
6
12
7
5
5
O10
O
HO
O
2
1
1
2
C
D
H+
6a,b
2
–
– H+
Han Hsyn
H
H'
9
1
1
10
12
1
8
2
1
7
O
6
H 7
10
2
O
O
He
5
3
6
9
4
3
8
11
OH
H
HO
Ha
5O
4
3
4
5
Scheme 1
D results in compound 5 by the interaction of the hydroxyl
group with the cationic centre.
signals appeared in the LRJMD spectrum on the suppression
of the signal of another methyl group at 1.17 ppm: a doublet at
81.80 ppm (C-1), a singlet at 72.41 ppm (C-6) and a triplet
at 31.12 ppm (C-7). Hence it follows that signals at 1.24 and
With the use of column chromatography, individual com-
pounds 2–5 were isolated, and compounds 6a,b were separated
as isomer mixtures in a ~1:1 ratio. The structures of compounds
1
11
1.17 ppm in the H NMR spectrum belong to the C H and
3
1
13
12
1
–6 were found by H and C NMR spectroscopy and mass
C H groups, respectively. The signals of methyl groups in the
C NMR spectrum were attributed based on a two-dimensional
C– H correlation spectrum. The isomerism of compounds
3
1
3
spectrometry. Spectroscopic data for compound 4 are consistent
6
13
1
with published data.
Let us consider in more detail the structural characterization
6a,b is likely due to different orientations of the methyl group
at the C-10 atom; it is believed that this group occurs in the β-
or α-position in isomer 6a or 6b, respectively. This is suggested
by the chemical shifts of C-10, C-5 and C-7 atoms, which are
most sensitive to changes in the position of a substituent at the
C-10 atom.8
of the compounds obtained. In the structure of 3, the occurrence
4
of the long-range spin–spin coupling constant J
1 Hz of the
1
0,3a
1
0
C H group suggests its axial orientation. According to Dreiding
3
models, the spin–spin coupling constant between H-2 and H-9an
4
1
protons ( J
1.5 Hz) observed in the H NMR spectrum of
2
,9an
compound 2 is consistent with a structure in which the pyran
Compounds 2, 5 and 6a,b were not described previously,
whereas compound 3 was isolated from the essential oil of
ring exhibits a chair rather than boat shape. Signals due to
1
7
methyl groups in the H NMR spectra of compound 5 were
Haplopappus multifolius, and (+)-bottrospicatol 4 is the product
6
attributed based on LRJMD spectra. Thus, on the suppression
of the signal due to a methyl group at 1.24 ppm, a singlet at
of the action of Streptomyces bottropensis on (–)-cis-carveol.
The oxirane ring is a structural unit of many synthetic and
natural biologically active compounds. Diepoxides can be formed
in nature as a result of the enzymatic oxidation or autoxidation
of terpene double bonds; therefore, studies of the reactions of
diepoxides in acidic media are of importance for modelling
reactions that occur under natural conditions and for supporting
various biogenetic schemes.
Thus, we examined the reactions of limonene diepoxides under
conditions of heterogeneous acid catalysis. Along with known
compounds, a number of bicyclic and tricyclic oxygen-contain-
ing products, which were not described previously, were obtained.
7
8.21 ppm, a triplet at 70.01 ppm, and a doublet at 41.40 ppm
appeared in the LRJMD spectra, which were attributed to the
C-3, C-4 and C-9 atoms, respectively, whereas another set of
§
Limonene diepoxide 1a,b (0.1 g, 0.6 mmol) was added to a suspension
of zeolite β (0.2 g, calcined for 3 h at 500 °C) and CH Cl (10 ml, dried).
2
2
The reaction mixture was stirred for 20 min at room temperature and
filtered. The crude product (0.08 g) was chromatographed (SiO , a
2
hexane/hexane–80% diethyl ether eluent was used) to give 0.002 g (2%)
of compound 2, 0.01 g (10%) of compound 3 and 0.02 g (20%) of
compound 5.
1
(1R,4R,5R)-4,8-Dimethyl-2-oxabicyclo[3.3.1]non-7-en-4-ol 3. H NMR
1
0
We are grateful to the Russian Foundation for Basic Research
for access to the STN International databases (grant no. 00-03-
32721) via the STN Centre at the N. N. Vorozhtsov Novosibirsk
Institute of Organic Chemistry, Siberian Branch of the Russian
Academy of Sciences, 630090 Novosibirsk, Russia.
(
H
3
H
2
1
400 MHz, CCl + CDCl ) d: 1.38 (d, 3H , J
1 Hz), 1.58 (dddd,
4
3
10,3a
9
an
, J9an,9syn 13 Hz, J9an,5 3.5 Hz, J9an,1 2 Hz, J9an,3e 1 Hz), 1.67 (m,
11
5
H , J
2.5 Hz, J11,6' 1.5 Hz, J11,7 1.5 Hz), 1.79 (m, H ), 2.03 (dddd,
1
1,6
9
syn
6
, J 13 Hz, J
3.5 Hz, J9syn,1 3.5 Hz, J9syn,6' 1.5 Hz), 2.05 (m, H ),
syn,5
9
6
'
.42 (dm, H , J 19 Hz, J 4.5 Hz, J6',5 1.5 Hz, J6',9syn 1.5 Hz, J6',11
6',6 6',7
3
e
.5 Hz), 3.16 (ddd, H , J
11 Hz, J 1.2 Hz, J3e,9an 1 Hz), 3.33 (dq,
3e,5
3
e,3a
3a
1
7
H , J 11 and 1 Hz), 3.86 (m, H , J
3.5 Hz, J1,9an 2 Hz), 5.67 (m, H ,
1
,9syn
References
1
3
J7,6' 4.5 Hz, J7,6 3 Hz, J7,11 1.5 Hz). C NMR, d: 69.46 (d, C-1), 67.46 (t,
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1
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+
20
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5
80
3
4
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–
sion of a TiO /SO solid superacid (0.02 g, calcined for 3 h at 400 °C)
2
4
2
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2
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(
6
0
Mendeleev Commun. 2005

,
2005, 15(2), 59–61
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Mendeleev Commun. 2005 61