Efficient synthesis of (1R,4S,6R)-4-Isopropenyl-1,3,3-trimethyl-7- oxabicyclo[4.1.0]heptan-2-one

Article abstract of DOI:10.1134/S1070428011020047

A simple and convenient one-pot synthesis of (1R,4S,6R)-4-isopropenyl-1,3, 3-trimethyl-7-oxabicyclo[4.1.0]heptan-2-one was developed consisting in a thermodynamic methylation of carvone (NaH, MeI, THF, 20°C) followed by the epoxidation with alkalinized hy

Full text of DOI:10.1134/S1070428011020047

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 2, pp. 173179. Pleiades Publishing, Ltd., 2011.
Original Russian Text  N.K. Selezneva, F.A. Gimalova, R.F. Valeev, M.S. Miftakhov, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 2,
pp. 185191.
Efficient Synthesis
of (1R,4S,6R)-4-Isopropenyl-1,3,3-trimethyl-7-
oxabicyclo[4.1.0]heptan-2-one
N. K. Selezneva, F. A. Gimalova, R. F. Valeev, and M. S. Miftakhov
Institute of Organic Chemistry, Ufa Scientific Center, Russian Academy of Sciences,
Ufa, 450054 Russia
e-mail: bioreg@anrb.ru
Received April 15, 2010
Abstract—A simple and convenient one-pot synthesis of (1R,4S,6R)-4-isopropenyl-1,3,3-trimethyl-7-
oxabicyclo[4.1.0]heptan-2-one was developed consisting in a thermodynamic methylation of carvone (NaH,
MeI, THF, 20°C) followed by the epoxidation with alkalinized hydrogen peroxide. The reduction of the obtained
epoxyketone with sodium borohydride proceeded stereoselectively to give a β-alcohol. The attempts to convert
its isopropenyl fragment into an acetate group by a rearrangement of products or intermediates of the oxidative
fragmentation resulted only in obtaining intermediate acyl derivatives.
DOI: 10.1134/S1070428011020047
Among chiral matrices from natural sources (sugars,
amino acids, monoterpenes etc.) d-carvone is attractive
by its availability, inexpensiveness, and unique topology
providing a possibility of a fast preparation of variously
functionalized cyclohexane block-synthons. A number
of these synthons and descriptions of their application
in targeted syntheses were mentioned in recent publica-
tions [1–5].
As the precursor of the target block I we selected the
known 6,6-dimethylcarvone [12] which fundamentally
like carvone [13] could be selectively epoxidized with
alkaline hydrogen peroxide. The introduction of the gem-
dimethyl group into the carvone structure was performed
by the alkylation of its kinetic enolate with MeI to obtain
monomethyl derivative III with repeating subsequently
the same alkylation as described in [12].
Because of the necessity to use organometallic com-
pounds (BuLi, LDA), to work in an inert atmosphere and
at low temperature, of the prolonged alkylation stages
(~12 h) the above procedure for the synthesis of compound
II is impractical and inconvenient. We developed a ver-
sion of the synthesis of compound I where the key stage
of carvone methylation occurred under the conditions of
the thermodynamic control by excess MeI using as the
We report here on a simple one-pot synthesis of new
gem-dimethyl-containing cyclohexane block I from
d-carvone, and on some its reactions. Cyclohexane
fragments with the gem-dimethyl group are present in
the structure of many naturally occurring compounds,
in particular, in diterpenoids of the types of atisane [6],
tapsane [7], spongnane [8], valeriananes А–С [9], taxoids
[10] etc. [11].
Scheme 1.
O
O
O
O
O
MeI
MeI
LDA
LDA
d-carvone
d-carbon
,-III
II
I
173

SELEZNEVA et al.
174
base NaH in the medium of THF–HMPA, 4 : 1, at room
temperature. The reaction mixture was stirred for 10 h,
then the crude product was filtered through a bed of silica
gel. The products obtained are difficult to separate on SiO2.
product, and the present more polar compounds were not
isolated. One of the possible minor compounds neces-
sary for its identification in the mixture, the epimers of
6-methylcarvones (III), were prepared by procedure [14]
through the kinetic alkylation of the carvone enolate with
MeI. The formed 6-methylcarvone was an isomeric mixture
of 6α- and 6β-methylcarvones in the ratio ~4 : 1 (from
the 1Н NMR spectrum according to the integral intensity
of the different signals of 6-Mе). For the assignment of
epimers III the doublet signals of the 6-methyl group are
characteristic. The signal of the β-epimer is located upfield,
besides, the signal of the methylene group of the α-(III)
is a two-proton singlet, whereas the methylene group of
β-(III) gives rise to two separate singlets.
1
According to the Н NMR data the mixture contained
two main compounds, 6,6-dimethylcarvone and residual
HMPA in about equal quantity. Therewith the fraction of
the minor side products of the mono- and polyalkylation
is also significant, but the precise quantitative estimation
of their amount is difficult. The analytically pure sample
of compound II was successfully prepared by the repeated
chromatography of the mixture on a longer column packed
with SiO2. Therewith the compound less retained on silica
gel than compound II proved to be the monomethylated
O
O
C 26.32
C 21.87
2
2


C Me 12.48,


C Me 10.46,
2
2
C H 0.9 ppm,
C H 1.3 ppm,
J 6 Hz
J 6 Hz
Н 4.77 s (2Н)
Н 4.71 s (1Н), 4.88 s (1H)
C 18.14
-III
C 21.87
-III
1
The comparison of the Н NMR spectra of the ob-
tained mixture of the products of carvone methylation
under the conditions of the thermodynamic control and
of the spectrum of the methylcarvones from the model
synthesis indicated the presence of the main compound
II, minor α-(III) and β-(III) in the ratio 4 : 1, and un-
identified compounds (presumably products of С4- and
О-alkylation) (Scheme 2). As seen, the ratio of isomers
of the methylcarvones is approximately the same as in
the products of the kinetic alkylation. The problem of
isolation of individual compound II for using it in further
reactions found an unexpected solution in the stage of the
epoxidation with the alkaline hydrogen peroxide. Into this
reaction we brought the mixture of compounds II, III,
and the others hoping that the arising epoxy compounds
would have higher Rf values and would be suitable for
the separation by the column chromatography on SiO2.
However as a result of the reaction we isolated a single
individual reaction product I. The expected epoxide IV
was not detected. Apparently epoxide IV originating
from monomethyl derivative III and the other epoxy by-
products unlike compound I enolized under the reaction
conditions and thus initiated intermolecular condensation
processes involving compounds III and IV or led to the
formation of more polar compounds of type VI through
Faworsky intermediate V [15] (Scheme 3).
As a whole, this “self-cleaning” reaction simplified
the isolation of epoxide I, and the elaborated route
carvone  (I) turned out to be convenient for the pre-
Scheme 2.
O
O
O
O
O
O
30% H2O2
MeI, NaH
Not identified
compounds
+
+
+
aqueous NaOH
HMFA, THF
I, ~50%
-III
-III
II
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 2 2011

EFFICIENT SYNTHESIS OF (1R,4S,6R)-4-ISOPROPENYL-1,3,3-
175
Scheme 3.
Products of intermolecular condensation
O
O
CH2O
O
O
_
OH
OH
O
OH
+
regio-isomers
+
IV
VI
V
The application of more severe conditions (the oxida-
parative accumulation of a considerable quantity of this
compound.
tion with m-CPBAin boiling dichloroethane) resulted in a
mixture of compounds, and the oxidation of compound X
with the use of CF3CO3H (prepared as described in [19])
afforded hydration product XII.
After development of the efficient synthetic way to
epoxide I we studied its reduction with NaBH4 and oxi-
dation aiming at possible conversion of its isopropenyl
fragment into an acetate group. The reduction of ketone
I with NaBH4 in MеОН occurred with a good stereose-
lectivity with the predominant formation of β-alcohol
VII (Scheme 4).
As seen, the lack of the expected products (acetates)
in the Criegee rearrangement of the ozonides obtained
from epoxy derivatives I and VIII, and also in the prod-
ucts of Baeyer–Villiger oxidation of methyl ketones X
and XI with m-CPBA demonstrated the impeding of
the desired reactions by the gem-dimethyl groups in
the substrates. Evidently in the Criegee intermediates
XIV leading to the acetates IX and XIII the migration
of the functionalized cyclohexane substituent does not
occur, and only the ejection of methyl peroxyacetyl takes
place (Scheme 6).
The content of the minor α-alcohol VII was no more
than 3–5%, and it was easily removed by chromatography
of the mixture on SiO2. The assumed stereochemistry
of the chiral center С2 in β-(VII) was confirmed by the
NOE data for methyl ketone XI obtained from its acetate
β-(VIII) (see the figure).
We further planned to obtain from compound I block
IX promising for further application.
In the absence of the gem-dimethyl substituents at
С6, namely, in carvone proper, the conversion of the
isopropenyl group into the acetyl group can be readily
performed by oxidation with m-CPBA of diketone XV
obtained by the ozonolytic cleavage of known epoxide
XVI [20].
O
O
O
O
Scheme 4.
OAc
I
IX
O
HO
NaBH4
In the case of methyl-free analogs of compound I two
approaches were used for the conversion of the propenyl
function into the acetyl group, involving the Criegee rear-
rangement of ozonides [16, 17] or oxidation by Baeyer–
Villiger method of methyl ketones obtained by oxidative
cleavage of the propenyl part of the substrate [18].
I
MeOH
-VII
O
O
Both versions of the Criegee rearrangement of ozon-
ides were tested on epoxiketone I and epoxyacetate VIII.
However in both cases only methyl ketones X and XI
were obtained (Scheme 5). We also failed to carry out
the Baeyer–Villiger oxidation of methyl ketones X and
XI with the use of m-CPBA at 20°С in CH2Cl2.
AcO
HO
Ac2O_Py
4-DMAP
-VII
-VIII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 2 2011

SELEZNEVA et al.
176
Scheme 5.
OH
(1) O3, CH2Cl2_MeOH
O
O
OH
O
6
(2) Ac2O, Et3N, 4-DMAP, 
CF3CO3H
1
2
5
4
I
CH2Cl2
3
O
O
m-CPBA,
CH2Cl2, 3 days
XII
X
IX
O
O
O
(1) O3, MeOH
(2) Cu(OAc)2, FeSO4. 7H2O
AcO
AcO
AcO
m-CPBA
CH2Cl2, 3 days
OAc
XIII
O
XI
VIII
Scheme 6.
O
O
O
O
O
O
O
_AcOOMe
_AcO_, _CH3+
OMe
OAc
IX
O
O Ac
X
XIV
EXPERIMENTAL
(1) O3, CH2Cl2, _78°C
(2) PPh3
O
O
O
IR spectra were recorded on a spectrophotom-
O
1
eter Shimadzu IR Prestige-21 from thin films. Н and
13С NMR spectra were registered on a spectrometer
Bruker AM-300 at operating frequencies 300.13 and
75.47 MHz respectively, internal eference TMS. Op-
tical rotation was measured on a polarimeter Perkin
Elmer-341. Mass spectra were obtained on instruments
Thermo Finnigan MAT 95XP(ionizing chamber tempera-
ture 200°С, sample admission at temperature 5–270°С,
heating rate 22 deg/min) and Shimadzu LCMS-2010
(chemical ionization at atmospheric pressure) electrons
energy 20eV with registration of positive and negative
ions. Liquid mobile phase MеОН–water, 1 : 1, flow rate
0.03 or 0.05 ml/min. The reaction progress was monitored
by TLC on Sorbfil plates (Russia), spots visualized with
acidified solution of anise aldehyde.
XV
XVI
O
O
m-CPBA, CH2Cl2
25°C, 24 h
OAc
XVII
Thus we described here the preparatively conve-
nient method of the synthesis of new functionalized
gem-dimethyl-containing cyclohexane block from the
d-carvone.
(1R,4S,6R)-4-Isopropenyl-1,3,3-trimethyl-7-
oxabicyclo[4.1.0]heptan-2-one (I). To a solution of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 2 2011

EFFICIENT SYNTHESIS OF (1R,4S,6R)-4-ISOPROPENYL-1,3,3-
177
5.0 g (33.3 mmol) of R-carvone in 50 ml of THF–HMPA (С5), 113.21 (=СН2), 134.79 (С2), 143.39 (С3), 145.69
mixture, 4 : 1, at 20°С was added 6.48 g (272.11 mmol)
of 55% NaH and 38.8 ml (272.11 mmol) of MeI, and
the reaction mixture was stirred for 10 h. To the reaction
mixture 5 ml of saturated water solution of NH4Cl was
added and then the mixture was diluted with 200 ml of
ЕtOAc, the organic phase was washed in succession with
saturated solutions of NaHCO3 and NaCl, dried with
Na2SO4, and evaporated. The residue was filtered through
a bed of SiO2, the elution with a mixture petroleum
ether–EtOAc, 20 : 1. We obtained 10.5 g of the mixture
of alkylation products and HMPA. To the solution of
10 g of the obtained mixture, 8.85 ml of 30% solution of
Н2О2 in 75 ml of MеОН cooled to 0°С was added 11 ml
of 4.0 N NaOH solution, and the reaction mixture was
stirred for 15 min at this temperature and then 10 h at room
temperature. The reaction mixture was diluted with 45 ml
of H2O, extracted with CH2Cl2 (3 × 10 ml), the combined
organic extracts were dried with MgSO4, and evaporated.
The residue was subjected to column chromatography
on SiO2 (eluent petroleum ether–EtOAc, 5 : 1). Yield 3.0
g (50%), colorless oily substance, [α]D20 +77.7° (с 1.995,
CHCl3). 1Н NMR spectrum (CDCl3), δ, ppm: 0.96 s and
1.09 s (6Н, gem-СН3), 1.41 s (3Н, СН3), 1.75 s (3Н,
СН3), 2.12–2.18 m (2Н, СН2), 2.54 d.d (1Н, Н4, J 9.6,
J 6.6 Hz), 3.37 t (1Н, ОСН, J 2.0 Hz), 4.73 s (1Н) and
4.95 s (1Н, =СН2). 13С NMR spectrum (CDCl3), δ, ppm:
16.59 (CH3), 19.71 and 24.36 (gem-CH3), 23.09 (CH2),
26.79 (СН2), 42.79 (С4), 45.99 (С3), 57.35 (С1), 60.49
(С6), 111.68 (=СН2), 144.26 (С1'), 209.11 (С2). Mass
spectrum, m/z (Irel, %): 194 [M]+ (2), 179 [M – CН3]+
(12), 166 [M – CO]+ (12), 151 (23), 110 (35), 85 (46), 81
(100). Found, %: C 73.89; H 9.22. C12H18O2. Calculated,
%: C 74.19; H 9.34. M 194.27.
(С1'), 201.77 (С1). Found, %: C 80.48; H 10.03. C12H18O.
Calculated, %: C 80.85; H 10.18.
(5R,5S)-5-Isopropenyl-2,6-dimethylcyclohex-2-en-
1-one α-(III). IR spectrum, ν, cm–1: 2953, 1674, 1645,
1
1436, 1365, 894. Н NMR spectrum (CDCl3), δ, ppm:
1.02 d (3Н, СН3, J 6.0 Hz), 1.68 s (3Н, СН3), 1.74 s (3Н,
СН3), 2.20–2.45 m (2Н) and 2.66 m (1Н, СН, СН2),
4.71 br.s (2Н, =СН2), 6.65 m (1Н, Н3). 13С NMR spec-
trum (CDCl3), δ, ppm: 12.48 (CH3), 16.09 (CH3), 18.14
(CH3), 31.17 (С4), 44.20 (С6), 50.61 (С5), 113.14 (=СН2),
133.62 (С2), 143.27 (С3), 145.58 (С1'), 201.41 (С1).
(5R,6R)-5-Isopropenyl-2,6-dimethylcyclohex-2-
1
en-1-one β-(III). Н NMR spectrum (CDCl3), δ, ppm:
0.89 d (3Н, СН3, J 6.0 Hz), 1.67 s (3Н, СН3), 1.74 s (3Н,
СН3), 2.20–2.40 m (3Н, СН, СН2), 4.71 s and 4.88 s (2Н,
=СН2), 6.65 m (1Н, Н3). 13С NMR spectrum (CDCl3),
δ, ppm: 10.46 (CH3), 15.92 (CH3), 21.87 (CH3), 26.32
(С4), 42.98 (С5), 44.80 (С6), 111.52 (=СН2), 134.69 (С2),
143.90 (С3), 144.80 (С1'), 203.17 (С1).
(1S,4S,6R)-4-Isopropenyl-1,3,3-trimethyl-7-
oxabicyclo[4.1.0]heptan-2-ol (VII). To a dispersion of
0.15 g (3.95 mmol) of NaBH4 in 5 ml of MeOH cooled to
0°С was added a solution of 0.25 g (1.30 mmol) of com-
pound I in 3 ml of MeOH, and the reaction mixture was
stirred at this temperature till complete consumption of
the initial compound (TLC monitoring). The 2 ml of H2O
was added to the reaction mixture, methanol was evapo-
rated, and the residue was extracted with CHCl3 (4 × 5
ml). The combined extracts were washed with brine, dried
with MgSO4, and evaporated. The residue was subjected
to chromatography on SiO2 (eluent EtOAc–petroleum
ether, 1 : 5) to obtain 0.16 g (64%) of oily compound
β-(VII) with a small (~5%) impurity of alcohol α-(VII).
[α]D20 –8.1° (с 2.17, CHCl3). IR spectrum, ν, cm–1: 3408,
3078, 1722, 1445, 1444, 1375, 1207, 1080, 1061, 1031,
985, 974, 897, 882, 788, 731. Main β-isomer. 1Н NMR
spectrum (CDCl3), δ, ppm: 0.82 s and 0.89 s (6Н, gem-
СН3), 1.35 s (3Н, СН3), 1.74 s (3Н, СН3), 1.98 m (3Н,
СН, СН2), 2.10 br.s (1Н, ОН), 3.09 s (1Н, Н6), 3.42 d
(1Н, Н2, J 4.2 Hz), 4.72 s (1Н) and 4.88 t (1Н, =СН2,
J 1.3, J 1.6 Hz). 13С NMR spectrum (CDCl3), δ, ppm:
13.38 (CH3), 20.04 and 24.99 (gem-CH3), 24.44 (CH3),
27.94 (СН2), 37.21 (С3), 44.12 (С4), 60.04 (С1), 61.35
(С6), 78.54 (С2), 113.49 (=СН2), 145.75 (С1'). Minor
(5S)-5-Isopropenyl-2,6,6-trimethylcyclohex-2-en-
1-one (II). The analytically pure sample of compound II
was obtained by the repeated chromatography on column
packed with SiO2 of 0.5 g of crude mixture obtained
by the methylation in the preceding experiment (eluent
petroleum ether–EtOAc, 20 : 1, 15 : 1, 10 : 1). Colorless
oily substance, [α]D20 –9.3° (с 1.11, CHCl3) {[α]D25 +1.8°
(с 3.8, CHCl3) [12]}. IR spectrum, ν, cm–1: 2970, 2924,
1701, 1670, 1451, 1377, 1358, 1201, 1039, 895, 842.
1Н NMR spectrum (CDCl3), δ, ppm: 1.02 s and 1.12 s (6Н,
gem-СН3), 1.69 s (3Н, СН3), 1.75 s (3Н, СН3), 2.42 m
(2Н, СН, СН2), 2.52 d.d (1Н, СН2, J 5.4, J 7.6 Hz), 4.76 s
(1Н) and 4.86 s (1Н, =СН2), 6.61 m (1Н, =СН). 13С NMR
spectrum (CDCl3), δ, ppm: 16.05 (CH3), 18.21 and 24.45
(gem-CH3), 20.35 (CH3), 31.21 (С4), 44.64 (С6), 50.62
1
α-isomer. Н NMR spectrum (CDCl3), δ, ppm: 0.84 s
and 0.91 s (6Н, gem-СН3), 1.37 s (3Н, СН3), 1.76 s (3Н,
СН3), 1.87 d (1Н, СН, J 2.2 Hz), 1.98 m (1Н, СН2) and
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 2 2011

SELEZNEVA et al.
178
(С4), 44.18 (С3), 57.47 (С1), 59.81 (С6), 206.59 (С1'),
209.44 (С2). Mass spectrum, m/z (Irel, %): 196 [M]+ (4),
168 [M – CO]+ (8), 153 [M – CН3CO]+ (10), 125 [M –
СО – CН3CO]+ (22), 111 (10), 83 (49), 43 (100). Found,
%: C 67.66; H 8.34. C11H16O3. Calculated, %: C 67.32;
H 8.22. M 196.25.
1.99 d (1Н, СН2, J 1.9 Hz), 2.10 br.s (1Н, ОН), 3.09 s
(1Н, Н6), 3.42 d (1Н, Н2, J 4.2 Hz), 4.72 s (1Н) and 4.88
t (1Н, =СН2, J 1.3, J 1.6 Hz).
(1R,2R,4S,6R)-4-Isopropenyl-1,3,3-trimethyl-7-
oxabicyclo[4.1.0]hept-2-yl acetate (VIII). To a stirred
solution of 0.1 g (0.51 mmol) of alcohol VII in 5 ml of
pyridine was added 0.29 ml (2.55 mmol) of acetic anhy-
dride and 1 mg of DMAP, and the reaction mixture was
stirred till complete consumption of the initial compound
(TLC monitoring) (~20 h). Then the reaction mixture was
diluted with 5 ml of ice water, extracted with CHCl3, the
extracts were dried with MgSO4 and evaporated. The
obtained substance was subjected to column chroma-
tography on SiO2 (eluent EtOAc–petroleum ether, 1 :
(1R,2R,4R,6R)-4-Acetyl-1,3,3-trimethyl-7-oxa-
bicyclo[4.1.0]hept-2-yl acetate (XI). Through a solution
of 0.15 g (0.63 mmol) of compound VIII in 20 ml of the
mixture of anhydrous methanol and dichloromethane in
the presence of 10 mg of NaHCO3 at –40°С while stirring
was passes the ozone-oxygen mixture till the solution
turned blue. The excess О3 was flushed from the reaction
mixture by the argon flow, at –40°С 0.25 g (1.27 mmol)
of Cu(OAc)2 was added, the reaction mixture was stirred
for 15 min, 0.21 g (0.76 mmol) of FeSO4·7H2O was
added, the mixture was warmed to room temperature,
and the stirring was continued for 18 h. Then 5 ml of
water was added, methanol was evaporated, the residue
was extracted with EtOAc, the organic phase was washed
in succession with saturated solutions of NaHCO3 and
NaCl, dried with MgSO4, and evaporated. The residue
was subjected to column chromatography on SiO2 (eluent
EtOAc–petroleum ether, 1 : 5). Yield 0.015 g (47%).
Colorless oily substance, [α]D20 –84.8° (с 0.885, CHCl3).
1Н NMR spectrum (CDCl3), δ, ppm: 0.87 s and 0.97 s
(6Н, gem-СН3), 1.20 s (3Н, СН3), 2.14 s (3Н, COСН3),
2.17 s (3Н, COСН3), 1.99 d.d (1Н, СН2, J 15.0, J 5.2 Hz)
and 2.59 d.d (1Н, СН2, J 5.2, J 11.9 Hz), 2.09 m (1Н,
СН), 3.09 s (1Н, Н6), 4.75 с (1Н, Н2). 13С NMR spec-
trum (CDCl3), δ, ppm: 14.38 (CH3), 19.49 and 24.86
(gem-CH3), 20.68 (CH3), 24.40 (СН3), 33.10 (СН2),
35.98 (С3), 48.92 (С4), 58.46 (С1), 59.96 (С6), 77.50 (С2),
170.50 (Ас), 210.21 (С=О). Found, %: C 65.45; H 8.30.
C13H20O4. Calculated, %: C 64.98; H 8.39.
1
4). Yield 0.12 g (98%). Н NMR spectrum (CDCl3), δ,
ppm: 0.77 s and 0.89 s (6Н, gem-СН3), 1.20 s (3Н, СН3),
1.75 s (3Н, СН3), 2.14 s (3Н, COСН3), 1.98 m (3Н, СН,
СН2), 3.09 s (1Н, Н6), 4.75 s (2Н, =СН2), 4.91 s (1Н,
Н2). 13С NMR spectrum (CDCl3), δ, ppm: 14.52 (CH3),
19.73 and 24.68 (gem-CH3), 20.82 (CH3), 24.55 (СН3),
27.92 (СН2), 36.51 (С3), 43.75 (С4), 58.49 (С1), 60.75
(С6), 78.85 (С2), 113.94 (=СН2), 145.22 (С1'), 170.36
(Ас). Found, %: C 70.13; H 9.19. C14H22O3. Calculated,
%: C 70.56; H 9.30.
(1R,4R,6R)-4-Acetyl-1,3,3-trimethyl-7-oxabi-
cyclo[4.1.0]heptan-2-one (X). Through a solution of
0.2 g (1.03 mmol) of compound I in 20 ml of the mix-
ture of anhydrous methanol and dichloromethane, 1 : 5,
at –70°С while stirring was passed the ozone-oxygen
mixture till the solution turned blue. The excess О3 was
flushed from the reaction mixture by the argon flow, the
reaction mixture was heated to room temperature and
evaporated. The residue was dissolved in 10 ml of ben-
zene, 1 ml of Ас2О, 0.7 ml of triethylamine, and 2 mg of
DMAP were added, the mixture was stirred for 30 min
at room temperature and then boiled for 7 h. The mixture
was cooled, diluted with H2O, the water layer was ex-
tracted with EtOAc, the combined organic solutions were
washed with 5% HCl, then with brine, dried with MgSO4,
and evaporated. The residue was subjected to column
chromatography on SiO2 (eluent EtOAc–petroleum ether,
1 : 5) Yield 0.1 g (50%). Colorless oily substance, [α]
(3R,5R,6S)-3-Acetyl-5,6-dihydroxy-2,2,6-
trimethylcyclohexan-1-one (XII). To 1.5 ml of CH2Cl2
at 0°С was added 0.02 ml of H2O2, 0.1 ml of trifluoro-
acetic anhydride, the mixture was stirred for 10 min, then
a solution was added of 0.03 g of epoxide X in 0.5 ml of
CH2Cl2, and the stirring was continued for 10–15 min
at this temperature. The reaction mixture was diluted
with CH2Cl2, was washed in succession with saturated
solutions of NaHCO3 and NaCl, dried with MgSO4, and
evaporated. The residue was subjected to column chro-
matography on SiO2 (eluent EtOAc–petroleum ether, 1 :
5). Yield 0.015 g (47%). Colorless oily substance, [α]D20
+16.4° (с 0.787, CHCl3). 1Н NMR spectrum (CDCl3), δ,
20 +18.8° (с 1.16, CHCl3). 1Н NMR spectrum (CDCl3),
D
δ, ppm: 1.03 s (3Н, СН3), 1.20 s and 1.42 s (6Н, gem-
СН3), 2.18 s (3Н, СН3), 2.19–2.26 m (2Н, СН2), 2.99
d.d (1Н, Н4, J 9.05, J 5.4 Hz), 3.35 t (1Н, Н6, J 2.3 Hz).
13С NMR spectrum (CDCl3), δ, ppm: 16.31 (CH3), 20.09
and 22.98 (gem-CH3), 23.73 (СН2), 32.14 (CH3), 50.02
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 2 2011

EFFICIENT SYNTHESIS OF (1R,4S,6R)-4-ISOPROPENYL-1,3,3-
179
ppm: 1.10 s (3Н, СН3), 1.28 s and 1.35 s (6Н, gem-СН3),
2.07 d.d (1Н, СН2, J 5.4, J 3.1 Hz), 2.14 d.d (1Н, СН2,
J 11.8, J 5.2 Hz), 2.22 s (3Н, СН3), 2.98 d.d (1Н, Н3,
J 5.4, J 3.4 Hz), 2.62 br.s (1Н, ОН), 3.93 d.d (1Н, Н5,
J 5.4, J 11.9 Hz), 4.13 br.s (1Н, ОН). 13С NMR spectrum
(CDCl3), δ, ppm: 21.91 and 26.22 (gem-CH3), 23.73
(CH3), 27.26 (С4), 30.95 (CH3), 44.16 (С2), 56.63 (С3),
73.07 (С5), 79.92 (С6), 209.88 (С1), 214.65 (С1').
(C2). Found, %: C 59.01; H 6.80. C9H12O4. Calculated,
%: C 58.69; H 6.57.
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(1R,4R,6R)-4-Acetyl-1-methyl-7-oxabicyclo-[4.1.0]
heptan-2-one (XV). Through a solution of 2 g (12.0 mmol)
of epoxycarvone XVI obtained from d-(–)-carvone [20]
in 40 ml of MеОН at –78°С while stirring was passed the
ozone-oxygen mixture till the solution turned blue. The
excess О3 was flushed from the reaction mixture by the
argon flow, 3.30 g (12.6 mmol) of PPh3 was added, the
temperature was raised to ambient, and the stirring was
continued for 3 h. Then the solvent was distilled off, and
the residue was distilled at 128–130°С (4 mm Hg). Yield
1.29 g (64%). Viscous light-yellow fluid. IR spectrum, ν,
cm–1: 2984, 2934, 1712. 1Н NMR spectrum (CDCl3) δ,
ppm: 1.38 s (3Н, СН3), 1.91–1.99 m (1Н, СН2), 2.15 s
(3Н, СН3), 2.19–2.25 m (1Н, СН2), 2.44–2.48 m (1Н,
СН2), 2.59 d.d (1Н, СН2, J 3.2, J 18.1 Hz), 3.04–3.13 m
(1Н, Н6), 3.42–3.43 m (1Н, Н4). 13С NMR spectrum
(CDCl3), δ, ppm: 15.06 (CH3), 25.80 (С5), 28.23 (СН3),
37.53 (C3), 41.83 (C4), 58.96 (C1), 60.55 (C6), 203.84
(C=O), 208.23 (C=O).
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hept-4-yl acetate (XVII). To a solution of 0.5 g
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added 5.9 g (23.8 mmol) of 70% m-CPBA, the mixture
was stirred for 48h at room temperature. Then 1.5 ml
of Me2S was added, the reaction mixture was washed
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less crystals, mp 84–86°C, [α]D20 +18.1° (с 1.98, СHCl3).
IR spectrum, ν, cm–1: 1740, 1720, 1242, 1040. 1Н NMR
spectrum (CDCl3), δ, ppm: 1.44 s (3Н, СН3), 2.03 s
(3Н, СН3), 2.10–2.16 m (1Н, СН2), 2.33 d.d (1Н, СН2,
J 6.2, J 15.7 Hz), 2.54 d.d (1Н, СН2, J 4.4, J 15.9 Hz),
2.96 d.d (1Н, СН2, J 3.54, J 15.7 Hz), 3.44 s (1Н, Н6),
5.24–5.26 m (1Н, Н4). 13С NMR spectrum (CDCl3), δ,
ppm: 14.67 (СH3), 20.99 (CH3), 29.37 (C5), 40.84 (C3),
59.38 (C1), 61.81 (C6), 69.40 (C4), 169.83 (C=O), 203.97
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 2 2011