Reaction of (±)-7,7-dichloro-4-(1-methylethylidene)-bicyclo[3.2.0] hept-2-en-6-one with ozone

Article abstract of DOI:10.1134/S1070428010070092

The reaction of (±)-7,7-dichloro-4-(1-methylethylidene)bicyclo[3.2. 0]hept-2-en-6-one with ozone involves mainly the exocyclic double bond, and subsequent unusual transformations of ozonides thus formed lead to anomalous products.

Full text of DOI:10.1134/S1070428010070092

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 7, pp. 1013–1016. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © Z.R. Valiullina, N.P. Akhmetdinova, N.A. Ivanova, A.A. Fatykhov, N.S. Vostrikov, M.S. Miftakhov, 2010, published in Zhurnal
Organicheskoi Khimii, 2010, Vol. 46, No. 7, pp. 1016–1018.
Reaction of (±)-7,7-Dichloro-4-(1-methylethylidene)-
bicyclo[3.2.0]hept-2-en-6-one with Ozone
Z. R. Valiullina, N. P. Akhmetdinova, N. A. Ivanova, A. A. Fatykhov,
N. S. Vostrikov, and M. S. Miftakhov
Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: bioreg@anrb.ru
Received June 5, 2009
Abstract—The reaction of (±)-7,7-dichloro-4-(1-methylethylidene)bicyclo[3.2.0]hept-2-en-6-one with ozone
involves mainly the exocyclic double bond, and subsequent unusual transformations of ozonides thus formed
lead to anomalous products.
DOI: 10.1134/S1070428010070092
Selective ozonolysis of one double bond in cyclic
polyene systems provides an effective route to syn-
thetically valuable unsaturated α,ω-dioxo compounds.
Although ozone is extremely reactive and nonselective
oxidant, available examples of selective ozonolysis
convincingly demonstrate wide potential of this proce-
dure [1–4]. In the present work we made an attempt to
build up bicyclic cyclopentenone intermediate product
II in one step (Scheme 1) from readily accessible
[2+2]-adduct I of dimethylfulvene and dichloroketene
[5]. For this purpose, we examined the possibility for
effecting selective ozonolysis of the exocyclic double
bond in compound I.
bonds), which precipitated from the solution [6]. Ac-
cording to the procedure described in [6], ozonolysis
of diene I was carried out in cyclohexane in the pres-
ence of methanol at 5°C; however, no solid separated
from the solution. Therefore, the reaction was stopped
after the required amount of ozone was passed and the
initial compound was completely consumed (TLC).
The mixture was subjected to standard treatment
(purging with argon and decomposition of ozonides
with Me2S), and TLC analysis revealed three products
which were isolated by column chromatography on
silica gel. On the basis of their spectral parameters the
products were assigned structures III–VI (Scheme 2).
Scheme 1.
Scheme 2.
Me
O
Me
O
COOMe
(1) O3, cyclo-C6H12–MeOH (10:1), 5°C
(2) Me2S
O
O
Ozone
Cl
I
Cl
Cl
Cl
Cl
Cl
I
II
III
Taking into account that the reactivities of exhaus-
tively substituted exocyclic double bond and endo-
cyclic double bond in I do not differ to a strong extent,
we used a procedure for selective ozonolysis of diene
(polyene) systems. This procedure implies fast remov-
al from the reaction zone of primary hydroperoxide
intermediates generated by ozonolysis of the more
reactive double bond (or one of equally reactive double
Me
Me
OH
O
O
O
O
MeO
O
+
+
+
COOMe
Cl
Cl
Cl
COOMe
Cl
IV
V
VI
1013

VALIULLINA et al.
1014
Scheme 3.
b
O–
O
O
O
Me
Me
O
O
a
O–
O
O
O
a
b
O
O
+
+
Me
Me
Me
Me
Cl
Cl
Cl
Cl
Cl
Cl
II
VIII
VII
IX
No expected recombination of compounds II and
Isomeric compounds IV and V could not be separated
by chromatography on silica gel; the spectral param-
eters of particular isomers were obtained from isomer
mixtures and were easy to interpret.
VIII occurred, and bicyclic dichloro diketone II under-
went fast rearrangement into compound X. Disrotatory
electrocyclic ring expansion in X leads to dichloro
tropone derivative XI. In the next step, intramolecular
Michael reaction of diketone XII (which is tautomeric
to tropone XI) yields Favorskii intermediate XIII. The
three-membered ring in the latter is opened by the
action of methanol with high regioselectivity to give
XIV. The subsequent allylic rearrangement of tauto-
mer XV afforded enone III (Scheme 4) whose struc-
ture unambiguously followed from the NMR and mass
spectra. The COSY spectrum revealed coupling of the
CHCl proton with protons both in the methylene group
and at the double bond. Here, it is important that the
described transformation series does not involve reduc-
ing agent: compound III was detected by TLC directly
in the course of ozonolysis before addition of Me2S.
It is seen that the ozonolysis of adduct I leads to
formation of several unusual compounds as a result of
oxidative cutting of the isopropylidene fragment. Ob-
viously, ring expansion products III–V and stable per-
oxide VI as precursor of enone II are formed via sub-
sequent transformations of primary intermediates in
the ozonolysis of compound I.
The formation of substituted cyclohexenone III
may be rationalized as follows. [3+2]-Cycloaddition
of ozone molecule to adduct I yields ozonide VII
whose subsequent fragmentation could follow two
paths, a and b (Scheme 3). It is known that the frag-
mentation of 1,2,3-trioxolanes derived from unsym-
metrically substituted olefins is determined by elec-
tronic and steric factors [7–9]. In our case, path a
seems to be preferred, taking into account that carbon-
yl oxide fragment VIII possesses electron-donating
substituents, whereas compound II has an electron-
withdrawing group. Path b seems to be less favorable,
for carbonyl oxide IX is sterically more crowded than
compound VIII and destabilized due to the presence of
the neighboring C=O group.
We failed to propose a reasonable mechanism for
the formation of cyclohexadienes IV and V. Scheme 5
illustrates the formation of peroxide VI. Presumably,
in the recombination step intermediate Criegee zwit-
terion XVI captures methanol molecule instead of
acetone, and only then methoxyperoxide ion (or hydro-
peroxide) XVII reacts with acetone as shown in
Scheme 5 to give peroxide VI. No molecular ion peak
Scheme 4.
O
O
O
O
Cl
Cl
Cl
O
O
OH
O
Cl
Cl
Cl
Cl
XI
Cl
XII
II
X
O
COOMe
Cl
COOMe
Cl
Cl
MeOH
MeOH
III
O–
OH
O
Cl
XIII
Cl
Cl
XIV
XV
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

REACTION OF (±)-7,7-DICHLORO-4-(1-METHYLETHYLIDENE)BICYCLO[3.2.0]...
1015
Scheme 5.
Me
Me
OH
O
Me
O–
–O
O
H
O
Me
Me
O
O
O
MeO
MeO
O
O
O
Cl
Cl
Cl
Cl
Cl
Cl
XVI
XVII
VI
acetate, 7:3). IR spectrum, ν, cm–1: 1747, 1714 (C=O);
was observed in the mass spectrum of VI, but a strong
peak was present due to ion [XVIII]+, m/z 207, result-
ing from elimination of O2, acetone, and H+ from the
molecular ion of VI. Also, ion peaks formed by frag-
mentation of [XVIII]+ were observed.
1
1267 (C–O); 833 (C–Cl). H NMR spectrum, δ, ppm:
3
2
2.42 d.d (1H, 6-H, J = 2.9, J = 18.7 Hz), 2.63 d.d
3
2
(1H, 6-H, J = 6.8, J = 18.7 Hz), 3.93 s (3H, OMe),
4
3
4.07 m (1H, 5-H), 6.40 d.d (1H, 3-H, J = 2.1, J =
3
3
5.8 Hz), 7.65 d.d (1H, 4-H, J4,5 = 2.3, J4,3 = 5.8 Hz).
13C NMR spectrum, δC, ppm: 38.15 (C6), 53.15 (OMe),
54.53 (C5), 84.07 (C1), 137.65 (C3), 159.69 (C4),
165.58 (C=O), 205.96 (C2). Mass spectrum, m/z
(Irel, %): 222 (9.2) [M]+, 187 (100) [M – Cl]+. Found,
%: C 43.12; H 3.54; Cl 31.88. C8H8Cl2O3. Calculated,
%: C 43.08; H 3.62; Cl 31.79.
+·
MeO
O
Cl
Cl
XVIII
(±)-Methyl 2-chloro-5-oxocyclohexa-1,3-diene-1-
carboxylate (IV). Rf 0.33 (petroleum ether–ethyl
acetate, 7:3). IR spectrum, ν, cm–1: 1734, 1710 (C=O);
EXPERIMENTAL
1
The IR spectra were recorded on a Shimadzu IR
Prestige-21 spectrophotometer from samples prepared
as thin films or dispersed in mineral oil. The NMR
spectra were measured on a Bruker AM-300 spectrom-
1604 (C=C); 1033 (C–O). H NMR spectrum, δ, ppm:
3.45 s (2H, 6-H), 3.89 s (3H, OMe), 6.63 d (1H, 4-H,
3
13
3J = 5.7 Hz), 8.25 d (1H, 3-H, J = 5.7 Hz). C NMR
spectrum, δC, ppm: 40.95 (C6), 53.57 (OMe), 119.34
(C2), 139.64 (C4), 146.43 (C1), 153.88 (C3), 162.46
(C=O), 203.94 (C5). Mass spectrum, m/z (Irel, %): 186
(100) [M]+, 158 (59) [M – CO]+, 151 (18.5) [M – Cl]+,
143 (62) [M – MeCO]+, 127 (30) [M – CO2Me]+.
Found, %: C 51.53; H 3.74; Cl 18.98. C8H7Cl2O3.
Calculated, %: C 51.50; H 3.78; Cl 19.00.
1
eter at 300.13 MHz for H or 75.47 MHz for 13C;
CDCl3 was used as solvent and reference (CHCl3,
δ 7.27 ppm; δC 77.00 ppm). The progress of reactions
was monitored by TLC (Silufol, petroleum ether–ethyl
acetate); spots were detected by treatment with a 10%
solution of p-methoxybenzaldehyde in ethanol contain-
ing sulfuric acid.
(±)-Methyl 2-chloro-4-oxocyclohexa-1,5-diene-1-
Ozonolysis of (±)-7,7-dichloro-4-(1-methylethyli-
dene)bicyclo[3.2.0]hept-2-en-6-one (I). An ozone–
oxygen mixture was bubbled through a solution of
0.20 g (0.92 mmol) of diene I in a mixture of 10 ml of
cyclohexane and 1 ml of methanol at 5°C until com-
plete conversion of the initial compound (TLC). The
mixture was purged with argon, 0.7 ml of dimethyl
sulfide was added, and the mixture was left overnight.
The mixture was then concentrated on a rotary evap-
orator, and the residue was subjected to column chro-
matography on silica gel using petroleum ether–ethyl
acetate (95:5) as eluent to isolate 0.064 g (32%) of
cyclohexenone III, 0.010 g (6%) of a mixture of IV
and V at a ratio of 1:3, and 0.013 g (5%) of VI.
carboxylate (V). Rf 0.33 (petroleum ether–ethyl
1
acetate, 7:3). H NMR spectrum, δ, ppm: 3.18 s (2H,
3-H), 3.91 s (3H, OMe), 6.55 d (1H, 5-H, 3J = 5.7 Hz),
3
8.72 d (1H, 6-H, J = 5.7 Hz). 13C NMR spectrum,
δC, ppm: 40.69 (C3), 53.11 (OMe), 117.66 (C2),
139.47 (C6), 147.93 (C1), 153.03 (C5), 161.88 (C=O),
201.74 (C4).
(±)-7,7-Dichloro-4-[(1-hydroxy-1-methylethyl)-
dioxy]-4-methoxybicyclo[3.2.0]hept-2-en-6-one (VI).
Rf 0.19 (petroleum ether–ethyl acetate, 7:3). IR spec-
trum, ν, cm–1: 3435 (OH), 1805 (C=O), 1091 (C–O).
1H NMR spectrum, δ, ppm: 1.06 s (3H, Me), 1.20 s
3
(3H, Me), 3.24 s (3H, OMe), 3.88 d.d (1H, 5-H, J5,1
=
3
3
7.3, J5,3 = 1.3 Hz), 4.32 d.d (1H, 1-H, J1,2 = 2.5,
3J1, 5 = 7.3 Hz), 6.16 d.d (1H, 3-H, J = 5.7, J =
4
3
(±)-Methyl 1,5-dichloro-2-oxocyclohex-3-ene-1-
carboxylate (III). Rf 0.26 (petroleum ether–ethyl
3
3
1.3 Hz), 6.22 d.d (1H, 2-H, J2,3 = 5.7, J2,1 = 2.5 Hz).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

VALIULLINA et al.
1016
13C NMR spectrum, δC, ppm: 23.34 (Me), 24.15 (Me),
51.20 (OMe), 56.96 (C1), 61.99 (C5), 74.93 (C7), 86.63
(CMe2), 98.67 (C4), 132.87 (C2), 136.22 (C3), 194.85
(C6). Mass spectrum, m/z (Irel, %): 207 (17.9) [M]+, 171
(100) [M – Cl]+, 143 (76) [M – CO=CCl2]+. Found, %:
C 44.49; H 4.70; Cl 23.90. C11H14Cl2O5. Calculated,
%: C 44.46; H 4.75; Cl 23.86.
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by the Federal Science and Innovation Agency (state
contract no. 02.512.12.2015).
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