A new class of herbicides that are derivatives of 8-oxabicyclo[3.2.1]oct-6-en-3-one

Article abstract of DOI:10.1071/CH99044

Treatment of 8-oxabicyclo[3.2.1]oct-6-en-3-one with a catalytic amount of osmium tetraoxide and excess hydrogen peroxide resulted in the formation of the acetonide exo-6,exo-7-isopropylidenedioxy-8-oxabicyclo[3.2.1]oct-3-one (2), in 96% yield. This aceton

Full text of DOI:10.1071/CH99044

C S I R O P U B L I S H I N G
Australian Journal
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Volume 52, 1999
© CSIRO Australia 1999
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Aust. J. Chem., 1999, 52, 929–935
A New Class of Herbicides that are Derivatives
of 8-Oxabicyclo[3.2.1]oct-6-en-3-one
Luiz Cláudio de A. Barbosa,A,B Gelson J. A. Conceição,A Antônio J. Demuner,A
Antônio A. Silva,C John MannD and Dorila Piló-VelosoE
A Laboratório de Análise e Síntese de Agroquímicos, Departamento de Química,
Universidade Federal de Viçosa, 36571-000 Viçosa-MG, Brazil.
B Author to whom correspondence should be addressed (e-mail: lcab@mail.ufv.br).
C Departamento de Fitotecnia, Universidade Federal de Viçosa, 36571-000 Viçosa-MG, Brazil.
D Chemistry Department, Reading University, Reading RG6 6AD, Berkshire, England.
E Departamento de Química, UFMG, 31270-901 Belo Horizonte-MG, Brazil.
Treatment of 8-oxabicyclo[3.2.1]oct-6-en-3-one with a catalytic amount of osmium tetraoxide and excess hydrogen
peroxide resulted in the formation of the acetonide exo-6,exo-7-isopropylidenedioxy-8-oxabicyclo[3.2.1]oct-3-one
(2), in 96% yield. This acetonide was converted into several aromatic alcohols (4a–k) through a Grignard reaction.
The alcohols were treated with aqueous HCl in acetone, and the corresponding alkenes (5a–c,e–g, j,k) were obtained
in 26–46% overall yield, from the ketone (2). The herbicidal activity of the alkenes was evaluated at a concentra-
tion of 6.6 µg g–1. All compounds showed an inhibitory effect (21–66%) on the Sorghum bicolor radicle growth.
The inhibition of the accumulation of fresh and dried weight of the aerial parts of Cucumis sativus, after 14 days,
varied from 7.1 to 60.7% and from 0.0 to 41.6%, respectively. Compounds (5a,e–g) caused 100% mortality of C.
sativus, after 20 days. Compound (5g) (exo-6,exo-7-isopropylidenedioxy-3-(3-methylphenyl)-8-oxabicy-
clo[3.2.1]oct-2-ene) was evaluated against several weeds, and it caused 100% mortality of Desmodium tortuosum
and Pennisetum setosum.
Introduction
described the preparation and plant growth regulatory
activity of several 8-oxabicyclo[3.2.1]oct-6-en-3-one (1)
derivatives.11,12
Continuing our research on the discovery of new
molecules with herbicidal and/or plant growth regulatory
activity, we describe in this paper the synthesis of a new class
of herbicidal compounds (5) derived from the oxabicy-
clooctenone (1). We investigated the effect on plant growth
of many substituents on the various positions of the aromatic
ring of (5).
Among the groups of agrochemicals, herbicides are the
most used, corresponding to almost 50% (US$12 billion) of
the world market.1
Despite concern about environmental contamination by
pesticide residues the global market has increased continu-
ously during the last two decades.2 In Brazil the agrochemi-
cal industry grew 30% in 19943 and by 1997 the selling of
agrochemicals reached US$2.1 million annually, corre-
sponding to 5–6% of the world market.4
One of the major problems concerning the use of herbi-
cides is the appearance of resistant weeds. Although several
strategies can be used to minimize this problem, the agro-
chemical industry is always searching for new classes of
chemicals, with new modes of action.5 Many of the new her-
bicides developed recently are analogues of existing prod-
ucts, obtained from QSAR studies.6 This strategy usually does
not result in any compounds with new sites of action.
According to Duke et al. (1996),7 among the several discov-
ery strategies for new herbicides the synthesize-and-screen
method is still interesting and could lead to compounds with
new molecular sites of action.
Results and Discussion
Synthesis
Compounds having the general structure (5) were synthe-
sized according to the strategy shown in Scheme 1. The
oxabicyclooctenone (1) was prepared on a large scale from
1,1,3,3-tetrabromopropanone and furan, according to the
methodology previously described.11
The alkene (1) was then subjected to an osmium tetraox-
ide-catalysed oxidation, with hydrogen peroxide. The crude
diol obtained was converted into the acetonide (2), by reac-
tion with acetone in the presence of a catalytic amount of p-
toluenesulfonic acid and CuSO4. This procedure led to
compound (2) in variable yield (96% was the best result) and
a small amount of the ‘dimer’ (3). Compound (3) has so far
We have been using a [3+4]cycloaddition methodology
to prepare several seven-membered ring compounds, many
of which possess biological activity.8–10 Very recently we
Manuscript received 6 April 1999
© CSIRO 1999
0004-9425/99/100929
10.1071/CH99044

L. C. de A. Barbosa et al.
930
(1991),13 where the magnesium is activated by stirring under
a nitrogen atmosphere overnight, the only product isolated
was the dimer (6) in 22–26% yield, together with some start-
ing material. The formation of (6) occurred by an aldol con-
densation between (2) and the enolate generated from the
reaction of acetonide (2) with the Grignard reagent.
not undergone X-ray structure elucidation, but the structure
assigned is consistent with the spectral data. The e.i. mass
spectrum showed an M+ ion peak at m/z 298, corresponding
to the molecular formula C14H18O7.
Scheme 1. Reagents and conditions: (i) OsO4, H2O2, acetone, Et2O,
room temp. 38 h; (ii) acetone, p-toluenesulfonic acid, CuSO4, room
temp., 4 days; (iii) ArMgBr, tetrahydrofuran; (iv) HCl, acetone, reflux.
During the preparation of (4b), a by-product was isolated
in 8% yield and identified as the alcohol (7). The structure of
(7) is consistent with the spectroscopic data presented in the
Experimental section, and the 1H n.m.r. and 13C n.m.r.
assignments were confirmed by DEPT, COSY and HETCOR
experiments. The cleavage of the ether bridge of 8-oxabicy-
clo[3.2.1]oct-6-en-3-one derivatives with organolithium and
organocuprates, to produce cycloheptanones, has been pre-
viously described,14,15 but we are not aware of this type of
reaction with a Grignard reagent. The regio- and stereo-
selectivity observed in the formation of (7) can be explained
by the mechanism proposed in Scheme 2. Another unex-
pected result was the formation of the alkene (5d), in 5%
yield, during the preparation of the corresponding alcohol
(4d). The formation of this alkene (5d) may be explained by
the proposed mechanism shown in Scheme 3.
The infrared spectrum of (3) showed absorption at 3400
and 1710 cm–1 due to OH and CO stretchings respectively.
The 13C n.m.r. spectrum had only seven signals, showing the
symmetry of this ‘dimer’. The 2D-COSY, 2D-HETCOR and DEPT
spectra were also consistent with the assigned structure. The
formation of this compound was unexpected, and, to the best
of our knowledge, this is the first report of such a side
product in this kind of oxidation.
The acetonide (2) was then treated with various Grignard
reagents to produce the corresponding alcohols (4) (Table 1).
Despite several attempts, the alcohols (4l) (R1 = F, R2 = R3 =
H) and (4m) (R1 = R3 = OMe, R2 = H) could not be obtained.
When the reactions for the preparation of (4l,m) were
carried out using the methodology developed by Baker et al.
Once the required alcohols were obtained, they were sub-
mitted to a dehydration procedure with HCl in acetone and
the results are summarized in Table 1. Although the alcohols
(4d,h,i) did not react under the conditions used, no other
methodology was attempted to dehydrate such compounds.
Table 1. Synthesized 8-oxabicyclo[3.2.1]oct-6-en-3-one derivatives
Substituents
R2
Com-
pound
Yield
(%)
Com-
pound
Yield
(%)
R1
R3
Biological Assays
H
H
H
(4a)
(4b)
(4c)
(4d)
(4e)
(4f)
(4g)
(4h)
(4i)
59
(5a)
(5b)
(5c)
(5d)
(5e)
(5f)
(5g)
(5h)
(5i)
64
84
64
—
61
59
74
—
—
58
68.5
H
H
OMe
Me
NMe2
F
54.5
77
A preliminary experiment on Petri dishes was carried out
to evaluate the effect of compounds (5a–g, j,k), at a concen-
tration of 6.6 µg of the active ingredient per g of sand,* on
the radicle growth of sorghum (Sorghum bicolor L.), and the
results are shown in Table 2. Compound (5d) had no effect
on the sorghum radicle growth but all the other compounds
caused a significant growth inhibition (21–66%).
The most active compounds were (5g) (66% inhibition),
(5a) (59%) and (5e) (54%). There was no statistical differ-
ence in the inhibitory effect (40–59%) caused by (5a,b,c,e),
H
H
H
H
48.5A
60
H
H
H
H
Cl
56
H
Me
Cl
F
H
47.5
53
H
H
H
H
37
Me
OMe
H
H
(4j)
46
(5j)
OMe
OMe
(4k)
61
(5k)
A The alkene (5d) was isolated in 5% yield.
* Tests at several concentrations indicated that, at this concentration, which corresponds to approximately 13 kg of active ingredient per hectare, dis-
crimination between the activities of the compounds was possible.

Derivatives of 8-Oxabicyclo[3.2.1]oct-6-en-3-one
931
Table 2. Effect of the alkenes (5), at 6.6 µg g–1, on radicle growth
of S. bicolor L. after 2 days incubation at 25°C
Compound
Radicle length (cm)A,B
Inhibition (%)
C
—
6.73 a
—
0.89
(5d)
(5k)
(5f)
(5j)
6.67 a
5.30 b
21.25
26.15
33.14
40.57
45.02
54.38
59.44
66.27
4.97 bc
4.50 bc
4.00 bcd
3.70 cd
3.07 de
2.73 de
2.27 e
(5c)
(5b)
(5e)
(5a)
(5g)
A Means, in the same column, with the same letter are not significantly
different at P = 0.05% by Tukey’s test.
B Variation coefficient 10.10% for the data series.
C Control.
A preliminary selectivity assay with several crops and
weeds was carried with compound (5g). The following crops
and weeds were sensitive to compound (5g): Cucumis
sativus (cucumber), Glycine max (soybean), Pennisetum
setosum and Desmodium tortuosum (Florida beggarweed).
In all these cases the seeds germinated, but after a few days
growth ceased and 100% mortality was observed for injured
plants.
Scheme 2. Proposed mechanism for the formation of the alcohol (7).
When compared with the control experiment, normal
growth was observed for Helianthus annuus (sunflower),
Lycopersicon esculentum (tomato), Phaseolus vulgaris
(bean), Zea mays (corn), and for the weeds Bidens pilosa
(hairy beggar-ticks), Brachiaria plantaginea (alexander-
grass), Cenchrus echinatus (southern sandbur), Emilia
sonchifolia (red tasselflower), Ipomoea grandifolia
(morning glory), Physalis angulata (ground-cherry), and
Setaria geniculata (knotroot foxtail).
In summary, our data indicate that the new compounds,
derived from 8-oxabicyclo[3.2.1]oct-6-en-3-one, have selec-
tive herbicidal activity. It is clear that a substantial number of
further modifications can be made on the aromatic ring, and
in other parts of the molecule, in order to increase the activ-
ity observed.
Experimental
Mass spectra were recorded under electron impact (70 eV) and
chemical ionization (NH3) conditions by using a VG Analytical ZAB-
E high-resolution spectrometer. Infrared spectra were obtained on a
Mattson Instruments Fourier-transform infrared 3000 instrument.
N.m.r. spectra were recorded on a JEOL EX400 (400 MHz) spec-
trometer, with tetramethylsilane (SiMe4) as internal standard.
Coupling constants (J ) are given in hertz. Flash chromatography was
performed by using Crosfield Sorbil C60 (40–60 µm), and the sol-
vents used were purified according to Perrin and Armarego (1988).16
Scheme 3. Proposed mechanism for the formation of (5d).
and also between the effect (26–45%) caused by (5b,c,f, j),
but compound (5f) was less active (26%).
Table 3 shows the effect of the alkenes (5) prepared on the
development of the roots and aerial parts of cucumber
(Cucumis sativus L.). The percentage of growth inhibition
was calculated for both dried and fresh material, and the
results were very similar. The most active of the compounds
had: phenyl (5a), para-fluorophenyl (5e), para-chlorophenyl
(5f), and meta-tolyl (5g) rings. The para- and ortho-tolyl
compounds (5c, j) showed only weak activity. It should be
pointed out that the results presented in Table 3 correspond
to evaluation after 14 days. After 20 days, the most active
compounds (5a,e–g), caused 100% mortality.
exo-6,exo-7-Isopropylidenedioxy-8-oxabicyclo[3.2.1]octan-3-one (2)
To a stirred solution of 8-oxabicyclo[3.2.1]oct-6-en-3-one (1)
(5.0 g, 40 mmol), in acetone (75 ml) and diethyl ether (10 ml), was
added a solution of osmium tetraoxide (2.5% w/w in t-butyl alcohol,
1.0 ml, 0.08 mmol), followed by hydrogen peroxide (30%, 10 ml, 88
mmol). A cloudy brown solution was produced and this was stirred at
room temperature for 38 h. After this period the mixture had became
chalky white in appearance, and t.l.c. analysis showed that all starting
material had been consumed. Several times, when the reaction was

L. C. de A. Barbosa et al.
932
Table 3. Effect of the alkenes (5), at 6.6 µg g–1, on the development of C. sativus L. after 14 days at 25°C
Com-
pound
Fresh wt (g)
Inhibition
(%)
Fresh wt (g)
of rootsA,C
Inhibition
(%)
Dried wt (g)
Inhibition
(%)
Dried wt (g)
of rootsA,E
Inhibition
(%)
of aerial partA,B
of aerial partA,D
F
—
1.12 a
—
0.37 a
—
0.0800 ab
0.0790 ab
0.0733 abc
0.0740 abc
0.0648 abcd
0.0573 cd
0.0525 cde
0.0475 de
0.0335 e
—
0.0185 a
0.0185 a
0.0188 a
0.0155 ab
0.0138 ab
0.0100 b
0.0095 b
0.0105 b
0.0108 b
—
(5c)
(5j)
1.04 ab
1.03 ab
0.97 abc
0.79 bcd
0.72 cde
0.71 cde
0.58 de
0.44 e
7.14
0.34 a
8.11
1.25
0.00
8.04
0.34 a
8.11
8.38
–1.62
16.22
25.41
45.95
48.65
43.24
41.62
(5b)
(5k)
(5e)
(5a)
(5f)
(5g)
13.39
29.46
35.71
36.61
48.21
60.71
0.30 abc
0.25 bcd
0.21 cd
0.22 cd
0.22 cd
0.19 d
18.92
32.43
43.24
40.54
40.54
48.65
7.50
19.00
28.38
34.38
40.63
58.13
A Means, in the same column, with the same letter are not significantly different at P = 0.05% by Tukey’s test.
B Variation coefficient 14.06% for data series.
C Variation coefficient 15.95% for data series.
D Variation coefficient 15.65% for data series.
E Variation coefficient 17.48% for data series.
F Control.
repeated, a white solid was formed in variable amount (0–10%); it was
removed by filtration and identified as the ‘dimer’ (3). The reaction
was then quenched by addition of Na2S2O3(s) until the excess perox-
ide had been decomposed. After filtration, the solvent was removed
under reduced pressure to yield a viscous clear oil. This oil was dis-
solved in dry acetone (60 ml); p-toluenesulfonic acid (0.1 g) and anhy-
drous CuSO4 were added. After stirring at room temperature for 4 days,
the solid material was removed by filtration and NaHCO3 added to the
filtrate to neutralize the acid. Then the solvent was removed under
reduced pressure to give a white solid that was purified by flash
column chromatography (hexane/diethyl ether 1 : 2) to give the desired
product (2) as a white solid in 96% yield (7.6 g, 38.3 mmol), m.p.
125–126°C (Found: C, 60.6; H, 7.1. C10H14O4 requires C, 60.6; H,
and the combined organic extracts were dried over MgSO4 and con-
centrated under reduced pressure to afford a white solid. This solid was
purified by column chromatography (hexane/diethyl ether 1 : 1) to
produce the required alcohol. The yields for the reactions are presented
in Table 1.
exo-6,exo-7-Isopropylidenedioxy-3-phenyl-8-oxabicyclo[3.2.1]octan-
endo-3-ol (4a)
M.p. 182–184°C.
3480, 3090, 3000, 2950, 2920, 1500, 1375,
1360, 1220, 1060, 870,m7a8x0, 700 cm-1. 1H n.m.r. (CDCl3) 1.31, s, CH3;
1.44, s, CH3; 1.50, s, OH; 1.80, d, J 15.1 Hz, H 2 and H 4 ; 2.31, dd,
J 15.1, 4.8 Hz, H2 and H4 ; 4.28, d, J 4.8 Hz, H1 and H 5; 5.15, s,
H6 and H7; 7.19, t, J 7.5 Hz, H4´;‡ 7.30, t, J 7.5 Hz, H3´ and H 5´;
7.38, d, J 7.5 Hz, H2´ and H 6´. 13C n.m.r. (CDCl3) 24.6, CH3; 26.1,
CH3; 41.3, C 2 and C 6; 72.0, C 3; 79.5, C 1 and C 5; 83.5, C 6 and C 7;
111.1, CMe2; 124.2, C2´ and C 6´; 127.3, C 4´; 128.5, C 3´ and C 5´;
147.9, C 1´. Mass spectrum m/z 261 ([M–Me]+•, 10%), 201 (25), 141
(30), 105 (100).
7.1%).
2980, 1710, 1390, 1380, 1275, 1235, 1175, 1080, 1055,
max
1020, 1000, 865, 830, 685 cm–1.1H n.m.r. (CDCl3) 1.29, s, CH3; 1.51,
s, CH3; 2.37, dd, J 16.0, 0.7 Hz, H 2 and H 4 ;* 2.74, dd, J 16.0, 5.8
Hz, H 2 and H 4; 4.52, s, H 6 and H 7; 4.58, dd, J 5.8, 0.7 Hz, H 1 and
H 5. 13C n.m.r. (CDCl3) 24.5, CH3; 25.9, CH3; 45.8, C 2 and C 4; 79.8,
C 1 and C 5; 83.4, C 6 and C 7 ; 112.0, CMe2; 204.8, C 3.
exo-6,exo-7-Isopropylidenedioxy-3-(4-methoxyphenyl)-8-
oxabicyclo[3.2.1]octan-endo-3-ol (4b)
Data for Compound (3)†
M.p. 263–265°C (Found: C, 56.0; H, 6.0. C14H18O7 requires C, 56.3;
H, 6.1%). max 3400, 2900, 1710, 1460, 1375, 1200, 1120, 1075, 1050,
870, 815 cm–1. 1H n.m.r. [(CD3)2SO] 2.22, d, J 16.0 Hz, H2 , H4 ,
H2´ and H 4´ ; 2.57, dd, J 16.0, 6.0 Hz, H 2 , H 4 , H 2´ and H 4´ ;
3.81, d, J 6.1 Hz, H6 and H6´; 3.96, dd, J 7.6, 6.1 Hz, H 7 and H7´;
4.29, d, J 6.0, H5 and H 5´; 4.53, d, J 6.0 Hz, H 1 and H 1´; 4.87, d, J
7.6 Hz, 7-OH and 7´-OH. 13C n.m.r. [(CD3)2SO] 46.6, C 4 and C 4´;
47.3, C 2 and C 2´; 75.5, C 7 and C 7´; 80.2, C 1 and C 1´; 83.1, C 5 and
C 5´; 83.5, C 6 and C 6´; 207.0, C 3 and C 3´. Mass spectrum m/z 298
([C14H18O7]+•, 5%), 281 (15), 197 (15), 169 (100), 141 (20), 123 (22),
113 (20), 97 (45), 71 (70), 43 (80).
M.p. 190–193°C.
3495, 3050, 3000, 2983, 2950, 2917, 1600,
max
1580, 1517, 1380, 1360, 1250, 1040 cm–1. 1H n.m.r. (CDCl3) 1.36, s,
CH3; 1.44, s, OH; 1.52, s, CH3; 1.85, d, J 15.5 Hz, H2 and H5 ; 2.34,
dm, J 15.5 Hz, H 2 and H4 ; 3.80, s, OCH3; 4.35, m, H 1 and H 5;
5.17, s, H6 and H7; 6.88, d, J 8.2 Hz, H3´ and H 5´; 7.33, d, J 8.2 Hz,
H2´ and H 6´. 13C n.m.r. (CDCl3) 24.6, CH3; 26.2, CH3; 41.4, C 2 and
C 4; 55.3, OCH3; 71.6, C 3; 79.6, C 1 and C 5; 83.5, C 6 and C 7; 111.1,
CMe2; 113.7, C 3´ and C 5´; 125.3, C 2´ and C 6´; 140.3, C 1´; 158.4,
C 4´. Mass spectrum m/z 306 (M+•, 10%), 291 ([M–Me]+, 100), 253
(37), 232 (25), 183 (57), 135 (95).
exo-6,exo-7-Isopropylidenedioxy-3-(4-methylphenyl)-8-
oxabicyclo[3.2.1]octan-endo-3-ol (4c)
Typical Procedure for the Grignard Reaction
To a round-bottom flask were added magnesium turnings (0.68 g,
28 mmol), a crystal of iodine and dry diethyl ether (3 ml) and about
one-tenth of a solution of the aryl bromide (25 mmol) in dry diethyl
ether (20 ml). After the reaction had begun the remainder of the aryl
bromide solution was added dropwise during 30 min. After a total stir-
ring of 1 h, a solution of the acetonide (2) (1.0 g, 5 mmol, in 20 ml of
dry tetrahydrofuran) was added dropwise over a period of 20 min. The
resultant mixture was stirred at room temperature for 12 h and then the
reaction was quenched by addition of NH4Cl saturated aqueous solu-
tion (60 ml). The products were extracted with ethyl acetate (3×60 ml)
M.p. 210–213°C.
3495, 2980, 2960, 2940, 1515, 1370, 1215,
max
1
1095, 1060, 870, 815 cm–1. H n.m.r. (CDCl3) 1.37, s, CH3; 1.52, s,
CH3; 1.62, s, OH; 1.85, dd, J 15.5, 1.1 Hz, H2 and H 4 ; 2.33, s,
ArCH3; 2.34, dd, J 15.5, 4.2 Hz, H 2 and H 4 ; 4.34, dd, J 4.2, 1.1 Hz,
H1 and H5; 5.16, s, H6 and H7; 7.16, d, J 8.2 Hz, H3´ and H5´; 7.31,
d, J 8.2 Hz, H 2´ and H6´. 13C n.m.r. (CDCl3) 20.9, ArCH3; 24.6, CH3;
26.2, CH3; 41.3, C 2 and C 4; 71.8, C 3; 79.6, C 1 and C 5; 83.5, C 6 and
C 7; 111.1, CMe2; 124.1, C 2´ and C 6´; 129.1, C 3´ and C 5´; 137.1,
C 4´; 145.2, C 1´. Mass spectrum m/z 308 ([M+NH4]+•, 4%), 291
* The stereodescriptors and correspond to endo and exo, respectively.
† exo-6,exo-6´-Oxybis(7-hydroxy-8-oxabicyclo[3.2.1]octan-3-one).
‡ Primes refer to the phenyl group.

Derivatives of 8-Oxabicyclo[3.2.1]oct-6-en-3-one
933
([M+1]+, 9), 290 (M+•, 3), 275 (31), 273 (11), 233 (10), 215 (13), 197
(10), 171 (8), 169 (10), 119 (69), 91 (38), 77 (5), 65 (8), 43 (100).
124.8, C 2´; 127.4, C 4´; 130.6, C 5´; 134.4, C 3´; 152.9, C 1´. Mass
spectrum m/z 328 ([M+NH4]+, 22%), 311 ([M+1]+, 61), 295 (100), 293
(4), 253 (14), 235 (39), 217 (32), 191 (14), 189 (13), 139 (63), 115 (8),
93 (15), 77 (7), 43 (90).
3-(4-Dimethylaminophenyl)-exo-6,exo-7-isopropylidenedioxy-8-
oxabicyclo[3.2.1]octan-endo-3-ol (4d)
3-(3-Fluorophenyl)-exo-6,exo-7-isopropylidenedioxy-8-
oxabicyclo[3.2.1]octan-endo-3-ol (4i)
M.p. 206–208°C.
3500, 2980, 2940, 1610, 1525, 1370, 1230,
1070, 875, 850, 800 cmm–1a.x1H n.m.r. (CDCl3) 1.36, s, CH3; 1.44, s, OH;
1.51, s, CH3; 1.86, d, J 14.6 Hz, H 2 and H 4 ; 2.32, dd, J 14.6, 4.4 Hz,
H2 and H 4 ; 2.94, s, 6H, NMe2; 4.33, d, J 4.4 Hz, H 1 and H5; 5.15,
s, H 6 and H 7; 6.70, d, J 9.0 Hz, H 3´ and H5´; 7.28, d, J 9.0 Hz, H2´
and H 6´. 13C n.m.r. (CDCl3) 26.2, CH3; 24.6, CH3; 40.5, NMe2; 41.3,
C 2 and C 4; 71.5, C 3; 79.7, C 1 and C 5; 83.5, C 6 and C 7; 111.0,
CMe2; 112.2, C 3´ and C 5´; 135.9, C 2´ and C 6´; 149.7, C 4´. Mass
spectrum m/z 319 (M+•, 7%), 301 (28), 272 (4), 243 (21), 214 (65), 200
(51), 185 (74), 171 (79), 157 (21), 148 (26), 128 (49), 115 (60), 91 (33),
77 (22), 65 (18), 43 (100).
M.p. 186–187°C (Found: C, 65.7; H, 6.3. C16H19FO4 requires C,
65.3; H, 6.5%). max 3440, 3345, 3075, 3000, 2925, 1590, 1490, 1380,
1265, 1225, 1155, 1100, 1050, 1020, 860, 780, 700 cm–1. 1H n.m.r.
(CDCl3) 1.36, s, CH3; 1.52, s, CH3; 1.83, d, J 14.9 Hz, H 2 and H 4 ;
1.92, s, OH; 2.29, dd, J 14.9, 4.7 Hz, H 2 and H 4 ; 4.30, d, J 4.7 Hz,
H 1 and H 5; 5.14, s, H 6 and H 7; 6.94, tdd, J5´,4´ = J5´,6´ 8.4, J5´,F 2.1,
J5´,2´ 0.7 Hz, H 5´; 7.11–7.20, m, H2´ and H 6´; 7.26–7.34, m, H 4´.
13C n.m.r. (CDCl3) 24.5, CH3; 26.1, CH3; 41.0, C 2 and C 4; 71.7, C 3;
79.5, C 1 and C 5; 83.3, C 6 and C 7; 111.2, d, JC,F 22.7 Hz, C 2´; 111.7,
CMe2; 114.2, d, JC,F 21.1 Hz, C 4´; 119.9, d, JC,F 2.6 Hz, C 6´; 130.0, d,
JC,F 7.3 Hz, C 5´; 148.0, d, JC,F 5.5 Hz, C 1´; 163.0, d, JC,F 243.2 Hz,
C 3´.
3-(4-Fluorophenyl)-exo-6,exo-7-isopropylidenedioxy-8-
oxabicyclo[3.2.1]octan-endo-3-ol (4e)
M.p. 202–203°C.
3440, 3000, 2950, 1600, 1510, 1375, 1360,
max
exo-6,exo-7-Isopropylidenedioxy-3-(2-methylphenyl)-8-
oxabicyclo[3.2.1]octan-endo-3-ol (4j)
1235, 1200, 1150, 1100, 1070, 1020, 870, 825, 700 cm–1. H n.m.r.
(CDCl3) 1.36, s, CH3; 1.52, s, CH3; 1.79, s, OH; 1.86, d, J 15.1 Hz, H 2
and H 4 ; 2.30, dm, J 15.1 Hz, H2 and H 4 ; 4.31, m, H1 and H5;
5.14, s, H 6 and H 7; 7.02, bt, J 8.2 Hz, H 3´ and H 5´; 7.40, dd, J 8.2,
5.7 Hz, H 2´ and H6´. 13C n.m.r. (CDCl3) 24.5, CH3; 26.1, CH3; 41.3,
C 2 and C 4; 71.6, C 3; 79.5, C 1 and C 5; 83.4, C 6 and C 7; 111.2,
CMe2; 115.2, d, JC,F 22 Hz, C 3´ and C 5´; 126.0, d, JC,F 7.3 Hz, C 2´ and
C 6´; 143.9, C 1´; 163.1, d, JC,F 245 Hz, C 4´. Mass spectrum m/z 312
([M+NH4]+, 5%), 295 ([M+1]+, 11), 294 (M+•, 7), 279 (26), 219 (27),
201 (35), 189 (17), 177 (17), 175 (47), 173 (58), 161 (22), 153 (24), 123
(78), 109 (17), 95 (15), 43 (100).
1
M.p. 177–180°C (Found: C, 70.3; H, 7.6. C17H22O4 requires C, 70.3;
H, 7.6%). max 3470, 3400, 3070, 2980, 2920, 1495, 1450, 1375, 1360,
1
1200, 1160, 870, 720 cm–1. H n.m.r. (CDCl3) 1.37, s, CH3; 1.49, s,
OH; 1.52, s, CH3; 1.85, br d, J 14.5 Hz, H2 and H 4 ; 2.56, dd, J14.5,
4.7 Hz, H 2 and H 4 ; 2.58, s, ArCH3; 4.37, br d, J 4.7 Hz, H 1 and H5;
5.15, s, H 6 and H7; 7.16–7.46, m, 4H, aromatic. 13C n.m.r. (CDCl3)
21.7, ArCH3; 24.7, CH3; 26.2, CH3; 39.8, C 2 and C 4; 72.8, C 3; 79.7,
C 1 and C 5; 83.7, C 6 and C 7; 111.2, CMe2; 124.2, C 6´; 125.8, C 5´;
127.5, C 4´; 133.5, C 3´; 135.1, C 2´; 144.7, C 1´.
exo-6,exo-7-Isopropylidenedioxy-3-(2,3,4-trimethoxyphenyl-8-
oxabicyclo[3.2.1]octan-endo-3-ol (4k)
3-(4-Chlorophenyl)-exo-6,exo-7-isopropylidenedioxy-8-
oxabicyclo[3.2.1]octan-endo-3-ol (4f)
M.p. 73–76°C.
3500, 3400, 2970, 2950, 2880, 1600, 1500,
M.p. 208–209°C. max 3495, 2980, 2960, 2930, 2800, 1495, 1350,
max
1460, 1380, 1370, 1300, 1200, 1100, 1060, 1050, 860, 790 cm–1. H
n.m.r. (CDCl3) 1.37, s, CH3; 1.51, s, CH3; 1.75, s, OH; 2.00, br d, J
14.3 Hz, H2 and H4 ; 2.37, dd, J 14.3, 4.6 Hz, H2 and H4 ; 3.83,
s, OCH3; 3,84, s, OCH3; 4.02, s, OCH3; 4.33, d, J 1.6 Hz, H 1 and H5;
5.20, s, 2H, H 6 and H7; 6.60, d, J 8.8 Hz, H5´; 6.92, d, J 8.8 Hz, H6´.
13C n.m.r. (CDCl3) 24.6, CH3; 26.1, CH3; 39.8, C 2 and C 4; 55.8,
OCH3; 60.5, OCH3; 61.3, OCH3; 71.9, C 3; 79.6, C 1 and C 5; 83.5, C 6
and C 7; 106.4, C 5´; 110.9, CMe2; 119.2, C 6´; 131.9, C 1´; 142.2, C 3´;
151.7, C 2´; 153.1, C 4´. Mass spectrum m/z 366 (M+•, 5%), 351 (3), 291
(3), 273 (2), 247 (3), 239 (5), 207 (15), 196 (10), 195 (100), 181 (5), 151
(5), 91 (4), 77 (7), 69 (8), 59 (11), 43 (45), (10).
1
1
1260, 1230, 1215, 1095, 1060, 1020, 870, 770, 700 cm–1. H n.m.r.
[(D6)acetone] 1.34, s, CH3; 1.47, s, CH3; 1.91, d, J 14.2 Hz, H 2 and
H4 ; 2.25, dd, J 14.2, 4.7 Hz, H 2 and H 4 ; 3.98, s, OH; 4.29, d, J 4.7
Hz, H 1 and H 5; 5.19, s, H6 and H7; 7.28, dm, J 8.8 Hz, H 3´ and H 5´;
7.42, dm, J 8.8 Hz, H 2´ and H 6´. 13C n.m.r. [(D6)acetone] 23.9, CH3;
25.4, CH3; 40.6, C 2 and C 4; 70.5, C 3; 79.1, C 1 and C 5; 82.8, C 6 and
C 7; 110.2, CMe2; 125.6, C 2´ and C 6´; 127.4, C 3´ and C 5´; 131.7,
C 4´; 147.1, C 1´. Mass spectrum m/z 311/313 ([M+1]+, 19/6%),
295/297 (7/2), 235/237 (8/2.5), 217 (10), 189 (15), 139/141 (21/6), 139
(63), 111 (17), 77 (8), 59 (14), 43 (100).
exo-6,exo-7-Isopropylidenedioxy-3-(3-methylphenyl)-8-
oxabicyclo[3.2.1]octan-endo-3-ol (4g)
Data for Compounds (6) and (7)
M.p. 170–172°C.
3480, 3400, 2960, 2910, 1600, 1500, 1370,
Compounds (6) and (7) were isolated as by-products during the
1210, 1165, 1070, 865,m7a8x0, 700 cm–1. 1H n.m.r. (CDCl3) 1.36, s, CH3;
1.51, s, CH3; 1.68, s, OH; 1.83, d, J 14.3, H 2 and H 4 ; 2.34, dd, J
14.3, 4.5 Hz, H 2 and H 4 ; 2.35, s, ArCH3; 4.33, d, J 4.5 Hz, H 1 and
H5; 5.15, s, H6 and H 7; 7.07–7.24, m, 4H, aromatic. 13C n.m.r.
(CDCl3) 21.5, ArCH3; 24.5, CH3; 41.3, C 2 and C 4; 71.8, C 3; 79.6, C 1
and C 5; 83.4, C 6 and C 7; 111.1, CMe2; 121.1, C 6´; 124.9, C 2´; 128.0,
C 4´; 128.3, C 5´; 138.1, C 3´; 147.9, C 1´. Mass spectrum m/z 308
([M+NH4]+, 100%), 291 ([M+1]+, 40), 290 (M+•, 29), 275 (19), 232
(13), 215 (18), 197 (4), 119 (10).
Grignard reactions as described previously.
Compound (6) had m.p. 200–201°C. max 3500, 3000, 2940, 1700,
1375, 1270, 1235, 1200, 1165, 1110, 1080, 1050, 870, 825, 715 cm–1.
1H n.m.r. (CDCl3) 1.30, s, 2×CH3; 1.47, s, CH3; 1.52, s, CH3 and
H 2 ; 1.84, dd, J 14.6, 2.2 Hz, H 4 ; 2.13, s, H 2´ ; 2.14, ddd, J 14.6,
8.4, 2.2 Hz, H 2 ; 2.22, ddd, J 14.6, 8.0, 2.2 Hz, H 4 ; 2.38, d, J 16.1
Hz, H 4´ ; 2.81, dd, J 16.1, 6.2 Hz, H 4´ ; 4.18, s, OH; 4.31, dd, J
8.0, 1.8 Hz, H 1; 4.35, dd, J 8.0, 1.8 Hz, H 5; 4.43, d, J 5.4 Hz, H 7´;
4.46, d, J 5.5 Hz, H 7; 4.52, d, J 5.5 Hz, H 6; 4.58, d, J 6.2 Hz, H 5´;
4.61, d, J 5.4 Hz, H 6´; 4.83, s, H 1´. 13C n.m.r. (CDCl3) 24.6, CH3;
24.8, CH3; 25.9, CH3; 26.0, CH3; 37.1, C 2; 37.6, C 4; 46.5, C 4´;
61.2, C 2´; 70.5, C 3; 77.8, C 1; 77.9, C 5; 79.9, C 5´; 80.4, C 1´; 83.2,
C 6; 83.9, C 7; 84.6, C 6´ and C 7´; 112.5, CMe2; 112.6, CMe2; 205.7,
C 3´. Mass spectrum m/z 414 ([M+NH4]+, 17%), 397 ([M+1]+, 19),
396 (M+•, 17), 381 (65), 379 (17), 363 (2), 338 (9), 323 (9), 321 (29),
199 (8), 184 (11), 183 (100), 141 (15), 123 (20), 97 (19), 81 (19), 55
(12), 43 (63).
3-(3-Chlorophenyl)-exo-6,exo-7-isopropylidenedioxy-8-
oxabicyclo[3.2.1]octan-endo-3-ol (4h)
M.p. 173–175°C.
3450, 3350, 3075, 3000, 2975, 2900, 1670,
max
1595, 1575, 1480, 1370, 1365, 1260, 1215, 1110, 1070, 1020, 565, 775,
700 cm–1. 1H n.m.r. [(D6)acetone] 1.28, s, CH3; 1.38, s, CH3; 1.87, d,
J 14.7 Hz, H 2 and H4 ; 2.20, dd, J 14.7, 4.8 Hz, H 2 and H4 ; 4.21,
d, J 4.8 Hz, H 1 and H 5; 4.30, s, OH; 5.16, s, H 6 and H 7; 7.25, d, J 7.7
Hz, H6´; 7.35, t, J 7.7 Hz, H 5´; 7.4, d, J 7.70 Hz, H 4´; 7.52, s, H 2´.
13C n.m.r. [(D6)acetone] 25.0, CH3; 26.6, CH3; 42.0, C 2 and C 4; 72.3,
C 3; 80.3, C 1 and C 5; 84.3, C 6 and C 7; 111.4, CMe2; 124.2, C 6´;
Compound (7) had m.p. 19l–192°C.
3400, 3100, 2850, 1700,
1610, 1500, 1380, 1370, 1080, 830 cm–1.m1Hax n.m.r. (CDCl3) 1.33, s,
CH3; 1.49, s, CH3; 1.67, s, OH; 2.60–2.75, m, H 2 and H 7 ; 2.75, dd,

L. C. de A. Barbosa et al.
934
J 14.3, 11.5 Hz, H 7 ; 3.05, ddd, J 14.3, 7.4, 1.8 Hz, H2 ; 3.53, ddd, J
11.5, 9.8, 1.8 Hz, H6; 3.79, s, OCH3; 4.32, m, H 3; 4.44, dd, J 7.1, 2.5
Hz, H 4; 4.53, dd, J 9.8, 7.1 Hz, H 5; 6.86, dm, J 8.8 Hz, H 3´ and H 5´;
7.11, dm, J 8.8 Hz, H2´ and H 6´. 13C n.m.r. (CDCl3) 24.0, CH3; 26.9,
CH3; 40.9, C 6; 46.1, C 2; 48.3, C 7; 55.1, OCH3; 67.5, C 3; 79.2, C 4;
81.3, C 5; 107.7, CMe2; 114.0, C 3´ and C 5´; 128.2, C 2´ and C 6´;
135.0, C 1´; 158.3, C 4´; 206.6, C 1. Mass spectrum m/z 306 (M+•, 26%),
288 (6), 248 (8), 231 (9), 188 (19), 161 (26), 134 (100), 121 (47), 91
(19), 43 (31).
3-(4-Dimethylaminophenyl)-exo-6,exo-7-isopropylidenedioxy-8-
oxabicyclo[3.2.1]oct-2-ene (5d)
M.p. 165–166°C (Found: C, 71.7; H, 7.6; N, 4.6. C18H23NO3
requires C, 71.7; H, 7.6; N, 4.6%). max 2970, 2950, 2940, 2800, 1610,
1525, 1375, 1360, 1270, 1200, 1175, 1070, 1040, 870, 810 cm–1. H
1
n.m.r. (CDCl3) 1.32, s, CH3; 1.53, s, CH3; 2.20, d, J 17.5 Hz, H 4 ;
2.91, ddd, J 17.5, 5.8, 1.1 Hz, H4 ; 2.95, s, NMe2; 4.51, d, J 5.8 Hz,
H5; 4.56, d, J 5.1 Hz, H1; 4.60, br d, J 5.5 Hz, H6; 4.70, d, J 5.5 Hz,
H7; 6.12, dm, J 5.1 Hz, H2; 6.67, dm, J 8.8 Hz, H3´ and H 5´; 7.25,
dm, J 8.8 Hz, H2´ and H 6´. 13C n.m.r. (CDCl3) 24.9, CH3; 26.2, CH3;
30.4, C 4; 40.4, NMe2; 76.9, C 1; 79.3, C 5; 85.7, C 6; 85.9, C 7; 112.1,
C 3´ and C 5´; 112.1, CMe2; 119.1, C 2; 125.4, C 2´ and C 6´; 126.6,
C 1´; 133.9, C 3; 150.2, C 4´. Mass spectrum m/z 302 ([M+1]+, 30%),
301 (M+•, 100), 286 (3), 243 (6), 226 (7), 215 (10), 214 (35), 200 (32),
185 (13), 184 (15), 146 (13), 144 (10), 120 (13), 59 (6), 43 (32).
Typical Procedure for the Dehydration Reaction
To a stirred solution of the alcohol (4 mmol) in dry acetone (50 ml)
was added concentrated HCl (37%, 0.2 ml). The resultant solution was
stirred under reflux until t.l.c. analysis revealed the complete consump-
tion of the starting material (this time varied from 3 h to 3 days). The
reaction was quenched by addition of a saturated aqueous solution of
sodium bicarbonate until complete neutralization of the acid. The
product was extracted with diethyl ether (3×20 ml); the extracts were
combined, dried over MgSO4, and concentrated under reduced pressure
to give the crude product as yellow solid. This solid was purified by
column chromatography (hexane/diethyl ether 1: 1 or 2 : 1) to yield the
expected alkene as a white solid.
3-(4-Fluorophenyl)-exo-6,exo-7-isopropylidenedioxy-8-
oxabicyclo[3.2.1]oct-2-ene (5e)
M.p. 143–144°C (Found: C, 69.5; H, 6.2. C16H17FO3 requires C,
69.5; H, 6.2%). max 3000, 2930, 1600, 1515, 1370, 1210, 1200, 1165,
1070, 1050, 870, 820 cm–1. 1H n.m.r. (CDCl3) 1.33, s, CH3; 1.54, s,
CH3; 2.19, d, J 17.6 Hz, H 4 ; 2.92, ddd, J 17.6, 5.8, 1.1 Hz, H4 ; 4.53,
d, J 5.8 Hz, H5; 4.58, d, J 5.1 Hz, H1; 4.61, d, J 5.5 Hz, H6; 4.72, br
d, J 5.5 Hz, H7; 6.22, dm, J 5.1 Hz, H 2; 7.01, br t, J 8.8 Hz, H3´ and
H5´; 7.32, dd, J 8.8, 5.5 Hz, H2´ and H 6´. 13C n.m.r. (CDCl3) 24.9,
CH3; 26.2, CH3; 30.6, C 4; 76.8, C 1; 85.6, C 6; 85.8, C 7; 112.3, CMe2;
115.4, C 3´ and C 5´; 123.0, C 2; 126.4, C 2´ and C 6´; 133.6, C 3; 134.8,
C 1´; 163.7, C 4´.
exo-6,exo-7-Isopropylidenedioxy-3-phenyl-8-oxabicyclo[3.2.1]oct-2-
ene (5a)
M.p. 139–141°C (Found: C, 74.1; H, 6.7. C16H18O6 requires C, 74.4;
H, 7.0%). max 3050, 2990, 2920, 1600, 1500, 1450, 1375, 1280, 1200,
1165, 1085, 1070, 1050, 810, 750, 690 cm–1. 1H n.m.r. (CDCl3) 1.33,
s, CH3; 1.54, s, CH3; 2.23, d, J 17.5 Hz, H 4 ; 2.95, dd, J 17.5, 5.8, Hz,
H4 ; 4.54, d, J 5.8 Hz, H 5; 4.59, d, J 5.1 Hz, H 1; 4.61, d, J 5.5 Hz,
H6; 4.72, d, J 5.5 Hz, H 7; 6.28, dm, J 5.1 Hz, H 2; 7.31–7.36, m, 5H,
aromatic. 13C n.m.r. (CDCl3) 24.9, CH3; 26.2, CH3; 30.4, C 4; 76.8,
C 1; 79.2, C 5; 85.1, C 6; 85.8, C 7; 112.2, CMe2; 123.1, C 2; 127.7, C 2´
and C 6´; 127.9, C 4´; 128.4, C 3´ and C 5´; 134.5, C 3; 138.6, C 1´. Mass
spectrum m/z 258 (M+•, 6%), 243 (6), 200 (21), 182 (10), 171 (100), 157
(75), 153 (32), 144 (25), 128 (39), 115 (40), 103 (15), 91 (16), 77 (31),
65 (10), 51 (14), 43 (54).
3-(4-Chlorophenyl)-exo-6,exo-7-isopropylidenedioxy-8-
oxabicyclo[3.2.1]oct-2-ene (5f)
M.p. 140–142°C (Found: C, 65.4; H, 5.8; Cl, 12.1. C16H17ClO3
requires C, 65.6; H, 5.8; Cl, 12.1%). max 3050, 2980, 2950, 2850, 1640,
1600, 1500, 1375, 1280, 1200, 1150, 1080, 1040, 1015, 870, 810, 750,
700 cm–1. 1H n.m.r. (CDCl3) 1.32, s, CH3; 1.54, s, CH3; 2.12, d, J 17.8
Hz, H 4 ; 2.92, dddd, J 17.8, 5.9, 1.7, 0.7 Hz, H4 ; 4.53, d, J 5.9 Hz,
H5; 4.59, d, J 5.1 Hz, H 1; 4.61, d, J 5.8 Hz, H 6; 4.72, d, J 5.8 Hz, H7;
6.28, dm, J 5.1 Hz, H 1; 7.26–7.30, m, 4H, aromatic. 13C n.m.r.
(CDCl3) 30.3, C 4; 76.7, C 1; 79.0, C 5; 85.6, C 6; 85.6, C 7; 112.3,
CMe2; 123.6, C 2; 125.9, C 2´ and C 6´; 128.5, C 3´ and C 5´; 133.53,
C 3; 133.6, C 4´; 137.0, C 1´. Mass spectrum m/z 310 ([M+NH4]+,
100%), 293 ([M+1]+, 2), 202 (M+•, 2), 277 (3), 252 (8), 191 (10), 52
(35).
exo-6,exo-7-Isopropylidenedioxy-3-(4-methoxyphenyl)-8-
oxabicyclo[3.2.1]oct-2-ene (5b)
M.p. 154–156°C (Found: C, 70.7; H, 7.0. C17H20O4 requires C, 70.8;
H, 7.0%). max 3015, 2990, 2955, 1610, 1515, 1380, 1365, 1330, 1280,
1260, 1200, 1180, 1040, 865, 815, 665 cm–1. 1H n.m.r. (CDCl3) 1.33,
s, CH3; 1.54, s, CH3; 2.20, d, J 17.7 Hz, H4 ; 2.92, dddd, J 17.7, 6.0,
1.8, 0.7 Hz, H4 ; 3.80, s, OCH3; 4.52, d, J 6.0 Hz, H 5; 4.57, d, J 5.1
Hz, H 1; 4.61, d, J 6.7 Hz, H 6; 4.71, d, J 6.7 Hz, H 7; 6.18, dm, J 5.1
Hz, H 2; 6.86, dm, H 3´ and H 5´; 7.29, dm, H 2´ and H 6´. 13C n.m.r.
(CDCl3) 24.8 CH3; 26.2, CH3; 30.5, C 4; 55.2, OCH3; 76.8, C 1; 79.2,
C 5; 85.6, C 6; 85.5, C 7; 112.2, CMe2; 113.7, C 3´ and C 5´; 121.1, C 2;
125.8, C 2´ and C 6´; 131.2, C 1´; 133.8, C 3; 159.4, C 4´. Mass spec-
trum m/z 288 (M+•, 22%), 230 (17), 213 (7), 201 (100), 187 (85), 174
(16), 158 (12), 128 (15), 115 (22), 103 (6), 89 (10), 77 (13), 65 (6), 43
(46).
exo-6,exo-7-Isopropylidenedioxy-3-(3-methylphenyl)-8-
oxabicyclo[3.2.1]oct-2-ene (5g)
M.p. 127–128°C (Found: C, 74.5; H, 7.2. C17H20O3 requires C, 74.9;
H, 7.4%). max 3020, 2975, 2920, 1375, 1250, 1200, 1115, 1080, 1065,
1
1035, 875, 780, 680 cm–1. H n.m.r. (CDCl3) 1.33, s, CH3; 1.54, s,
CH3; 2.22, dd, J 17.5, 0.7 Hz, H4 ; 2.35, s, ArCH3; 2.94, dddd, J 17.5,
6.0, 1.8, 0.7 Hz, H4 ; 4.53, d, J 6.0 Hz, H 5; 4.58, br d, J 5.0 Hz, H1;
4.61, d, J 5.5 Hz, H 6; 4.72, d, J 5.5 Hz, H 7; 6.26, dm, J 5.0 Hz, H2;
7.10, d, J 7.3 Hz, H6´; 7.15, d, J 7.7 Hz, H4´; 7.16, s, H2´; 7.22, br t,
J 7.5 Hz, H 5´. 13C n.m.r. (CDCl3) 21.4, ArCH3; 24.9, CH3; 26.2, CH3;
30.5, C 4; 76.8, C 1; 79.2, C 5; 85.7, C 6; 85.8, C 7; 112.2, CMe2; 121.9,
C 6´; 122.9, C 2; 125.5, C 2´; 128.3, C 5´; 128.7, C 4´; 134.6, C 3; 138.0,
C 3´; 138.6, C 1´. Mass spectrum m/z 272 (M+•, 8%), 257 (3), 214 (14),
199 (7), 185 (74), 171 (100), 158 (17), 142 (18), 128 (21), 115 (24), 105
(7), 91 (13), 77 (6), 65 (8), 51 (6), 43 (32).
exo-6,exo-7-Isopropylidenedioxy-3-(4-methylphenyl)-8-
oxabicyclo[3.2.1]oct-2-ene (5c)
M.p. 160–161°C (Found: C, 75.0; H, 7.4. C17H20O3 requires C, 75.0;
H, 7.4%). max 3050, 2990, 2950, 2910, 1680, 1515, 1375, 1275, 1200,
1165, 1080, 1065, 1045, 875, 800, 650 cm–1. 1H n.m.r. (CDCl3) 1.33,
s, CH3; 1.54, s, CH3; 2.21, br d, J 17.6 Hz, H 4 ; 2.34, s, ArCH3; 2.94,
ddd, J17.6, 5.9, 1.1 Hz, H 4 ; 4.53, br d, J 5.9 Hz, H 5; 4.58, d, J4.7 Hz,
H1; 4.61, br d, J 5.5 Hz, H6; 4.72, d, J 5.5 Hz, H 7; 6.24, dm, J 4.7 Hz,
H2; 7.13, d, J 8.1 Hz, H3´ and H 5´; 7.25, d, J 8.1 Hz, H 2´ and H6´.
13C n.m.r. (CDCl3) 21.1, ArCH3; 24.9, CH3; 26.2, CH3; 30.5, C 4;
76.8, C 1; 79.2, C 5; 85.1, C 6; 85.8, C 7; 112.2, CMe2; 122.1, C 2;
124.6, C 2´ and C 6´; 129.1, C 3´ and C 5´; 134.3, C 3; 135.8, C 1´;
137.8, C 4´. Mass spectrum m/z 272 (M+•, 10%), 257 (3), 214 (18), 199
(7), 185 (92), 171 (100), 157 (18), 141 (18), 141 (18), 128 (17), 105 (8),
91 (19), 77 (7), 65 (10), 43 (10).
exo-6,exo-7-Isopropylidenedioxy-3-(2-methylphenyl)-8-
oxabicyclo[3.2.1]oct-2-ene (5j)
M.p. 109–110 oC (Found: C, 75.0; H, 7.4. C17H20O3 requires C, 75.0;
H, 7.4%). max 3055, 3010, 2950, 2850, 1650, 1480, 1410, 1375, 1275,
1200, 1075, 1050, 860, 750, 730, 670 cm–1. 1H n.m.r. (CDCl3) 1.36, s,
CH3; 1.54, s, CH3; 1.99, dd, J 18.1, 0.7 Hz, H4 ; 2.27, s, ArCH3; 2.81,
m, H4 ; 4.46, br d, J 5.8 Hz, H5; 4.50, d, J 4.7 Hz, H1; 4.74, br d, J 5.5
Hz, H6; 4.78, d, J 5.5 Hz, H7; 5.74, dm, J 4.7 Hz, H2; 7.19, d, J 6.2 Hz,
H3´ or H6´; 7.12–7.74, m, 3H, aromatic. 13C n.m.r. (CDCl3) 19.7,

Derivatives of 8-Oxabicyclo[3.2.1]oct-6-en-3-one
935
ArCH3; 24.9, CH3; 26.2, CH3; 33.4, C 4; 76.6, C1; 79.4, C5; 85.8, C6;
86.1, C7; 112.3, CMe2; 125.7, C2; 125.8, C6´; 127.3, C5´; 127.8, C4´;
130.2, C 3´; 134.7, C 3´; 137.1, C 2´; 140.5, C 1´. Mass spectrum m/z 272
(M+•, 6%), 257 (10), 214 (7), 199 (33), 185 (56), 171 (100), 153 (18), 141
(13), 128 (28), 115 (35), 105 (7), 91 (17), 77 (10), 65 (15), 43 (43).
Qualitative Effect of the Synthesized Compounds on the Development
of Several Weeds and Cultures
The same procedure as described above was used to evaluate the
effect of compound (5g) on the growth of the crops Cucumis sativus,
Glycine max, Helianthus annuus, Lycopersicon esculentum, Phaseolus
vulgaris and Zea mays, and on the weeds Bidens pilosa, Brachiaria
plantaginea, Cenchrus echinatus, Desmodium tortuosum, Emilia
sonchifolia, Ipomoea grandifolia, Pennisetum setosum, Physalis angu-
lata and Setaria geniculata,
exo-6,exo-7-Isopropylidenedioxy-3-(2,3,4-trimethoxyphenyl)-8-
oxabicyclo[3.2.1]oct-2-ene (5k)
M.p. 85–86°C (Found: C, 65.5; H, 6.7. C19H24O6 requires C, 65.5;
H, 6.9%). max 3050, 2980, 2950, 2850, 1600, 1500, 1420, 1415, 1375,
1285, 1215, 1110, 1070, 975, 880, 770, 700 cm–1. 1H n.m.r. (CDCl3)
1.35, s, CH3; 1.54, s, CH3; 2.27, d, J 18.0 Hz, H 4 ; 2.89, ddd, J 18.0,
5.8, 1.5 Hz, H 4 ; 3.81, s, OCH3; 3.85, s, OCH3; 3.64, s, OCH3; 4.45, d,
J 5.8 Hz, H5; 4.52, d, J 5.1 Hz, H1; 4.68, d, J 5.5 Hz, H6; 4.76, br d, J
5.5 Hz, H 7; 5.97, dm, J 5.1 Hz, H 2; 6.62, d, J 8.7 Hz, H 5´; 6.81, d, J
8.7 Hz, H6´. 13C n.m.r. (CDCl3) 24.9, CH3; 26.2, CH3; 32.4, C 4; 55.9,
OCH3; 60.8, 2×OCH3; 76.8, C 1; 79.4, C 5; 85.7, C 6; 86.0, C 7; 107.1,
C 5´; 112.2, CMe2; 123.0, C 2; 125.3, C 6´; 127.4, C 1´; 134.5, C 3;
142.2, C 3´; 151.5, C 2´; 153.3, C 4´. Mass spectrum m/z 349 ([M+1]+,
4%), 348 (M+•, 18), 333 (2), 291 (3), 260 (15), 259 (100), 247 (39), 230
(7), 217 (7), 191 (10), 168 (5), 115 (10), 91 (7), 77 (9) 65 (7), 59 (13),
43 (59), 41 (12).
In this experiment only qualitative evaluations of susceptibility or
resistance of each species were made.
Acknowledgments
L.C.A.B. is very grateful to the Royal Society of
Chemistry for a Research Grant. We also thank the Brazilian
Agencies: Conselho Nacional de Desenvolvimento
Científico e Tecnológico (CNPq) for research fellowships
(L.C.A.B. and D.P.V.); Coordenação de Aperfeiçoamento de
Pessoal de Nível Superior (CAPES) for an MSs studentship
(G.J.A.C.) and Fundação de Amparo à Pesquisa do Estado de
Minas Gerais (FAPEMIG) for financial support. We are also
very grateful to Professor Franciso Affonso Ferreira from
the Department of Plant Science, Universidade Federal de
Viçosa, for helping us with the biological assays.
Bioassays
Three different bioassays were carried out to evaluate the plant
growth regulatory activity of the synthesized compounds. In all cases, a
stock solution was prepared by dissolving each compound (50 mg) in
xylene (3 ml). To this solution was added sodium dodecyl sulfate (0.12
g), the surfactant Tween 40 (0.7 ml) and water (10 ml). The resultant
suspension was sonicated for 3 min and then transferred to a volumet-
ric flask (1 litre), and the volume adjusted to 1 litre with water. A solu-
tion with the same composition described above, but without the
compound to be tested, was used as a control.
References
1 Evans, D., Chem. Br., 1998, 34, 20.
2 Radgale, N. N., Kearney, P. C., and Plimmer, J. R., ‘Eight
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Washington, DC, 1995).
3 Folha de São Paulo, 3/1/95.
Assay of Root Elongation in Petri Dishes
4 Oliveira Júnior, R. S., Ph.D. Thesis, Federal University of Viçosa,
1998.
Groups of eight pregerminated Sorghum bicolor L. cv. BR007B
were placed in Petri dishes (diameter 9 cm) containing washed sand
(150 g) and the solution (20 ml) containing the compound to be tested.
The Petri dishes were sealed with Parafilm and incubated at 28°C, in
darkness and inclined at 75o. After 48 h, the root length was measured
to the nearest millimetre. All treatments were replicated six times in a
completely randomized design. The percentage of root growth inhibi-
tion was calculated in relation to the root length of the control that was
6.73 cm. The data were analysed by using Tukey´s test at 0.05 proba-
bility level.17
5 Gressel, J., in ‘XXI Congresso Brasileiro da Ciência das Plantas
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D. C., J. Chem. Soc., Perkin Trans. 1, 1992, 3251.
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Braz. Chem. Soc., 1997, 8, 19.
Effect of the Synthesized Compounds on the Development of the Root
and Aereal Parts of Cucumber
To each plastic pot of 0.35 litre3 was added washed sand saturated
with the solution of the test compound (60 ml/450 g of sand). Six seeds
of Cucumis sativus L. (cv. Caipira AG 22, obtained from the local
market) were planted in each pot. The pots were placed in a greenhouse,
watered regularly to maintain the humidity at 13.3% w/w, and three
times a week a solution containing the required nutrients was applied.
The plants were harvested 14 days after sowing, and the roots and aerial
parts were separated and weighted. They were then dried at 72°C, until
constant weight and the mass of the dried matter was determined. The
percentage of root and aerial part growth inhibition was calculated in
relation to the mass of the control.
12 Demuner, A. J., Barbosa, L. C. A., and Veloso, D. P., J. Agric. Food
Chem., 1998, 46, 1173.
13 Baker, K. Y., Brown, J. M., Hughes, N., Skarnulis, A. J., and Sexton,
A., J. Org. Chem., 1991, 56, 698.
14 Lautens, M., Synlett, 1993, 3, 177.
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16 Perrin, D. D., and Armarego, W. L. F., ‘Purification of Laboratory
Chemicals’ (Pergamon: Oxford 1988).
17 Gomes, F. P., ‘Curso de Estatística Experimental’ (Nobel:
Piracicaba 1990).
The data were analysed by using Tukey´s test at 0.05 probability
level.17