Stereochemistry of terpene derivatives. Part 5: Synthesis of chiral lactones fused to a carane system - Insect feeding deterrents

Article abstract of DOI:10.1016/j.tetasy.2005.11.025

Chiral iodo- 9, bromo- 10 and hydroxylactones 12 condensed with the carane system were obtained. In each case, the synthetic pathway led to an enantiomerically pure diastereoisomer to generate two stereogenic centers. Iodo- 9 and bromolactone 10 possess a γ-lactone group while the hydroxylactone 12 possesses a δ-lactone moiety situated trans to the gem- dimethylcyclopropyl ring. The structures of the products were confirmed by X-ray crystallography. These lactones were tested for antifeedant activity against storage pest insects.

Full text of DOI:10.1016/j.tetasy.2005.11.025

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 17 (2006) 124–129
Stereochemistry of terpene derivatives. Part 5: Synthesis of chiral
lactones fused to a carane system—insect feeding deterrentsq
a
a
b
b
_
´
Bozena Fra˛ckowiak, Katarzyna Ochalik, Agata Białonska, Zbigniew Ciunik,
c
a,
*
´
´
Czesław Wawrzenczyk and Stanisław Lochynski
aDepartment of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzez_e Wyspian´skiego 27,
50-370 Wrocław, Poland
bFaculty of Chemistry, University of Wrocław, F. Joliot-Curie 14, 50-383 Wrocław, Poland
cDepartment of Chemistry, Agricultural University, Norwida 25, 50-375 Wrocław, Poland
Received 3 November 2005; accepted 28 November 2005
Available online 9 January 2006
Dedicated to Professor Prezemysław Mastalerz on his 80th birthday
Abstract—Chiral iodo- 9, bromo- 10 and hydroxylactones 12 condensed with the carane system were obtained. In each case, the
synthetic pathway led to an enantiomerically pure diastereoisomer to generate two stereogenic centers. Iodo- 9 and bromolactone
10 possess a c-lactone group while the hydroxylactone 12 possesses a d-lactone moiety situated trans to the gem-dimethylcyclopropyl
ring. The structures of the products were confirmed by X-ray crystallography. These lactones were tested for antifeedant activity
against storage pest insects.
Ó 2005 Published by Elsevier Ltd.
1. Introduction
We were interested in an investigation of the structure–
activity correlation for sesquiterpenoid lactones with
antifeedant activity. Many such derivatives have already
been synthesized using monoterpenes as starting materi-
als.5 We have used (+)-3-carene as a substrate for opti-
cally active lactones. The presence of a double bond and
the easy introduction of a hydroxy group into the mole-
cule of this monoterpene make it a convenient starting
material for the synthesis of lactones. Previously, we
obtained a series of spirolactones from (+)-3-carene.6
Herein, we report the synthesis of chiral lactones fused
to a carane system.
(+)-3-Carene 1, which belongs to the Ôchiral poolÕ, is a
valuable substrate in the syntheses of optically active
compounds. Easily obtained derivatives of this monoter-
pene have been used as chiral auxiliaries in enantioselec-
tive transformations.2a Organoborane reagents obtained
from (+)-3-carene were used in the enantioselective allyl-
boration of aldehydes.2b The enantioselective addition
of diethylzinc to aldehydes was catalyzed by an amino
alcohol derivative of carane.2c The same chiral auxiliary
was used in the addition of lithium cyclopropylacetylide
to ketimine to give the chiral HIV-1 non-nucleoside
reverse transcriptase inhibitor DPC963.2d (+)-3-Carene
was also used as a starting material in the synthesis of
natural products, for example, artemisin3a or pyrethroic
acids.3b This monoterpene was also a substrate in the
synthesis of chiral, biologically active products in which
the carane moiety is preserved, such as b-amino acids4a
and sulfides.4b
2. Results and discussion
The key compound in the synthesis of lactones is allylic
alcohol 5, which was obtained in a four-step procedure
from (+)-3-carene (Scheme 1).7a In a reaction of this
compound with m-chloroperbenzoic acid, trans-3,4-
epoxycarane 2 was obtained. Next, the ring opening of
epoxide 2 with diethylaluminum tetramethylpiperidine
provided allylic alcohol 3 as the only product. The
synthesis of compound 3 was broadly investigated
earlier.7a–d We chose the most efficient strategy (above
q See Ref. 1.
*
Corresponding author. Tel.: +48 71 320 2400; fax: +48 71 347
7175; e-mail: stanislaw.lochynski@pwr.wroc.pl
0957-4166/$ - see front matter Ó 2005 Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2005.11.025

B. Fra˛ckowiak et al. / Tetrahedron: Asymmetry 17 (2006) 124–129
125
hol 5 only one diastereoisomer of ester 7 was formed
in this reaction. In the crystal of 8, the configuration
of the stereogenic center at the C-4 carbon atom was
assigned on the basis of the known configuration at the
C-1 and C-6 atoms of this unsaturated carboxylic acid
(Fig. 1), obtained after hydrolysis of ester 7 (Scheme 2).
O
OH
a
b
1
2
3
c
OR
O
g
d
CO2Et
7
4
5, R = H
e
f
6, R = p-NB
Scheme 1. Reagents: (a) m-CPBA, CH2Cl2; (b)
N AlEt , benzene; (c)
2
Na2Cr2O7, H2SO4; (d) NaBH4; (e) p-NO2PhCOCl, Py; (f) KOH,
MeOH; (g) CH3C(OC2H5)3, C2H5COOH.
90% yield from 1).7a Other methods, such as the isomeri-
zation of 2 with aluminum isopropoxide give a mixture
of products containing predominantly 3.7d
Compound 3 was converted into aldehyde 4 with chro-
mic acid, as reported by Gollnick and Schade7b and by
Paquette et al.7a This reaction afforded product 4 in
good yield only, when substrate 3 was pure (above
99%). The specific rotation of our sample of 4 (ꢀ47.6)
was different from those reported in the literature
(ꢀ25.8)7b and (ꢀ131).7a The 1H NMR spectrum of alde-
hyde 4 obtained was identical to that previously
reported.7a
Figure 1. Molecular structure of 8.
Iodolactonization9 of the c,d-unsaturated acid 8 affor-
ded the tricyclic product 9, in which the lactone ring is
condensed with the carane skeleton. The other halolac-
tone–bromolactone 10 was formed in a reaction of ester
7 with N-bromosuccinimide in a water/tetrahydrofuran
solution. In all these reactions, c-lactones 9 and 10 were
obtained as single diastereoisomers. The lactone moiety
in both compounds 9 and 10 is situated in the trans
position to the gem-dimethylcyclopropyl group. The trans
orientation of the lactone ring in these molecules was
confirmed by X-ray crystallographic analysis (Figs. 2
and 3).
The reduction of aldehyde 4 with sodium borohydride
gave allylic alcohol 5 (yield 72% from (+)-3-carene).
This alcohol was converted into p-nitrobenzoate 6,
which was purified by column chromatography and then
hydrolyzed back to 5. Next, c,d-unsaturated ester 7 was
obtained from 5 in the Claisen rearrangement (Johnson
modification)8 (Scheme 1). Due to the steric hindrance
created by the gem-dimethylcyclopropyl group in alco-
Epoxy ester 11 was obtained by oxidation of the
c,d-unsaturated ester 7 with m-chloroperbenzoic acid
O
O
I
a
b
CO2Et
COOH
7
8
9
d
c
O
O
O
O
O
HO
Br
e
CO2Et
10
11
12
Scheme 2. Reagents: (a) KOH, EtOH; (b) I2, KI, NaHCO3; (c) NBS, THF; (d) m-CPBA; (e) HClO4, H2O–THF.

126
B. Fra˛ckowiak et al. / Tetrahedron: Asymmetry 17 (2006) 124–129
Figure 2. Molecular structure of 9.
Figure 4. Molecular structure of 12.
almost 200.5 These tests demonstrated the influence of
the additional groups on the biological activity. Bromo-
lactone 10 was the most active compound against all
three species, displaying the highest deterrence for
Trogoderma granarium (T = 120.9). Replacement of
the bromine atom with iodine (compound 9) lowered
the activity (T = 7.5).
3. Experimental
(+)-3-Carene was purchased from Sigma–Aldrich. The
course of all the reactions, composition of products,
and their purities were checked by thin-layer chromatog-
raphy (TLC) and gas chromatography (GC). TLC was
carried out on silica gel DC-Alufolien Kieselgel 60
(Merck). Plates were developed in a mixture of hexane,
diethyl ether and acetone in various ratios and visual-
ized with 20% ethanolic H2SO4, containing 0.1% of anis-
aldehyde. Preparative column chromatography was
carried out on silica gel (230–400 mesh, Merck) with a
mixture of hexane, diethyl ether, ethyl acetate and
acetone (various ratios) as eluent. Analytical GC was
performed on a Hewlett Packard 5890 (seria II) instru-
ment using the capillary column HP-5 (length 25 m,
temperature 120–180 °C). Melting points (uncorrected)
were determined on a Boetius apparatus. IR spectra
were taken from liquid films or in KBr on a Perkin–
Elmer 621 spectrometer. 1H and 13C NMR spectra were
recorded in CDCl3 with TMS as an internal standard on
a Bruker AvanceTM DRX 300 instrument. Chemical
shifts (d) are reported in ppm and coupling constants
(J) are given in Hz. 13C–H substitution was determined
with a DEPT-135 experiments. Optical rotation mea-
surements were obtained on an Autopol IV automatic
polarimeter (Rudolph). X-ray data were collected at
100 K using an Oxford Cryosystem device on a Kuma
KM4CCD j-axis diffractometer with graphite-mono-
chromated MoKa radiation. The data were corrected
for Lorentz and polarization effects. Absorption correc-
tion was applied for the data of 9 and 10. Data reduc-
Figure 3. Molecular structure of 10.
(Scheme 2). Next, hydroxylactone 12 was synthesized by
the acidic lactonization of 11. The IR spectrum of 12
(1740 cmꢀ1) confirmed that the d-lactone ring was
formed. The structure of this compound was determined
by X-ray analysis (Fig. 4) served us as a basis for the
assignment of the configuration of 11. According to
the mechanism of the hydroxylactonization,10a,b the
cis-hydroxy- trans-d-lactone 12 can only be obtained
from 11, in which the oxirane ring is in the cis position
to the gem-dimethylcyclopropane ring.
Lactones 9, 10 and 12 were tested for feeding deterrent
activity against three storage pest insects: the grain
weevil (Sitophilus granaries, adults), the confused flour
beetle (Trogoderma granarium, larvae) and the khapra
beetle (Tribolium confusum, larvae and adults). All com-
pounds tested exhibited low or moderate activity
towards these pests. The total coefficients of deterrence
(T) determined by means as described earlier5 reach val-
ues that fall between 7.5 and 120.9. For comparison, the
coefficient for the most potent antifidant, azadirachtin
determined in the same manner reaches a value of

B. Fra˛ckowiak et al. / Tetrahedron: Asymmetry 17 (2006) 124–129
127
tion and analysis were carried out with the Oxford Dif-
3.3. Synthesis of (ꢀ)-3-carene-10-yl p-nitrobenzoate 6
fraction (Wrocław) programs.11 The structures were
solved by direct methods and refined by the full-matrix
least-squares method on all F2 data using programs.12
Non-hydrogen atoms were refined with anisotropic ther-
mal parameters; all H atoms were found in Dq maps or
placed in calculated positions. Before the last cycle of
refinement all H atoms were fixed and were allowed to
ride on their parent atoms. Crystallographic data for
structures reported in this paper have been deposited
with the Cambridge Crystallographic Data Centre as a
supplementary publication numbers.
Alcohol 5 (3.06 g, 20.11 mmol) was dissolved in anhy-
drous pyridine (12.2 ml). p-Nitrobenzoic chloride
4.27 g (22.85 mmol) was added to the solution in por-
tions and the mixture stirred overnight. Next, the reac-
tion was warmed up to 60 °C and stirred for 2 more
hours. After this time, the mixture was diluted with
water (60 ml), saturated NaHCO3 solution (21 ml) was
added and the product was extracted with diethyl ether.
The combined organic layers were washed with a 5%
H2SO4 solution, then with water and dried over MgSO4.
Crude product 6 was purified by column chromatogra-
3.1. Synthesis of (+)-3-caren-10-al 4
phy (eluent: hexane–ethyl acetate 30:1) to give pure
20
compound 6 (5.71 g, 18.96 mmol) ½aꢁD ¼ ꢀ2:9 (c 1.2,
Aldehyde 4 was synthesized according to a known pro-
CHCl3); IR (film, cmꢀ1): 3112(w), 2900(s), 1725(vs),
1
cedure.7a The crude product was purified by column
1607(s), 1529(vs), 1346(vs), 1271(v), 873(s), 719(vs); H
chromatography (silica gel, hexane–ethyl acetate 30:1)
NMR (CDCl3): 0.70 (t, J = 8.3 Hz, 1H at C-6); 0.75–
0.90 (m, 1H at C-1); 0.79 (s, 3H at C-8 or C-9); 1.05
(s, 3H at C-8 or C-9); 1.93–2.17 (m, 2H at C-2); 2.27–
2.51 (m, 2H at C-5); 4.72 (s, 2H at C-10); 5.71–5.80
(m, 1H at C-4); 8.24 (m, 4H at C-13, C-14, C-16 and
C-17); 13C NMR (CDCl3): 13.27 (C-8 or C-9), 16.91
(C-6), 17.14 (C-7), 17.78 (C-1), 20.78 (C-5), 21.09 (C-
2), 28.29 (C-8 or C-9), 70.39 (C-10), 123.56 (C-4),
126.23 (C-14 and C-16), 130.23 (C-12), 130.70 (C-13
and C-17), 135.86 (C-3), 150.56 (C-15), 164.57 (C-11).
Anal. Calcd for C17H19NO4: C, 67.76; H, 6.36; N,
4.65. Found: C, 67.83; H, 6.32; N, 4.61.
20
to give 4 as an oil: ½aꢁD ¼ ꢀ27:6 (c 1.2, CHCl3);
20
20
½aꢁD ¼ ꢀ47:6 (c 0.61, benzene); Lit.7a: ½aꢁD ¼ ꢀ131:0
20
(c 2.1, benzene); Lit.7b: ½aꢁD ¼ ꢀ25:8 (c 2.3, benzene);
IR (film, cmꢀ1): 2941(vs), 2732(m), 2708(m), 1683(vs),
1
1420(s), 1170(vs), 744(m); H NMR (CDCl3): 0.69 and
1.07 (2 s, 6H: 3H at C-8 and 3H at C-9); 0.76–0.87 (m,
2H: 1H at C-6 and 1H at C-1); 2.12–2.36 (m, 2H: 1H
at C-5 and 1H at C-2); 2.44–2.54 (m, 1H at C-2);
2.65–2.76 (m, 1H at C-5); 6.67–6.72 (m, 1H at C-4);
9.40 (s, 1H at C-10).
3.2. Synthesis of (+)-3-caren-10-ol 5
3.4. Synthesis of ethyl [(ꢀ)-3(10)-carene-trans-4-yl]-
Sodium borohydride (0.43 g, 11.37 mmol) in ethyl alco-
hol (22.00 ml) was added in portions to a solution of
aldehyde 4 (4.31 g, 28.73 mmol) in ethyl alcohol
(65 ml). The mixture was stirred until TLC monitoring
showed the absence of substrate 4 (about 1 h). Then,
saturated NaHCO3 solution was added and ethyl alco-
hol removed on a rotary evaporator. The water layer was
extracted three times with diethyl ether. The combined
organic layers were dried over MgSO4 and the crude
product converted to p-nitrobenzoate 6. After purifica-
tion (the procedure and spectroscopic data described
below), the pure product 6 (5.71 g, 18.96 mmol) was di-
luted in methanol (45 ml) and potassium hydroxide
(22.75 mmol) added. The reaction mixture was stirred
overnight and after TLC analysis did not show the pres-
ence of p-nitrobenzoate 6, the solvent was removed.
Next, water was added and the aqueous phase extracted
three times with diethyl ether and the organic phase
dried over MgSO4. After removing the solvent, alcohol
acetate 7
A mixture of alcohol 5 (2.5 g, 16.44 mmol), triethyl ort-
hoacetate (15 ml, 82.20 mmol) and propionic acid (one
drop) was heated at 138 °C until TLC analysis did not
show the presence of substrate 5. The unreacted ortho-
acetate was then distilled off and the crude product 7
purified by column chromatography (eluent: hexane–
diethyl ether from 100:1 to 50:1) to give pure pro-
20
duct 7 (3.21 g, 14.47 mmol, 88% yield): ½aꢁD ¼ ꢀ54:2 (c
1.2, CHCl3); n20 ¼ 1:4701; IR (film, cmꢀ1): 3040(m)
D
2934(m), 1737(vs), 1252(m), 1156(m), 887(m); 1H
NMR (CDCl3): 0.64 (td, J = 9.2, 4.4 Hz, 1H at C-6);
0.74 (t, J = 8.2 Hz, 1H at C-1); 0.90 and 0.99 (2 s, 6H:
3H at C-8 and 3H at C-9); 1.25 (t, J = 7.1 Hz, 3H at
C-14); 1.52 (dt, J = 14.6, 4.5 Hz, 1H at C-5); 1.94
(ddd, J = 14.6, 9.5, 2.4 Hz, 1H at C-5); 2.24 (d,
J = 16.8 Hz, 1H at C-2); 2.43–2.52 (m, 2H at C-11);
2.53–2.66 (m, 2H: 1H at C-2 and 1H at C-4); 4.12 (q,
J = 7.1 Hz, 2H at C-13); 4.63–4.70 (m, 2H at C-10);
13C NMR (CDCl3): 14.29 (C-8 or C-9), 14.57 (C-14),
16.26 (C-6), 18.21 (C-7), 20.64 (C-1), 25.42 (C-5),
25.96 (C-2), 28.68 (C-8 or C-9), 38.13 (C-11), 38.58 (C-
4), 60.12 (C-13), 108.39 (C-10), 149.54 (C-3), 172.79
(C-12). Anal. Calcd for C14H22O2: C, 75.63; H, 9.97.
Found: C, 75.76; H, 9.84.
5 was obtained (2.84 g, 18.67 mmol, 65% yield) as an
20
oil 95% purity (GC). ½aꢁD ¼ þ7:1 (c 1.1, CHCl3); IR
(film, cmꢀ1): 3330(bs), 2866(s), 1681(w), 1430(s),
1034(m), 1000(s); 1H NMR (CDCl3): 0.67 (t,
J = 8.3 Hz, 1H at C-6); 0.72–0.80 (m, 1H at C-1); 0.76
(s, 3H at C-8 or C-9); 1.04 (s, 3H at C-8 or C-9); 1.56
(s, 1H at –OH); 1.90–2.03 (m, 2H at C-2); 2.27–2.50
(m, 2H at C-5); 3.96 (s, 2H at C-10); 5.46–5.67 (m, 1H
at C-4); 13C NMR (CDCl3): 13.33 (C-8 or C-9), 16.97
(C-7), 17.10 (C-6), 17.86 (C-1), 20.51 (C-5), 20.54 (C-
2), 28.33 (C-8 or C-9), 67.85 (C-10), 121.83 (C-4),
135.36 (C-3). Anal. Calcd for C10H16O: C, 78.90; H,
10.59. Found: C, 78.96; H, 10.50.
3.5. Synthesis of [(ꢀ)-3(10)-Caren-trans-4-yl]acetic acid 8
Ester 7 (0.60 g, 2.7 mmol) was diluted in ethyl alcohol
(20 ml) after which potassium hydroxide (0.22 g,
3.8 mmol) was added. Next, the reaction was warmed

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B. Fra˛ckowiak et al. / Tetrahedron: Asymmetry 17 (2006) 124–129
up to 70 °C and stirred until TLC analysis did not show
the presence of substrate 7 (3 h) and the solvent
removed. Water was then added and the organic impuri-
ties extracted with diethyl ether. The aqueous solution
was acidified to pH about 4–5 by the addition of
0.01 M HCl and extracted three times with diethyl ether.
The organic phase was washed with brine and dried over
MgSO4. After removing of the solvent, the crude pro-
1.715 Mg mꢀ3, l = 2.563 mmꢀ1, R = 0.022, wR = 0.048
(6240 reflections, all data) for 136 parameters. CCDC
285889.
3.7. Synthesis of (1S,3S,7S,9R)-(+)-3-bromomethyl-10,10-
dimethyl-4-oxatricyclo[7.1.0.1.903.7]decan-5-one 10
Ester 7 (0.20 g, 0.9 mmol) was diluted in THF (14 ml)
and water (6 ml) and N-bromosuccinimide (0.97 g,
5.43 mmol) then added. The mixture was stirred at the
room temperature until TLC analysis did not show the
presence of substrate 7. The reaction mixture was then
diluted with diethyl ether and washed with saturated
NaHCO3 solution, water and dried over MgSO4. Crude
product 10 was purified by column chromatography
(eluent: hexane–acetone 5:1) to give bromolactone 10
duct 8 was obtained (0.37 g, 1.9 mmol, 72% yield):
20
mp = 57–59 °C; ½aꢁD ¼ ꢀ55:4 (c 2.0, CHCl3); IR
(KBr, cmꢀ1): 3080(w), 2960(m), 1696(s), 1431(m),
1
1260(s), 801(m); H NMR (CDCl3): 0.65 (td, J = 9.2,
4.4 Hz, 1H at C-6); 0.76 (t, J = 8.4 Hz, 1H at C-1);
0.91 and 1.00 (2 s, 6H: 3H at C-8 and 3H at C-9); 1.26
(s, 1H from –OH); 1.54 (dt, J = 4.7, 4.3 Hz, 1H at
C-5); 1.99 (dd, J = 9.4, 1.8 Hz, 1H at C-5); 2.26
(d, J = 16.6 Hz, 1H at C-2); 2.47–2.67 (m, 4H: 2H at
C-11, 1H at C-2 and 1H at C-4); 4.86–4.76 (m, 2H at
C-10); 13C NMR (CDCl3): 14.49 (C-8 or C-9), 16.22
(C-6), 18.27 (C-7), 20.60 (C-1), 25.42 (C-5), 25.94 (C-
2), 28.68 (C-8 or C-9), 37.82 (C-11), 38.30 (C-4),
108.72 (C-10), 149.19 (C-3), 178.78 (C-12). Anal. Calcd
for C12H18O2: C, 74.19; H, 9.34. Found: C, 74.05; H,
9.41. Crystal data: C12H18O2, Mw = 194.26, T = 100
(2) K, Mo-Ka radiation, monoclinic, space group P21,
as a white solid (0.21 g, 0.77 mmol, yield 85%):
20
mp = 86–88 °C; ½aꢁD ¼ þ28:7 (c 2.4, CHCl3); IR
(KBr, cmꢀ1): 2951(s), 1765(vs), 1411(m), 1164(s); 1H
NMR (CDCl3): 0.66–0.81 (m, 1H at C-9); 0.95–1.15
(m, 3H: 2H at C-8 and 1H przy C-1); 1.01 and 1.06 (2
s, 6H: 3H at C-11 and 3H at C-12); 1.82 (dd, J = 14.9,
6.5 Hz, 1H at C-2); 2.13 (dd, J = 15.2, 7.0 Hz, 1H at
C-2); 2.46 (dd, J = 18.5, 4.6 Hz, 1H at C-6); 2.62–2.70
(m, 1H at C-7); 2.98 (dd, J = 18.5, 11.2 Hz, 1H at C-
6); 3.39 and 3.56 (2 d, J = 10.8 Hz, 2H at C-13); 13C
NMR (CDCl3): 14.66 (C-11 or C-12), 16.80 (C-9),
17.47 (C-1), 19.19 (C-10), 23.23 (C-8), 27.62 (C-2),
28.20 (C-11 or C-12), 35.40 (C-7), 35.89 (C-13), 40.66
(C-6), 86.14 (C-3), 175.95 (C-5). Anal. Calcd for
C12H17BrO2: C, 52.76; H, 6.27; Br, 29.25. Found: C,
52.61; H, 6.34; Br, 29.20. Crystal data: C12H17BrO2,
Mw = 273.17, T = 100(2) K, Mo-Ka radiation, ortho-
˚
˚
˚
a = 13.518(3) A, b = 5.9290(12) A, c = 13.755(3) A,
3
˚
b = 91.50(3)°, V = 1102.1(4) A , Z = 4, Dc = 1.171
Mg mꢀ3, R = 0.066, wR = 0.110 (1943 reflections, all
data) for 253 parameters. CCDC 285888.
3.6. Synthesis of (1S,3S,7S,9R)-(+)-10,10-Dimethyl-
3-iodomethyl-4-oxatricyclo[7.1.0.1.903.7]decan-5-one 9
˚
The mixture of acid 8 (0.28 g, 1.4 mmol) in diethyl ether
(6 ml) and 0.5 M solution of NaHCO3 was stirred at
room temperature for 30 min. Next, a solution of I2
(0.58 g, 2.3 mmol) and KI (1.15 g, 6.9 mmol) in water
(7 ml) was dropped. The mixture was stirred until
TLC monitoring showed the absence of substrate 8
and diluted with diethyl ether. The organic phase was
washed with Na2S2O3 solution and saturated NaHCO3
solution, brine and dried over MgSO4. The crude prod-
uct 9 was purified by column chromatography (eluent:
hexane–acetone 5:1) to give iodolactone 9 as a white
rhombic, space group P212121, a = 7.1367(4) A, b =
3
˚
˚
˚
9.8459(5) A, c = 17.2841(8) A, V = 1214.51(11) A , Z = 4,
Dc = 1.494 Mg mꢀ3, l = 3.364 mm ꢀ1, R = 0.038, wR =
0.070 (3429 reflections, all data) for 136 parameters.
CCDC 285890.
3.8. Synthesis of ethyl [(ꢀ)-cis-3,10-epoxy-trans-
caran-trans-4-yl]acetate 11
m-Chloroperbenzoic acid (70%, 0.81 g, 3.6 mmol) in dry
methylene chloride (17 ml) was dropped to the solution
of ester 7 (0.80 g, 3.6 mmol) in dry methylene chloride
(17 ml). When the reaction was complete (TLC, 1 h),
the mixture was diluted with diethyl ether and the
organic phase washed with 10% aqueous Na2S2O3
solution, saturated NaHCO3 solution, water and dried
over MgSO4. Crude product 10 was purified by column
chromatography (eluent: hexane–ethyl acetate 15:1) to
solid (0.36 g, 1.1 mmol, yield 78%); mp = 84–86 °C;
20
½aꢁD ¼ þ48:6 (c 2.3, CHCl3); IR (KBr, cmꢀ1): 2926(s),
1770(vs), 1410(m), 1167(s), 1410(w), 1168(m); 1H
NMR (CDCl3): 0.65–0.80 (m, 1H at C-9); 0.95–1.30
(m, 3H: 2H at C-8 and 1H at C-1); 1.01 and 1.06 (2 s,
6H: 3H at C-11 and 3H at C-12); 1.82 (dd, J = 14.5,
6.0 Hz, 1H at C-2); 2.16 (dd, J = 15.2, 7.1 Hz, 1H at
C-2); 2.45 (dd, J = 18.4, 4.7 Hz, 1H at C-6); 2.51–2.60
(m, 1H at C-7); 2.98 (dd, J = 18.4, 11.0 Hz, 1H at
C-6); 3.27 and 3.43 (2 d, J = 10.6 Hz, 2H at C-13);
13C NMR (CDCl3): 14.68 (C-11 or C-12), 16.21 (C-8),
16.94 (C-9), 18.13 (C-1), 19.50 (C-10), 23.46 (C-2),
28.24 (C-11 or C-12), 28.61 (C-6), 35.97 (C-8), 37.02
(C-7), 85.65 (C-3). Anal. Calcd for C12H17IO2: C,
45.02; H, 5.35; I, 39.64. Found: C, 44.95; H, 5.48;
I, 39.57. Crystal data: C12H17IO2, Mw = 320.16,
T = 100(2) K, Mo-Ka radiation, orthorhombic, space
give epoxyester 11 (0.42 g, 1.8 mmol, yield 49%);
20
½aꢁD ¼ ꢀ27:2 (c 1.1, CHCl3); IR (film, cmꢀ1): 2988(m),
1
2936(s), 1735(vs), 1259(m), 1160(s); H NMR (CDCl3):
0.66 (td, J = 9.3, 4.3 Hz, 1H at C-6); 0.89 (td, J = 8.8,
1.1 Hz, 1H at C-1); 0.95 and 1.01 (2 s, 6H: 3H at C-8
and 3H at C-9); 1.26 (t, J = 7.1 Hz, 3H at C-14); 1.37
(dd, J = 15.2, 0.7 Hz, 1H at C-2); 1.54–1.64 (m, 2H:
1H at C-2 and 1H at C-4); 2.04 (dd, J = 11.8, 9.5 Hz,
1H at C-5); 2.15 (ddd, J = 15.1, 8.5, 1.1 Hz, 1H at C-
5); 2.48–2.53 (m, 3H: 2H at C-10 and 1H at C-11);
2.63 (dd, J = 5.0, 1.2 Hz, 1H at C-11); 4.13 (dd,
J = 14.3, 7.1 Hz, 2H at C-13); 13C NMR (CDCl3):
˚
˚
group P212121, a = 7.8214(2) A, b = 10.0159(3) A,
3
˚
˚
c = 15.8284(5) A, V = 1239.97(6) A , Z = 4, Dc =

B. Fra˛ckowiak et al. / Tetrahedron: Asymmetry 17 (2006) 124–129
129
14.23 (C-8 or C-9), 15.47 (C-14), 16.23 (C-6), 17.76 (C-
7), 21.50 (C-1), 23.79 (C-5), 24.74 (C-2), 28.48 (C-8 or
C-9), 34.45 (C-11), 36.09 (C-4), 57.39 (C-10), 60.32
(C-13), 172.84 (C-12), 204.50 (C-3). Anal. Calcd
for C14H22O3: C, 70.56; H, 9.30. Found: C, 70.63; H,
9.25.
(Poznan, Poland) for evaluation of antifeedant
activities.
References
1. For part 4, see: Fra˛ckowiak, B.; Olejniczak, T.; Latajka,
´
´
R.; Białonska, A.; Ciunik, Z.; Lochynski, S. Tetrahedron:
3.9. Synthesis of (1S,3S,8S,10R)-(+)-11,11-dimethyl-3-
hydroxy-5-oxatricyclo[8.1.0.1.1003.8]undecan-6-one 12
Asymmetry, in press.
2. (a) Blaser, H. U. Chem. Rev. 1992, 92, 935–952; (b) Brown,
H. C.; Randad, R. S.; Bhat, K. S.; Zaidlewicz, M.;
Racherla, U. S. J. Am. Chem. Soc. 1990, 112, 2389–2392;
(c) Joshi, S. N.; Malhotra, S. V. Tetrahedron: Asymmetry
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Dorow, R. L.; Stone, B. R. P.; Parsons, R. L.; Pesti, J. A.;
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hedron Lett. 2003, 44, 387–389; (b) Krief, A. Pestic. Sci.
1994, 41, 237–257.
4. (a) Gyonfalvi, S.; Szakonyi, Z.; Fulop, F. Tetrahedron:
Asymmetry 2003, 14, 3965–3972; (b) Startseva, V. A.;
Nikitina, L. E.; Artemova, N. P.; Dieva, S. A.; Plemenkov,
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469.
Epoxy ester 11 (0.40 g, 1.7 mmol) in THF (4 ml) was
dropped into a mixture of tetrahydrofuran (4 ml), water
(4 ml) and perchloric acid (four drops), pH of this mix-
ture was 1.0. The reaction mixture was stirred at room
temperature for 72 h. Product 12 was extracted with
diethyl ether. After solvent evaporation the crude prod-
uct 12 was chromatographed (eluent: hexane–acetone
4:1). Pure hydroxy lactone 12 was obtained (0.19 g,
20
54%): mp = 99–100 °C; ½aꢁD ¼ þ19:2 (c 3.3, CHCl3);
IR (KBr, cmꢀ1): 3396(bw), 2932(w), 1740(m) 1459(w),
1
1051(m); H NMR (CDCl3): 0.53–0.66 (m, 1H at C-
10); 1.04 (s, 6H: 3H at C-12 and 3H at C-13); 1.53–
1.75 (m, 3H: 1H at C-9 and 2H at C-2); 1.82–2.10 (m,
3H: 1H at C-9, 1H at C-8 and 1H from –OH); 2.36
(dd, J = 16.0, 8.9 Hz, 1H at C-7); 2.64 (dd, J = 16.0,
5.7 Hz, 1H at C-7); 4.07(dd, J = 12.1, 1.1 Hz, 1H at C-
4); 4.34 (d, J = 12.1 Hz, 1H at C-4); 13C NMR (CDCl3):
14.67 (C-12 or C-13), 18.02 (C-10), 19.40 (C-1), 23.96
(C-9), 28.48 (C-12 or C-13), 29.35 (C-2), 34.31 (C-7),
38.14 (C-8), 70.33 (C-3), 75.47 (C-4), 172.43 (C-6). Anal.
Calcd for C12H18O3: C, 68.55; H, 8.63. Found: C, 68.32;
H, 8.73. Crystal data: C12H18O3, Mw = 210.26, T =
100(2) K, Mo-Ka radiation, triclinic, space group P1,
´
5. Wawrzenczyk, C.; Dams, I.; Szumny, A.; Szczepanik, M.;
´
´
Nawrot, J.; Pra˛dzynska, A.; Gabrys, B.; Dancewicz, K.;
Magnucka, E.; Gawdzik, B.; Obara, R.; Wzorek, A. Pol.
J. Environ. Stud. (Supl. III) 2005, 14, 69–84, and
references cited therein.
´
6. Lochynski, S.; Fra˛ckowiak, B.; Olejniczak, T.; Ciunik, Z.;
´
Wawrzenczyk, C. Tetrahedron: Asymmetry 2002, 13,
1761–1767.
7. (a) Paquette, L. A.; Ross, R. J.; Shi, Y.-J. J. Org. Chem.
1990, 55, 1589–1598; (b) Gollnick, K.; Schroeter, S.;
Ohloff, G.; Schade, G.; Schenck, G. O. Chem. Ber. 1965,
˚
˚
˚
a = 6.3234(19) A, b = 7.0852(14) A, c = 12.403(3) A,
a = 86.821(18)°, b = 85.69(2)°, c = 84.77(2)°, V =
´
´
687, 14; (c) Lochynski, S.; Kowalska, K.; Wawrzenczyk,
C. Flavour Frag. J. 2002, 27, 181–186; (d) Lajunen, M.;
Kujala, J. Acta Chem. Scand. 1989, 43, 813–815.
551.1(2) A , Z = 2, Dc = 1.267 Mg mꢀ3
, R = 0.117,
3
˚
8. Johnson, W. S.; Werthemann, L.; Bartlett, W. R.; Brock-
som, T. J.; Li, T. T.; Faulkner, D. J.; Petersen, M. R. J.
Am. Chem. Soc. 1970, 92, 741–743.
wR = 0.164 (2107 reflections, all data) for 271 para-
meters. CCDC 285891.
9. Mori, K.; Nakazono, Y. Tetrahedron 1986, 42, 283–290.
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Liebigs Ann. Chem. 1985, 275–300; (b) Olejniczak, T.;
Acknowledgements
´
Nawrot, J.; Ciunik, Z.; Wawrzenczyk, C. Pol. J. Chem.
2000, 74, 673–680.
The authors wish to express their thanks to the Polish
State Committee for Scientific Research for supporting
this work (Grant no. PBZ-KBN-060/T09/2001/15) and
Professor Jan Nawrot from Plant Protection Institute
11. Oxford Diffraction, Poland Sp. z o.o., CrysAlis CCD and
CrysAlis Red, V166, 2001.
12. Bruker AXS, SHELXTL V5.1, 1999.