Synthesis of aryl-containing terpenoids based on 1,4-dihydronaphthalene

Article abstract of DOI:10.1134/s1070428008030093

Successive transformations including oxidation of 1,4-dihydronaphthalene into 1,2,3,4-tetrahydronaphthalen-2-one, Reformatskii reaction of the latter with methyl bromoacetate, ozonolysis of the Reformatsky reaction product, and Emmons olefination of the aldehyde group in methyl 3-oxo-5-(2-formylphenyl) pentanate thus formed gave analogs of highly active dienoate juvenoids having an aromatic ring in their molecules.

Full text of DOI:10.1134/s1070428008030093

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 3, pp. 362–368. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © O.S. Kukovinets, M.I. Kislitsyn, R.A. Zainullin, A.A. Mukhamedzyanova, F.Z. Galin, M.I. Abdullin, 2008, published in Zhurnal
Organicheskoi Khimii, 2008, Vol. 44, No. 3, pp. 369–374.
Dedicated to G.A. Tolstikov
on his 75th anniversary
Synthesis of Aryl-Containing Terpenoids
Based on 1,4-Dihydronaphthalene
O. S. Kukovinetsa, b, M. I. Kislitsynb, R. A. Zainullina, A. A. Mukhamedzyanovab,
F. Z. Galina, and M. I. Abdullinb
a Institute of Organic Chemistry, Ural Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
b Bashkir State University, ul. Mingazheva 100, Ufa, 450014 Bashkortostan, Russia
e-mail: pmsv@bsu.bashedu.ru
Received September 21, 2006; revised July 12, 2007
Abstract—Successive transformations including oxidation of 1,4-dihydronaphthalene into 1,2,3,4-tetrahydro-
naphthalen-2-one, Reformatskii reaction of the latter with methyl bromoacetate, ozonolysis of the Reformatsky
reaction product, and Emmons olefination of the aldehyde group in methyl 3-oxo-5-(2-formylphenyl)pentanate
thus formed gave analogs of highly active dienoate juvenoids having an aromatic ring in their molecules.
DOI: 10.1134/S1070428008030093
It is known that in most cases introduction of
an aromatic ring into molecules of insect and plant
growth regulators enhances their biological effect and
in some cases extends the scope of their application
[1, 2]. It was also found that many aryl-substituted
terpenoids exhibit strong pharmacological activity
[3, 4] and that an important factor is the overall size of
juvenile hormone molecule [5]. We now propose a new
synthetic approach to difficultly accessible ortho-sub-
stituted aryl-containing terpenoids and polyenes on the
basis of 1,4-dihydronaphthalene (I).
completely the formation of tetrahydronaphthalene and
somewhat enhance the yield of target 1,4-dihydro-
naphthalene (I). The fraction of minor 1,2-dihydro-
naphthalene (II) was as low as 5% (Scheme 1).
The transformation of compound I into ortho-sub-
stituted benzene derivatives having an isoprenoid or
polyene side chain may be accomplished via ozonol-
ysis, as well as through intermediate epoxy derivative
III or 1,2,3,4-tetrahydronaphthalen-2-one (IV), as
shown in Scheme 2. However, after passing 1 equiv of
ozone through a solution of compound I in methanol
and subsequent reduction of peroxide products with
dimethyl sulfide, we detected no dialdehyde V in the
reaction mixture, and only unsaturated ketone VI was
isolated in a poor yield (Scheme 3); its subsequent
ozonolysis produced a complex mixture of products.
Epoxide III can readily be obtained from dihydro
derivative I by the action of tert-butyl hydroperoxide
in the presence of molybdenum hexacarbonyl. How-
ever, all our attempts to involve compound III in reac-
tion with organometallic reagents were unsuccessful.
Initial compound I was synthesized by reduction of
naphthalene according to Birch. In keeping with pub-
lished data, partial reduction of one aromatic ring in
the naphthalene molecule with metallic sodium in
alcoholic medium gives a mixture of 1,4-dihydro- and
1,2-dihydronaphthalenes I and II and tetrahydronaph-
thalene (89:9:2) [6, 7]. We tried to reduce naphthalene
to 1,4-dihydro derivative I using metallic sodium in
aqueous isopropyl alcohol. Additional ultrasonic ac-
tivation of the process allowed us to avoid almost
Scheme 1.
Na, i-PrOH–H2O
+
I, 95%
II, 5%
362

SYNTHESIS OF ARYL-CONTAINING TERPENOIDS
363
Scheme 2.
O
R
Me
O
R
COOR
O
or
III
IV
I
COOR
Me
CHO
CHO
Me
COOR
V
The transformation of 1,4-dihydronaphthalene (I) into
1,2,3,4-tetrahydronaphthalen-2-one (IV) was accom-
plished by treatment with sodium tetrahydridoborate
in the presence of boron trifluoride–ether complex,
subsequent oxidation of intermediate organoboron
compound to alcohol VII, and oxidation of the latter
with CrO3·Py·HCl (Scheme 4). We failed to effect
initially planned functionalization of ketone IV via re-
action with alkylmagnesium halides. Compound VIII
was not obtained in such a way, and in all cases the
Grignard compound acted as reducing agent, yielding
alcohol VII.
ly contained absorption bands due to stretching vibra-
tions of the ester C=O group (1740 cm–1) and OH
group (3350–3560 cm–1). The 1H and 13C NMR spectra
of IX were fully consistent with the assumed structure.
According to the GLC data, dehydration of alcohol
IX on heating with iodine in toluene gave a mixture
of two products at a ratio of 8:1. The IR spectrum of
this mixture contained weak absorption bands assign-
able to stretching vibrations of double C=C bond
(1635 and 1660 cm–1) and two ester carbonyl bands
(1730 and 1745 cm–1). The absence of signal in the
region δC 110–120 ppm of the 13C NMR spectrum
indicated that no compound X with exocyclic double
bond is present in the product mixture. Among iso-
meric compounds XI and XII, the major product was
assigned the structure of 1,2-dihydronaphthalene deriv-
ative XI on the basis of intensities of the olefinic
proton signals at δ 6.41 (XI) and 5.32 ppm (XII).
Scheme 3.
(1) O3–MeOH
O
(2) Me2S
I
VI, 24%
We failed to separate olefins XI and XII by column
chromatography. The major component was isolated
during purification of further transformation products.
Ozonolysis of the double bond in the partially hydro-
genated benzene ring of XI and XII (1 equiv of ozone
was passed through a solution of a mixture of com-
pounds XI and XII in methanol), followed by re-
duction of peroxide ozonolysis products with dimethyl
We succeeded in introducing a methoxycarbonyl
group into the β-position with respect to the aromatic
ring by Reformatsky reaction of 1,2,3,4-tetrahydro-
naphthalen-2-one (IV) with methyl bromoacetate in
the presence of activated zinc (Scheme 5). The IR
spectrum of methyl 2-hydroxy-1,2,3,4-tetrahydronaph-
thalen-2-yl-acetate (IX) thus obtained characteristical-
Scheme 4.
CrO3 ·Py·HCl
IV
(1) BF3 ·Et2O–NaBH4
(2) H2O2–NaOH
AlkMgHlg
OH
AlkMgHlg
I
OH
R
VII
VIII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 3 2008

KUKOVINETS et al.
Scheme 5.
364
COOMe
OH
BrCH2COOMe, Zn
I2, PhMe
COOMe
COOMe
IV
+
IX
XI
XII
COOMe
X
sulfide and chromatographic separation, gave methyl
5-(2-formylphenyl)-3-oxopentanoate (XIIIa/XIIIb)
(Scheme 6). The absence of signal at δ 9.50 ppm, typ-
ical of an aliphatic aldehyde proton, and the presence
of a singlet at δ 10.53 ppm (proton in the aldehyde
ketone tautomer XIIIa give rise to doublets at
δ 2.98 and 3.30 ppm (2J = –16.8 Hz).
Olefination of dicarbonyl compound XIII with
ethyl 4-(diisopropoxyphosphoryl)-3-methylbut-2-eno-
ate afforded methyl (2ξ,4E)-3-methyl-5-[2-(5-ethoxy-
3,5-dioxopentyl)phenyl]penta-2,4-dienoate (XIV)
(Scheme 6). The IR spectrum of the product lacked
absorption band at 1715 cm–1, which is typical of alde-
hyde carbonyl group, but contained a band at 1620 cm–1
characteristic of conjugated dienes. These data in
combination with the 1H and 13C NMR spectra of com-
pound XIV indicated completeness of the transforma-
tion of XIII. Like keto ester XIII, compound XIV is
capable of undergoing keto–enol tautomerism. The re-
action of XIV with methylmagnesium iodide, followed
by dehydration of the alcohols thus formed by heating
with p-toluenesulfonic acid gave ortho-substituted
arylterpenoid XV.
1
group attached to an aromatic ring) in the H NMR
spectrum of the isolated ozonolysis product provide
additional proofs for predominant formation of unsatu-
rated ester XI in the dehydration of hydroxy ester IX.
Compound XIII displayed in the IR spectrum three
carbonyl bands at 1710 (C=O), 1715 (CHO), and
1735 cm–1 (COOMe), a strong absorption band at
1685 cm–1, and medium-intensity bands at 1655 and
3200–3400 cm–1. These data suggest that compound
XIII in solution exists as enol tautomer XIIIb, which
is very typical of β-oxo esters. The olefinic proton of
1
enol XIIIb resonates in the H NMR spectrum at
δ 6.98 ppm, while signals from the CH2 group in
Scheme 6.
CHO
CHO
(1) O3–MeOH
(2) Me2S
XI
COOMe
COOMe
Me
O
OH
XIIIb
XIIIa
Me
(i-PrO)2P(O)CH2C(CH3)=CHCOOEt
COOEt
COOEt
NaOH
COOMe
COOMe
O
OH
XIVa
XIVb
Me
(1) MeMgI
(2) TsOH, Δ
COOEt
COOMe
Me
XV
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 3 2008

SYNTHESIS OF ARYL-CONTAINING TERPENOIDS
365
EXPERIMENTAL
–17.6 Hz), 3.55 s (2H, CHO), 7.12 d.d (2H, 8-H, 9-H,
J8, 7 = J9, 10 = 7.5 Hz), 7.27 d (2H, 8-H, 10-H, J =
7.5 Hz). 13C NMR spectrum, δC, ppm: 29.35 t (C1, C4),
51.27 d (C2, C3), 126.12 d (C8, C9), 128.88 d (C7, C10),
131.27 s (C5, C6). Mass spectrum, m/z (Irel, %): 146
(12) [M]+, 131 (46) [M – CH3]+, 130 (34) [M – O]+, 29
(56) [M – OH]+, 128 (51) [M – H2O]+, 117 (18) [M –
CHO]+, 43 (100). Found, %: C 82.54; H 6.50. C10H10O.
Calculated, %: C 82.19; H 6.85.
The IR spectra were recorded on a UR-20 spec-
trometer from samples prepared as thin films or dis-
1
persed in Nujol. The H and 13C NMR spectra were
recorded on a Bruker AM-300 spectrometer at 300.13
and 75.25 MHz, respectively, using CDCl3 as solvent
and tetramethylsilane as internal reference. GLC anal-
ysis was performed on a Chrom-5 chromatograph
equipped with a 1200 ×3-mm column packed with
5% of SE-30 on Chromaton N-AW-DMCS (0.16–
0.20 mm); oven temperature programming from 50 to
300°C at a rate of 12 deg/min; carrier gas helium.
1,2,3,4-Tetrahydronaphthalen-2-one (IV). A solu-
tion of 10.0 g (0.07 mol) of alcohol VII in 50.0 ml of
anhydrous methylene chloride was added to a suspen-
sion of 29.30 g (0.14 mol) of Py·CrO3·HCl in 250 ml
of anhydrous methylene chloride under stirring at 20°C
in a stream of argon. The mixture was stirred for 2 h
and filtered through a layer of silica gel. The solvent
was distilled off, and the residue, 9.85 g, was subjected
to vacuum distillation to isolate 5.12 g (52%) of ketone
IV with bp 65–65.5°C (2 mm). IR spectrum, ν, cm–1:
750 m, 1170 w, 1510 m, 1615 w, 1715 s, 3060 w.
1H NMR spectrum, δ, ppm: 2.53 t (2H, 3-H, J =
6.0 Hz), 3.05 t (2H, 4-H, J = 6.0 Hz), 3.56 s (2H, 1-H),
7.11 d (1H, 7-H, J = 8.0 Hz), 7.21 m (3H, 5-H, 6-H,
8-H). 13C NMR spectrum, δC, ppm: 28.01 t (C4), 37.80 t
(C3), 44.79 t (C1), 126.89 d (C8, C8a), 127.32 d (C4a),
127.90 d (C7), 133.01 s (C6), 136.47 s (C5), 210.26 s
(C=O). Mass spectrum, m/z (Irel, %): 146 (1.14) [M]+,
131 (4.6) [M – CH3]+, 128 (51) [M – H2O]+, 104 (100).
Found, %: C 82.50; H 6.90. C10H10O. Calculated, %:
C 82.19; H 6.85.
1,4-Dihydronaphthalene (I). A reactor was charged
with 3.4 ml of hexane, and 0.76 g (0.03 mol) of finely
cut metallic sodium was added and dispersed under
ultrasound. Naphthalene, 2.56 g (0.02 mol), and hex-
ane, 6.0 ml, were added to the suspension, the mixture
was heated to 70°C, a mixture of 2.0 ml of isopropyl
alcohol and 0.6 ml of water was added dropwise over
a period of 3 h, and the mixture was activated by
ultrasound for 1 h. The mixture was diluted with 15 ml
of water, the organic layer was separated, and the
aqueous phase was extracted with two portions of
hexane. The extracts were combined with the organic
phase, dried over MgSO4, and filtered, and the solvent
was distilled off under reduced pressure (water-jet
pump) to obtain 2.18 g of a product containing 95% of
compound I (according to the GLC data). The spectral
parameters of 1,4-dihydronaphthalene (I) thus obtained
were identical to those reported in [8, 9].
1,2-Dihydronaphthalen-2-one (VI). A stream of
an ozone–oxygen mixture was passed through a solu-
tion of 1.5 g (0.012 mol) of compound I in 40 ml of
anhydrous methylene chloride, cooled to –40°C, until
the initial compound disappeared (according to the
TLC data; silica gel, hexane). Excess ozone was re-
moved by purging with argon, 1.2 ml of dimethyl
sulfide was added to the mixture, and the mixture was
stirred for 15 min at –40°C, allowed to warm up to
room temperature, and left to stand for 12 h (until
negative test for peroxide compounds with an acidified
aqueous solution of potassium iodide). The mixture
was washed with a saturated solution of sodium chlo-
ride, dried over MgSO4, and filtered, the solvent was
distilled off under reduced pressure, and the residue,
1.05 g, was subjected to chromatography on silica gel
using petroleum ether–ethyl acetate (4:1) as eluent to
isolate 0.40 g (24%) of unsaturated ketone VI. IR
spectrum, ν, cm–1: 770 s, 1495 m, 1605 w, 1660 m,
1a,2,7,7a-Tetrahydronaphtho[2,3-b]oxirane (III).
Compound I, 5.0 g (0.04 mol), was dissolved in
34.5 ml of anhydrous benzene, 0.05 g (0.19 mmol) of
Mo(CO)6 was added, and 8.5 ml of a 2.75 N solution
of tert-butyl hydroperoxide in methylene chloride was
added dropwise under stirring. The mixture was stirred
for 20 min at 20°C, ~15 ml of the solvent was distilled
off, and the residue was heated for 5 h under reflux,
cooled, and diluted with 50 ml of ethyl acetate. The
resulting solution was washed in succession with
a 10% aqueous solution of NaHCO3, a saturated solu-
tion of NaHCO3, and a saturated solution of NaCl,
dried over MgSO4, filtered, and evaporated. The resi-
due, 5.09 g, was subjected to column chromatography
on silica gel using petroleum ether–ethyl acetate (4:1)
as eluent to isolate 4.43 g (79%) of compound III with
mp 45°C (from hexane). IR spectrum, ν, cm–1: 775 s,
960 s, 1435 s, 1620 s, 2845 m, 3040 w. 1H NMR spec-
2
1
trum, δ, ppm: 3.22 d and 3.38 d (2H each, CH2, J =
1695 s. H NMR spectrum, δ, ppm: 2.98 br.s (2H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 3 2008

KUKOVINETS et al.
366
CH2), 6.49 d (1H, 2-H, J = 8.0 Hz), 7.54 d (1H, 1-H,
separated, the aqueous layer was extracted with ben-
zene (2×20 ml), and the extracts were combined with
the organic phase and washed in succession with cold
5% sulfuric acid, a 10% solution of NaHCO3, and
water, dried over MgSO4, filtered, and evaporated. The
residue, 0.72 g, was subjected to column chromatog-
raphy on silica gel using hexane–ethyl acetate (4:1) as
eluent to isolate 0.51 g (68%) of compound IX. IR
spectrum, ν, cm–1: 780 s, 1100 s, 1200 s, 1475 m,
1505 m, 1610 m, 1740 s, 2980 s, 3090 m, 3350–
13
J = 8.0 Hz), 7.10–7.38 m (5H, Harom). C NMR spec-
trum, δC, ppm: 49.50 t (C1), 123.64 d (C7), 125.94 d
(C8), 127.18 d (C3), 128.80 d (C8a), 129.93 d (C4a),
137.18 s (C5), 138.45 s (C6), 145.03 d (C4), 192.96
(C=O). Found, %: C 83.62; H 5.36. C10H8O. Calcu-
lated, %: C 83.33; H 5.56.
1,2,3,4-Tetrahydronaphthalen-2-ol (VII). A sus-
pension of 33.82 g (0.89 mol) of sodium tetrahydrido-
borate in 150.0 ml of anhydrous tetrahydrofuran was
cooled to 0°C, 57.68 g (0.44 mol) of 1,4-dihydronaph-
thalene (I) was added, and 117.6 ml of boron tri-
fluoride–ether complex was then added dropwise at 5–
10°C. The mixture was stirred for 35 min at 20°C and
cooled to 0°C, 260 ml of a 3 N aqueous solution of
sodium hydroxide was added, the mixture was heated
to 35°C, 240 ml of 30% hydrogen peroxide was added,
and the mixture was kept for 2 h at 35°C. The tetra-
hydrofuran was distilled off, the residue was dissolved
in ethyl acetate, and the solution was washed in suc-
cession with saturated solutions of NaCl, NaHCO3,
and NaCl again, dried over MgSO4, filtered, and evap-
orated. The residue, 61.75 g, was subjected to vacuum
distillation to isolate 42.80 g (65%) of alcohol VII,
bp 92°C (2 mm). IR spectrum, ν, cm–1: 775 s, 1070 s,
1
3560 br, s. H NMR spectrum, δ, ppm: 1.72 m and
1.89 m (2H, 3-H), 2.48 s (2H, CH2CO), 2.55–3.00 m
(4H, 1-H, 4-H), 3.62 s (3H, OCH3), 4.15 br.s (1H,
13
OH), 6.96 m and 7.02 m (4H, Harom). C NMR spec-
trum, δC, ppm: 25.85 t (C4), 33.56 t (C3), 41.32 t (CH2),
43.69 t (C1), 51.35 q (OCH3), 69.03 s (C2), 125.53 d
(C8), 125.64 d (C8a), 128.28 d (C7), 129.11 d (C4a),
133.71 s (C6), 134.71 s (C5), 172.65 s (C=O). Found,
%: C 70.60; H 7.54. C13H16O3. Calculated, %: C 70.91;
H 7.27.
Methyl 5-(2-formylphenyl)-3-oxopentanoate
(XIIIa/XIIIb, tautomer mixture). A mixture of 7.05 g
(0.03 mol) of alcohol IX and 4.06 g (0.02 mol) of
iodine in 150 ml of toluene was heated under reflux in
a flask equipped with a Dean–Stark trap until water no
longer separated. The mixture was cooled, washed in
succession with a 10% solution of Na2S2O3, a saturated
solution of NaHCO3, and a saturated solution of NaCl,
dried over MgSO4, filtered, and evaporated. The resi-
due, 6.03 g, was subjected to column chromatography
on silica gel using hexane–ethyl acetate (4:1) as eluent
to isolate 4.89 g (76%) of isomer mixture XI/XII at
a ratio of 8:1 (GLC). IR spectrum, ν, cm–1: 770 m,
780 s, 1260 s, 1280 s, 1445 s, 1610 w, 1635 w, 1660 w,
1730 s, 1745 s, 2855 m, 3030 m.
1
1465 m, 1620 w, 2945 s, 3280–3520 br.s. H NMR
spectrum, δ, ppm: 1.92 m (2H, 3-H), 2.75 m (4H, 1-H,
4-H), 3.06 m (1H, CHO), 4.18 br.s (1H, OH), 7.18 m
(4H, Harom). 13C NMR spectrum, δC, ppm: 26.92 t (C4),
31.20 t (C3), 38.03 t (C1), 66.79 d (CHO), 125.57 d and
158.68 d (C8, C8a), 128.34 d (C4a), 129.24 d (C7),
134.21 s (C6), 135.47 s (C5). Mass spectrum, m/z
(Irel, %): 148 (0.13) [M]+, 130 (52) [M – H2O]+, 104
(24) [M – CH2=CH–OH]+, 117 (31), 115 (62), 91 (18),
78 (73), 77 (100). Found, %: C 81.24; H 8.03. C10H12O.
Calculated, %: C 81.08; H 8.11.
A 1.0-g (4.98-mmol) portion of isomer mixture
XI/XII was dissolved in 40 ml of anhydrous methanol,
the solution was cooled to –78°C, and an ozone–oxy-
gen mixture was bubbled through the solution at a flow
rate of 30 l/h (ozonator efficiency 41 mmol/h) until
the mixture turned blue. The mixture was purged with
argon, 0.5 ml of dimethyl sulfide was added, and the
mixture was allowed to warm up to room temperature
and stirred for 2 h. The solvent was distilled off, and
the residue, 1.36 g, was subjected to column chroma-
tography on silica gel using hexane–ethyl acetate (4:1)
as eluent to isolate 0.97 g (84%) of tautomer mixture
XIIIa/XIIIb. IR spectrum, ν, cm–1: 1510 m, 1595 w,
1655 m, 1685 s, 1710 s, 1715 s, 1735 s, 3200–
Methyl (2-hydroxy-1,2,3,4-tetrahydronaphtha-
len-2-yl)acetate (IX). A 1-ml portion of a mixture
of 0.50 g (3.42 mmol) of compound IV, 0.52 g
(3.42 mmol) of methyl bromoacetate, and 30 ml of
anhydrous benzene was added dropwise to 0.27 g
(4.15 mmol) of zinc dust preliminarily activated with
5% hydrochloric acid. The mixture was carefully
heated on a water bath until the reaction started, and
the remaining solution was added at such a rate that the
mixture moderately boiled. When the addition was
complete, the mixture was heated under reflux with
stirring over a period of 1 h, cooled to room tempera-
ture, and treated with 10.5 ml of 20% sulfuric acid
preliminarily cooled to 5°C. The organic layer was
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SYNTHESIS OF ARYL-CONTAINING TERPENOIDS
367
1
3400 br, s. Found, %: C 66.97; H 6.02. C13H14O4. Cal-
culated, %: C 66.67; H 5.98.
Enol tautomer XIVb. H NMR spectrum, δ, ppm:
1.15 t (3H, CH3, J = 7.0 Hz), 2.03 d (Z) and 2.28 d (E)
(3H, CH3C=C, J = 0.9 Hz), 2.36 t (2H, 1′-H, J =
7.0 Hz), 2.66 t (2H, 2′-H, J = 7.0 Hz), 3.84 s (3H,
OCH3), 4.12 q (2H, CH2O, J = 7.0 Hz), 5.60 d (1H,
4-H, J = 0.9 Hz), 6.38 d (1H, 5-H, J = 16.0 Hz), 6.80 d
(2E) and 7.94 d (2Z) (1H, 2-H, J = 16.0, 12.0 Hz),
6.98 br.s (1H, 4′-H).
1
Ketone tautomer XIIIa. H NMR spectrum, δ,
ppm: 2.49 t (2H, 4-H, J = 6.5 Hz), 2.78 t (2H, 5-H,
2
J = 6.5 Hz), 2.98 d and 3.30 d (1H each, 2-H, J =
–16.8 Hz), 3.71 s (3H, OCH3), 7.21 d (1H, 3′-H, J =
7.5 Hz), 7.56 m (2H, 4′-H, 5′-H), 7.85 d (1H, 6′-H, J =
7.5 Hz), 10.53 s (1H, CHO). 13C NMR spectrum, δC,
ppm: 30.77 t (C5), 44.25 t (C4), 48.86 t (C2), 51.43 q
(OCH3), 128.53 d (C6′), 130.19 d (C3′), 131.29 d (C5′),
Methyl (2ξ,4E)-5-{2-[(3ξ)-5-methoxy-3-methyl-5-
oxopent-3-en-1-yl]phenyl}-3-methylpenta-2,4-dien-
oate (XV). Keto ester XIVa/XIVb, 0.82 g (2.4 mmol),
was added under argon to a solution of Grignard com-
pound prepared from 0.06 g of magnesium and 0.35 g
of methyl iodide in 20 ml of anhydrous diethyl ether,
cooled to 0°C. The mixture was stirred for 30 min at
0°C and was left to stand for 12 h at room temperature.
The mixture was then cooled to 0°C, 20 ml of a satu-
rated solution of ammonium chloride was added, the
ether layer was separated, and the aqueous layer was
extracted with diethyl ether. The extract was combined
with the organic layer, washed with a saturated solu-
tion of sodium chloride, dried over MgSO4, filtered,
and evaporated to obtain 0.64 g of intermediate alcohol
(ν 3560 cm–1, br, s). It was mixed with 0.2 g of
p-toluenesulfonic acid in 30 ml of anhydrous benzene,
and the mixture was heated under reflux in a flask
equipped with a Dean–Stark trap until water no longer
separated (~3 h). The solution was washed with satu-
rated solutions of NaHCO3 and NaCl, dried over
MgSO4, and filtered, the solvent was distilled off, and
the residue, 0.48 g, was subjected to chromatography
on silica gel using petroleum ether–ethyl acetate (3:1)
as eluent to isolate 0.36 g (44%) of compound XV. IR
spectrum, ν, cm–1: 840 m, 920 m, 1505 m, 1600 m,
138.38 d (C4′), 135.51 s (C1 ), 142.51 s (C2′), 171.39 s
′
(COO), 197.59 d (CHO), 201.50 s (C=O).
1
Enol tautomer XIIIb. H NMR spectrum, δ, ppm:
2.29 t (2H, 4-H, J = 7.0 Hz), 2.76 t (2H, 5-H, J =
7.0 Hz), 3.84 s (3H, OCH3), 6.08 br.s (1H, OH),
6.98 br.s (1H, C=CH), 7.26 d (1H, 6′-H, J = 7.5 Hz),
7.49 m (2H, 4′-H, 5′-H), 7.79 d (1H, 3′-H, J = 7.5 Hz),
10.53 s (1H, CHO). 13C NMR spectrum, δC, ppm:
27.19 t (C4), 30.89 t (C5), 52.16 q (OCH3), 116.18 d
(C2), 128.53 d (C6′), 130.20 d (C3′), 131.26 d (C4′),
131.30 d (C5′), 138.13 s (=COH), 135.51 s (C1′),
142.51 s (C2′), 167.86 s (COO), 194.80 d (CHO).
Methyl (2ξ,4E)-5-[2-(5-ethoxy-3,5-dioxopentyl)-
phenyl]-3-methylpenta-2,4-dienoate (XIVa/XIVb,
tautomer mixture). Sodium hydride, 0.07 g
(2.9 mmol), was added under stirring at 15°C to a solu-
tion of 0.84 g (2.9 mmol) of ethyl 4-(diisopropoxy-
phosphoryl)-3-methylbut-2-enoate in 10 ml of anhy-
drous THF. The mixture was stirred for 30 min and
cooled to 5°C, a solution of 0.52 g (2.23 mmol) of
compound XIII in 7.5 ml of anhydrous THF was ad-
ded, and the mixture was stirred at 5°C until aldehyde
XIII disappeared completely (TLC). The mixture was
washed in succession with saturated solutions of
ammonium chloride and sodium chloride, dried over
MgSO4, filtered, and evaporated, and the residue,
0.69 g, was subjected to column chromatography on
silica gel using hexane–ethyl acetate (4:1) as eluent to
isolate 0.47 g (62%) of tautomer mixture XIVa/XIVb.
IR spectrum, ν, cm–1: 1605 m, 1620 m, 1690 s, 1710 s,
1745 s. Found, %: C 69.53; H 6.71. C20H24O5. Calcu-
lated, %: C 69.77; H 6.98.
1
1725 s, 3080 m. H NMR spectrum, δ, ppm: 1.13 t
(3H, CH3, J = 6.5 Hz), 1.86 s (3H, 3′-CH3, J = 0.9 Hz),
1.86 d and 2.05 d (3-CH3, J = 1.0 Hz), 2.10 t (2H,
2′-H, J = 6.5 Hz), 2.44 t (2H, 1′-H, J = 6.5 Hz), 4.12 q
(2H, OCH2, J = 6.5 Hz), 5.60 m (2H, E-2-H, E-4′-H),
6.38 d (1H, 5-H, J = 16.5 Hz), 6.80 d (1H, 4-H,
J = 16.5 Hz), 7.6–8.1 m (Harom, Z-2-H, 4′-H). Found,
%: C 73.45; H 7.79. C21H26O4. Calculated, %: C 73.68;
H 7.60.
1
Ketone tautomer XIVa. H NMR spectrum, δ,
REFERENCES
ppm: 1.15 t (3H, CH3, J = 7.0 Hz), 2.03 d (Z) and
2.28 d (E) (3H, CH3C=C, J = 0.9 Hz), 2.36 t (2H, 1′-H,
J = 6.5 Hz), 2.47 t (2H, 2′-H, J = 6.5 Hz), 2.96 d and
1. Phadnis, A.P., Nanda, B., Patwardhan, S.A., and
Gupta, A.S., Indian J. Chem., Sect. B, 1984, vol. 23,
p. 1098.
2
3.28 d (1H each, 4′-H, J = –16.8 Hz), 3.76 s (3H,
OCH3), 4.12 q (2H, CH2O, J = 7.0 Hz), 5.60 d (E, 2-H,
J = 0.9 Hz), 6.38 d (1H, 5-H, J = 16.5 Hz), 6.80 d (1H,
4-H, J = 16.5 Hz), 7.6–8.1 m (4H, Harom, Z-4-H).
2. Phadnis, A.P., Nanda, B., Patwardhan, S.A., Powar, P.,
and Charma, R.N., Indian J. Chem., Sect. B, 1988,
vol. 27, p. 867.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 3 2008

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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 3 2008