Chromium arene complexes in synthesis of trans-resveratrol

Article abstract of DOI:10.1023/A:1020921101384

Two variants of synthesis of resveratrol (3,5,4′ -trans-trihydroxystilbene) from dimethyl ether and anisaldehyde were performed using the chromium η⁶-benzenetricarbonyl complex. The Wittig-Horner reactions or aldol condensation in four stages followed by demethylation by EtSLi were applied.

Full text of DOI:10.1023/A:1020921101384

Russian Chemical Bulletin, International Edition, Vol. 51, No. 7, pp. 1319—1324, July, 2002
1319
Organometallic Chemistry
Chromium arene complexes in synthesis of transꢀresveratrol
K. E. Polunin,a H.ꢀG. Schmalz,a and I. A. Poluninab
ꢀ
аInstitute of Organic Chemistry, Technical University of Berlin,
17 Juni str. 135, Dꢀ10623, Berlin, Germany.*
Fax: (505 7) 221 470 3064. Eꢀmail: schmalz@uniꢀkoeln.de
bInstitute of Physical Chemistry, Russian Academy of Sciences,
31 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 952 5308. Eꢀmail: polunina@phyche.ac.ru
Two variants of synthesis of resveratrol (3,5,4´ꢀtransꢀtrihydroxystilbene) from dimethyl
6
ether and anisaldehyde were performed using the chromium η ꢀbenzenetricarbonyl complex.
The Wittig—Horner reactions or aldol condensation in four stages followed by demethylation
by EtSLi were applied.
6
Key words: chromium(0) η ꢀarenetricarbonyl complex, transꢀresveratrol, phytoalexin,
hydroxystilbenes, methoxystilbenes, aldol condensation, Wittig—Horner reaction, deꢀ
methylation.
Chromium arene complexes find wide use in fine
organic synthesis in recent years.1—5 The employment of
chromium η ꢀarenetricarbonyl complexes as synthons
grapes, in some species of pineꢀtree and acacia, in peaꢀ
nut, orchid, lilies, etc.12—13 As found in the recent studꢀ
ies,14—15 transꢀisomer of 2 with the 3,4´,5ꢀtrihydroxyꢀ
stilbene structure is an antioxidant and an antimutagene;
it retards the development and growth of human cancerꢀ
ous cells and prevents organism intoxication from the
tumor development. It is the strongest antiviral mediꢀ
cine, which decomposes viruses of influenza, herpes,
and even, presumably, acquired immunodeficiency.
6
provided the development of new competitive methods
for the synthesis of complicated natural compounds, some
of which can barely be prepared by any other method.6—8
Such biologically active substances as helioporin,
D(+)ꢀptilocaulin, olivetol, and other 5ꢀ and 2,5ꢀsubstiꢀ
tuted resorcinol derivatives were synthesized in high yields
due to the use of Cr arenecarbonyl complexes, such as
tricarbonylꢀ1,3ꢀdimethoxybenzenechromium (1).9—11
In this work we pursued these studies and attempted
to synthesize plant antibiotic phytoalexin (resveratrol)
(2), which is contained in the vine bark, leaves, and
* Institut für Organische Chemie der Technischen Universität
Berlin, Strasse des 17 Juni, 135, Dꢀ10623 Berlin, BRD.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1219—1223, July, 2002.
1066ꢀ5285/02/5107ꢀ1319 $27.00 © 2002 Plenum Publishing Corporation

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Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
Polunin et al.
The above properties of resveratrol (2) attracted great
attention because it can serve as a polyfunctional drug
without noxious side effect. Some other polyhydroxyꢀ
stilbenes also exhibit high biological activity.16 However,
stilbeneꢀderived phytoalexins are not virtually used in
official pharmacology because their biochemical properꢀ
ties are poorly studied and technological procedures for
their isolation in the pure state from plants are difficult.
Hydroxystilbenes manifest several other valuable physiꢀ
cochemical properties, due to which they can be used for
the development of photoconductors, laser dyes, disꢀ
plays, data mapping devices, etc.17
for the syntheses of other pharmacologically valuable
hydroxystilbenes.
Two variants of the synthesis of 2 were proposed. In
both variants, the initial complex 1 was silylated in posiꢀ
tion 2 resulting in the protected complex 3, which was
methylated in position 5 (Scheme 1). The overall yield
of complex 4 prepared in three stages from 1,3ꢀdiꢀ
methoxybenzene was 61%. Dimethoxymethylꢀtrimethylꢀ
silyl derivative 4 that formed is the common intermediꢀ
ate for two routes of resveratrol synthesis (Scheme 2).
In the first variant, complex 4 was deprotonated at
the benzyl position and then underwent aldol condensaꢀ
tion with anisaldehyde to produce disubstituted ethaꢀ
nol 5. After the chromium complex was decomposed
and the silylic protection was removed, the trimethoxy
derivative of ethanol 6 formed and transformed into stilꢀ
bene 7 by dehydration.
The second variant of synthesis of 2 is based on the
preparation of phosphonate 8 as a component of the
subsequent Wittig—Horner reaction with anisaldehyde,
which affords complex stilbene 9. This compound is transꢀ
formed into trimethoxystilbene 7 in high yield via two
stages (removal of protection and decomposition of the
complex). The reaction of complex 4 deprotonated at
the benzyl position with diethyl chlorophosphate was
not earlier studied.
The four stages in the first variant, including the aldol
condensation (85%), occur in 51% yield based on comꢀ
plex 4. The yield of trimethoxystilbene 7 synthesized
from 4 by the Wittig—Horner reaction (80%) was 48%.
The final stage in both syntheses is the removal of the
methyl protection of the hydroxy groups in compound 7.
The known procedures for this process (using BBr3,
MeMgI, or LiPPh2 21—24) give moderate (30—60%)
yields. We studied demethylation by lithium thioethoxide,
whose application affords monomethoxystilbene 10 in
98% yield. An increase in the reaction time from 2 to
12 h provides only 30% yield of the target product 2.
All synthesized compounds were characterized by IR,
1Н and 13С NMR, and mass spectra, which entirely corꢀ
respond to the proposed structures.
Results and Discussion
We developed a method for the synthesis of comꢀ
pound 2 from fairly cheap, accessible, and preparatively
convenient tricarbonylꢀ1,3ꢀdimethoxybenzenechromium
(1), whose preparation and properties were first deꢀ
scribed18 in 1958. Compound 1 is usually prepared by
heating the arene with Cr(CO)6 in a highꢀboiling solꢀ
vent.19 In this complex the arene ligand can readily be
modified by introducing various groups.1,20—21 It has reꢀ
cently11 been found that complex 1 can regiospecifically
be alkylated in high yield to any position by variation of
the reaction conditions. Its analog 3 is methylated by
lithium tetramethylpiperidide only to the αꢀposition.11,20
The oxidative elimination of the tricarbonylchromium
ligand and desilylation occur easily in ∼100% yield.1,11
These data enabled us to develop a synthetic scheme for
the formation of the stilbene and diarylethanol frameꢀ
works, which was used as a basis for the synthesis of
resveratrol 2. This scheme is believed also to be used
Scheme 1
Note that the approach to synthesis of 2 using chroꢀ
mium arene complexes as reactants for regiospecific synꢀ
thesis can be extended to other hydroxystilbenes, for
example, piceatannol (3,5,4´,5´ꢀtetrahydroxystilbene),
pterostilbene (3,5ꢀdimethoxyꢀ4´ꢀhydroxystilbene), pinoꢀ
stilbene (3,4´ꢀdihydroxyꢀ5ꢀmethoxystilbene), tunalbene
(3,3´ꢀdihydroxyꢀ5ꢀmethoxystilbene), and others.
Thus, compared to other known methods for prepaꢀ
ration of resveratrol,23—27 the arene complexes of chroꢀ
mium(0) are promising for application in stoichiometric
amounts because they exhibit high stereoꢀ and regioꢀ
selectivity, require mild reaction conditions, and afford
target products in fairly high yields.
Reagents and conditions: a. BunLi, THF, TMSCl, –78 °C;
b. LiTMP, THF, MeI, –50 °C.

Synthesis of transꢀresveratrol
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
1321
Scheme 2
Reagents and conditions: a. BunLi, THF, –40 °C, anisaldehyde, –20 °C→0 °C, 1 h; b. Bun4NF, H2O, 2 h; c. hν, Et2O, 2 days;
d. TsOH, PhH, 80 °C, 13 h; e. BunLi, THF, –40 °C, 15 min, ClP(O)(OEt)2, –10 °C, 30 min; f. I2, Et2O, 20 °C, 12 h; g. MeMgI,
100 °C, 30 min; h. LiSEt, DMF, 160 °C, 2 h.
argon in a Schlenk flask using a syringe technique. Reagents
and solvents were dried using standard methods. Glassware was
calcined before use and cooled in an argon flow.
Experimental
1
6
Н NMR spectra were recorded on Bruker AMꢀ400
Tricarbonylꢀ[η ꢀ1,3ꢀdimethoxyꢀ2ꢀtrimethylsilylbenꢀ
(400 MHz) and Bruker AMꢀ270 (270 MHz) spectrometers in
СDCl3, using CHCl3 for CDCl3 and CH3OD for CD3OD as
internal standards. 13С NMR spectra were obtained using Bruker
AMꢀ400 (100.64 MHz) and Bruker AMꢀ270 (67.7 MHz) inꢀ
struments. Mass spectra were obtained on Varian MAT 711 and
Varian MAT 44 mass spectrometers (electron impact, 70 eV,
direct injection into an ion source). IR spectra were recorded
on a Magna FTꢀIR 750 spectrometer (Nicolet) with KBr winꢀ
dows. Melting points were measured with a Buchi 510 instruꢀ
ment without correction. The reaction courses and purity of
isolated products were monitored by TLC on the Kieselgel 60F254
plates (Merck) in an AcOEt—hexane system. Compounds were
detected by UV absorption after irradiation with a Fluotest
lamp (λ 254 or 365 nm).11 Individual compounds were isolated
from reaction products by preparative TLC on a Harrison Reꢀ
search 7924 T chromatotron using glass circular plates covered
with Kieselgel PFꢀ60F254 (Merck) (hexane—AcOEt as eluꢀ
ent) and by column chromatography (Kieselgel 60, Merck,
230—400 mesh) using АсOEt—petroleum ether as eluent. The
yields of compounds were not optimized.
zene]chromium(0) (3). A solution of complex 1 (2.00 g, 1.4 mmol)
in anhydrous THF (50 mL) was placed in a 100ꢀmL Schlenk
flask and cooled to –78 °С. A 1.6 М solution of BunLi (4.78 mL,
7.65 mmol) in hexane was added with stirring. After stirring for
0.5 h, trimethylchlorosilane (SiMe3Cl) (2.3 mL, 18.3 mmol)
was added. The solution was stirred for 15 min at –78 °С, after
which the temperature was raised to 0 °С for 1 h. Ethyl acetate
(50 mL) was added to the mixture, and the solution was washed
with saturated solutions of NaHCO3 (2×60 mL) and NaCl
(50 mL), dried over MgSO4, and evaporated in vacuo. Yellow
crystals of compound 3 were obtained in 99% yield (2.50 g)
with m.p. 150 °С (cf. Ref. 11: m.p. 150 °С) and Rf 0.3 (hexꢀ
ane—AcOEt, 5 : 1). IR, ν/cm–1: 2975, 2957, 2903, 1943, 1871,
1843, 1524, 1505, 1453, 1442, 1415, 1285, 1238, 1096, 847, 669.
1Н NMR (270 MHz, CDCl3), δ: 0.34 (s, 9 H, CH3—Si); 3.68
(s, 6 H, OCH3); 4.71 (d, 2 H, C(4)H/C(6)H, J = 7.0 Hz); 5.72
(t, 1 H, C(5´)H, J = 7.0 Hz). 13С NMR (67.7 MHz, CDCl3), δ:
1.6 (q, CH3—Si); 55.4 (q, OCH3); 73.2, 69.7 (d, C(4)/C(6));
80.9 (s), 93.2 (d, C(5)); 148.4 (s); 234.2 (s, Cr(CO)3). MS (EI,
70 eV), m/z (Irel (%)): 346 [M]+ (15), 334 (57), 290 (10), 262
(100), 217 (9), 190 (11), 135 (9), 52 (26).
All reagents and solvents (Aldrich, Fluka, Acros, Merck)
were 99% purity and used as received. Hexacarbonylchromium
(Fluka) with 99% purity was used in synthesis of complex 1.
All reactions involving complex 4 were carried out under a
low pressure of the moistureꢀ and oxygenꢀfree highly purified
6
Tricarbonylꢀ[η ꢀ1,3ꢀdimethoxyꢀ5ꢀmethylꢀ2ꢀtrimethylsilylꢀ
benzene]chromium(0) (4). A 1.5 M solution of BunLi (0.2 mL,
0.32 mmol) in hexane was added at –78 °С to a solution of
2,2,6,6ꢀtetramethylpiperidine (0.055 mL, 0.32 mmol) in anꢀ

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Polunin et al.
hydrous THF (1 mL) placed in a 25ꢀmL Schlenk flask. The
mixture was stirred for 40 min at –40 °С and cooled to –78 °С.
Complex 3 (100 mg, 0.288 mmol) was added, and the mixture
was stirred for 30 min at –78 °С. A solution of СH3I (90 µL,
1.4 mmol) in anhydrous THF (4 mL) was placed into another
25ꢀmL Schlenk flask and cooled to –50 °С. A solution of the
anion of complex 3 from the first flask was rapidly added through
a pumping pipe to a solution in the second flask. The mixture
was stirred for 30 min at –50 °С and 1 h at 25 °С, then heptane
(20 mL) was added, and ∼50% solvent were evaporated in vacuo.
Ethyl acetate (20 mL) was added to the residue, and the resultꢀ
ing solution was washed successively with 2 N HCl (2×20 mL)
and saturated solutions of NaHCO3 (20 mL) and NaCl (20 mL).
The organic layer was dried with MgSO4 and concentrated in
vacuo. Complex 4 was obtained as yellow crystals in 75% yield
(78 mg), m.p. 158 °С (cf. Ref. 11: m.p. 158 °С), Rf 0.27 (hexꢀ
ane—AcOEt, 5 : 1). IR, ν/cm–1: 2950, 2901, 1937, 1863 (C=O,
Cr(CO)3), 1849, 1320, 1229, 1112, 839. 1Н NMR (270 MHz,
CDCl3), δ: 0.33 (s, 9 H, CH3—Si); 2.35 (s, 3 Н, CH3); 3.68 (s,
6 H, OCH3); 4.65 (s, 2 H, C(4)H/C(6)H). 13С NMR (67.7
MHz, CDCl3), δ: 1.5 (q, CH3—Si); 21.3 (q, CH3); 55.3
(q, С—OCH3); 72.6 (d, C(4)/C(6)); 77.2 (s); 108.4 (s); 148.2 (s);
234.6 (s). MS (EI, 70 eV), m/z (Irel (%)): 360 [M]+ (18), 304
(15), 276 (100), 261 (8), 201 (5), 149 (12), 52 (10).
obtained in 99% yield (437 mg) with Rf 0.55 (hexane—МТВЕ,
1 : 1). Decomposition of chromium arene complex 5. Desilylated
complex 5 (450 mg, 0.9 mmol) was dissolved in an AcOH—Et2O
(1 : 10) mixture (60 mL), and the resulting solution was stored
for 2 days in sunlight. Then the green residue was filtered
through a zeolite layer 1 cm thick, and the colorless filtrate was
concentrated in vacuo. Alcohol 6 was obtained as yellow visꢀ
cous oil in 99% yield (285 mg), Rf 0.27 (hexane—МТВЕ, 1 : 1).
IR, ν/cm–1: 3450 (OH), 2927, 1596, 1512, 1246, 1149, 1066.
1Н NMR (400 MHz, CDCl3), δ: 1.94 (d, 1 H, OH, J = 3.0 Hz);
2.91 (dd, 1 H, CH2, J = 14.0 Hz, J = 8.0 Hz); 2.96 (dd, 1 H,
CH2, J = 14.0 Hz, J = 5.0 Hz); 3.77 (s, 6 H, OCH3);
3.81 (s, 3 H, OCH3); 4.85 (m, 1 H, CH—OH); 6.36 (br.s,
3 H, C(2)H/C(6)H/C(4)H); 6.89 (d, 2 H, C(2´)H/C(6´)H,
J = 9.0 Hz); 7.3 (d, 2 H, C(3´)H/C(5´)H, J = 9.0 Hz).
13С NMR (67.7 MHz, CDCl3), δ: 46.4 (t, CH2); 55.2, 55.3
(both q, OCH3); 74.7 (q, OCH3); 98.6 (d, CH—OH); 107.4
(d, C(2)/C(6)); 113.7 (d, C(3´)/C(5´)); 127.1 (d, C(2´)/C(6´));
135.9 (s); 143.5 (s); 140.4 (s), 159.0 (s), 160.8 (с). MS (EI,
70 eV), m/z (Irel (%)): 288 [M]+ (1), 270 (4), 152 (100), 137 (98),
109 (18).
(Е)ꢀ2ꢀ(3,5ꢀDimethoxy)ꢀ1ꢀ(4´ꢀmethoxyphenyl)ethylene (7).
To a solution of alcohol 6 (250 mL, 0.59 mmol) TsOH (20 mg,
0.012 mmol) in benzene (10 mL) was added, and the mixture
was refluxed for 13 h. Then AcOEt (20 mL) was added, and the
solution was washed with a 10% solution of NaHCO3 (3×30 mL)
and a saturated solution of NaCl (30 mL), dried with MgSO4,
and concentrated in vacuo. After purification by preparative
TLC (hexane—AcOEt (8 : 1) eluent), stilbene 7 (94 mg,
61% yield) was obtained with m.p. 47 °C and Rf 0.16 (hexꢀ
ane—AcOEt, 10 : 1). IR, ν/cm–1: 3027, 2935, 1590, 1511, 1251,
1150, 1066. 1Н NMR (400 MHz, CDCl3), δ: 2.83 (s, 9 H,
OCH3); 6.37 (t, 1 H, C(2)H, J = 2.0 Hz); 6.65 (d, 2 H,
C(2)H/C(4)H, J = 2.0 Hz); 6.99 (d, 2 H, C(2´)H/C(6´)H, J =
9.0 Hz); 7.01 (d, 1 H, olefin, J = 17.0 Hz); 7.03 (d, 2 H,
C(3´)H/C(5´)H, J = 9.0 Hz); 7.45 (d, 1 H, olefin, J = 17.0 Hz).
13С NMR (67.7 MHz, CDCl3): 55.2, 55.3, 55.32 (all q, OCH3);
99.6 (q, C(4)); 104.3 (d, C(2)/C(6)); 114.1 (d, C(3´)H/C(5´)H);
126.5 (d, olefin); 127.8 (d, C(2´)/C(6´)); 128.7 (d, olefin);
139.9 (s); 139.6 (s); 159.4 (с); 160.9 (с). MS (EI, 70 eV),
m/z (Irel (%)): 270 [M]+ (100), 239 (8), 196 (7), 115 (3).
6
Tricarbonylꢀ[2ꢀ(η ꢀ3,5ꢀdimethoxyꢀ4ꢀtrimethylsilylꢀphenyl)ꢀ
1ꢀ(4´ꢀmethoxyphenyl)ethanol]chromium(0) (5). A solution of
complex 4 (500 mg, 1.38 mL) in anhydrous THF (10 mL) was
placed in a 50ꢀmL Schlenk flask and cooled to –40 °С, and a
1.6 M solution of BunLi (0.95 mL, 1.53 mmol) in hexane was
added with stirring. The mixture was stirred for 15 min at
–40 °С and 30 min at 0 °С until the solution became dark red,
after which it was cooled to –40 °С. Anisaldehyde (0.25 mg,
2.08 mmol) was added to the cooled solution, and the mixture
was stirred for 30 min at –20 °С and for 1 h at 0 °С. Methyl
tertꢀbutyl ether (MTBE) (40 mL) was added to the reaction
mixture. The organic layer was washed with water (2×40 mL)
and a saturated solution of NaCl (30 mL), dried with MgSO4,
and concentrated in vacuo. The crude product was purified by
preparative TLC (hexane—AcOEt (10 : 1) eluent). Compound
5 was obtained in 85% yield (584 mg) as yellow oil with Rf 0.06
(hexane—AcOEt, 5 : 1). IR, ν/cm–1: 3586 (OH), 2954, 1950,
1865 (C=O, Cr(CO)3), 1513, 1496, 1248, 1227. 1Н NMR
(400 MHz, CDCl3), δ: 0.34 (s, 9 H, CH3—Si); 2.04 (d, 1 H,
OH, J = 3.0 Hz); 2.85 (dd, 1 H, CH2, J = 14.0 Hz, J = 5.0 Hz);
2.93 (dd, 1 H, CH2, J = 14.0 Hz, J = 8.0 Hz); 3.61, 3.64
(both s, 3 H, OCH3); 3.82 (s, 3 H, OCH3); 4.58, 4.65 (both s,
1 H, C(2)H/C(6)H); 4.93 (m, 1 H, CH—OH); 6.91 (d, 2 H,
C(2´)H/C(6´)H, J = 9.0 Hz); 7.29 (d, 2 H, C(3´)H/C(5´)H,
J = 9.0 Hz). 13С NMR (67.7 MHz, CDCl3), δ: 1.5 (q, CH3—Si);
26.9 (d, CH—OH); 45.4 (t, CH2); 55.4, 55.29, 55.27 (all q,
OCH3); 73.2, 74.6 (both d, C(2)/C(6)); 108.3 (s); 114.0
(d, C(3´)/C(5´)); 127.2 (d, C(2´)/C(6´)); 135.3 (s); 148.1 (s);
159.5 (s); 234.5 (s, Cr(CO)3). MS (EI, 70 eV), m/z (Irel (%)):
496 [M]+ (8), 412 (100), 394 (20), 224 (48), 137 (52), 52 (7).
2ꢀ(3,5ꢀDimethoxyphenyl)ꢀ1ꢀ(4´ꢀmethoxyphenyl)ethanol (6).
Desilylation. One water droplet and 5.75 mL (5.75 mmol) of
Bun4NF (1 М solution in THF) were added with stirring to
complex 5 (517 mg, 1.04 mmol) in THF (20 mL). After stirring
for 2 h at 20 °С, AcOEt (30 mL) was added. The solution was
washed with water (40 mL) and a saturated solution of NaCl
(40 mL), dried with MgSO4, and concentrated. Complex 5 was
6
Tricarbonylꢀ[1ꢀ(η ꢀ3,5ꢀdimethoxyꢀ4ꢀtrimethylsilylꢀ
phenyl)methyldiethylphosphonate]chromium(0) (8). Complex 4
(200 mg, 0.554 mmol) in anhydrous THF (6 mL) was placed in
a 25ꢀmL Schlenk flask, and BunLi (0.38 mL, 0.71 mmol) as a
1.6 M solution in hexane was added at –40 °C. The mixture
was stirred for 15 min at –40 °C and 30 min at –10 °C (the
dark red color appeared). Then the mixture was cooled to
–30 °C, and diethyl chlorophosphate (104 µL, 0.72 mmol) was
added. After stirring for 30 min at –10 °C and for 1 h at 0 °C,
AcOEt (20 mL) was added. The solution was washed with a
saturated solution of NaCl (2×30 mL), water (30 mL), and a
saturated solution of NaCl (30 mL), dried with MgSO4, and
concentrated in vacuo. Purification on a column packed with
silica gel (10 g) yielded phosphonate 8 (162 mg, 59% yield) as
yellow crystals with m.p. 130 °C and initial compound 4 (75 mg,
37% yield) with Rf 0.18 (hexane—AcOEt, 1 : 1). The corrected
yield of compound 4 was 94% (taking into account converꢀ
sion). IR, ν/cm–1: 2903, 1951, 1866 (С=О, Cr(CO)3), 1230,
1104, 1054, 1026. 1Н NMR (400 MHz, CDCl3), δ: 0.32 (s,
9 H, CH3—Si), 1.34 (t, 6 Н, CH3, J = 7.0 Hz); 2.96 (d, 2 H,

Synthesis of transꢀresveratrol
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 7, July, 2002
1323
3
СН2, JР,Н = 20.5 Hz); 3.69 (s, 6 Н, ОCH3); 4.13 (m, 4 H,
54%) was obtained as solid white needles with m.p. 247 °C
(cf. Ref. 23: m.p. 247 °C) and Rf 0.24 (hexane—AcOEt, 1 : 1).
IR, ν/cm–1: 3329, 3029, 1604, 1238, 1147, 836. 1Н NMR
(400 MHz, CDCl3), δ: 6.13 (t, 1 H, C(4)H, J = 2.0 Hz);
6.42 (d, 2 H, C(2)H/C(6)H, J = 2.0 Hz); 6.74 (d, 2 H,
C(2´)H/C(6´)H, J = 9.0 Hz); 6.78 (d, 1 H, olefin, J = 17.0 Hz);
6.93 (d, 1 H, olefin, J = 17.0 Hz); 7.33 (d, 2 H, C(3´)H/C(5´)H,
J = 9.0 Hz). 13С NMR (100.64 MHz, CD3OD), δ: 102.6
(d, C(4)); 105.8 (d, C(2)/C(6)); 116.5 (d, C(3´)/C(5´)); 127
(d, olefin); 128.8 (d, C(2´)/C(6´)); 129.4 (d, olefin); 130.3 (s);
141.3 (s); 158.4 (s); 159.7 (s). MS (EI, 70 eV), m/z (Irel (%)):
228 [M]+ (56), 165 (18), 107 (10), 85 (100), 57 (8).
(Е)ꢀ2ꢀ(5ꢀHydroxyꢀ3ꢀmethoxyphenyl)ꢀ1ꢀ(4´ꢀhydroxyꢀ
phenyl)ethylene (10). Trimethoxystilbene 7 (30 mg, 0.11 mmol)
and lithium thioethoxide (135 mg, 1.33 mmol) in DMF (4 mL)
were placed in a 25ꢀmL Schlenk flask connected with a reflux
condenser and a paraffinic bubble counter. After this apparatus
was thoroughly degassed by tenfold evacuation and filling with
argon, and the mixture was heated for 2 h at 160 °C. After
cooling, 0.1 M HCl (15 mL) and AcOEt (20 mL) were slowly
added to the solution, and the latter was washed with water
(6×30 mL). The organic layer was washed with a saturated
solution of NaCl (50 mL), dried with MgSO4, and concenꢀ
trated in vacuo. The crude product was purified by preparative
TLC (hexane—AcОEt (7 : 1) eluent). Stilbene 10 was obtained
in 98% yield (26 mg) as colorless oil with Rf 0.4 (hexane—AcОEt,
1 : 1). IR, ν/cm–1: 3365, 2960, 1604, 1589, 1343, 1148, 836.
1Н NMR (400 MHz, CDCl3), δ: 3.82 (s, 3 Н, ОСН3); 4.86
(br.s, 1 Н, ОН); 4.91 (br.s, 1 Н, ОН); 6.32 (t, 1 H, C(4), J =
2.0 Hz); 6.58, 6.63 (both d, 2 H, C(2)H/C(6)H, J = 2.0 Hz);
6.83 (d, 2 H, C(2´)H/C(6´)H, J = 9.0 Hz); 6.85 (d, 1 H, olefin,
J = 17.0 Hz); 7.00 (d, 1 H, olefin, J = 17.0 Hz); 7.39 (d, 2 H,
C(3´)H/C(5´)H, J = 9.0 Hz). 13С NMR (100.64 MHz, CD3Cl3),
δ: 55.6 (q, ОСН3); 101.4 (d, C(4)); 104.4, 106.6 (both d,
C(2)/C(6)); 116.5 (d, C(3´)/C(5´)); 129.9 (d, olefin); 128.9 (d,
C(2´)/C(6´)); 129.8 (d, olefin); 130.3 (s); 141.3 (s); 158.4 (s);
159.7 (s); 162.5 (s). MS (EI, 70 eV), m/z (Irel (%)): 228 [M]+
(56), 165 (18), 107 (10), 85 (100), 57 (8). According to the
1Н NMR data, the product contains ∼3% cisꢀisomer.
ОСН2); 4.74 (s, 2 Н, C(2)H/C(6)H). 13С NMR (67.7 MHz,
CDCl3), δ: 1.5 (q, CH3—Si); 16.4, 16.5 (both q, CH3);
32.7, 34.9 (both t, ОСН2); 62.5 (t, СН2Р); 72.27, 72.31
(both d, C(2)/C(6)); 79.3 (s, С(1)); 102.3 (s, С(4)); 148.0
(s, C(3)/C(5´)); 234.2 (s, Cr(CO)3. MS (EI, 70 eV), m/z (Irel
(%)): 496 [M]+ (2), 412 (100), 360 (30), 345 (61), 315 (10),
285 (68), 52 (40).
6
Tricarbonylꢀ[1ꢀ(η ꢀ3,5ꢀdimethoxyꢀ4ꢀtrimethylsilylphenyl)ꢀ2ꢀ
(4´ꢀmethoxyphenyl)ethylene]chromium(0) (9). Phosphonate 8
(265 mg, 0.735 mmol) in anhydrous THF (10 mL) was placed
in a 25ꢀmL Schlenk flask, and a 1.5 М solution of BunLi (0.5 mL,
0.81 mmol) in hexane was added at –40 °C. The mixture was
stirred for 15 min at –40 °C and 30 min at –10 °C (the red
color appeared). Then anisaldehyde (0.25 mL, 2.08 mmol) was
added. The mixture was heated during 1 h to boiling and cooled
to 20 °C, and AcOEt (30 mL) was added. The solution was
washed with water (2×40 mL), a saturated solution of NaНСО3
(30 mL), and a saturated solution of NaCl (30 mL), dried with
MgSO4, and concentrated in vacuo. The crude product was
purified on a column packed with kiesel gel (10 g) (hexꢀ
ane—AcOEt, 50 : 1). Stilbene 9 was obtained in 80% yield
(280 mg) as red needles with m.p. 202 °C and Rf 0.57 (hexꢀ
ane—AcOEt, 1 : 1). IR, ν/cm–1: 2978, 2956, 1935, 1843 (С=О,
Cr(CO)3), 1605, 1535, 1228, 839. 1Н NMR (400 MHz, CDCl3),
δ: 0.45 (s, 9 Н, CH3—Si); 3.76 (s, 6 Н, ОCH3); 3.83 (s, 3 Н,
ОCH3); 4.93 (s, 2 Н, C(2)H/C(6)H); 6.72 (d, 1 H, olefin, J =
17.0 Hz); 6.91 (d, 2 H, C(2´)H/C(6´)H, J = 9.0 Hz); 6.98 (d,
1 H, olefin, J = 17.0 Hz); 7.44 (d, 2 H, C(3´)H/C(5´)H, J =
9.0 Hz). 13С NMR (67.7 MHz, CDCl3), δ: 1.5 (q, CH3—Si);
55.2, 55.3, 55.4 (all q, OCH3); 68.9 (d, C(2)/C(6)); 79.4 (s);
106.5 (s); 114.4 (d, C(3´)/C(5´)); 123.9 (d, olefin); 128.3 (d,
C(2´)/C(6´)); 128.4 (s); 131.8 (d, olefin); 148.3 (s); 160.2 (s);
234.0 (s, Cr(CO)3). MS (EI, 70 eV), m/z (Irel (%)): 478 [M]+
(1), 394 [M – 3 СО]+ (8), 342 [M – 3 СО – Cr]+ (92), 327
(21), 267 (100), 223 (45).
Desilylation of stilbene 9 was similar to desilylation in the
synthesis of alcohol 6. The yield was 99%.
Synthesis of trimethoxystilbene 7 was carried out by the
decomposition of its chromium complex. Desilylated complex
9 (115 mg) was dissolved in an AcOEt—Et2O (1 : 10) mixture
(50 mL), and diiodine (300 mg) was added. The mixture was
stirred for 12 h at 20 °C, and Et2O (50 mL) was added. The
solution was washed with a saturated solution of NaCl (50 mL),
dried with MgSO4, and concentrated in vacuo. Stilbene 7 was
obtained in 99% yield (76 mg) and exhibited the above deꢀ
scribed characteristics.
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Received January 14, 2002