Plant coumarins: VI.* synthesis of 3-vinylfurocoumarin derivatives based on oreoselone

Article abstract of DOI:10.1134/S1070428011070190

Palladium-catalyzed Heck reaction of oreoselone trifluoromethanesulfonate with various terminal alkenes (methyl acrylate, styrene, vinylpyridines, N-vinylpyrrole, and N-vinyl-1,2,4-triazole) led to the formation of the corresponding (E)-3-vinyl-7H-furo[3,

Full text of DOI:10.1134/S1070428011070190

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 7, pp. 1083–1090. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © A.V. Lipeeva, E.E. Shul’ts, I.Yu. Bagryanskaya, M.M. Shakirov, G.A. Tolstikov, 2011, published in Zhurnal Organicheskoi Khimii,
2011, Vol. 47, No. 7, pp. 1065–1072.
Plant Coumarins: VI.* Synthesis of 3-Vinylfurocoumarin
Derivatives Based on Oreoselone
A. V. Lipeeva, E. E. Shul’ts, I. Yu. Bagryanskaya, M. M. Shakirov, and G. A. Tolstikov
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences,
pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia
e-mail: schultz@nioch.nsc.ru
Received October 27, 2010
Abstract—Palladium-catalyzed Heck reaction of oreoselone trifluoromethanesulfonate with various terminal
alkenes (methyl acrylate, styrene, vinylpyridines, N-vinylpyrrole, and N-vinyl-1,2,4-triazole) led to the forma-
tion of the corresponding (E)-3-vinyl-7H-furo[3,2-g]chromen-7-ones. The yield was found to depend on the
catalytic system and initial olefin structure.
DOI: 10.1134/S1070428011070190
Interest in linearly fused furocoumarins is deter-
mined by important role of these compounds in vital
activity of plants and animals, as well as by their
strong and diverse biological activity. Such furocou-
marins as psoralens exert various biological effects on
eukaryotic cells (inhibit cell division in the G-2 and
S-phases and induce apoptosis) and are used in therapy
of skin diseases (PUVA therapy) [2, 3]. Studies on
structure–activity relationships showed that introduc-
tion of additional substituents into the 3-position of the
furocoumarin system reduces phototoxic effect (skin
phototoxicity) of fused psoralens [3]. 3-Aryl-substi-
tuted furocoumarins were found to possess cardio-
tropic activity [4]. A number of metabolites of the
dihydrofurocoumarin series containing a substituent on
C3 were isolated and found to exhibit vasodilator
activity [5].
(I) [6]. Treatment of peucedanin (I) with hydrochloric
acid in methanol quantitatively afforded oreoselone
(II) which reacted with trifluoromethanesulfonic anhy-
dride in the presence of a base to give 2-isopropyl-7-
oxo-7H-furo[3,2-g]chromen-3-yl trifluoromethanesul-
fonate (III) in up to 72% yield (Scheme 1). The struc-
ture of oreoselone trifluoromethanesulfonate III was
proved by X-ray analysis.
Furocoumarins having functionalized olefinic frag-
ments in the furan ring were synthesized by the Heck
reaction [7] of trifluoromethanesulfonate III with
various terminal alkenes. Initially, the reaction of III
with methyl acrylate (IV) was carried out using
Pd(OAc)2/(o-Tol)3P (2/8 mol %) as catalytic system,
which was shown to be effective in the cross coupling
of functionally substituted bromides with acrylates; tri-
ethylamine was used as base, and dimethylformamide,
as solvent [8]; however, 3-(3-methoxy-3-oxoprop-1-
en-1-yl) derivative V was obtained in a poor yield. It
was more effective to use as ligand tris(tert-butyl)phos-
The goal of the present work was to synthesize new
furocoumarin derivatives having various substituents
on C3 from an accessible plant coumarin, peucedanin
Scheme 1.
MeO
O
TfO
4
9
5
3
Me
Me
Me
Me
Me
Me
i
ii or iii
6
7
2
O
O
O
O
O
O
O
O
O
I
II
III
i: Concentrated hydrochloric acid, MeOH, 55°C; ii: (CF3SO2)2O, pyridine, –10°C (30 min), 25°C (12 h); iii: (CF3SO2)2O,
2,4,6-trimethylpyridine, CH2Cl2, 10°C (10 min), 25°C (16 h).
* For communication V, see [1].
1083

LIPEEVA et al.
1084
Scheme 2.
O
MeO
Ph
CH2=CHCOOMe (IV)
i, ii
PhCH=CH2 (VI)
i, ii
Me
Me
III
O
O
Me
Me
O
O
O
O
V
IX
Me
4''
N
2''
H2C
N
1''
CH2
N
N
Me
1'
VII
i, iii–vi
VIII
i
Me
Me
Me
III
O
O
Me
O
O
O
O
X
XI
i: Pd(OAc)2, (o-Tol)3P, Et3N, DMF, 115°C; ii: Pd(OAc)2, (t-Bu)3P, Et3N, DMF, 115°C; iii: Pd(OAc)2, BINAP, Et3N, DMF, 115°C;
iv: Pd(dba)2, (o-Tol)3P, Et3N, DMF, 115°C; v: Pd(dba)2, BINAP, Et3N, DMF, 115°C; vi: Pd(dba)2, BINAP, t-BuONa, dioxane, 100°C.
Taking into account interest in psoralen derivatives
having an aza heteroring fused to the furan ring [9], we
examined cross coupling of trifluoromethanesulfonate
III with N-vinyl-substituted heterocyclic compounds,
1-vinyl-1H-1,2,4-triazole (XII) and 2-phenyl-1-vinyl-
1H-pyrrole (XIII) (Scheme 3). The condensation of III
with vinyltriazole XII in the presence of Pd(OAc)2/
(o-Tol)3P (2/8 mol %) gave (E)-3-[2-(1H-1,2,4-triazol-
1-yl)vinyl]-7H-furo[3,2-g]chromen-7-one (XIV) in
48% yield; according to the 1H NMR data, the reaction
mixture also contained a small amount (no more than
3%) of the corresponding Z isomer. In the reaction of
III with pyrrole XIII under analogous conditions we
isolated 42% of (E)-3-[2-(2-phenyl-1H-pyrrol-1-yl)-
vinyl]-7H-furo[3,2-g]chromen-7-one (XV), and only
traces of its Z isomer were detected. Replacement of
the ligand in the catalytic system by BINAP or
(t-Bu)3P in the condensation of III with XII did not
increase the fraction of the Z isomer, but the yield of
the E isomer was considerably lower. An efficient
catalyst for the condensation of compound III with
vinyltriazole XII was dichlorobis(triphenylphosphine)-
palladium (5 mol %); the yield of (E)-3-[2-(1H-1,2,4-
triazol-1-yl)vinyl]-7H-furo[3,2-g]chromen-7-one
(XIV) was 40%.
phine; in this case, the yield of V was 42%, and the
optimal ratio Pd(OAc)2/(t-Bu)3P was 2/8 mol %
(Scheme 2). It should be noted that in all cases the con-
version of the initial compound was complete.
By condensation of furocoumarin trifluoromethane-
sulfonate III with styrene VI or vinylhetarenes
[2-vinylpyridine (VII) and 2-methyl-5-vinylpyridine
(VIII)] in DMF on heating to 115°C in the presence of
Pd(OAc)2/(o-Tol)3P (2/8 mol %) as catalytic system we
obtained (E)-2-isopropyl-3-styryl- and (E)-2-iso-
propyl-3-[pyridinyl)vinyl]-7H-furo[3,2-g]chromen-7-
ones IX–XI (Scheme 2; yield 38–45%). Interestingly,
the reaction of III with styrene VI at 80°C gave no
more than 10% of condensation product IX. Replace-
ment of the ligand by tris(tert-butyl)phosphine (ii) in
the reaction of III with styrene (VI) or by BINAP (iii)
in the reaction with 2-vinylpyridine (VII) did not im-
prove the yield of condensation products IX and X. Bis-
(dibenzylideneacetone)palladium [Pd(dba)2] (5 mol %)
in combination with (o-Tol)3P or BINAP (10 mol %) as
ligand ensured, respectively, only 28 or 23% yield of
X. By reaction of compound III with 2-vinylpyridine
(VII) in dioxane in the presence of Pd(dba)2/BINAP
(5/10 mol %) and sodium tert-butoxide we obtained
20% of 3-[2-(pyridin-2-yl)vinyl]furocoumarin X. Thus
the best yields in the Heck reactions of trifluoro-
methanesulfonate III with vinylarenes VI–VIII were
attained using Pd(OAc)2/(o-Tol)3P as catalytic system.
The structure of the synthesized compounds was
determined on the basis of their spectral parameters
and elemental composition. The structure of oreo-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 7 2011

PLANT COUMARINS: VI.
1085
Scheme 3.
N
3''
2''
Ph
N
N
N1''
N
CH2
CH2
N
N
2'
2'
N
1'
1'
XII
i–iv
XIII
i
Me
Me
Me
Me
III
O
O
O
O
O
O
XIV
XV
i: Pd(OAc)2, (o-Tol)3P, Et3N, DMF, 115°C; ii: Pd(OAc)2, BINAP, Et3N, DMF, 115°C; iii: Pd(OAc)2, (t-Bu)3P, Et3N, DMF, 115°C;
iv: Pd(PPh3)2Cl2, Et3N, DMF, 125°C.
constant for 1′-H and 2′-H in compounds V and IX–XI
(J = 15.1–16.2 Hz) and hetarylvinyl derivatives XIV
and XV (J = 12.8–14.2 Hz) indicates trans configura-
tion of the exocyclic double bond.
selone trifluoromethanesulfonate III was proved by
X-ray analysis. A unit cell of compound III in crystal
contains two independent molecules, one of which is
shown in figure. The bond lengths and bond angles in
the two independent molecules coincide within 3σ and
approach the corresponding standard values [10]. The
tricyclic skeleton in both molecules is almost planar.
The mean-square deviation from the plane is 0.029 Å
for one molecule, and 0.046 Å, for the other.
Thus Heck reaction of oreoselone trifluoromethane-
sulfonate with various alkenes may be used to synthe-
size various 3-substituted derivatives of a linearly
fused furocoumarin, peucedanin; the products attract
interest as potential biologically active substances.
Molecules III in crystal are linked to couples via π-
stacking interaction [intercentroid distance 3.665(3) Å,
interplanar distance 3.27 Å], and these couples are
packed to form parquet-like pattern through
C9a–H9aa · · · O2b hydrogen bonds [H9aa · · · O2b 2.37,
C9a···O2b 3.262(7) Å, ∠C9aH9aaO2b 155°]. In addition,
molecules III are linked to each other via numerous
O···π interactions [the distance between the oxygen
atom and the centroid of the neighboring π-system
ranges from 3.150(4) to 3.504(5) Å].
EXPERIMENTAL
The NMR spectra were recorded from solutions
in CDCl3 or CDCl3–CD3OD on Bruker AV-300
1
[300.13 MHz for H and 75.47 MHz for 13C), AV-400
1
[400.13 MHz for H and 100.78 MHz for 13C), and
1
AV-600 spectrometers (600.30 MHz for H and
150.96 MHz for 13C). Signals in the NMR spectra were
assigned using various proton–proton and carbon–
Oreoselone trifluoromethanesulfonate III and Heck
coupling products V, IX–XI, XIV, and XV are charac-
terized by electronic absorption spectra typical of
coumarin derivatives. For example, the spectrum of III
contains absorption bands with their maxima at λ 250,
284, and 337 nm. The cross-coupling products dis-
played in the UV spectra a larger number of absorption
bands and increased intensity of absorption maxima
due to extension of conjugation chain. For instance, the
spectrum of IX contains absorption maxima at λ 222,
F1
C10
O3
O4
S1
F2
F3
C5
O5
C4
C4a
C6
C7
C3a
C3
C8a
C2
1
232, 255, 301, 310, 344, and 352 nm. The H and 13C
O2
C1′
O8
C9a
C9
C2′
NMR spectra of the synthesized compounds were con-
sistent with the assumed structures; only one set of
signals from the furocoumarin skeleton and the corre-
sponding substituent was observed. Protons at the exo-
cyclic double C=C bond (1′-H and 2′-H) resonated in
O1
C3′
1
the H NMR spectra of condensation products V, IX–
Structure of 2-isopropyl-7-oxo-7H-furo[3,2-g]chromen-3-yl
trifluoromethanesulfonate (III) according to the X-ray dif-
fraction data.
XI, XIV, and XV as doublets at δ 6.88–7.04 and 7.11–
7.66 or 6.64–7.16 and 6.98–7.44 ppm. The coupling
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 7 2011

LIPEEVA et al.
1086
proton shift correlation techniques (COSY, XHCO,
COLOC). Signal multiplicities in the 13C NMR spectra
were determined using J modulation technique. The IR
spectra were recorded in KBr on a Bruker Vector-22
spectrometer. The UV spectra were measured on
an HP 8453 UV-Vis spectrophotometer. The elemental
compositions were determined on a Carlo Erba 1106
CHN-analyzer.
b. Oreoselone (II), 500 mg (2 mmol), was dissolved
in 10 ml of anhydrous methylene chloride, 290 mg
(2.4 mmol) of 2,4,6-trimethylpyridine was added under
argon, the mixture was cooled to 10°C, 1.128 g
(4 mmol) of trifluoromethanesulfonic anhydride was
added dropwise at 10–20°C, and the mixture was
stirred for 16 h. The mixture was then treated with
8 ml of water, the organic phase was separated, and the
aqueous phase was extracted with methylene chloride
(4 × 5 ml). The extracts were combined with the
organic phase, washed with water, dried over MgSO4,
and evaporated to isolate 0.52 g (69%) of compound
III with mp 132–133°C (from diethyl ether). IR spec-
trum, ν, cm–1: 3487, 2929, 2857, 1665, 1640, 1626,
1600, 1280, 1253, 1174, 1110, 1050, 1037, 767, 645.
UV spectrum (CHCl3), λmax, nm (logε): 250 (4.29),
The X-ray diffraction data for compound III were
acquired at –100°C on a Bruker Kappa Apex II diffrac-
tometer with a two-coordinate CCD detector (MoKα
irradiation, graphite monochromator, ω–φ scanning up
to 2θ = 51°). Analysis of the geometric parameters and
intermolecular interactions was performed using
PLATON [11] and MERCURY programs [12].
1
The products were isolated by column chromatog-
raphy on silica gel (0.035–0.070 mm, Acros Organics)
or aluminum oxide using chloroform or chloroform–
ethanol (50:3) as eluent. The progress of reactions was
monitored by TLC on Silufol UV-254 plates using
chloroform–ethanol (3:1) or benzene as eluent; spots
were visualized by treatment with iodine vapor and
under UV light.
284 (3.80), 337 (3.73). H NMR spectrum, δ, ppm:
1.04 d [6H, (CH3)2CH, J = 7 Hz], 2.93 m [1H,
CH(CH3)2], 6.08 d (1H, 6-H, J = 9.8 Hz), 6.95 s (1H,
9-H), 7.07 s (1H, 4-H), 7.50 d (1H, 5-H, J = 9.8 Hz).
13C NMR spectrum, δC, ppm: 20.95 q [(CH3)2CH],
23.48 d [CH(CH3)2], 101.12 d (C9), 114.05 d (C6),
114.19 s (C4a), 121.52 d (C4), 125.99, 127.70, 129.41,
131.12 q (CF3), 125.62 s (C3), 143.51 s (C3a), 144.39 d
(C5), 151.18 s (C8a); 160.04 s, 160.49 s, and 161.74 s
(C2, C7, C9a). 19F NMR spectrum (relative to C6F6 as
internal reference): δF 89.12 ppm, s (CF3). Found, %:
C 47.03; H 2.99; F 15.08; S 8.30. C15H11F3O6S. Cal-
culated, %: C 47.88; H 2.95; F 15.15; S 8.52.
Commercial (o-Tol)3P, (R)-(+)BINAP, (t-Bu)3P, and
trifluoromethanesulfonic anhydride (Alfa Aesar) were
used. The solvents (dioxane, DMF, and CH2Cl2), Et3N,
2-methyl-5-vinylpyridine, 2-vinylpyridine, styrene,
and methyl acrylate were distilled in a stream of argon
just before use; Pd(OAc)2 was synthesized as de-
scribed in [13]; Pd(dba)2 was prepared according to the
procedure reported in [14] and was used without
recrystallization; Pd(PPh3)2Cl2 was synthesized as re-
ported in [15]; oreoselone was prepared by hydrolysis
of peucedanin [16]; peucedanin was isolated from
Peucedanum morisonii roots according to [6].
Methyl (E)-3-(2-isopropyl-7-oxo-7H-furo[3,2-g]-
chromen-3-yl)prop-2-enoate (V). a. Oreoselone tri-
fluoromethanesulfonate III, 250 mg (0.67 mmol), was
dissolved in 5 ml of anhydrous DMF, 118 mg
(1.3 mmol) of methyl acrylate, 2.2 mg (2 mol %) of
Pd(OAc)2, 30 mg (8 mol %) of (o-Tol)3P, and 0.07 ml
(1.3 equiv) of Et3N were added under argon, and the
mixture was heated for 5 h at 115°C (until initial
compound III disappeared according to the TLC data).
The mixture was cooled under argon and poured onto
a Petri dish for evaporation. The residue was subjected
to column chromatography on silica gel using chloro-
form as eluent. The amount of the product thus isolated
was insufficient for further purification.
2-Isopropyl-7-oxo-7H-furo[3,2-g]chromen-3-yl
trifluoromethanesulfonate (III). a. A solution of
500 mg (2 mmol) of oreoselone (II) in 3 ml of anhy-
drous pyridine was cooled to (–10°C), 2.256 g
(8 mmol) of trifluoromethanesulfonic anhydride was
added dropwise under argon, and the mixture was
stirred for 30 min at –10°C, allowed to warm up to
room temperature, and stirred for 12 h under argon.
When the reaction was complete (TLC), the mixture
was treated with 5 ml of water and extracted with
diethyl ether (5×10 ml). The extracts were combined,
washed with water (2×10 ml), dried over MgSO4, and
evaporated, and the residue was additionally dried by
azeotropic distillation with benzene and recrystallized
from diethyl ether. Yield 0.54 g (72%).
b. Oreoselone trifluoromethanesulfonate III,
250 mg (0.67 mmol), was dissolved in 5 ml of anhy-
drous DMF, 118 mg (1.3 mmol) of methyl acrylate,
2.2 mg (2 mol %) of Pd(OAc)2, 10 mg (8 mol %) of
(t-Bu)3P, and 0.07 ml (1.3 equiv) of Et3N were added
under argon, and the mixture was heated for 7 h at
115°C (TLC), cooled, and poured onto a Petri dish for
evaporation. The residue was subjected to column
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 7 2011

PLANT COUMARINS: VI.
1087
chromatography on silica gel using chloroform as
eluent. Recrystallization from chloroform gave 88 mg
(42%) of compound V. No Z isomer was detected by
1H NMR spectroscopy. mp 113–114°C. IR spectrum, ν,
cm–1: 1741, 1625, 1590, 1391, 1369, 1195, 1139, 1100,
(CH3)2CH, J = 7.0 Hz], 3.15 m [1H, CH(CH3)2],
6.27 d (1H, 6-H, J = 9.7 Hz), 6.99 s (1H, 9-H), 7.06 d
(1H, 2′-H, J = 15.0 Hz), 7.14 d (1H, 1′-H, J =
15.0 Hz), 7.29 m (1H, 4″-H), 7.34 m (2H, 3″-H, 5″-H),
7.37 s (1H, 4-H), 7.61 d (2H, 2″-H, 6″-H), 7.71 d (1H,
5-H, J = 9.7 Hz). 13C NMR spectrum, δC, ppm: 18.41 q
[(CH3)2CH], 27.09 d [CH(CH3)2], 99.99 d (C9),
114.11 d (C6), 114.33 s (C4a), 117.05 s (C3a), 120.58 d
(C4), 126.90 d (C1′), 127.47 d (C2″ C6″), 128.06 d (C3″,
C5″), 128.69 s (C3), 128.99 d (C4″) 132.90 d (C2′),
136.82 s (C1″), 144.48 d (C5), 144.54 s (C8a), 151.31 s
(C9a), 159.32 s (C2), 160.36 s (C7). Found, %: C 79.45;
H 5.25. C22H18O3. Calculated, %: C 79.98; H 5.49.
1020, 938, 816, 742, 638. UV spectrum (CHCl3), λmax
,
nm (logε): 253 (3.90), 295 (3.49), 309 (3.47), 340
1
(3.48), 354 (3.45). H NMR spectrum, δ, ppm: 0.92 d
and 1.02 d [3H each, (CH3)2CH, J = 7.0 Hz], 2.58 m
[1H, CH(CH3)2], 3.56 s (3H, OCH3) 6.23 d (1H, 6-H,
J = 9.6 Hz), 6.74 s (1H, 9-H), 6.84 d (1H, 2′-H, J =
15.5 Hz), 7.53 d (1H, 5-H, J = 9.6 Hz), 7.66 d (1H,
1′-H, J = 15.5 Hz), 7.88 s (1H, 4-H). 13C NMR spec-
trum, δC, ppm: 20.65 q [(CH3)2CH], 26.96 d
[CH(CH3)2], 51.39 q (OCH3), 99.54 d (C9), 111.85 s
and 112.33 s (C3, C4a), 115.63 d and 116.18 d (C4, C6),
121.28 s (C3a), 128.53 d (C2′), 143.54 d and 144.40 d
(C5, C1′), 150.40 s and 151.22 s (C8a, C9a), 158.05 s
(C2), 159.49 s (C7), 167.17 s (C3′). Found, %: C 68.85;
H 5.25. C18H16O5. Calculated, %: C 69.22; H 5.16.
2-Isopropyl-3-[(E)-2-(pyridin-2-yl)vinyl]-
7H-furo[3,2-g]chromen-7-one (X). a. Compound III,
250 mg (0.67 mmol), was dissolved in 5 ml of anhy-
drous DMF, 136 mg (1.3 mmol) of 2-vinylpyridine
(VII), 2.2 mg (2 mol %) of Pd(OAc)2, 32 mg
(8 mol %) of (o-Tol)3P, and 0.07 ml (1.3 equiv) of Et3N
were added under argon, and the mixture was heated
for 8 h at 115°C (TLC), cooled, and poured onto
a Petri dish for evaporation. The residue was subjected
to column chromatography on silica gel using chloro-
form as eluent. The subsequent recrystallization from
diethyl ether gave 100 mg (38%) of compound X.
2-Isopropyl-3-[(E)-2-phenylvinyl]-7H-furo-
[3,2-g]chromen-7-one (IX). a. Compound III, 250 mg
(0.67 mmol), was dissolved in 5 ml of anhydrous
DMF, 135 mg (1.3 mmol) of styrene (VI), 2.2 mg
(2 mol %) of Pd(OAc)2, 32 mg (8 mol %) of (o-Tol)3P,
and 0.07 ml (1.3 equiv) of Et3N were added under
argon, and the mixture was heated for 7 h at 115°C
(TLC), cooled, and poured onto a Petri dish for evap-
oration. The residue was subjected to column chroma-
tography on silica gel using chloroform as eluent.
Recrystallization from diethyl ether gave 80 mg (40%)
of IX. When the reaction was carried out at 80°C (7 h),
evaporation of the solvent and subsequent chromato-
graphic separation (silica gel, chloroform) gave a frac-
tion containing 88% of initial compound III and
a fraction containing 10% of compound IX.
b. Compound III, 250 mg (0.67 mmol), was dis-
solved in 5 ml of anhydrous DMF, 136 mg (1.3 mmol)
of 2-vinylpyridine (VII), 2.2 mg (2 mol %) of
Pd(OAc)2, 34 mg (8 mol %) of BINAP, and 0.07 ml
(1.3 equiv) of Et3N were added under argon, and the
mixture was heated for 7 h at 115°C (TLC) and treated
as described above to isolate 93 mg (35%) of com-
pound X.
c. Compound III, 250 mg (0.67 mmol), was dis-
solved in 5 ml of anhydrous DMF, 211 mg (2 mmol) of
2-vinylpyridine (VII), 21 mg (5 mol %) of Pd(dba)2,
46 mg (10 mol %) of (o-Tol)3P, and 0.07 ml (1.3 equiv)
of Et3N were added under argon, and the mixture was
heated for 7 h at 115°C and treated as described above
to isolate 50 mg (18%) of compound X.
b. Compound III, 250 mg (0.67 mmol), was dis-
solved in 5 ml of anhydrous DMF, 135 mg (1.3 mmol)
of styrene (VI), 2.2 mg (2 mol %) of Pd(OAc)2, 10 mg
(8 mol %) of (t-Bu)3P, and 0.07 ml (1.3 equiv) of Et3N
were added under argon, and the mixture was heated
for 7 h at 115°C (TLC), cooled, and poured onto
a Petri dish for evaporation. The residue was subjected
to column chromatography on silica gel using chloro-
form as eluent. Yield 72 mg (33%), mp 133–134°C. IR
spectrum, ν, cm–1: 3082, 3060, 3026, 1730, 1678,
1625, 1577, 1491, 1353, 1286, 1216, 1140, 1100,
1046, 1031, 950, 907, 850, 825, 807, 756, 700, 666.
UV spectrum (CHCl3), λmax, nm (logε): 243 (3.41),
249 (3.40), 253 (3.39), 264 sh (3.23), 330 sh (2.97),
d. Compound III, 250 mg (0.67 mmol), was dis-
solved in 5 ml of anhydrous DMF, 211 mg (2 mmol) of
2-vinylpyridine (VII), 21 mg (5 mol %) of Pd(dba)2,
42 mg (10 mol%) of BINAP, and 0.07 ml (1.3 equiv)
of Et3N were added under argon, and the mixture was
heated for 7 h at 115°C and treated as described above
to isolate 62 mg (23%) of compound X.
e. Compound III, 250 mg (0.67 mmol), was dis-
solved in 5 ml of anhydrous dioxane, 211 mg (2 mmol)
of 2-vinylpyridine (VII), 21 mg (5 mol %) of Pd(dba)2,
1
355 (2.62). H NMR spectrum, δ, ppm: 1.43 d [6H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 7 2011

LIPEEVA et al.
1088
42 mg (10 mol %) of BINAP, and 84 mg (1.3 equiv) of
t-BuONa were added under argon, and the mixture was
heated for 9 h at 105°C (TLC), cooled, and poured
onto a Petri dish for evaporation. The residue was
subjected to column chromatography on silica gel
using chloroform as eluent. Recrystallization from
diethyl ether gave 44 mg (15%) of compound X,
mp 201–202°C. IR spectrum, ν, cm–1: 1732, 1715,
1626, 1571, 1353, 1289, 1148, 1097, 1066, 919, 881,
826, 756, 742, 689, 668, 654. UV spectrum (CHCl3),
(1H, 2″-H, J = 2.0 Hz). 13C NMR spectrum, δC, ppm:
20.71 q [(CH3)2CH], 23.36 q (4″-CH3), 27.02 d
[CH(CH3)2], 99.48 d (C9), 114.04 s (C4a), 114.27 d
(C6), 117.42 s (C3a), 120.51 d (C4), 122.13 d (C5″),
127.82 s (C1″), 129.38 d (C1′), 130.55 s (C3), 132.21 d
(C2′), 133.43 d (C6″), 144.47 d (C5), 146.22 d (C2″),
151.18 s (C8a), 151.28 s (C9a), 157.84 s (C4″), 159.12 s
(C2), 160.86 s (C7). Found, %: C 72.71; H 5.82;
N 3.68. C22H19NO3 ·H2O. Calculated, %: C 72.73;
H 5.78; N 3.85.
λ
max, nm (logε): 255 (4.60), 301 (4.20), 310 (4.20), 344
2-Isopropyl-3-[(E)-2-(1H-1,2,4-triazol-1-yl)-
vinyl]-7H-furo[3,2-g]chromen-7-one (XIV). a. Com-
pound III, 250 mg (0.67 mmol), was dissolved in 5 ml
of anhydrous DMF, 123 mg (1.3 mmol) of 1-vinyl-1H-
1,2,4-triazole (XII), 2.2 mg (2 mol %) of Pd(OAc)2,
32 mg (8 mol %) of (o-Tol)3P, and 0.07 ml (1.3 equiv)
of Et3N were added under argon, and the mixture was
heated for 8 h at 115°C (TLC), cooled, and poured
onto a Petri dish for evaporation. The residue was sub-
jected to column chromatography on silica gel using
chloroform as eluent to isolate a fraction containing
compound XIV and a small amount of its Z isomer
1
(4.23). H NMR spectrum, δ, ppm: 1.42 d [6H,
(CH3)2CH, J = 7.0 Hz], 3.15 m [1H, CH(CH3)2],
6.26 d (1H, 6-H, J = 9.7 Hz), 6.98 s (1H, 9-H), 7.06 d
(1H, 2′-H, J = 16.1 Hz), 7.18 m (1H, 4″-H), 7.37 s
(1H, 4-H), 7.49 d (1H, 6″-H, J = 8.0 Hz), 7.70 d (1H,
5-H, J = 9.7 Hz), 7.73 d.d (1H, 5″-H, J = 7.8, 8.0 Hz),
7.82 d (1H, 1′-H, J = 16.1 Hz), 8.52 d (1H, 3″-H, J =
7.8 Hz). 13C NMR spectrum, δC, ppm: 20.73 q
[(CH3)2CH], 27.04 d [CH(CH3)2], 99.11 d (C9),
114.06 s (C4a), 114.39 d (C6), 115.48 s (C3a), 120.53 d
(C4), 120.88 d and 121.60 d (C2″, C6″), 128.94 d (C1′),
130.77 s (C3), 131.88 d (C2′), 136.33 d (C5″), 144.48 d
(C5), 149.22 d (C3″), 149.34 s (C8a), 151.20 s (C9a),
154.95 s (C1″), 159.14 s (C2), 160.52 s (C7). Found, %:
C 57.79; H 4.21; Cl 23.12; N 3.12. C21H17NO3·CHCl3.
Calculated, %: C 58.21; H 3.97; Cl 23.60; N 3.09.
1
(according to the H NMR data). Recrystallization
from diethyl ether gave 100 mg (48%) of XIV.
b. Compound III, 250 mg (0.67 mmol), was dis-
solved in 5 ml of anhydrous DMF, 123 mg (1.3 mmol)
of 1-vinyl-1H-1,2,4-triazole (XII), 4.4 mg (4 mol %)
of Pd(OAc)2, 34 mg (8 mol %) of BINAP, and 0.07 ml
(1.3 equiv) of Et3N were added under argon, and the
mixture was heated for 8 h at 115°C (TLC) and treated
as described above in a to isolate 96 mg (45%) of
compound XIV.
2-Isopropyl-3-[(E)-2-(4-methylpyridin-3-yl)-
vinyl]-7H-furo[3,2-g]chromen-7-one (XI). Com-
pound III, 250 mg (0.67 mmol), was dissolved in 5 ml
of anhydrous DMF, 153 mg (1.3 mmol) of 2-methyl-5-
vinylpyridine (VIII), 2.2 mg (2 mol %) of Pd(OAc)2,
32 mg (8 mol %) of (o-Tol)3P, and 0.07 ml (1.3 equiv)
of Et3N were added under argon, and the mixture was
heated for 8 h at 115°C (TLC), cooled, and poured
onto a Petri dish for evaporation. The residue was sub-
jected by column chromatography on aluminum oxide
using chloroform–ethanol (50:3), and the isolated frac-
tion was subjected to repeated chromatography on
silica gel using chloroform as eluent. Yield 87 mg
(38%), oily substance. IR spectrum, ν, cm–1: 1733,
1710, 1648, 1620, 1574, 1541, 1491, 1291, 1260,
1203, 1143, 1098, 1036, 826, 689, 669, 651. UV spec-
trum (CHCl3), λmax, nm (logε): 244 (4.14), 275 sh
c. Compound III, 250 mg (0.67 mmol), was dis-
solved in 3 ml of anhydrous DMF, 123.5 mg
(1.3 mmol) of 1-vinyl-1H-1,2,4-triazole (XII), 23 mg
(5 mol %) of Pd(PPh3)2Cl2, and 0.07 ml (1.3 equiv) of
Et3N were added under argon, and the mixture was
heated for 5 h at 115°C (TLC) and treated as described
above in a to isolate 86 mg (40%) of compound XIV.
d. Compound III, 250 mg (0.67 mmol), was dis-
solved in 3 ml of anhydrous DMF, 123 mg (1.3 mmol)
of 1-vinyl-1H-1,2,4-triazole (XII), 2.2 mg (2 mol %)
of Pd(OAc)2, 10 mg (8 mol %) of tris(tert-butyl)-
phosphine, and 0.07 ml (1.3 equiv) of Et3N were added
under argon, and the mixture was heated for 5 h at
115°C (TLC) and treated as described above in a to
isolate 42 mg (20%) of compound XIV, mp 181–
184°C. IR spectrum, ν, cm–1: 3432, 3124, 3059, 2853,
1726, 1628, 1577, 1142, 1190, 1219, 1274, 1510,
1458, 1392, 1347, 1318, 1070, 1043, 1002, 960, 935,
1
(3.99), 300 (3.54), 331 (3.96). H NMR spectrum, δ,
ppm: 1.42 d [6H, (CH3)2CH, J = 7.0 Hz], 3.19 m [1H,
CH(CH3)2], 2.54 s (3H, CH3), 6.30 d (1H, 6-H, J =
9.7 Hz), 6.98 d (1H, 2′-H, J = 16.2 Hz), 7.02 s (1H,
9-H), 7.16 d (1H, 1′-H, J = 16.2 Hz), 7.31 d (1H, 5″-H,
J = 8.0 Hz), 7.41 s (1H, 4-H), 7.54 d (1H, 5-H, J =
9.7 Hz), 8.02 d.d (1H, 6″-H, J = 8.0, 2.0 Hz), 8.96 d
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 7 2011

PLANT COUMARINS: VI.
900, 876, 827, 778, 671. UV spectrum (CHCl3), λmax
1089
,
m-H), 7.57 s (1H, 4-H), 7.61 d (2H, o-H, J = 7.0 Hz),
7.65 d (1H, 5-H, J = 9.7 Hz). 13C NMR spectrum, δC,
ppm: 29.58 q [(CH3)2CH], 34.40 d [CH(CH3)2],
100.68 d (C9), 105.26 d (C4″), 110.60 s (C4a), 111.76 d
(C3″), 114.31 d (C6), 115.09 s (C3a), 118.45 d (C4),
125.21 d (C4), 129.06 d (C2′), 129.69 d and 130.10 d
(Co), 130.22 d (Cp), 131.00 s (C3), 132.43 d and
132.92 d (Cm), 133.71 s (C2″), 144.44 d (C5), 144.27 s
(Ci), 147.08 d (C1′), 150.63 s (C9a), 156.61 s (C2, C9a),
160.15 s (C7). Found, %: C 78.28; H 5.81; N 3.02.
C26H21NO3. Calculated, %: C 78.97; H 5.35; N 3.54.
nm (logε): 259 (4.27), 302 (4.23), 348 sh (3.73).
1H NMR spectrum, δ, ppm: 1.21 d [6H, (CH3)2CH, J =
7.0 Hz], 3.19 [1H, CH(CH3)2], 6.21 d (1H, 6-H, J =
9.7 Hz), 7.06 s (1H, 9-H), 7.16 d (1H, 2′-H, J =
14.2 Hz), 7.41 d (1H, 1′-H, J = 14.2 Hz), 7.57 s (1H,
4-H), 7.65 d (1H, 5-H, J = 9.7 Hz), 7.88 br.s (1H,
3″-H), 8.20 br.s (1H, 5″-H). 13C NMR spectrum, δC,
ppm: 21.01 q [(CH3)2CH], 26.89 d [CH(CH3)2],
100.02 d (C9), 111.47 s (C4a), 114.90 d (C6), 114.80 s
(C3a), 118.35 d (C4), 121.86 d (C2′), 131.23 s (C3),
142.98 d (C1′), 143.84 d (C5), 152.26 s (C8a), 152.40 d
(C5″), 155.20 d (C3″), 155.96 s (C9a), 160.29 s (C7),
165.13 s (C2). Found, %: C 66.88; H 4.01; N 13.02.
C18H15N3O3. Calculated, %: C 67.28; H 4.71; N 13.08.
X-Ray diffraction data for compound III. Mono-
clinic crystals. C15H11F3O6S. Unit cell parameters: a =
5.540(1), b = 16.060(3), c = 17.041(4) Å; β =
92.34(1)°, V = 1515.0(6) Å3; space group P21; Z = 4;
dcalc = 1.650 g/cm3. Total of 11068 reflections were
When the reaction was carried out as described in
a, the corresponding Z isomer was detected among the
products but was not isolated as individual substance.
1H NMR spectrum of the Z isomer (from Z/E isomer
mixture at a ratio of 1 : 4), δ, ppm: 1.08 d [6H,
(CH3)2CH, J = 7.0 Hz], 3.34 [1H, CH(CH3)2], 6.35 d
(1H, 6-H, J = 9.6 Hz), 6.96 s (1H, 9-H), 7.02 d (1H,
2′-H, J = 9.2 Hz), 7.28 d (1H, 1′-H, J = 9.2 Hz), 7.57 s
(1H, 4-H), 7.62 d (1H, 5-H, J = 9.7 Hz), 7.95 br.s (1H,
3″-H), 8.39 br.s (1H, 5″-H).
measured, 4898 of which were independent (Rint
=
0.060). Corrections for absorption were introduced
using SADABS program [17] which removed equiv-
alent reflections measured at different orientations of
the single crystal (transmission 0.59–0.97). The struc-
ture was solved by the direct method using SHELXS-
97 software package [18] and was refined by the least-
squares procedure in full-matrix anisotropic approxi-
mation using SHELXL-97 [18]. The positions of
hydrogen atoms were calculated in each iteration cycle
from the coordinates of the corresponding carbon
atoms (riding model). Isotropic thermal parameters of
all hydrogen atoms were equal to 1.2Ueq (where Ueq is
the equivalent thermal parameter of the corresponding
carbon atom). The final divergence factors were R =
0.0608 (for 3686 reflections with F > 4σ) and wR2 =
0.1494 (with respect to F2); S = 1.07; 451 refined
parameters; maximal and minimal electron density
differences 0.45 and –0.49 e/Å3. The coordinates of
atoms, their thermal parameters, and geometric param-
eters of molecule III in crystal were deposited to the
Cambridge Crystallographic Data Center (entry
no. CCDC 780428) and are available at http:\\www.
ccdc.cam.ac.uk/data_request/cif.
2-Isopropyl-3-[(E)-2-(2-phenyl-1H-pyrrol-1-yl)-
vinyl]-7H-furo[3,2-g]chromen-7-one (XV). Com-
pound III, 250 mg (0.67 mmol), was dissolved in 5 ml
of anhydrous DMF, 220 mg (1.3 mmol) of 2-phenyl-
1-vinyl-1H-pyrrole (XIII), 2.2 mg (2 mol %) of
Pd(OAc)2, 32 mg (8 mol %) of (o-Tol)3P, and 0.07 ml
(1.3 equiv) of Et3N were added under argon, and the
mixture was heated for 8 h at 115°C (TLC), cooled,
and poured onto a Petri dish for evaporation. The resi-
due was subjected to column chromatography on silica
gel using chloroform as eluent to isolate a fraction
containing compound XV and traces of its Z isomer
1
(according to the H NMR data). Recrystallization
from diethyl ether gave 110 mg (42%) of compound
XV with mp 162–164°C. IR spectrum, ν, cm–1: 3325,
3080, 3059, 2853, 1733, 1715, 1626, 1572, 1510,
1290, 1261, 1197, 1149, 1353, 1468, 1098, 1050,
1027, 919, 879, 850, 825, 800, 744, 700, 660. UV
spectrum (CHCl3), λmax, nm (logε): 254 (4.34), 299
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 10-03-93 162-Mong_a) and by the Program for
Support of Leading Scientific Schools (project
no. 7005.2010.03). The authors thank B.A. Trofimov
for providing samples of 1-vinyl-1H-1,2,4-triazole and
2-phenyl-1-vinyl-1H-pyrrole.
1
(3.92), 310 (3.91), 349 (3.93). H NMR spectrum, δ,
ppm (CDCl3–CD3OD): 1.49 d [6H, (CH3)2CH, J =
7.0 Hz], 3.19 m [1H, CH(CH3)2], 6.26 d (1H, 6-H, J =
9.7 Hz), 6.64 d (1H, 2′-H, J = 12.8 Hz), 6.79 d.d (1H,
4″-H, J = 2.6, 2.2 Hz), 6.95 d (1H, 3″-H, J = 2.6 Hz),
6.98 d (1H, 1′-H, J = 12.8 Hz), 7.10 s (1H, 9-H), 7.11 d
(1H, 5″-H, J = 2.2 Hz), 7.32 m (1H, p-H), 7.42 m (2H,
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