Plant coumarins: VIII. Suzuki reaction in the synthesis of 3-Aryl(hetaryl)furocoumarins

Article abstract of DOI:10.1134/S1070428011090247

Suzuki cross coupling of oreoselone trifluoromethanesulfonate with substituted phenyl- and hetarylboronic acids in the presence of palladium complexes with uni- and bidentate ligands gave the corresponding 3-substituted furocoumarins. Pleiades Publishing,

Full text of DOI:10.1134/S1070428011090247

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2011, Vol. 47, No. 9, pp. 1404–1409. © Pleiades Publishing, Ltd., 2011.
Original Russian Text © A.V. Lipeeva, E.E. Shul’ts, M.M. Shakirov, G.A. Tolstikov, 2011, published in Zhurnal Organicheskoi Khimii, 2011, Vol. 47, No. 9,
pp. 1380–1385.
Plant Coumarins: VIII.* Suzuki Reaction in the Synthesis
of 3-Aryl(hetaryl)furocoumarins
A. V. Lipeeva, E. E. Shul’ts, 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 April 4, 2011
Abstract—Suzuki cross coupling of oreoselone trifluoromethanesulfonate with substituted phenyl- and
hetarylboronic acids in the presence of palladium complexes with uni- and bidentate ligands gave the corre-
sponding 3-substituted furocoumarins.
DOI: 10.1134/S1070428011090247
Natural linear furocoumarins such as psoralen and
8-methoxypsoralen are traditionally used as photo-
chemotherapeutic agents in PUVA therapy of skin
diseases, in particular of psoriasis, vitiligo, and atopic
eczema [2]. However, their application in combination
with UV irradiation gives rise to side effects (muta-
genic etc.), so that search for new psoralen derivatives
is strongly desirable. It was found that application of
synthetic derivatives, e.g., of 3-ethoxycarbonylpsora-
len, reduces side effects in therapy of skin diseases [3].
Derivatives of 3-alkyl- and 3-aryl-substituted furocou-
marins are known as inhibitors of leukotriene LTB4
biosynthesis, and they may be promising from the
viewpoint of design of anti-inflammatory photoactive
agents [4]. In addition, extensive search for Kv-1.3
potassium channel blockers is performed in the series
of amino-substituted furocoumarins [5]. Garazd et al.
[6] synthesized 3-aryl-substituted furocoumarins which
exhibited cardiotropic activity [6].
3-Aryl-substituted linear furocoumarins were syn-
thesized according to MacLeod (Williamson reaction
of 7-hydroxycoumarins with α-halo ketones in the
presence of K2CO3 and cyclization in the presence of
1 N NaOH with subsequent acidolysis [4–7]). This
approach includes a number of steps and requires the
corresponding 7-hydroxycoumarins as starting com-
pounds. In the present work we made an attempt to
synthesize furocoumarin derivatives containing an aro-
matic or heteroaromatic substituent on C3 by palla-
dium-catalyzed cross-coupling of oreoselone trifluoro-
methanesulfonate (I) with boronic acid (Suzuki reac-
tion). 4-Halo- and 4-trifluoromethylsulfonyloxycou-
marins were successfully involved in Suzuki–Miyaura
reaction to synthesize 4-aryl(hetaryl or alkynyl)cou-
marins [8, 9], while analogous reactions with substi-
tuted furocoumarins were not reported previously.
Cross-coupling of oreoselone trifluoromethanesul-
fonate (I) with o-tolylboronic acid (II) was used as
Scheme 1.
4'
3'
5'
2'
Me
TfO
6'
1'
4
5
3
B(OH)2
Me
Me
Me
6
[Pd], i–v
2
+
7
1
8
O
O
O
Me
O
O
Me
O
9
I
II
III
For reaction conditions (i–v), see table.
* For communication VII, see [1].
1404

PLANT COUMARINS: VIII.
1405
Suzuki reaction of oreoselone trifluoromethanesulfonate (I) with o-methylphenylboronic acid (II)
Conditions
Catalyst
Base
Solvent
Dope
Temperature, °C Reaction time, h Yield of III, %
i
PdCl2(dppf)
PdCl2(dppf)
PdCl2(dppf)
PdCl2(dppf)
Pd(PPh3)4
K3PO4
K2CO3
K2CO3
Et3N
MeCN
MeCN
MeCN
MeCN
Dioxane
–
080
080
080
080
100
6
6
35
68
75
55
70
ii
iii
iv
v
–
Bu4N+ Br–
0.4.5
6
–
K2CO3
Bu4N+ Br–
6
model reaction to optimize the conditions (see table,
Scheme 1). The reaction in acetonitrile in the presence
of PdCl2(dppf) [dppf is 1,1′-bis(diphenylphosphino)-
ferrocene] as catalyst and K3PO4 as base was accom-
panied by considerable tarring, and arylation product
III was isolated in 35% yield. The process turned out
to be sensitive to the nature of the base. Using potas-
sium carbonate we succeeded in isolating compound
III in 68% yield. It is known that addition of ammo-
nium salts initiates cross coupling with boronic acids
[9, 10]. We found that the reaction of oreoselone tri-
fluoromethanesulfonate (I) with o-tolylboronic acid
(II) in the presence of Bu4N+ Br– (10%) requires
shorter time (4.5 h) and ensures increased yield of
compound III (to 75%). Replacement of K2CO3 by
NEt3 was not successful: the yield of arylfurocoumarin
III was 55%, and 22% of unreacted compound I was
recovered. The results were not improved to an appre-
ciable extent when the reaction was carried in dioxane
in the presence of palladium complex with unidentate
ligand, Pd(PPh3)4, which is often used in Suzuki cross
couplings; in this case, 70% of III was isolated.
Thus the optimal conditions included the use of
5 mol % of PdCl2(dppf) as catalyst, 3 equiv of K2CO3
as base, 0.1 equiv of Bu4N+ Br–, and acetonitrile as
solvent. Under these conditions we performed cross-
couplings of oreoselone trifluoromethanesulfonate (I)
with 2-chloro-5-trifluoromethylphenylboronic acid
(IV) and 2-aminophenylboronic acid (V). Arylation
products VI and VII were isolated in high yield (71–
Scheme 2.
R2
R1
NHAc
R2
B(OH)2
R1
Me
Me
i
Ac2O, pyridine
I
+
O
O
Me
Me
O
O
O
O
O
IV, V
VI, VII
VIII
O
O
, i
, i
B(OH)2
B(OH)2
O
Me
Me
Me
Me
IX
X
I
O
O
O
O
O
O
XI
XII
HN
B(OH)2
Me
i, ii
I
+
N
H
O
Me
O
O
XIII
XIV
IV, VI, R1 = Cl, R2 = CF3; V, VII, R1 = NH2, R2 = H; VIII, R1 = AcNH, R2 = H; i: PdCl2(dppf), K2CO3, Bu4N+ Br–, MeCN, 80°C;
ii: Pd(PPh3)4, K2CO3, Bu4N+ Br–, dioxane, 100°C.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

LIPEEVA et al.
1406
72%; Scheme 2). Compound VII was converted into
the corresponding N-acetyl derivative VIII. Likewise,
compound I reacted with 2-furylboronic acid (IX) and
3-furylboronic acid (X) to give 2-isopropyl-3-(2-
furyl)- and 2-isopropyl-3-(3-furyl)psoralens XI and
XII in 58 and 67% yield, respectively. By cross-cou-
pling of trifluoromethanesulfonate I with 1H-indol-5-
ylboronic acid (XIII) we obtained 42% of psoralen
derivative XIV containing an indole fragment. The
reaction of I with XIII in dioxane in the presence of
Pd(PPh3)4 on heating at 100°C afforded only 35% of
indolyl-substituted furocoumarin XIV.
and V, and hetarylboronic acids IX, X, and XIII (Alfa
Aesar) were used. The solvents (acetonitrile, dioxane)
and triethylamine were purified by standard procedures
and were distilled in a stream of argon just before use.
Oreoselone trifluoromethanesulfonate (I) was synthe-
sized from natural plant coumarin, peucedanin [11],
according to the procedure described in [12].
2-Isopropyl-3-(2-methylphenyl)-7H-furo[3,2-g]-
chromen-7-one (III). a. Compound I, 200 mg
(0.5 mmol), was dissolved in 3 ml of acetonitrile,
690 mg (0.65 mmol, 1.3 equiv) of o-tolylboronic acid
(II), 18 mg (0.025 mmol, 0.05 equiv) of PdCl2(dppf),
and 318 mg (1.5 mmol, 3 equiv) of K3PO4 were added
under argon, and the mixture was stirred for 6 h at
80°C until initial compound I disappeared (TLC). The
mixture was cooled, diluted with 3 ml of water, and
extracted with methylene chloride (4×3 ml), the ex-
tracts were combined, dried over magnesium sulfate,
and evaporated, and the residue was subjected to col-
umn chromatography on silica gel. A fraction contain-
ing compound III was treated with hexane to isolate
56 mg (35%) of product III and a large amount of tars.
b. Compound I, 200 mg (0.5 mmol), was dissolved
in 3 ml of acetonitrile, 690 mg (0.65 mmol) of
o-tolylboronic acid (II), 18 mg (0.025 mmol) of
PdCl2(dppf), and 200 mg (1.5 mmol) of K2CO3 were
added under argon, and the mixture was stirred for 6 h
at 80°C (TLC). The mixture was cooled, diluted with
3 ml of water, and extracted with methylene chloride
(4×3 ml), the extracts were combined, dried, and evap-
orated. The residue was subjected to column chroma-
tography on silica gel, and a fraction containing the
product was ground with diethyl ether to isolate
108 mg (68%) of compound III and 26 mg (14%) of
unreacted oreoselone trifluoromethanesulfonate (I).
c. Compound I, 200 mg (0.5 mmol), was dissolved
in 3 ml of acetonitrile, 690 mg (0.65 mmol) of o-tolyl-
boronic acid (II), 18 mg (0.025 mmol) of PdCl2(dppf),
200 mg (1.5 mmol) of K2CO3, and 11 mg (10 mol %)
of Bu4N+Br– were added under argon, and the mixture
was stirred for 4.5 h at 80°C until initial compound I
disappeared (TLC). The mixture was cooled, diluted
with 3 ml of water, and extracted with CH2Cl2 (4×
3 ml), the extracts were combined, washed with water,
dried over magnesium sulfate, and evaporated, and the
residue was subjected to column chromatography on
silica gel. A fraction containing compound III was
treated with diethyl ether. Yield 119 mg (75%).
The structure of the newly synthesized compounds
was determined on the basis of their spectral param-
1
eters and elemental compositions. Their H and 13C
NMR spectra were fully consistent with the assumed
structures, and only one set of signals typical of the
furocoumarin fragment and the corresponding substit-
uent was present.
To conclude, Suzuki cross-coupling of oreoselone
trifluoromethanesulfonate with various aryl(hetaryl)-
boronic acids ensures preparation of 3-substituted furo-
coumarin (peucedanin) derivatives which attract inter-
est as potential pharmacologically active compounds.
EXPERIMENTAL
The NMR spectra were recorded on Bruker AV-300
1
(300.13 MHz for H and 75.47 MHz for 13C), AV-400
(400.13 MHz for 1H and 100.78 MHz for 13C), and AV-
600 spectrometers [600.30 for 1H and 150.96 MHz for
13C); the chemical shifts were measured relative to
residual proton and carbon signals of the solvent
(CHCl3, δ 7.24 ppm; CDCl3, δC 76.90 ppm). Multi-
plicity of signals in the 13C NMR spectra was deter-
mined using J modulation technique. Signals in the
NMR spectra of VIII, XI, XII, and XIV were assigned
on the basis of carbon–proton shift correlation spectra
(COXH, COLOC). The IR spectra were obtained in
KBr on a Bruker Vector-22 spectrometer. The UV
spectra were recorded on an HP 8453 UV Vis spectro-
photometer. The elemental compositions were deter-
mined using a Carlo Erba 1106 CHN analyzer.
The products were isolated by column chromatog-
raphy on silica gel (0.035–0.070 mm, Acros Organics)
using chloroform and chloroform–ethanol (50:3) as
eluents. The progress of reactions was monitored by
TLC on Silufol UV-254 plates; eluent chloroform or
chloroform–ethanol (50:2); detection under UV light
or by treatment with iodine vapor.
d. Compound I, 200 mg (0.5 mmol), was dissolved
in 3 ml of acetonitrile, 690 mg (0.65 mmol) of o-tolyl-
boronic acid (II) and 18 mg (0.025 mmol) of
Commercially available palladium complexes
PdCl2(dppf) and Pd(PPh3)4, arylboronic acids II, IV,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

PLANT COUMARINS: VIII.
1407
PdCl2(dppf) were added under argon, and 200 mg
(2 mmol, 4 equiv) of triethylamine was then added in
portions. The mixture was stirred for 6 h at 80°C,
cooled, diluted with 3 ml of water, and extracted with
methylene chloride (5×6 ml). The extracts were com-
bined, washed with water, dried over MgSO4, and
evaporated, and the residue was subjected to column
chromatography on silica gel. By treatment of the cor-
responding fraction with Et2O we isolated 20 mg
(22%) of unreacted initial compound I and 67 mg
(55%) of cross-coupling product III. Conversion 78%.
argon, and the mixture was stirred for 5 h at 80°C until
the initial compound disappeared (TLC). The mixture
was cooled, diluted with 3 ml of water, and extracted
with methylene chloride (4×5 ml), the extracts were
combined, dried over magnesium sulfate, and evap-
orated, and the residue was subjected to column chro-
matography on silica gel. A fraction containing the
product was treated with diethyl ether. Yield 187 mg
(71%), mp 131–133°C (from diethyl ether). IR spec-
trum, ν, cm–1: 3103, 3066, 3055, 2981, 2936, 2878,
1732, 1685, 1636, 1610, 1578, 1472, 1431, 1369,
1331, 1296, 1248, 1213, 1196, 1138, 1078, 1047,
1038, 930, 870, 837, 820, 764, 748, 678, 648. UV
spectrum (EtOH), λmax, nm (logε): 203 (4.43), 222
e. Compound I, 200 mg (0.5 mmol), was dissolved
in 3 ml of anhydrous dioxane, 690 mg (0.65 mmol) of
o-tolylboronic acid (II), 14 mg (0.025 mmol) of
Pd(PPh3)4, 200 mg (1.5 mmol) of K2CO3, and 11 mg
(10 mol %) of Bu4N+Br– were added under argon, and
the mixture was stirred for 6 h at 100°C until the initial
compound disappeared (TLC). The mixture was cooled,
diluted with 3 ml of water, and extracted with CH2Cl2
(4×3 ml), the extracts were combined, washed with
water, dried over MgSO4, and evaporated, and the
product was isolated by column chromatography on
silica gel, followed by treatment with diethyl ether.
Yield 110 mg (70%), mp 181–182°C (from Et2O). IR
spectrum, ν, cm–1: 3059, 3018, 2970, 2927, 2871,
1734, 1687, 1633, 1597, 1576, 1477, 1452, 1388,
1284, 1220, 1165, 1146, 1130, 1113, 1042, 1000, 960,
939, 881, 850, 825, 754, 729, 702. UV spectrum
(EtOH), λmax, nm (logε): 209 (4.44), 253 (4.21), 295
(3.82), 337 (3.53). 1H NMR spectrum (CDCl3), δ, ppm
(J, Hz): 1.38 d [6H, (CH3)2CH, J = 7], 2.04 s (3H,
CH3), 3.55 m [1H, CH(CH3)2], 6.23 d (1H, 6-H, J =
9.6), 7.12 s (1H, 9-H), 7.34 m (2H, 3′-H, 4′-H), 7.38 s
(1H, 4-H), 7.47 m (1H, 5′-H), 7.52 d (1H, 6′-H, J =
7.4), 7.68 d (1H, 5-H, J = 9.6). 13C NMR spectrum, δC,
ppm: 20.31 q [(CH3)2CH], 23.09 q (CH3), 25.91 d
[CH(CH3)2], 100.54 d (C9), 115.64 s (C3), 116.07 s
(C4a), 116.65 d (C6), 120.72 d (C4), 122.39 s (C3a),
125.24 d (C6′), 130.54 d (C5′), 131.05 d (C4′), 131.11 s
(C1′), 132.16 d (C3′), 133.54 s (C2′), 143.65 d (C5),
146.20 s and 150.82 s (C8a, C9a), 157.20 s (C2),
160.83 s (C7). Found, %: C 78.92; H 5.57.
m/z 318.1246 [M]+. C21H18O3. Calculated, %: C 79.22;
H 5.70. M 318.1251.
1
(4.18), 250 (4.27), 285 (3.75), 333 (3.62). H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 1.38 d [6H,
(CH3)2CH, J = 7], 3.55 m [1H, CH(CH3)2], 6.24 d (1H,
6-H, J = 9.6), 7.11 s (1H, 9-H), 7.46 d (1H, 3′-H, J =
8.4), 7.57 s (1H, 6′-H), 7.58 s (1H, 4-H), 7.68 d (1H,
5-H, J = 9.6), 7.90 d (1H, 4′-H, J = 8.4). 13C NMR
spectrum, δC, ppm: 20.34 q [(CH3)2CH], 25.96 d
[CH(CH3)2], 97.81 d (C9), 105.27 s (C3), 116.23 s
(C4a), 116.64 d (C6), 119.18 d (C4), 123.38 s (C3a),
124.20 q (CF3), 126.34 d (C4′), 129.02 d (C6′), 130.16 d
(C3′), 130.82 s (C5′), 134.33 s (C2′), 136.84 s (C1′),
143.66 d (C5), 151.35 s (C8a, C9a), 157.26 s (C2),
160.92 s (C7). Found, %: C 61.82; H 3.21; Cl 18.00;
F 13.52. C21H14ClF3O3. Calculated, %: C 62.00;
H 3.47; Cl 18.72; F 14.01.
3-(2-Aminophenyl)-2-isopropyl-7H-furo[3,2-g]-
chromen-7-one (VII). Compound I, 200 mg
(0.5 mmol), was dissolved in 3 ml of acetonitrile,
89 mg (0.65 mmol) of 2-aminophenylboronic acid (V),
18 mg (0.025 mmol) of PdCl2(dppf), 200 mg
(1.5 mmol) of K2CO3, and 11 mg (10 mol %) of
Bu4N+ Br– were added under argon, and the mixture
was stirred for 4.5 h at 80°C until the initial compound
disappeared (TLC), cooled, diluted with 3 ml of water,
and extracted with methylene chloride (4×3 ml), and
the extract was dried and evaporated. By column chro-
matography on silica gel using chloroform and chloro-
form–ethanol (50:2) as eluents we isolated 114 mg
(72%) of compound VII as an oily substance. IR spec-
trum, ν, cm–1: 3439, 3396, 3363, 3344, 3047, 3025,
2978, 2937, 2880, 1730, 1690, 1610, 1575, 1499,
1462, 1420, 1384, 1319, 1303, 1288, 1242, 1210,
1142, 1115, 1049, 1020, 860, 763, 756, 680, 654. UV
spectrum (EtOH), λmax, nm (logε): 208 (4.43), 245
3-[2-Chloro-5-(trifluoromethyl)phenyl]-2-isopro-
pyl-7H-furo[3,2-g]chromen-7-one (VI). Compound I,
200 mg (0.5 mmol), was dissolved in 3 ml of aceto-
nitrile, 145 mg (0.65 mmol) of 2-chloro-5-(trifluoro-
methyl)phenylboronic acid (IV), 18 mg (0.025 mmol)
of PdCl2(dppf), 200 mg (1.5 mmol) of K2CO3, and
11 mg (10 mol %) of Bu4N+ Br– were added under
1
(3.96), 304 (3.49), 353 (3.30). H NMR spectrum
(CDCl3–CD3OD), δ, ppm (J, Hz): 1.42 d [6H,
(CH3)2CH, J = 7.0], 3.38 m [1H, CH(CH3)2], 6.40 d
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

LIPEEVA et al.
1408
(1H, 6-H, J = 9.6), 6.78 m (3H, NH2, 3′-H), 6.90 m
(1H, 5′-H), 7.15 m (1H, 4′-H), 7.27 s (1H, 9-H),
7.68 m (1H, 6′-H), 7.89 s (1H, 4-H), 8.03 d (1H, 5-H,
J = 9.6). 13C NMR spectrum, δC, ppm: 19.88 q
[(CH3)2CH], 25.85 d [CH(CH3)2], 100.31 d (C9),
114.96 s (C3), 115.44 d (C3′), 115.78 d (C6), 116.19 s
(C4a), 116.78 s (C1′), 119.03 d (C5′), 120.02 d (C4),
121.43 s (C3a), 120.71 d (C6′), 128.96 d (C4′), 141.99 s
(C2′), 144.30 d (C5), 152.01 s (C8a), 153.03 s (C9a),
156.99 s (C2), 161.25 s (C7). Found, %: C 74.92;
H 5.12; N 4.21. C20H17NO3. Calculated, %: C 75.22;
H 5.37; N 4.39.
added under argon, and the mixture was stirred for 5 h
at 80°C until the initial compound disappeared (TLC).
The mixture was cooled, diluted with 3 ml of water,
and extracted with CH2Cl2 (4×5 ml). The extract was
washed with water, dried over MgSO4, and evaporated,
the residue was subjected to column chromatography
on silica gel using chloroform and chloroform–ethanol
(50:2) as eluents, and a fraction containing the product
was treated with diethyl ether. Yield 89 mg (58%),
mp 160–163°C (from diethyl ether). IR spectrum, ν,
cm–1: 3105, 2981, 2837, 1732, 1635, 1576, 1485, 1429,
1389, 1346, 1311, 1290, 1250, 1195, 1140, 1116, 1084,
1049, 1009, 960, 906, 869, 819, 758, 695, 650. UV
spectrum (CHCl3–EtOH, 3:1), λmax, nm (logε): 242
3-[(2-Acetylamino)phenyl]-2-isopropyl-7H-furo-
[3,2-g]chromen-7-one (VIII). Acetic anhydride,
0.066 ml (0.7 mmol), was added dropwise under stir-
ring to a solution of 150 mg (0.47 mmol) of compound
VII in 3 ml of pyridine, and the mixture was left to
stand for 3 h at room temperature, treated with a solu-
tion of ammonia to pH 7–8, and extracted with
CH2Cl2. The extract was evaporated, the residue was
treated with a 10% solution of H2SO4 and extracted
with CH2Cl2 (5×10 ml), and the extracts were com-
bined, washed with water, dried over MgSO4, and
evaporated. The product was purified by recrystalliza-
tion from diethyl ether. Yield 110 mg (65%), mp 123–
125°C (from Et2O). IR spectrum, ν, cm–1 : 3436, 3396,
3052, 3022, 2981, 2883, 1730, 1710, 1650, 1610,
1576, 1494, 1464, 1421, 1386, 1319, 1248, 1211,
1142, 1100, 1049, 1000, 960, 866, 822, 760, 700, 656.
UV spectrum (EtOH), λmax, nm (logε): 210 (4.58), 245
1
(4.32), 287 (3.77), 297 (3.76), 338 (3.67). H NMR
spectrum (CDCl3), δ, ppm (J, Hz): 1.39 d [6H,
(CH3)2CH, J = 6.9], 3.54 m [1H, CH(CH3)2], 6.20 d.d
(1H, 3′-H, J = 3.4, 0.8 ), 6.25 d (1H, 6-H, J = 9.6),
6.38 d.d (1H, 4′-H, J = 3.4, 1.6), 7.14 s (1H, 4-H),
7.46 d (1H, 5′-H, J = 1.6, 0.8), 7.58 s (1H, 4-H), 7.68 d
(1H, 5-H, J = 9.6). 13C NMR spectrum, δC, ppm:
20.75 q [(CH3)2CH], 25.87 d [CH(CH3)2], 100.38 d
(C9), 103.66 d (C3′), 108.92 d (C4′), 112.30 s (C3),
114.55 s (C4a), 114.91 d (C6), 122.44 s (C3a), 124.85 d
(C4), 142.93 d (C5′), 145.19 d (C5), 151.67 s (C8a),
152.77 s (C9a), 158.51 d (C2′), 159.96 s (C2), 160.86 s
(C7). Found, %: C 72.98; H 4.49. C18H14O4. Calculat-
ed, %: C 73.46; H 4.79.
3-(Furan-3-yl)-2-isopropyl-7H-furo[3,2-g]chro-
men-7-one (XII). Compound I, 200 mg (0.5 mmol),
was dissolved in 3 ml of acetonitrile, 76 mg
(0.65 mmol) of furan-3-ylboronic acid (X), 18 mg
(0.025 mmol) of PdCl2(dppf), 200 mg (1.5 mmol) of
K2CO3, and 11 mg (10 mol %) of Bu4N+ Br– were
added under argon, and the mixture was stirred for
4.5 h at 80°C until the initial compound disappeared
(TLC). The mixture was cooled, diluted with 3 ml of
water, and extracted with CH2Cl2 (4×5 ml). The
extract was washed with water, dried over MgSO4, and
evaporated, the residue was subjected to column
chromatography on silica gel using chloroform and
chloroform–ethanol (50:2) as eluents, and a fraction
containing the product was treated with diethyl ether.
Yield 102 mg (67%), mp 132–133°C (from Et2O). IR
spectrum, ν, cm–1: 3130, 3067, 3049, 2981, 1732,
1718, 1634, 1564, 1504, 1468, 1431, 1410, 1387,
1371, 1362, 1350, 1288, 1213, 1198, 1140, 1114, 1068,
1047, 1020, 934, 905, 878, 820, 781, 748, 744, 700,
681. UV spectrum (CHCl3–EtOH, 3:1), λmax, nm
(logε): 252 (4.26), 288 (3.83), 295 (3.76), 334 (3.63).
1H NMR spectrum (CDCl3–CD3OD), δ, ppm (J, Hz):
1
(4.33), 249 (4.33), 295 (3.83), 320 (3.77). H NMR
spectrum (CDCl3–CD3OD), δ, ppm (J, Hz): 1.36 d
[6H, (CH3)2CH, J = 6.9], 2.09 s (COCH3), 3.25 m [1H,
CH(CH3)2], 6.40 d (1H, 6-H, J = 9.4), 7.05 m (1H,
5′-H), 7.24 s (1H, 9-H), 7.25 m (1H, 4-H), 7.45 m (2H,
3′-H, 6′-H), 7.63 s (1H, 4-H), 7.90 d (1H, 5-H, J =
9.5). 13C NMR spectrum, δC, ppm: 19.60 q
[(CH3)2CH], 19.65 q (COCH3), 22.94 d [CH(CH3)2],
100.04 d (C9), 114.68 s (C3), 115.68 d (C6), 116.02 s
(C4a), 117.42 d (C3′), 118.94 d (C6′), 120.33 d (C4),
119.66 d (C5′), 121.19 s (C3a), 123.64 s (C1′), 128.25 s
(C4′), 138.07 s (C2′, 143.91 d (C5), 151.75 s (C8a),
152.94 s (C9a), 156.77 s (C2), 160.70 s (C7), 169.76 s
(NHC=O). Found, %: C 72.92; H 5.18; N 3.93.
C22H19NO4. Calculated, %: C 73.12; H 5.30; N 3.88.
3-(Furan-2-yl)-2-isopropyl-7H-furo[3,2-g]chro-
men-7-one (XI). Compound I, 200 mg (0.5 mmol),
was dissolved in 3 ml of acetonitrile, 76 mg
(0.65 mmol) of furan-2-ylboronic acid (IX), 18 mg
(0.025 mmol) of PdCl2(dppf), 200 mg (1.5 mmol) of
K2CO3, and 11 mg (10 mol %) of Bu4N+ Br– were
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011

PLANT COUMARINS: VIII.
1409
1.39 d [6H, (CH3)2CH, J = 6.9], 3.31 m [1H,
CH(CH3)2], 6.26 d (1H, 6-H, J = 9.6), 6.37 br.s (2H,
9-H, 4′-H), 7.29 br.s (1H, 5′-H), 7.48 s (1H, 4-H),
7.54 br.s (1H, 2′-H), 7.77 d (1H, 5-H, J = 9.6).
13C NMR spectrum, δC, ppm: 19.85 q [(CH3)2CH],
25.81 d [CH(CH3)2], 100.28 d (C9), 112.71 d (C4′),
113.24 s (C3), 114.95 d (C6), 116.18 s (C4a), 116.71 d
(C4), 117.27 s (C3a), 126.07 s (C3′), 142.35 d (C2′),
144.17 d (C5), 149.76 d (C5′), 151.97 s (C8a), 152.97 s
(C9a), 156.99 s (C2), 161.11 s (C7). Found, %: C 73.28;
H 4.92. C18H14O4. Calculated, %: C 73.46; H 4.79.
137.32 s (C5′), 144.03 d (C5), 151.78 s (C8a), 152.86 s
(C9a), 156.81 s (C2), 161.14 s (C7). Found, %: C 76.69;
H 5.21; N 4.14. C22H17NO3. Calculated, %: C 76.95;
H 4.99; N 4.08.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 11-03-00 242-a) and by the President of the
Russian Federation (program for support of leading
scientific schools, project no. NSh 7005.2010.03).
REFERENCES
3-(1H-Indol-5-yl)-2-isopropyl-7H-furo[3,2-g]-
chromen-7-one (XIV). a. Compound I, 200 mg
(0.5 mmol), was dissolved in 3 ml of acetonitrile,
104 mg (0.65 mmol) of 1H-indol-5-ylboronic acid
(XIII), 18 mg (0.025 mmol) of PdCl2(dppf), 200 mg
(1.5 mmol) of K2CO3, and 11 mg (10 mol %) of
Bu4N+Br– were added, and the mixture was stirred for
6 h at 80°C until the initial compound disappeared
(TLC). The mixture was cooled, diluted with 3 ml of
water, and extracted with CH2Cl2 (3×4 ml), the ex-
tracts were combined, dried over MgSO4, and evap-
orated, and the product was isolated by column chro-
matography on silica gel, followed by treatment of the
corresponding fraction with Et2O. Yield 72 mg (42%).
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1732, 1718, 1689, 1634, 1610, 1578, 1514, 1471,
1433, 1412, 1337, 1310, 1248, 1211, 1196, 1136, 1094,
1047, 1029, 980, 902, 892, 870, 820, 735, 679. UV
spectrum (EtOH), λmax, nm (log ε): 203 (4.42), 228
(4.72), 250 (4.11), 261 (3.96), 277 (3.92), 281 (3.92),
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1
331 (3.32). H NMR spectrum (CDCl3–CD3OD), δ,
ppm (J, Hz): 1.40 d [6H, (CH3)2CH, J = 7.0], 3.31 m
[1H, CH(CH3)2], 6.39 d (1H, 6-H, J = 9.6), 6.46 d (1H,
3′-H, J = 2.6 ), 7.22 s (1H, 9-H), 7.36 d (1H, 2′-H, J =
2.6), 7.46 d (1H, 7′-H, J = 7.8), 7.54 d (1H, 6′-H, J =
7.8), 7.61 s (1H, 4-H), 7.76 d (1H, 5-H, J = 9.6),
7.82 br.s (1H, 4′-H), 8.01 br.s (1H, NH). 13C NMR
spectrum, δC, ppm: 19.85 q [(CH3)2CH], 25.73 d
[CH(CH3)2], 100.13 d (C9), 101.65 d (C3′), 110.22 d
(C7′), 110.34 s (C3), 114.75 d (C6), 115.84 s (C4a),
116.50 d (C4), 118.80 d (C5′), 119.94 s (C3a), 126.24 d
(C6′), 124.02 d (C2′), 126.32 s (C3a′), 126.56 s (C7a′),
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2011, vol. 47, p. 1083.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 47 No. 9 2011