Plant coumarins: XI. Cross coupling reactions with 2-(tosyl)oreoselone

Article abstract of DOI:10.1134/S107042801301017X

The reaction of a linearly fused furocoumarin, oreoselone, with p-toluenesulfonyl chloride gave 2-tosyloreoselone which showed a high reactivity in palladium-catalyzed cross-coupling reactions with formation of a new carbon-carbon bond. 2-Tosyloreoselone reacted with terminal alkynes in the presence of Pd(PPh₃)₂Cl₂ to give the corresponding 2-alkynylfuro[3,2-g]chromen-3-ones. 2-Aryl(hetaryl) alkynyloreoselones were obtained in high yield directly by palladium-catalyzed reaction of oreoselone with tosyl chloride and aryl(hetaryl)acetylenes. The reaction of 2-tosyloreoselone with aryl(hetaryl)boronic acids in the presence of palladium complexes with uni- and bidentate ligands, tetrabutylammonium bromide, and a base afforded 2-aryl(hetaryl)-substituted oreoselones. 2-Vinyloreoselone was synthesized from 2-tosyloreoselone and potassium trifluoro(vinyl)borate.

Full text of DOI:10.1134/S107042801301017X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2013, Vol. 49, No. 1, pp. 99–107. © Pleiades Publishing, Ltd., 2013.
Original Russian Text © A.B. Lipeeva, E.E. Shul’ts, M.M. Shakirov, G.A. Tolstikov, 2013, published in Zhurnal Organicheskoi Khimii, 2013, Vol. 49, No. 1,
pp. 105–112.
Plant Coumarins: XI.* Cross Coupling Reactions
with 2-(Tosyl)oreoselone
A. B. Lipeeva, E. E. Shul’ts, M. M. Shakirov, and G. A. Tolstikov
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences,
pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia
e-mail: schultz@nioch.nsc.ru
Received July 26, 2012
Abstract—The reaction of a linearly fused furocoumarin, oreoselone, with p-toluenesulfonyl chloride gave
2-tosyloreoselone which showed a high reactivity in palladium-catalyzed cross-coupling reactions with forma-
tion of a new carbon–carbon bond. 2-Tosyloreoselone reacted with terminal alkynes in the presence of
Pd(PPh3)2Cl2 to give the corresponding 2-alkynylfuro[3,2-g]chromen-3-ones. 2-Aryl(hetaryl)alkynyloreo-
selones were obtained in high yield directly by palladium-catalyzed reaction of oreoselone with tosyl chloride
and aryl(hetaryl)acetylenes. The reaction of 2-tosyloreoselone with aryl(hetaryl)boronic acids in the presence
of palladium complexes with uni- and bidentate ligands, tetrabutylammonium bromide, and a base afforded
2-aryl(hetaryl)-substituted oreoselones. 2-Vinyloreoselone was synthesized from 2-tosyloreoselone and potas-
sium trifluoro(vinyl)borate.
DOI: 10.1134/S107042801301017X
pounds IV–VI by palladium-catalyzed reactions [2–4]
(Scheme 1).
While studying transformations of peucedanin (I,
2-isopropyl-3-methoxy-7H-furo[3,2-g]chromen-7-one)
in the presence of metal complex catalysts, we found
that oreoselone trifluoromethanesulfonate II prepared
from peucedanin (I) through intermediate oreoselone
(III) can be involved in the Heck, Suzuki, and amina-
tion reactions. We succeeded in synthesizing com-
By reaction of oreoselone (III) with p-toluenesul-
fonyl chloride we obtained 2-tosyloreoselone (VIII)
instead of expected 3-tosyloxy derivative VII. The
highest yield of VIII (87%) was attained when a mix-
ture of III, TsCl (1.2 equiv), and Et3N (1.3 equiv) was
Scheme 1.
MeO
O
TfO
Me
Me
Me
Me
Me
Me
HCl, MeOH
Tf2O, pyridine
O
O
O
O
O
O
O
O
O
I
III
II
Me
N
Me
S
H
H
N
COOMe
Ar
HN
Me
Me
O
Pr-i
O
O
O
Me
Me
O
O
O
O
O
O
IV
V
VI
* For communication X, see [1].
99

LIPEEVA et al.
100
Scheme 2.
TsO
Me
i
O
O
Me
Me
O
O
Me
Me
VII
O
O
Me
O
O
O
Me
Me
i, ii
III
+
Ts
O
O
O
O
O
O
VIII
IX
O
Me
iii, iv
Me
III + R–C CH
≡
O
O
O
R
XII, XIII, XV, XVII
v
vi
VIII
+
X, XI
XII, XIII
VIII
+
XVI
XVII
X, XII, R = Ph; XI, XIII, R = pyridin-2-yl; XIV, XV, R = 4-MeOC6H4; XVI, XVII, R = Me3Si. i: TsCl, Et3N, THF, 60°C, 4 h;
ii: TsCl, Pd(PPh3)2Cl2, THF, 60°C, 5 h; iii: (1) TsCl, Pd(PPh3)2Cl2, THF, 60°C, 5 h; (2) Et3N, X or XI, THF, 60ºC, 5–7 h; iv: TsCl,
Pd(PPh3)2Cl2, (i-Pr)2NEt, THF, 60ºC, 5 h; v: Pd(PPh3)2Cl2, Et3N, THF, 60ºC, 7 h; vi: Pd(PPh3)2Cl2, CuI, THF, 60ºC, 7 h.
heated in boiling THF. In addition, we isolated previ-
ously described 2-(propan-2-ylidene)-7H-furo[3,2-g]-
chromene-3,7(2H)-dione (IX) [5–7]; presumably, the
latter was formed as a result of elimination of
p-toluenesulfonic acid molecule from compound VIII
(Scheme 2).
as a convenient method for the preparation of 2-aryl-
ethynylfurocoumarines XII, XIII, and XV. Cross cou-
pling of alkynes with 2-tosyloreoselone (VIII) requires
no copper(I) iodide which is commonly used in the
Sonogashira reactions. A successful example of direct
cross coupling of alkynes with 4-hydroxycoumarins in
the presence of TsCl but without copper iodide was
described in [8].
2-Tosyloreoselone (VIII) turned out to be a reactive
substrate in C–C bond formation processes. It reacted
with phenylacetylene (X) and (pyridin-2-yl)acetylene
(XI) in THF in the presence of Pd(PPh3)2Cl2 (5 mol %)
and Et3N (1.3 equiv) to produce [2-2-phenyl(pyridin-
2-yl)ethynyl]furocoumarins XII and XIII (yield 62–
70%) and compound IX as by-product. It was interest-
ing to perform direct Pd-catalyzed cross coupling of
oreoselone (III) with terminal acetylenes using tosyl
chloride as activator. In fact, by reactions of oreoselone
(III) with tosyl chloride (1.2 equiv) and aryl(hetaryl)-
alkynes X, XI, and XIV in the presence of
Pd(PPh3)2Cl2 (5 mol %) and Et3N (1.3 equiv) in THF
we obtained alkynyl-substituted dioxofurocoumarins
XII, XIII, and XV in 72–88% yield.
In the reaction of III with trimethylsilylacetylene
(XVI) in the presence of TsCl, the corresponding
ethynyl derivative XVII was isolated in a poor yield
(22%), whereas the major product was 2-tosyloreo-
selone (VIII). The reaction of VIII with alkyne XVI in
the presence of CuI gave 52% of XVII.
Thus we have proposed a procedure for the direct
ethynylation of oreoselone at C2. Taking into account
synthetic potential of β-oxo acetylene derivatives, the
obtained products may be promising as precursors of
various heteropolycyclic structures [9].
It should be noted that cross coupling reactions of
compounds activated by sulfonylation have attracted
considerable attention in recent time. Successful
migration of endocyclic double bond to exo position in
palladium-catalyzed desulfonation of allyl sulfones
was reported in [10], facile aminospirocyclization of
tertiary allyl sulfones in the presence of palladium(0)
compounds was described in [11], and a procedure for
The use of ethyl(diisopropyl)amine (Hunig’s base)
in the reaction of III with TsCl and 4-methoxyphenyl-
acetylene (XIV) afforded compound XV in up to 75%
yield. Thus, the direct cross coupling of oreoselone
(III) with aryl(hetaryl)acetylenes and tosyl chloride
occurs under mild conditions, and it may be regarded
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 1 2013

PLANT COUMARINS: XI.
101
Scheme 3.
O
Me
B(OH)2
R
i, ii
Me
Me
III +
O
O
O
R
XVIII, XX
B(OH)2
XIX, XXIII
O
ii
Me
O
III +
+
IX
O
O
O
O
XXI
XXIV
O
O
Me
Me
B(OH)2
ii
HBr
Me
Me
III +
N
Br–
O
O
O
O
O
O
N
NH
XXII
XXV
XXVa
O
Me
iii, iv
Me
2'
H2C
BF3 K+
VIII
+
+
IX
H2C
O
O
O
1'
XXVI
XXVII
iii
VIII
+ XVIII
XIX
i: TsCl, Pd(PPh3)4, K2CO3, Bu4N+ Br–, THF, 60°C; ii: TsCl, PdCl2(dppf), K2CO3, Bu4N+ Br–, MeCN, 80°C; iii: PdCl2(dppf), K2CO3,
Bu4N+ Br–, MeCN, 80°C; iv: Pd(OAc)2, dioxane, 100°C.
cross coupling of Grignard reagents with sulfonyl-
activated sp3-carbon–nitrogen bonds in the presence of
copper salts was proposed [12].
reactions of III with 2-methylphenylboronic acid
(XX), furan-3-ylboronic acid (XXI), and pyridin-4-yl-
boronic acid (XXII) in acetonitrile in the presence of
tosyl chloride, PdCl2(dppf), K2CO3, and (Bu)4N+ Br–
afforded the corresponding 2-substituted furocouma-
rins XXIII–XXV (yield 80, 57, and 46%, respectively)
through intermediate formation of sulfonyl ketone
VIII. Compound XXV was isolated as hydrobromide
XXVa. In addition, 2-isopropylidene derivative IX was
isolated in 28 and 38% yield, respectively, in the reac-
tions of III with hetarylboronic acids XXI and XXII.
We were interested in performing cross coupling of
oreoselone (III) with aryl(hetaryl)boronic acids in the
presence of tosyl chloride as activator. Direct reactions
of phenols and heteroaromatic compounds with aryl-
boronic acids via activation of the C–OH bond by
various compounds, including tosyl chloride, were
described in some publications [13]. The reaction of
III with TsCl and phenylboronic acid (XVIII) in THF
in the presence of Pd(PPh3)4 (which is widely used
in the Suzuki cross couplings), K2CO3 (3 equiv), and
Bu4N+ Br– (10 mol %) at 60°C led to the formation of
45% of 2-isopropyl-2-phenylfurocoumarin (XIX)
(Scheme 3). When the reaction was carried out in
acetonitrile using PdCl2(dppf) as catalyst (80°C), the
yield of XIX increased to 78%. Compound XIX was
also formed in 76% yield in the reaction of VIII with
phenylboronic acid (XVIII) in acetonitrile in the
presence of PdCl2(dppf), K2CO3, and (Bu)4N+ Br–. The
With a view to introduce a vinyl substituent into the
2-position of furocoumarins we examined the reaction
of VIII with potassium trifluoro(vinyl)borate (XXVI)
which showed high reactivity in cross couplings with
aryl halides and trifluoromethanesulfonates [14, 15].
2-Vinyl derivative XXVII was isolated in 19% yield in
the Pd(OAc)2-catalyzed reaction of VIII with potas-
sium salt XXVI in dioxane, whereas the cross-cou-
pling in the presence of PdCl2(dppf) [15] quantitatively
produced compound IX (Scheme 3).
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LIPEEVA et al.
102
The structure of the isolated compounds was deter-
izer temperature 240°C), and the molecular weights
and elemental compositions were determined from the
high-resolution mass spectra.
mined on the basis of their spectral parameters. Their
1H and 13C NMR spectra contained only one set of
signals typical of the furocoumarin skeleton and the
corresponding substituent. Compound VIII displayed
in the 13C NMR spectrum a signal at δC 190.39 ppm
due to C3 carbonyl carbon atom. In the mass spectrum
of VIII we observed the molecular ion peak, ion peak
with m/z 243 [M – 4-MeC6H4SO2], and fragment ion
peaks with m/z 229, 202, 189, and 188, the latter being
characteristic of oreoselone fragmentation [16]. The
formation of alkynylfurocoumarins XII, XIII, XV, and
XVII was also confirmed by the IR spectra which
contained strong absorption bands at 2216–2251 and
2068–2195 cm–1.
Elemental analyses were obtained on a Carlo Erba
1106 CHN analyzer. The molecular weight of XXVa
was determined with the aid of a Knauer vapor pres-
sure osmometer. The products were isolated by column
chromatography on silica gel (Acros, 0.035–
0.070 mm) using chloroform and chloroform–ethanol
(50:2) as eluents. The progress of reactions was moni-
tored by TLC on Silufol UV-254 plates (chloroform–
ethanol, 50:2; detection under UV light or by treat-
ment with iodine vapor).
2-Ethynylpyridine (XI), 4-ethynyl-1-methoxyben-
zene (XIV), trimethylsilylacetylene (XVI), aryl-
(hetaryl)boronic acids XVIII and XX–XXII, and
PdCl2(dppf) were commercial products (Alfa Aesar);
Pd(PPh3)4 was synthesized as described in [17]. The
solvents (acetonitrile and tetrahydrofuran) and triethyl-
amine were purified according to standard procedures
and were distilled in a stream of argon just before use.
Oreoselone (III) was synthesized from peucedanin (I)
as reported in [6].
1
In the H NMR spectrum of XXVII, protons in
the vinyl group resonated at δ 4.97 (2H, CH2=) and
5.39 ppm (1H, CH=). Signals from the corresponding
carbon atoms were located in the JMOD 13C NMR
spectrum at δC 120.95 (t, C2′) and 139.72 ppm (d, C1′).
Thus modification of oreoselone via palladium-
catalyzed cross coupling of its 2-tosyl derivative gives
rise to various 2-substituted furocoumarins which
attract interest as potentially pharmacologically active
compounds.
2-Isopropyl-2-(4-methylphenylsulfonyl)-2H-furo-
[3,2-g]chromene-3,7-dione (VIII). a. p-Toluenesul-
fonyl chloride, 0.456 g (2.4 mmol), and triethylamine,
0.26 g (2.6 mmol), were added at 20°C under argon to
a solution of 0.5 g (2 mmol) of oreoselone (III) in 3 ml
of THF. The mixture was heated for 4 h under reflux
(TLC) and cooled, 5 ml of water was added, the mix-
ture was extracted with methylene chloride (4×5 ml),
the extract was dried over MgSO4 and evaporated, and
the residue was recrystallized from ethanol to isolate
0.69 g (87%) of VIII and traces of IX.
EXPERIMENTAL**
The NMR spectra were recorded from solutions in
1
CDCl3 on Bruker AV-300 (300.13 MHz for H and
1
75.47 MHz for 13C), AV-400 (400.13 MHz for H and
100.78 MHz for 13C), and AV-600 spectrometers
1
(600.30 MHz for H and 150.96 MHz for 13C). The
chemical shifts were measured relative to the residual
proton signal and carbon signal of the solvent (δ 7.24,
δC 76.90 ppm). Signal multiplicity in the 13C NMR
spectra was determined by recording the J modulation
spectra. The IR spectra were obtained on a Bruker
Vector-22 instrument from samples prepared as KBr
pellets. The UV spectra were measured on an HP 8453
UV Vis spectrophotometer. The melting points were
determined using a Stuart SMF-38 melting point
apparatus. The optical rotations [α]D20 were measured
from solutions in chloroform on a PolAAr3005
polarimeter.
b. p-Toluenesulfonyl chloride, 0.47 g (2.5 mmol),
and Pd(PPh3)Cl2, 0.07 g (0.1 mmol), were added to
a solution of 0.5 g (2 mmol) of III in 3 ml of anhy-
drous THF. The mixture was heated for 5 h under
reflux and cooled, 5 ml of water was added, and the
mixture was treated as described above in a to isolate
0.35 g (44%) of VIII and 0.058 g (12%) of IX.
Compound VIII. [α]D20 = –8.8° (c = 0.5, CHCl3),
mp 91–92°C (from EtOH). IR spectrum, ν, cm–1: 3119,
3047, 2974, 2935, 2854, 1736, 1702, 1628, 1585,
1473, 1390, 1356, 1286, 1195, 1121, 1100, 1034, 1011,
972, 912, 866, 827, 756, 741, 698, 681. UV spectrum
(EtOH), λmax, nm (logε): 200 (4.38), 220 (4.23), 258
The mass spectra were recorded on a DFS Thermo
Scientific high-resolution mass-spectrometer (vapor-
1
(4.38), 305 (3.88), 347 (3.86). H NMR spectrum, δ,
** Analytical and spectral studies were performed at the Shared
Chemical Service Center, Siberian Division, Russian Academy
of Sciences.
ppm (J, Hz): 0.81 d and 0.95 d [3H each, (CH3)2CH,
J = 7], 2.26 s (3H, CH3), 2.92 m [1H, (CH3)2CH],
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 1 2013

PLANT COUMARINS: XI.
103
6.33 d (1H, 6-H, J = 9.4), 7.08 d (2H, 3′-H, 5′-H),
7.39 s (1H, 9-H), 7.63 d (2H, 2′-H, 6′-H), 7.80 d (1H,
5-H, J = 9.4), 7.96 s (1H, 4-H). 13C NMR spectrum,
δC, ppm: 14.51 q and 16.12 q [(CH3)2CH], 21.26 d
[(CH3)2CH], 36.83 q (CH3), 100.30 s (C2), 102.78 d
(C9), 114.84 s (C4a), 115.79 d (C6), 117.03 s (C3a),
124.42 s (C1′), 125.86 d (C2′, C6′), 126.58 d (C4),
128.58 d (C3′, C5′), 139.24 s (C4′), 143.43 d (C5),
158.31 s (C9a), 161.84 s (C8a), 170.89 s (C7), 190.39 s
(C3). Mass spectrum, m/z (Irel, %): 398 (2), 359 (5),
344 (15), 316 (22), 290 (17), 244 (12), 243 (55), 242
(11), 229 (28), 202 (21), 189 (30), 188 (64), 160 (19),
144 (34), 116 (86), 102 (100), 85 (35), 83 (54), 76
(22). Found: m/z 398.0820 [M]+. C21H18O6S. Calculat-
ed: M 398.0814.
Compound XII. [α]D20 = +6° (c = 0.5, CHCl3),
mp 95–96°C (from EtOH). IR spectrum, ν, cm–1: 3078,
3061, 3050, 2962, 2926, 2874, 2854, 2216, 2195,
1742, 1726, 1713, 1626, 1597, 1576, 1485, 1441,
1392, 1355, 1317, 1302, 1178, 1141, 1121, 1105, 1090,
1070, 1045, 1026, 935, 914, 881, 826, 814, 756, 723,
688. UV spectrum (EtOH), λmax, nm (logε): 251 (4.39),
291 (4.20), 309 (4.28), 330 (4.22), 354 (3.72).
1H NMR spectrum, δ, ppm (J, Hz): 0.82 d and 1.12 d
[3H each, (CH3)2CH, J = 7], 2.29 m [1H, (CH3)2CH],
6.24 d (1H, 6-H, J = 9.4), 6.92 s (1H, 9-H), 7.33 m
(3H, 2′-H, 4′-H, 6′-H), 7.43 m (2H, 3′-H, 5′-H), 7.61 d
(1H, 5-H, J = 9.4), 7.71 s (1H, 4-H). 13C NMR spec-
trum, δC, ppm: 15.83 q and 19.01 q [(CH3)2CH],
31.25 d [(CH3)2CH], 74.02 s (C1a), 81.39 s (C1b),
91.13 s (C2), 101.06 d (C9), 114.29 d (C2′, C6′),
114.78 d (C6), 115.61 s (C4a), 117.87 s (C3a), 119.36 d
(C4′), 124.50 d (C4), 130.49 d (C1′), 134.19 d (C3′, C5′),
143.89 d (C5), 159.61 s (C9a), 161.14 s (C8a), 172.56 s
(C7), 199.66 s (C3). Mass spectrum, m/z (Irel, %): 345
(2), 344 (15), 278 (4), 277 (5), 263 (18), 262 (100),
247 (67), 243 (28), 229 (36), 202 (95), 189 (27),
188 (21), 174 (8), 160 (11), 155 (18), 91 (32), 88
(10). Found, %: C 76.39; N 4.38. m/z 344.1000
[M]+. C22H16O4. Calculated, %: C 76.73; H 4.68.
M 344.1020.
2-Isopropyl-2-(phenylethynyl)-2H-furo[3,2-g]-
chromene-3,7-dione (XII). a. A mixture of 0.6 g of
compound VIII, 0.4 g of phenylacetylene (X), 0.42 g
of triethylamine, and 0.07 g of Pd(PPh3)Cl2 in 5 ml of
anhydrous THF was heated for 7 h under reflux in
a stream of argon. The mixture was evaporated, the
residue was treated with 10 ml of water and extracted
with methylene chloride (4×5 ml), the combined
extracts were dried over MgSO4 and evaporated, and
the residue was subjected to column chromatography
on silica gel to isolate 0.32 g (62%) of XII and 0.09 g
(26%) of IX.
2-Isopropyl-2-(pyridin-2-ylethynyl)-2H-furo-
[3,2-g]chromene-3,7-dione (XIII). a. The reaction of
0.5 g of oreoselone (III) with 0.47 g of tosyl chloride
and 0.42 g of 2-ethynylpyridine (XI) in the presence of
0.42 g of triethylamine and 0.07 g of Pd(PPh3)Cl2
(60°C, 5 h) gave 0.48 g (70%) of XIII.
b. A solution of 0.5 g (2 mmol) of oreoselone (III),
0.47 g (2.5 mmol) of tosyl chloride, and 0.07 g
(0.1 mmol) of Pd(PPh3)Cl2 in 5 ml of anhydrous THF
was heated for 5 h at 60°C under argon, 0.40 g
(2 equiv) of phenylacetylene (X), 0.42 g (3 equiv) of
triethylamine, and 0.07 g of Pd(PPh3)Cl2 in 5 ml of
THF were added, and the mixture was heated for 7 h
more at 60°C until the initial compound disappeared
(TLC). The mixture was treated with 10 ml of water
and extracted with methylene chloride (4×5 ml), the
combined extracts were dried over MgSO4 and evap-
orated, and the residue was subjected to column chro-
matography on silica gel. The solvent was distilled off
from the eluate, and the residue was recrystallized
from ethanol. Yield 0.49 g (72%).
b. A mixture of 0.6 g (1.5 mmol) of 2-tosyloreo-
selone (VIII), 0.3 g (2.9 mmol) of 2-ethynylpyridine
(XI), 0.42 g of triethylamine, and 0.07 g of
Pd(PPh3)Cl2 in THF was heated for 7 h under reflux
in a stream of argon. The mixture was evaporated and
treated with 10 ml of water, and the subsequent extrac-
tion followed by column chromatography on silica gel
gave 0.49 g (72%) of XIII. mp 105–106°C (from
EtOH). IR spectrum, ν, cm–1: 3433, 3064, 3041, 2964,
2931, 2989, 2875, 2185, 1739, 1726, 1710, 1629,
1575, 1485, 1469, 1394, 1355, 1334, 1303, 1247,
1155, 1143, 1105, 1045, 975, 935, 881, 844, 831, 813,
744. UV spectrum (EtOH), λmax, nm (logε): 193 (3.98),
209 (4.24), 221 (4.28), 251 (4.54), 295 (4.07), 306
c. A solution of 0.5 g (2 mmol) of oreoselone (III),
0.47 g (2.5 mmol) of tosyl chloride, and 0.07 g
(0.1 mmol) of Pd(PPh3)Cl2 in 5 ml of anhydrous THF
was heated for 5 h at 60°C under argon, 2 equiv of
phenylacetylene (X) and 0.62 g (3 equiv) of ethyl-
(diisopropyl)amine were added, and the mixture was
heated for 5 h until the initial compound disappeared
(TLC) and treated as described above in b.
1
(4.05), 343 (4.19), 351 (4.21). H NMR spectrum, δ,
ppm (J, Hz): 0.82 d and 1.09 d [3H each, (CH3)2CH,
J = 7], 2.31 m [1H, (CH3)2CH], 6.26 d (1H, 6-H, J =
9.4), 6.94 s (1H, 9-H), 7.20 m (1H, 4′-H), 7.42 d (1H,
2′-H), 7.59 m (1H, 3′-H), 7.68 d (1H, 5-H, J = 9.4),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 1 2013

LIPEEVA et al.
104
7.74 s (1H, 4-H), 8.52 d (1H, 5′-H). 13C NMR spec-
trum, δC, ppm: 15.38 q and 18.32 q [(CH3)2CH],
30.76 d [(CH3)2CH], 76.43 s (C1a), 82.26 s (C1b),
90.64 s (C2), 100.53 d (C9), 114.12 d (C6), 118.92 s
(C4a), 119.53 s (C3a), 123.15 d (C4′), 124.07 d (C4),
127.19 d (C2′), 135.94 d (C3′), 141.99 s (C1′), 143.29 d
(C5), 149.67 d (C5′), 159.18 s (C8a), 160.67 s (C9a),
173.55 s (C7), 199.11 s (C3). Found, %: C 73.53;
H 4.28; N 4.00. C21H15NO4. Calculated, %: C 73.03;
H 4.38; N 4.06.
heated for 7 h at 60°C (TLC), and the mixture was
treated as described above for compound XII (method
a). Yield 0.39 g (52%), [α]D20 = +4° (c = 0.5, CHCl3),
mp 98–99°C (from EtOH). IR spectrum, ν, cm–1: 3062,
3044, 2966, 2930, 2876, 2854, 2210, 2068, 1738,
1726, 1711, 1628, 1600, 1578, 1485, 1468, 1387,
1354, 1335, 1285, 1250, 1190, 1180, 1155, 1138, 1105,
1045, 976, 953, 934, 901, 843, 826, 814, 760, 744,
706, 683, 671. UV spectrum (CHCl3), λmax, nm (logε):
253 (4.44), 296 (4.00), 308 (3.98), 342 (4.00), 354
(4.01). 1H NMR spectrum, δ, ppm (J, Hz): 0.10 s [9H,
(CH3)3Si], 0.81 d and 1.08 d [3H each, (CH3)2CH, J =
7], 1.57 m [1H, (CH3)2CH], 6.25 d (1H, 6-H, J = 9.4),
6.91 s (1H, 9-H), 7.50 d (1H, 5-H, J = 9.4), 7.74 s (1H,
4-H). 13C NMR spectrum, δC, ppm: 2.39 q [(CH3)3Si],
17.71 q and 18.37 q [(CH3)2CH], 31.03 d [(CH3)2CH],
98.59 s (C2), 100.93 d (C9), 113.82 d (C6), 114.07 s
(C3a), 114.55 s (C4a), 124.28 d (C4), 143.47 d (C5),
158.71 s (C8a), 159.41 s (C9a), 173.83 s (C=O), 199.38 s
(C=O). Found, %: C 66.13; H 5.12; Si 8.07.
C19H20O4Si. Calculated, %: C 67.03; H 5.92; Si 8.25.
2-Isopropyl-2-[(4-methoxyphenyl)ethynyl]-2H-
furo[3,2-g]chromene-3,7-dione (XV). a. As described
above for compound XII (method a), the reaction with
0.5 g of III afforded 0.66 g (88%) of XV.
b. The reaction of 0.5 g of III with 0.47 g of tosyl
chloride and 0.40 g of 4-methoxyphenylacetylene
(XII) in the presence of 0.07 g of Pd(PPh3)Cl2 and
0.62 g of ethyl(diisopropyl)amine in 5 ml of THF (5 h,
60°C) gave 0.56 g (75%) of XV. [α]D20 = +5.2° (c = 0.5,
CHCl3), mp 103–104°C (from EtOH). IR spectrum, ν,
cm–1: 3035, 2999, 2956, 2931, 2835, 2251, 2190, 1742,
1717, 1626, 1605, 1576, 1508, 1462, 1441, 1290,
1247, 1174, 1137, 1107, 1085, 1030, 908, 829, 729.
UV spectrum (EtOH), λmax, nm (logε): 232 (4.11), 253
(4.29), 269 (4.23), 281 (4.20), 299 (4.15), 320 (4.09),
2-Isopropyl-2-phenyl-2H-furo[3,2-g]chromene-
3,7-dione (XIX). a. Tosyl chloride, 0.456 g
(2.4 mmol), and Pd(PPh3)4, 17 mg (5 mol %), were
added under stirring in a stream of argon to a solution
of 0.5 g (2 mmol) of oreoselone (III) in 5 ml of THF,
and the mixture was heated for 4 h under reflux until
the initial compound disappeared (TLC). Phenylboro-
nic acid (XVIII), 0.49 g (4 mmol), tetrabutylammo-
nium bromide, 0.05 g (10 mol %), and potassium
carbonate, 1.27 g (6 mmol), were then added, and the
mixture was heated for 4 h under reflux (TLC). The
mixture was cooled, 10 ml of water was added, the
mixture was extracted with methylene chloride
(4×5 ml), the combined extracts were dried over
MgSO4 and evaporated, and the residue was subjected
to column chromatography on silica gel, followed by
recrystallization from ethanol. Yield 0.288 g (45%).
1
343 (4.06), 355 (3.92). H NMR spectrum, δ, ppm
(J, Hz): 0.87 d and 1.15 d [3H each, (CH3)2CH, J = 7],
3.46 m [1H, (CH3)2CH], 3.80 s (3H, OMe), 6.32 d
(1H, 6-H, J = 9.4), 6.83 d.d (2H, 2′-H, 6′-H), 7.00 s
(1H, 9-H), 7.43 d.d (2H, 3′-H, 5′-H), 7.68 d (1H, 5-H,
J = 9.4), 7.77 s (1H, 4-H). 13C NMR spectrum, δC,
ppm: 15.61 q and 18.62 q [(CH3)2CH], 31.03 d
[(CH3)2CH], 55.28 q (CH3), 72.89 s (C1a), 81.18 s
(C1b), 90.91 s (C2), 100.82 d (C9), 114.07 d (C3′, C5′),
114.53 d (C6), 117.18 s (C3a), 119.13 s (C4a), 124.27 d
(C4), 131.40 s (C1′), 133.96 d (C2′, C6′), 143.48 d (C5),
159.45 s (C8a), 160.16 d (C4′), 160.90 s (C9a), 173.81 s
(C=O), 199.39 s (C=O). Found, %: C 73.46; H 5.05.
C23H18O5. Calculated, %: C 73.79; H 4.85.
b. Tosyl chloride, 0.47 g (2.5 mmol), and
Pd(dppf)Cl2, 0.011 g (5 mol %), were added to a solu-
tion of 0.5 g (2 mmol) of oreoselone (III) in 5 ml of
anhydrous acetonitrile. The mixture was heated for 4 h
under reflux, 0.49 g (4 mmol) of phenylboronic acid
(XVIII), 0.05 g (10 mol %) of Bu4NBr, and 1.27 g
(6 mmol) of K2CO3 were added, and the mixture was
heated for 4 h under reflux (TLC). The mixture was
cooled, diluted with 10 ml of water, and extracted with
methylene chloride (4×5 ml), the combined extracts
were dried over MgSO4, and evaporated, and the
residue was subjected to column chromatography on
2-Isopropyl-2-[(trimethylsilyl)ethynyl]-2H-furo-
[3,2-g]chromene-3,7-dione (XVII). a. The reaction of
0.5 g of III with 0.47 g of TsCl and 0.47 g of tri-
methylsilylacetylene (XVI) in the presence of 0.07 g
of Pd(PPh3)Cl2 and 0.42 g of triethylamine in 5 ml of
THF gave 0.16 g (22%) of XVII.
b. A solution of 0.5 g (1.26 mmol) of 2-tosyloreo-
selone (VIII), 0.23 g (2.4 mmol) of trimethylsilyl-
acetylene (XVI), 0.12 g (1.6 mmol) of triethylamine,
0.042 g (0.06 mmol) of Pd(PPh3)Cl2, and 0.011 g
(0.06 mmol) of CuI in 5 ml of anhydrous THF was
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 1 2013

PLANT COUMARINS: XI.
105
silica gel, followed by recrystallization from ethanol.
Yield 0.5 g (78%).
8.17 d (1H, 3′-H). 13C NMR spectrum, δC, ppm:
16.70 q and 17.55 q [(CH3)2CH], 23.05 d [(CH3)2CH],
36.49 q (CH3), 98.90 s (C2), 101.63 d (C9), 115.40 d
(C6), 115.69 s (C3a), 115.73 s (C4a), 125.08 d (C4),
125.95 s (C6′), 130.47 d (C5′), 131.32 s (C1′), 132.08 d
(C3′), 132.98 d (C4′), 137.13 d (C2′), 143.07 d (C5),
158.88 s (C9a), 161.15 s (C8a), 169.61 s (C7), 192.69 s
(C3). Found, %: C 74.94; H 5.41. C21H18O4. Calculat-
ed, %: C 75.43; H 5.43.
c. Compound VIII, 0.5 g (1.2 mmol), and phenyl-
boronic acid (XVIII), 0.3 g (2.4 mmol), were dis-
solved in 4 ml of acetonitrile, 0.042 g (5 mol %) of
PdCl2(dppf), 0.028 g (10 mol %) of Bu4NBr, and
0.76 g (3.6 mmol) of K2CO3 were added, and the
mixture was heated for 5 h under reflux until the initial
compound disappeared (TLC). The mixture was
cooled, treated with 10 ml of water, and extracted with
methylene chloride (4×5 ml), the extract was dried
over MgSO4 and evaporated, and the residue was
subjected to column chromatography on silica gel,
followed by recrystallization from ethanol. Yield
0.28 g (74%), mp 98–99°C. IR spectrum, ν, cm–1:
3078, 3047, 3026, 2979, 2945, 1741, 1724, 1629,
1581, 1481, 1467, 1442, 1390, 1352, 1307, 1284,
1145, 1101, 1018, 933, 837, 702, 626. UV spectrum
(EtOH), λmax, nm (logε): 348 (3.70), 308 (3.74), 260
2-(Furan-3-yl)-2-isopropyl-2H-furo[3,2-g]chro-
mene-3,7-dione (XXIV) was synthesized from 0.5 g
(2 mmol) of III and 0.45 g (4 mmol) of furan-3-yl-
boronic acid (XXI) using 0.47 g (2.5 mmol) of tosyl
chloride, 0.011 g (5 mol %) of Pd(dppf)Cl2, 0.05 g
(10 mol %) of Bu4NBr, and 1.27 g (6 mmol) of K2CO3.
When the reaction was complete (TLC), the mixture
was treated with 10 ml of water and extracted with
methylene chloride (4×5 ml), the extract was dried
over MgSO4 and evaporated, and the residue was
subjected to column chromatography on silica gel,
followed by recrystallization from ethanol and diethyl
ether. Yield of XXIV 0.35 g (57%). Recrystallization
from acetone gave 28% of IX.
1
(4.25), 221 (4.17), 200 (4.24), 193 (3.95). H NMR
spectrum, δ, ppm (J, Hz): 0.90 d and 1.30 d [3H each,
(CH3)2CH, J = 7], 2.48 m [1H, (CH3)2CH], 6.34 d (1H,
6-H, J = 9.7), 6.99 s (1H, 9-H), 7.25–7.32 m (5H, 2′-H,
3′-H, 4′-H, 5′-H, 6′-H), 7.72 d (1H, 5-H, J = 9.7),
7.90 s (1H, 4-H). 13C NMR spectrum, δC, ppm: 16.60 q
and 17.43 q [(CH3)2CH], 36.50 d [(CH3)2CH], 98.81 s
(C2), 101.84 d (C9), 115.23 d (C6), 115.66 s (C3a),
115.74 s (C4a), 122.48 s (C3′, C5′), 126.03 d (C4),
126.87 s (C1′), 127.53 d (C2′, C6′), 133.30 d (C1′),
143.25 d (C5), 159.15 s (C9a), 161.06 s (C8a), 169.60 s
(C7), 192.93 s (C3). Found, %: C 74.05; H 4.95.
C20H16O4. Calculated, %: C 74.99; H 5.03.
Compound XXIV. mp 100–101°C, [α]D20 = +3.2°
(c = 0.5, CHCl3). IR spectrum, ν, cm–1: 3082, 3066,
2974, 2934, 2876, 1732, 1630, 1584, 1564, 1502,
1467, 1430, 1398, 1387, 1369, 1356, 1335, 1283,
1227, 1157, 1126, 1100, 1072, 1055, 1013, 997, 934,
902, 878, 824, 814, 743, 725, 689, 617, 601. UV spec-
trum (EtOH), λmax, nm (logε): 204 (4.22), 249 (4.03),
253 (4.03), 270 (3.88), 290 (3.84), 299 (3.83), 349
1
(3.65). H NMR spectrum, δ, ppm (J, Hz): 0.88 d and
1.26 d [3H each, (CH3)2CH, J = 7], 2.44 m [1H,
(CH3)2CH], 6.32 d (1H, 6-H, J = 9.4), 6.46 s (2H,
4′-H), 6.96 s (1H, 9-H), 7.32 s (2H, 3′-H), 7.60 s (2H,
2′-H), 7.69 d (1H, 5-H, J = 9.4), 7.88 s (1H, 4-H).
13C NMR spectrum, δC, ppm: 16.53 q and 17.24 q
[(CH3)2CH], 36.34 d [(CH3)2CH], 98.69 s (C2),
101.77 d (C9), 114.65 d (C6), 115.07 d (C5′), 115.53 s
(C3a), 115.73 s (C4a), 124.04 d (C4), 126.04 s (C1′),
135.01 d (C2′), 142.53 d (C5), 143.34 d (C4′), 159.24 s
(C9a), 160.99 s (C8a), 169.54 s (C7), 192.95 s (C3).
Found, %: C 69.51; H 4.32. C18H14O5. Calculated, %:
C 69.67; N 4.55.
2-Isopropyl-2-(2-methylphenyl)-2H-furo[3,2-g]-
chromene-3,7-dione (XXIII) was synthesized from
0.5 g (2 mmol) of compound III and 0.54 g (4 mmol)
of 2-methylphenylboronic acid (XX) using 0.47 g
(2.5 mmol) of tosyl chloride, 0.011 g (5 mol %) of
Pd(dppf)Cl2, 0.05 g (10 mol %) of Bu4NBr, and 1.27 g
(6 mmol) of K2CO3. Yield 0.53 g (80%), mp 96–97°C
(from Et2O). IR spectrum, ν, cm–1 : 3080, 3064, 2979,
2925, 2854, 1741, 1726, 1629, 1598, 1581, 1483,
1440, 1392, 1353, 1299, 1282, 1253, 1145, 1116, 1101,
1076, 1018, 933, 918, 837, 734, 723, 686, 626. UV
spectrum (EtOH), λmax, nm (logε): 227 (4.17), 236
(4.23), 255 (4.34), 296 (3.96), 310 (3.90), 344 (3.80),
2-Isopropyl-2-(pyridin-4-yl)-2H-furo[3,2-g]chro-
mene-3,7-dione (XXV) was synthesized from 0.5 g
(2 mmol) of oreoselone (III) and 0.5 g (4 mmol) of
pyridin-4-ylboronic acid (XXII) using 0.47 g
(2.5 mmol) of tosyl chloride, 0.011 g (5 mol %) of
Pd(dppf)Cl2, 0.05 g (10 mol %) of Bu4NBr, and 1.27 g
1
354 (3.80). H NMR spectrum, δ, ppm (J, Hz): 0.95 d
and 1.37 d [3H each, (CH3)2CH, J = 7], 2.54 m [1H,
(CH3)2CH], 2.78 s (CH3), 6.37 d (1H, 6-H, J = 9.4),
7.03 s (1H, 9-H), 7.23 m (2H, 4′-H, 5′-H), 7.42 d (1H,
5-H, J = 9.4), 7.72 d (1H, 6′-H), 7.92 s (1H, 4-H),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 49 No. 1 2013

LIPEEVA et al.
106
(6 mmol) of K2CO3. A fraction isolated by column
chromatography on silica gel was recrystallized from
acetone to isolate compound IX (yield 38%). The
residue, 0.3 g contained compound XXV (46%), which
extract was dried over MgSO4 and evaporated, and the
residue was subjected to column chromatography on
silica gel to isolate 30 mg (19%) of XXVII and
110 mg (76%) of IX.
1
was identified by H NMR spectrum. It was dried and
Compound XXVII. mp 93–94°C (from Et2O). IR
spectrum, ν, cm–1: 3398, 3066, 2927, 2854, 1732,
1627, 1573, 1535, 1483, 1473, 1390, 1352, 1288,
1226, 1193, 1132, 1122, 1014, 912, 867, 829, 742, 675,
609. UV spectrum (EtOH), λmax, nm (logε): 343 (3.76),
310 (3.89), 277 (4.04), 255 (4.24), 236 (4.12), 225
dissolved in 4 ml of water, a solution of 0.05 ml
(0.0009 mol) of HBr in 4 ml of water was added, and
the mixture was stirred overnight. The yellow precip-
itate was filtered off, washed with diethyl ether, and
dried. We thus isolated 0.23 g (66%) of hydrobromide
XXVa. mp 232–233°C (from EtOH). IR spectrum, ν,
cm–1: 3398, 3130, 3105, 3066, 2927, 2854, 1732, 1627,
1535, 1483, 1473, 1390, 1352, 1288, 1226, 1153,
1132, 1122, 1014, 912, 867, 829, 742, 675, 513. UV
spectrum (EtOH), λmax, nm (logε): 348 (3.70), 306
1
(4.00), 190 (3.97). H NMR spectrum, δ, ppm (J, Hz):
0.93 d and 1.33 d [3H each, (CH3)2CH, J = 7], 2.51 m
[1H, (CH3)2CH], 4.97 d (2H, 2′-H), 5.39 d (1H, 1′-H),
6.36 d (1H, 6-H, J = 9.4), 7.02 s (1H, 9-H), 7.71 d (1H,
5-H, J = 9.4), 7.92 s (1H, 4-H). 13C NMR spectrum,
δC, ppm: 16.79 q and 17.64 q [(CH3)2CH], 36.65 d
[(CH3)2CH], 99.99 s (C2), 101.79 d (C9), 115.45 d (C6),
115.85 s (C3a), 115.96 s (C4a), 120.95 t (C2′), 127.75 d
(C4), 139.72 d (C1′), 143.47 d (C5), 159.37 s (C9a),
161.28 s (C8a), 169.82 s (C=O), 193.15 s (C=O).
Found, %: C 70.92; H 5.26. C16H14O4. Calculated, %:
C 71.10; H 5.22.
1
(3.65), 257 (4.21), 224 (3.79), 201 (4.35). H NMR
spectrum (CDCl3–CD3OD), δ, ppm (J, Hz): 0.86 d and
0.95 d [3H each, (CH3)2CH, J = 7], 3.29 m [1H,
(CH3)2CH], 6.15 d (1H, 6-H, J = 9.4), 6.78 s (1H,
9-H), 7.62 s (1H, 4-H), 7.73 d (1H, 5-H, J = 9.4),
7.90 d (2H, 2′-H, 6′-H), 8.44 d (2H, 3′-H, 5′-H).
13C NMR spectrum (CDCl3–CD3OD), δC, ppm:
14.72 q and 16.11 q [(CH3)2CH], 37.17 d [(CH3)2CH],
100.65 s (C2), 102.54 d (C9), 115.22 s (C3a), 116.59 d
(C6), 117.69 s (C4a), 124.93 s (C1′), 126.42 d (C4),
129.56 d (C2′, C6′), 143.54 d (C5), 147.14 d (C3′, C5′),
159.04 s (C9a), 162.56 s (C8a), 170.96 s (C=O),
190.35 s (C=O). Found, %: C 56.18; H 3.97; Br 19.88,
N 3.35. m/z 399 [M]+. C19H15BrNO4. Calculated, %:
C 56.88; H 3.77; Br 19.91; N 3.49. M 401.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 12-03-92200) and by the Program for Support
of Leading Scientific Schools (project no. NSh-
3986.2012.3).
REFERENCES
2-Isopropyl-2-vinyl-2H-furo[3,2-g]chromene-
3,7-dione (XXVII). a. Compound VIII, 0.25 g
(0.6 mmol), and potassium trifluoro(vinyl)borate
(XXVI), 0.16 g (1.2 mmol), were dissolved in 4 ml of
acetonitrile, 0.021 g (5 mol %) of PdCl2(dppf), 0.014 g
(10 mol %) of Bu4NBr, and 0.38 g (3.6 mmol) of
K2CO3 were added, and the mixture was heated for 5 h
under reflux (TLC). The mixture was cooled, 10 ml of
water was added, and the mixture was extracted with
methylene chloride (4×5 ml). The extract was dried
over MgSO4 and evaporated, and the residue was
subjected to column chromatography on silica gel,
followed by recrystallization from acetone, to isolate
0.13 g (93%) of compound IX and traces of XXVII.
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