Plant coumarins: V.* Palladium-catalyzed amination of 2-(1,3-dibromopropan-2-ylidene)oreoselone

Article abstract of DOI:10.1134/S1070428010120158

Palladium-catalyzed amination of 2-(1,3-dibromopropan-2-ylidene)-7H-furo[3, 2-g]chromene-3,7(2H)-dione with various amines and amino acid derivatives led to the formation of the corresponding 2-(1,3-diaminopropan-2-ylidene)-substituted oreoselones. The yields depended on the catalytic system, base, and amine structure. Di-and polyazamacrocyclic furocoumarin derivatives were obtained by reactions of 2-(1,3-dibromopropan-2-ylidene)-7H-furo[3,2-g]chromene-3,7(2H)- dione with linear di-and polyamines (hexamethylenediamine, spermine, spermidine, and 3,6-dithiaoctane-1,8-diamine), catalyzed by palladium complexes. Pleiades Publishing, Ltd., 2010.

Full text of DOI:10.1134/S1070428010120158

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 12, pp. 1858–1868. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © A.V. Lipeeva, E.E. Shul’ts, M.M. Shakirov, G.A. Tolstikov, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 12,
pp. 1845–1854.
Plant Coumarins: V.* Palladium-Catalyzed Amination
of 2-(1,3-Dibromopropan-2-ylidene)oreoselone
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 16, 2010
Abstract—Palladium-catalyzed amination of 2-(1,3-dibromopropan-2-ylidene)-7H-furo[3,2-g]chromene-
3,7(2H)-dione with various amines and amino acid derivatives led to the formation of the corresponding
2-(1,3-diaminopropan-2-ylidene)-substituted oreoselones. The yields depended on the catalytic system, base,
and amine structure. Di- and polyazamacrocyclic furocoumarin derivatives were obtained by reactions of
2-(1,3-dibromopropan-2-ylidene)-7H-furo[3,2-g]chromene-3,7(2H)-dione with linear di- and polyamines
(hexamethylenediamine, spermine, spermidine, and 3,6-dithiaoctane-1,8-diamine), catalyzed by palladium
complexes.
DOI: 10.1134/S1070428010120158
Linear furocoumarins are widely used in therapy of
skin diseases (PUVA therapy) [2], which is based on
the joint action of psoralen drugs (furocoumarin deriv-
atives) and long-wave ultraviolet irradiation. Photo-
initiated cycloaddition of psoralens in the excited
triplet state to thymine bases of DNA is the main factor
determining therapeutic effect of these compounds. On
the other hand, a number of serious side effects were
revealed, in particular possible cross-linking of two
DNA molecules with one psoralen molecule, which
could give rise to genotoxicity, keratoses, skin cancer,
and other oncological diseases [2]. At present, exten-
sive studies are performed on the synthesis of new
psoralen derivatives and design of photosensitizers for
PUVA therapy so that to avoid the above side effects.
Fusion of a cyclopentane, cyclohexane, benzene, or
pyridazine ring at the furan fragment of the psoralen
skeleton and introduction of a (dimethylamino)prop-
oxy group into position 5 or 8 (to improve solubility in
water) resulted in change of phototoxicity, and in the
case of fused pyridazine derivatives, in considerable
increase of photoantiproliferative activity [3].
An accessible source of fourocoumarins is Peuce-
danum morisonii Bes which is widespread in West
Siberia; its main metabolite is peucedanin (I) which
can be isolated from the root of the plant in up to
4% yield (calculated on the dry raw material) [4]. In
continuation of our studies on peucedanin modifica-
tions [1, 5], in the present work we made an attempt to
synthesize diamino-substituted furocoumarins via pal-
ladium-catalyzed amination of 2-(1,3-dibromopropan-
2-ylidene)-7H-furo[3,2-g]chromene-3,7(2H)-dione (II)
which was prepared as described previously [1].
The reaction conditions were selected using the
amination of dibromide II with L-valinol (IIIa) as
model reaction (Scheme 1). Initially, the reaction was
carried out in the presence of Pd(dba)2/BINAP
(8/9 mol %) since this catalytic system ensured good
results in the amination of 3,24-bis(haloaryloxy)cho-
lanes (sodium tert-butoxide was used as base and di-
oxane was used as solvent) [6]. The target amination
product IVa was obtained in a poor yield (23%),
whereas the major product was that resulting from
reduction of dibromide II, 2-(1-methylethylidene)oreo-
selone (V, yield 52%) [5, 7]. When the amounts of the
catalyst and ligand were reduced to 1/3 mol % and the
reaction was carried out in boiling toluene (i.e., under
the conditions described in [8]), compound IVa was
formed in 25% yield. Replacement of Pd(dba)2 by
Pd2(dba)3 did not change the reaction outcome to
Taking into account the above stated, it seemed
reasonable to synthesize and examine new furocou-
marin derivatives with various nitrogen-containing
substituents on the furan ring.
* For communication IV, see [1].
1858

PLANT COUMARINS: V. PALLADIUM-CATALYZED AMINATION
1859
Scheme 1.
MeO
O
Me
Me
Br
Br
O
O
O
O
O
O
I
II
5'
Me
Me
Me
Me
OH
4'
O
O
5
4
9
HN3'
Me
Me
2'
NH2
3a
4a
8a
6
Pd/L (i–vi)
3
1
HO
Me
2
II
+
+
7
1'
8
O
9a
O
O
HN
O
O
O
O
Me
OH
IIIa
IVa
V
Me
OH
OH
NH2
Pd(OAc)2/BINAP
Et3N, DMF
Me
Me
Me
HN
HO
+
Me
II
O
HN
O
O
Me
IIIb
IVb
Reagents and conditions: i: Pd(dba)2, BINAP, t-BuONa, dioxane, 100°C; ii: Pd(dba)2, BINAP, t-BuONa, toluene, 80°C; iii: Pd2(dba)3,
BINAP, t-BuONa, toluene, 80°C; iv: Pd(OAc)2, (o-MeC6H4)3P, Et3N, DMF, 110°C; v: Pd(OAc)2, BINAP, Et3N, DMF, 110°C; vi: Pd
(OAc)2, Xantphos, Et3N, DMF, 110°C.
of the amination products in the reactions of dibromo-
furocoumarin II with L- and D-valinols IIIa and IIIb
were obtained in the presence of Pd(OAc)2/BINAP.
an appreciable extent: the yield of IVa was 18%. We
succeeded in raising the yield of IVa to 45% by carry-
ing out the amination of II with L-valinol (IIIa) in the
presence of Pd(OAc)2)/(o-MeC6H4)3P (2/8 mol %) as
catalytic system and triethylamine (1.3 equiv) as base
in dimethylformamide; in this case, the yield of V did
not exceed 10%. The use of BINAP as ligand was
more effective. At the optimal Pd(OAc)2/BINAP ratio
(4/8 mol %) amination product IVa was isolated in
72% yield, and its optical rotation was twice as large.
The same catalytic system ensured formation of 64%
of optically active stereoisomer IVb in the amination
of dibromofurocoumarin II with D-valinol (IIIb).
Inhibition of racemization was observed previously in
palladium-catalyzed coupling of aryl bromides with
various optically active amines in the presence of
BINAP as ligand [9].
By amination of dibromofurocoumarin II with
L-phenylalanine methyl ester (IIIc) in the presence of
Pd(OAc)2/BINAP and triethylamine (1.3 equiv) in
DMF we obtained optically active coumarin derivative
VI (yield 66%; Scheme 2). In the reaction of II with
2-aminobutanoic acid (IIId) in the presence of
Pd(OAc)2)/(o-MeC6H4)3P (2/8 mol %) diaminoisopro-
pylidene derivative VII was formed in 48% yield.
Compound II reacted with substituted anilines
[4-fluoroaniline (VIIIa), 2-piperidinoaniline (VIIIb),
and 3,4,5-trimethoxyaniline (VIIIc)] in DMF in the
presence of Pd(OAc)2/BINAP (4/8 mol %) as catalytic
system and triethylamine as base to afford the corre-
sponding bis-anilino derivatives IXa–IXc which were
isolated in 48–54% yield.
Catalytic systems Pd/Xantphos were effectively
used to build up C–N bonds [10]. We found that the
yield of amination product IVa decreased (45%) while
the yield of compound V increased (30%) when the
reaction of furocoumarin II with L-valinol IIIa was
carried out in the presence of Pd(OAc)2)/Xantphos
(2/8 mol %) as catalytic system. Thus, the best yields
The reactions of cyclic secondary amines, morpho-
line (X) and N-methylpiperazine (XI), with dibromide
II were characterized by lower yields of the amination
products (Scheme 3). These reactions were carried out
using Pd(OAc)2)/(o-MeC6H4)3P (2/8 mol %) as cata-
lytic system, and the yields of amination products XIIa
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 12 2010

LIPEEVA et al.
1860
Scheme 2.
COOMe
5′ 4′
O
3′
2′
O
Ph
Ph
HN
Pd/L (v)
1′
II
+
Ph
OMe
O
HN
O
O
NH2
COOMe
COOH
IIIc
VI
O
O
Me
Me
HN
Pd/L (iv)
II
+
Me
OH
O
HN
O
O
NH2
COOH
IIId
VII
R3
R2
R4
R1
R1
1''
O
R2
NH2
Pd(OAc)2/BINAP
Et3N, DMF, 110°C
HN
II
+
O
R3
HN
O
O
R4
R4
R1
R3
R2
VIIIa–VIIIc
IXa–IXc
R1 = R2 = R4 = H, R3 = F (a); R1 = piperidino, R2 = R3 = R4 = H (b); R1 = H, R2 = R3 = R4 = MeO (c).
and XIIb were 22 and 34%, respectively. Increase of
the amount of catalyst (4/8 mol %), as well as addition
of morpholine (X) in 30 min after mixing the initial
furocoumarin, catalyst, and base (in keeping with the
recommendations given in [8]), did not improve the
yield of amination products XIIa and XIIb. In addi-
tion, 32–42% of V was isolated in each case.
Dibromide II readily reacted with linear amines,
such as 2-aminoethanol (XIIIa), 3-aminopropan-1-ol
(XIIIb), and ethylenediamine (XIIIc) (Scheme 4). The
reaction of coumarin II with aminopropanol XIIIb in
the presence of Pd(OAc)2)/(o-MeC6H4)3P gave 42% of
2-[1,3-bis(2-hydroxypropylamino)propan-2-ylidene]-
oreoselone (XIVb). By reactions of compound II with
2-aminoethanol (XIIIa) and ethylenediamine (XIIIc)
in the presence of Pd(OAc)2/BINAP (4/8 mol %) we
obtained amination products XIVa and XIVc in 36–
38% yield. 2-[1,3-Bis(2-aminoethylamino)propan-2-
ylidene]oreoselone (XIVc) was also formed in the
amination of dibromide II with excess (2 equiv) of
Scheme 3.
O
X
Pd(OAc)2/(o-MeC6H4)3P
Et3N, DMF, 110°C
N
N
NH
II
+
+
V
X
O
O
O
X
X, XI
XIIa, XIIb
X, XIIa, X = O; XI, XIIb, X = NMe.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 12 2010

PLANT COUMARINS: V. PALLADIUM-CATALYZED AMINATION
1861
Scheme 4.
5'
4'
O
3'
Pd(OAc)2/L, Et3N
DMF, 110°C
2'
R
R
HN
NH2
II
+
1'
R
O
HN
O
O
XIII–XIIIc
XIVa–XIVc
R = OH (a), CH2OH (b), NH2 (c).
Scheme 5.
O
H
N
1' 2'
10'
7'
Pd/L (i, v, vii)
9'
8'
11'
6'
H2N
NH2
3'
II
+
+
V
( )6
5' 4'
N
O
O
O
H
XV
XVI
Reagents and conditions: i: Pd(dba)2, BINAP, t-BuONa, dioxane, 100°C; v: Pd(OAc)2, BINAP, Et3N, DMF, 110°C;
vii: Pd(dba)2, BINAP, Cs2CO3, toluene, 80°C.
7 h] [6]. In this case, the major product was
2-(1-methylethylidene)oreoselone (V, yield 50%). In
order to reduce the yield of side product V and obtain
acyclic polyamine derivatives, sodium tert-butoxide as
base was replaced by cesium carbonate, the catalytic
system being Pd(dba)2/BINAP [11]. By contrast, the
yield of V increased even to a stronger extent (68%),
while amination product XVI was isolated in 14%
yield. Thus the reaction of II with diamine XV gives
only macrocyclic furocoumarin derivative XVI.
diamine XIIIc; no formation of dicoumarin derivatives
or cyclization products was observed.
The reaction of dibromide II with hexamethylene-
diamine (XV, 2 equiv) in DMF in the presence of
Pd(OAc)2/BINAP (4/8 mol %) and triethylamine on
heating to 110°C (6 h) resulted in the formation of
cyclization product XVI (yield 56%, Scheme 5). The
same product was obtained when increased amount of
amine XV was used. The yield of amination product
XVI sharply decreased (to 26%) when the reaction of
II with diamine XV was carried out using a larger
amount of the catalyst [Pd(dba)2/BINAP, 8/9 mol %;
t-BuONa; heating in boiling dioxane over a period of
Taking into account interest in hybrid nitrogen-
containing macrocyclic compounds, including natural
ones [12], we examined the possibility for synthesizing
Scheme 6.
O
7' 6'
Pd(OAc)2/BINAP
Et3N, DMF, 110°C
8'
HN
4'
2'
H
HN9'
5'
H2N
+
N
NH2
3'
II
( )4 ( )3
10'
1'
11'
O
HN
O
O
12'
13'
XVII
XIXa
13'
12'
O
O
HN
2'
11'
8'
1'
10'
3'
4'
+
HN9'
5'
HN
7' 6'
O
O
XIXb
O
H
H
17'
Pd(OAc)2/BINAP
Et3N, DMF, 110°C
1'
H
N
H
N
N14'
N9'
H
N
H2N
+
NH2
II
3'
( )3 ( )4
( )3
N
H
O
5'
O
O
XVIII
XX
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 12 2010

LIPEEVA et al.
1862
Scheme 7.
O
H
S
S
S
Pd/L (i, v)
11' N
7'N
H
1'
NH2
NH2
13'
9'
II
+
4'
S
O
O
O
XXI
XXII
i: Pd(dba)2, BINAP, t-BuONa, dioxane, 100°C; v: Pd(OAc)2, BINAP, Et3N, DMF, 110°C.
polyamines possessing a coumarin fragment via
amination of dibromide II with polyamines, in partic-
ular with spermidine (XVII) and spermine (XVIII)
(Scheme 6). The reaction of II with spermidine (XVII)
[Pd(OAc)2/BINAP (4/8 mol %)–Et3N] on heating in
DMF gave a mixture of E/Z-isomeric macrocyclic
compounds XIXa and XIXb in an overall yield of
55%. Isomers XIXa and XIXb were formed at a ratio
of 1:1 which was determined from the intensity ratio
of the singlet signals from 2′-H and 4′-H of each
isomer in the 1H NMR spectrum. We failed to separate
the isomer mixture. By reaction of II with spermine
(XVIII) under analogous conditions we obtained 60%
of macrocyclic compound XX. The yield of XX in the
reaction of dibromide II with diamine XVIII was con-
siderably lower (35%) in the presence of Pd(OAc)2)–
(o-MeC6H4)3P (2/8 mol %) as catalytic system.
High yields of macrocyclic furocoumarin deriva-
tives stimulated our further study on the amination of
compound II with heteroatom-containing diamines.
The reaction of II with dithia diamine XXI [13] was
carried out using Pd(OAc)2/BINAP (4/8 mol %) as
catalytic system (Scheme 7), and the only amination
product was macrocyclic compound XXII which was
isolated in 44% yield. In the reaction of II with
diamine XXI in the presence of Pd(dba)2/BINAP
(8/9 mol %) and sodium tert-butoxide [6] the yield of
XXII was 28%. No acyclic polyamino-substituted cou-
marin derivatives were detected among the amination
products in the reactions of dibromide II with di- and
polyamines XVI, XIX, XX, and XXII.
the coumarin fragment and those of the corresponding
substituents on the nitrogen atoms. Compounds IVa,
IVb, VI, and VII were characterized by magnetic non-
equivalence of the 2′-H protons which had different
chemical shifts and showed geminal coupling. In the
1H NMR spectra of IXa–IXc, XIIa, XIIb, XIVa–
XIVc, XVI, XIXa, XIXb, XX, and XXII, methylene
protons neighboring to the nitrogen atoms resonated as
a broadened singlet. The latter was located most up-
field in the spectra of macrocyclic compounds XVI,
XIXa, XIXb, XX, and XXII (δ 2.68–2.92 ppm).
Diamino derivatives XIIa, XIIb, and XIVa–XIVc
displayed 2′-H signals in a weaker field, at δ 3.03–
3.24 ppm, and the most downfield position of these
signals (δ 3.93–4.04 ppm) was typical of bis-anilino
derivatives IXa–IXc. The structure of macrocyclic
coumarin derivatives XVI, XIXa, XIXb, XX, and
XXII and compound XIVc was also confirmed by
determination of their molecular weights.
To conclude, we have developed catalytic proce-
dures for the synthesis of various 2-(1,3-aminoprop-2-
ylidene)-substituted oreoselone derivatives and nitro-
gen- and sulfur-containing macrocyclic furocoumarin
derivatives. The results of the catalytic amination are
determined by the reaction conditions and amine struc-
ture. The best catalytic system for the amination of
2-(1,3-dibromoprop-2-ylidene)furocoumarin II with
various amines is Pd(OAc)2/BINAP.
EXPERIMENTAL
The structure of the obtained compounds was deter-
mined on the basis of their spectral parameters, ele-
mental compositions, and molecular weight measure-
ment. The IR spectra of bis-amino derivatives IVa,
IVb, VII, XIIa, and XIIb characteristically contained
absorption bands belonging to stretching vibrations of
the N–H bonds and carboxy groups in the regions
1604–1695 and 1700–1746 cm–1, as well as broad
bands due to associated hydroxy groups at 2340–2470
The NMR spectra were recorded 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) from solutions in CDCl3. Signals
in the NMR spectra were assigned using several
proton–proton and carbon–proton shift correlation
techniques (COSY, COXH, COLOC). Multiplicity of
13C signals was determined from the J-modulation
spectra. The IR spectra were measured in KBr on
a Vector-22 instrument. The UV spectra were recorded
1
and 3430–3520 cm–1. In the H NMR spectra of these
compounds we observed signals typical of protons in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 12 2010

PLANT COUMARINS: V. PALLADIUM-CATALYZED AMINATION
1863
on an HP 8453 UV Vis spectrophotometer from solu-
tions in ethanol. The optical rotations [α]D20 were meas-
ured on a PolAAr3005 polarimeter. The molecular
weights of compounds XIVc, XVI, XIXa, XIXb, XX,
and XXII were determined using a Knauer vapor pres-
sure osmometer. The elemental compositions were
determined on a Carlo Erba 1106 CHN analyzer.
isolate chromatographically pure compound IV,
XV, or XXI.
ii. Dibromide II, 300 mg (0.75 mmol), was dis-
solved in 6 ml of anhydrous toluene, 4.3 mg (1 mol %)
of Pd(dba)2, 15 mg (3 mol %) of BINAP, 210 mg
(3 equiv) of t-BuONa, and 85 mg (0.825 mmol) of
L-valinol (IIIa) were added in succession under argon,
and the mixture was heated for 8 h at 80°C until initial
coumarin II disappeared (TLC). The mixture was then
cooled in a stream of argon and evaporated, and the
residue was subjected to column chromatography on
aluminum oxide to isolate a fraction containing com-
pounds IVa and V. The product mixture was recrys-
tallized from acetone to remove the main part of com-
pound V, and the residue was subjected to chroma-
tography on silica gel. A fraction containing the
amination product was dissolved in diethyl ether, the
solution was cooled, and the precipitate of compound
IVa was filtered off.
The products were isolated by column chromatog-
raphy on silica gel (0.035–0.070 mm, Acros Organics)
or aluminum oxide using chloroform and chloroform–
ethanol (50:3) as eluents. The progress of reactions
and the purity of products were monitored by TLC on
Silufol UV-254 plates using chloroform–ethanol (3:1),
benzene, or benzene–ethyl acetate (1:1) as eluent;
spots were visualized by treatment with iodine vapor
or under UV light.
The solvents (dioxane, toluene, DMF), triethyl-
amine, 2-aminoethanol, 3-aminopropan-1-ol, and
ethylenediamine were distilled in a stream of argon
just before use. Commercial L- and D-valinol,
L-phenylalanine methyl ester, 2-aminobutanoic acid,
2-piperidinoaniline, 4-fluoroaniline, and 3,4,5-trime-
thoxyaniline (from Alfa Aesar), morpholine, spermine,
and spermidine (from Aldrich), and N-methylpiper-
azine (from Acros) were used without additional
purification.
iii. Dibromide II, 300 mg (0.75 mmol), was dis-
solved in 6 ml of anhydrous toluene, 7.8 mg (1 mol %)
of Pd2(dba)3, 15 mg (3 mol %) of BINAP, 210 mg
(3 equiv) of t-BuONa, and 154 mg (1.5 mmol) of
L-valinol (IIIa) were added in succession under argon,
and the mixture was heated for 8 h at 80°C and treated
as described above to isolate compounds IVa and V.
Palladium(II) acetate was synthesized according to
the procedure described in [14]; Pd(dba)2 was prepared
as reported in [15] and was not subjected to additional
recrystallization; Pd2(dba)3, (o-MeC6H4)3P, (R)-(+)-
BINAP, and Xantphos were commercial products
(from Alfa Aesar).
iv. Compound II, 300 mg (0.75 mmol), was dis-
solved in 5 ml of anhydrous dimethylformamide,
3.2 mg (2 mol %) of Pd(OAc)2, 34 mg (8 mol %) of
(o-MeC6H4)3P, 0.07 ml (1.3 equiv) of Et3N, and
1.5 mmol of amine IIIa, IIId, X, XI, or XIIIb were
added under argon, and the mixture was heated for 5 h
at 110°C (TLC). The mixture was cooled in a stream of
argon and poured into a Petri dish for evaporation. The
residue was subjected to chromatography first on
aluminum oxide and then on silica gel. A fraction
containing the amination product was dissolved in
diethyl ether, the solution was cooled, and the precip-
itate (compound IVa, VII, XIIa, XIIb, or XIVb) was
filtered off.
Amination of 2-(1,3-dibromoprop-2-ylidene)-
7H-furo[3,2-g]chromene-3,7(2H)-dione (II). i. Di-
bromide II, 300 mg (0.75 mmol), was dissolved in
4 ml of anhydrous dioxane, 34 mg (8 mol %) of
Pd(dba)2, 46 mg (9 mol %) of BINAP, 210 mg
(3 equiv) of t-BuONa, and 310 mg (3 mmol) of
L-valinol (IIIa) or 2 mmol of diamine XIV or XX
were added in succession under argon, and the mixture
was heated for 10 h at 100°C until the initial com-
pound (II) disappeared (according to the TLC data).
The mixture was evaporated, and the residue was
subjected to column chromatography on silica gel to
isolate fractions containing amination product IVa,
XV, or XXI and compound V. The main portion of
compound V was separated by recrystallization from
acetone, the precipitate of V was filtered off, the
mother liquor was evaporated, and the residue was
subjected again to chromatography on silica gel to
v. Compound II, 300 mg (0.75 mmol), was dis-
solved in 4 ml of anhydrous dimethylformamide,
4.4 mg (4 mol %) of Pd(OAc)2, 34 mg (8 mol %) of
BINAP, 0.07 ml (1.3 equiv) of Et3N, and 1.5 mmol of
amine IIIa–IIIc, VIIIa–VIIIc, or XIIIa or 2.0 mmol
of diamine XIIIc, XV, XVII, XVIII, or XXI were
added under argon, and the mixture was heated for 6 h
at 110°C (TLC). The mixture was then cooled in
a stream of argon and poured into a Petri dish. After
evaporation, the residue was subjected to column chro-
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LIPEEVA et al.
1864
matography on aluminum oxide or silica gel to isolate
amination product IVa, IVb, VI, IXa–IXc, XIVa,
XIVc, XVI, XIXa, XIXb, XX, and XXII.
123.53 d (C4), 143.26 d (C5), 144.19 s (C2), 157.62 s
(C8a), 161.82 s (C9a), 171.35 s (C7), 198.79 s (C3).
Found, %: C 64.62; H 6.83; N 5.94. C24H32N2O6. Cal-
culated, %: C 64.85; H 7.26; N 6.30.
vi. Compound II, 300 mg (0.75 mmol), was dis-
solved in 4 ml of anhydrous dimethylformamide,
4.4 mg (4 mol %) of Pd(OAc)2, 44 mg (8 mol %) of
Xantphos, 0.07 ml (1.3 equiv) of Et3N, and 154 mg
(1.5 mmol) of L-valinol (IIIa) were added under
argon, and the mixture was heated for 6 h at 110°C
(TLC). The mixture was then cooled in a stream of
argon and poured into a Petri dish. After evaporation,
the residue was subjected to column chromatography
on aluminum oxide to isolate compounds IVa (yield
44%) and V (30%).
2-[(1S,3S)-1,3-Bis(1-hydroxy-3-methylbutan-2-
ylamino)propan-2-ylidene]-7H-furo[3,2-g]chro-
mene-3,7(2H)-dione (IVb) was synthesized from
300 mg (0.75 mmol) of compound II and 154 mg
(1.5 mmol) of D-valinol in the presence of 4.4 mg
(4 mol %) of Pd(OAc)2, 34 mg (8 mol %) of BINAP,
and 0.07 ml (1.3 equiv) of Et3N in 4 ml of DMF. Yield
213 mg (64%), [α]D20 = +7.2 (c = 0.5, CHCl3), mp 135–
136°C (from Et2O). The spectral parameters of IVb
were similar to those of its stereoisomer IVa.
vii. Dibromide II, 300 mg (0.75 mmol), was dis-
solved in 6 ml of anhydrous toluene, 8.6 mg (2 mol %)
of Pd(dba)2, 10 mg (2 mol %) of BINAP, 1200 mg
(5 equiv) of Cs2CO3, and 174 mg (2 mmol) of hexa-
methylenediamine (XV) were added in succession
under argon, and the mixture was heated for 8 h at
80°C (TLC). The mixture was then cooled in a stream
of argon and evaporated, and the residue was subjected
to column chromatography on aluminum oxide to
isolate a fraction containing compounds XVI and V.
The product mixture was recrystallized from acetone
to remove the main part of compound V, and the
residue was subjected to chromatography on silica gel.
We isolated 37 mg (14%) of macrocyclic compound
XVI and 123 mg (68%) of compound V.
Dimethyl N,N′-[2-(3,7-dioxo-7H-furo[3,2-g]-
chromen-2-ylidene)propane-1,3-diyl]bis[(2S)-2-
amino-3-phenylpropanoate] (VI) was synthesized
from 300 mg (0.75 mmol) of compound II and 324 mg
(1.5 mmol) of phenylalanine methyl ester (IIIc) in the
presence of 4.4 mg (4 mol %) of Pd(OAc)2, 34 mg
(8 mol %) of BINAP, and 0.07 ml (1.3 equiv) of Et3N
in 4 ml of anhydrous DMF (v). Yield 295 mg (66%),
[α]D20 = –10.8° (c = 0.5, CHCl3), mp 231–233°C (from
Et2O). IR spectrum, ν, cm–1: 3420, 3220, 3171, 3029,
1737, 1698, 1680, 1656, 1621, 1590, 1392, 1353,
1297, 1143, 1130, 906, 839, 752, 740, 702, 586. UV
spectrum, λmax, nm (logε): 237 (3.59), 276 (4.17), 307
1
(4.40), 355 (3.52). H NMR spectrum, δ, ppm (J, Hz):
2.84 d.d.d (2H, 5′-H, J = 11.6, 6.6, 2.0), 3.05 d.d.d
(2H, 5′-H, J = 11.6, 3.8, 1.0), 3.20 d (2H, 2′-H, J =
12.0), 3.34 d (2H, 2′-H, J = 12.0), 3.61 s (6H, OCH3),
3.67 d.d.d (2H, 4′-H, J = 6.6, 3.8, 1.5), 6.23 d (1H,
6-H, J = 9.8), 6.95 s (1H, 9-H), 7.12 m (4H, o-H),
7.23–7.28 m (6H, m-H, p-H), 7.55 d (1H, 5-H, J =
9.8), 8.16 s (1H, 4-H), 11.05 br.s (2H, NH). 13C NMR
spectrum, δC, ppm: 40.89 t (C2′), 51.89 t (C5′), 55.65 q
(OCH3), 62.06 d (C4′), 101.51 d (C9), 112.83 d (C6),
113.66 s (C4a), 115.48 s (C3a), 123.50 d (C4), 126.16 s
(C1′), 126.72 d (Cp), 128.44 d (Cm), 129.14 d (Co),
137.01 s (Ci), 143.13 d (C5), 144.72 s (C2), 158.83 s
(C8a), 161.95 s (C9a), 168.82 s (C7), 175.23 s
(COOCH3), 189.99 s (C3). Found, %: C 68.26; H 6.61;
N 4.32. C34H32N2O8. Calculated, %: C 68.45; H 5.41;
N 4.70.
2-[(1R,3R)-1,3-Bis(1-hydroxy-3-methylbutan-2-
ylamino)propan-2-ylidene]-7H-furo[3,2-g]chro-
mene-3,7(2H)-dione (IVa). Yield 23 (i), 25 (ii), 18%
(iii); 45%, [α]D20 = –7.6° (c = 0.5, EtOH) (iv); 72%,
[α]D20 = –8.8° (c = 0.5, CHCl3) (v); 30%, [α]D20 = –5.6
(c = 0.5°, EtOH) (vi); mp 135–136°C (from Et2O). IR
spectrum, ν, cm–1: 3388, 3084, 2965, 2470, 2030,
1702, 1680, 1620, 1521, 1392, 1330,1260, 1133, 1050,
970, 804, 721, 669. UV spectrum, λmax, nm (logε): 202
1
(4.18), 259 (3.72), 306 (3.74), 345 (3.48). H NMR
spectrum, δ, ppm (J, Hz): 0.89 d and 0.97 d [6H each,
(CH3)2CH, J = 7.0], 1.84 m [2H, CH(CH3)2], 2.57 d.d
(2H, 4′-H, J = 6.6, 2.2), 3.15 d.d.d (2H, 5′-H, J = 10.6,
1.8, 1.5), 3.30 d.d (2H, NH, J = 2.2, 1.8), 3.34 m (2H,
OH), 3.32 d.d (2H, 2′-H, J = 12.0, 1.0), 3.38 d (2H,
2′-H, J = 12.0), 6.25 d (1H, 6-H, J = 9.8), 6.98 s (1H,
9-H), 7.55 d (1H, 5-H, J = 9.8), 7.95 s (1H, 4-H).
13C NMR spectrum, δC, ppm: 17.18 q and 20.28 q
[CH(CH3)2], 28.68 d [CH(CH3)2], 44.19 t (C2′),
60.28 d (C4′), 66.41 d (C5′), 101.23 d (C9), 112.80 d
(C6), 113.49 s (C4a), 115.60 s (C3a), 119.56 s (C1′),
N,N′-[2-(3,7-Dioxo-2H-furo[3,2-g]chromen-2-
ylidene)propane-1,3-diyl]bis[2-aminobutanoic
acid] (VII) was synthesized from 300 mg (0.75 mmol)
of compound II and 150 mg (1.5 mmol) of 2-amino-
butanoic acid in 5 ml of anhydrous DMF in the
presence of 3.2 mg (2 mol %) of Pd(OAc)2, 34 mg
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 12 2010

PLANT COUMARINS: V. PALLADIUM-CATALYZED AMINATION
1865
(8 mol %) of (o-MeC6H4)3P, and 0.07 ml (1.3 equiv) of
Et3N (iv). Yield 160 mg (48%), mp 138–139°C (from
Et2O). IR spectrum, ν, cm–1: 3600, 3330, 3250, 3057,
2967, 2916, 2542, 1737, 1702, 1653, 1620, 1586,
1517, 1354, 1141, 1115, 1067, 980, 900, 806, 763, 698,
664. UV spectrum, λmax, nm (logε): 224 (3.93), 228
(3.94), 241 (4.02), 278 (4.0), 306 (4.09), 335 (3.74).
1H NMR spectrum, δ, ppm (J, Hz): 0.97 t (6H, C6′H3,
J = 7.0), 1.54 m and 1.70 m (2H each, 5′-H), 3.19 d
and 3.33 d (2H each, 2′-H, J = 11.8), 3.36 d.d.d (2H,
4′-H, J = 6.6, 3.2, 1.2), 4.25 br.s (4H, NH, OH), 6.24 d
(1H, 6-H, J = 9.8), 6.97 s (1H, 9-H), 7.54 d (1H, 5-H,
J = 9.8), 7.94 s (1H, 4-H), 11.05 br.s (2H). 13C NMR
spectrum, δC, ppm: 10.73 q (C6′), 21.89 t (C5′), 43.47 t
(C2′), 63.26 d (C4′), 98.23 d (C9), 113.02 d (C6),
113.71 s (C4a), 116.63 s (C3a), 120.06 s (C1′), 123.52 d
(C4), 144.41 d (C5), 145.01 s (C2), 158.05 s (C9a),
162.04 s (C8a), 171.83 s (C7), 173.01 s (COOH),
193.22 s (C3). Found, %: C 59.16; H 5.53; N 6.22.
C22H24N2O8. Calculated, %: C 59.45; H 5.44; N 6.30.
Pd(OAc)2, 34 mg (8 mol %) of BINAP, and 0.07 ml
(1.3 equiv) of Et3N in 4 ml of anhydrous DMF (v).
Yield 212 mg (48%), mp 183–184°C (from Et2O). IR
spectrum, ν, cm–1: 3432, 3068, 2839, 1737, 1704,
1657, 1620, 1600, 1507, 1139, 1124, 1003, 908, 888,
829, 764, 750, 686. UV spectrum, λmax, nm (logε): 224
(4.48), 261 (4.19), 277 (4.16), 308 (4.10), 350 sh
1
(3.77). H NMR spectrum (CDCl3), δ, ppm (J, Hz):
1.57 m and 1.61 m [6H each, (CH2)3], 3.18 m and
3.32 m (4H each, CH2NCH2), 3.99 br.s (4H, 2′-H),
6.03 d (2H, 6″-H, J = 8.8), 6.25 d (1H, 6-H, J = 10.1),
6.58 d (2H, 3″-H, J = 8.6), 6.78 d.d (2H, 4″-H, J = 8.0,
8.6), 6.82 d.d (2H, 5″-H, J = 8.0. 8.8), 6.97 s (1H,
9-H), 7.56 d (1H, 5-H, J = 10.1), 7.94 s (1H, 4-H).
13C NMR spectrum, δC, ppm: 24.19 t (C4′′′), 26.19 t
(C3′′′, C5′′′), 42.60 t (C2′), 51.30 t (C2′′′, C6′′′), 99.73 d
(C9), 113.02 d (C6), 113.71 s (C4a), 114.03 d (C3″),
116.63 s (C3a), 118.24 d (C6″), 119.55 s (C1′), 120.10 d
(C4″), 123.52 d (C4), 133.48 s (C5″), 140.61 s (C2″),
144.11 s (C1″), 144.41 d (C5), 147.27 s (C2), 157.64 s
(C9a), 161.56 s (C8a), 171.56 s (C7), 192.15 s (C3).
Found, %: C 73.56; H 6.21; N 9.68. C36H38N4O4. Cal-
culated, %: C 73.20; H 6.48; N 9.48.
2-[1,3-Bis(4-fluorophenylamino)propan-2-yli-
dene]-7H-furo[3,2-g]chromene-3,7(2H)-dione (IXa)
was synthesized from 300 mg (0.75 mmol) of com-
pound II and 168 mg (1.5 mmol) of 4-fluoroaniline in
the presence of 4.4 mg (4 mol %) of Pd(OAc)2, 34 mg
(8 mol %) of BINAP, and 0.07 ml (1.3 equiv) of Et3N
in 4 ml of anhydrous DMF (v). Yield 179 mg (52%),
mp 113–114°C (from Et2O). IR spectrum, ν, cm–1:
3413, 3023, 2778, 2439, 1737, 1704, 1615, 1587,
1508, 1392, 1350, 1223, 1155, 1140, 1098, 1024, 836,
720, 616. UV spectrum, λmax, nm (logε): 235 (4.10),
2-[1,3-Bis(3,4,5-trimethoxyphenylamino)propan-
2-ylidene]-7H-furo[3,2-g]chromene-3,7(2H)-dione
(IXc) was synthesized from 300 mg (0.75 mmol) of
compound II and 295 mg (1.5 mmol) of 3,4,5-trime-
thoxyaniline in the presence of 4.4 mg (4 mol %) of
Pd(OAc)2, 34 mg (8 mol %) of BINAP, and 0.07 ml
(1.3 equiv) of Et3N in 4 ml of anhydrous DMF (v).
Yield 244 mg (54%), mp 192–193°C (from Et2O). IR
spectrum, ν, cm–1: 3437, 3080, 3043, 2839, 1737,
1704, 1657, 1620, 1600, 1507, 1139, 1124, 1004, 909,
888, 829, 764, 750, 688, 674. UV spectrum, λmax, nm
(logε): 231 (4.27), 276 (4.41), 305 (4.54), 365 sh
(3.82). 1H NMR spectrum, δ, ppm (J, Hz): 3.64 s (6H,
4″-OCH3), 3.82 br.s (12H, 3″-OCH3, 5″-OCH3), 4.04 s
(4H, 2′-H), 5.67 s (4H, 2″-H, 6″-H), 6.36 d (1H, 6-H,
J = 9.8), 7.08 s (1H, 9-H), 7.67 d (1H, 5-H, J = 9.8),
8.05 s (1H, 4-H). 13C NMR spectrum, δC, ppm: 42.59 t
(C2′), 55.80 q (3″-OCH3, 5″-OCH3), 60.15 q
(4″-OCH3), 98.08 d (C9), 98.38 d (C2″, C6″), 113.03 s
(C4a), 113.68 d (C6), 114.95 s (C3a), 116.12 s (C1′),
123.49 d (C4), 133.62 s (C4″), 135.11 s (C1″), 141.94 d
(C5), 147.24 s (C2), 152.85 d (C3″, C5″), 157.61 s (C9a),
161.53 s (C8a), 172.85 s (C7), 193.22 s (C3). Found, %:
C 63.08; H 5.12; N 4.22. C32H32N2O10. Calculated, %:
C 63.57; H 5.33; N 4.63.
1
301 (3.93), 328 (3.98), 440 (2.62). H NMR spectrum,
δ, ppm (J, Hz): 3.93 br.s (4H, 2′-H), 6.26 d (1H, 6-H,
J = 10.2), 6.98 s (1H, 9-H), 7.02 d and 7.04 d (2H
each, m-H, J = 8.3), 7.38 d and 7.39 d (2H each, o-H,
J = 8.3), 7.54 d (1H, 5-H, J = 10.2), 7.94 s (1H, 4-H).
13C NMR spectrum, δC, ppm: 42.26 t (C2′), 97.86 d
(C9), 112.77 d (C6), 113.02 s (C4a), 113.67 s (C3a),
115.55 d (Cm), 118.38 s (C1′), 119.29 d (Co), 122.24 d
(C4), 144.16 d (C5), 144.97 s (Ci), 147.33 s (C2),
157.12 d (Cp, JCF = 251.2 Hz), 160.02 s (C9a), 161.49 s
(C8a), 172.21 s (C7), 192.58 s (C3). 19F NMR spectrum:
δF 83.34 ppm (relative to C6F6 as reference). Found, %:
C 68.08; H 3.25; F 8.02; N 6.26. C26H18F2N2O4. Cal-
culated, %: C 67.82; H 3.94; F 8.29; N 6.08.
2-[1,3-Bis(2-piperidinophenylamino)propan-2-
ylidene]-7H-furo[3,2-g]chromene-3,7(2H)-dione
(IXb) was synthesized from 300 mg (0.75 mmol) of
compound II and 265 mg (1.5 mmol) of 2-piperidino-
aniline in the presence of 4.4 mg (4 mol %) of
2-(1,3-Dimorpholinopropan-2-ylidene)-7H-furo-
[3,2-g]chromene-3,7(2H)-dione (XIIa) was synthe-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 12 2010

LIPEEVA et al.
1866
in the presence of 4.4 mg (4 mol %) of Pd(OAc)2,
34 mg (8 mol %) of BINAP, and 0.07 ml (1.3 equiv) of
Et3N in 4 ml of anhydrous DMF (v). Yield 97 mg
(36%), mp 112–113°C (from Et2O). IR spectrum, ν,
cm–1: 3344, 3300, 3003, 2550, 1731, 1663, 1640, 1571,
1315, 1155, 1071, 1026, 860, 820, 703. UV spectrum,
λmax, nm (logε): 239 (2.95), 272 (2.96), 319 (3.87), 350
sized from 300 mg (0.75 mmol) of compound II and
0.13 ml (1.5 mmol) of morpholine in the presence of
3.2 mg (2 mol %) of Pd(OAc)2, 34 mg (8 mol %) of
(o-MeC6H4)3P, and 0.07 ml (1.3 equiv) of Et3N in 5 ml
of anhydrous DMF (iv). Yield 68 mg (22%), mp 165–
166°C (from Et2O). IR spectrum, ν, cm–1: 3414, 3054,
2780, 2449, 1733, 1623, 1582, 1479, 1353, 1140, 1110,
1102, 1085, 1043, 994, 929, 900, 871, 826, 810, 750,
725, 683. UV spectrum, λmax, nm (logε): 263 (4.25),
1
(2.82), 360 sh (2.80). H NMR spectrum, δ, ppm
(J, Hz): 2.15 br.s (4H, NH, OH), 2.83 m (4H, 4′-H),
3.23 m (4H, 2′-H), 3.66 m (4H, 5′-H), 6.26 d (1H, 6-H,
J = 9.8), 6.99 s (1H, 9-H), 7.57 d (1H, 5-H, J = 9.8),
7.95 s (1H, 4-H). 13C NMR spectrum, δC, ppm: 45.59 t
(C2′), 51.40 t (C4′, 59.83 t (C5′), 99.00 d (C9), 112.97 d
(C6), 113.66 s (C4a), 116.70 s (C3a), 119.73 s (C1′),
123.47 d (C4), 144.44 d (C5), 144.96 s (C2), 157.59 s
(C9a), 161.51 s (C8a), 172.51 s (C7), 192.12 s (C3).
Found, %: C 59.72; H 5.76; N 8.09. C18H20N2O6. Cal-
culated, %: C 59.99; H 5.59; N 7.77.
1
299 (4.04), 349 (3.61). H NMR spectrum, δ, ppm
(J, Hz): 2.33–2.41 m and 2.43–2.50 m (4H each,
CH2NCH2), 3.03 br.s (4H, 2′-H), 3.42–3.51 m and
3.54–3.60 m (4H each, CH2OCH2), 6.25 d (1H, 6-H,
J = 9.8), 6.97 s (1H, 9-H), 7.55 d (1H, 5-H, J = 9.8),
7.94 s (1H, 4-H). 13C NMR spectrum, δC, ppm: 53.13 t
(CH2NCH2), 57.45 t (C2′), 66.75 t (CH2OCH2),
101.78 d (C9), 112.87 s (C4a), 113.56 d (C6), 116.42 s
(C3a), 119.18 s (C1′), 126.48 d (C4), 144.67 d (C5),
144.86 s (C2), 157.55 s (C9a), 161.96 s (C8a), 172.85 s
(C7), 193.22 s (C3). Found, %: C 57.30; H 5.24;
N 5.89. C22H24N2O6 · 1/2 CHCl3. Calculated, %:
C 57.20; H 5.08; N 5.93.
2-[1,3-Bis(3-hydroxypropylamino)propan-2-yli-
dene]-7H-furo[3,2-g]chromene-3,7(2H)-dione
(XIVb) was synthesized from 300 mg (0.75 mmol) of
compound II and 112 mg (1.5 mmol) of amine XIIIb
in the presence of 3.2 mg of Pd(OAc)2, 34 mg of
(o-MeC6H4)3P, and 0.07 ml (1.3 equiv) of Et3N in 5 ml
of anhydrous DMF (v). Yield 122 mg (42%), mp 97–
99°C (from Et2O). IR spectrum, ν, cm–1: 3338, 3290,
3083, 2500, 1727, 1670, 1563, 1311, 1148, 1064, 960,
911, 820, 770, 700. UV spectrum, λmax, nm (logε): 236
2-[1,3-Bis(4-methylpiperazin-1-yl)propan-2-yli-
dene]-7H-furo[3,2-g]chromene-3,7(2H)-dione
(XIIb) was synthesized from 300 mg (0.75 mmol) of
compound II and 150 mg (1.5 mmol) of N-methylpi-
perazine in the presence of 3.2 mg (2 mol %) of
Pd(OAc)2, 34 mg (8 mol %) of (o-MeC6H4)3P, and
0.07 ml (1.3 equiv) of Et3N in 5 ml of anhydrous DMF
(iv). Yield 111 mg (34%), mp 132–133°C (from Et2O).
IR spectrum, ν, cm–1: 3417, 3026, 2469, 1722, 1624,
1574, 1500, 1354, 1292, 1215, 1142, 1050, 920, 900,
826. UV spectrum, λmax, nm (logε): 202 (4.37), 257
1
(3.98), 276 (3.92), 350 (3.23). H NMR spectrum, δ,
ppm (J, Hz): 1.75 m (4H, 5′-H), 2.78 m (4H, 4′-H),
2.95 br.s (4H, NH, OH), 3.20 m (4H, 2′-H), 3.81 m
(4H, 6′-H), 6.25 d (1H, 6-H, J = 9.8), 6.98 s (1H, 9-H),
7.55 d (1H, 5-H, J = 9.8), 7.94 s (1H, 4-H). 13C NMR
spectrum, δC, ppm: 31.21 t (C5′), 45.60 t (C2′), 46.75 t
(C4′), 62.59 t (C6′), 98.39 d (C9), 112.48 d (C6),
112.98 s (C4a), 116.38 s (C3a), 120.12 s (C1′), 123.46 d
(C4), 144.35 d (C5), 144.95 s (C2), 157.58 s (C9a),
161.70 s (C8a), 173.07 s (C7), 192.93 s (C3). Found, %:
C 61.72; H 6.01; N 7.63. C20H24N2O6. Calculated, %:
C 61.84; H 6.23; N 7.21.
1
(4.27), 320 (4.04), 345 (3.56). H NMR spectrum, δ,
ppm (J, Hz): 2.25 s (6H, NCH3), 2.26 m and 2.35 m
(4H each, 2″-H, 6″-H), 2.54 m and 2.63 m (4H each,
3″-H, 5″-H), 3.04 br.s (4H, 2′-H), 6.25 d (1H, 6-H, J =
9.8), 6.98 s (1H, 9-H), 7.55 d (1H, 5-H, J = 9.8), 7.94 s
(1H, 4-H). 13C NMR spectrum, δC, ppm: 42.69 q
(NCH3), 45.66 t (C2′), 50.50 t (C2′′, C6′′), 56.17 t
(C3′′, C5′′), 99.30 d (C9), 112.91 d (C6), 113.60 s (C4a),
116.52 s (C3a), 118.17 s (C1′), 124.39 d (C4), 143.11 d
(C5), 144.90 s (C2), 157.53 s (C9a), 161.94 s (C8a),
172.20 s (C7), 192.36 s (C3). Found, %: C 58.73;
H 6.24; N 11.55. C24H30N4O4·1/2CHCl3. Calculated,
%: C 59.03; H 6.22; N 11.24.
2-[1,3-Bis(2-aminoethylamino)propan-2-yli-
dene]-7H-furo[3,2-g]chromene-3,7(2H)-dione
(XIVc) was synthesized from 300 mg (0.75 mmol) of
compound II and 90 mg (1.5 mmol) of ethylene-
diamine in the presence of 4.4 mg (4 mol %) of
Pd(OAc)2, 34 mg (8 mol %) of BINAP, and 0.07 ml
(1.3 equiv) of Et3N in 4 ml of anhydrous DMF (v).
Yield 102 mg (38%), mp 132–133°C (from Et2O). IR
spectrum, ν, cm–1: 3260, 3160, 3048, 2883, 2800,
2678, 1657, 1537, 1459, 1392, 1322, 1258, 1228,
2-[1,3-Bis(2-hydroxyethylamino)propan-2-yli-
dene]-7H-furo[3,2-g]chromene-3,7(2H)-dione
(XIVa) was synthesized from 300 mg (0.75 mmol) of
compound II and 91 mg (1.5 mmol) of 2-aminoethanol
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 12 2010

PLANT COUMARINS: V. PALLADIUM-CATALYZED AMINATION
1867
1119, 982, 842, 752, 709. UV spectrum, λmax, nm
(logε): 227 (3.03), 231 (3.04), 241 (3.38), 282 (2.56),
331 (2.08), 363 (1.48). H NMR spectrum, δ, ppm
J = 9.8), 7.90 s (1H, 4-H). 13C NMR spectrum, δC,
ppm: 20.47 t (C12′), 21.42 t (C11′), 26.18 t (C7′), 46.39 t
(C6′), 47.38 t (C13′), 48.12 t (C8′), 49.36 t (C10′), 50.13 t
(C2′, C4′), 99.03 d (C9), 113.76 s (C4a), 115.10 d (C6),
117.41 d (C4), 118.64 s (C3a), 123.07 s (C3′), 144.61 s
(C2), 146.07 d (C5), 153.04 s (C8a), 160.07 s (C9a),
171.17 s (C7), 191.71 s (C3). Found, %: C 65.48;
H 6.25; N 10.39. [M]+ 383. C21H25N3O4. Calculated,
%: C 65.78; H 6.57; N 10.96. M 383.14.
1
(J, Hz): 2.65–2.72 m (8H, 4′-H, 5′-H), 3.23 br.s (4H,
2′-H), 4.54 br.s (6H, NH2, NH), 6.25 d (1H, 6-H, J =
9.8), 6.98 s (1H, 9-H), 7.55 d (1H, 5-H, J = 9.8), 7.94 s
(1H, 4-H). 13C NMR spectrum, δC, ppm: 41.12 t (C5′),
45.45 t (C2′), 51.90 t (C4′), 99.73 d (C9), 112.89 d (C6),
113.57 s (C4a), 116.88 s (C3a), 119.07 s (C1′), 123.39 d
(C4), 144.28 d (C5), 144.88 s (C2), 157.51 s (C9a),
161.00 s (C8a), 171.54 s (C7), 192.15 s (C3). Found, %:
C 60.05; H 6.43; N 15.90. [M]+ 358. C18H22N4O4. Cal-
culated, %: C 60.32; H 6.19; N 15.63. M 358.16.
2-(1,5,9,13-Tetraazacycloheptadecan-7-ylidene)-
7H-furo[3,2-g]chromene-3,7(2H)-dione (XX). Yield
35 (iv), 60% (v); mp 201–203°C (from Et2O). IR spec-
trum, ν, cm–1: 3437, 3061, 2975, 2934, 2853, 2676,
2592, 2452, 1727, 1624, 1482, 1393, 1350, 1289, 1193,
1138, 1023, 909, 829, 741. UV spectrum, λmax, nm
(logε): 202 (4.83), 223 (4.7), 255 (4.96), 299 (4.73),
348 (4.56). 1H NMR spectrum, δ, ppm (J, Hz): 1.93 m
(4H, 15′-H, 16′-H), 2.02 m (4H, 3′-H, 11′-H), 2.57 m
(4H, 14′-H, 17′-H), 2.70 m (4H, 2′-H, 12′-H), 2.72 s
(4H, 6′-H, 8′-H), 3.50 m (4H, 4′-H, 10′-H), 6.24 d (1H,
6-H, J = 9.8), 6.98 s (1H, 9-H), 7.55 d (1H, 5-H, J =
9.8), 7.94 s (1H, 4-H), 8.92 br.s (4H, NH). 13C NMR
spectrum, δC, ppm: 27.54 t (C15′, C16′), 28.59 t (C3′,
C11′), 45.88 t (C4′, C10′), 49.13 t (C2′, C12′), 49.84 t (C14′,
C17′), 51.31 t (C6′, C8′), 99.65 d (C9), 112.77 d (C6),
113.46 s (C4a), 116.38 s (C3a), 123.23 d (C4), 126.10 s
(C7′), 144.16 d (C5), 144.76 s (C2), 157.33 s (C8a),
161.79 s (C9a), 171.58 s (C7), 192.36 s (C3). Found, %:
C 54.33; H 6.00; N 10.29. [M]+ 443. C24H32N4O4. Cal-
culated, %: C 53.71; H 5.90; N 10.01. M 442.23.
2-(1,5-Diazacycloundecan-3-ylidene)-7H-furo-
[3,2-g]chromene-3,7(2H)-dione (XVI). Yield 26 (i),
56 (v), 14% (vii), mp 186–188°C (from hexane). IR
spectrum, ν, cm–1: 3282, 3035, 2854, 1649, 1633,
1531, 1387, 1239, 1213, 1171, 1120, 1090, 1082,
1035, 779, 750, 715. UV spectrum, λmax, nm (logε):
225 (3.51), 255 (3.40), 297 (3.31), 346 (3.13).
1H NMR spectrum, δ, ppm (J, Hz): 0.75 m (4H, 8′-H,
9′-H), 1.63 m (4H, 7′-H, 10′-H), 2.39 m (4H, 6′-H,
11′-H), 2.84 br.s (4H, 2′-H, 4′-H), 6.26 d (1H, 6-H, J =
9.8), 6.98 s (1H, 9-H), 7.56 d (1H, 5-H, J = 9.8), 7.95 s
(1H, 4-H). 13C NMR spectrum, δC, ppm: 27.04 t (C8′,
C9′), 29.78 t (C7′, C10′), 48.88 t (C2′, C4′), 51.92 t (C6′,
C11′), 98.66 d (C9), 112.91 d (C6), 113.60 s (C4a),
115.60 s (C3a), 123.31 d (C4), 126.75 s (C3′), 144.30 d
(C5), 144.90 s (C2), 157.53 s (C8a), 161.93 s (C9a),
171.78 s (C7), 193.86 s (C3). Found, %: C 67.25;
H 6.34; N 8.01. [M]+ 354. C20H22N2O4. Calculated, %:
C 67.78; H 6.26; N 7.90. M 354.16.
2-(1,4-Dithia-7,11-diazacyclotridecan-9-ylidene)-
7H-furo[3,2-g]chromene-3,7(2H)-dione (XXII).
Yield 28 (i), 44% (v); mp 101–103°C (from Et2O). IR
spectrum, ν, cm–1: 3437, 3061, 2975, 2934, 2853,
2676, 2592, 2452, 1727, 1624, 1482, 1393, 1350, 1289,
1193, 1138, 1023, 909, 829, 741. 1H NMR spectrum, δ,
ppm (J, Hz): 2.86 m (8H, 5′-H, 8′-H, 10′-H, 13′-H),
2.92 m (4H, 6′-H, 12′-H), 2.98 m (4H, 2′-H, 3′-H),
6.24 d (1H, 6-H, J = 9.8), 6.97 s (1H, 9-H), 7.55 d (1H,
5-H, J = 9.8), 7.94 s (1H, 4-H), 8.60 br.s (2H, NH).
13C NMR spectrum, δC, ppm: 28.76 t (C5′, C13′), 38.32 t
(C2′, C3′), 50.63 t (C8′, C10′), 54.62 t (C6′, C12′), 103.81 d
(C9), 112.29 d (C6), 113.46 s (C4a), 116.13 s (C3a),
123.08 d (C4), 126.10 s (C9′), 144.04 d (C5), 145.00 s
(C2), 157.04 s (C8a), 161.59 s (C9a), 171.63 s (C7),
192.69 s (C3). Found, %: C 57.65; H 5.62; N 6.35;
S 15.56. [M]+ 418. C20H22N2O4S2. Calculated, %:
C 57.39; H 5.30; N 6.69; S 15.32. M 418.16.
(E)- and (Z)-2-(1,5,9-Triazacyclotridecan-3-yli-
dene)-7H-furo[3,2-g]chromene-3,7(2H)-diones
(XIXa/XIXb) were synthesized from 300 mg
(0.75 mmol) of compound II and 210 mg (1.5 mmol)
of spermidine in the presence of 4.4 mg (4 mol %) of
Pd(OAc)2, 34 mg (8 mol %) of BINAP, and 0.07 ml
(1.3 equiv) of Et3N in 4 ml of anhydrous DMF (v).
Yield 158 mg (55%), mp 187–189°C (from Et2O). IR
spectrum, ν, cm–1: 3424, 3300, 3069, 2782, 1725,
1637, 1615, 1578, 1520, 1364, 1305, 1284, 1216,
1142, 1121, 1039, 980, 956, 877, 847, 823, 757. UV
spectrum, λmax, nm (logε): 201 (4.25), 217 (4.14), 257
1
(4.30), 297 (3.98), 336 (3.65). H NMR spectrum, δ,
ppm (J, Hz): 1.30 m and 1.47 m (1H each, 12′-H),
1.88 m (4H, 11′-H), 1.98 m (4H, 7′-H), 2.40 m (4H,
13′-H), 2.53 m and 2.55 m (4H each, 6′-H, 10′-H),
2.68 br.s and 2.79 br.s (4H each, 2′-H, 4′-H in E and Z
isomers), 3.46 m (4H, 8′-H), 3.60 br.s (3H, NH), 6.22 d
(1H, 6-H, J = 9.8), 6.93 s (1H, 9-H), 7.51 d (1H, 5-H,
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 09-03-00183 and 08-03-00340).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 12 2010

LIPEEVA et al.
8. Wolfe, J.P. and Buchwald, S.L., J. Org. Chem., 2000,
1868
REFERENCES
vol. 65, p. 1144.
1. Lipeeva, A.V., Shul’ts, E.E., Shakirov, M.M., and Tolsti-
kov, G.A., Khim. Prirodn. Soedin., 2009, vol. 45, p. 338.
2. Lowes, M.A., Bowcock, A.M., and Krueger, J.G., Nature,
9. Wagaw, S., Rennels, R.A., and Buchwald, S.L., J. Am.
Chem. Soc., 1997, vol. 119, p. 8451.
10. Harris, M.C., Geis, O., and Buchwald, S.L., J. Org.
Chem., 1999, vol. 64, p. 6019; Artamkina, G.A.,
Sergeev, A.G., and Beletskaya, I.P., Tetrahedron Lett.,
2001, vol. 42, p. 4381; Kamer, P.C.J., Van Leeu-
wen, P.W.N.M., and Reek, J.N.H., Acc. Chem. Res.,
2001, vol. 34, p. 895; Klingensmith, L.M., Strieter, E.R.,
Barder, T.E., and Buchwald, S.L., Organometallics,
2006, vol. 25, p. 82.
2007, vol. 445, p. 866.
3. González-Gómez, J.C., Santana, L., and Uriarte, E.,
Tetrahedron, 2003, vol. 59, p. 8171; Dalla Via, L.,
Uriarte, E., Santana, L., Marciani Magno, S., and Gia, O.,
Arkivoc, 2004, part (v), p. 131; Dalla Via, L., González-
Gómez, J.C., Pérez-Montoto, L.G., Santana, L., Uri-
arte, E., Marciani Magno, S., and Gia, O., Bioorg. Med.
Chem. Lett., 2009, vol. 19, p. 2874.
4. Shul’ts, E.E., Petrova, T.N., Shakirov, M.M., Cher-
nyak, E.I., Pokrovskii, L.M., Nekhoroshev, S.A., and
Tolstikov, G.A., Khim. Inter. Ustoich. Razv., 2003, no. 4,
p. 683.
11. Meyers, C., Maes, B.U.W., Loones, K.T.J., Bal, G.,
Lemière, G.L.F., and Dommisse, R.A., J. Org. Chem.,
2004, vol. 69, p. 6010.
12. Newman, D.J., Cragg, G.M., and Snader, K.M., Nat.
Prod. Rep., 2000, vol. 17, p. 215; Rogoza, L.N.,
Salakhutdinov, N.F., and Tolstikov, G.A., Usp. Khim.,
2005, vol. 74, p. 411; Nicolaou, K.C., J. Org. Chem.,
2005, vol. 70, p. 7007.
5. Osadchii, S.A., Shul’ts, E.E., Shakirov, M.M., and Tol-
stikov, G.A., Izv. Ross. Akad. Nauk, Ser. Khim., 2006,
p. 362.
6. Averin, A.D., Ranyuk, E.R., Lukashev, N.V., Golub, S.L.,
Buryak, A.K., and Beletskaya, I.P., Tetrahedron Lett.,
2008, vol. 49, p. 1188; Averin, A.D., Uglov, A.N.,
Ranyuk, E.R., Lukashev, N.V., and Beletskaya, I.P., Russ.
J. Org. Chem., 2009, vol. 45, p. 273; Ranyuk, E.R.,
Averin, A.D., Lukashev, N.V., Buryak, A.K., and Belets-
kaya, I.P., Russ. J. Org. Chem., 2009, vol. 45, p. 1755.
13. Voronkov, M.G., Knutov, V.I., Usov, V.A., Butin, M.K.,
and Bannikova, O.B., Khim. Geterotsikl. Soedin., 1979,
p. 1474.
14. Shul’pin, G.B., Organicheskie reaktsii, kataliziruemye
kompleksami metallov (Organic Reactions Catalyzed by
Metal Complexes), Moscow: Nauka, 1988, p. 275.
15. Ukai, T., Kawazura, H., Ishii, Y., Bonnet, J.I., and
7. Bruchhausen, F. and Hoffman, H., Chem. Ber., 1941,
vol. 74, p. 1584.
Ibe
rs, J.A., J. Organomet. Chem., 1974, vol. 65, p. 253.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 12 2010