Synthetic transformations of sesquiterpene lactones 6. Alantolactone and isoalantolactone derivatives in the Heck reaction

Article abstract of DOI:10.1007/s11172-012-0274-4

The Heck reaction of the eudesman-type methylidenelactones (alantolactone, alloalantolactone, and 4,15-epoxyisoalantolactone) with haloarenes afforded the corresponding (E)-13-aryleudesma-4(15),11(13)-dien-8β,12-olides and 11-arylmethyl-13-noreudesma-4(15

Full text of DOI:10.1007/s11172-012-0274-4

Russian Chemical Bulletin, International Edition, Vol. 61, No. 10, pp. 1975—1985, October, 2012
1975
Synthetic transformations of sesquiterpene lactones
6.* Alantolactone and isoalantolactone derivatives in the Heck reaction
E. E. Shul´ts, A. V. Belovodskii, M. M. Shakirov, and G. A. Tolstikov
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences,
9 prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383) 330 9752. Eꢀmail: schultz@nioch.nsc.ru
The Heck reaction of the eudesmanꢀtype methylidenelactones (alantolactone, alloalantoꢀ
lactone, and 4,15ꢀepoxyisoalantolactone) with haloarenes afforded the corresponding (E)ꢀ13ꢀ
aryleudesmaꢀ4(15),11(13)ꢀdienꢀ8,12ꢀolides and 11ꢀarylmethylꢀ13ꢀnoreudesmaꢀ4(15),7(11)ꢀ
dienꢀ8,12ꢀolides. The yields and the ratios of the arylation products depended on the reaction
conditions and the structure of lactone. Certain side processes were found to take place.
Key words: alantolactone, isoalantolactone, epoxyisoalantolactone, alloalantolactone,
Heck reaction.
In the preceding works,1—3 we have shown that sesꢀ
Scheme 1
quiterpene ꢀmethylidenelactones, viz., isoalantolactone
(1) and alantolactone (2) taken as examples, can be modꢀ
ified by the Heck reaction with aryl halides via the introꢀ
duction of aromatic substituents at position C(13). Such
a modification of sesquiterpenoids was of interest, since it
was found that the presence of an arylidene fragment in
the lactone ring is responsible for the valuable pharmacoꢀ
logical properties of the indicated metabolites and their
derivatives.4 Thus, certain 13ꢀaryleudesmanolides have
been patented as promising antiulcer agents.5 In the present
work, we report the results of our studies of the arylation
reaction of available isoalantolactone (1) derivatives:
4,15ꢀepoxyisoalantolactone (3)6 and alloalantolactone
(4),7 as well as alantolactone 2 (Scheme 1).
The reaction of 4,15ꢀepoxyisoalantolactone 3 with
4ꢀfluoroiodobenzene (5a), 4ꢀiodoveratrole (5b), and
4ꢀbromopyrochatehol (5c) catalyzed by the system
Reagents and conditions: i. MCPBA; CH2Cl2, 20 C; ii. CF3COOH,
CHCl3, 20 C.
Pd(OAc)2—tri(oꢀtolyl)phosphine (4/16 mol.%) in DMF
in the presence of triethylamine as a base (120 C, 8 h,
Scheme 2) led to the corresponding mixtures of (E)ꢀ13ꢀ
aryleudesmaꢀ4(15),11(13)ꢀdienꢀ8,12ꢀolides (6—8) (yields
55—80%) and endocyclic isomeric 11ꢀarylmethylꢀ13ꢀnorꢀ
eudesmaꢀ4(15),7(11)ꢀdienꢀ8,12ꢀolides (9—11) (yields
10—20%). The highest total yield of the mixture of comꢀ
pounds 7 and 10 (90%) was achieved in the reaction of
lactone 3 with 4ꢀiodoveratrole 5b; in the reaction of comꢀ
pound 3 with 4ꢀbromopyrochatehol 5c under the same
experimental conditions, a decrease in the total yield of
products 8 and 11 (to 65%) was observed. In the reaction
of methylydenelactone 3 with 4ꢀfluoroiodobenzene 5a,
besides compounds 6 (60%) and 9 (10%), (Z)ꢀisomer (12)
was also isolated (yield 6%). The reaction of methylꢀ
idenelactone 3 with 4ꢀbromoiodobenzene (5d) proceeded
in acetonitrile under conditions of nonꢀligand catalysis
with the formation of compounds 13 and 14 in 60 and
20% yields, respectively.
Earlier,2 we have shown that the reaction of alantolacꢀ
tone 2 with 4ꢀiodoveratrole 5b in DMF in the presence of
catalytic amounts of palladium acetate and tri(oꢀtolyl)ꢀ
phosphine, as well as triethylamine, (120 C, 8 h) gave rise
to arylꢀsubstituted derivatives 15 and 16 in low yields (the
conversion was 75%; the yields were 20 and 36%, respecꢀ
* For Part 5, see Ref. 1.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1959—1968, October, 2012.
1066ꢀ5285/12/6110ꢀ1975 © 2012 Springer Science+Business Media, Inc.

1976
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 10, October, 2012
Shul´ts et al.
Scheme 2
i. Pd(OAc)2, (2ꢀMeC6H4)3P, DMF, Et3N, 120 C, 8 h; ii. Pd(OAc)2, MeCN, Et3N, 80 C, 12 h.
R1 = F, R2 = H (5a, 6, 9, 12); R1 = R2 = OMe (5b, 7, 10); R1 = R2 = OH (5c, 8, 11); R1 = Br, R2 = H (5d, 13, 14)
Hal = I (5a,b,d), Br (5c)
tively). The reaction of lactone 2 with 4ꢀfluoroiodobenzꢀ
ene (5a), 4ꢀiodoanisole (5e), 2,4ꢀdimethoxyiodobenzene
(5f), and 4ꢀiodobenzonitrile (5g) also led to the correꢀ
sponding mixtures of two isomeric products (17—20 and
of methylidenelactones 1 and 2 (1 : 1) (the mixture with
such a ratio of lactones is easily isolated by the extraction
of the root Inula helenium) with iodide 5b, four comꢀ
pounds were identified in the reaction mixture: the isoꢀ
meric arylꢀsubstituted eudesmanolides 25 and 26 (the conꢀ
tent of ~70 and 20%, respectively, calculated based on the
converted lactone); isoalantolactone 1 (20% from the startꢀ
ing amount), and alantolactone 2 (90% from the startꢀ
ing amount) (according to the 1H NMR spectroscopic
and chromatoꢀmass spectrometric data for the reaction
mixture).
The reaction of alloalantolactone 4 with 4ꢀiodoveratꢀ
role 5b catalyzed by the system palladium acetate—triꢀ
(oꢀtolyl)phosphine in DMF in the presence of triethylꢀ
amine (120 C, 10 h) proceeded with the formation of
compounds 27 and 28 (yields 30 and 35%, respectively)
(Scheme 3).
As it is seen, the yield and the composition of the
reaction products significantly depended on the structure
of methylidenelactone. The reaction of epoxyisoalantoꢀ
lactone 3 with haloarenes was distinguished by the formaꢀ
tion of high yields of the exocyclic lactones 6—8 and 13.
The endocyclic alkenes 16, 21—24, and 28 were isolated
as the major reaction products of arylation of methylꢀ
idenelactones 2 and 4. In the specially designed experiꢀ
ments, it was found that no isomerization of 13ꢀaryleudesꢀ
manolides 6 or 17 to compounds 9 or 21 occurred when
the starting methylidenelactones were subjected to the reꢀ
action conditions (Pd(OAc)2—(2ꢀMeC6H4)3P—Et3N—
DMF, 120 C, 15 h).
The fact that the outcome of the Heck reaction is signiꢀ
ficantly influenced by the structure of methylidenelactone
is also confirmed by the literature data. Thus, the arylaꢀ
tion of eudesmanolides of partenolide or 11,13ꢀdehydroꢀ
santonine containing transꢀannulated lactone ring was reꢀ
ported to be selective and exclusively resulted to the correꢀ
sponding exocyclic 13(E)ꢀarylidenelactones.9 The arylaꢀ
tion of unsubstituted ꢀmethylideneꢀꢀbutyrolactone with
1
21—24). Based on the analysis of the H NMR spectra
and the chromatoꢀmass spectrometric data of the reaction
mixtures, it was determined that the conversion of lactone 2
was 70—75%, whereas the ratios of lactones 17 : 21,
18 : 22, 19 : 23, and 20 : 24 were within the range 1.0 : 1.0 
 0.75 : 1.0. After the reaction mixtures were subjected to
chromatography, compounds 17—20 and 21—24 were
isolated in 15—21 and 22—29% yields, respectively. The
conversion of the starting compounds and the selectivity
of the reaction are considerably influenced by the temperꢀ
ature regime. Thus, when the reaction of lactone 2 with
2,4ꢀdimethoxyiodobenzene 5f was carried out at 90, 105,
and 120 C, the ratios of products 19 and 23 were 1.4 : 1,
1.05 : 1, and 0.85 : 1, respectively, and the conversions of
the starting compounds were 20, 30, and 75%. An elevaꢀ
tion of the temperature to 140 C caused a deep resinificaꢀ
tion of the reaction mixture (to 60%). A twoꢀfold increase
in the time of the reaction of lactone 2 with 4ꢀiodoaniꢀ
sole 5e did not result in any noticeable changes in the
conversion (~35% of the starting lactone remained unꢀ
consumed). If the amount of palladium acetate was
increased (8—10 mol.%), the conversion of lactone 2
increased to 85—95%, with the ratio of the products reꢀ
maining virtually unchanged.
It should be noted that the activity of alantolactone 2
in the reaction with aryl bromides, such as bromobenzene
and 4ꢀbromotoluene, is low. When the reaction with these
bromides was carried out in DMF in the presence of
Pd(OAc)2/(2ꢀMeC6H4)3P and triethylamine (120 C), the
conversion of substrate 2 after 20 h did not exceed 10%.
The reaction of methylidenelactone 2 with 4ꢀiodoꢀ
veratrole 5b under conditions of nonꢀligand catalysis
[Pd(OAc)2—Et3N—MeCN] was also slow: 80% of comꢀ
pound 2 was recovered. A competing reaction of a mixture

Heck reaction of alantolactones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 10, October, 2012
1977
Scheme 3
R1 = R2 = OMe, R3 = H (15, 16); R1 = F, R2 = R3 = H (5a, 17, 21); R1 = OMe, R2 = R3 = H (5e, 18, 22); R1 = R3 = OMe, R2 = H (5f, 19, 23);
1 = CN, R2 = R3 = H (5g, 20, 24)
R
iodoarenes in the presence of the catalytic system
Pd(OAc)2/(2ꢀMeC6H4)3P and triethylamine in DMF proꢀ
ceeded with the formation of two isomeric products with
exoꢀ and endocyclic position of the double bond.10 The
structure of ꢀmethylidenelactones 1—4 is distinguished
by the cisꢀannulation of the lactone ring to the octaꢀ
hydronaphthalene fragment, and in this case compounds
2 and 4 do not contain an Hꢀatom at position C(5) that,
probably, is the reason for the increase in the yield of the
products with the endocyclic double bond in the Heck
reaction of the lactones indicated.
A thorough examination of the minor reaction prodꢀ
ucts of alantolactone 2 with iodoarenes 5a,g resulted in
the isolation of isomerization products: alantolactone (29)
(yield 3—5%) and spiro compounds (30 or 31) (yields 2
and 3%, respectively) (Scheme 4).
The most plausible scheme for the formation of spiroꢀ
lactones 30 and 31 is based on the [4+2] cycloaddition
reaction of alantolactone 2 (see Scheme 4). It can be sugꢀ
gested that the forming 13ꢀaryleudesmanolides 17 and 21
upon the action of the catalytic system undergo decarbꢀ
oxylation, leading to trienes A. Then follows a diene synꢀ
thesis through the formation of the transition state B. Earꢀ
lier, the C(11)=C(13) double bond in lactones 1 and 2 was
found to be active in the Diels—Alder reaction.11
The structures of compounds synthesized were estabꢀ
lished based on the combination of the elemental analysis
data and spectroscopic characteristics. The (E)ꢀconfiguꢀ
ration of the C(11)=C(13) double bond in arylidenelacꢀ
tones 6—8, 13, 15, 17—20, and 27 was concluded from
the presence in the 13C NMR spectrum (monoresonance
mode) of the cisꢀspinꢀspin coupling constant between the
olefin proton and the carbonyl carbon atom of the lactone
(3Jcis = 6.9—7.5 Hz); the corresponding transꢀconstant
for the (Z)ꢀisomer 12 is equal to 13.2 Hz. The signal for
1
the proton H(13) in the H NMR spectra of (E)ꢀisomers
6—8, 13, 15, 17—20, and 27 was found in the region of
 7.34—7.46, whereas for the (Z)ꢀisomer 12, at  6.81. The
1H NMR spectra of compounds 6—8, 13, 15, 17—20, and
27 are characterized by a downfield shift of the signal for
the proton H(7) ( 3.28—4.07) as compared to the signal
for the corresponding proton in the spectrum of lactone 1
or in the spectrum of (Z)ꢀisomer 12 ( 2.89).
An indicative feature of the 1H NMR spectra of comꢀ
pounds 9—11, 14, 16, 21—24, 26, and 28 is the presence
of signals for the protons of the methylene group at the

1978
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 10, October, 2012
Shul´ts et al.
Scheme 4
i. Pd(OAc)2, (2ꢀMeC6H4)3P, Et3N, DMF.
R = F (30), CN (31)
C(13) atom (for example, for compound 14,  = 3.43 and
3.49 (both d, 2 H, H(13), J = 14.8 Hz)) and a significant
increase in the difference of chemical shifts for the proꢀ
tons H(9) ( 1.0—1.3 ppm). The upfield signal for the
proton H(9) ( 1.06 for 14) has an axialꢀaxial constant
with the proton H(8) (J = 11.9 Hz). The (8S)ꢀconfiguraꢀ
tion of compounds 14, 16, 22, 28, and 29 was confirmed
by the data of the NOESY experiments: the crossꢀpeaks
between the signals for the protons of the methyl group
C(14)H3 and the proton H(8) were observed.
peaks with the H atoms at  1.48, 1.87, 1.27, 1.57, 3.68,
and 5.23. The spinꢀspin coupling constants of the indicatꢀ
ed proton obtained from the NMR experiments with the
decoupling of one of the signals for compound 31 indicate
the presence of two axialꢀaxial (J = 12.2, J = 10.9 Hz) and
two axialꢀequatorial interactions with protons H(9´) and
H(13). All the interactions were found and assignment for
all the signals were made using the data of 2D NMR specꢀ
troscopy (COSY, HMBC, HSQC, JꢀResolved, NOESY,
HOESY).
The chromatoꢀmass spectra of dimeric compounds 30
and 31 exhibited peaks with the m/z 514 and 521, respecꢀ
tively. According to the data of 13C NMR spectroscopy,
the number of carbon atoms is equal to 35 and 36, respecꢀ
tively. The 1H NMR spectra of compounds 30 and 31
contain signals for the protons of the aromatic substituent
and a set of signals for the terpene framework correspondꢀ
ing to the framework of alantolactone. The splitting of the
signals H(7) and H(13) indicates that the C(11) carbon
atom is quaternary. The formation of the regioisomers
indicated (the orientation of the aromatic substituent in
the diene at position C(11)) can be concluded from the
pattern of the signal for the H(13´) proton ( 3.68, J = 4.5,
J = 1.0, J = 1.5 Hz) interacting with the methine proton
H(11´) ( 5.23), as well as with the protons H(7) and
H(8´) (J = 1.0 and J = 1.5 Hz). A characteristic feature of
the 1H NMR spectra is the presence of an unresolved
multiplet at  3.38—3.41 (for compound 31, the halfꢀ
height width is equal to 28 Hz), corresponding to the proꢀ
ton H(8´) and having in the 1H—1H COSY spectra crossꢀ
The configuration of the chiral centers formed can be
concluded from the consideration of the interactions of
protons H(7), H(8), H(8´), H(9´), H(13), and H(13´).
The presence of the NOE between the atom H(13´) and
the atoms H (H(7) and H(8)), as well as between the
atoms H(13´) and H(8´) indicates their sinꢀarrangement
(Fig. 1). The presence of the indicated interactions conꢀ
firms the 13´(S)ꢀconfiguration. According to the molecuꢀ
lar mechanics data (the MM2 method), in the case when
the 13´(S)ꢀconfiguration is effected, the atom H(13´) is
equidistant from the atoms H(7) and H(8), whereas in the
13´(R)ꢀconfiguration the distance H(8)—H(13´) is signifꢀ
icantly larger than the H(7)—H(13´) (in this case, the
NOE observed with the atom H(8) is stronger than in the
case of H(7)). The configuration of the atoms C(10´) and
C(4´) is also postulated based on the calculated data
(MM2), according to which only in such arrangement of
the atoms the conformation, in which the atom H(8´) has two
axialꢀaxial interactions with hydrogen atoms of the neighꢀ
boring methylene groups, is possible and a NOEꢀeffect

Heck reaction of alantolactones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 10, October, 2012
1979
lation of the individual products by column chromatography was
complicated by their lability in the adsorbed state and close valꢀ
ues of the separation factor. For the separation of mixtures of
compounds 17—20 and 21—24 obtained by the reaction of alanꢀ
tolactone 2 with iodides 5a,e,f,g, the silica gel impregnated with
AgNO3 (10%)12 was used. For the separation of compounds 15
and 16, the use of alumina has proved preferable, with the mixꢀ
ture of benzene—ethyl acetate (100 : 0  10 : 1) being an eluent.
Lactones 1 and 2 were isolated by the extraction of Inula
helenium with subsequent separation through the morpholine
adducts according to the procedures described earlier.13 In this
work, we used commercially available iodoarenes 5a,b,e,g.
3,4ꢀDihydroxybromobenzene 5c,14 4ꢀiodobromobenzene 5d,15
2,4ꢀdimethoxyiodobenzene 5f,16 as well as Pd(OAc)2 (see
Ref. 17), were obtained according to the known procedures.
The Heck reaction of methylidenelactones 1—4 with aryl
halides (general procedure). A twoꢀneck glass tube was filled with
argon. The tube was sequentially loaded with lactone 1—4
(1.0—2.15 mmol), haloarene (1.10—2.36 mmol), palladium
acetate (4 mol.%), tri(oꢀtolyl)phosphine (16 mol.%), DMF
(4—12 mL), triethylamine (1.5—2.0 equiv.), and molecular sieves
3 Å under a constant flow of argon, then the tube was sealed
(with slight excessive pressure of argon). The reaction mixture
was heated for 8—16 h at 120 C. Then, the system was allowed
to cool down, the tube was unsealed, and the content was poured
in a Petri dish. The solid residue was dissolved in minimum
amount of chloroform and subjected to chromatography on siliꢀ
ca gel (eluent chloroform—ethanol, 100 : 0  10 : 1). The folꢀ
lowing compounds were sequentially eluted: tri(oꢀtolyl)phosꢀ
phine, the starting lactone, a mixture of the lactone and the
reaction product, and a mixture of two reaction products (eluent
chloroform). For the isolation of individual compounds, an addiꢀ
tional chromatographic separation and recrystallization from the
corresponding solvent were used. Analytically pure samples were
purified using preparative TLC. Spectroscopic characteristics of
compounds 15, 16 and 25, 26 have been published earlier.1,2
The reaction of (534 mg, 2.15 mmol) epoxyisoalantolacꢀ
tone 3 and 4ꢀiodofluorobenzene 5a (525 mg, 2.36 mmol) in
the presence of palladium acetate (19 mg, 0.086 mmol), triꢀ
(oꢀtolyl)phosphine (103 mg, 0.34 mmol), DMF (10 mL), and
Fig. 1. Configurations of chiral centers and indicative interacꢀ
tions of protons in the 1H—1H NOESY spectrum of comꢀ
pound 31.
between protons H(8´) and H(13´) will be observed in the
8´(R)ꢀconfiguration. The 11(S)ꢀconfiguration also folꢀ
lowed from the stereoselectivity of the Diels—Alder reacꢀ
tion and was confirmed by the result of the reaction of
lactone 1 with ꢀphellandren.11
Experimental
1
H and 13C NMR spectra of solutions of compounds in
CDCl3 were recorded on Bruker AVꢀ300 (300.13 (1H) and
75.47 MHz (13C)), Bruker AVꢀ400 (400.13 (1H) and 100.78 MHz
13C)), Bruker AVꢀ600 (600.13 (1H) and 150.96 MHz (13C))
(
spectrometers using signals of the solvent as references (H 7.24
and  77.0). The numeration of atoms of the sesquiterpene
C
framework given in Scheme 1 was used in the description of the
1H and 13C NMR spectra. Different types of protonꢀproton and
carbonꢀproton shift correlation spectroscopy (COSY, COXH,
COLOC, NOESY) were used to assign signals in the NMR specꢀ
tra. Recording spectra in the Jꢀmodulation mode was useded to
determine the splitting of the signals in the 13C NMR spectra. To
obtain mass spectra and to determine molecular masses and eleꢀ
mental composition, a DFS Thermo Scientific high resolution
mass spectrometer was used (EI, 70 eV, the temperature of the
injector was 230—280 C). Melting points were measured on a
Stuart SMFꢀ38 heating stage.
triethylamine (0.5 mL, 3.61 mmol) during
8 h gave
(2´R,3aR,4aR,8aR,9aR,E)ꢀ3ꢀ(4ꢀfluorobenzylidene)ꢀ8aꢀmethylꢀ
decahydroꢀ2Hꢀspiro[naphtho[2,3ꢀb]furanꢀ5,2´ꢀoxiran]ꢀ2ꢀone
(6) (440 mg, 60%), (2´R,4aR,8aR,9aR)ꢀ3ꢀ(4ꢀfluorobenzyl)ꢀ
8aꢀmethylꢀ4,4a,6,7,8,8a,9,9aꢀoctahydroꢀ2Hꢀspiro{naphthoꢀ
[2,3ꢀb]furanꢀ5,2´ꢀoxiran}ꢀ2ꢀone (9) (74 mg, 10%), and
(2´R,3aR,4aR,8aR,9aR,Z)ꢀ3ꢀ(4ꢀfluorobenzylidene)ꢀ8aꢀmethylꢀ
decahydroꢀ2Hꢀspiro{naphtho[2,3ꢀb]furanꢀ5,2´ꢀoxiran}ꢀ2ꢀone
(12) (45 mg, 6%). Compound 6, m.p. 178—180 C (from ethanol),
[]D20 +292 (c 0.8, CHCl3). IR (KBr), /cm–1: 839, 996, 1161,
1224, 1507, 1598, 1661, 1755, 2934. UV, max/nm (log): 201
(4.02), 220 (4.04), 226 (3.94), 284 (4.26). 1H NMR (600.13 MHz),
: 0.94 (ddd, 1 H, H(6), J = 13.2 Hz, J = 13.2 Hz, J = 12.8 Hz);
0.99 (s, 3 H, C(14)H3); 1.19 (m, 1 H, H(1)); 1.33 (dm, 1 H,
H(3), J = 11.9 Hz); 1.51 (dd, 1 H, H(9), J = 15.7 Hz, J = 4.6 Hz);
1.59 (dm, 1 H, H(5), J = 13.7 Hz); 1.65—1.71 (m, 2 H, H(1),
H(2)); 1.75 (dd, 1 H, H(6), J = 13.0 Hz, J = 2.4 Hz); 1.83—1.90
(m, 2 H, H(2), H(3)); 2.22 (dd, 1 H, H(9), J = 15.7 Hz, J = 1.5 Hz);
2.51 (d, 1 H, H(15), J = 4.4 Hz); 2.61 (dd, 1 H, H(15), J = 4.4 Hz,
J = 1.9 Hz); 3.29 (ddd, 1 H, H(7), J = 11.9 Hz, J = 6.0 Hz,
J = 5.5 Hz); 4.45 (ddd, 1 H, H(8), J = 4.6 Hz, J = 4.6 Hz,
IR spectra were recorded on a Vectorꢀ22 spectrometer, UV
absorption spectra were recorded on a HР 8453 UV—Vis spectroꢀ
meter (in ethanol). Specific rotation []D was measured on
20
a PolAAr3005 polarimeter. Reaction mixtures were examined
by chromatoꢀmass spectrometry on a Hewlett—Packard 5890/II
MSD gas chromatograph equipped with a HP MSD 5971 quadruꢀ
pole mass spectrometer as a detector. A 30ꢀm HPꢀ5MS quartz
column was used (copolymer diphenyl (5%)—dimethylenesilꢀ
oxane (95%)) with the internal diameter of 0.25 mm and the
stationary phase film thickness of 0.25 m; the temperature was
raised within the range of 50—280 C at the speed of 4 C min–1
then kept for 15 min at 280 C.
,
Elemental analysis was performed on a Carlo Erba CHNꢀ
analyzer (model 1106).
Reaction products were isolated by column chromatography
on silica gel (Acros, 0.035—0.070 mm) and, if necessary, addiꢀ
tionally by preparative TLC on a nonꢀbound 1ꢀmm thick layer of
silica gel containing 1% Kꢀ35 luminophore on 20×20ꢀcm plates
(eluents: benzene—ethyl acetate, chloroform—ethanol). The isoꢀ

1980
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 10, October, 2012
Shul´ts et al.
J = 1.3 Hz); 7.07 (dddd, 2 H, H(3´), H(5´), J = 8.8 Hz,
J = 8.4 Hz, J = 2.9 Hz, J = 1.5 Hz); 7.34 (br.s, 1 H, H(13)); 7.49
(dddd, 2 H, H(2´), H(6´), J = 8.9 Hz, J = 5.3 Hz, J = 2.9 Hz,
J = 2.1 Hz). 13C NMR, : 18.47 (C(14)); 20.23 (C(2), C(6));
34.33 (C(10)); 35.25 (C(3)); 39.16 (C(7)); 41.27 (C(9)); 41.70
(C(1)); 44.17 (C(5)); 50.54 (C(15)); 58.46 (C(4)); 76.62 (C(8));
116.17 (C(3´), C(5´)); 130.13 (C(1´)); 131.41 (C(11)); 131.51
(C(2´), C(6´)); 134.04 (C(13)); 163.25 (C(4´), JC—F = 252.0 Hz);
172.10 (C(12)). MS, m/z (Irel (%)): 342 (2), 328 (8), 327 (34),
189 (7), 161 (8), 147 (7), 140 (11), 139 (100), 138 (9), 137 (33),
135 (9), 133 (13), 109 (10), 108 (21), 107 (14), 105 (7), 91 (10),
79 (13). Found: m/z 342.1615 [M]+. C21H23FO3. Calculated:
M = 342.1626.
238 (4.03), 300 (4.11), 327 (4.25). 1H NMR (400.13 MHz),
: 0.92 (ddd, 1 H, H(6), J = 13.1 Hz, J = 13.0 Hz, J = 12.8 Hz);
0.98 (s, 3 H, C(14)H3); 1.18 (m, 1 H, H(1)); 1.31 (dm, 1 H,
H(3), Jgem = 12.6 Hz); 1.49 (dd, 1 H, H(9), J = 15.7 Hz, J = 4.7 Hz);
1.55—1.74 (m, 3 H, H(1), H(2), H(5)); 1.81—1.96 (m, 3 H,
H(2), H(3), H(6)); 2.20 (dd, 1 H, H(9), J = 15.7 Hz, J = 1.2 Hz);
2.47 (d, 1 H, H(15), J = 4.4 Hz); 2.59 (dd, 1 H, H(15), J = 4.3 Hz,
J = 1.6 Hz); 3.28 (ddd, 1 H, H(7), J = 11.8 Hz, J = 5.9 Hz,
J = 5.4 Hz); 3.85 (s, 3 H, OMe); 3.87 (s, 3 H, OMe), 4.42 (ddd,
1 H, H(8), J = 4.8 Hz, J = 4.7 Hz, J = 1.5 Hz); 6.86 (d, 1 H,
H(5´), J = 8.4 Hz); 6.94 (d, 1 H, H(2´), J = 2.0 Hz); 7.08 (dd,
1 H, H(6´), J = 8.4 Hz, J = 2.0 Hz); 7.30 (br.s, 1 H, H(13)).
13C NMR, : 18.43 (C(14)); 20.15 (C(6)); 20.25 (C(2)); 34.30
(C(10)), 35.13 (C(3)); 39.39 (C(7)); 41.24 (C(9)); 41.71 (C(1));
44.27 (C(5)); 50.52 (C(15)), 55.48 (OMe); 55.51 (OMe); 58.29
(C(4)); 76.46 (C(8)); 111.21 (C(2´)); 112.43 (C(5´)); 123.13
(C(6´)); 126.74 (C(1´)); 129.30 (C(11)); 135.31 (C(13)); 148.90
(C(4´)); 150.42 (C(3´)); 172.36 (C(12)). Found (%): C, 71.42;
H, 7.60. C23H28O5. Calculated (%): C, 71.85; H, 7.34.
Compound 10. 1H NMR (300.13 MHz), : 1.01 (s, 3 H,
C(14)H3); 1.15 (dd, 1 H, H(9), J = 12.3 Hz, J = 11.8 Hz); 1.35
(m, 2 H, H(1), H(3)); 1.57—1.72 (m, 3 H, H(1), H(2), H(6));
1.82 (m, 1 H, H(2)); 1.95 (m, 1 H, H(3)); 2.36 (dd, 1 H, H(9),
J = 12.3 Hz, J = 6.2 Hz); 2.47 (d, 1 H, H(15), J = 4.2 Hz); 2.58
(dd, 1 H, H(15), J = 4.2 Hz, J = 1.9 Hz); 2.80 (dd, 1 H, H(6),
J = 11.0 Hz, J = 3.5 Hz); 3.45 (d, 1 H, H(13), J = 14.5 Hz); 3.52
(d, 1 H, H(13), J = 14.6 Hz); 3.82 (s, 3 H, OMe); 3.85 (s, 3 H,
OMe); 4.79 (ddd, 1 H, H(8), J = 11.3 Hz, J = 6.3 Hz); 6.72 (dd,
1 H, H(6´), J = 8.1 Hz, J = 2.0 Hz); 6.76 (d, 1 H, H(5´),
J = 8.2 Hz); 6.81 (d, 1 H, H(2´), J = 2.0 Hz). 13C NMR, : 16.45
(C(14)); 21.25 (C(2)); 25.77 (C(6)); 29.01 (C(13)); 35.51 (C(3)),
38.18 (C(10)); 40.75 (C(1)); 47.18 т (C(9)); 50.32 (C(5)); 51.80
(C(15)), 55.12 (OMe); 56.02 (OMe); 58.22 (C(4)); 78.80 (C(8));
111.13 (C(2´)); 112.48 (C(5´)); 122.82 (C(6´)); 123.58 (C(11));
126.41 (C(1´)); 147.26 (C(4´)); 151.05 (C(3´)); 163.65 (C(7));
174.25 (C(12)). Found (%): C, 71.64; H, 7.65. C23H28O5. Calꢀ
culated (%): C, 71.85; H, 7.34.
The reaction of epoxyisoalantolactone 3 (248 mg, 1 mmol)
and 4ꢀbromopyrochatehol 5c (207 mg, 1.1 mmol) in the presꢀ
ence of palladium acetate (9 mg, 0.04 mmol), tri(oꢀtolyl)ꢀ
phosphine (49 mg, 0.16 mmol), DMF (4 mL), and triethylamine
(0.28 mL, 2.0 mmol) during 10 h resulted in the synthesis of
(2´R,3aR,4aR,8aR,9aR,E)ꢀ3ꢀ(3,4ꢀdihydroxybenzylidene)ꢀ8aꢀ
methyldecahydroꢀ2Hꢀspiro[naphtho[2,3ꢀb]furanꢀ5,2´ꢀoxiran]ꢀ
2ꢀone (8) (196 mg, 55%). According to the chromatoꢀmass specꢀ
trometric data, the content of isomer 11 can reach 10%. This
compound was not isolated in the pure form. Compound 8, m.p.
80—84 C (from chloroform), []D20 +298 (c 1.06, CHCl3). IR
(neat), /cm–1: 755, 1149, 1171, 1218, 1247, 1264, 1288, 1298,
1446, 1517, 1524, 1603, 1646, 1723, 1738. UV, max/nm (log):
201 (3.99), 221 (3.87), 239 (3.76), 249 (3.76), 316 (3.90), 336
(4.06). 1H NMR (600.13 MHz), : 0.95 (m, 1 H, H(6)); 0.97
(s, 3 H, C(14)H3); 1.20 (m, 1 H, H(1)); 1.38 (dm, 1 H, H(3),
J = 12.4 Hz); 1.49 (dd, 1 H, H(9), J = 15.6 Hz, J = 4.0 Hz);
1.59—1.75 (m, 3 H, H(1), H(2), H(5)); 1.87—1.97 (m, 3 H,
H(2), H(3), H(6)); 2.23 (br.d, 1 H, H(9), J = 15.6 Hz); 2.61
(d, 1 H, H(15), J = 4.0 Hz); 2.72 (d, 1 H, H(15), J = 3.0 Hz);
3.30 (ddd, 1 H, H(7), J = 11.2 Hz, J = 5.5 Hz, J = 5.0 Hz); 4.45
(dd, 1 H, H(8), J = 4.6 Hz, J = 4.0 Hz); 6.90 (m, 2 H, H(5´),
H(6´)); 7.10 (br.s, 1 H, H(2´)); 7.30 (br.s, 1 H, H(13)); 8.81
(br.s, 1 H, OH). 13C NMR, : 18.42 (C(14)); 20.13 (C(2), C(6));
20
Compound 9, oily substance, []D +102 (c 0.3, CHCl3).
1H NMR (400.13 MHz), : 0.98 (s, 3 H, C(14)H3); 1.14 (dd, 1 H,
H(9), J = 12.1 Hz, J = 11.6 Hz); 1.32 (m, 2 H, H(1), H(3)); 1.57
(m, 2 H, H(1), H(5)); 1.63 (m, 2 H, H(2), H(6)); 1.80 (m, 1 H,
H(2)); 1.95 (m, 1 H, H(3)); 2.38 (dd, 1 H, H(9), J = 12.1 Hz,
J = 5.8 Hz); 2.47 (d, 1 H, H(15), J = 4.2 Hz), 2.58 (dd, 1 H, H(15),
J = 4.2 Hz, J = 1.9 Hz); 2.74 (dd, 1 H, H(6), J = 10.8 Hz,
J = 3.9 Hz); 3.50 (d, 1 H, H(13), J = 14.6 Hz); 3.56 (d, 1 H,
H(13), J = 14.6 Hz); 4.82 (dd, 1 H, H(8), J = 10.7 Hz, J = 6.8 Hz);
6.95 (dd, 2 H, H(3´), H(5´), J = 9.1 Hz, J = 8.5 Hz); 7.17 (m, 2 H,
H(2´), H(6´)). 13C NMR, : 16.33 (C(14)); 21.78 (C(2)); 25.66
(C(6)); 28.78 (C(13)); 36.42 (C(3)); 37.21 (C(10)); 40.61 (C(1));
47.54 (C(9)); 50.16 (C(5)); 51.26 (C(15)); 58.13 (C(4)); 78.11
(C(8)); 115.55 (C(3´), C(5´)); 123.87 (C(11)); 129.88 (C(2´),
C(6´)); 133.65 (C(1´)); 161.46 (C(4´), JC—F = 244.7 Hz); 163.88
(C(7)); 174.11 (C(12)). Found (%): C, 73.48; H, 6.52; F, 5.34.
C21H23FO3. Calculated (%): C, 73.66; H, 6.77; F, 5.55.
Compound 12, m.p. 110—114 C, []D20 +50 (c 0.8, CHCl3).
1H NMR (400.13 MHz), : 0.95 (m, 1 H, H(6)); 1.01 (s, 3 H,
C(14)H3); 1.20—1.36 (m, 3 H, H(1), H(3), H(9)); 1.53 (m, 1 H,
H(5)); 1.63—172 (m, 2 H, H(1), H(2)); 1.78 (dd, 1 H, H(6),
J = 12.8 Hz, J = 2.6 Hz); 1.85—1.94 (m, 2 H, H(2), H(3)); 2.21
(dd, 1 H, H(9), J = 15.6 Hz, J = 1.9 Hz); 2.52 (d, 1 H, H(15),
J = 4.2 Hz); 2.64 (br.d, 1 H, H(15), J = 4.2 Hz); 2.89 (ddd, 1 H,
H(7), J = 11.6 Hz, J = 5.9 Hz, J = 5.5 Hz); 4.45 (m, 1 H, H(8));
6.81 (s, 1 H, H(13)); 7.08 (m, 2 H, H(3´), H(5´)); 7.86 (dddd,
2 H, H(2´), H(6´), J = 8.8 Hz, J = 8.6 Hz, J = 2.9 Hz, J = 2.3 Hz).
13C NMR, : 18.11 (C(14)); 22.77 (C(2)); 27.69 (C(6)); 34.45
(C(10)); 36.88 (C(3)); 41.78 (C(9)); 42.56 (C(1)); 44.76 (C(7));
46.28 (C(5)); 52.04 (C(15)); 58.81 (C(4)); 79.88 (C(8)); 115.31
(C(3´), C(5´)); 129.45 (C(1´)); 132.07 (C(11)); 133.11 (C(2´),
C(6´)); 136.68 (C(13)); 163.57 (C(4´), JC—F = 251.1 Hz); 169.08
(C(12)). Found (%): C, 73.29; H, 7.05; F, 5.44. C21H23FO3.
Calculated (%): C, 73.66; H, 6.77; F, 5.55.
The reaction of epoxyisoalantolactone 3 (248 mg, 1 mmol)
and 4ꢀiodoveratrole 5b (290 mg, 1.1 mmol) in the presence of
palladium acetate (9 mg, 0.04 mmol), tri(oꢀtolyl)phosphine
(49 mg, 0.16 mmol), DMF (4 mL), and triethylamine (0.28 mL,
2.0 mmol) during 10
h resulted in the synthesis of
(2´R,3aR,4aR,8aR,9aR,E)ꢀ3ꢀ(3,4ꢀdimethoxybenzylidene)ꢀ8aꢀ
methyldecahydroꢀ2Hꢀspiro{naphtho[2,3ꢀb]furanꢀ5,2´ꢀoxiran}ꢀ2ꢀ
one (7) (307 mg, 80%) and (2´R,4aR,8aR,9aR)ꢀ3ꢀ(3,4ꢀdimethoxꢀ
ybenzyl)ꢀ8aꢀmethylꢀ4,4a,6,7,8,8a,9,9aꢀoctahydroꢀ2Hꢀspiroꢀ
[naphtho[2,3ꢀb]furanꢀ5,2´ꢀoxiran]ꢀ2ꢀone (10) (38 mg, 10%).
Compound 7, m.p. 84—86 C (from diethyl ether), []D20 +352
(c 0.56, CHCl3). IR (KBr), /cm–1: 772, 818, 952, 997, 1022,
1090, 1101, 1140, 1173, 1215, 1249, 1270, 1334, 1461, 1519,
1596, 1649, 1743, 2848, 2933. UV, max/nm (log): 221 (3.96),

Heck reaction of alantolactones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 10, October, 2012
1981
34.34 (C(10)); 35.13 (C(3)); 39.12 (C(7)); 41.13 (C(9)); 41.63
(C(1)); 43.93 (C(5)); 51.17 (C(15)); 59.49 (C(4)); 76.98 (C(8));
115.61 (C(2´)); 116.07 (C(5´)); 124.04 (C(6´)); 126.35 (C(1´));
128.34 (C(11)); 136.21 (C(13)); 144.24 (C(3´)); 146.59 (C(4´));
173.45 (C(12)). MS, m/z (Irel (%)): 357 (4), 356 (17), 338 (5),
310 (4), 228 (5), 225 (6), 219 (6), 218 (12), 217 (13), 204 (23),
199 (11), 178 (19), 176 (27), 175 (17), 174 (17), 173 (33), 162
(11), 161 (14), 123 (12), 87 (12), 85 (67), 83 (100), 77 (8). Found:
m/z 356.1617 [M]+. C21H24O5. Calculated: M = 356.1618. Sigꢀ
nals characteristic of compound 11 in the 1H NMR spectrum
(400.13 MHz),  (the data were obtained for the sample with the
purity of 82%): 1.05 (s, 3 H, C(14)H3); 1.18 (m, 1 H, H(9)); 1.35
(m, 2 H, H(1), H(3)); 1.53—1.70 (m, 3 H, H(1), H(2), H(6));
1.85 (m, 1 H, H(2)); 1.98 (m, 1 H, H(3)); 2.38 (dd, 1 H, H(9),
J = 12.1 Hz, J = 6.0 Hz); 2.49 (d, 1 H, H(15), J = 4.1 Hz); 2.60
(dd, 1 H, H(15), J = 4.1 Hz, J = 1.9 Hz); 2.88 (dd, 1 H, H(6),
J = 11.2 Hz, J = 3.6 Hz); 3.48 (d, 1 H, H(13), J = 14.5 Hz); 3.55
(d, 1 H, H(13), J = 14.5 Hz); 4.79 (ddd, 1 H, H(8), J = 11.3 Hz,
J = 6.3 Hz, J = 2.0 Hz); 6.78 (m, 2 H, H(6´), H(5´)); 6.92
(d, 1 H, H(2´), J = 1.8 Hz).
The heating of a mixture of epoxyisoalantolactone 3 (500 mg,
2.01 mmol) and 4ꢀiodobromobenzene 5d (630 mg, 2.21 mmol)
in the presence of palladium acetate (22.5 mg, 0.1 mmol) and
triethylamine (0.39 mL, 2.8 mmol) in acetonitrile (10 mL) in a
sealed tube during 16 h, concentration, and subsequent separaꢀ
tion of the reaction products by column chromatography resultꢀ
ed in the preparation of (2´R,3aR,4aR,8aR,9aR,E)ꢀ3ꢀ(4ꢀbroꢀ
mobenzylidene)ꢀ8aꢀmethyldecahydroꢀ2Hꢀspiro[naphtho[2,3ꢀb]ꢀ
furanꢀ5,2´ꢀoxiran]ꢀ2ꢀone (13) (486 mg, 60%) and (2´R,4aR,
8aR,9aR)ꢀ3ꢀ(4ꢀbromobenzyl)ꢀ8aꢀmethylꢀ3ꢀ4,4a,6,7,8,8a,9,9aꢀ
octahydroꢀ2Hꢀspiro[naphtho[2,3ꢀb]furanꢀ5,2´ꢀoxiran]ꢀ2ꢀone
J = 12.9 Hz, J = 11.7 Hz, J = 6.3 Hz); 1.33 (dddd, 1 H, H(3),
J = 12.8 Hz, J = 3.5 Hz, J = 2.8 Hz, J = 1.5 Hz); 1.56 (dddd,
1 H, H(1), J = 13.2 Hz, J = 3.4 Hz, J = 3.1 Hz, J = 1.5 Hz); 1.63
(dd, 1 H, H(5), J = 13.1 Hz, J = 3.7 Hz); 1.67—1.73 (m, 2 H,
H(2)); 1.78 (dd, 1 H, H(6), J = 13.3 Hz, J = 12.9 Hz); 1.79
(m, 1 H, H(3)); 2.36 (dd, 1 H, H(9), J = 12.0 Hz, J = 6.3 Hz);
2.59 (d, 1 H, H(15), J = 4 Hz); 2.73—2.75 (m, 2 H, H(6),
H(15)); 3.43 (d, 1 H, H(13), J = 14.8 Hz); 3.49 (d, 1 H, H(13),
J = 14.8 Hz); 4.75 (dd, 1 H, H(8), J = 11.9 Hz, J = 6.3 Hz); 7.06
(dm, 2 H, H(2´), H(6´), J = 8.4 Hz, J = 2.6 Hz, J = 1.9 Hz); 7.34
(dm, 2 H, H(3´), H(5´), J = 8.4 Hz, J = 2.6 Hz, J = 1.9 Hz).
13C NMR, : 17.03 (C(14)); 20.03 (C(2)); 21.69 (C(6)); 28.44
(C(13)); 34.75 (C(3)); 36.88 (C(10)); 39.76 (C(1)); 47.63 (C(5));
47.76 (C(9)); 50.14 (C(15)); 58.67 (C(4)); 77.60 (C(8)); 120.12
(C(4´)); 123.29 (C(11); 130.03 (C(2´), C(6´)); 131.44 (C(3´),
C(5´)); 137.10 (C(1´)); 162.63 (C(7)); 173.44 (C(12)). Found (%):
C, 62.18; H, 5.45; Br, 19.60. C21H23BrO3. Calculated (%):
C, 62.54; H, 5.75; Br, 19.81.
The reaction of alantolactone 2 (464 mg, 2.0 mmol) and
4ꢀiodofluorobenzene 5a (489 mg, 2.2 mmol) in the presence of
palladium acetate (17.7 mg, 0.08 mmol),tri(oꢀtolyl)phosphine
(97 mg, 0.32 mmol), DMF (10 mL), and triethylamine (0.5 mL,
3.61 mmol) during 16 h and subsequent column chromatograꢀ
phy on an impregnated silica gel resulted in the isolation of
(3aR,5S,8aR,9aR,E)ꢀ3ꢀ(4ꢀfluorobenzylidene)ꢀ5,8aꢀdimethylꢀ
3,3a,6,7,8,8a,9,9aꢀoctahydronaphtho[2,3ꢀb]furanꢀ2(5H)ꢀone
(17) (117 mg, 18%), (5S,8aR,9aS)ꢀ3ꢀ(4ꢀfluorobenzyl)ꢀ5,8aꢀdiꢀ
methylꢀ6,7,8,8a,9,9aꢀhexahydronaphtho[2,3ꢀb]furanꢀ2(5H)ꢀone
(21) (182 mg, 28%), (5S,8aR,9aS)ꢀ3,5,8aꢀtrimethylꢀ6,7,8,
8a,9,9aꢀhexahydronaphtho[2,3ꢀb]furanꢀ2(5H)ꢀone (29) (12 mg,
5%), and (2S,3S,3a´R,5R,5´S,8aS,8a´R,9aR,9a´R)ꢀ3ꢀ(4ꢀfluꢀ
orophenyl)ꢀ5,5´,8a,8a´ꢀtetramethylꢀ3,3a´,5,5´,6,6´,7,7´,8,8a,
8´,8a´,9,9a,9´,9a´ꢀhexadecahydroꢀ1H,2´Hꢀspiro[anthraceneꢀ
2,3´ꢀnaphtho[2,3ꢀb]furan]ꢀ2´ꢀone (30) (21 mg, 2%). Comꢀ
pound 17, oily substance, []D20 +213 (c 1.1, CHCl3). IR (KBr),
/cm–1: 760, 1024, 1140, 1185, 1230, 1250, 1275, 1331, 1510,
1590, 1650, 1740. UV, max/nm (log): 235 (3.96), 330 (3.54).
1H NMR (400.13 MHz), : 1.05 (d, 3 H, C(15)H3, J = 7.6 Hz);
1.14 (ddd, 1 H, H(1), J = 13.5 Hz, J = 13.2 Hz, J = 3.5 Hz); 1.25
(s, 3 H, C(14)H3); 1.35—1.66 (m, 5 H, H(1), H(2), H(3), H(3),
H(9)); 1.83 (m, 1 H, H(2)); 2.15 (dd, 1 H, H(9), J = 14.5 Hz,
J = 3.1 Hz); 2.40 (ddd, 1 H, H(3), J = 7.9 Hz, J = 4.4 Hz,
J = 3.0 Hz); 4.05 (ddd, 1 H, H(7), J = 6.5 Hz, J = 3.2 Hz,
J = 1.6 Hz); 4.79 (ddd, 1 H, H(8), J = 6.5 Hz, J = 3.0 Hz,
J = 2.6 Hz); 5.39 (d, 1 H, H(6), J = 3.2 Hz); 7.07 (m, 2 H, H(3´),
H(5´)); 7.21 (ddd, 2 H, H(2´), H(6´), J = 8.0 Hz, J = 6.5 Hz,
J = 2.0 Hz); 7.39 (d, 1 H, H(13), J = 1.6 Hz). 13C NMR, : 16.70
(C(2)); 22.38 (C(15)); 28.46 (C(14)); 32.57 (C(10)); 32.91 (C(3));
38.31 (C(4)); 38.73 (C(7)); 42.31 (C(1)); 43.08 (C(9)); 77.36
(C(8)); 117.27 (C(3´), C(5´)); 115.09 (C(6)); 128.64 (C(11));
130.98 (C(1´)); 132.71 (C(2´), C(6´)); 136.34 (C(13)); 151.87
(C(5)); 161.83 (C(4´), JC—F = 287.0 Hz); 173.81 (C(12)).
Found (%): C, 77.05; H, 6.78; F, 5.65. C21H23FO2. Calculated
(%): C, 77.27; H, 7.10; F, 5.82.
(14) (162 mg, 20%). Compound 13, m.p. 171—173 C (from
acetonitrile), []D +320 (c 0.56, CHCl3). IR (KBr), /cm–1
:
20
761, 817, 830, 899, 950, 997, 1071, 1172, 1220, 1250, 1302,
1357, 1405, 1445, 1488, 1585, 1655, 1664, 1755, 2851, 2927. UV,

max/nm (log): 201 (4.14), 223 (4.07), 230 (3.99), 291 (4.38), 296
1
(3.90), 306 (4.29). H NMR (600.13 MHz), : 0.92 (ddd, 1 H,
H(6), J = 13.1 Hz, J = 12.9 Hz, J = 12.9 Hz); 0.99 (s, 3 H,
C(14)H3); 1.19 (m, 1 H, H(1)); 1.33 (dm, 1 H, H(3), J = 12.5 Hz);
1.48 (dd, 1 H, H(9), J = 15.7 Hz, J = 4.6 Hz); 1.59 (dm, 1 H,
H(5), J = 13.7 Hz); 1.64—1.73 (m, 2 H, H(1), H(2)); 1.77—1.93
(m, 3 H, H(2), H(3), H(6)); 2.22 (dd, 1 H, H(9), J = 15.6 Hz,
J = 1.6 Hz); 2.50 (d, 1 H, H(15), J = 4.4 Hz); 2.60 (dd, 1 H,
H(15), J = 4.4 Hz, J = 1.8 Hz); 3.28 (ddd, 1 H, H(7), J = 11.8 Hz,
J = 6.0 Hz, J = 5.3 Hz); 4.45 (ddd, 1 H, H(8), J = 4.6 Hz,
J = 4.6 Hz, J = 1.4 Hz); 7.30 (br.s, 1 H, H(13)); 7.31 (ddd, 2 H,
H(2´), H(6´), J = 8.4 Hz, J = 2.1 Hz, J = 1.7 Hz); 7.51 (ddd,
2 H, H(3´), H(5´), J = 8.6 Hz, J = 2.1 Hz, J = 1.9 Hz). 13C NMR,
: 18.13 (C(14); 19.85 (C(2), C(6)); 33.98 (C(10)); 34.90 (C(3));
38.93 (C(7)); 40.94 (C(9)); 41.35 (C(1)); 43.84 (C(5)); 50.20
(C(15)); 58.11 (C(4)); 76.29 (C(8)); 123.81 (C(4´)); 130.85
(C(2´), C(6´)); 131.91 (C(3´), C(5´)); 132.25 (C(11)); 132.45
(C(1´)); 133.67 (C(13)); 171.61 (C(12)). Found (%): C, 62.25;
H, 5.74; Br, 20.18. C21H23BrO3. Calculated (%): C, 62.54;
H, 5.75; Br, 19.81.
Compound 21, oily substance, []D20 –78 (c 0.7, CHCl3). UV,
Compound 14, m.p. 157—159 C (from ethanol), []D20 +28
(c 0.6, CHCl3). IR (KBr), /cm–1: 783, 816, 827, 840, 897, 966,
1011, 1024, 1057, 1094, 1132, 1146, 1264, 1449, 1485, 1687,
1741, 2864, 2935. UV, max/nm (log): 218 (4.20), 282 (3.26).
1H NMR (600.13 MHz), : 1.00 (s, 3 H, C(14)H3); 1.06 (dd, 1 H,
H(9), J = 12.0 Hz, J = 11.9 Hz); 1.21 (1 H, ddd, H(1),

max/nm (log): 230 (4.00), 276 (3.79). 1H NMR (400.13 MHz),
: 1.16 (d, 3 H, C(15)H3, J = 6.8 Hz); 1.28 (m, 1 H, H(1)); 1.30
(s, 3 H, C(14)H3); 1.36—1.49 (m, 2 H, H(2), H(9)); 1.55—1.69
(m, 2 H, H(1), H(3)); 1.80 (m, 2 H, H(2), H(3)); 2.12 (dd, 1 H,
H(9), J = 11.7 Hz, J = 5.1 Hz); 2.57 (ddd, 1 H, H(4), J = 12.9 Hz,
J = 7.0 Hz, J = 5.2 Hz); 3.43 (d, 1 H, H(13), J = 14.2 Hz); 3.58

1982
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 10, October, 2012
Shul´ts et al.
(d, 1 H, H(13), J = 14.2 Hz); 4.99 (dd, 1 H, H(8), J = 13.2 Hz,
J = 5.1 Hz); 6.10 (s, 1 H, H(6)); 7.08 (m, 2 H, H(3´), H(5´)); 7.29
(m, 2 H, H(2´), H(6´)). 13C NMR, : 16.48 (C(2)); 22.56 (C(15));
26.63 (C(14)); 27.91 (C(13)), 32.60 (C(3)), 37.88 (C(10)); 38.08
(C(4)); 41.98 (C(1)); 46.71 (C(9)); 77.18 (C(8)); 113.97 (C(6));
117.59 (C(3´), C(5´)); 119.60 (C(11)); 130.11 (C(1´)); 131.93
(C(2´), C(6´)); 157.70 (C(7)); 160.82 (C(4´)); 162.25 (C(5));
174.76 (C(12)). Found (%): C, 76.89; H, 6.81; F, 5.58. C21H23FO2.
Calculated (%): C, 77.27; H, 7.10; F, 5.82.
Compound 29, the yield was 5%, oily substance, []D +156
(c 1.1, CHCl3). 1H NMR (400.13 MHz), : 1.23 (s, 3 H,
C(14)H3); 1.25 (d, 3 H, C(15)H3, J = 7.5 Hz); 1.45 (dd, 1 H,
H(9), J = 13.3 Hz, J = 12.6 Hz); 1.50—1.57 (m, 3 H, H(1),
H(2), H(3)); 1.64 (ddd, 1 H, H(1), J = 13.0 Hz, J = 12.6 Hz,
J = 4.2 Hz); 1.69 (dm, 1 H, H(3), J = 12.0 Hz); 1.82 (d, 3 H,
C(13)H3, J = 1.5 Hz); 1.91 (ddddd, 1 H, H(2), J = 12.5 Hz,
J = 12.5 Hz, J = 12.4 Hz, J = 4.3 Hz, J = 3.8 Hz); 2.11 (dd, 1 H,
H(9), J = 12.7 Hz, J = 5.1 Hz); 2.74 (quint, 1 H, H(4), J = 7.2 Hz);
4.72 (ddd, 1 H, H(8), J = 13.3 Hz, J = 5.7 Hz, J = 1.5 Hz); 6.18
(br.s, 1 H, H(6)). 13C NMR, : 17.99 (C(2)); 20.66 (C(15));
29.41 (C(14)); 29.59 (C(13)); 34.02 (C(3)); 38.57 (C(10)); 39.79
(C(1)); 40.40 (C(4)); 43.68 (C(9)); 75.85 (C(8)); 112.89 (C(6));
116.07 (C(11)); 158.89 (C(7)); 161.12 (C(5)); 175.67 (C(12)).
Found (%): C, 77.81; H, 8.51. C15H20O2. Calculated (%):
C, 77.55; H, 8.68.
0.32 mmol), DMF (10 mL), and triethylamine (0.5 mL, 3.61 mmol)
during 16 h and subsequent column chromatography on an imꢀ
pregnated silica gel resulted in the isolation of (3aR,5S,8aR,
9aR,E)ꢀ3ꢀ(4ꢀmethoxybenzylidene)ꢀ5,8aꢀdimethylꢀ3,3a,6,7,8,8a,
9,9aꢀoctahydronaphtho[2,3ꢀb]furanꢀ2(5H)ꢀone (18) (122 mg,
18%) and (5S,8aR,9aS)ꢀ3ꢀ(4ꢀmethoxybenzyl)ꢀ5,8aꢀdimethylꢀ
6,7,8,8a,9,9aꢀhexahydronaphtho[2,3ꢀb]furanꢀ2(5H)ꢀone (22)
(149 mg, 22%).
In the reaction of lactone 2 (232 mg, 1.0 mmol) and 4ꢀiodoꢀ
anisole 5e (258 mg, 1.1 mmol) in the presence of palladium
acetate (17.7 mg, 0.08 mmol), tri(oꢀtolyl)phosphine (97 mg, 0.32
mmol), DMF (10 mL), and triethylamine (0.25 mL, 1.8 mmol)
during 16 h, the conversion of lactone 2 was 95% (according to
the chromatoꢀmass spectrometric data, the ratio 18 : 22 =
= 1 : 1.4). The isolation by column chromatography gave comꢀ
pound 18 (102 mg, 30%) and compound 22 (119 mg, 35%).
20
Compound 18, oily substance, []D +248 (c 1.6, CHCl3).
1H NMR (400.13 MHz), : 1.04 (d, 3 H, C(15)H3, J = 7 Hz);
1.12 (ddd, 1 H, H(1), J = 13.2 Hz, J = 12.9 Hz, J = 3.2 Hz); 1.24
(s, 3 H, C(14)H3); 1.40—1.64 (m, 5 H, H(1), H(2), H(3), H(3),
H(9)); 1.80 (m, 1 H, H(2)); 2.16 (dd, 1 H, H(9), J = 14.9 Hz,
J = 3.0 Hz); 2.41 (m, 1 H, H(4)); 3.83 (s, 3 H, OMe); 4.06
(m, 1 H, H(7)); 4.77 (ddd, 1 H, H(8), J = 6.4 Hz, J = 3.2 Hz,
J = 2.5 Hz); 5.37 (d, 1 H, H(6), J = 3.3 Hz); 6.94 (dm, 2 H,
H(3´), H(5´), J = 8.4 Hz); 7.39 (d, 1 H, H(13), J = 1.7 Hz); 7.54
(dm, 2 H, H(2´), H(6´), J = 8.4 Hz). 13C NMR, : 16.76 (C(2));
22.25 (C(15)); 28.51 (C(14)); 32.76 (C(10)); 32.83 (C(3)); 38.02
(C(4)); 38.91 (C(7)); 42.02 (C(1)); 42.45 (C(9)); 55.97 (OMe);
76.09 (C(8)); 114.47 (C(3´), C(5´)); 114.62 (C(6)); 127.31
(C(11)); 127.83 (C(1´)); 131.54 (C(2´), C(6´)); 135.88 (C(13));
151.02 (C(5)); 159.13 (C(4´)); 172.14 (C(12)). Found (%):
C, 77.68; H, 7.57. C22H26O3. Calculated (%): C, 78.07; H, 7.74.
Compound 22, m.p. 118—121 C (from ethanol), []D20 –46
(c 1.3, CHCl3). 1H NMR (400.13 MHz), : 1.20 (d, 3 H,
C(15)H3, J = 7.5 Hz); 1.29 (ddd, 1 H, H(1), J = 13.5 Hz,
J = 13.4 Hz, J = 3.8 Hz); 1.33 (s, 3 H, C(14)H3); 1.36 (dd, 1 H,
H(9), J = 12.9 Hz, J = 11.2 Hz); 1.48—1.65 (m, 4 H, H(1),
H(2), H(3), H(3)); 1.85 (m, 1 H, H(2)); 2.30 (dd, 1 H, H(9),
J = 11.7 Hz, J = 4.7 Hz); 2.62 (m, 1 H, H(4)); 3.50 (d, 1 H,
H(13), J = 14.9 Hz); 3.60 (d, 1 H, H(13), J = 14.9 Hz); 3.77
(s, 3 H, OMe); 4.96 (dd, 1 H, H(8), J =13.7 Hz, J = 4.3 Hz);
6.11 (s, 1 H, H(6)); 6.82 (dm, 2 H, H(3´), H(5´), J = 8.2 Hz);
7.17 (dm, 2 H, H(2´), H(6´), J = 8.2 Hz). Found (%): C, 77.87;
H, 7.60. C22H26O3. Calculated (%): C, 78.07; H, 7.74.
Compound 30, white amorphous substance, []D +78 (c 0.8,
CHCl3). IR (neat), /cm–1: 839, 987, 1018, 1042, 1099, 1120,
1159, 1185, 1227, 1375, 1457, 1509, 1604, 1760, 2868, 2929. UV,

max/nm (log): 201 (4.67), 250 (4.08). 1H NMR (600.13 MHz),
: 1.01 (ddd, 1 H, H(1), J = 13.2 Hz, J = 12.9 Hz, J = 3.7 Hz);
1.13 (d, 3 H, C(15)H3, J = 7.6 Hz); 1.19 (d, 3 H, C(15´)H3,
J = 7.5 Hz); 1.24 (s, 3 H, C(14)H3); 1.24—1.30 (m, 2 H, H(1´),
H(9´)); 1.31 (s, 3 H, C(14´)H3); 1.36 (dd, 1 H, H(9), J = 15.0 Hz,
J = 3.2 Hz); 1.37 (m, 1 H, H(2)); 1.47 (dd, 1 H, H(13),
J = 13.4 Hz, J = 11.3 Hz); 1.47 (m, 1 H, H(2´)); 1.51—1.63 (m,
7 H, H(1), H(1´), H(3), H(3), H(3´), H(3´), H(9´)); 1.77 (ddddd,
1 H, H(2), J = 13.4 Hz, J = 13.4 Hz, J = 13.4 Hz, J = 3.2 Hz,
J = 3.2 Hz); 1.84 (m, 1 H, H(2´)); 1.84 (dd, 1 H, H(13),
J = 13.9 Hz, J = 5.9 Hz); 2.02 (dd, 1 H, H(9), J = 14.9 Hz,
J = 3.5 Hz); 2.34 (dd, 1 H, H(7), J = 6.0 Hz, J = 3.7 Hz); 2.36
(m, 1 H, H(4)); 2.48 (m, 1 H, H(4´)); 3.40 (ddd.ddd, 1 H, H(8´),
J = 12.1 Hz, J = 10.9 Hz, J = 6.2 Hz, J = 3.6 Hz, J = 2.5 Hz,
J = 1.4 Hz); 3.61 (dd, 1 H, H(13´), J = 4.7 Hz, J = 1.8 Hz); 4.72
(ddd, 1 H, H(8), J = 5.8 Hz, J = 3.1 Hz, J = 2.8 Hz); 4.87
(d, 1 H, H(6), J = 3.6 Hz); 5.28 (dd, 1 H, H(11´), J = 4.7 Hz,
J = 2.3 Hz); 5.75 (s, 1 H, H(6´)); 7.01 (dddd, 2 H, H(3), H(5),
J = 8.5 Hz, J = 8.5 Hz, J = 2.0 Hz, J = 1.9 Hz); 7.15 (dddd, 2 H,
H(2), H(6), J = 8.6 Hz, J = 5.3 Hz, J = 3.0 Hz, J = 2.3 Hz).
13C NMR, : 16.78 (C(2)); 17.26 (C(2´)); 22.58 (C(15´)); 22.90
(C(15)); 26.75 (C(14´)); 26.88 (C(8´)); 28.55 (C(14)); 30.05
(C(13)); 32.72 (C(10)); 32.85 (C(3)); 32.95 (C(3´)); 36.05
(C(10´)); 37.40 (C(4´)); 38.40 (C(4)); 41.75 (C(1´)); 42.09 (C(1));
42.92 (C(9)); 43.11 (C(7)); 46.27 (C(13´)); 49.19 (C(9´)); 50.59
(C(11)); 74.23 (C(8)); 115.55 (C(3), C(5)); 115.56 (C(6));
119.88 (C(11´)); 123.60 (C(6´)); 130.88 (C(2), C(6)); 137.32
(C(1)); 138.22 (C(7´)); 149.60 (C(5)); 150.57 (C(5´)); 161.93
(C(4)); 178.48 (C(12)). Found (%): C, 81.37; H, 8.18; F, 3.28.
C35H43FO2. Calculated (%): C, 81.67; H, 8.42; F, 3.69.
The reaction of alantolactone 2 (464 mg, 2.0 mmol) and
2,4ꢀdimethoxyiodobenzene 5f (580 mg, 2.2 mmol) in the presꢀ
ence of palladium acetate (17.7 mg, 0.08 mmol), tri(oꢀtolyl)ꢀ
phosphine (97 mg, 0.32 mmol), DMF (10 mL), and triethyꢀ
lamine (0.5 mL, 3.61 mmol) during 16 h and subsequent column
chromatography on an impregnated silica gel resulted in the
isolation of (3aR,5S,8aR,9aR,E)ꢀ3ꢀ(2,4ꢀdimethoxybenzylidene)ꢀ
5,8aꢀdimethylꢀ3,3a,6,7,8,8a,9,9aꢀoctahydronaphtho[2,3ꢀb]ꢀ
furanꢀ2(5H)ꢀone (19) (154 mg, 21%) and (5S,8aR,9aS)ꢀ3ꢀ
(2,4ꢀdimethoxybenzyl)ꢀ5,8aꢀdimethylꢀ6,7,8,8a,9,9aꢀhexahydroꢀ
naphtho[2,3ꢀb]furanꢀ2(5H)ꢀone (23) (214 mg, 29%). Comꢀ
1
pound 19, oily substance, []D +188 (c 1.8, CHCl3). H NMR
(300.13 MHz), : 1.04 (d, 3 H, C(15)H3, J = 7.7 Hz); 1.18 (m, 1 H,
H(1)); 1.22 (s, 3 H, C(14)H3); 1.28 (m, 1 H, H(2)); 1.44 (dd, 1 H,
H(9), J = 12.8 Hz, J = 10.6 Hz); 1.58—1.64 (m, 2 H, H(1),
H(2)); 1.78—2.01 (m, 2 H, H(3), H(5)); 2.13 (dd, 1 H, H(9),
J = 15.1 Hz, J = 2.7 Hz); 2.41 (m, 1 H, H(4)); 3.82 (s, 6 H,
The reaction of alantolactone 2 (464 mg, 2.0 mmol) and
4ꢀiodoanisole 5e (515 mg, 2.2 mmol) in the presence of palladiꢀ
um acetate (17.7 mg, 0.08 mmol), tri(oꢀtolyl)phosphine (97 mg,

Heck reaction of alantolactones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 10, October, 2012
1983
2 OMe); 4.00 (ddd, 1 H, H(7), J = 6.0 Hz, J = 2.5 Hz, J = 1.9 Hz);
4.75 (ddd, 1 H, H(8), J = 6.0 Hz, J = 3.0 Hz, J = 2.9 Hz); 5.33
(d, 1 H, H(6), J = 3.4 Hz); 6.46 (d, 1 H, H(3´), J = 2.2 Hz); 6.52
(dd, 1 H, H(5´), J = 8.6 Hz, J = 2.2 Hz); 7.58 (d, 1 H, H(6´),
J = 8.6 Hz); 7.86 (d, 1 H, H(13), J = 1.8 Hz). Found: m/z 368.1980
[M]+. C23H28O4. Calculated: M = 368.1982.
J = 13.4 Hz, J = 3.8 Hz); 1.34 (s, 3 H, C(14)H3); 1.26 (dd, 1 H,
H(9), J = 12.9 Hz, J = 12.5 Hz); 1.48—1.65 (m, 4 H, H(1),
H(2), 2 H(3)); 1.85 (ddddd, 1 H, H(2), J = 13.3 Hz, J = 13.3 Hz,
J = 12.8 Hz, J = 4.3 Hz, J = 3.8 Hz); 2.24 (dd, 1 H, H(9),
J = 11.7 Hz, J = 5.0 Hz); 2.63 (quint, 1 H, H(4), J = 7.0 Hz);
3.60 (d, 1 H, H(13), J = 15.6 Hz); 3.68 (d, 1 H, H(13),
J = 15.6 Hz); 5.01 (dd, 1 H, H(8), J = 13.4 Hz, J = 5.0 Hz); 6.10
(s, 1 H, H(6)); 7.35 (d, 2 H, H(2´), H(6´), J = 8.2 Hz); 7.56
(d, 2 H, H(3´), H(5´), J = 8.2 Hz). 13C NMR, : 17.90 (C(2));
20.66 (C(15)); 29.50 (C(14)); 29.74 (C(13)); 33.92 (C(3)); 38.65
(C(10)); 38.73 (C(1)); 41.17 (C(4)); 46.50 (C(9)); 75.99 (C(8));
110.37 (C(4´)); 112.19 (C(6)); 117.65 (CN); 117.86 (C(11));
129.31 (C(2´), C(6´)); 132.32 (C(3´), C(5´)); 143.87 (C(1´));
158.57 (C(7)); 163.60 (C(5)); 174.54 (C(12)). Found (%):
C, 79.16; H, 6.59; N, 4.11. C22H23NO2. Calculated (%):
C, 79.25; H, 6.95; N, 4.20.
Compound 31, white amorphous substance, []D +109
(c 0.8, CHCl3). IR (neat), /cm–1: 756, 843, 890, 1018, 1122, 1181,
1375, 1456, 1606, 1763, 2229, 2867, 2928. UV, max/nm (log):
201 (4.57), 238 (4.39). 1H NMR (600.13 MHz), : 1.02 (ddd,
1 H, H(1), J = 13.5 Hz, J = 13.2 Hz, J = 3.3 Hz); 1.12 (d, 3 H,
C(15)H3, J = 7.5 Hz); 1.16 (d, 3 H, C(15´)H3, J = 7.5 Hz); 1.22
(s, 3 H, C(14)H3); 1.24 (m, 1 H, H(1´)); 1.27 (dd, 1 H, H(9´),
J = 13.0 Hz, J = 12.2 Hz); 1.29 (s, 3 H, C(14´)H3); 1.37—1.40
(m, 2 H, H(2), H(9)); 1.47 (dd, 1 H, H(13), J = 14.0 Hz,
J = 10.9 Hz); 1.48 (m, 1 H, H(2´)); 1.49—1.55 (m, 3 H, H(1),
H(3), H(3)); 1.57 (dd, 1 H, H(9´), J = 13.0 Hz, J = 3.5 Hz);
1.59—1.61 (m, 3 H, H(1´), 2 H(3´)); 1.77 (ddddd, 1 H, H(2),
J = 13.6 Hz, J = 13.3 Hz, J = 13.2 Hz, J = 3.3 Hz, J = 2.9 Hz);
1.85 (m, 1 H, H(2´)); 1.87 (dd, 1 H, H(13), J = 14.0 Hz,
J = 6.2 Hz); 2.02 (dd, 1 H, H(9), J = 14.7 Hz, J = 3.5 Hz); 2.25
(ddd, 1 H, H(7), J = 5.8 Hz, J = 3.7 Hz, J = 1.0 Hz); 2.36
(m, 1 H, H(4)); 2.49 (m, 1 H, H(4´)); 3.41 (ddd.ddd, 1 H, H(8´),
J = 12.2 Hz, J = 10.9 Hz, J = 6.2 Hz, J = 3.5 Hz, J = 2.5 Hz,
J = 1.5 Hz); 3.68 (ddd, 1 H, H(13´), J = 4.5 Hz, J = 1.5 Hz,
J = 1.0 Hz); 4.72 (ddd, 1 H, H(8), J = 5.8 Hz, J = 3.4 Hz,
J = 3.0 Hz); 4.84 (d, 1 H, H(6), J = 3.7 Hz); 5.23 (dd, 1 H,
H(11´), J = 4.5 Hz, J = 1.5 Hz); 5.74 (s, 1 H, H(6´)); 7.29
(d, 2 H, H(2), H(6), J = 8.6 Hz); 7.60 (d, 2 H, H(3), H(5),
J = 8.6 Hz). 13C NMR, : 16.71 (C(2)); 17.18 (C(2´)); 22.52
(C(15´)); 22.85 (C(15)); 26.64 (C(14´)); 26.85 (C(8´)); 28.51
(C(14)); 30.02 (C(13)); 32.70 (C(10)); 32.77 (C(3)); 32.87
(C(3´)); 36.06 (C(10´)); 37.40 (C(4´)); 38.38 (C(4)); 41.67
(C(1´)); 42.00 (C(1)); 42.78 (C(9)); 43.09 (C(7)); 46.90 (C(13´));
49.05 (C(9´)); 50.29 (C(11)); 74.21 (C(8)); 111.18 (C(4)); 115.93
(C(6)); 118.39 (C(11)); 118.42 (CN); 123.29 (C(6´)); 130.22
(C(2), C(6)); 132.32 (C(3), C(5)); 139.15 (C(7´)); 147.24
(C(1)); 150.10 (C(5)); 151.41 (C(5´)); 178.48 (C(12)). Found (%):
C, 82.68; H, 8.24; N, 2.77. C36H43NO2. Calculated (%): C, 82.87;
H, 8.31; N, 2.68.
20
Compound 23, oily substance, []D –46 (c 1.2, CHCl3).
1H NMR (300.13 MHz), : 1.22 (d, 3 H, C(15)H3, J = 6.3 Hz);
1.23 (s, 3 H, C(14)H3); 1.25—1.44 (m, 3 H, H(1), H(2), H(9));
1.53—1.62 (m, 3 H, H(1), H(3), H(3)); 1.81 (m, 1 H, H(2));
2.29 (dd, 1 H, H(9), J = 12.4 Hz, J = 5.1 Hz); 2.64 (m, 1 H,
H(4)); 3.47 (d, 1 H, H(13), J = 15.5 Hz); 3.54 (d, 1 H, H(13),
J = 15.5 Hz); 3.76 (s, 6 H, 2 OMe); 4.67 (dd, 1 H, H (8),
J = 13.3 Hz, J = 5.9 Hz); 6.06 (s, 1 H, H(6)); 6.44 (d, 1 H, H(3´),
J = 2.4 Hz); 6.50 (dd, 1 H, H(5´), J = 8.6 Hz, J = 2.4 Hz); 7.82
(d, 1 H, H(6´), J = 8.6 Hz). 13C NMR, : 17.20 (C(2)); 21.02
(C(15)); 28.01 (C(14)); 29.74 (C(13)); 33.15 (C(3)); 38.24
(C(10)); 38.73 (C(4)); 41.17 (C(1)); 46.50 (C(9)); 55.72 (2 OMe);
75.99 (C(8)); 100.50 (C(3´)); 102.23 (C(5´)); 113.97 (C(6));
118.65 (C(1´)); 119.60 (C(11)); 130.98 (C(6´)); 157.7 (C(7));
157.93 (C(2´)); 162.25 (C(5)); 162.82 (C(4´)); 174.76 (C(12)).
MS, m/z (Irel (%)): 370 (3), 369 (29), 368 (100), 323 (77), 324
(24), 246 (26), 215 (13), 201 (21), 171 (12), 151 (44). Found:
m/z 368.1986 [M]+. C23H28O4. Calculated: M = 368.1982.
The reaction of alantolactone 2 (464 mg, 2.0 mmol) and
4ꢀiodobenzonitrile 5g (504 mg, 2.2 mmol) in the presence of
palladium acetate (17.7 mg, 0.08 mmol), tri(oꢀtolyl)phosphine
(97 mg, 0.32 mmol), DMF (10 mL), and triethylamine (0.5 mL,
3.61 mmol) during 16 h resulted in the obtaining of a reaction
mixture containing the starting lactone 2 (the conversion was
78%) and a mixture of products. Column chromatography on an
impregnated silica gel and subsequent TLC of the enriched fracꢀ
tions resulted in the isolation of the following individual comꢀ
pounds: (5S,8aR,9aS)ꢀ3ꢀ(4ꢀcyanobenzyl)ꢀ5,8aꢀdimethylꢀ6,7,8,
8a,9,9aꢀhexahydronaphtho[2,3ꢀb]furanꢀ2(5H)ꢀone (24) (160 mg,
24%), 4ꢀ{(2S,3S,3a´R,5R,5´S,8aS,8a´R,9aR,9a´R)ꢀ5,5´,8a,
8a´ꢀtetramethylꢀ2´ꢀoxoꢀ3,3a´,5,5´,6,6´,7,7´,8,8a,8´,8a´,9,
9a,9´,9a´ꢀhexadecahydroꢀ1H,2´Hꢀspiro[anthraceneꢀ2,3´ꢀnaphꢀ
tho[2,3ꢀb]furan]ꢀ3ꢀyl}benzonitrile (31) (32 mg, 3%), lactone 29
(7 mg, 3%), and (3aR,5S,8aR,9aR,E)ꢀ3ꢀ(4ꢀcyanobenzylidene)ꢀ
5,8aꢀdimethylꢀ3,3a,6,7,8,8a,9,9aꢀoctahydronaphtho[2,3ꢀb]ꢀ
furanꢀ2(5H)ꢀone (20) (103 mg, 15%). Compound 20, oily subꢀ
stance, []D +102 (c 1.3, CHCl3). 1H NMR (300.13 MHz),
: 0.88 (s, 3 H, C(14)H3); 1.21 (m, 1 H, H(1)); 1.39 (m, 1 H,
H(6)); 1.47—1.68 (m, 4 H, H(1), H(2), H(2), H(9)); 1.90—2.06
(m, 3 H, H(3), H(5), H(6)); 2.28 (dd, 1 H, H(9), J = 13.3 Hz,
J = 1.2 Hz), 2.39 (m, 1 H, H(3)); 3.42 (ddd, 1 H, H(7),
J = 11.8 Hz, J = 5.8 Hz, J = 5.1 Hz); 4.40 (br.s, 1 H, H(15));
4.51 (dd, 1 H, H(8), J = 4.8 Hz, J = 3.6 Hz); 4.74 (br.s, 1 H,
H(15)); 7.30 (d, 2 H, H(2´), H(6´), J = 8.8 Hz); 7.37 (s, 1 H,
H(13)); 7.58 (d, 2 H, H(3´), H(5´), J = 8.8 Hz). 13C NMR,
: 16.40 (C(2)); 22.20 (C(15)); 26.00 (C(14)); 32.76 (C(10));
32.45 (C(3)); 38.25 (C(4)); 38.32 (C(7)); 41.76 (C(1)); 43.63
(C(9)); 76.18 (C(8)); 110.37 (C(4´)); 113.45 (C(6)); 117.65 (CN),
129.54 (C(2´), C(6´)); 132.32 (C(3´), C(5´)); 127.77 (C(11));
128.19 (C(1´)); 137.87 (C(13)), 152.68 (C(5)); 172.28 (C(12)).
Found (%): C, 79.18; H, 6.78; N, 4.37. C22H23NO2. Calculatꢀ
ed (%): C, 79.25; H, 6.95; N, 4.20.
The reaction of a mixture of eudesmanolides of isoalantolacꢀ
tone 1 (232 mg, 1.0 mmol) and alantolactone 2 (232 mg,
1.0 mmol) with 4ꢀiodoveratrole 5b (580 mg, 2.2 mmol) in
the presence of palladium acetate (17.7 mg, 0.08 mmol), triꢀ
(oꢀtolyl)phosphine (97 mg, 0.32 mmol), DMF (10 mL), and
triethylamine (0.5 mL, 3.61 mmol) during 16 h afforded a mixꢀ
ture containing compounds 25, 26, and the starting lactones 1,
2. Column chromatography on silica gel gave the following indiꢀ
vidual compounds: isoalantolactone 1 (20 mg), alantolactone 2
(160 mg), (3aR,4aS,8aR,9aR,E)ꢀ3ꢀ(3,4ꢀdimethoxybenzylidene)ꢀ
8aꢀmethylꢀ5ꢀmethylidenedecahydronaphtho[2,3ꢀb]furanꢀ2(3H)ꢀ
Compound 24, m.p. 66—69 C (from diethyl ether), []D –68
(c 0.9, CHCl3). 1H NMR (600.13 MHz), : 1.20 (d, 3 H,
C(15)H3, J = 7.5 Hz); 1.32 (ddd, 1 H, H(1), J = 13.5 Hz,

1984
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 10, October, 2012
Shul´ts et al.
one (25) (202 mg, 55%), and (4aS,8aR,9aS)ꢀ3ꢀ(3,4ꢀdimethoxyꢀ
benzyl)ꢀ8aꢀmethylꢀ5ꢀmethylideneꢀ4a,5,6,7,8,8a,9,9aꢀoctahydroꢀ
naphtho[2,3ꢀb]furanꢀ2(4H)ꢀone (26) (56 mg). Compound 25,
m.p. 160—162 C (from ethanol), []D +534 (c 1.05, CHCl3).
IR (KBr), /cm–1: 808, 890, 1001, 1033, 1139, 1172, 1214, 1248,
1272, 1327, 1337, 1464, 1520, 1594, 1651, 1743. UV, max/nm
(log): 202 (4.20), 246 (4.13), 326 (4.32). 1H NMR (600.13 MHz),
: 0.81 (s, 3 H, C(14)H3); 1.22 (m, 1 H, H(1)); 1.34 (ddd, 1 H,
H(6), J = 13.0 Hz, J = 12.8 Hz, J = 12.6 Hz); 1.45—1.58 (m, 4 H,
H(1), H(2), H(2), H(2), H(9)); 1.87 (d, 1 H, H(5), J = 12.9 Hz);
1.91—2.04 (m, 2 H, H(3), H(6)); 2.19 (d, 1 H, H(9), J = 15.5 Hz);
2.28 (d, 1 H, H(3), J = 13.2 Hz); 3.37 (ddd, 1 H, H(7),
J = 11.4 Hz, J = 5.6 Hz, J = 5.5 Hz); 3.82 (s, 3 H, OMe); 3.85
(s, 3 H, OMe); 4.36 (br.s, 1 H, H(15)); 4.44 (dd, 1 H, H(8),
J = 4.1 Hz, J = 3.6 Hz); 4.70 (br.s, 1 H, H(15)); 6.86 (d, 1 H,
H(5´), J = 8.5 Hz); 6.97 (s, 1 H, H(2´)); 7.12 (d, 1 H, H(6´),
J = 7.0 Hz); 7.30 (s, 1 H, H(13)). 13C NMR, : 17.47 (C(14));
22.53 (C(2)); 24.56 (C(6)); 34.34 (C(10)); 36.68 (C(3)); 39.40
(C(7)); 41.21 (C(9)); 42.02 (C(1)); 46.20 (C(5)); 55.76 (2 OMe);
76.66 (C(8)); 106.48 (C(15)); 111.22 (C(6´)); 112.72 (C(2´));
122.92 (C(5´)); 126.97 (C(1´)); 129.93 (C(11)); 134.84 (C(13));
148.88 (C(4), C(3´)); 150.37 (C(4´)); 172.44 (C(12). Found (%):
C, 74.90; H, 7.92. C23H28O4. Calculated (%): C, 74.97; H, 7.66.
Compound 26, oily substance. 1H NMR (600.13 MHz),
: 0.87 (s, 3 H, C(14)H3); 1.12 (dd, 1 H, H(9), J = 11.8 Hz,
J = 11.8 Hz); 1.29 (ddd, 1 H, H(1), J = 13.3 Hz, J = 13.3 Hz,
J = 5.3 Hz); 1.55—1.64 (m, 3 H, H(1), H(2), H(2)); 1.80 (dddd,
1 H, H(5), J = 12.5 Hz, J = 3.3 Hz, J = 1.7 Hz, J = 1.3 Hz); 1.93
(ddd, 1 H, H(3), J = 12.8 Hz, J = 12.8 Hz, J = 5.8 Hz); 2.28
(m, 1 H, H(6)); 2.30 (dd, 1 H, H(9), J = 12.3 Hz, J = 6.4 Hz);
2.36 (dddd, 1 H, H(3), J = 13.4 Hz, J = 3.8 Hz, J = 2.2 Hz,
J = 1.8 Hz), 2.77 (dd, 1 H, H(6), J = 13.8 Hz, J = 3.8 Hz); 3.50
(d, 1 H, H(13), J = 15.5 Hz); 3.56 (d, 1 H, H(13), J = 14.8 Hz);
3.83 (s, 3 H, OMe); 3.84 (s, 3 H, OMe); 4.55 (dd, 1 H, H(15),
J = 3.0 Hz, J = 1.2 Hz); 4.84 (dd, 1 H, H(8), J = 11.5 Hz,
J = 6.3 Hz); 4.85 (dd, 1 H, H(15), J = 2.8 Hz, J = 1.4 Hz); 6.73
(dd, 1 H, H(6´), J = 8.2 Hz, J = 2.0 Hz); 6.76 (d, 1 H, H(5´),
J = 8.2 Hz); 6.97 (d, 1 H, H(2´), J = 2.0 Hz). 13C NMR, d: 16.35
(C(14)); 22.18 (C(2)); 25.70 (C(6)); 28.77 (C(13)); 36.14 (C(10));
36.83 (C(3)); 40.68 (C(1)); 47.55 (C(9)); 49.97 (C(5)); 55.72
(2 OMe); 77.82 (C(8)); 106.89 (C(15)); 111.15 (C(6´)); 111.67
(C(2´)); 120.04 (C(5´)); 123.76 (C(1´)); 130.97 (C(11)); 147.53
(C(3´)); 148.17 (C(4)); 148.99 (C(4´)); 163.41 (C(7)); 174.05
(C(12)). Found (%): C, 74.90; H, 7.92. C23H28O4. Calculatꢀ
ed (%): C, 74.97; H, 7.66.
H(1)); 1.50—1.58 (m, 3 H, H(1), H(2), H(2)); 1.66 (s, 3 H,
C(15)H3); 1.68 (dd, 1 H, H(9), J = 15.0 Hz, J = 4.7 Hz);
1.85—1.96 (m, 3 H, H(3), H(3), H(6)); 2.07 (dd, 1 H, H(9),
J = 15.0 Hz, J = 3.9 Hz); 2.91 (dd, 1 H, H(6), J = 14.5 Hz,
J = 6.4 Hz); 3.38 (dddd, 1 H, H(7), J = 12.2 Hz, J = 6.4 Hz,
J = 5.4 Hz, J = 1.5 Hz); 3.89 (s, 3 H, OMe); 3.90 (s, 3 H, OMe);
4.49 (ddd, 1 H, H(8), J = 5.4 Hz, J = 4.8 Hz, J = 3.9 Hz); 6.88
(d, 1 H, H(5´), J = 8.4 Hz); 7.04 (d, 1 H, H(2´), J = 2.0 Hz);
7.13 (dd, 1 H, H(6´), J = 8.4 Hz, J = 2.0 Hz); 7.37 (d, 1 H,
H(13), J = 1.5 Hz). 13C NMR, : 18.55 (C(2)), 19.39 (C(15));
25.09 (C(6)); 32.25 (C(3)); 33.26 (C(10)); 39.27 (C(9)); 40.77
(C(7)); 42.04 (C(1)); 55.87 (2 OMe); 76.95 (C(8));
111.06 (C(6´)); 111.85 (C(2´)); 123.75 (C(5´)); 127.11 (C(1´));
127.20 (C(11)); 129.39 (C(4)); 131.21 (C(5)); 135.41 (C(13));
149.01 (C(3´)); 150.44 (C(4´)); 163.08 (C(7)); 172.70 (C(12)).
Found (%): C, 74.57; H, 7.43. C23H28O4. Calculated (%):
C, 74.97; H, 7.66.
20
Compound 28, oily substance, []D +61 (c 0.53, CHCl3).
IR (neat), /cm–1: 693, 760, 795, 1028, 1106, 1237, 1262, 1341,
1377, 1462, 1514, 1592, 1680,1752, 2834, 2864, 2932. UV,

max/nm (log): 204 (4.49), 225 (4.26), 279 (3.60). 1H NMR
(400.13 MHz), : 1.05 (dd, 1 H, H(9), J = 12.2 Hz, J = 11.8 Hz);
1.15 (s, 3 H, C(14)H3); 1.34 (ddd, 1 H, H(1), J = 13.9 Hz,
J = 13.2 Hz, J = 3.0 Hz); 1.53 (s, 3 H, C(15)H3); 1.56—1.62
(m, 3 H, H(1), H(2), H(2)); 1.90 (m, 2 H, H(3), H(3)); 2.25 (dd,
1 H, H(9), J = 11.8 Hz, J = 6.1 Hz); 2.77 (dm, 1 H, H(6),
J = 15.6 Hz); 3.49 (d,1 H, H(13), J = 15.2 Hz); 3.57 (d, 1 H,
H(13), J = 15.2 Hz); 3.70 (d, 1 H, H(6), J = 15.5 Hz); 3.80
(s, 3 H, OMe); 3.82 (s, 3 H, OMe); 4.96 (dd, 1 H, H(8),
J = 11.8 Hz, J = 5.0 Hz); 6.73—7.12 (m, 3 H, H(2´), H(5´),
H(6´)). 13C NMR, : 18.34 (C(2)); 19.50 (C(15)); 24.58 (C(14));
26.72 (C(6)); 28.84 (C(13)); 32.83 (C(3)); 35.01 (C(10)); 39.13
(C(1)); 47.61 (C(9)); 55.59 (OMe); 55.79 (OMe); 77.92 (C(8));
111.16 (C(6´)); 111.50 (C(2´)); 120.21 (C(5´)); 122.16 (C(1´));
129.02 (C(11)); 129.33 (C(4)); 130.79 (C(5)); 147.53 (C(3´));
148.90 (C(4´)); 163.08 (C(7)); 174.20 (C(12)). Found (%):
C, 75.12; H, 7.81. C23H28O4. Calculated (%): C, 74.97; H, 7.66.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 11ꢀ03ꢀ00242ꢀa).
References
1. A. V. Belovodskii, E. E. Shul´ts, M. M. Shakirov, I. Yu.
Bagryanskaya, Yu. V. Gatilov, G. A. Tolstikov, Zh. Org.
Khim., 2010, 46, 1710 [Russ. J. Org. Chem. (Engl. Transl.),
2010, 46, 1719].
2. A. V. Belovodskii, E. E. Shul´ts, M. M. Shakirov, G. A.
Tolstikov, Dokl. Akad. Nauk, 2009, 426, 762 [Dokl. Chem.
(Engl. Transl.), 2009].
3. A. V. Belovodskii, E. E. Shul´ts, M. M. Shakirov, V. E.
Romanov, B. Zh. Elmuradov, Kh. M. Shakhidoyatov, G. A.
Tolstikov, Khim. Prirod. Soedin., 2010, 747 [Chem. Nat.
Compd. (Engl. Transl.), 2010, 46, 880].
4. S. Zhang, Y. K. Wong, C. N. Ong, H. M. Shen, Curr. Med.
Chem. Anticancer Agents, 2005, 5, 239.
The reaction of alloalantolactone 4 (464 mg, 2 mmol) and
4ꢀiodoveratrole 5b (580 mg, 2.2 mmol) in the presence of pallaꢀ
dium acetate (18 mg, 0.08 mmol), tri(oꢀtolyl)phosphine (98 mg,
0.32 mmol), DMF (10 mL), and triethylamine (0.5 mL,
4.2 mmol) during 10 h and subsequent chromatography of the
reaction mixture on silica gel gave (3aR,8aR,9aR,E)ꢀ3ꢀ(3,4ꢀdiꢀ
methoxybenzylidene)ꢀ5,8aꢀdimethylꢀ3a,4,6,7,8,8a,9,9aꢀoctaꢀ
hydronaphtho[2,3ꢀb]furanꢀ2(3H)ꢀone (27) (221 mg, 30%) and
(8aR,9aS)ꢀ3ꢀ(3,4ꢀdimethoxybenzyl)ꢀ5,8aꢀdimethylꢀ6,7,8,8a,
9,9aꢀhexahydronaphtho[2,3ꢀb]furanꢀ2(4H)ꢀone (28) (258 mg,
35%). Compound 27, m.p. 96—98 C (from ethanol), []D20 +155
(c 0.76, CHCl3). IR (KBr), /cm–1: 625, 758, 814, 843, 891, 920,
951, 1024, 1075, 1140, 1165, 1215, 1269, 1333, 1372, 1416, 1246,
1447, 1518, 1593, 1647, 1746, 2737, 2837, 2862, 2930, 2974,
3082. UV, max/nm (log): 201 (4.25), 238 (3.94), 327 (4.15).
1H NMR (400.13 MHz), : 1.12 (s, 3 H, C(14)H3); 1.36 (m, 1 H,
5. Pat. No. 2413724 RF, E. E. Shul´ts, A. V. Belovodskii, T. G.
Tolstikova, M. P. Dolgikh, E. A. Morozova, G. A. Tolsꢀ
tikov, Byul. isobret. [Invention Bull.], 2011, No. 7, 10
(in Russian).

Heck reaction of alantolactones
Russ.Chem.Bull., Int.Ed., Vol. 61, No. 10, October, 2012
1985
6. G. Schlewer, J. L. Stampf, C. Benezra, J. Med. Chem., 1980,
23, 1031.
13. S. C. Srivastava, M. M. Mehra, G. K. Trivedi, S. C. Bhattaꢀ
charyy, Ind. J. Chem., 1971, 9, 512.
7. S. G. Klochkov, S. V. Afanas´eva, A. N. Pushchin, Khim.
Prirod. Soedin., 2006, 325 [Chem. Nat. Compd. (Engl. Transl.),
2006, 42, 400].
8. M. Larhed, A. Hallberg, The Heck Reaction, in Handbook of
Organopalladium Chemistry for Organic Synthesis, Wiley, New
York, 2002, p. 1133; I. P. Beletskaya, A. V. Cheprakov, Chem.
Rev., 2000, 100, 3009.
14. S. T. Caldwell, H. M. Petersson, L. J. Farrugia, W. Mullen,
A. Crozier, R. C. Hartley, Tetrahedron, 2006, 62, 7257.
15. V. K. Chaikovskii, A. N. Novikov, Zh. Prikl. Khim., 1984,
57, 134 [Russ. J. Appl. Chem. (Engl. Transl.), 1984, 57].
16. J. Pavlinac, M. Zupan, S. Stavber, J. Org. Chem., 2006,
71, 1027.
17. G. B. Shul´pin, Organicheskie reaktsii, kataliziruemye kompꢀ
leksami metallov [Organic Reactions Catalyzed by Metal Comꢀ
plexes], Nauka, Moscow, 1988, 275 pp. (in Russian).
9. C. Han, F. J. Barrios, M. V. Riofski, D. A. Colby, J. Org.
Chem., 2009, 74, 7176.
10. A. Arcadi, M. Chiarini, F. Marinelli, Z. Berente, L. Kollar,
Org. Lett., 2000, 2, 69; A. Arcadi, M. Chiarini, F. Marinelli,
Z. Berente, L. Kollar, Eur. J. Org. Chem., 2001, 16, 3165.
11. R. Matusch, H. Häberlein, Liebigs Ann. Chem., 1987, 455.
12. H. Erdman, L. Westfeld, Acta Chem. Scand., 1963, 17, 1826.
Received November 7, 2011;
in revised form August 17, 2012