Reductive coupling of polyfunctionalized organobismuth and organolead arylating reagents in the synthesis of benzopyran derivatives

Article abstract of DOI:10.1007/s11172-006-0163-9

Benzopyran derivatives were synthesized in good yields by the reactions of tris[2-(chloromethyl)phenyl]bismuth diacetate and 2-(halomethyl)aryllead triacetates with phenols and naturally occurring 4-hydroxycoumarins in the presence of bases according to a

Full text of DOI:10.1007/s11172-006-0163-9

2602
Russian Chemical Bulletin, International Edition, Vol. 54, No. 11, pp. 2602—2611, November, 2005
Reductive coupling of polyfunctionalized
organobismuth and organolead arylating reagents
in the synthesis of benzopyran derivatives
b
A. Yu. Fedorov,a J.ꢀP. Finet, O. G. Ganina,a,c M. I. Naumov,a and A. S. Shavyrind
ꢀ
aNizhny Novgorod N. I. Lobachevsky State University,
23 prosp. Gagarina, 603950 Nizhny Novgorod, Russian Federation.
Fax: +7 (831 2) 65 8592. Eꢀmail: afnn@rambler.ru
bFaculty of Science of St. Jerome,
University of AixꢀMarseille I and III, 13397 Marseille, France.*
Fax: +33 (0) 4 9128 8758. Eꢀmail: jeanꢀpierre.finet@up.univꢀmrs.fr
cDepartment of Chemistry, M. V. Lomonosov Moscow State University,
1 Leninskie Gory, 119992 Moscow, Russian Federation.
Eꢀmail: gognn@rambler.ru
dG. A. Razuvaev Institute of Organometallic Chemistry, Russian Academy of Sciences,
49 ul. Tropinina, 603600 Nizhny Novgorod, Russian Federation.
Fax: +7 (831 2) 12 7497. Eꢀmail: andrew@imoc.sinn.ru
Benzopyran derivatives were synthesized in good yields by the reactions of
tris[2ꢀ(chloromethyl)phenyl]bismuth diacetate and 2ꢀ(halomethyl)aryllead triacetates with
phenols and naturally occurring 4ꢀhydroxycoumarins in the presence of bases according to a
threeꢀstep oneꢀpot procedure.
Key words: reductive coupling, αꢀarylation, benzopyran derivatives, tris[2ꢀ(chloroꢀ
methyl)phenyl]bismuth diacetate, 2ꢀ(halomethyl)arylboronic acids, 2ꢀ(halomethyl)aryllead
triacetates.
Benzopyran fragments are present in many natural
and benzofuran fragments, is used as an antidote for rattleꢀ
snake bites.7
compounds exhibiting a wide spectrum of biological acꢀ
tivities.1 The aim of the present study was to synthesize
oxaphenanthrene derivatives 1 with the use of electronꢀ
donating phenols and to prepare benzopyran derivatives 2
based on polymethoxyꢀsubstituted 4ꢀhydroxycoumarins.
Being isostructural analogs of polymethoxyꢀ and/or polyꢀ
hydroxyꢀsubstituted cisꢀstilbenes 3, which are inhibitors
of tumor growth,2 derivatives 1 potentially can have high
therapeutic activity. At the same time, benzazepine anaꢀ
logs 4 of derivatives 2 are efficient antitumor agents against
60 types of human cancer cells.3 Structurally similar
alloxanthoxyletinꢀtype pyranocoumarins 5 possess a numꢀ
ber of unique pharmacological properties, including antiꢀ
tumor4 and antiꢀHIV5 activities. Dihydropyranocoumaꢀ
rins belonging to the same family of organic compounds
can be used for the treatment of neurodegenerative disꢀ
eases, for example, of Alzheimer's disease.6 Wedelolacꢀ
tone 6, which is a tetracyclic natural compound conꢀ
structed by combining polyhydroxyꢀsubstituted coumarin
Unlike various known approaches to the synthesis of
benzopyran derivatives,7—12 our procedure is based on
arylation involving polyfunctionalized organobismuth and
organolead reagents.
Organobismuth reagents have attracted interest beꢀ
cause they are mild regioselective Oꢀ, Nꢀ, and Cꢀarylating
reagents stable to atmospheric oxygen and moisture.13—15
In addition, although bismuth is the heaviest of nonradioꢀ
active elements, its aryl derivatives have a low toxicity16
due to which this class of arylating reagents holds promise
for the functionalization of a broad range of physiologiꢀ
cally active molecules.17
We chose tris[2ꢀ(chloromethyl)phenyl]bismuth as a
model reagent for the synthesis of benzopyran compounds
with the use of organobismuth derivatives. This compound
was prepared in 27% yield by the reaction of a funcꢀ
tionalized aryl Grignard reagent18,19 with bismuth trichloꢀ
ride (Scheme 1). The next three steps of the synthesis of
benzopyran compounds were carried out without isolation
of intermediates. Oxidation of tris[2ꢀ(chloromethyl)pheꢀ
nyl]bismuth (9) with iodobenzene diacetate20 affords
* UMRꢀCNRS 6517, Universités d’AixꢀMarseille 1 et 3, Faculté
des Sciences SaintꢀJérôme, 13397 Marseille Cedex 20, France.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2520—2529, November, 2005.
1066ꢀ5285/05/5411ꢀ2602 © 2005 Springer Science+Business Media, Inc.

Synthesis of benzopyran derivatives
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005 2603
Table 1. Synthesis of benzopyran derivatives according to a casꢀ
cade procedure with the use of tris[2ꢀ(chloromethyl)pheꢀ
nyl]bismuth 9
triarylbismuth diacetate 10 (see Scheme 1). In the followꢀ
ing step, the latter reacts with various enolizable subꢀ
strates in the presence of triethylamine. This step is called
reductive coupling and is typical not only of bismuth deꢀ
rivatives13—15 but also of aryl compounds of lead,13,14,21
iodine,13,22 and some other mainꢀgroup elements.13 Preꢀ
sumably, reductive coupling proceeds through the formaꢀ
tion of intermediate 11,23 which is subject to reductive
elimination giving rise to αꢀarylation product 12. In the
final step, the intramolecular nucleophilic substitution
affords benzopyran product 13. Therefore, this procedure
provides an approach to the threeꢀstep oneꢀpot synthesis
of benzopyran derivatives.
We chose βꢀnaphthol 14, substituted phenols 16—20,
natural βꢀketo lactone 30b, and βꢀdiketone 33 as subꢀ
strates for the synthesis of benzopyran derivatives.
The reactions with the use of βꢀnaphthol 14 and
phenols 16 and 17 as the starting compounds produced
oxaphenanthrene derivatives 15, 23, and 24 in good
overall yields after three steps (55, 48, and 49%, respecꢀ
tively, see Table 1). The reaction with weaker electronꢀ
donating 4ꢀtertꢀbutylphenol 19 gave a benzopyran derivaꢀ
tive in low yield (27%), whereas the reaction with its
4ꢀmethoxyꢀsubstituted analog 18 afforded cyclization
product 25 in trace amounts (see Table 1). It should be
noted that phenols containing electronꢀwithdrawing
groups, for example, 4ꢀbromoꢀ2ꢀmethylphenol 20, do
not react with organobismuth compound 10. These reꢀ
sults are consistent with the traditional reactivity of aryl
derivatives of pentavalent bismuth in reactions with
phenols.24
Substrate
Conditionsa
τ/h T/°C
Product
Yieldb
(%)
14
16
30
3
25
∆
15
23
55
48
30
3
30
4
30
4
30
4
25
∆
25
∆
25
∆
25
∆
25
∆
17
24
25
26
31b
34
49
5
18
19
27
46
35
30b
33c
30
4
30
25
a All reactions involved three steps without isolation of intermeꢀ
diates: I, a mixture of BiIII derivative 9 (1.0 equiv.) and
PhI(OAc)2 (1.1 equiv.) in CH2Cl2 was stirred at room temperaꢀ
ture under argon for 6—8 h; II, the substrate (1.0 equiv.) and
triethylamine (3.0 equiv.) were added to the reaction mixture
and the reaction was performed as described in the table;
III, annelation.
b The overall yields after three steps without isolation of interꢀ
mediates.
c Sodium hydride was used instead of triethylamine; freshly disꢀ
tilled acetylacetone was used.
Therefore, the proposed strategy is efficient in the
synthesis of benzopyran derivatives based on electronꢀ
donating phenols and βꢀdicarbonyl compounds. Howꢀ
ever, an essential drawback of tris[2ꢀ(chloromethyl)pheꢀ
nyl]bismuth diacetate 10 as the reagent is that it does not
satisfy the principle of "ligand saving" because only one
2ꢀ(chloromethyl)phenyl fragment of the three aryl groups,
Triarylbismuth diacetate 10 reacts not only with
phenols but also with βꢀketo esters and βꢀdicarbonyl comꢀ
pounds. For example, the reactions with cyclic βꢀketo
ester 30b and pentaneꢀ2,4ꢀdione 33 produced tetracyclic
and bicyclic derivatives 31b and 34, respectively, in good
yields (see Table 1).

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Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005
Fedorov et al.
Scheme 1
Compound
R1
R2
R3
R4
Compound
R1
R2
R3
H
MeO
H
MeO
H
MeO
H
R4
—
—
H
H
H
16, 23
17, 24
18, 25
19, 26
20, 27
21, 28
22, 29
30a
H
H
H
H
Me
H
H
H
MeO
MeO
MeO
H
H
H
MeO
But
H
H
MeO
MeO
But
Br
H
H
H
MeO
MeO
MeO
H
H
H
H
But
—
30c
30d
31a
31b
31c
31d
32a
32b
32c
32d
MeO
MeO
H
MeO
MeO
MeO
H
MeO
MeO
MeO
MeO
MeO
H
H
MeO
MeO
H
H
MeO
MeO
H
MeO
MeO
MeO
MeO
MeO
H
MeO
30b
H
—
which are present in the coordination polyhedron of bisꢀ
muth, is involved in αꢀarylation. To resolve this problem,
we used organolead reagents 35a,b and 36 containing the
2ꢀ(bromomethyl)aryl or 2ꢀ(chloromethyl)phenyl fragꢀ
ments (Scheme 2). These compounds can easily be synꢀ
thesized from the corresponding arylboronic acids 37a,b
and 38. Derivatives 37a and 37b were synthesized in 60
and 48% yields, respectively, as colorless crystals by radiꢀ
cal bromination of 2ꢀmethylphenylboronic acid25 (39a)
and 4ꢀmethoxyꢀ2ꢀmethylphenylboronic acid26 (39b) with
Nꢀbromosuccinimide in CCl4 in the presence of benzoyl
peroxide. It should be noted that 2ꢀbromomethylꢀ4ꢀ
methoxyphenylboronic acid 37b is unstable in air at room
temperature (it turns black within 24 h). Under analogous
conditions, the reaction with Nꢀchlorosuccinimide does
not give 2ꢀ(chloromethyl)phenylboronic acid 38. Howꢀ
ever, the reaction of 2ꢀ(chloromethyl)phenylmagnesium
bromide19 with triisopropyl borate allowed us to prepare
arylboronic acid 38 in 52% yield. Aryllead triacetates 35a,b
and 36 were synthesized according to a procedure,27 which
involves transmetallation between arylboronic acids and
lead tetraacetate in the presence of catalytic amounts of
mercury diacetate. This approach enabled us to syntheꢀ
size airꢀstable 2ꢀ(bromomethyl)phenyl derivative of lead

Synthesis of benzopyran derivatives
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005 2605
Scheme 2
R = H (a), OMe (b)
Reagents: (a) BuLi/B(OPri)3; (b) benzoyl peroxide/Nꢀbromosuccinimide/CCl4; (c) Pb(OAc)4/Hg(OAc)2; (d) PriMgBr/B(OPri)3.
35a in 48% yield and its chlorineꢀcontaining analog 36 in
78% yield. The latter analog is sensitive to atmospheric
oxygen and moisture. We failed to prepare aryllead triacꢀ
etate 35b in pure form, and we used it in the synthesis of
benzopyran derivatives without isolation.
step oneꢀpot synthesis with the use of aryllead triacetate
prepared in situ (see Table 2, entry 2). An increase in the
amount of the base to 6 equivalents with the aim of achievꢀ
ing more efficient neutralization of HBr that was liberated
in the course of the reaction did not lead to an increase in
the yield of annelation product 15 (see Table 2, entry 3).
However, pyridine evidently not only can serve as a base
but also can be involved as a ligand in the coordination
environment of the lead atom.31 Moreover, the kinetics
of reductive coupling and the yields of the main products
of these reactions were demonstrated32,33 to depend subꢀ
stantially on the nature of the base or the complexꢀformꢀ
ing agent. To optimize the conditions of the synthesis of
benzopyran derivatives and elucidate the role of bases in
these processes, we studied the reactions of organolead
reagents 35a,b and 36 with phenols and cyclic βꢀketo
esters 30a—d in the presence of bases, such as triethylꢀ
amine (TEA), N,N,N´,N´ꢀtetramethylguanidine (TMG),
and orthoꢀphenanthroline (oꢀphen), and systems of bases,
such as pyridine—triethylamine, 4ꢀdimethylaminopyriꢀ
dine (DMAP)—triethylamine, and orthoꢀphenanthroꢀ
line—potassium tertꢀbutoxide.
The use of TEA and TMG, which are the most effiꢀ
cient bases in reductive coupling with organobismuth deꢀ
rivatives,13—15 led only to the formation of benzopyran
derivative 15 in trace amounts (see Table 2, entries 4
and 5). However, the addition of a stronger base (TEA) to
pyridine resulted in a substantial increase in the yields of
annelation products (see Table 2, entries 6 and 9). Cyꢀ
clization products were prepared in satisfactory yields with
a combined use of pyridine and TMG (see Table 2, enꢀ
try 7), as well as with the use of the DMAP—TEA system
(see Table 2, entries 8 and 10), as bases. It is worthy of
note that the reaction of 35a with 3ꢀmethoxyphenol afꢀ
forded oxaphenanthrene derivative 28 as the only product
in moderate yield as a result of orthoꢀarylation at the most
The reactions of organolead derivatives 35a,b and 36
with phenols and enolizable substrates proceed by a
mechanism analogous to that presented in Scheme 1. It
should be noted that aryllead triacetates have found wide
application in Cꢀarylation,13,14,21 both in racemic and
enantioselective28 modifications, and are particularly efꢀ
ficient for the insertion of electronꢀdonating aromatic
fragments, which are often present in natural compounds,
into organic substrates. A drawback of this method is that
organolead reagents do not always provide high regioꢀ
selectivity of arylation of phenols and βꢀketo esters. For
example, the reactions with phenols almost always afford,
along with monoꢀorthoꢀarylation products, 2,6ꢀdiarylꢀ
substituted compounds.29 Arylation of enolizable carbonyl
derivatives also gives mixtures of monoꢀ and diꢀαꢀarylation
products30 regardless of the stoichiometric reagentꢀtoꢀ
substrate ratio. Hence, in the presence of the second elecꢀ
trophilic center in an appropriate position of an organolead
reagent (for example, in derivatives 35a,b and 36), the
first αꢀarylation event is followed by cyclization, which
renders the formation of a diarylation product impossible.
However, for this sequence of reactions to occur, the
center bound to the lead atom must be more reactive than
the other electrophilic center in the organolead reagent.
Arylation of phenols according to a classical proceꢀ
dure14,21 with the use of aryllead triacetates (βꢀnaphthol
14 (1.0 equiv.), organolead reagent 35a (1.1 equiv.), and
pyridine (3.0 equiv.) in CHCl3 at 45 °C) afforded oxaꢀ
phenanthrene derivative 15 in 25% yield (Table 2, enꢀ
try 1). This reaction did not yield the diarylation product.
An analogous result was obtained in the successive threeꢀ

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Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005
Fedorov et al.
Table 2. Synthesis of oxaphenanthrene derivatives with the use of organolead reagent 35aa
Entry
Substrate
35a (equiv.)
Reaction conditions
Reagents (3 equiv. each) T/°C
Product
Yield (%)
τ/h
1
2
3
4
5
6
7
8
14
14
14
14
14
14
14
14
16
16
17
17
21
22
1.1b
1.1c
1.1b
1.1b
1.1b
1.4c
1.4c
1.4c
1.4c
1.4c
1.4c
1.4c
1.4c
1.4c
Pyridine
Pyridine
Pyridined
Et3N
TMG
Pyridine, Et3N
Pyridine, TMG
DMAP, Et3N
Pyridine, Et3N
DMAP, Et3N
DMAP, Et3N
Pyridine, Et3N
DMAP, Et3N
Pyridine, Et3N
45
45
45
45
45
25
25
25
25
25
25
25
25
25
10
10
10
10
10
1
1
1
1
1
15
15
15
15
15
15
15
15
23
23
24
24
28
29
25
20
19
2
—
55
45
65
65
60
25
38
37
13
9
10
11
12
13
14
10
10
1
10
a All reactions were carried out in CHCl3 (5 mL per mmole of the substrate).
b Compound 35a, which was isolated in individual form, was used.
c Compound 35a, which was prepared in situ, was used.
d 6 equiv.
sterically accessible position 6 of the substrate (see Table 2,
entry 13). It is also of interest that tricyclic derivative 29
can be constructed based on sterically hindered 3,5ꢀdiꢀ
tertꢀbutylphenol 22 (see Table 2, entry 14).
All analogous reactions (phenol, aryllead triacetate,
and two bases) with 2ꢀ(chloromethyl)phenyl derivative of
lead 36 produced the corresponding oxaphenanthrene deꢀ
rivatives in lower yields and under more drastic condiꢀ
tions compared to the reactions with the use of 2ꢀ(bromoꢀ
methyl)phenyl analog 35a (Table 3).
(Table 4, entries 4 and 5). The results of optimization of
the conditions for the synthesis of benzopyran derivatives
based on phenols (see Table 2) confirm the earlier suggesꢀ
tion that pyridine or related DMAP serve as ligands in the
coordination environment of the lead atom.31—33 In this
connection, we decided to use orthoꢀphenanthroline,
which is often used as a bidentate ligand in Ullmann
reactions,34 as a complexꢀforming agent. Actually, the
use of this ligand resulted in a substantial increase in the
yields of annelation products to 33—41% in the reacꢀ
tions with polymethoxyꢀsubstituted 4ꢀhydroxycoumarins
30b—d and to 58% in the reactions with the use of
unsubstituted coumarin 30a as the substrate (see Table 4,
The reactions of 2ꢀ(bromomethyl)aryllead triacetates
35a,b with natural keto lactones 30a—d in the presence of
binary pyridine—TEA and DMAP—TEA systems as bases
gave tetracyclic products 31 and 32a—d in low yields
Table 4. Influence of coordinating additives on the cascade synꢀ
thesis of tetracyclic products 31a—d based on 4ꢀhydroxyꢀ
coumarins 30a—d with the use of 2ꢀ(bromomethyl)phenyllead
triacetate 35a prepared without isolation*
Table 3. Synthesis of oxaphenanthrene derivatives with the use
of organolead reagent 36a
Substrate
Conditions
Products
Yield
(%)
Entry
Coordinating
additive
Total yield after
threeꢀstep synthesis (%)
T/°C
τ/h
(equiv.)
14
16
17
19
22
25
50
50
50
50
10b
10b
6b
15
23
24
26
29
55
42
33
26
6
31a
31b
31c 31d
1
2
3
4
5
6
7
Py (3)
15
11
6c
Et3N (3)
TMG (3)
Py + Et3N (3 : 3)
Py + DMAP (3 : 3)
oꢀPhen (3)
oꢀPhen + ButOK (3 : 1) 76
Traces Traces
Traces Traces
24
20
58
—
—
—
—
6c
25
25
34
45
18 11
a All reactions were carried out with organolead derivative 36,
which was prepared without isolation in the presence of pyridine
or DMAP (3 equiv.) and Et3N (3 equiv.) in CHCl3 (5 mL per
mmole of the substrate).
b DMAP was used as the ligand.
c Pyridine was used as the ligand.
—
—
41 33
47 47
* The substrate 30a—d : arylboronic acid 37a reagent ratio was
1 equiv. : 1.2 equiv.

Synthesis of benzopyran derivatives
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005 2607
entry 6). The binary 3 : 1 orthoꢀphenanthroline—potasꢀ
sium tertꢀbutoxide system appeared to be even more effiꢀ
cient. This pair of bases allowed us to prepare tetracyclic
derivative 31a from unsubstituted 4ꢀhydroxycoumarin in
an overall yield of 76% after three steps and to synthesize
derivatives 31b—d in 45, 47, and 47% yields, respectively
(see Table 4, entry 7). The reactions with the use of this
system of coordinating additives and organolead reagent
35b produced also benzopyran derivatives 32a—d in 51,
39, 44, and 31% yields, respectively.
Presumably, the introduction of the bidentate ligand
into the coordination polyhedron of the lead atom results
in a substantial increase in the solubility of polar organoꢀ
lead intermediate 11 in chloroform, which can influence
the kinetics of reductive coupling. In addition, bidentate
orthoꢀphenanthroline saturates the coordination polyꢀ
hedron of the lead atom, resulting in the shift of the
equilibrium between the monomeric and oligomeric forms
of organolead reagents 35a,b to the more reactive monoꢀ
meric form. These effects can be observed in enantioꢀ
selective arylation involving aryllead triacetates in the presꢀ
ence of sterically hindered chiral bases.28 The function of
the second component of this binary system viz., potasꢀ
sium tertꢀbutoxide, is to efficiently neutralize HBr, which
is liberated in the annelation step (Fig. 1) and which can
cause not only decomposition of the organolead reagent
but also cleavage of the lactone bond in 4ꢀhydroxyꢀ
coumarin.
skeleton and to the methoxy group at the C(4´) atom of
the aryl fragment C. This coordination of the potassium
cation, on the one hand, can decrease the nucleophilicity
of the enolate anion and, on the other hand, results in less
efficient neutralization of HBr that is eliminated. An inꢀ
crease in the amount of potassium tertꢀbutoxide results in
the formation of byꢀproducts. The use of solvents other
than chloroform, which are more tolerant to ButOK
(THF, toluene, benzene, or diethyl ether), does not lead
to an increase in the yields of tetracyclic derivatives 31a—d
and 32a—d.
In conclusion, let us note that interconversions of
the functional groups are accompanied by inversion of
the reactivities of the electrophilic centers in the diꢀ
cationic equivalent I (Scheme 3). Thus, the benzyl elecꢀ
trophilic center in arylboronic acids 37a,b and 38 (see
Scheme 3, compound II) is more reactive with respect to
nucleophilic reagents than the reaction center at the aroꢀ
matic fragment.35 Transmetallation is accompanied by
the transfer of the aryl group from the boron atom to the
lead atom giving rise to aryllead triacetates 35a,b and 36,
in which the aromatic electrophilic center is more reacꢀ
tive than the benzyl reaction center (see Scheme 3, comꢀ
pound III).
Scheme 3
Noteworthy is the decrease in the yields of cyclization
products 31b—d (45—47%, see Table 4) prepared from
polymethoxyꢀsubstituted 4ꢀhydroxycoumarins 30b—d
compared to the yield of unsubstituted analog 31a (76%).
Moreover, the yields of 4´ꢀmethoxyꢀsubstituted prodꢀ
ucts 32a—d were lower than those of unsubstituted
tetracyclic analogs 31a—d. The results of the present study
were unexpected taking into account that aryllead triacꢀ
etates are most efficient in Cꢀ and Nꢀarylation for the
transfer of electronꢀdonating aryl fragments to the subꢀ
strate.
The observed differences in the yields of cyclization
products can be attributed to complexation of the potasꢀ
sium cation at the enol oxygen atom to the oxygen atoms
of the methoxy substituents at the C(5), C(6), and C(7)
atoms of the fragment A (see Fig. 1) of the coumarin
Note. The electrophilic center is indicated by an arrow.
The presence of the halogen atom in compounds 35a,b
and 36 or in bismuth(V) derivative 10 has virtually no
effect on the reactivity of aryllead triacetates or organoꢀ
bismuth compounds with respect to mild nucleophilic
reagents.
To summarize, we found new polyfunctionalized
organobismuth and organolead reagents containing
2ꢀ(halomethyl)aryl fragments, which allow one to synꢀ
thesize benzopyran derivatives by cascade reactions acꢀ
cording to a threeꢀstep oneꢀpot procedure.
Fig. 1. Influence of complexation of the potassium cation on
cyclization.

2608
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005
Fedorov et al.
oil in 55% yield. Found (%): C, 87.64; H, 5.34. C17H12
O
Experimental
(232.09). Calculated (%): C, 87.90; H, 5.21. 1H NMR (CDCl3),
δ: 5.04 (s, 2 H, OCH2); 7.23 (d, 1 H, H(3), J = 8.9 Hz);
7.29—7.56 (m, 5 H); 7.73 (d, 1 H, J = 8.7 Hz); 7.83 (d, 1 H, J =
8.2 Hz); 8.01 (d, 1 H, J = 7.8 Hz), 8.53 (d, 1 H, J = 8.5 Hz).
13C NMR (CDCl3), δ: 69.3 (OCH2); 117.7 (C(1)); 118.2 (C(3));
123.9, 124.7, 125.2, 126.2, 126.8, 127.0, 128.1, 128.8, 130.1,
130.2, 130.3, 130.6, 132.9, 154.2.
1,3ꢀDimethoxyꢀ6Hꢀbenzo[c]chromene (23) was isolated by
PTLC (diethyl ether—hexane, 3 : 17, as the eluent) as a colorꢀ
less viscous oil in 48% yield. Found (%): C, 74.61; H, 5.74.
C15H14O3 (242.09). Calculated (%): C, 74.36; H, 5.82. 1H NMR
(CDCl3), δ: 3.81 and 3.92 (s, 6 H, OMe); 4.98 (s, 2 H, CH2);
6.24 (m, 2 H, H(4) and H(6)); 7.13 (d, 1 H, H(3´), J = 7.4 Hz);
7.19 (t, 1 H, H(4´), J = 7.1 Hz); 7.32 (dt, 1 H, H(5´), J =
7.5 Hz, J = 1.0 Hz); 8.25 (d, 1 H, H(6´), J = 7.9 Hz). 13C NMR
(CDCl3), δ: 55.4 and 55.6 (OMe); 69.1 (CH2); 93.6 and 94.3
(C(4) and C(6)); 124.2, 125.6, 126.0, and 128.0 (C(3´), C(4´),
C(5´), and C(6´)); 129.4 and 130.6 (C(2) and C(1´)); 157.7
(C(2´)); 158.9 and 160.7 (C(3) and C(5)).
The NMR spectra were recorded on a Bruker ACꢀ200 specꢀ
trometer at 200.13 (1H) and 50.32 MHz (13C). The chemical
shifts are given on the δ scale relative to Me4Si. The IR spectra
were measured on a Specord IRꢀ75 spectrometer. 4ꢀHydroxyꢀ
coumarin derivatives 30a—d were prepared according to known
procedures.30,36 Commercial (Lancaster) Pb(OAc)4, Hg(OAc)2,
and orthoꢀphenanthroline were used without prepurification.
Acetylacetone 33 was distilled immediately before use.
Tris[2ꢀ(chloromethyl)phenyl]bismuth (9). The reaction was
carried out under an inert atmosphere. A solution of isopropyl
bromide (1.9 mL) in anhydrous THF (20 mL) was added
dropwise with continuous stirring and cooling (an ice bath) to
magnesium chips (2.26 g 0.094 mol) (we failed to synthesize
derivative 9 with the use of an activated magnesium powder) in
anhydrous THF (3 mL). Then the reaction mixture was kept at
room temperature for 16 h. The resulting solution of isopropylꢀ
magnesium bromide was filtered through a porous filter under
an inert atmosphere. A solution of 2ꢀiodobenzyl chloride 7 (4 g,
0.016 mol) in anhydrous THF (20 mL) was placed into a threeꢀ
neck flask. Then isopropylmagnesium bromide was added
dropwise with continuous stirring and cooling (–18 °C). The
reaction mixture was kept at –10 °C for 3 h, and bismuth trichloꢀ
ride (1.58 g, 0.005 mol) was added portionwise with cooling
(–10 °C). The reaction mixture was kept at –10 °C with conꢀ
tinuous stirring for 1.5 h and kept at room temperature for 16 h.
A saturated NH4Cl solution (20 mL) was added. The organic
layer was separated in a separatory funnel, and the aqueous layer
was extracted with CH2Cl2 (3×15 mL). The organic extract
was dried over anhydrous Na2SO4. After removal of volatile
products under reduced pressure and recrystallization of the
solid residue from a CH2Cl2—hexane mixture, tris[2ꢀ(chloroꢀ
methyl)phenyl]bismuth was isolated as gray crystals in a yield
of 0.6 g (27%), m.p. (dichloromethane—hexane) 143 °C.
Found (%): C, 43.34; H, 3.31; Bi, 35.35. C21H18Cl3Bi. Calcuꢀ
lated (%): C, 43.04; H, 3.07; Bi, 35.70. 1H NMR (CDCl3), δ:
4.69 (s, 2 H, CH2); 7.25 (dt, 1 H, H(4), J = 7.4 Hz, J = 1.6 Hz);
7.36 (dt, 1 H, H(5), J = 7.4 Hz, J = 1.6 Hz); 7.52 (dd, 1 H, H(3),
J = 7.6 Hz, J = 1.4 Hz); 7.77 (dd, 1 H, H(6), J = 7.4 Hz, J =
1.2 Hz). 13C NMR (CDCl3), δ: 51.2 (CH2); 129.1 (C(3)); 130.7
(C(4)); 131.8 (C(5)); 140.5 (C(6)); 142.2 (C(2)).
Synthesis of benzopyran derivatives 15, 23—26, 31b, and 34
with the use of organobismuth reagent 9 (general method).
Iodobenzene diacetate (1.2 equiv.) was added to tris[2ꢀ(chloroꢀ
methyl)phenyl]bismuth 9 (1 equiv.) in CH2Cl2 (1 mL per 4 mmol
of compound 9). The reaction mixture was stirred at room temꢀ
perature under an inert atmosphere for 6—8 h until the starting
product 9 completely disappeared (TLC, diethyl ether—hexane,
1 : 4, as the eluent). Then a solution of triethylamine (3 equiv.)
and the substrate (0.9 equiv.) in CH2Cl2 (1 mL per 6 mmol of
the substrate) was added dropwise to the reaction mixture, and
the mixture was worked up as described in Table 1. After compleꢀ
tion of the reaction, the solvent was removed under reduced
pressure. Nonvolatile products were filtered through a layer of
silica gel on a porous filter. Benzopyran derivatives were isolated
by preparative TLC. To remove traces of finely dispersed silica
gel from the reaction products, the latter were filtered through a
layer of Celite.
1,2,3ꢀTrimethoxyꢀ6Hꢀbenzo[c]chromene (24) was isolated
by PTLC (diethyl ether—hexane, 1 : 4, as the eluent) as colorꢀ
less crystals, m.p. 70 °C (diethyl ether—hexane); the yield
was 49%. Found (%): C, 70.86; H, 5.71. C16H16O4 (272.10).
1
Calculated (%): C, 70.57; H, 5.92. H NMR (CDCl3), δ: 3.86,
3.88, and 3.42 (s, 9 H, OMe); 4.98 (s, 2 H, CH2); 6.41 (s, 1 H,
H(6)); 7.15—7.41 (m, 3 H, H(3´), H(4´) and H(5´)); 8.26 (d,
1 H, H(6´), J = 7.9 Hz). 13C NMR (CDCl3), δ: 55.9, 60.8, and
61.2 (OMe); 69.1 (CH2); 97.0 (C(6)); 109.8 (C(2)); 124.4, 125.2,
126.6.5 (C(3´), C(4´), C(5´) and C(6´)); 129.1 (C(1´)); 130.9
(C(2, 128´)); 137.8 (C(1´)); 152.2, 152.3, and 153.8 (C(3), C(4),
and C(5)).
2ꢀMethoxyꢀ6Hꢀbenzo[c]chromene (25) was isolated by
PTLC (diethyl ether—hexane, 1 : 3, as the eluent) as a viscous
paleꢀgreen oil in 5% yield. Found (%): C, 78.97; H, 5.87.
C14H12O2 (212.08). Calculated (%): C, 79.22; H, 5.70. 1H NMR
(CDCl3), δ: 3.87 (s, 3 H, OMe); 4.99 (s, 2 H, CH2); 7.34—7.57
(m, 7 H, Ar—H).
2ꢀtertꢀButylꢀ6Hꢀbenzo[c]chromene (26) was isolated by
PTLC (diethyl ether—hexane, 1 : 9, as the eluent) as a viscous
colorless oil in 27% yield. Found (%): C, 85.77; H, 7.42. C17H18
O
(238.14). Calculated (%): C, 85.67; H, 7.61. 1H NMR (CDCl3),
δ: 1,37 (s, 9 H, Me); 5.10 (s, 2 H, CH2); 6.93 (d, 1 H, H(6), J =
8.1 Hz); 7.17 (d, 1 H, H(3´), J = 7.4 Hz); 7.23—7.41 (m, 3 H,
H(3), H(5) and H(6´)); 7.65—7.74 (m, 2 H, H(4´) and H(5´)).
13C NMR (CDCl3), δ: 29.7 (C(CH3)3); 30.9 (Me); 68.5 (CH2);
116.8 (C(6)); 119.9 (C(3´)); 121.9, 124.7, 126.6, 127.5, 128.3
(C(3), C(5), C(4´), C(5´), and C(6´)); 122.1 (C(4)); 125.9
(C(2´)); 131.6 (C(1´)); 144.8 (C(2)); 152.5 (C(1)).
2,4ꢀDimethoxyꢀ6H,11Hꢀ[2]benzopyrano[4,3ꢀc][1]benzoꢀ
pyranꢀ11ꢀone (31b) was isolated by PTLC (diethyl ether—hexꢀ
ane—chloroform, 2 : 1 : 2, as the eluent) and recrystallized from
a chloroform—hexane mixture. Colorless crystals with m.p.
202 °C were obtained in 46% yield. Found (%): C, 69.48; H, 4.39.
C
18H14O5 (310.31). Calculated (%): C, 69.67; H, 4.55. 1H NMR
(CDCl3), δ: 3.84 and 3.87 (both s, 3 H each, OMe); 5.28 (s, 2 H,
CH2); 6.29 (d, 1 H, H(6), J = 2.3 Hz); 6.43 (d, 1 H, H(8), J =
2.3 Hz); 7.09 (d, 1 H, H(3´), J = 7.3 Hz); 7.27 (dt, 1 H, H(4´),
J = 7.3 Hz, J = 1.1 Hz); 7.38 (dt, 1 H, H(5´), J = 7.9 Hz, J =
1.3 Hz); 8.46 (d, 1 H, H(6´), J = 7.6 Hz). 13C NMR (CDCl3), δ:
55.7 and 56.3 (OMe); 69.6 (CH2); 93.0 (C(6)); 96.0 (C(8)); 99.7
5HꢀBenzo[d]naphtho[2,1ꢀb]pyran (15) was isolated by PTLC
(diethyl ether—hexane, 1 : 9, as the eluent) as a colorless viscous

Synthesis of benzopyran derivatives
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005 2609
and 99.8 (C(10) and C(2´)); 123.6, 124.4, 127.0, 127.3, and
128.8 (C(3´), C(4´), C(5´), C(1´), and C(6´)); 156.4 and 158.8
(C(5) and C(7)); 160.2 (C(9)); 163.5 (C(3)); 164.1 (C(4));
171.0 (C(2)).
and the volatile products were removed under reduced pressure.
The solid residue was recrystallized from a CH2Cl2—diethyl
ether—pentane mixture. Compound 38 was isolated as a paleꢀ
yellow polycrystalline powder in a yield of 1.28 g (52%), m.p.
147 °C. Found (%): C, 49.38; H, 4.95. C7H8BClO2 (170.03).
Calculated (%): C, 49.34; H, 4.73. 1H NMR (CDCl3), δ: 5.16
(s, 2 H, CH2Cl); 7.45—7.57 (m, 3 H, H(3), H(4), and H(5));
8.30—8.34 (m, 1 H, H(6)). 13C NMR (CDCl3), δ: 45.9 (CH2Cl);
128.3, 130.5, 132.9, and 137.8 (C(3), C(4), C(5), and C(6));
144.8 (C(2)).
2ꢀ(Chloromethyl)phenyllead triacetate (36). A solution of
2ꢀ(chloromethyl)phenylboronic acid 39 (0.76 g, 0.45 mmol) in
CHCl3 (12 mL) was added dropwise to a solution of lead
tetraacetate (1.98 g, 4.5 mmol) and mercury diacetate (0.14 g,
0.45 mmol) in anhydrous CHCl3 (6 mL) at 40 °C under argon.
The reaction mixture was stirred at 40 °C for 1 h, kept at room
temperature for 16 h, and twice filtered through a layer of Celite.
The solvent was removed under reduced pressure. The solid
product was recrystallized from a CHCl3—diethyl ether—penꢀ
tane mixture at –10 °C. Compound 36 was isolated as paleꢀ
yellow prismatic crystals in a yield of 1.7 g (74%), m.p. 118 °C.
Found (%): C, 30.45; H, 3.16. C13H15ClO6Pb (510.03). Calcuꢀ
lated (%): C, 30.62; H, 2.97. 1H NMR (CDCl3), δ: 2.12 (s, 9 H,
OC(O)CH3); 4.77 (s, 2 H, CH2Cl); 7.52 (td, 1 H, H(4), J =
7.6 Hz, J = 1.3 Hz); 7.58 (td,1 H, H(5), J = 7.6 Hz, J = 1.8 Hz);
7.64 (dd, 1 H, H(3), J = 7.6 Hz, J = 8.0 Hz); 7.78 (dd, 1 H,
H(6), J = 7.6 Hz, J = 1.3 Hz). 13C NMR (CDCl3), δ: 20.2
(OC(O)CH3); 45.1 (CH2Cl); 131.2, 131.6, 132.2, 132.6 (C(3),
C(4), C(5), and C(6)); 140.0 (C(2)); 162.5 (C(1)) and 180.5
(OC(O)CH3).
Reactions of aryllead triacetates 35a and 36 with phenols and
enolizable substrates (general procedure). A solution of aryllead
triacetate 35a or 36 (1.1 equiv.) in anhydrous CHCl3 (5 mL per
mmole of 35a or 36) was added dropwise to a solution of the
substrate (1 equiv.) and a base (the ratios are given in Tables 2
and 3) in anhydrous CHCl3 (5 mL per mmole of substrate). The
reaction was carried out under an inert atmosphere. The reacꢀ
tion mixture was worked up as described in Tables 2 and 3.
Volatile products were removed under reduced pressure. Benzoꢀ
pyran products were isolated by silica gel column chromatoꢀ
graphy.
Synthesis of benzopyran derivatives with the use of a threeꢀ
step oneꢀpot procedure (general procedure). A mixture of
Pb(OAc)4 (1.2 equiv.), Hg(OAc)2 (0.12 equiv.), and arylboronic
acid 35a,b or 36 (1.2 equiv.) in anhydrous CHCl3 (5 mL per
mmole of Pb(OAc)4) was heated at 40 °C under an inert atmoꢀ
sphere for 1—1.5 h. Then the reaction mixture was kept at room
temperature for 10—12 h. The substrate (1.0 equiv.) and a base
(the ratios are given in Tables 2—4) were added to the resulting
solution, and the reaction mixture was stirred (see Tables 2—4).
The solvent was removed under reduced pressure, and the resiꢀ
due was purified by silica gel column chromatography.
1ꢀ(3ꢀMethylꢀ1Hꢀisochromenꢀ4ꢀyl)ethanone (34). Iodobenꢀ
zene diacetate (0.12 g, 0.38 mmol) was added to a solution of
tris[2ꢀ(chloromethyl)phenyl]bismuth 9 (0.20 g, 0.34 mmol) in
dichloromethane (3 mL). The reaction mixture was stirred at
room temperature for 10 h, and the solvent was removed under
reduced pressure. A solution of pentaneꢀ2,4ꢀdione (0.03 g,
0.31 mmol) and sodium hydride (0.03 g, 0.70 mmol) in dry
freshly distilled THF (4 mL) was added to the reaction mixture
(before the reaction, the solution of pentaneꢀ2,4ꢀdione and soꢀ
dium hydride in THF has been kept at room temperature for
10 min). The reaction mixture was refluxed under argon for 4 h
and then kept at room temperature for 16 h. The solution was
filtered through a layer of silica gel on a porous filter (diethyl
ether—hexane, 3 : 7, as the eluent). After PTLC (chloroform—diꢀ
ethyl ether—hexane, 1 : 2 : 7, as the eluent), product 34 was
isolated as a viscous oil in a yield of 0.02 g (0.11 mmol, 35%).
Found (%): C, 76.81; H, 6.28. C12H12O2 (188.08). Calcuꢀ
lated (%): C, 76.57; H, 6.43. 1H NMR (CDCl3), δ: 2.17 (s, 3 H,
Me); 2.46 (s, 3 H, C(O)Me), 5,01 (s, 2 H, CH2); 7.05—7.35 (m,
4 H, Ar—H). 13C NMR (CDCl3), δ: 29.7 (Me); 31.6 (C(O)Me);
69.0 (CH2); 115.3 (C(10)); 127.4 (C(3)); 129.7 (C(5)); 122.4,
124.1, 126.4, and 128.4 (C(5), C(6), C(7), and C(8)); 160.4
(C(9)); 200.8 (C=O).
2ꢀ(Bromomethyl)phenyllead triacetate (35a). A solution of
2ꢀ(bromomethyl)phenylboronic acid 37a (0.96 g, 4.5 mmol) in
CHCl3 (12 mL) was added dropwise to a solution containing
lead tetracetate (1.98 g, 4.5 mmol) and mercury diacetate (0.14 g,
0.45 mmol) in anhydrous CHCl3 (6 mL) at 40 °C under argon.
The reaction mixture was stirred at 40 °C for 1 h, kept at room
temperature for 16 h, and twice filtered through a layer of Celite.
The solvent was removed under reduced pressure. The solid
product was recrystallized from a CHCl3—diethyl ether—penꢀ
tane mixture. Compound 35a was isolated as colorless needleꢀ
like crystals in a yield of 1.1 g (48%), m.p. 142 °C. Found (%):
C, 28.01; H, 2.86. C13H15BrO6Pb (553.98). Calculated (%):
C, 28.17; H, 2.73. 1H NMR (CDCl3), δ: 2.12 (s, 9 H,
OC(O)CH3); 4.65 (s, 2 H, CH2Br); 7.46—7.54 (m, 2 H, H(4)
and H(5)); 7.61 (dd, 1 H, H(3), J = 2.5 Hz, J = 6.8 Hz); 7.76
(dd, 1 H, H(6), J = 1.7 Hz, J = 7.2 Hz). 13C NMR (CDCl3), δ:
20.3 (CH3); 31.7 (CH2Br); 131.1, 131.6, and 132.2 (C(3), C(4),
and C(5)); 133.2 (C(6)); 140.6 (C(2)); 162.5 (C(1));
180.6 (C=O).
2ꢀ(Chloromethyl)phenylboronic acid (38). A solution of
isopropylmagnesium bromide (2.58 g, 0.0176 mol) in THF
(10 mL) was added dropwise with continuous stirring and coolꢀ
ing (–18 °C) to a solution of 2ꢀiodobenzyl chloride 7 (4 g,
0.016 mol) in anhydrous THF (20 mL). The reaction mixture
was kept at –10 °C for 3 h and cooled to –78 °C. Then
triisopropyl borate (3.3 mL, 0.014 mol) was added dropwise into
the flask using a syringe. The reaction mixture was kept at –78 °C
for 1.5 h, slowly warmed to room temperature, and stirred for
16 h. The solvent was removed under reduced pressure. The
solid product was dissolved in diethyl ether (200 mL), 10% HCl
(40 mL) was added, and the reaction mixture was vigorously
shaken in a separatory funnel for 15 min. The organic layer was
separated and washed with 10% HCl (2×30 mL) and water
(3×20 mL). The organic layer was dried over anhydrous MgSO4,
3ꢀMethoxyꢀ6Hꢀbenzo[c]chromene (28) was isolated by colꢀ
umn chromatography (Et2O—petroleum ether, 1 : 19, as the
eluent) as a colorless oil. The yield was 37%. Found (%):
C, 78.96; H, 5.87. C14H12O2 (212.08). Calculated (%): C, 79.22;
H, 5.70. 1H NMR (CDCl3), δ: 3.81 (s, 3 H, OMe); 5.10 (s, 2 H,
OCH2); 6.54 (d, 1 H, H(3), J = 2.5 Hz); 6.63 (dd, 1 H, H(5), J =
8.5 Hz, J = 2.5 Hz); 7.12 (d, 1 H, H(3´), J = 7.5 Hz); 7.22 (t,
1 H, H(4´), J = 7.5 Hz); 7.34 (t, 1 H, H(5´), J = 7.5 Hz); 7.60
(d, 1 H, H(6´), J = 7.5 Hz); 7.64 (d, 1 H, H(6), J = 8.5 Hz).

2610
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 11, November, 2005
Fedorov et al.
13C NMR (CDCl3), δ: 55.4 (OMe); 68.7 (OCH2); 102.3 (C(3));
108.8 (C(5)); 115.9 (C(1)); 121.2, 124.2, 124.6, 126.7, and 128.4
(C(6), C(3´), C(4´), C(5´), and C(6´)); 130.2 and 130.3 (C(1´)
and C(2´)); 156.0 and 160.9 (C(2) and C(4)).
1 H, H(6´), J = 8.6 Hz). 13C NMR (CDCl3), δ: 55.4 (OMe);
69.6 (CH2); 110.2 (C(3´)); 113.5, 116.5, 122.9, 124.0, 124.7,
and 132.0 (C(5), C(6), C(7), C(8), C(5´), and C(6´)); 102.8,
123.6, 126.6, 129.3, 152.5, 159.6, 159.7, and 161.4 (quaternary
C atoms).
2,4,8ꢀTrimethoxyꢀ6H,11Hꢀ[2]benzopyrano[4,3ꢀc][1]benzoꢀ
pyranꢀ11ꢀone (32b) was isolated by column chromatography
(ethyl acetate—petroleum ether, 1 : 1, as the eluent) as colorless
crystals, m.p. 183 °C. The yield was 39%. Found (%): C, 66.94;
H, 4.96. C19H16O6 (340.33). Calculated (%): C, 67.06; H, 4.74.
1H NMR (CDCl3), δ: 3.83 (s, 3 H, OMe); 3.94 (s, 6 H, OMe);
5.33 (s, 2 H, CH2); 6.64 (d, 1 H, H(6), J = 2.6 Hz); 6.82 (s, 1 H,
H(8)); 6.91 (dd, 1 H, Ar—H, J = 8.8 Hz, J = 2.8 Hz); 7.18 (s,
1 H, Ar—H); 8.47 (d, 1 H, H(6´), J = 8.8 Hz). 13C NMR
(CDCl3), δ: 55.4, 56.3, and 56.4 (all OMe); 69.6 (CH2); 99.5,
102.9 (C(6) and C(8)); 110.1 (C(3´)); 113.4 (C(5´)); 126.2
(C(6´)); 100.4, 107.4 119.5, 128.9, 146.3, 148.6, 153.2, 159.3,
159.9, and 160.8 (quaternary C atoms).
2,3,8ꢀTrimethoxyꢀ6H,11Hꢀ[2]benzopyrano[4,3ꢀc][1]benzoꢀ
pyranꢀ11ꢀone (32c) was isolated by column chromatography
(ethyl acetate—petroleum ether, 1 : 1, as the eluent) as colorless
crystals, m.p. 207 °C. The yield was 44%. Found (%): C, 67.31;
H, 4.62. C19H16O6 (340.33). Calculated (%): C, 67.06; H, 4.74.
1H NMR (CDCl3), δ: 3.83 (s, 3 H, OMe); 3.94 (s, 6 H, OMe);
5.33 (s, 2 H, CH2); 6.64 (d, 1 H, H(3´), J = 2.6 Hz); 6.82 (s,
1 H, H(5)); 6.91 (dd, 1 H, H(5´), J = 8.8 Hz, J = 2.8 Hz); 7.18
(s, 1 H, H(8)); 8.47 (d, 1 H, H(6´), J = 8.8 Hz). 13C NMR
(CDCl3), δ: 55.4, 56.3, and 56.4 (all OMe); 69.6 (CH2); 99.5
and 102.9 (C(5) and C(8)); 110.1 (C(3´)); 113.4 (C(5´)); 126.2
(C(6´)); 100.4, 107.4, 119.5, 128.9, 146.3, 148.6, 153.2, 159.3,
159.9, and 160.8 (quaternary C atoms).
2 , 3 , 4 , 8 ꢀ T e t r a m e t h o x y ꢀ 6 H , 1 1 H ꢀ [ 2 ] b e n z o p y r a ꢀ
no[4,3ꢀc][1]benzopyranꢀ11ꢀone (32d) was isolated by column
chromatography (ethyl acetate—petroleum ether, 1 : 1, as the
eluent) as colorless crystals, m.p. 137 °C. The yield was 31%.
Found (%): C, 64.57; H, 5.11. C20H18O7 (370.35). Calcuꢀ
lated (%): C, 64.86; H, 4.90. 1H NMR (CDCl3), δ: 3.84 and
3.88 (both s, 3 H each, OMe); 3.91 (s, 6 H, OMe); 5.32 (s, 2 H,
CH2); 6.65—6.68 (m, 2 H, Ar—H); 6.91 (dd, 1 H, H(5´), J =
8.8 Hz, J = 2.6 Hz); 8.43 (d, 1 H, H(6´), J = 8.8 Hz). 13C NMR
(CDCl3), δ: 55.4, 56.3, 61.4, and 62.3 (all OMe); 69.7 (CH2);
96.3 (C(8)); 109.9 (C(3´)); 113.6 (C(5´)); 129.2 (C(6´)); 96.6,
111.4, 119.6, 126.4, 148.7, 150.4, 150.7, 156.8, 159.5, 160.3,
and 161.3 (quaternary C atoms).
1,3ꢀDiꢀtertꢀbutylꢀ6Hꢀbenzo[c]chromene (29) was isolated by
column chromatography (Et2O—petroleum ether, 1 : 19, as the
eluent) as a colorless oil. The yield was 13%. Found (%):
C, 85.40; H, 8.96. C21H26O (294.43). Calculated (%): C, 85.67;
1
H, 8.90. H NMR (CDCl3), δ: 1.33 and 1.48 (both s, 9 H each,
But); 6.90 (d, 1 H, H(3), J = 2.6 Hz); 7.22—7.32 (m, 3 H,
H(4´), H(5´) and H(6´)); 7.34 (d, 1 H, H(5), J = 2.6 Hz); 7.56
(d, 1 H, H(3´), J = 7.8 Hz). 13C NMR (CDCl3), δ: 31.2 and 33.8
(both But); 34.8 and 37.2 (C(4) and C(6)); 69.3 (OCH2); 110.7
(C(3)); 120.6 (C(5)); 121.3 (C(1)); 124.4, 126.2, 126.8, and
129.9 (C(3´), C(4´), C(5´), and C(6´)); 132.7 and 132.9 (C(1´)
and C(2´)); 149.0 and 151.5 (C(4) and C(6)); 156.6 (C(2)).
6H,11Hꢀ[2]Benzopyrano[4,3ꢀc][1]benzopyranꢀ11ꢀone (31a)
was isolated by column chromatography (diethyl ether—petroꢀ
leum ether, 1 : 1, as the eluent) as a paleꢀyellow powder, m.p.
154 °C. The yield was 76%. Found (%): C, 76.85; H, 4.09.
C
16H10O3 (250.25). Calculated (%): C, 76.79; H, 4.03. 1H NMR
(CDCl3), δ: 5.41 (s, 2 H, CH2), 7.13 (d, 1 H, Ar—H, J =
7.2 Hz); 7.27—7.48 (m, 4 H, Ar—H); 7.57 (t, 1 H, Ar—H, J =
7.6 Hz); 7.87 (d, 1 H, Ar—H, J = 7.8 Hz); 8.55 (d, 1 H, H(6´),
J = 7.6 Hz). 13C NMR (CDCl3), δ: 69.7 (CH2); 116.5, 123.1,
123.9, 124.0, 124.9, 128.2, 129.0, and 132.5 (C—H arom.);
102.6, 115.2, 126.6, 127.4, 152.9, 160.1, and 161.2 (quaternary
C atoms).
2,3ꢀDimethoxyꢀ6H,11Hꢀ[2]benzopyrano[4,3ꢀc][1]benzoꢀ
pyranꢀ11ꢀone (31c) was isolated by column chromatography
(ethyl acetate—petroleum ether, 3 : 7, as the eluent) as a paleꢀ
yellow powder, m.p. 158 °C. The yield was 47%. Found (%):
C, 69.81; H, 4.67. C18H14O5 (310.31). Calculated (%): C, 69.67;
H, 4.55. 1H NMR (CDCl3), δ: 3.96 (s, 6 H, OMe); 5.38 (s, 2 H,
CH2); 6.84 (s, 1 H, H(5)); 7.21 (s, 1 H, H(8)); 7.26—7.41 (m,
3 H, Ar—H); 8.56 (d, 1 H, H(6´), J = 7.6 Hz). 13C NMR
(CDCl3), δ: 56.3 and 56.4 (both OMe); 69.7 (CH2); 99.5 and
103.1 (C(5) and C(8)); 123.8, 127.0, 127.7, and 129.0 (C(3´),
C(4´), C(5´), and C(6´)); 100.4, 107.2, 124.5, 146.4, 149.0,
153.6, 159.6, 160.6, and 161.4 (quaternary C atoms).
2,3,4ꢀTrimethoxyꢀ6H,11Hꢀ[2]benzopyrano[4,3ꢀc][1]benzoꢀ
pyranꢀ11ꢀone (31d) was isolated by column chromatography
(diethyl ether as the eluent) as a paleꢀyellow powder, m.p. 152 °C.
The yield was 47%. Found (%): C, 67.26; H, 4.51. C19H16O6
(340.33). Calculated (%): C, 67.06; H, 4.74. 1H NMR (CDCl3),
δ: 3.88, 3.92, and 3.93 (all s, 3 H each, OMe); 5.69 (s, 2 H,
CH2); 6.69 (s, 1 H, H(8)); 7.12 (d, 1 H, H(3´), J = 7.2 Hz);
7.29—7.44 (m, 3 H, Ar—H); 8.46 (d, 1 H, H(6´), J = 7.0 Hz).
13C NMR (CDCl3), δ: 56.3, 61.4, and 62.3 (all OMe); 69.8
(CH2); 96.3 (C(8)); 123.7, 124.6, 127.7, 128.9 (C(3´), C(4´),
C(5´), and C(6´)); 100.9, 103.4, 127.0, 127.1, 140.2, 150.8,
150.9, 157.2, 160.1, and 162.9 (quaternary C atoms).
We thank I. P. Beletskaya for helpful discussion.
This study was financially supported by the Russian
Foundation for Basic Research (Project No. 02ꢀ03ꢀ
33021), the Competition Center for Fundamental Natuꢀ
ral Sciences (Project No. PD02ꢀ1.3ꢀ443), and INTAS
(Grant 03ꢀ514915).
8ꢀMethoxyꢀ6H,11Hꢀ[2]benzopyrano[4,3ꢀc][1]benzopyranꢀ
11ꢀone (32a) was isolated by column chromatography (diethyl
ether—petroleum ether, 1 : 1, as the eluent) as colorless crystals,
m.p. 137 °C. The yield was 51%. Found (%): C, 72.61; H, 4.72.
C17H12O4 (280.27). Calculated (%): C, 72.85; H, 4.32. 1H NMR
(CDCl3), δ: 3.85 (s, 3 H, OMe); 5.37 (s, 2 H, CH2); 6.67 (d,
1 H, Ar—H, J = 2.4 Hz); 6.94 (dd, 1 H, Ar—H, J = 8.9 Hz, J =
2.4 Hz); 7.27—2.38 (m, 2 H, Ar—H); 7.54 (dt, 1 H, Ar—H, J =
7.9 Hz, J = 1.4 Hz); 7.84 (d, 1 H, Ar—H, J = 7.8 Hz); 8.50 (d,
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Received May 26, 2005;
in revised form August 30, 2005