A new, expeditious entry to the benzophenanthrofuran framework by a Pd-catalyzed C- And O-arylation/PIFA-M ediated oxidative coupling sequence

Article abstract of DOI:10.1002/ejoc.200400856

The synthesis of a series of 2,3-diarylbenzo[b]furans starting from 1,2-diarylethanones and 1,2-dibromoarenes proceeds by means of both homogeneous and polymer-anchored palladium catalysts. This tandem process can be effectively halted at the C-arylation

Full text of DOI:10.1002/ejoc.200400856

FULL PAPER
A New, Expeditious Entry to the Benzophenanthrofuran Framework by a Pd-
Catalyzed C- and O-Arylation/PIFA-Mediated Oxidative Coupling Sequence
Fátima Churruca,[a] Raul SanMartin,*[a] Imanol Tellitu,[a] and Esther Domínguez*[a]
Keywords: Fused-ring systems / Heterogeneous catalysis / Oxidative coupling / Oxygen heterocycles / Palladium
The synthesis of a series of 2,3-diarylbenzo[b]furans starting
from 1,2-diarylethanones and 1,2-dibromoarenes proceeds
by means of both homogeneous and polymer-anchored pal-
ladium catalysts. This tandem process can be effectively
ficient oxidative coupling leading to benzo[b]phen-
anthro[9,10-d]furans is carried out using the safer hyperval-
ent iodine reagent PIFA.
halted at the C-arylation step, thus providing key o-bromoar- (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
ylated deoxybenzoin intermediates in good yields. The ef-
Germany, 2005)
Encouraged by the above illustrated interest in both di-
arylbenzofurans and phenanthroheterocycles, we envisaged
a synthetic pathway to benzo[b]phenanthro[9,10-d]furans 1
starting from 1,2-diarylethanones 2. Besides their availabil-
ity, the choice of such starting materials was made consider-
ing our recently developed procedure for the access to deoxy-
benzoins, which is a more environmentally friendly protocol
based on a palladium-catalysed monoarylation of acetophe-
nones performed by polymer-anchored catalysts.[14] This
paper describes the most noteworthy results obtained
towards the completion of such a synthetic task.
Introduction
The remarkable biological significance of 2,3-di-
arylbenzo[b]furans is clearly exemplified by the resveratrol-
derived natural oligomers anigopreissin A and amurensins
L and M inter alia,[1] and the pharmacological use of some
other derivatives bearing the same framework.[2] Conse-
quently, several synthetic approaches to such interesting
systems, classified according to the number of bonds
formed in the construction of the heterocycle, have been
designed so far.[3,4] Among the protocols based on the se-
quential formation of two bonds of the furan moiety,[4] the
palladium-catalysed coupling reaction between deoxyben-
zoins and dibromoarenes, first reported by Miura et al.,[5]
is an elegant example of a tandem C-arylation/O-arylation
reaction, although, in our opinion, it is still underexploited.
Phenanthro[9,10] heterocycles are also a target skeleton
in the field of molecular materials. Apart from their use as
large planar building blocks in supramolecular chemistry,[6]
their unique photophysical properties make them suitable
for a range of industrial and biological applications, includ-
ing molecular tweezers for explosives, superradiant laser
dyes,[7] chemical sensors,[8] pH-induced luminescent
switches for energy conversion and information storage,[9]
anisotropic liquid crystals in birefringent films,[10] photo-
chromic dyes and sensitizers[11] or electroluminescent layers
in light-emitting devices,[12] inter alia.[13]
Results and Discussion
Tandem C-Arylation/O-Arylation
[a] Kimika Organikoa II Saila, Zientzia eta Teknologia Fakultatea,
Euskal Herriko Unibertsitatea,
P.O. Box 644, 48080 Bilbao, Spain
Fax: +34-94-601-2748
Keeping in mind the pioneering work of Miura et al.,[5]
we initially carried out several assays in order to optimise
E-mail: qopsafar@lg.ehu.es
Eur. J. Org. Chem. 2005, 2481–2490
DOI: 10.1002/ejoc.200400856
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2481

F. Churruca, R. SanMartin, I. Tellitu, E. Domínguez
Table 1. Selected palladium-catalysed coupling assays with ketones 2a,b and dibromobenzene 4a.
FULL PAPER
Entry
Reaction conditions
Product (yield [%])[a]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
2a, 5 mol-% Pd(OAc)2, 20 mol-% PPh3, Cs2CO3, o-xylene, 160 °C, 4 h[b][c]
2a, 5 mol-% Pd(OAc)2, 20 mol-% PPh3, K2CO3, o-xylene, 160 °C, 24 h[b][c]
2b, 5 mol-% Pd(OAc)2, 20 mol-% PPh3, Cs2CO3, o-xylene, 160 °C, 4 h[b][c]
2b, 5 mol-% Pd(OAc)2, 20 mol-% PPh3, K2CO3, o-xylene, 160 °C, 24 h[b][c]
2a, 2 mol-% Pd(OAc)2, 8 mol-% PPh3, Cs2CO3, DMF, 150 °C, 6 h[b][c]
2a, 2 mol-% Pd(OAc)2, 8 mol-% PPh3, Cs2CO3, DMF, 170 °C, 6 h[b][c]
2a, 5 mol-% Pd(OAc)2, 20 mol-% PPh3, Cs2CO3, DMF, 150 °C, 6 h[b][c]
2a, 5 mol-% Pd(OAc)2, 20 mol-% PPh3, Cs2CO3, DMF, 135 °C, 6 h[b][c]
2a, 1 mol-% Pd(OAc)2, 4 mol-% PPh3, Cs2CO3, DMF, 150 °C, 16 h[c][e]
2a, 5 mol-% Pd(OCOCF3)2, 20 mol-% PPh3, Cs2CO3, o-xylene, 165 °C, 1.5 h[c][e]
2a, 0.5 mol-% Pd(PPh3)4, Cs2CO3, o-xylene, 165 °C, 6 h[b][c]
3a (62), 2a (5)
3a (42), 5a (37)
3b (57), 2b (9)
3b (33), 5b (36)
3a (38), 5a (5), 2a (3)
3a (16)
3a (21), 5a (2)
[d]
–
3a (32), 5a (5), 2a (8)
3a (53)
3a (3), 5a (82), 2a (3)
5b (87), 2b (5)
3a (5), 5a (8)
2a (96)
2b, 0.5 mol-% Pd(PPh3)4, Cs2CO3, o-xylene, 165 °C, 6 h[b][c]
2a, 0.5 mol-% Pd(PPh3)4, Cs2CO3, DMF, 150 °C,1,5 h[c][e]
2a, 5 mol-% PdCl2, 20 mol-% PPh3, K2CO3, DMF, 130 °C, 6 h[b][f]
2a, 5 mol-% PdCl2, 20 mol-% PPh3, K2CO3, DMF, 150 °C, 2 h[b][f]
2a, 5 mol-% PdCl2, 20 mol-% PPh3, Cs2CO3, o-xylene, 165 °C, 1.5 h[c][e]
2a, 1 mol-% Pd(OAc)2, 4 mol-% PPh3, K2CO3, o-xylene, 150 °C, 8 h[b][c]
2b, 1 mol-% Pd(OAc)2, 4 mol-% PPh3, K2CO3, o-xylene, 150 °C, 8 h[b][c]
2a, 5 mol-% Pd(OAc)2, 20 mol-% PPh3, Cs2CO3, o-xylene, 165 °C, 1.5 h[c][e]
2b, 5 mol-% Pd(OAc)2, 20 mol-% PPh3, Cs2CO3, o-xylene, 165 °C, 1.5 h[c][e]
[d]
–
3a (14), 2a (4)
5a (92), 3a (3)
5b (95), 2b (1)
3a (91)
3b (84)
[a] GC-MS ratios of detected products measured on the basis of the starting amount of deoxybenzoins 2a,b. Propiophenone was used as
the internal standard. The rest of the reaction crude contained complex mixtures of unidentified products. [b] 1.2 Equiv. of 1,2-dibro-
mobenzene 4a was used. [c] 2.5 Equiv. of base was used. [d] Complex mixtures of products. [e] 1.5 Equiv. of 1,2-dibromobenzene 4a was
used. [f] 3.0 Equiv. of base was used.
the generation of 2,3-diarylbenzofurans 3a,b by means of
a palladium-catalysed coupling of deoxybenzoins 2a,b and
dibromobenzene 4a. To our surprise, the application of the
above-mentioned bibliographic conditions[5] (entries 1–4 in
Table 1) provided unexpected results, such as lower ratios
of the target diarylbenzofurans 3 and the presence of re-
markable amounts of triarylethanones 5a,b. A brief mech-
anistic proposal based on previous work[5] is shown in
Scheme 1. Accordingly, a more comprehensive study with a
larger array of assays, summarised in Table 1, was per-
formed. Not only were furan derivatives 3a,b obtained in
fair ratios (Table 1, entries 19 and 20), but the monoaryl-
ated intermediates 5a,b were also efficiently prepared by a
slight modification of the reaction conditions (Table 1, en-
tries 17 and 18). Although our synthetic goal was not the
latter, the easy preparation of such appealing building
blocks[15] should not be underestimated. At this point, the
noteworthy differences in terms of yield when performing
only slight modifications in the reaction conditions (com-
pare entries 1 and 19 in Table 1), and the great influence of
the base employed, on the progress of the reaction (Table 1,
entries 18 and 20) must be outlined. The optimised condi-
tions for the preparation of furans 3a,b were applied to a Scheme 1.
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A New Entry to the Benzophenanthrofuran Framework
FULL PAPER
range of diarylethanones 2 and dibromoarenes 4 to give the couraged not only by the current tendency, based on sus-
corresponding derivatives 3a–l (Table 2).
tainable chemistry principles, towards heterogeneous cataly-
sis, but also by the scarcity of bibliographic examples fea-
turing the use of heterogeneous catalysis in the preparation
(non-related) of simple benzofurans[17] or in arylation reac-
tions involving the formation of C–O bonds;[18] reports de-
scribing a sequence of synthetic transformations performed
by the same heterogeneous palladium catalyst are even
rarer.[19]
Table 2. Diarylbenzofurans 3 prepared by homogeneous and
heterogeneous catalysis.
On the basis of the excellent results obtained when per-
forming the arylation of ketone enolates by means of poly-
mer-anchored catalysts FibreCatTM [14]
we conceived that,
,
as the first step of the tandem reactions leading to diaryl-
benzofurans 3 is again a palladium-catalysed arylation of
deoxybenzoins,[20] the application of the latter polymer-sup-
ported catalyst[21] could constitute an interesting alternative
to the homogeneous protocol. In consequence, different re-
action conditions were assayed with ketone 2a, dibro-
mobenzene 4a and commercially available FibreCatTM
1001, FibreCatTM 1007 and FibreCatTM 1026 catalysts[22]
(Table 3). A brief comparison with another established
heterogeneous system (Pd-C) was also made.
In a similar way to the monoarylation of deoxybenzo-
ins,[14] the best yield of benzofuran 3a was obtained when
FibreCatTM 1026 was used. Such a result is a bit surprising
because, unlike FibreCatTM 1001, which is clearly related to
the homogeneous Pd(OAc)2/PPh3 system and is therefore
the expected heterogeneous alternative, FibreCatTM 1026
features Cl–, PPh3 and CH3CN ligands attached to palla-
dium metal. Anyway, although slightly lower than under
homogeneous conditions, the ratio attained was good
enough to suggest application to the rest of the substrates
2 and 4.
Precisely in the same way as in the above-mentioned
monoarylation of deoxybenzoins, the results, although sim-
ilar (see Table 2), were slightly inferior to the ones obtained
by homogeneous catalysis. An explanation for such behav-
iour that can be shared by both transformations is that,
unlike the homogeneous system, the sterically crowded
catalytic centres attached to the polymer backbone of Fib-
reCatTM 1026 are relatively hindered and cannot be ef-
ficiently reached by the common substrate, deoxybenzoins
2. Nevertheless, weighed against the homogeneous reaction,
the ease of work-up, catalyst separation and purification
must be emphasised.
Regarding catalyst recycling, the relatively harsh condi-
tions required, with temperatures above the thermal sta-
bility of the employed catalyst (ca. 120 °C) provoked its
complete deactivation for further use.
Finally, the complete absence of aryl–phenyl exchange
products generated by phenyl migration from the PPh3 li-
gand, which is a side reaction observed in our previous re-
search on arylation of ketones,[14,23a] suggests not only a
high reactivity of both dibromoarenes 4 and intermediates
5 under these reaction conditions, but also that the forma-
Entry
R1
R2
R3
R4
3 (yield [%])[a]
1
2
3
4
5
6
7
8
H
OMe
H
H
OMe
H
H
H
H
H
H
OMe
OMe
OMe
OMe
H
H
OMe
H
Me
F
H
H
OMe
H
Me
F
3a (87) 60
3b (77) 74
3c (65) 58
3d (70) 69
3e (87) 68
3f (73) 71
3g (79) 75
3h (76) 70
3i (78) 65
3j (62) 68
3k (81) 70
3l (75) 68
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OCH2OOMe
9
Me
F
OMe
Me
F
OMe
10
11
12
OCH2OOMe
[a] Yield of pure crystalline compound (EtOAc). Yields of com-
pounds obtained with method A are shown in parentheses and
those with method B are given in italics.
The generality of the presented procedure relies on the
fact that no substantial difference can be found when using
electronically quite divergent dibromides 4, since target de-
rivatives 3 were obtained with good yields in all cases. With
regard to deoxybenzoins, the choice of ketone precursors 2
was in our case heavily influenced by the next scheduled
step of the synthetic sequence − the intramolecular coup-
ling of the aryl rings attached to the C-2 and C-3 positions
− as such oxidative ring-closure usually requires hydroxyl-
ated or alkoxylated coupling partners.[16]
Synthesis of Diarylbenzofurans by Means of Polymer-
Anchored Palladium Catalysts
Nevertheless, before attempting the above-mentioned tion of the heteroaromatic system 3 is energetically favoured
oxidative coupling we decided to explore the synthesis of in comparison with a hypothetical α-phenylated deoxyben-
benzofurans 3 using heterogeneous palladium catalysts, en- zoin product.
Eur. J. Org. Chem. 2005, 2481–2490
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F. Churruca, R. SanMartin, I. Tellitu, E. Domínguez
FULL PAPER
Table 3. Selected coupling assays performed with heterogeneous palladium catalysts.
Entry
Reaction conditions
Product (yield [%])[a]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
5% Pd/C, Na2CO3, MeOH, 80 °C, 6 h[b]
5a (9), 2a (79)
3a (5), 5a (16), 2a (74)
3a (17), 2a (55)
3a (7), 5a (22), 2a (51)
3a (38), 5a (24)
3a (32), 5a (21), 2a (8)
3a (47)
3a (60), 2a (2)
3a (4), 5a (16), 2a (45)
3a (3), 5a (8), 2a (74)
3a (5), 5a (4), 2a (65)
3a (8), 5a (21), 2a (46)
3a (27), 5a (16), 2a (2)
3a (18), 5a (5)
5% Pd/C, NaOH, NH4HCO2, 100 °C, H20, 2 h[b]
5% Pd/C, Na2CO3, DMF, 150 °C, 1.5 h[b]
2% FC 1007, K2CO3, o-xylene, 165 °C, 2 h[c]
5% FC 1007, K2CO3, o-xylene, 165 °C, 8 h[c]
2% FC 1007, Cs2CO3, o-xylene, 165 °C, 8 h[c]
5% FC 1007, Cs2CO3, o-xylene, 165 °C, 8 h[c]
5% FC 1007, Cs2CO3, o-xylene, 165 °C, 8 h[d]
5% FC 1007, Cs2CO3, toluene, 130 °C, 8 h[d]
5% FC 1001, K2CO3, o-xylene, 165 °C, 8 h[d]
5% FC 1001, Cs2CO3, o-xylene, 165 °C, 8 h[d]
5% FC 1001, Cs2CO3, o-xylene, 165 °C, 8 h[c]
5% FC 1026, Cs2CO3, DMF, 150 °C, 8 h[c]
5% FC 1026, Cs2CO3, DMF, 165 °C, 8 h[c]
5% FC 1026, Cs2CO3, o-xylene, 165 °C, 8 h[d]
5% FC 1026, Cs2CO3, o-xylene, 165 °C, 2 h[c]
5% FC 1026, Cs2CO3, o-xylene, 165 °C, 8 h[c]
3a (43), 5a (31)
3a (15), 5a (3), 2a (72)
3a (63)
[a] GC-MS ratios of detected products measured on the basis of the starting amount of deoxybenzoin 2a. Propiophenone was used as
the internal standard. The rest of the reaction crude contained complex mixtures of unidentified products. [b] 1.2 Equiv. of 1,2-dibro-
mobenzene (4a), a 5% Pd/C mixture and 2.3 equiv. of base were used. [c] 1.6 Equiv. of 1,2-dibromobenzene (4a), 2.5 equiv. of base and
the indicated FibreCatTM catalyst (FC) were used. The disclosed proportion of FC (%) refers to the relative amount of Pd metal from
the FC catalyst. The average content of Pd in the employed FC samples is 3%. [d] 1.2 Equiv. of 1,2-dibromobenzene (4a) was used.
Intramolecular Oxidative Coupling
Depending on the electronic nature of the substrate em-
ployed, the reaction conditions were efficiently modulated.
Hence, the coupling of furans 3b and 3i–l (Table 4, entries 2
and 9–12) was effected under milder conditions (method A)
probably due to the activation of both arene rings to be
coupled (R1 = R2 = OMe), and the absence of alkoxy
groups in the aryl ring attached to the benzofuran C-2 posi-
tion in substrates 3d–f (R1 = OMe; R2 = H) conditioned
the process to the use of more equivalents of the oxidizing
agent PIFA/BF3·OEt2 and a higher temperature (Method
B), a behaviour already reported in other PIFA-mediated
reactions.[27d] The same hypothesis can be applied to ex-
plain the lack of reactivity of derivatives 3a and 3c (R1 =
R2 = H) under both reaction conditions.
However, other factors must also be taken into account
in order to understand the behaviour of furans 3g,h
(Table 4, entries 8 and 9). Although the aryl rings to be cou-
pled are the same as in 3d–f, the presence of electron-donat-
ing groups in the benzofuran moiety of 3g,h is likely the
cause of such dissimilar results. Our proposal is that, in the
case of substrates 3g,h, the corresponding intermediates B
(Scheme 2) are highly stabilized by delocalisation of the
charge within the electron-rich alkoxylated benzofuran sys-
In spite of its longevity, oxidative coupling between two
phenolic or alkoxylated arene partners[16,24] is still a good
alternative to modern (Stille, Suzuki, Negishi) and old
(Ullmann) metal-catalysed cross-coupling reactions since it
avoids the use of halogenated/sulfonated substrates.[25] It is
also favourably compared to photochemical approaches, as
these often show limitations concerning substitution pat-
terns in the substrates or regiochemistry of the process.[26]
However, an important disadvantage of most oxidative
coupling procedures is the need for heavy metal oxidants in
stoichiometric amounts. Therefore, the use of peroxides
and, above all, hypervalent iodine reagents has attracted
much attention.[27]
In previous works we have proved the applicability of
PIFA (phenyliodo(iii) bis(trifluoroacetate), which is an envi-
ronmentally safer reagent of low toxicity and ready biode-
gradability, to the synthesis of several phenanthro-fused
heterocycles, such as isoxazoles, thiazoles, pyrazoles and
pyrimidines.[28] In an attempt to extend the scope of the
PIFA-mediated oxidative coupling methodology, the latter
protocol was applied to diarylbenzofurans 3 (Table 4).
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A New Entry to the Benzophenanthrofuran Framework
FULL PAPER
Table 4. Benzo[b]phenanthro[9,10-d]furans 1 prepared by intramol-
ecular oxidative coupling.
En-
try
3
R1
H
R2
H
R3
R4
Method 1 (yield
[%])[a]
[b]
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3d
3e
3f
3g
3h
3i
H
H
H
H
A, B
A
–
OMe OMe
H
1a (80)
[b]
H
H
H
H
H
H
H
OMe OMe A, B
H
H
Me
F
–
OMe
OMe
OMe
OMe
OMe
OMe
H
H
Me
F
A
B
B
B
1b (40)
1b (79)
1c (71)
1d (85)
[b]
OMe OMe A, B
–
[b]
9
OCH2O
Me
A, B
A
A
A
A
–
10
11
12
13
OMe OMe Me
OMe OMe
OMe OMe OMe OMe
OMe OMe OCH2O
1e (84)
1f (79)
1g (73)
1h (83)
3j
3k
3l
F
F
[a] Yield of pure crystallised compound (Et2O). [b] Complex mix-
ture containing unreacted starting material whatever the method
used.
tem (B ↔ X), thus hindering the nucleophilic attack of the
phenyl ring and allowing other side-reactions, such as the
oxidation of the benzofuran moiety, a process that is al-
ready known.[29] In contrast, the absence of alkoxy groups
in the benzofuran core of substrates 3d–f meanss that a
more reactive B, in which charge remains at the 3,4-dimeth-
oxyphenyl ring (DЈ), readily undergoes attack of the adja-
cent phenyl nucleophile.
The above theoretical explanation was corroborated by
the fact that no coupling was achieved with derivatives 3a,
3c and 3g,h with a range of other oxidants.[30] The latter
results, along with the good yields obtained in the rest of
the cases, constitute a comparative proof of the potential of
the chosen hypervalent iodine reagent.
Moreover, the presented coupling strategy is the only al-
ternative to the currently existing photochemical approach
to the benzo[b]phenanthro[9,10-d]furan nucleus,[31] an alter-
native protocol that is highly advantageous if the absence
of specific instrumentation and the good overall yields are
considered.
Scheme 2.
Conclusions
To sum up, a tandem C-/O-arylation conducted by
homogeneous and polymer-anchored palladium catalysts
has been applied to a series of 1,2-diarylethanones and 1,2-
dibromoarenes to furnish the corresponding 2,3-diarylben-
zofurans in a regioselective way. The latter intermediates
can be oxidatively coupled in the presence of the iodine(iii)
reagent PIFA, thus avoiding the use of heavy metal oxidants
or photochemical procedures and providing a new entry to
the pentacyclic benzo[b]phenanthro[9,10-d]furan system.
Experimental Section
General Remarks: General experimental details have been reported
previously.[32]
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F. Churruca, R. SanMartin, I. Tellitu, E. Domínguez
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General Procedure for the Synthesis of 2,3-Diarylbenzofurans 3 by
Homogeneous Catalysis: Dry, degassed o-xylene (2.5 mL) was
added to an oven-dried reaction flask charged with Pd(OAc)2
(0.02 mmol), Cs2CO3 (1.27 mmol), PPh3 (0.10 mmol), ketone 2
(0.51 mmol) and dibromoarene 4 (0.76 mmol) under argon at room
temperature. The resultant stirred suspension was heated to 165 °C
for 1.5–4 h. After cooling, HCl (8 mL of a 1.4 m solution in water)
was added and the aqueous layer was extracted with CH2Cl2
(3×5 mL). The combined organic extracts were dried with anhy-
drous sodium sulfate and the solvents evaporated in vacuo. The
residue was purified by flash chromatography on silica gel with 10–
40% EtOAc/hexane as eluent. This procedure gave compounds 3a–
d, 3g and 3l. The preparation of diarylbenzofurans 3e,f and 3h–k
required the use of 0.56 mmol of dibromoarene 4.
OCH3), 6.82 (d, J = 8.3 Hz, 1 H, ArH), 7.11 (d, J = 1.9 Hz, 1 H,
ArH), 7.22 (s, 1 H, 7-H), 7.26 (dd, J = 8.3, 1.9 Hz, 1 H, ArH), 7.33
(s, 1 H, 4-H), 7.38–7.54 (m, 5 H, ArH) ppm. 13C NMR (63 MHz,
CDCl3): δ = 19.9 (CH3), 20.5 (CH3), 55.4 (OCH3), 55.7 (OCH3),
109.7 (CH), 110.8 (CH), 111.3 (C-7), 115.9 (C-3), 119.4 (C-4), 119.7
(CH), 123.6 (C), 127.3 (CH), 128.2 (C-3a), 128.8 (CH), 129.8 (CH),
131.4 (C-5, C-6), 133.3 (C-5, C-6, C), 133.4 (C-5, C-6, C), 148.4
(C-OCH3), 148.8 (C-OCH3), 149.7 (C-2), 152.6 (C-7a) ppm. FTIR
(neat): ν = 1256 cm–1 (C–O), 1025 (C–O). EIMS: m/z (%) = 358
˜
(100) [M+], 343 (13). HRMS: calcd. for C24H22O3 [M+] 358.1569;
found 358.1564. C24H22O3 (358.43): calcd. C 80.42, H 6.19; found
C 80.47, H 6.15.
2-(3,4-Dimethoxyphenyl)-5,6-difluoro-3-phenylbenzo[b]furan
(3f):
Yield: 73%. White powder, m.p. 108–109 °C (EtOAc). Rf = 0.33
1
2,3-Diphenylbenzo[b]furan (3a): Yield: 87%. White powder, m.p.
(30% EtOAc/hexane). H NMR (250 MHz, CDCl3): δ = 3.66 (s, 3
122.5–123 °C (EtOAc) [ref.[5] 121 °C (EtOH)].
H, OCH3), 3.88 (s, 3 H, OCH3), 6.81 (d, J = 8.3 Hz, 1 H, ArH),
7.08 (d, J = 1.6 Hz, 1 H, ArH), 7.15–7.25 (m, 3 H, 7-H, ArH), 7.34
(dd, J = 9.5, 6.3 Hz, 1 H, 4-H), 7.40–7.48 (m, 4 H, ArH) ppm. 13C
NMR (63 MHz, CDCl3): δ = 55.5 (OCH3), 55.8 (OCH3), 100.1 [d,
J(C,F) = 21.5 Hz, C-7), 106.5 (d, JC,F = 21.5 Hz, C-4), 109.6 (CH),
2,3-Bis(3,4-dimethoxyphenyl)benzo[b]furan (3b): Yield: 77%. Yellow
powder, m.p. 148–150 °C (EtOAc). Rf = 0.59 (50% EtOAc/hexane).
1H NMR (250 MHz, CDCl3): δ = 3.74 (s, 3 H, OCH3), 3.82 (s, 3
H, OCH3), 3.89 (s, 3 H, OCH3), 3.95 (s, 3 H, OCH3), 6.81 (d, J =
8.3 Hz, 1 H, ArH), 6.97–7.02 (m, 2 H, ArH), 7.08 (dd, J = 7.9,
1.6 Hz, 1 H, ArH), 7.20–7.44 (m, 4 H, 5-H, 6-H, ArH), 7.48 (d, J
= 7.5 Hz, 1 H, 7-H), 7.54 (d, J = 7.9 Hz, 1 H, 4-H) ppm. 13C NMR
(63 MHz, CDCl3): δ = 55.3 (OCH3), 55.4 (OCH3), 55.6 (OCH3),
109.4 (CH), 110.5 (C-7), 110.6 (CH), 111.2 (CH), 112.4 (CH), 115.7
(C-3), 119.4 (C-4), 119.5 (CH), 121.9 (CH), 122.6 (C-6), 123.1 (C),
124.0 (C-6), 125.1 (C), 130.2 (C-3a), 148.1 (C-OCH3), 148.2 (C-
OCH3), 148.8 (C-OCH3), 148.9 (C-OCH3), 150.0 (C-2), 153.3 (C-
110.9 (CH), 116.0 (C-3), 119.6 (CH), 122.7 (C), 126.0 (d, JC,F
=
6.8 Hz, C-3a), 127.9 (CH), 129.1 (CH), 129.6 (CH), 132.2 (C),
148.2 (dd, JC,F = 246.0, 14.4 Hz, C-5, C-6), 148.3 (C-OCH3), 148.5
(C-OCH3), 148.7 (dd, JC,F = 242.3, 16.2 Hz, C-5, C-6), 149.3 (C-
2), 152.2 (d, JC,F = 5.3 Hz, C-7a) ppm. FTIR (neat): ν = 1254 cm–1
˜
(C–O), 1023 (C–O). EIMS: m/z (%) = 366 (100) [M+], 351 (17), 295
(10), 291 (13). HRMS: calcd. for C22H16F2O3 [M+] 366.1068; found
366.1066. C22H16F2O3 (366.36): calcd. C 72.13, H 4.40, F 10.37;
found C 72.18, H 4.42, F 10.35.
7a) ppm. FTIR (neat): ν = 1252 cm–1 (C–O), 1026 (C–O). EIMS:
˜
m/z (%) = 390 (100) [M+], 375 (11). HRMS: calcd. for C24H22O5
[M+] 390.1467; found 390.1458. C24H22O5 (390.43): calcd. C 73.83,
H 5.68; found C 73.79, H 5.76.
2-(3,4-Dimethoxyphenyl)-5,6-dimethoxy-3-phenylbenzo[b]furan (3g):
Yield: 79%. Yellow powder, m.p. 133–134 °C (EtOAc). Rf = 0.79
1
(40% EtOAc/hexane). H NMR (250 MHz, CDCl3): δ = 3.65 (s, 3
5,6-Dimethoxy-2,3-diphenylbenzo[b]furan (3c):[33] Yield: 65%. White
powder, m.p. 159–160 °C (EtOAc). Rf = 0.35 (20% Et2O/hexane).
1H NMR (250 MHz, CDCl3): δ = 3.88 (s, 3 H, OCH3), 3.97 (s, 3
H, OCH3), 6.90 (s, 1 H, 7-H), 7.13 (s, 1 H, ArH), 7.19 (s, 1 H, 4-
H), 7.27–7.32 (m, 3 H, ArH), 7.42–7.51 (m, 4 H, ArH), 7.58–7.62
(m, 2 H, ArH) ppm. 13C NMR (63 MHz, CDCl3): δ = 56.3
(OCH3), 95.0 (C-7), 100.9 (C-4), 117.6 (C-3), 122.0 (C-3a), 126.3
(CH), 127.5 (CH), 127.6 (CH), 128.2 (CH), 128.9 (CH), 129.5
(CH), 130.8 (C), 133.0 (C), 146.6 (C-5, C-6), 148.2 (C-5, C-6, C-2),
H, OCH3), 3.86 (s, 6 H, OCH3), 3.95 (s, 3 H, OCH3), 6.79 (d, J =
8.7 Hz, 1 H, ArH), 6.86 (s, 1 H, 7-H), 7.05 (d, J = 1.9 Hz, 1 H,
ArH), 7.11 (s, 1 H, 4-H), 7.21 (dd, J = 8.3, 1.9 Hz, 1 H, ArH),
7.35–7.53 (m, 5 H, ArH) ppm. 13C NMR (63 MHz, CDCl3): δ =
55.3 (OCH3), 55.7 (OCH3), 56.2 (OCH3), 56.3 (OCH3), 94.9 (C-7),
100.7 (C-4), 109.3 (CH), 110.8 (CH), 116.3 (C-3), 118.9 (CH), 122.1
(C-3a), 123.6 (C), 127.4 (CH), 128.9 (CH), 129.7 (CH), 133.2 (C),
146.5 (C-5, C-6), 147.9 (C-5, C-6), 148.2 (C-2), 148.4 (C-OCH3),
148.6 (C-OCH ), 149.5 (C-7a) ppm. FTIR (neat): ν = 1260 cm–1
˜
3
(C–O), 1026 (C–O). EIMS: m/z (%) = 390 (100) [M+], 375 (32), 319
(10). HRMS: calcd. for C24H22O5 [M+] 390.1467; found 390.1467.
C24H22O5 (390.43): calcd. C 73.83, H 5.68; found C 73.80, H 5.65.
148.5 (C-5, C-6, C-2), 149.5 (C-7a) ppm. FTIR (neat): ν =
˜
1261 cm–1 (C–O), 1027 (C–O). EIMS: m/z (%) = 330 (100) [M+],
315 (11).
2-(3,4-Dimethoxyphenyl)-5,6-methylenedioxy-3-phenylbenzo[b]furan
(3h): Yield: 76%. Yellow powder, m.p. 156–157 °C (EtOAc). Rf =
0.42 (30% EtOAc/hexane). H NMR (250 MHz, CDCl3): δ = 3.66
2-(3,4-Dimethoxyphenyl)-3-phenylbenzo[b]furan (3d): Yield: 70%.
Yellow oil. Rf = 0.45 (20% EtOAc/hexane). H NMR (250 MHz,
1
1
CDCl3): δ = 3.67 (s, 3 H, OCH3), 3.88 (s, 3 H, OCH3), 6.82 (d, J
= 8.7 Hz, 1 H, ArH), 7.14 (d, J = 1.8 Hz, 1 H, ArH), 7.19–7.35
(m, 3 H, 5-H, 6-H, ArH), 7.39–7.56 (m, 7 H, 4-H, 7-H, ArH) ppm.
13C NMR (63 MHz, CDCl3): δ = 55.4 (OCH3), 55.8 (OCH3), 109.8
(CH), 110.8 (CH), 110.9 (C-7), 116.2 (C-3), 119.6 (C-4, CH), 119.7
(C-4, CH), 122.8 (C-5), 123.3 (C), 124.2 (C-6), 127.5 (CH), 128.8
(CH), 129.8 (CH), 130.5 (C-3a), 133.0 (C), 148.5 (C-OCH3), 149.1
(s, 3 H, OCH3), 3.87 (s, 3 H, OCH3), 5.98 (s, 2 H, CH2), 6.79 (d,
J = 8.7 Hz, 1 H, ArH), 6.82 (s, 1 H, 7-H), 7. 04 (s, 1 H, 4-H), 7.05
(d, J = 1.9 Hz, 1 H, ArH), 7.19 (dd, J = 8.3, 1.9 Hz, 1 H, ArH),
7,35–7,48 (m, 5 H, ArH) ppm. 13C NMR (63 MHz, CDCl3): δ =
55.3 (OCH3), 55.6 (OCH3), 93.1 (C-7), 98.1 (C-4), 101.1 (CH2),
109.2 (CH), 110.7 (CH), 116.6 (C-3), 118.9 (CH), 123.4 (C-3a, C),
123.6 (C-3a, C), 127.4 (CH), 128.8 (CH), 129.6 (CH), 133.0 (C),
144.5 (C-5, C-6), 146.0 (C-5, C-6), 148.2 (C-2), 148.6 (C-OCH3),
(C-OCH ), 150.5 (C-2), 153.7 (C-7a) ppm. FTIR (neat): ν =
˜
3
1251 cm–1 (C–O), 1025 (C–O). EIMS: m/z (%) = 330 (100) [M+],
315 (13), 255 (12). HRMS: calcd. for C22H18O3 [M+] 330.1256;
found 330.1244. C22H18O3 (330.38): calcd. C 79.98, H 5.49; found
C 79.91, H 5.52.
148.7 (C-OCH ), 149.9 (C-7a) ppm. FTIR (neat): ν = 1260 cm–1
˜
3
(C–O), 1026 (C–O). EIMS: m/z (%) = 374 (100) [M+], 359 (20).
HRMS: calcd. for C23H18O5 [M+] 374.1154; found 374.1172.
C23H18O5 (374.39): calcd. C 73.79, H 4.85; found C 73.74, H 4.92.
2-(3,4-Dimethoxyphenyl)-5,6-dimethyl-3-phenylbenzo[b]furan (3e):
Yield: 87%. Yellow powder, m.p. 125–126 °C (EtOAc). Rf = 0.48
2,3-Bis(3,4-dimethoxyphenyl)-5,6-dimethylbenzo[b]furan (3i): Yield:
78%. Yellow powder, m.p. 138.5–140 °C (EtOAc). Rf = 0.76 (40%
1
(20% EtOAc/hexane). H NMR (250 MHz, CDCl3): δ = 2.31 (s, 3
H, CH3), 2.39 (s, 3 H, CH3), 3.67 (s, 3 H, OCH3), 3.88 (s, 3 H, EtOAc/hexane). 1H NMR (250 MHz, CDCl3): δ = 2.32 (s, 3 H,
2486
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 2481–2490

A New Entry to the Benzophenanthrofuran Framework
FULL PAPER
CH3), 2.39 (s, 3 H, CH3), 3.73 (s, 3 H, OCH3), 3.82 (s, 3 H, OCH3),
3.88 (s, 3 H, OCH3), 3.95 (s, 3 H, OCH3), 6.81 (d, J = 8.3 Hz, 1
H, ArH), 6.97–7.00 (m, 2 H, ArH), 7.07 (dd, J = 8.3, 1.6 Hz, 1 H,
ArH), 7.20–7.22 (m, 3 H, 7-H, ArH), 7.32 (s, 1 H, 4-H) ppm. 13C
NMR (63 MHz, CDCl3): δ = 19.8 (CH3), 20.4 (CH3), 55.5 (OCH3),
55.6 (OCH3), 55.8 (OCH3), 56.0 (OCH3), 109.4 (CH), 110.7 (CH),
111.3 (C-7), 112.6 (CH), 115.6 (C-3), 119.3 (C-4), 119.6 (CH), 122.0
(CH), 123.6 (C), 125.7 (C), 128.3 (C-3a), 131.3 (C-5, C-6), 133.3
(C-5, C-6), 148.2 (C-OCH3), 148.4 (C-OCH3), 148.7 (C-OCH3),
(100) [M+], 419 (19). HRMS: calcd. for C25H22O7 434.1366; found
434.1363. C25H22O7 (434.44): calcd. C 69.12, H 5.10; found C
69.09, H 5.12.
General Procedure for the Synthesis of Intermediate o-Bromoaryl-
ated Deoxybenzoins 5: Dry, degassed o-xylene (2.5 mL) was added
to an oven-dried reaction flask charged with Pd(OAc)2
(0.005 mmol), K2CO3 (1.27 mmol), PPh3 (0.02 mmol), ketone 2
(0.51 mmol) and dibromoarene 4 (0.61 mmol) under argon at room
temperature. The resultant stirred suspension was heated to 150 °C
for 8 h. After cooling, HCl (8 mL of a 1.4 m solution in water) was
added and the aqueous layer was extracted with CH2Cl2 (3×5 mL).
The combined organic extracts were dried with anhydrous sodium
sulfate and the solvents evaporated in vacuo to give a residue,
which was purified by flash chromatography on silica gel with 10–
30% EtOAc/hexane as eluent.
149.0 (C-OCH ), 149.4 (C-2), 152.4 (C-7a) ppm. FTIR (neat): ν =
˜
3
1259 cm–1 (C–O), 1026 (C–O). EIMS: m/z (%) = 418 (100) [M+].
HRMS: calcd. for C26H26O5 [M+] 418.1780; found 418.1779.
C26H26O5 (418.48): calcd. C 74.62, H 6.26; found C 74.69, H 6.22.
2,3-Bis(3,4-dimethoxyphenyl)-5,6-difluorobenzo[b]furan (3j): Yield:
62%. White powder, m.p. 120–122 °C (EtOAc). Rf = 0.64 (15%
EtOAc/CH2Cl2). 1H NMR (250 MHz, CDCl3): δ = 3.72 (s, 3 H,
OCH3), 3.82 (s, 3 H, OCH3), 3.88 (s, 3 H, OCH3), 3.95 (s, 3 H,
OCH3), 6.80 (d, J = 8.3 Hz, 1 H, ArH), 6.94–7.04 (m, 3 H, ArH),
7.16–7.26 (m, 3 H, 7-H, ArH), 7.35 (dd, J = 9.9, 6.4 Hz, 1 H, 4-
H) ppm. 13C NMR (63 MHz, CDCl3): δ = 55.6 (OCH3), 55.8
(OCH3), 55.9 (OCH3), 100.1 (d, JC,F = 21.5 Hz, C-7), 106.4 (d, JC,F
= 19.7 Hz, C-4), 109.5 (CH), 110.8 (CH), 111.6 (CH), 112.4 (CH),
115.9 (C-3), 119.6 (CH), 122.0 (CH), 122.8 (C), 124.4 (C), 126.1
(d, JC,F = 7.2 Hz, C-3a), 148.2 (dd, JC,F = 246.0, 16.2 Hz, C-5, C-
6), 148.3 (C-OCH3), 148.4 (C-OCH3), 148.6 (C-OCH3), 148.7 (dd,
JC,F = 242.3, 14.4 Hz, C-5, C-6), 148.7 (C-OCH3), 149.3 (C-2),
2-(2-Bromophenyl)-1,2-diphenylethanone (5a): Yield: 84%. White
powder, m.p. 99–100 °C (MeOH). Rf = 0.43 (10% EtOAc/hexane).
1H NMR (250 MHz, CDCl3): δ = 6.56 (s, 1 H, CH), 7.12–7.17 (m,
2 H, ArH), 7.24 (dd, J = 6.7, 1.2 Hz, 1 H, ArH), 7.33–7.53 (m, 8
H, ArH), 7.65 (dd, J = 7.5, 1.6 Hz, 1 H, ArH), 8.01 (dd, J = 7.1,
1.6 Hz, 2 H, ArH) ppm. 13C NMR (63 MHz, CDCl3): δ = 58.8
(CH-C=O), 124.7 (CBr), 127.4 (CH), 128.5 (CH), 128.6 (CH),
128.7 (CH), 129.4 (CH), 130.9 (CH), 132.7 (CH), 132.9 (CH), 136.3
(C), 136.8 (C), 138.9 (C), 197.3 (C=O) ppm. FTIR (neat): ν =
˜
1684 cm–1 (C=O). EIMS: m/z (%) = 105 (100). HRMS: calcd. for
C20H15BrO [M+] 352.0286; found 352.0271. C20H15BrO (351.24):
calcd. C 68.39, H 4.30; found C 68.33, H 4.35.
152.0 (d, JC,F = 3.6 Hz, C-7a) ppm. FTIR (neat): ν = 1254 cm–1
˜
(C–O), 1024 (C–O). EIMS: m/z (%) = 426 (100) [M+]. HRMS:
calcd. for C24H20F2O5 [M+] 426.1279; found 426.1284. C24H20F2O5
(426.41): calcd. C 67.60, H 4.73, F 8.91; found C 67.52, H 4.76, F
8.95.
2-(2-Bromophenyl)-1,2-bis(3,4-dimethoxyphenyl)ethanone (5b):
Yield: 87%. Orange powder, m.p. 139–140 °C (MeOH). Rf = 0.44
1
(50% EtOAc/hexane). H NMR (250 MHz, CDCl3): δ = 3.81 (s, 3
H, OCH3), 3.82 (s, 3 H, OCH3), 3.87 (s, 6 H, OCH3), 6.34 (s, 1 H,
CH), 6.80–6.83 (m, 4 H, ArH), 7.07–7.12 (m, 2 H, ArH), 7.20 (d,
J = 7.1 Hz, 1 H, ArH), 7.55–7.58 (m, 2 H, ArH), 7.66 (dd, J = 8.3,
1.6 Hz, 1 H, ArH) ppm. 13C NMR (63 MHz, CDCl3): δ = 55.7
(OCH3), 55.8 (OCH3), 55.9 (OCH3), 58.1 (CH-C=O), 110.0 (CH),
110.8 (CH), 111.1 (CH), 112.3 (CH), 121.7 (CH), 123.4 (CH), 124.6
(CBr), 127.5 (CH), 128.6 (CH), 129.3 (C), 129.5 (C), 130.8 (CH),
132.7 (CH), 139.4 (C), 148.1 (C-OCH3), 148.7 (C-OCH3), 149.0
2,3-Bis(3,4-dimethoxyphenyl)-5,6-dimethoxybenzo[b]furan
(3k):
Yield: 81%. Orange powder, m.p. 144–145 °C (EtOAc). Rf = 0.61
1
(40% EtOAc/hexane). H NMR (250 MHz, CDCl3): δ = 3.67 (s, 3
H, OCH3), 3.77 (s, 3 H, OCH3), 3.81 (s, 3 H, OCH3), 3.82 (s, 3 H,
OCH3), 3.89 (s, 6 H, OCH3), 6.73 (d, J = 8.3 Hz, 1 H, ArH), 6.83
(s, 1 H, 7-H), 6.95–6.97 (m, 2 H, ArH), 7.03 (dd, J = 8.3, 1.6 Hz,
1 H, ArH), 7,05 (s, 1 H, 4-H), 7.12–7.16 (m, 2 H, ArH) ppm. 13C
NMR (63 MHz, CDCl3): δ = 55.3 (OCH3), 55.6 (OCH3), 55.7
(OCH3), 56.0 (OCH3), 56.1 (OCH3), 94.8 (C-7), 100.6 (C-4), 109.0
(CH), 110.6 (CH), 111.4 (CH), 112.5 (CH), 116.0 (C-3), 118.4
(CH), 121.8 (CH), 122.2 (C-3a), 123.5 (C), 125.4 (C), 146.4 (C-5,
C-6), 147.8 (C-5, C-6), 148.0 (C-2, C–OCH3), 148.1 (C-2, C–
OCH3), 148.2 (C-2, C–OCH3), 148.4 (C-OCH3), 148.9 (C-OCH3),
(C-OCH ), 152.9 (C-OCH ), 195.9 (C=O) ppm. FTIR (neat): ν =
˜
3
3
1675 cm–1 (C=O), 1262 (C–O), 1024 (C–O). EIMS: m/z (%) = 472
(1) [M + 1], 470 (1) [M – 1], 165 (100). HRMS: calcd. for
C24H23BrO5 [M+] 470.0729; found 470.0724. C24H23BrO5 (471.34):
calcd. C 61.16, H 4.92; found C 61.14, H 4.93.
General Procedure for the Synthesis of 2,3-Diarylbenzofurans 3 in
the Presence of Polymer-Anchored Palladium Catalysts: Dry, de-
gassed o-xylene (1 mL) was added to an oven-dried reaction flask
charged with FibreCatTM 1026 (0.01 mmol of Pd), Cs2CO3
(0.5 mmol), ketone 2 (0.2 mmol) and dibromoarene 4 (0.32 mmol)
under argon at room temperature. The resultant stirred suspension
was heated to 165 °C for 8 h. After cooling, the mixture was fil-
tered, washed with CH2Cl2 and the filtrate was evaporated in vacuo
to give a residue that was purified by flash chromatography on
silica gel with 10–40% EtOAc/hexane as eluent. Compounds 3a–c,
3e, 3g–i and 3k,l were prepared by this procedure. However, the
preparation of diarylbenzofurans 3d, 3f and 3j required the use of
0.24 mmol of dibromoarene 4.
149.1 (C-7a) ppm. FTIR (neat): ν = 1260 cm–1 (C–O), 1020 (C–
˜
O). EIMS: m/z (%) = 450 (100) [M+], 435 (24). HRMS: calcd. for
C26H26O7 450.1679; found 450.1673. C26H26O7 (450.48): calcd. C
69.32, H 5.82; found C 69.36, H 5.84.
2,3-Bis(3,4-dimethoxyphenyl)-5,6-(methylenedioxy)benzo[b]furan
(3l): Yield: 75%. Orange powder, m.p. 161–162 °C (EtOAc). Rf =
1
0.53 (5% EtOAc/CH2Cl2). H NMR (250 MHz, CDCl3): δ = 3.71
(s, 3 H, OCH3), 3.81 (s, 3 H, OCH3), 3.86 (s, 3 H, OCH3), 3.93 (s,
3 H, OCH3), 5.96 (s, 2 H, CH2), 6.78 (d, J = 8.3 Hz, 1 H, ArH),
6.81 (s, 1 H, 7-H), 6.93–6.97 (m, 2 H, ArH), 7.01 (s, 1 H, 4-H),
7.02 (dd, J = 8.3, 1.6 Hz, 1 H, ArH), 7.13–7.19 (m, 2 H, ArH)
ppm. 13C NMR (63 MHz, CDCl3): δ = 55.6 (OCH3), 55.8 (OCH3),
56.0 (OCH3), 56.2 (OCH3), 93.1 (C-7), 98.2 (C-4), 101.1 (CH2), General Procedure for the PIFA-Mediated Oxidative Coupling of
109.1 (CH), 110.7 (CH), 111.4 (CH), 112.5 (CH), 116.4 (C-3), 118.9 Diarylbenzofurans 3. Synthesis of Benzo[b]phenanthro[9,10-d]furans
(CH), 122.0 (CH), 123.5 (C-3a), 123.8 (C), 125.3 (C), 144.5 (C-5, (1). Method A: A solution of PIFA (0.11 mmol) in dry dichloro-
C-6), 146.0 (C-5, C-6), 148.3 (C-OCH3), 148.4 (C-OCH3), 148.6 methane (1 mL) was added to a stirred solution of diarylbenzofu-
(C-OCH3), 148.7 (C-OCH3), 149.1 (C-2), 149.8 (C-7a) ppm. FTIR
ran 3 (0.1 mmol) in dry dichloromethane (1.5 mL) at –40 °C under
(neat): ν = 1259 cm–1 (C–O), 1023 (C–O). EIMS: m/z (%) = 434 argon. After addition of BF3·Et2O (0.12 mmol), the resulting blue
˜
Eur. J. Org. Chem. 2005, 2481–2490
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2487

F. Churruca, R. SanMartin, I. Tellitu, E. Domínguez
FULL PAPER
solution was stirred for 30 min at –40 °C and then quenched with
Na2CO3 (3 mL of a 10% solution in water). The aqueous layer was
extracted with CH2Cl2 (3×2 mL), the combined organic extracts
were dried with anhydrous sodium sulfate and the solvents were
then evaporated in vacuo to give a residue which was purified by
flash chromatography on silica gel with 30% EtOAc/hexane or 0–
10% EtOAc/CH2Cl2 as eluent. Compounds 1a and 1e–h were pre-
pared by this procedure.
13C NMR (63 MHz, CDCl3): δ = 55.6 (OCH3), 55.9 (OCH3), 56.2
(OCH3), 56.7 (OCH3), 95.6 (CH), 101.0 (CH), 103.3 (CH), 103.6
(CH), 104.0 (CH), 104.1 (CH), 112.9 (C), 115.6 (C), 117.1 (C),
121.4 (C), 121.8 (C), 123.4 (C), 145.9 (C-OCH3), 147.1 (C-OCH3),
148.1 (C-OCH3), 148.7 (C-OCH3), 148.7 (C-OCH3), 149.5 (C-
OCH ), 150.3 (C-OCH ) ppm. FTIR (neat): ν = 1252 cm–1 (C–O),
˜
3
3
1038 (C–O). EIMS: m/z (%) = 448 (100) [M+], 433 (40), 374 (23).
HRMS: calcd. for C26H24O7 [M+] 448.1522; found 448.1513.
C26H24O7 (448.46): calcd. C 69.63, H 5.39; found C 69.59, H 5.36.
2,3,6,7-Tetramethoxybenzo[b]phenanthro[9,10-d]furan (1a): Yield:
80%. Pink powder, m.p. 229–230 °C (Et2O). Rf = 0.43 (5% EtOAc/
2,3,6,7-Tetramethoxy-11,12-(methylenedioxy)benzo[b]phenanthro-
1
CH2Cl2). H NMR (250 MHz, CDCl3): δ = 4.09 (s, 3 H, OCH3), [9,10-d]furan (1h): Yield: 83 %. Beige powder, m.p. 260–261 °C
4.11 (s, 3 H, OCH3), 4.13 (s, 3 H, OCH3), 4.14 (s, 3 H, OCH3), (Et2O). Rf = 0.45 (5 % EtOAc/CH2Cl2). 1H NMR (250 MHz,
7.44–7.50 (m, 2 H, ArH), 7.67–7.71 (m, 4 H, ArH), 7.76 (s, 1 H,
CDCl3): δ = 4.14 (s, 6 H, OCH3), 4.15 (s, 3 H, OCH3), 4.16 (s, 3
H, OCH3), 6.11 (s, 2 H, CH2), 7.23 (s, 1 H, ArH), 7.60 (s, 1 H,
ArH), 8.16 (ddd, J = 9.1, 8.7, 1.6 Hz, 1 H, ArH) ppm. 13C NMR
(63 MHz, CDCl3): δ = 55.6 (OCH3), 55.8 (OCH3), 55.9 (OCH3), ArH), 7.71 (s, 1 H, ArH), 7.73 (s, 1 H, ArH), 7.82 (s, 1 H, ArH),
101.2 (CH), 103.2 (CH), 103.6 (CH), 104.0 (CH), 111.4 (CH), 112.2 7.87 (s, 1 H, ArH) ppm. 13C NMR (63 MHz, CDCl3): δ = 55.9
(C), 115.1 (C), 120.8 (CH), 121.2 (C), 121.9 (C), 122.8 (CH), 124.2 (OCH3), 56.0 (OCH3), 94.1 (CH), 99.9 (CH2), 101.2 (CH), 101.6
(C), 124.4 (CH), 125.5 (C), 147.0 (C-OCH3), 148.5 (C-OCH3), (CH), 103.8 (CH), 104.1 (CH), 104.4 (CH), 113.2 (C), 115.7 (C),
148.7 (C-OCH3), 149.0 (C-OCH3), 149.7 (C-OCH3), 155.2 (C- 118.4 (C), 121.6 (C), 122.0 (C), 123.6 (C), 144.5 (C-OCH2, C-
OCH ) ppm. FTIR (neat): ν = 1258 cm–1 (C–O), 1022 (C–O).
OCH3), 146.1 (C-OCH2, C-OCH3), 147.4 (C-OCH2, C-OCH3),
149.0 (C-OCH2, C-OCH3), 149.1 (C-OCH2, C-OCH3), 149.1 (C-
˜
3
EIMS: m/z (%) = 388 (100) [M+], 373 (13), 314 (13), 194 (15).
HRMS: calcd. for C24H20O5 [M+] 388.1311; found 388.1313. OCH2, C-OCH3), 150.1 (C-OCH2, C-OCH3), 150.8 (C-OCH2, C-
C24H20O5 (388.41): calcd. C 74.21, H 5.19; found C 74.18, H 5.25.
OCH ) ppm. FTIR (neat): ν = 1260 cm–1 (C–O), 1030 (C–O).
˜
3
EIMS: m/z (%) = 432 (100) [M+], 417 (21), 359 (12). HRMS. calcd.
for C25H20O7 [M+] 432.1209; found 432.1206. C25H20O7 (432.42):
calcd. C 69.44, H 4.66; found C 69.49, H 4.61.
2,3,6,7-Tetramethoxy-11,12-dimethylbenzo[b]phenanthro[9,10-d]fu-
ran (1e): Yield: 84%. White powder, m.p. 271–272 °C (Et2O). Rf =
0.40 (10% EtOAc/CH2Cl2). 1H NMR (250 MHz, CDCl3): δ = 2.47
(s, 6 H, CH3), 4.05 (s, 3 H, OCH3), 4.07(s, 3 H, OCH3), 4.10 (s, 3
H, OCH3), 4.11 (s, 3 H, OCH3), 7.44 (s, 1 H, ArH), 7.55 (s, 1 H,
Method B: A solution of PIFA (0.15 mmol) in dry dichloromethane
(1 mL) was added to a stirred solution of diarylbenzofuran 3
ArH), 7.57 (s, 1 H, ArH), 7.59 (s, 1 H, ArH), 7.62 (s, 1 H, ArH), (0.1 mmol) in dry dichloromethane (1.5 mL) at –20 °C under ar-
7.32 (s, 1 H, ArH) ppm. 13C NMR (63 MHz, CDCl3): δ = 20.4 gon. After addition of BF3·Et2O (0.3 mmol), the resulting blue
(CH3), 20.6 (CH3), 55.9 (OCH3), 56.0 (OCH3), 101.4 (CH), 103.7 solution was stirred for 2.5 h at –20 °C and then quenched with
(CH), 104.1 (CH), 104.6 (CH), 112.2 (CH), 112.6 (C), 115.8 (C), Na2CO3 (3 mL of 10% solution in water). The same work-up as
121.2 (CH), 121.5 (C), 122.4 (C), 123.3 (C), 124.1 (C), 131.3 (CH), described in method A provided a residue which was purified by
133.9 (CH), 147.3 (C-OCH3), 148.9 (C-OCH3), 149.0 (C-OCH3),
flash chromatography on silica gel with 15% EtOAc/hexane as elu-
149.1 (C-OCH3), 149.7 (C-OCH3), 154.3 (C-OCH3) ppm. FTIR ent. Compounds 1b–d were prepared by this procedure.
(neat): ν = 1255 cm–1 (C–O), 1022 (C–O). EIMS: m/z (%) = 416
˜
6,7-Dimethoxybenzo[b]phenanthro[9,10-d]furan (1b): Yield: 79%.
(100) [M+], 401 (30), 358 (16), 345 (11), 342 (21), 208 (10). HRMS:
Orange powder, m.p. 176–177 °C (Et2O). Rf = 0.21 (30% EtOAc/
calcd. for C26H24O5 [M+] 416.1624; found 416.1618. C26H24O5
(416.47): calcd. C 74.98, H 5.81; found C 74.95, H 5.83.
hexane). 1H NMR (250 MHz, CDCl3): δ = 4.16 (s, 3 H, OCH3),
4.17 (s, 3 H, OCH3), 7.47 (d, J = 5.9 Hz, 1 H, ArH), 7.48 (d, J =
11,12-Difluoro-2,3,6,7-tetramethoxybenzo[b]phenanthro[9,10-d]fu-
5.9 Hz, 1 H, ArH), 7.62–7.77 (m, 3 H, ArH), 7.84 (s, 1 H, ArH),
ran (1f): Yield: 79%. Pink powder, m.p. Ͼ300 °C (Et2O). Rf = 0.40
8.08 (s, 1 H, ArH), 8.37 (dd, J = 5.9, 2.7 Hz, 1 H, ArH), 8.64 (d,
1
(5% EtOAc/CH2Cl2). H NMR (250 MHz, CDCl3): δ = 4.13 (s, 9 J = 7.9 Hz, 2 H, ArH) ppm. 13C NMR (63 MHz, CDCl3): δ = 56.0
H, OCH3), 4.14 (s, 3 H, OCH3), 7.49 (dd, J = 9.5, 5.9 Hz, 1 H, (OCH3), 56.1 (OCH3), 101.7 (CH), 104.3 (CH), 111.7 (CH), 113.6
ArH), 7.58 (s, 1 H, ArH), 7.66 (s, 1 H, ArH), 7.77 (s, 1 H, ArH), (C), 116.7 (C), 121.5 (CH), 123.2 (CH), 123.3 (CH), 124.2 (CH),
7.80 (s, 1 H, ArH), 7.84 (dd, J = 10.3, 7.9 Hz, 1 H, ArH) ppm. 13
C
124.6 (CH), 125.0 (CH), 125.3 (C), 125.8 (C), 126.5 (CH), 127.5
NMR (63 MHz, CDCl3): δ = 55.9 (OCH3), 56.0 (OCH3), 100.9 (d, (C), 127.8 (C), 148.5 (C-OCH3), 149.7 (C-OCH3), 149.8 (C-OCH3),
JC,F = 21.5 Hz, CH), 101.4 (CH), 103.7 (CH), 103.8 (CH), 104.3
155.5 (C-OCH ) ppm. FTIR (neat): ν = 1260 cm–1 (C–O), 1028 (C–
˜
3
(CH), 107.9 (d, JC,F = 21.5 Hz, CH), 112.0 (C), 115.2 (C), 121.0 O). EIMS: m/z (%) = 328 (100) [M+], 313 (24), 257 (40), 255 (19),
(d, JC,F = 10.8 Hz, C), 121.5 (C), 121.7 (C), 124.6 (C), 147.7 (dd, 242 (23). HRMS: calcd. for C22H16O3 [M+] 328.1099; found
JC,F = 240.0, 14.4 Hz, CF), 147.8, 148.3 (dd, JC,F = 246.0, 16.2 Hz,
328.1087. C22H16O3 (328.36): calcd. C 80.47, H 4.91; found C
CF), 149.2 (C-OCH3), 149.4 (C-OCH3), 149.7 (C-OCH3), 149.7 (C- 80.52, H 4.93.
OCH3), 150.4 (d, JC,F = 5.4 Hz, C-OCH ) ppm. FTIR (neat): ν =
˜
3
6,7-Dimethoxy-11,12-dimethylbenzo[b]phenanthro[9,10-d]furan (1c):
Yield: 71%. White powder, m.p. 225–226 °C (Et2O). Rf = 0.25 (30%
EtOAc/hexane). 1H NMR (250 MHz, CDCl3): δ = 2.47 (s, 3 H,
CH3), 2.50 (s, 3 H, CH3), 4.15 (s, 3 H, OCH3), 4.15 (s, 3 H, OCH3),
7.51 (s, 1 H, ArH), 7.60–7.79 (m, 2 H, ArH), 7.80 (s, 1 H, ArH),
8.00 (s, 1 H, ArH), 8.10 (s, 1 H, ArH), 8.62 (d, J = 7.9 Hz, 1 H,
ArH) ppm. 13C NMR (63 MHz, CDCl3): δ = 20.3 (CH3), 20.5
1253 cm–1 (C–O), 1026 (C–O). EIMS: m/z (%) = 424 (100) [M+],
409 (22), 381 (12), 366 (14), 353 (12), 350 (26). HRMS: calcd. for
C24H18F2O5 [M+] 424.1112; found 424.1109. C24H18F2O5 (424.39):
calcd. C 67.92, H 4.28, F 8.95; found C 67.96, H 4.25, F 8.91.
2,3,6,7,11,12-Hexamethoxybenzo[b]phenanthro[9,10-d]furan (1g):
Yield: 73%. Pink powder, m.p. 264–265 °C (Et2O). Rf = 0.25 (15%
EtOAc/CH2Cl2). 1H NMR (250 MHz, CDCl3): δ = 4.03 (s, 3 H, (CH3), 56.0 (OCH3), 56.1 (OCH3), 101.6 (CH), 104.3 (CH), 112.1
OCH3), 4.08 (s, 3 H, OCH3), 4.15 (s, 9 H, OCH3), 4.17 (s, 3 H, (CH), 112.2 (C), 116.9 (C), 121.8 (CH), 123.1 (CH), 123.5 (C),
OCH3), 7.31 (s, 1 H, ArH), 7.67 (s, 1 H, ArH), 7.73 (s, 1 H, ArH),
7.81 (s, 1 H, ArH), 7.84 (s, 1 H, ArH), 7.88 (s, 1 H, ArH) ppm.
124.2 (CH), 124.4 (CH), 124.8 (C), 126.2 (CH), 127.4 (C), 127.8
(C), 131.7 (CH), 134.1 (CH), 149.3 (C-OCH3), 149.7 (C-OCH3),
2488
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 2481–2490

A New Entry to the Benzophenanthrofuran Framework
150.5 (C-OCH ), 154.5 (C-OCH ) ppm. FTIR (neat): ν =
FULL PAPER
(Idemitsu Kasan Co., Japan) 2000, JP 20000711 (Chem. Abstr.
133:96595).
˜
3
3
1255 cm–1 (C–O), 1022 (C–O). EIMS: m/z (%) = 356 (100) [M+],
341 (26), 298 (23), 285 (23), 283 (11), 270 (15). HRMS: calcd. for
C24H20O3 [M+] 356.1412; found 356.1410. C24H20O3 (356.41):
calcd. C 80.88, H 5.66; found C 80.84, H 5.69.
[3]
The common methods involving the formation of one bond
(single or double) of the heterocycle are i) arylation of 2-arylfu-
ran precursors: a) W.-M. Dai, K. W. Lai, Tetrahedron Lett.
2002, 43, 9377–9380; ii) cyclodehydration of 2-aryloxy-1,2-di-
arylethanones: b) M. Jørgensen, F. C. Krebs, K. Bechgaard, J.
Org. Chem. 2000, 65, 8783–8785; iii) McMurry coupling of o-
acyloxybenzophenones: c) A. Fürstner, A. Hupperts, G. Seidel,
Org. Synth. 1999, 76, 142–150; iv) intramolecular [2+2] cyclo-
addition of carbonyl and ketene moieties: d) W. T. Brady, Y. F.
Giant, A. P. Marchand, A. H. Wu, J. Org. Chem. 1987, 52,
3457–3461; v) photocyclisation of 2-benzyloxybenzophenones:
e) G. R. Lappin, J. S. Zannuci, J. Org. Chem. 1971, 36, 1808–
1811; vi) treatment of 2Ј-alkoxybenzoins with HI,: f) R. E. Ko-
enigkramer, H. Zimmer, J. Org. Chem. 1980, 45, 3994–3998;
vii) photolysis of arylvinyl bromides and vinylbenzoquinones:
g) C. Galli, P. Gentili, A. Guarnieri, S. Kobayashi, Z. Rappo-
port, J. Org. Chem. 1998, 63, 9292–9299; h) H. Iwamoto, A.
Takuwa, K. Hamada, R. Fujiwara, J. Chem. Soc., Perkin
Trans. 1 1999, 575–581; viii) electrocyclisation of diaryl-α-acyl-
carbocationic species: i) M. Schmittel, A. Burghart, H. Werner,
M. Laubender, R. Söllner, J. Org. Chem. 1999, 64, 3077–3085;
j) N. Yoshida, T. Ohwada, Synthesis 2001, 1487–1494,. See
also: k) M. A. Ashraf, M. A. Jones, N. E. Kelly, A. Mullaney,
J. S. Snaith, I. Williams, Tetrahedron Lett. 2003, 44, 3151–3154.
The access to diarylbenzofurans has been reported by sequen-
tial formation of two or more bonds of the furan ring, using the
following procedures: i) condensation between benzoins and
phenols in acidic media: a) B. J. Morrison, O. C. Musgraves,
Tetrahedron 2002, 58, 4225–4260; ii) intermolecular nucleo-
philic attack of phenols to diaryl cations: b) H. D. Choi, P. J.
Seo, S. W. Son, J. Korean Chem. Soc. 2001, 45, 500–504; iii)
1,3-dipolar cycloadditions of o-substituted phenols and al-
kynes: c) S. Spyroudis, J. Org. Chem. 1986, 51, 3453–3456; iv)
palladium-catalysed multi-component coupling of arylalkynes,
haloarenes and o-halophenols, see ref. [2c]; v) tandem α-aryl-
ation/heterocyclisation of deoxybenzoins: d) V. R. Veeram-
aneni, M. Pal, K. R. Yeleswarapu, Tetrahedron 2003, 59, 3283–
3290.
11,12-Difluoro-6,7-dimethoxybenzo[b]phenanthro[9,10-d]furan (1d):
Yield: 85 %. Orange powder, m.p. 230–230.5 °C (Et2O); Rf 0.33
1
(50% EtOAc/hexane). H NMR (250 MHz, CDCl3): δ = 4.11 (s, 3
H, OCH3), 4.12 (s, 3 H, OCH3), 7.46 (dd, J = 9.5, 6.3 Hz, 1 H,
ArH), 7.57–7.60 (m, 3 H, ArH), 7.93–8.00 (m, 2 H, ArH), 8.51 (d,
J = 6.7 Hz, 1 H, ArH), 8.52 (d, J = 7.1 Hz, 1 H, ArH) ppm. 13C
NMR (63 MHz, CDCl3): δ = 55.9 (OCH3), 56.0 (OCH3), 100.7 (d,
JC,F = 21.6 Hz, CH), 101.2 (CH), 103.9 (CH), 108.3 (d, JC,F
=
20.74 Hz, CH), 112.1 (C), 116.0 (C), 120.9 (d, JC,F = 5.4 Hz, C),
123.0 (CH), 123.3 (CH), 124.9 (CH), 125.0 (C), 126.4 (CH), 126.6
(C), 127.2 (C), 147.6 (dd, JC,F = 240.0, 14.4 Hz, CF), 148.6 (dd,
JC,F = 246.0, 16.2 Hz, CF), 149.6 (C-OCH3), 149.7 (C-OCH3),
150.3 (C-OCH3), 152.0 (d, JC,F = 3.6 Hz, C-OCH3) ppm. FTIR
(neat): ν = 1260 cm–1 (C–O), 1023 (C–O). EIMS: m/z (%) = 364
˜
(100) [M+], 349 (21), 293 (47), 291 (22), 278 (24). HRMS: calcd. for
C22H14F2O3 [M+] 364.0911; found 364.0909. C22H14F2O3 (364.34):
calcd. C 72.52, H 3.87, F 10.43; found C 72.58, H 3.84, F 10.46.
[4]
Acknowledgments
This research was supported by the University of the Basque
Country (Project UPV 41.310-13656) and the Spanish Ministry of
Science and Technology (MCYT BQU2001-0313). Both insti-
tutions are gratefully acknowledged. F.C. also thanks the Ministry
of Education, Culture and Sports (MECD) for a predoctoral schol-
arship. Johnson–Matthey Chemicals is acknowledged for a gener-
ous donation of FibreCatTM catalysts.
[1] Resveratrol dimers anigopreissin A and gnetuhainins B and F
are isolated from the roots of Anigozanthos preissi, Musu caven-
dishii and the lianas of Gnetum hainanense, respectively. The
tetrameric compounds vitisifurans A and B and amurensins L
and M are isolated from the roots and corks of Vitis vinifera
and Vitis amurensis, respectively. For their isolation, strong
anti-inflammatory and anti-histaminic properties, and their use
as traditional antihepatotoxic drugs in Oriental medicine, see:
a) Y. Oshima, A. Kamijou, H. Moritani, K.-I. Namao, Y. Ohi-
zumi, J. Org. Chem. 1993, 58, 850–853; b) J. Ito, Y. Takaya, Y.
Oshima, M. Niwa, Tetrahedron 1999, 55, 2529–2544; c) K.-S.
Huang, M. Lin, G.-F. Cheng, Phytochemistry 2001, 58, 357–
362 and references cited therein; d) B. Scheneider, Phytochemis-
try 2003, 64, 459–462; see also: e) T. S. Wu, M. Y. Hsu, A. G.
Damu, P. C. Kuo, C. R. Su, C. Y. Li, H. D. Sun, Heterocycles
2003, 60, 397–404.
[2] The employment of diarylbenzofurans as cyclooxygenase-2
(COX-2) inhibitors has been claimed for the treatment of in-
flammatory disorders. See, for example: a) H.-C. Huang, T. S.
Chamberlain, K. Seibert, C. M. Koboldt, P. C. Isakson, D. B.
Reitz, Bioorg. Med. Chem. Lett. 1995, 5, 2377–2380; b) F. S.
Caruso, (Algos Pharmaceutical Corp., USA) 2000, WO
20000525 (Chem. Abstr. 132:343345); c) H. M. Elokdah, G. R.
Mcfarlane, S. C. Mayer, D. L. Crandall, (Wyeth, John, and
Brother Ltd., USA), 2003, WO 2003000671 (Chem. Abstr.
138:73168); Diarylbenzofurans have been reported to show
noteworthy activity against certain types of cancer, probably
due to their ability to inhibit polymerisation of tubulin, see: d)
B. L. Flynn, E. Hamel, M. K. Jung, J. Med. Chem. 2002, 45,
2670–2673; for some technological applications of diarylbenzo-
furans, such as their use as organic electroluminescent devices,
see: e) M. Funabashi, H. Kawamura, H. Azuma, C. Hosokawa
[5]
[6]
Y. Terao, T. Satoh, M. Miura, M. Nomura, Bull. Chem. Soc.
Jpn. 1999, 72, 2345–2350; for a recent application, see also ref.
[4d].
For the employment of phenanthro[9,10] heterocycles in the
construction of calixarenes applicable to molecular recognition
and/or catalysis, see: E. Botana, K. Nättinen, P. Prado, K. Ris-
sanen, J. de Mendoza, Org. Lett. 2004, 6, 1091–1094.
F. C. Krebs, H. S. Spanggaard, J. Org. Chem. 2002, 67, 7185–
7192 and references cited therein.
L. Bu, T. Sawada, H. Shosenji, K. Yoshida, S. Mataka, Dyes
Pigments 2003, 57, 181–195.
K. Z. Wang, L.-H. Gao, G.-Y. Bai, L.-P. Jin, Inorg. Chem.
Commun. 2002, 5, 841–843.
[7]
[8]
[9]
[10]
[11]
[12]
E. N. Sidorenko, T. Y. Dutova (Optiva, USA), 2003, US
6583284 8 (Chem. Abstr. 139:69282).
W. Zhao, E. M. Carreira (Johnson & Johnson Vision Care,
USA), 2003, WO 2003042195 (Chem. Abstr. 138:403077).
a) T. Tominaga, A. Makiyama, T. Kohama (Toray Industries,
Japan), 2003, JP 2003059670 (Chem. Abstr. 138:212567); b) T.
Ishida, T. Shimamura, M. Nakatsuka (Mitsui Chemicals, Ja-
pan), 2002, JP 2002043061 (Chem. Abstr. 136:158603).
Their application to the manufacture of several electronic de-
vices, such as diodes, transistors and wiring materials has been
reported, see: a) S. Ogawa, K. Ogawa, N. Yoshimoto, Y. Hiroi,
(Japan Science and technology Corp., Japan) 2002,
JP2002265466 (Chem. Abstr. 137:247701); as a consequence of
their planar structure, DNA intercalation of phenanthro[9,10]
heterocycles has attracted much attention, closely related to the
fact that interaction with DNA can be monitored by the
change of fluorescence intensity, see: b) S.-H. Yang, J.-J. Shie,
[13]
Eur. J. Org. Chem. 2005, 2481–2490
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2489

F. Churruca, R. SanMartin, I. Tellitu, E. Domínguez
FULL PAPER
J.-M. Fang, S. K. Nandy, H.-Y. Chang, S.-H. Lu, G. Wang, J.
Org. Chem. 2002, 67, 5208–5215; c) H. Zeytinoglu, E. Ergene,
B. A. Tueylue, Drug. Chem. Toxicol. 2003, 26, 245–257; finally,
antibacterial and antifungal activity have been claimed in: d)
A. A. Pechkin, M. M. El’chaninov, V. M. Stoyanov, Russ. J.
8864–8865; e) F. Y. Kwong, C. W. Lai, K. S. Chan, Tetrahedron
Lett. 2002, 43, 3537–3539.
[24] A. D. Whiting, in Comprehensive Organic Synthesis (Eds.:
B. M. Trost, I. Fleming), Pergamon, Exeter, 1991, vol. 3, pp.
659–703.
Org. Chem. 2002, 38, 726–730; e) M. Huesca, R. Alqawasmeh, [25] a) Metal-Catalysed Cross-Coupling Reactions (Eds.: F. Dieder-
A. H. Young, Y. Lee, (Lorus Therapeutics, Canada) 2004, WO
2004016086 (Chem. Abstr. 140:193035).
[14] F. Churruca, R. SanMartin, M. Carril, I. Tellitu, E. Domíng-
uez, Tetrahedron 2004, 60, 2393–2408.
[15] In fact, triarylethanones of type 5 are currently being employed
in our research group for the synthesis of several heterocyclic
systems, such as diarylindoles. The corresponding results will
be published in due course.
[16] For a recent review, see: G. Lessene, K. S. Feldman, in Modern
Arene Chemistry (Ed.: D. Astruc), Wiley VCH, Weinheim (Ger-
many), 2002, pp. 479–538.
ich, P. J. Stang), Wiley-VCH, Weinheim, Germany, 1998; b) H.
Abe, S. Takeda, Y. Takeuchi, T. Harayama, Heterocycles 2003,
61, 521–528.
[26] L. Hazai, G. Hornyak, ACH Models Chem. 1998, 135, 494–
514.
[27] a) G. Bringmann, S. Tasler, Tetrahedron 2001, 57, 331–343; b)
I. Moreno, I. Tellitu, M. T. Herrero, R. SanMartin, E. Domin-
guez, Curr. Org. Chem. 2002, 6, 1433–1452; c) H. Hamamoto,
G. Anilkumar, H. Tohma, Y. Kita, Chem. Eur. J. 2002, 8, 5377–
5383; d) D. Mirk, A. Willner, R. Froehlich, S. R. Waldvogel,
Adv. Synth. Catal. 2004, 346, 675–681.
[17] a) C. Amatore, E. Blart, J. P. Genêt, A. Jutand, S. Lemaire-
Audoire, M. Savignac, J. Org. Chem. 1995, 60, 6829–6839; b)
D. E. Bergbreiter, B. L. Case, Y.-S. Liu, J. W. Caraway, Macro-
molecules 1998, 31, 6053–6062.
[18] For arylation reactions that imply formation of C–heteroatom
bonds, see: a) M. R. Buchmeiser, K. Wurst, J. Am. Chem. Soc.
1999, 121, 11 101–11 107; b) T. Hashizume, K. Yonehara, K.
Ohe, S. Uemure, J. Org. Chem. 2000, 65, 5197–5201; c) C. A.
Parrish, S. L. Buchwald, J. Org. Chem. 2001, 66, 3820–3827;
d) M. R. Buchmeiser, T. Schareina, R. Kempe, K. Wurst, J.
Organomet. Chem. 2001, 634, 34–46.
[28] a) R. Olivera, R. SanMartin, E. Domínguez, J. Org. Chem.
2000, 65, 7010–7019; b) R. Olivera, R. SanMartin, I. Tellitu,
E. Domínguez, Tetrahedron 2002, 58, 3021–3037.
[29] a) W. Adam, M. Sauter, Chem. Ber. 1993, 126, 2697–2699; b)
M. Schmittel, A. Langels, J. Org. Chem. 1998, 63, 7328–7337.
[30] The oxidants assayed, along with their literature sources, are
as follows: VOF3/BF3·OEt2 and VOF3/TFA: a) D. L. Comins,
X. Chen, L. A. Morgan, J. Org. Chem. 1997, 62, 7435–7438; b)
D. A. Evans, M. R. Wood, B. W. Trotter, T. I. Richardson, J. C.
Barrow, J. L. Katz, Angew. Chem. Int. Ed. 1998, 37, 2700–2704.
FeCl3: c) F. Dötz, J. D. Brand, S. Ito, L. Gherghel, K. Müllen,
J. Am. Chem. Soc. 2000, 122, 7707–7717. RuO2·H2O/TFA/
BF3·OEt2: d) D. Planchenault, R. Dhal, Tetrahedron 1995, 51,
1395–1404. TTFA (1.05 equiv.)/BF3·OEt2: e) M. Ihara, Y. Ta-
kino, K. Fukumoto, T. Kametani, Tetrahedron Lett. 1988, 29,
4135–4138. TiCl4: f) J. Doussot, A. Guy, C. Ferroud, Tetrahe-
dron Lett. 2000, 41, 2545–2547. Ag2O: g) T. R. Hoye, M. Chen,
B. Hoang, L. Mi, O. P. Priest, J. Org. Chem. 1999, 64, 7184–
7201. Cu[OH]Cl·TMEDA and CuCl2·2H2O/BnNH2: h) S. Vys-
kocil, M. Smrcina, M. Lorenc, I. Tislerová, R. D. Brooks, J. J.
Kulagowski, V. Langer, L. J. Farrugia, P. Kocovsky, J. Org.
Chem. 2001, 66, 1359–1365. Pd[OAc]2/Cu[OAc]2: i) H.-J.
Knölker, K. R. Reddy, A. Wagner, Tetrahedron Lett. 1998, 39,
8267–8270.
[31] Several benzophenanthrofurans have been prepared, mostly in
moderate yields, by photochemical cyclisation of the corre-
sponding diarylbenzofurans, see: a) A. Couture, A. Lablache-
Combier, H. Ofenberg, Tetrahedron 1975, 31, 2023–2028; b) C.
Galli, P. Gentili, A. Guarnieri, S. Kobayashi, Z. Rappoport, J.
Org. Chem. 1998, 63, 9292–9299; c) G. R. Lappin, J. S. Zan-
nucci, J. Org. Chem. 1971, 36, 1808–1811; d) T. Suzuki, T. Kita-
mura, T. Sonoda, S. Kobayashi, H. Taniguchi, J. Org. Chem.
1981, 46, 5324–5328; e) P. R. West, S. K. Chaudhary, J. M. Ver-
non, R. H. Mitchell, J. Chem. Soc., Chem. Commun. 1984, 613–
614. For another entry to the benzophenanthrofuran system
also based on photochemistry, see: f) T. Yamazaki, H. Shechter,
Tetrahedron Lett. 1973, 14, 1417–1420.
[19] Bifunctional palladium and/or other metal catalysts are re-
quired. An elegant example can be found in: B. M. Choudary,
N. S. Chowdary, S. Madhi, M. Kantam, J. Org. Chem. 2003,
68, 1736–1746.
[20] The above-described isolation of intermediate triarylethanones
5a,b is in clear accordance with such a mechanistic proposal.
For a more detailed discussion on this subject see ref. [5].
[21] Among heterogeneous palladium catalysts, the use of polymer-
supported and polymer-incarcerated catalysts has gained much
attention in the last few years. In fact, catalysis has become an
obvious and important area of application for functionalised
polymers, and is already established in fundamental synthetic
protocols, such as hydrogenation, allylic alkylation or Suzuki
and Heck coupling reactions. For some recent examples, see:
a) K. Okamoto, R. Akiyama, S. Kobayashi, Org. Lett. 2004, 6,
1987–1990; b) J. W. Byun, Y. S. Lee, Tetrahedron Lett. 2004, 45,
1837–1840; c) A. Drelinkiewicza, A. Waksmundzka, W.
Makowski, J. W. Sobczak, A. Krol, A. Zieba, Catal. Today
2004, 93, 143–146.
[22] For a schematic view of these FibreCatTM catalysts, see ref.
[14]. The FibreCatTM 1000 series is commercialized by Johnson
Matthey Chemicals, Orchard Road, Royston, Herts, SG8 5HE,
UK. Further information about FibreCatTM catalysts, includ-
ing their practical application to Suzuki and Heck coupling
reactions, can be found at http://www.chemicals.matthey.com.
[23] a) F. Churruca, R. SanMartin, I. Tellitu, E. Domínguez, Tetra-
hedron Lett. 2003, 44, 5925–5929. For other examples of such
phenyl–aryl exchange, see: b) V. V. Grushin, Organometallics
2000, 19, 1888–1900; c) M. Jayakannan, J. L. J. van Dongen,
R. A. J. Janssen, Macromolecules 2001, 34, 5386–5393; d) F. Y.
Kwong, C. W. Lai, K. S. Chan, J. Am. Chem. Soc. 2001, 123,
[32] E. Domínguez, E. Ibeas, E. Martínez de Marigorta, J. K. Pala-
cios, R. SanMartin, J. Org. Chem. 1996, 61, 5435–5439.
[33] W. Z. Antkoviak, S. Szwarc, Bull. Acad. Pol. Sci. Ser. Sci.
Chim. 1979, 27, 109–114.
Received: December 02, 2004
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