FeCl3-Diorganyl dichalcogenides promoted cyclization of 2-alkynylanisoles to 3-chalcogen benzo[ b ]furans

Article abstract of DOI:10.1021/jo101126q

A general synthesis of 3-chalcogen benzo[b]furans from the readily available 2-alkynylanisoles, via FeCl₃/diorganyl dichalcogenides intramolecular cyclization, has been developed. Aryl and alkyl groups directly bonded to the chalcogen atom were used as cycling agents. The results revealed that the reaction significantly depends on the electronic effects of substituents in the aromatic ring bonded to the selenium atom of the diselenide species. We observed that the pathway of reaction was not sensitive to the nature of substituents in the aromatic ring of anisole since both the electron-donating and the electron-withdrawing groups delivered the products in similar yields. In addition, the obtained heterocycles were readily transformed to more complex products by using a chalcogen/lithium exchange reaction with n-BuLi followed by trapping of the lithium intermediate with aldehydes, furnishing the desired secondary alcohols in good yields.

Full text of DOI:10.1021/jo101126q

pubs.acs.org/joc
FeCl3-Diorganyl Dichalcogenides Promoted Cyclization of
2-Alkynylanisoles to 3-Chalcogen Benzo[b]furans
ꢀ
Rafaela M. Gay, Flavia Manarin, Caroline C. Schneider, Daniela A. Barancelli,
Michael D. Costa, and Gilson Zeni*
ꢀ ~ ^
Laboratorio de Sıntese, Reatividade, Avaliac-ao Farmacologica e Toxicologica de Organocalcogenios,
´
ꢀ
CCNE, UFSM, Santa Maria-Rio Grande do Sul, Brazil 97105-900
ꢀ
gzeni@pq.cnpq.br
Received June 9, 2010
A general synthesis of 3-chalcogen benzo[b]furans from the readily available 2-alkynylanisoles, via
FeCl3/diorganyl dichalcogenides intramolecular cyclization, has been developed. Aryl and alkyl
groups directly bonded to the chalcogen atom were used as cycling agents. The results revealed that
the reaction significantly depends on the electronic effects of substituents in the aromatic ring bonded
to the selenium atom of the diselenide species. We observed that the pathway of reaction was not
sensitive to the nature of substituents in the aromatic ring of anisole since both the electron-donating
and the electron-withdrawing groups delivered the products in similar yields. In addition, the
obtained heterocycles were readily transformed to more complex products by using a chalcogen/
lithium exchange reaction with n-BuLi followed by trapping of the lithium intermediate with
aldehydes, furnishing the desired secondary alcohols in good yields.
Introduction
years. In this context, palladium is probably the most versatile
and widely used metal for the synthesis of these O-heterocycles.3
For example, alkenes bearing a phenol at an appropriate
distance from the carbon-carbon bond can readily undergo
palladium(II)-catalyzed intramolecular cyclization to generate a
wide variety of benzo[b]furans under mild reaction conditions.4
The first report of the synthesis of benzofurans by such a
cyclization appeared in 1973 when the sodium salts of phenols
were cyclized to 2-substituted benzofurans with stoichiometric
amounts of PdCl2-(PhCN)2.5 Similarly, other palladium-based
catalytic systems have also been successfully adopted in hetero-
cyclic chemistry for the construction of furan derivatives.6
Meanwhile, an efficient synthesis of 3-chalcogen benzo[b]furans
Substituted benzo[b]furans are structural units present in
many natural products and pharmaceutical synthetic inter-
mediates.1 They were found to exhibit antiviral, antiparasitic,
antifungal, and antidiabetic activities.2 Therefore, significant
efforts to prepare benzo[b]furans have been made in the past few
(1) (a) Crenshaw, R. R.; Jeffries, A. T.; Luke, G. M.; Cheney, L. C.; Bialy,
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DOI: 10.1021/jo101126q
r
Published on Web 07/26/2010
J. Org. Chem. 2010, 75, 5701–5706 5701
2010 American Chemical Society

Gay et al.
JOCArticle
via palladium-promoted annulation reactions of 2-alkynylphe-
nol derivatives with dichalcogenides and iodide has been
developed.7 More recently, significant advances have been made
in the synthesis of benzo[b]furans by using the halocyclization
reactions of the appropriate functional substituted aryl acety-
lenes.8 Among them, the use of o-alkynylanisoles, as substrate in
the electrophilic cyclization,9 has some advantages in compar-
ison to palladium cyclization, including the presence of halogen
atoms which are suitable to suffer further transformations. For
instance, the resulting halogenated heterocycles are particularly
useful intermediates in many palladium-catalyzed processes,
such as Sonogashira,10 Suzuki,11 Heck,12 and carbonylation13
cross-couplings, providing the corresponding coupling products
in excellent yields. In addition, during the past years there has
been an impressive increasing attention in the development of
environmentally benign protocols and the great challenge for
chemists is to apply cost-effective, green, mild, and alternative
methodologies.14 In this context, iron has appeared as a versatile
alternative, due to its low price, nontoxicity, and environmen-
tally benign properties. Considering these aspects, many find-
ings concerning iron-mediated organic transformations have
been reported. For example, iron trichloride was applied in the
cross-coupling of Grignard reagents with several organic elec-
trophiles,15 iron-catalyzed C-N,16 C-O,17 and C-S18 bond
formation. Among these transformations iron salts have also
emerged as alternative and promising catalysts or promoters
for the cyclization process.19 To date, cyclization of aryl ke-
tones,20 carbocyclization via FeCl3-oxidative coupling reac-
tions,21 intramolecular Friedel-Crafts cyclization,22 synthesis
SCHEME 1
of benzoxazole derivatives,23 and diastereoselective synthesis of
substituted piperidines24 are examples of a large number of
methodologies which have successfully used FeCl3 in the synth-
esis of interesting heterocycle or carbocycle compounds. Com-
bining the knowledge that our group has accumulated in the
synthesis of heterocycles containing a chalcogen25 with the fact
that iron-promoted cyclization of alkynylanisole derivatives
remains unexplored, in this paper, we reported an inexpensive
and environmentally friendly synthetic method for the synthesis
of 3-chalcogen benzo[b]furans starting from 2-alkynylanisoles.
Our idea is outlined in Scheme 1, which consists of treatment of
2-alkynylanisoles 1 with iron trichloride and diorganyl disele-
nides with the intention of the activation of both Y-Y and triple
bonds, with concomitant cyclization to yield 3-chalcogen benzo-
[b]furans 2. The synthesis of the starting material 1 was facile
and scalable, starting from standard Sonogashira cross-
coupling between 2-haloanisoles and terminal alkynes, in one
step (Scheme 1).26
Results and Discussion
We have investigated the procedure with respect to four key
variables: (1) solvent, (2) diorganyl diselenide loading, (3) iron
trichloride loading, and (4) temperature. We employed the
reaction of alkynylanisole 1a and diphenyl diselenide as a model
to study the key variables. Thus, a mixture of diphenyl disele-
nide (0.5 mmol) and FeCl3 (0.5 mmol), using methanol as
solvent, was reacted with 1a (0.5 mmol) under heating of 65 °C
for 12 h. As shown in Table 1, using this reaction condition the
desired product 2a was obtained in 60% yield. To identify the
solvent potentially suitable for the cyclization we initially chose
CH3CN, toluene, THF, DMSO, and CH2Cl2. The use of CH3-
CN, toluene, and THF instead of MeOH delivered moderate to
low yields (Table 1, entries 6-8), whereas DMSO did not give
the cyclized product (Table 1, entry 9). The use of CH2Cl2 gave
the best yield of the desired product (Table 1, entry 10). Con-
cerning the amount of FeCl3 a good yield of desired product
was obtained in the presence of 1.0 equiv of FeCl3. Intending to
carry out the cyclization in a catalytic system we reduced the
amount of FeCl3 to 0.2 and 0.5 equiv. These reaction conditions
gave the cyclized product in inacceptable 20% and 42% yields,
respectively, even with oxygen atmosphere or different ligands
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JOCArticle
TABLE 1. Influence of Reaction Conditions in the FeCl3/PhSeSePh
Cyclization of 2-Alkynylanisoles 1a
of their usefulness in organic synthesis, including palladium
cross-coupling reactions27 and synthesis of natural products.28
In an attempt to broaden the scope of our methodology, the
possibility of performing the reaction with other 2-alkynylani-
sole derivatives, which have Me 1b and F 1c groups in the
aromatic ring, was also investigated. Both the electron-donating
(Me) and the electron-withdrawing (F) groups delivered pro-
ducts with good yields (Table 2, entries 10-16). We have also
investigated the possibility of carrying out double cyclizations,
which might be quite useful for the quick assembly of systems
with extended conjugation. Alkynyl-anisole 1f underwent Fe/
PhSeSePh condition to afford double cyclization product in
78% yield (Table 2, entry 19).
The 3-chalcogen benzo[b]furans obtained appear highly
promising as intermediates for the preparation of more highly
substituted benzo[b]furans. To further prove the utility of
our methodology, we have carried out the selenium-lithium
exchange reaction of products 2 with n-butyllithium. The
selenium-lithium exchange is a very attractive transformation
of selenides, since it affords the corresponding organolithium
species,29 which could react with a wide range of electrophiles
generating directly polyfunctionalized molecules.30 The genera-
tion of the organolithium reagent from selenide 2a was at-
tempted under a variety of reaction conditions by changing the
medium, temperature, and amount of n-BuLi. On the basis of
these experiments we have concluded that the best condition for
the Se/Li exchange reaction was as follows: n-Butyllithium
(1.0 equiv) was added to a solution of 3-phenylselanylbenzo-
[b]furans 2a (1.0 equiv) and THF (2 mL), at -78 °C. The re-
sulting solution was stirred for 10 min at -78 °C and quenched
by H2O, producing the corresponding hydrogenated product in
almost quantitative yield. After standardizing the conditions of
the Se/Li exchange reaction, the reaction of the lithium inter-
mediate with aldehydes was screened in order to determine the
scope and limitations of our method.
entry FeCl3 (equiv) PhSe)2 (equiv) solvent temp (°C) yield (%)a
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1.0
0.2
0.5
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.5
2.0
0.1
1.0
1.0
1.0
1.0
0.5
MeOH
MeOH
MeOH
MeOH
MeOH
CH3CN
toluene
THF
DMSO
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
65
65
65
65
65
82
110
65
100
45
rt
60
20
42
48
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
40
50
17
71
55
45
45
45
45
65
45
20b
68c
aYields are given by GC analysis. bReaction performed under air
atmosphere. cThis reaction was carried out with 1 equiv of methanol.
as the oxidizing agent (Table 1, entries 2 and 3). Iron trichloride
in the amount of 1.5 and 2.0 equiv was also found to be
insufficient to improve the yields (Table 1, entries 12 and 13).
Regarding the influence of the diselenide loading, optimal re-
sults were achieved by using 1.0 equiv of diselenide (Table 1,
entry 10), while 0.5 equiv was less effective (Table 1, entry 4).
Remarkably, in the absence of diselenide the reaction failed to
give the unsubstituted benzofuran (Table 1, entry 5). In fact,
complete recovery of the starting material, even under forcing
conditions, led to the conclusion that the amount of diselenide
was critical for the success of this cyclization reaction.
The application of the above standardized conditions to other
anisoles with different diorganyl diselenides was studied, and the
results are summarized in Table 2. Both hindered and unhin-
dered diaryl diselenides gave the desired benzo[b]furans in good
yields (Table 2, entries 1 and 7). The reaction seems to be
sensitive to electronic effects of the substituents in the aromatic
ring of dichalcogenides. For example, diaryl diselenides with
-CF3 and Cl groups gave worst yields than a methyl group
(Table 2, entries 2, 4, and 5). Gratifyingly, dialkyl diselenide or
dibenzyl diselenide were also suitable for the reaction, which
gave the desired products in 80% and 64% yields, respectively
(Table 2, entries 3 and 6). It is worth mentioning that, through
our methodology it was possible to prepare highly functiona-
lized benzo[b]furans, using not only diorganyl diselenides but
also diorganyl ditelluride and disulfide (Table 2, entries 8 and 9).
The introduction of the organotellurium moiety in the structure
of benzo[b]furans is significant since many classes of organo-
tellurium compounds have been prepared and studied to date.
Moreover, the structures having a C(sp2)-Te bond are certainly
the most useful and promising of these compounds in view
As demonstrated in Table 3, many functional groups were
compatible with the reaction conditions. In general, all the
reactions proceeded smoothly with good results. The experi-
ments showed that the reaction of the lithium intermediate
with aldehydes having an aromatic ring was not sensitive to
the electronic effects of the substituents. For example, the
aromatic ring having either neutral, electron-donating, or
electron-withdrawing substituents gave the cyclized pro-
ducts in very similar yields, although the presence of halogen
in the aromatic ring led to a little reduced yield of 3 (Table 3,
entries 7 and 8). In addition to aromatic aldehydes, the
reaction with alkyl aldehydes also led to the formation of
the desired products in a comparable yield to that obtained
for aromatic aldehydes (Table 3, entry 5).
Considering what little we have known about the reaction
of diorganyl diselenides with FeCl3,31 our working mecha-
nism for the FeCl3/RYYR conversion of alkynylanisole to
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TABLE 2. Synthesis of 3-Chalcogen Benzo[b]furan Derivatives 3 via FeCl3/R2YYR2 Cyclization of 2-Alkynylanisoles
3-chalcogen benzo[b]furans is based on the following experi-
mental data obtained in this study: (1) In all reactions, we
isolated the RYMe as byproduct. This indicates that a chal-
cogenolate anion (RY-) is acting as a nucleophile agent to
remove the methyl group from methoxyl. (2) The reaction
did not work with FeCl3 in the absence of diorganyl dichal-
cogen. (3) When we reacted FeCl3 with PhSeSePh, in the
same reaction condition used to obtain the cyclized products,
in the absence of the substrate anisole, no PhSeCl was
formed (Scheme 2). This indicates that the pathway does
not follow the typical electrophilic cyclization, where the
electrophilic source is PhSeCl (Scheme 3).9 (4) The decrease
in the yields to 48%, when we used 0.5 equiv of PhSeSePh,
supports the hypothesis that one-half of diselenide is incor-
porated in the structure of benzo[b]furan, whereas the other
one acts as nucleophile. (5) FeCl3 did not work as catalyst
(Table 1, entry 2). Then, with these data in mind the working
mechanism could involve the following: (a) Fe(III) could
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TABLE 3. Reactions of Intermediate 3-Lithio Benzo[b]furan with
Aldehydes
SCHEME 3
SCHEME 4
philic attack of selenolate anion on the methyl group bonded to
the oxygen atom affords the product (Scheme 4).
Conclusion
We have shown the synthesis of 3-chalcogen benzo-
[b]furans using inexpensive and environmentally friendly
FeCl3-promoted cyclization and readily available diorganyl
dichalcogenides and 2-alkynylanisoles as the starting mate-
rials, and no additional ligand or additive was required. Aryl
and alkyl groups directly bonded to the chalcogen atom were
used as cycling agents. The results revealed that the reaction
significantly depends on the electronic effects of substituents
in the aromatic ring bonded to the selenium atom of the
diselenide species. We observed that the pathway of reaction
was not sensitive to the nature of substituents in the aromatic
ring of anisole since both the electron-donating and the
electron-withdrawing groups delivered the products with
good yields. We have also investigated the possibility of
carrying out double cyclizations, which might be quite useful
for the quick assembly of systems with extended conjugation.
The benzo[b]furans obtained in the current protocol appear
highly promising and attractive intermediates for the synth-
esis of more highly substituted benzo[b]furans. For instance,
3-chalcogen benzo[b]furans were treated under selenium/
lithium exchange conditions with n-BuLi, and trapping the
lithium intermediates with aldehydes provided the corre-
sponding secondary alcohols in good yields. We believe that
this approach to benzo[b]furans should prove quite useful in
synthesis, particularly when one considers that there are
SCHEME 2
be first reduced to Fe(II);31a (b) Fe(III) tetracoordinated
square-planar selenolate is formed from diphenyl diselenide
and Fe(II), via an oxidation addition with displacement of
chlorine; (c) alkyne coordination to the metal center gives
the cationic organo-Fe(III) complex; (d) antiattack of the
oxygen atom on the activated triple bond produces the
intermediate a; (e) a coupling reaction32 produces the salt b
and the Fe(II) anionic complex [FeCl(SePh)]-; and (f) nucleo-
(32) Hatakeyama, T.; Yoshimoto, Y.; Gabriel, T.; Nakamura, M. Org.
Lett. 2008, 10, 5341.
J. Org. Chem. Vol. 75, No. 16, 2010 5705

Gay et al.
JOCArticle
many ways to transform the resulting chalcogen functional-
ities into other substituents.33
(CDCl3, 100 MHz) δ (ppm) 157.5, 152.6, 133.0, 132.1, 131.6,
130.3, 129.2, 129.1, 129.0, 128.3, 127.7, 126.5, 126.2, 120.9,
110.6, 99.5, 21.3; MS (EI, 70 eV) m/z (rel intensity) 364 (32),
284 (100), 255 (8), 178 (40), 152 (9). Anal. Calcd for C21H16OSe:
C 69.42, H 4.44. Found: C 69.35, H 4.68.
Experimental Section
General Procedure for Iron-Promoted Cyclization of 2-Alky-
nylanisole and Diorganoyl Dichalcogenides. To a two-necked
round-bottomed flask equipped with a reflux condenser, under
argon, containing a solution of FeCl3 (0.081 g, 0.5 mmol) in
CH2Cl2 (3 mL) was added 2-alkynylanisole 1a-e (0.5 mmol) in
CH2Cl2 (2 mL). The reaction mixture was stirred for the desired
time at 45 °C. After this, the mixture was diluted with dichlor-
ometane (20 mL) and washed with a saturated solution of
NH4Cl (20 mL). The organic phase was separated, dried over
MgSO4, and concentrated under vacuum. The residue was
purified by flash chromatography and eluted with hexane.
2-Phenyl-3-(phenylselanyl)benzofuran (2a): yield0.123g(71%);
white solid, mp 41 °C dec; 1H NMR (CDCl3, 400 MHz) δ(ppm) 8.20
(d, J = 7.8 Hz, 2H), 7.53-7.49 (m, 2H), 7.43-7.40 (m, 2H), 7.37-
7.26 (m, 4H), 7.22-7.18 (m, 2H), 7.12-7.09 (m, 2H); 13C NMR
(CDCl3, 100 MHz) δ (ppm) 157.2, 154.0, 131.8, 131.4, 131.3, 129.2,
129.1, 128.4, 127.7, 127.6, 126.2, 125.2, 123.4, 121.1, 111.1, 99.6;
77Se NMR (CDCl3, 400 MHz) δ (ppm) 221.8; MS (EI, 70 eV) m/z
(rel intensity) 349 (36), 270 (100), 255 (7), 241 (16), 165 (42). Anal.
Calcd for C20H14OSe: C 68.77, H 4.04. Found: C 68.85, H 4.26.
2-Phenyl-3-(p-tolylselanyl)benzofuran (2e): yield 0.162 g (90%);
yellow solid, mp 77 °C dec; 1H NMR (CDCl3, 400 MHz) δ (ppm)
8.21 (dt, J = 7.3 Hz and J = 1.5 Hz, 2H), 7.52 (t, J = 8.8 Hz, 2H),
7.46-7.36 (m, 3H), 7.31 (td, J = 7.1 Hz and J = 1.5 Hz, 1H),
7.23-7.19 (m, 3H), 6.97 (d, J= 8.3 Hz, 2H), 2.23 (s, 3H); 13CNMR
(CDCl3, 100 MHz) δ (ppm) 154.0, 136.2, 131.9, 130.2, 130.0, 129.5,
129.2, 128.4, 127.7, 127.4, 125.1, 123.3, 121.2, 111.1, 100.1, 20.9; MS
(EI, 70 eV) m/z (rel intensity) 363 (32), 284 (100), 269 (12), 255 (9),
241 (12), 165 (31). Anal. Calcd for C21H16OSe: C 69.42, H 4.44.
Found: C 69.60, H 4.58.
5-Methyl-2-phenyl-3-(3-(trifluoromethyl)phenylselanyl)ben-
zofuran (2l): yield 0.107 g (50%); yellow solid, mp 63 °C dec; 1H
NMR (CDCl3, 400 MHz) δ (ppm) 8.15-8.13 (m, 2H), 7.60 (s,
1H), 7.44-7.30 (m, 7H), 7.20 (t, J = 7.8 Hz, 1H), 7.14 (dd,
J = 7.3 Hz and J = 1.2 Hz, 1H), 2.39 (s, 3H); 13C NMR (CDCl3,
100 MHz) δ (ppm) 157.8, 152.6, 133.3, 132.9, 129.6 (q, J = 32
Hz), 128.5, 128.4, 126.5 (q, J = 272 Hz), 127.6, 126.7, 125.4 (q,
J = 3.6 Hz), 124.8, 122.9 (q, J = 3.6 Hz), 120.7, 120.5, 110.8,
110.6, 101.0, 98.2, 21.3; MS (EI, 70 eV) m/z (rel intensity) 432
(29), 352 (100), 178 (43), 152 (9); HRMS calcd for C22H15F3OSe
432.0240, found 432.0234.
General Procedure for the Reaction of Intermediate 2-Phenyl-
3-lithiobenzo[b]furan with Aldehydes. To a two-necked round-
bottomed flask, under argon, containing a solution of 2a (0.5 mmol)
in THF (4 mL) at -78 °C was added n-BuLi (0.5 mmol, of a 2.5 M
solution in hexane) in one portion. The reaction mixture was stirred
for 30 min, and then a solution of the appropriated aldehyde
(0.5 mmol) in THF (2 mL) at -78 °C was added. The reaction mix-
ture was allowed to stir at room temperature for 1 h. After this, the
mixture was diluted with ethyl acetate (20 mL) and washed with a
saturated solution of NH4Cl (20 mL). The organic phase was
separated, dried over MgSO4, and concentrated under vacuum.
The residue was purified by flash chromatography and eluted with
ethyl acetate/hexane.
(2-Phenylbenzofuran-3-yl)(p-tolyl)methanol (3a): yield 0.109 g
(70%); colorless oil; 1H NMR (CDCl3, 400 MHz) δ (ppm) 7.72
(d, J = 7.6 Hz, 2H), 7.50-7.36 (m, 6H), 7.27-7.21 (m, 2H),
7.17-7.09 (m, 3H), 6.28 (s, 1H), 2.40 (s, 1H), 2.32 (s, 3H); 13
C
NMR (CDCl3, 100 MHz) δ (ppm) 154.4, 152.6, 139.0, 137.2,
130.3, 129.2, 128.9, 128.9, 128.7, 127.8, 126.9, 126.3, 124.4,
122.6, 121.9, 117.6, 111.1, 68.6, 21.0; MS (EI, 70 eV) m/z (rel
intensity) 314 (100), 298 (49), 221 (63), 205 (27), 165 (88), 119
(98); HRMS calcd for C22H18O2 314.1307, found 314.1311.
(2-Phenylbenzofuran-3-yl)(o-tolyl)methanol (3b): yield 0.125 g
(80%); white solid, mp 129 °C dec; 1H NMR (CDCl3, 400 MHz) δ
(ppm) 7.73-7.69 (m, 3H), 7.48-7.39 (m, 4H), 7.30 (d, J = 7.8Hz,
1H), 7.24-7.19 (m, 3H), 7.12-7.10 (m, 1H), 7.06 (td, J = 7.1 Hz
3-(Naphthalen-1-ylselanyl)-2-phenylbenzofuran (2g): yield
1
0.168 g (84%); yellow solid, mp 86 °C dec; H NMR (CDCl3,
400 MHz) δ (ppm) 8.23 (d, J = 7.3 Hz, 1H), 8.10-8.00 (m, 1H),
7.73-7.66 (m, 4H), 7.58-7.26 (m, 9H), 7.20-7.15 (m, 1H); 13
C
NMR (CDCl3, 100 MHz) δ (ppm) 157.3, 154.1, 133.9, 131.8,
130.3, 129.3, 128.7, 128.6, 128.4, 127.7, 127.6, 127.3, 127.0, 126.9,
126.5, 126.4, 126.1, 125.6, 125.2, 123.4, 121.1, 111.1; MS (EI, 70 eV)
m/z (rel intensity) 399 (62), 320 (100), 291 (32), 165 (52), 115 (30);
HRMS calcd for C24H16OSe 400.0366, found 400.0360.
and J = 1.0 Hz, 1H), 6.26 (s, 1H), 2.41 (s, 1H), 2.08 (s, 3H); 13
C
NMR (CDCl3, 100 MHz) δ (ppm) 154.2, 153.0, 139.7, 135.8,
130.7, 130.2, 128.9, 128.7, 128.0, 127.8, 127.7, 126.2, 125.9, 124.3,
122.7, 121.6, 116.5, 111.1, 67.2, 19.0; MS (EI, 70 eV) m/z (rel
intensity) 314 (91), 298 (22), 223 (33), 165 (79), 119 (100). Anal.
Calcd for C22H18O2: C 84.05, H 5.77. Found: C 84.29, H 5.83.
Naphthalen-1-yl(2-phenylbenzofuran-3-yl)methanol (3d): yield
2-Phenyl-3-(phenylthio)benzofuran7 (2h): yield 0.096 g (60%);
white solid, mp 76 °C dec; 1H NMR (CDCl3, 400 MHz) δ (ppm)
8.24-8.21 (m, 2H), 7.55 (d, J = 8.0 Hz, 1H), 7.48-7.28 (m, 6H),
7.23-7.18 (m, 5H); 13C NMR (CDCl3, 100 MHz) δ (ppm) 157.5,
153.9, 136.1, 131.6, 129.7, 129.3, 129.0, 128.5, 127.3, 126.5, 125.5,
125.2, 123.4, 111.3, 104.6; MS (EI, 70 eV) m/z (rel intensity) 302
(100), 241 (13), 225 (27), 197 (27), 165 (33), 105 (20). Anal. Calcd
for C20H14OS: C 79.44, H 4.67. Found: C 79.66, H 4.73.
1
0.134 g (77%); colorless oil; H NMR (CDCl3, 400 MHz) δ
(ppm) 7.98 (s, 1H), 7.76-7.71 (m, 5H), 7.47 (d, J = 8.4 Hz, 2H),
7.42-7.36 (m, 5H), 7.31 (d, J = 7.9 Hz, 1H), 7.19 (t, J = 8.2 Hz,
1H), 6.99 (t, J = 7.6 Hz, 1H), 6.41 (s, 1H), 2.62 (s, 1H); 13C NMR
(CDCl3, 100 MHz) δ (ppm) 154.3, 152.9, 139.3, 133.1, 132.7, 130.2,
129.0, 128.7, 128.2, 128.1, 127.7, 127.6, 127.5, 126.0, 125.8, 124.6,
124.5, 122.7, 121.7, 117.2, 111.1, 68.7; MS (EI, 70 eV) m/z (rel
intensity) 350 (99), 334 (89), 221 (100), 165 (85), 127 (72); HRMS
calcd for C25H18O2 350.1307, found 350.1311.
2-Phenyl-3-(phenyltellanyl)benzofuran (2i): yield 0.071
g
(36%); yellow solid, mp 80 °C dec; 1H NMR (CDCl3, 400 MHz)
δ (ppm) 8.13-8.11 (m, 2H), 7.54 (d, J = 8.0 Hz, 2H), 7.46-7.43
(m, 4H), 7.41-7.31 (m, 2H), 7.26-7.22 (m, 1H), 7.17-7.07
(m, 3H); 13C NMR (CDCl3, 100 MHz) δ (ppm) 159.2, 154.7,
134.9, 134.3, 130.6, 129.5, 129.3, 128.5, 128.3, 127.2, 125.2,
123.3, 123.1, 114.8, 111.0, 82.6; MS (EI, 70 eV) m/z (rel intensity)
397 (15), 270 (100), 241 (18), 165 (82), 139 (14), 77 (16). Anal.
Calcd for C20H14OTe: C 60.37; H 3.55. Found: C 60.42, H 3.63.
5-Methyl-2-phenyl-3-(phenylselanyl)benzofuran7 (2j): yield
Acknowledgment. We are grateful to FAPERGS (PRO-
NEX-10/0005-1), CAPES (SAUX), and CNPq (CNPq/
INCT-catalise) for the financial support. CNPq is also
acknowledged for the fellowship (G.Z. and F.M.).
1
0.108 g (60%); yellow solid, mp 47 °C dec; H NMR (CDCl3,
400 MHz) δ (ppm) 8.17 (d, J = 7.8 Hz, 2H), 7.40-7.36 (m, 3H),
7.33-7.26 (m, 4H), 7.12-7.08 (m, 4H), 2.36 (s, 3H); 13C NMR
Supporting Information Available: Experimental procedures,
additional experimental details for the preparation of all compounds,
and 1Hand13C NMR spectra for all reaction products. This material
is available free of charge via the Internet at http://pubs.acs.org.
~
(33) (a) Perin, G.; Lenardao, E. J.; Jacob, R. G.; Panatieri, R. B. Chem.
Rev. 2009, 109, 1277. (b) Silveira, C. C.; Braga, A. L.; Vieira, A. S.; Zeni, G.
J. Org. Chem. 2003, 68, 662.
5706 J. Org. Chem. Vol. 75, No. 16, 2010