Selective base-promoted synthesis of substituted selenophenes by carbocyclization of (Z)-benzylselenoenynes

Article abstract of DOI:10.1039/c0ob00844c

We herein described the synthesis of several 3-benzyl-2,5-diarylselenophene derivatives in moderate to good yields using (Z)-benzylselenoenynes as starting material in carbocyclization reactions. The reactions were carried out under mild conditions using

Full text of DOI:10.1039/c0ob00844c

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PAPER
Selective base-promoted synthesis of substituted selenophenes by
carbocyclization of (Z)-benzylselenoenynes†
Daniela A. Barancelli,a Carmine I. Acker,a Paulo H. Menezesb and Gilson Zeni*a
Received 6th October 2010, Accepted 15th November 2010
DOI: 10.1039/c0ob00844c
We herein described the synthesis of several 3-benzyl-2,5-diarylselenophene derivatives in moderate to
good yields using (Z)-benzylselenoenynes as starting material in carbocyclization reactions. The
reactions were carried out under mild conditions using only t-BuOK as base, in the complete absence of
transition metals or additives. The cyclized 3-benzyl-2,5-diarylselenophenes obtained in the current
protocol appear highly promising and attractive intermediates for the synthesis of polysubstituted
selenophenes. For instance, 3-benzyl-2,5-diphenylselenophene was treated with Br2 provided the
corresponding 3-benzyl-4-bromo-2,5-diphenylselenophene in high yield. 4-Bromoselenophene
derivative was applied as substrate in the palladium catalyzed cross-coupling reactions with boronic
acids to give the Suzuki type products in excellent yields.
The role of selenophene compounds in organic synthesis is well
Introduction
established and in recent years much effort has been devoted to
the study of the electrical properties, thermal and environmental
stability, reactivity and their application in organic synthesis.22
Selenoheterocycles, specially selenophenes are important and
central structural units present in various biologically active com-
pounds. Some selenophene derivatives have shown antioxidant,23
antinociceptive24 and anti-inflammatory properties,25 as well as
efficacy as a maturation inducing agents.26
In addition, during the past years there has been an impres-
sive 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.27
Selenium stabilized carbanions from selenoacetals, a-alkylseleno
or a-arylselenocarbonyl compounds, benzyl and vinyl selenides,
generated by bases, can be an useful and environmental strategy
for the construction, in few synthetic steps, of complex molecules,
including high substituted Se-heterocycles.28 As a part of our
ongoing research in this area,29 combined with the fact that base-
promoted cyclization30 of (Z)-benzylselenoenynes as substrate
remains unexplored, in this paper, we reported an inexpensive
and environmentally friendly synthetic method for the synthesis
of selenophene derivatives. Our work hypothesis is outlined in
Scheme 1, whichconsistedof the base-promotedcyclization of(Z)-
benzylselenoenyne precursors 3, through a C–C bond formation
process, leading to a broad range of selenophenes 4 in complete
absence of transition metals or additives (Scheme 1).
Carbocyclization of unsaturated species, particularly alkenes and
alkynes, is an effective synthetic method for the synthesis of a
variety of carbo and heterocyclic compounds.1 Enynes have been
also employed as key substrates in carbocyclization reactions2
for the construction of ring systems and these reactions usually
proceed with high efficiency and selectivity. In this context,
transition metals such as Pd,3 Pt,4 Au,5 Co,6 Ni7 and Rh,8 are
generally used to promote these carbocyclization reactions. Tradi-
tionally, alkenyl and alkynyl tethers attached to a nucleophilic
heteroatom have been cyclized in the presence of palladium
salts.9 Some of these methods, however, do require a significant
number of steps for preparation of the starting materials, employ
toxic metal reagents for the cyclization event and sometimes
display intolerance to some functionalities or proceed with a
lack of regioselectivity. During the last years the electrophilic
cyclization has been developed for converting alkenes, alkynes,
allenes, conjugated dienes and other carbon-carbon multiple
bonds, bearing an internal nucleophile, such as imines,10 ketones,11
esters,12 amides,13 benzyl sulfides,14 alkyl selenides,15 anisoles,16
thioanisole,17 alkynyl selenides18 into heterocycles. This is a very
versatile method which can be applied to a wide variety of sub-
strates employing electrophiles, like I2, ICl, chalcogen derivatives,19
gold20 and silver.21 Another emerging area in the heterocycles
chemistry is the preparation of selenophene and their derivatives.
aLaborato´rio de S´ıntese, Reatividade, Avaliac¸a˜o Farmacolo´gica e Toxi-
colo´gica de Organocalcogeˆnios, CCNE, UFSM, Santa Maria, Rio Grande
do Sul, Brazil 97105-900
Results and discussion
bUniversidade Federal de Pernambuco, Departamento Qu´ımica Fundamental,
Recife-Pernambuco, Brazil 50670-901
Unfortunately, the scope of benzylselenoenynes 3, needed for
cyclization, appear limited to relatively different substituents in the
structure. This limitation prompted us to investigate a complete
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c0ob00844c
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Table 1 Synthesis of (Z)-benzylselenoenynes 3a
#
1
Dibenzyl diselenide Diyne
Product yield (%)b
Scheme 1
study in the preparation of these compounds. In the course of stud-
ies designed to expand the scope of (Z)-benzylselenoenynes 3 to the
more substituted structures, a hydroselenation of alkynes process31
was envisioned as a highly efficient and selective method for the
formation of Z-double bond required. Treatment of a variety of
dibenzyl diselenides 1 bearing methyl, methoxyl and naphthyl
groups with different diynes 2 using NaBH4 in ethanol–THF,
under reflux, gave the corresponding (Z)-benzylselenoenynes 3 as
the only isomer (Table 1). Many functional groups were compatible
with the reaction conditions. In general, all the reactions proceeded
smoothly with good results. Most important, the hydroselenation
turned out to be general with respect of a diverse array of
functionalities. Inspecting Table 1, we can observe a significant
decrease in yields of (Z)-benzylselenoenynes when the reaction
was performed with bulky diynes (Table 1, entries 4 and 6) or
bulky dinaphthyl diselenide (Table 1, entry 14).
Since the Se/Li exchange reaction occurs with total retention
of configuration,32 the Z stereochemistry of benzylselenoenynes
was readily determined by the multiplicity of the vinylic hydrogen
signals of compound 5, which was prepared by addition of n-BuLi
(1.1 equiv) to a solution of benzylselenoenyne 3a (0.5 mmol) in
THF (3 mL) at -78 ◦C. After 30 min, the reaction was quenched by
H2O, producing the corresponding Z-enyne 5 as a single isomer
(Scheme 2). The stereochemistry of 5 was clearly indicated by
coupling constant (J = 16 Hz) of the doublets attributed to the
vinylic hydrogens, which is characteristic of trans vinyl coupling.
2
1a
3
1a
4
5
1a
1a
Scheme 2
After the success in the synthesis of (Z)-benzylselenoenynes 3,
we next focus our attention on the development of an optimum
set for the base-promoted intramolecular cyclization. For this
purpose, the reaction of 3a with bases in DMSO as solvent was
chosen as a model system. Thus, the substrate 3a (0.4 mmol)
was reacted with KOH (1 equiv) as base in DMSO (4 mL) at
◦
90 C, yielding the desired product 4a in 55% (Table 2, entry 1).
Encouraged by this result, we further investigated the reaction
behavior with other bases and solvents with the aim to improve
the protocol. The outcome of this study and an investigation of
other reaction parameters are depicted in Table 2. A comparison
of the effectiveness of bases showed that all of them were effective
to give the cyclized product (Table 2, entries 1–12), whereas
t-BuOK was the most efficient since the product was obtained
in 67% yield (Table 2, entry 12). It is important to note that
when the amount of base was changed from 1.0 to 2.0 equiv
or when the reaction was carried out at room temperature a
decrease in the yields was observed (Table 2, entries 13 and 14).
6
1a
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Table 1 (Contd.)
Table 1 (Contd.)
#
7
Dibenzyl diselenide Diyne
Product yield (%)b
#
Dibenzyl diselenide Diyne
Product yield (%)b
2a
13 1d 2b
8
1b
2b
2c
2f
14 1d
2f
9
1b
15
2a
2b
10 1b
16 1e
17 1e
2f
11
2a
2a
12
a Reactions were performed with dibenzyl diselenide 1 (1 mmol), diyne 2
(2 mmol), EtOH (25 mL), THF (10 mL) and NaBH4 (3.2 mmol) at reflux
for 5 h. b Yields correspond to isolated products.
The study to screen the solvent showed the best results
were obtained with DMSO and DMF (Table 2, entries 12 and
15) while toluene, 1,4-dioxane, CH2Cl2 and acetonitrile gave the
target products in unacceptable yields (Table 2, entries 16–19).
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Table 2 Optimization of reaction conditionsa
Table 3 Synthesis of 3-benzyl-2,5-diarylselenophenes 4 via carbocycliza-
tion of (Z)-benzylselenoenynes 3a
Entry
Base
Solvent
Yield (%)b
#
1
Substrate
Time (h) Product yield (%)b
2
1
2
3
4
5
6
7
8
KOH
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
55 (54)c
24
23
23
22
15
33
14
15
14
14
67
16
KOHd
NaOH
K3PO4
K3PO4/H2O
Na2CO3
Cs2CO3
K2CO3
9
Et3N
10
11
12
13
14
15
16
17
18
19
Pyrrolidine
Pyridine
t-BuOK
t-BuOKd
t-BuOKe
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
2
2
59
70 (67)c
15
Toluene
1,4-Dioxane
CH2Cl2
14
14
22
f
CH3CN
a Reaction performed in the presence of 3a (0.4 mmol), base (1equiv) and
4 mL of solvent at 90 ◦C. b Yields are given by GC analysis. c Yields
in parentheses correspond to isolated products. d Reaction performed
using 2 equiv of t-BuOK. e Reaction was performed at room temperature.
f Reaction was performed at 40 ◦C.
3
4
Thus, the careful analysis of the optimized reactions revealed that
the best conditions for this carbocyclization reaction were found
to be the use of (Z)-benzylselenoenyne 3a (0.4 mmol), 1 equiv of
t-BuOK as base in DMF (4 mL) at 90 ◦C. Using this reaction
condition we were able to prepare the selenophene 4a in 70%
yield. In order to demonstrate the efficiency of this protocol, we
explored the generality of our method extending the conditions
to several (Z)-benzylselenoenynes 3a–q and these results are
summarized in Table 3.
Studies defining the scope and limitations of this reaction led
us to a good understanding of this process. First, to determine
the real influence of the substituent at aromatic ring of alkyne,
we kept the selenobenzyl group directly bonded to double bond
invariable. The results demonstrated that the cyclization efficiency
was significantly influenced by the steric effects of aromatic ring,
since the cyclization reaction gave lower yields with aromatic rings
having a methyl substituent at orto position or a bulky naphthyl
group than those having no substituent (Table 3, entries 1–6).
We also observed that the reaction was sensitive to electronic
effects of aromatic ring. For example, no product was obtained
with (Z)-benzylselenoenynes having an aromatic ring with a MeO
group, directly bonded to Csp of alkyne (Table 3, entry 5). In
addition, the reactions of (Z)-benzylselenoenynes containing dif-
ferent substituents at benzyl group directly bonded to the selenium
atom were also investigated. In most cases the corresponding
selenophenes 3 were obtained in good yields. Inspecting Table 3,
we can observe that the methodology showed only a limitation to
(Z)-benzylselenoenynes having a methoxyl group bonded to the
benzyl group (Table 3, entry 11).
4
5
5
4
Trace
n.r.c
6
2
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Table 3 (Contd.)
Table 3 (Contd.)
#
7
Substrate
Time (h) Product yield (%)b
2
#
Substrate
Time (h) Product yield (%)b
6
13
8
2
2
3
14
3
9
15
16
2
2
10
17
3
11
3
n.r.c
12
3
a Reactions performed in the presence of (Z)-benzylselenoenynes 3
(0.4 mmol), t-BuOK (0.4 mmol) and DMF (4 mL) at 90 ◦C. b Yields
of 4a–q are given for isolated products. c No reaction observed.
We believe that the mechanism of this carbocyclization re-
action involves; (i) deprotonation of 3 by t-BuOK to generate
selenium stabilized carbanion a; (ii) intramolecular nucleophilic
attack of carbanion on the carbon-carbon triple bond produces
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Table 4 Cross-coupling
reaction
of
3-benzyl-4-bromo-2,5-
intermediate b; (iii) subsequent protonation of b by the conjugate
acid t-BuOH provides the intermediate c; (iv) isomerization
of c gives the selenophene product 4 (Scheme 3). Regarding
the possibility to form five (pathway a, Scheme 3) versus six
(pathway b, Scheme 3) membered ring, it is important to point
out that the unique regioisomer obtained during the curse of
this cyclization was the five-membered selenophene derivatives,
which were determined by the presence of a signal from 3.65 to
4.16 ppm in H1 NMR spectra referring to two hydrogens (Ha) from
the benzyl group at 3-selenophene, observed for all compounds
prepared (Scheme 3).
diphenylselenophene 6a and boronic acids 7a–fa
#
1
Substrate Ar
Product
Yield (%)b
86
6a
2
6a
93
3
6a
89
4
5
6a
6a
80
95
Scheme 3
Since haloselenophenes15,33 are important derivatives that
provide an useful opportunity for the further functionaliza-
tion, we wonder if it would be possible to obtain 4-bromo-
selenophenes from 2,5-diarylselenophenes prepared by our
methodology. Gratifyingly, we found that the reaction of 3-
benzyl-2,5-diphenylselenophene 4a (1 equiv) with Br2 (2,5 equiv)
in CHCl3 at room temperature gave the 3-benzyl-4-bromo-2,5-
diphenylselenophene 6a in 92% yield (Scheme 4).34
6
6a
90
a Reaction performed in the presence of 6a (0.4 mmol), 7a–f (0.6 mmol),
Pd(PPh3)4 (5 mol%), K3PO4 (1 mmol) in H2O (0.6 mL), dioxane (1.6 mL),
toluene (1.6 mL) at 90 ◦C. b Yields of 8a–f are given for isolated products.
Scheme 4
The 3-benzyl-4-bromo-2,5-diphenylselenophene 6a obtained
appear highly attractive as intermediate for the preparation of
polysubstituted selenophenes. This class of compound plays an
important role in organic synthesis because many of them are use-
ful compounds for both pharmaceutical35 and material sciences.36
Thus, the potential of the compound 6a as precursor for increas-
ing molecular complexity by palladium-catalyzed Suzuki cross-
coupling reaction was briefly investigated (Table 4). The Suzuki
cross-coupling37 was carried out using 4-bromoselenophene 6a
(0.4 mmol) with boronic acids 7a–f (0.6 mmol), Pd(PPh3)4
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(5 mol%) as catalyst and aqueous solution of K3PO4 (1 mmol)
as base, in a mixture of and dioxane (1.6 mL)/toluene (1.6 mL)
as solvent at 90 C. The results, summarized in Table 4, showed
(49), 296 (24), 229 (27), 215 (45), 115 (15), 91 (100). HRMS calcd
for C25H22Se: 420.0887. Found: 402.0890.
◦
(Z)-(1,4-Diphenylbut-1-en-3-ynyl)(4-methyl)selane
(3g).
that the reaction worked well for a variety of arylboronic acids.
A closer inspection of the results revealed that the reaction was
not sensitive to the electronic effects of an aromatic ring attached
in the arylboronic acid. For example, the aromatic rings having
neutral 7a, electron-donating 7b–c or electron-withdrawing 7d–
f substituents gave the desired products 8a–f in similar yields
(Table 4, entries 1–6). Most importantly, this method well tolerates
ketone, nitro and halogen functional groups; the corresponding
products 8a–f have been isolated in 80–95% yields.
1
Yield: 0.423 g (55%). H NMR (CDCl3, 200 MHz): d 7.52–7.45
(m, 4H), 7.38–7.30 (m, 6H), 7.25–7.23 (m, 1H), 7.02 (s, 3H), 6.22
(s, 1H), 3.84 (s, 2H), 2.28 (s, 3H). 13C NMR (CDCl3, 100 MHz): d
147.9, 140.1, 136.4, 135.1, 131.4, 129.0, 128.7, 128.5, 128.4, 128.3,
128.2, 128.1, 123.4,, 111.4, 97.2, 88.3, 30.4, 21.0. MS (relative
intensity) m/z: 388 (13), 202 (16), 105 (100), 77 (9). Elem. Anal.
(%) Calcd for C24H20Se: C 74.41, H 5.20. Found: C 74.68, H 5.16.
(Z)-(1,4-Di(naphtalen-2-yl)but-1-en-3-ynyl)(4methylbenzyl)-
selane (3j). Yield: 0.669 g (69%). 1H NMR (CDCl3, 200 MHz):
d 8.02 (s, 1H), 7.95 (s, 1H), 7.87–7.77 (m, 6H), 7.66–7.47 (m, 6H),
7.08–6.96 (m, 4H), 6.41 (s, 1H), 3.89 (s, 2H), 2.27 (s, 3H). 13C NMR
(CDCl3, 50 MHz): d 147.9, 137.5, 136.4, 135.1, 133.2, 133.2, 133.0,
132.8, 131.2, 129.1, 128.8, 128.3, 128.2, 128.1, 127.9, 127.8, 127.7,
127.6, 126.6, 126.5, 126.4, 126.0, 120.7, 112.1, 97.9, 97.5, 88.9,
30.6, 21.0. MS (relative intensity) m/z: 488 (20), 384 (14), 302
(28), 151 (10), 105 (100). Elem. Anal. (%) Calcd for C32H24Se: C
78.84, H 4.96. Found: C 78.79, H 4.92.
Conclusion
In summary, we have demonstrated the synthesis of several (Z)-
benzylselenoenynes which were used as starting material in car-
bocyclization reactions establishing an alternative route to obtain
3-benzyl-2,5-diarylselenophenes in moderate to good yields. The
reaction was carried out under mild conditions using only t-BuOK
as base, in the complete absence of transition metals or addi-
tives. The 3-benzyl-2,5-diarylselenophenes obtained in the current
protocol appear highly promising and attractive intermediates
for the synthesis of polysubstituted selenophenes. For instance,
3-benzyl-2,5-diphenylselenophene was treated with Br2 provided
the corresponding 3-benzyl-4-bromo-2,5-diphenylselenophene in
high yield. The 4-bromo-selenophene derivatives were applied as
substrate in the palladium catalyzed cross-coupling reactions with
boronic acids, to give the Suzuki type products in high yields.
(Z)-(1,4-Diphenylbut-1-en-3-ynyl)(naphthalen-2ylmethyl)selane
(3o). Yield: 0.551 g (65%). 1H NMR (CDCl3, 200 MHz): d
7.77–7.58 (m, 3H), 7.51–7.17 (m, 14H), 6.20 (s, 1H), 4.01 (s, 2H).
13C NMR (CDCl3, 100 MHz): d 147.5, 139.9, 135.7, 133.1, 132.3,
131.4, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1, 127.6, 127.3, 127.2,
125.9, 125.6, 123.4, 111.7, 97.3, 88.3, 30.9. MS (relative intensity)
m/z: 424 (84), 344 (31), 282 (11), 141 (100), 77 (15). Elem. Anal.
(%) Calcd for C27H20Se: C 76.59, H 4.76. Found: C 76.72, H 4.80.
Experimental section
General procedure for the preparation of the 3-benzyl-2,5-
diarylselenophenes 4a–q. To a Schlenck tube, under argon,
containing the appropriate (Z)-benzylselenoenyne 3 (0.4 mmol) in
DMF (4 mL) was added the t-BuOK (0.4 mmol) and the resulting
solution was stirred at 90 ◦C for 2–6 h. After this the mixture
was diluted with ethyl acetate (10 mL), and washed with brine
(3 ¥ 10 mL). The organic phase was separated, dried over MgSO4,
and concentrated under vacuum. The residue was purified by flash
chromatography on silica gel using hexane as the eluent.
General procedure for the preparation of the (Z)-
benzylselenoenynes 3a–q. To a solution of the diyne (2.0 mmol)
in THF (10 mL) and appropriate dibenzyl diselenide (1 mmol)
in 95% ethanol (25 mL) under an argon atmosphere, NaBH4
(0.12 g; 3.2 mmol) was added at room temperature, under
vigorous stirring. Gas evolution was observed during addition.
The reaction mixture was stirred under reflux for 5 h, allowed
to reach room temperature, diluted with ethyl acetate (30 mL)
and washed with brine (3 ¥ 20 mL) and water (3 ¥ 20 mL). After
drying the organic phase over anhydrous MgSO4, the solvent was
removed under reduced pressure and the residue purified by flash
chromatography on silica gel using hexane as eluent.
3-Benzyl-2,5-diphenylselenophene (4a). Yield: 0.104 g (70%).
1H NMR (CDCl3, 200 MHz): d 7.53–7.16 (m, 16H), 3.99 (s, 2H).
13C NMR (CDCl3, 100 MHz): d 148.4, 144.1, 140.8, 138.6, 136.2,
136.1, 129.2, 128.9, 128.8, 128.6, 128.5, 128.4, 127.6, 127.5, 126.0,
125.9, 35.7. MS (relative intensity) m/z: 370 (100), 293 (19), 212
(43), 114 (11), 90 (14). Elem. Anal. (%) Calcd for C23H18Se: C
73.99, H 4.86. Found: C 74.03, H 4.90.
(Z)-Benzyl(1,4-diphenylbut-1-en-3-ynyl)selane
(3a). Yield:
0.524 g (70%). 1H NMR (CDCl3, 200 MHz): d 7.60–7.28 (m, 9H),
7.23–7.04 (m, 6H), 6.23 (s, 1H), 3.87 (s, 2H). 13C NMR (CDCl3,
100 MHz): d 147.6, 140.0, 138.3, 131.4, 128.9, 128.5, 128.4, 128.3,
128.2, 128.1, 126.7, 123.3, 111.6, 97.3, 88.3, 30.5. MS (relative
intensity) m/z: 373 (28), 282 (13), 202 (50), 126 (5), 91 (100), 77
(5). Elem. Anal. (%) Calcd for C23H18Se: C 73.99, H 4.86. Found:
C 74.26, H 4.92.
3-Benzyl-5-phenyl-2-p-tolylselenophene (4g). Yield: 0.105 g
(70%). 1H NMR (CDCl3, 400 MHz): d 7.50–7.48 (m, 2H), 7.36–
7.29 (m, 5H), 7.27–7.23 (m, 3H), 7.22–7.17 (m, 5H), 3.98 (s, 2H),
2.37 (s, 3H). 13C NMR (CDCl3, 100 MHz): d 147.9, 144.3, 140.9,
138.4, 137.4, 136.3, 133.2, 129.3, 129.1, 128.9, 128.8, 128.5, 128.4,
127.4, 126.0, 125.9, 35.77, 21.2. MS (relative intensity) m/z: 388
(100), 311 (11), 215 (39), 115 (13), 91 (17). Elem. Anal. (%) Calcd
for C24H20Se: C 74.41, H 5.20. Found: C 74.46, H 5.24.
(Z)-Benzyl(1,4-dim-tolylbut-1-en-3-ynyl)selane
(3c). Yield:
1
0.584 g (73%). H NMR (CDCl3, 200 MHz): d 7.45–7.02 (m,
13H), 6.21 (s, 1H), 3.87 (s, 2H), 2.36 (s, 3H), 2.33 (s, 3H). 13C
NMR (CDCl3, 100 MHz): d 147.6, 140.0, 138.5, 138.1, 137.9,
131.9, 129.2, 129.1, 128.9, 128.5, 128.3, 128.2, 126.7, 125.4, 123.2,
111.4, 97.3, 87.9, 30.6, 21.3, 21.2. MS (relative intensity) m/z: 402
5-(Napthalen-2-yl)-3-(naphthalen-2-ylmethyl)-2-p-tolylse-
lenophene (4j). Yield: 0.038 g (20%). 1H NMR (CDCl3,
200 MHz): d 7.92–7.75 (m, 5H), 7.65–7.31 (m, 6H), 7.26–7.07 (m,
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8H), 3.68 (s, 2H), 2.32 (s, 3H). 13C NMR (CDCl3, 100 MHz): d
148.1, 144.6, 138.5, 138.3, 137.5, 136.2, 136.1, 133.6, 133.2, 132.7,
132.1, 129.3, 129.2, 129.1, 128.9, 128.3, 128.1, 127.9, 127.7, 127.6,
127.3, 126.6, 126.5, 125.9, 125.8, 125.3, 124.4, 124.3, 36.1, 21.1.
MS (relative intensity) m/z: 487 (100), 315 (26), 265 (30), 141 (23),
115 (24). Elem. Anal. (%) Calcd for C32H24Se: C 78.84, H 4.96.
Found: C 78.92, H 5.01.
(3 ¥ 20 mL). The organic phase was separated, dried over MgSO4,
and concentrated under vacuum. The residue was purified by flash
chromatography on silica gel using ethyl acetate–hexane (8 : 2) as
the eluent.
3-Benzyl-2,4,5-triphenylselenophene (8a). Yield: 0.155
g
(86%). 1H NMR (CDCl3, 200 MHz): d 7.52–7.47 (m, 2H), 7.41–
7.28 (m, 4H), 7.18–7.03 (m, 10H), 6.96–6.92 (m, 2H), 6.78–6.73
(m, 2H), 3.84 (s, 2H). 13C NMR (CDCl3, 100 MHz): d 145.1, 144.3,
142.3, 140.8, 138.5, 138.4, 136.6, 136.3, 130.5, 129.5, 129.2, 128.5,
128.2, 128.0, 127.9, 127.8, 127.5, 126.8, 126.7, 125.4, 35.0. MS
(relative intensity) m/z: 450 (100), 370 (14), 291 (39), 145 (29), 91
(19). Elem. Anal. (%) Calcd for C29H22Se: C 77.50, H 4.93. Found:
C 77.69, H 4.99.
3-Benzyl-2-(naphthalen-2-yl)-5-phenylselenophene (4o). Yield:
0.150 g (88%). 1H NMR (CDCl3, 400 MHz): d 7.90 (s, 1H), 7.86–
7.79 (m, 3H), 7.59–7.56 (m, 1H), 7.54–7.46 (m, 4H), 7.37–7.31 (m,
4H), 7.30–7.26 (m, 2H), 7.22–7.19 (m, 3H), 4.05 (s, 2H). 13C NMR
(CDCl3, 50 MHz): d 148.6, 144.0, 140.8, 138.9, 136.1, 133.4, 133.2,
132.4, 129.0, 128.8, 128.5, 128.4, 128.1, 128.0, 127.9, 127.6, 127.5,
127.4, 126.4, 126.1, 126.0, 125.9, 35.8. MS (relative intensity) m/z:
424 (100), 346 (15), 265 (45), 252 (20), 91 (14). Elem. Anal. (%)
Calcd for C27H20Se: C 76.59, H 4.76. Found: C 76.29, H 4.71.
3-Benzyl-4-(4-methoxyphenyl)-2,5-diphenylselenophene
(8b).
1
Yield: 0.177 g (93%). H NMR (CDCl3, 200 MHz): d 7.51–7.43
(m, 3H), 7.39–7.28 (m, 3H), 7.17–7.05 (m, 7H), 6.98–6.72 (m,
4H), 6.69–6.62 (m, 2H), 3.83 (s, 2H), 3.74 (s, 3H). 13C NMR
(CDCl3, 100 MHz): d 158.6, 145.0, 144.1, 142.0, 141.0, 138.7,
136.7, 136.5, 131.5, 130.8, 129.4, 129.2, 128.5, 128.2, 128.1, 127.9,
127.7, 127.5, 125.4, 113.5, 55.1, 35.0. MS (relative intensity) m/z:
480 (100), 291 (12), 191 (14), 153 (14), 91 (15). Elem. Anal. (%)
Calcd for C30H24OSe: C 75.15, H 5.05. Found: C 75.28, H 5.17.
2,5-Di(naphthalen-2-yl)-3-(naphthalen-2-ylmethyl)selenophene
(4q). Yield: 0.080 g (76%). 1H NMR (CDCl3, 200 MHz): d 7.95
(s, 2H), 7.89–7.77 (m, 9H), 7.67–7.62 (m, 3H), 7.52–7.34 (m, 8H),
4.05 (s, 2H). 13C NMR (CDCl3, 100 MHz): d 148.8, 144.5, 139.0,
138.4, 133.7, 133.6, 133.5, 133.3, 132.7, 132.6, 132.1, 129.5, 128.4,
128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 127.5, 127.4,
127.3, 126.7, 126.6, 126.5, 126.3, 126.0, 125.9, 125.4, 124.5, 124.3,
36.2. MS (relative intensity) m/z: 523 (100), 315 (59), 302 (16), 141
(19), 128 (28). Elem. Anal. (%) Calcd for C35H24Se: C 80.30, H
4.62. Found: C 80.52, H 4.70.
3-Benzyl-2,5-diphenyl-4-p-tolylselenophene (8c). Yield: 0.160 g
(89%). 1H NMR (CDCl3, 200 MHz): d 7.50–7.45 (m, 2H), 7.37–
7.22 (m, 3H), 7.19–7.01 (m, 8H), 6.94–6.72 (m, 6H), 3.83 (s, 2H),
2.26 (s, 3H). 13C NMR (CDCl3, 50 MHz): d 144.8, 144.1, 142.2,
140.9, 138.4, 136.5, 136.3, 136.2, 135.1, 130.1, 129.3, 129.2, 128.6,
128.5, 128.1, 128.0, 127.8, 127.4, 126.7, 125.3, 34.8, 21.2. MS
(relative intensity) m/z: 464 (100), 384 (12), 291 (21), 191 (15),
145 (29). Elem. Anal. (%) Calcd for C30H24Se: C 77.74, H 5.22.
Found: C 77.85, H 5.29.
General procedure for the preparation of the
3-benzyl-4-bromo-2,5-diphenylselenophene (6a)31
A solution of bromine (2.0 g, 12.5 mmol) in CHCl3 (15 mL) was
added dropwise to a solution of 3-benzyl-2,5-diphenylselenophene
4a (1.870 g, 5 mmol) in CHCl3 (40 mL) at room temperature.
After the addition was complete, the reaction was stirred at room
temperature for 1 h. After this the mixture was diluted with CH2Cl2
(30 mL), and washed with brine (3 ¥ 20 mL). The organic phase was
separated, dried over MgSO4, and concentrated under vacuum.
The residue was purified by flash chromatography on silica gel
using hexane as the eluent.
1-(4-(4-Benzyl-2,5-diphenylselenophen-3-yl)-phenyl)ethanone
(8d). Yield: 0.152 g (80%). 1H NMR (CDCl3, 200 MHz): d 7.70
(d, J = 8.5 Hz, 2H), 7.52–7.47 (m, 2H), 7.42–7.32 (m, 3H), 7.13 (s,
5H), 7.08–7.02 (m, 5H), 6.77–6.72 (m, 2H), 3.84 (s, 2H), 2.54 (s,
3H). 13C NMR (CDCl3, 100 MHz): d 197.6, 145.7, 145.0, 143.6,
141.1, 140.4, 137.7, 136.2, 135.8, 135.5, 130.7, 129.4, 129.2, 128.5,
128.2, 128.1, 127.9, 127.8, 127.7, 127.1, 125.5, 34.9, 26.3. MS
(relative intensity) m/z: 492 (100), 291 (39), 191 (22), 145 (27),
91 (41). Elem. Anal. (%) Calcd for C31H24OSe: C 75.76, H 4.92.
Found: C 75.91, H 4.98.
3-Benzyl-4-bromo-2,5-diphenylselenophene (6a). Yield: 2.079 g
(92%). 1H NMR (CDCl3, 200 MHz): d 7.66–7.61 (m, 2H), 7.45–
7.28 (m, 9H), 7.22–7.12 (m, 4H), 4.11 (s, 2H). 13C NMR (CDCl3,
100 MHz): d 145.2, 142.2, 139.8, 136.8, 135.7, 135.2, 129.5, 128.9,
128.6, 128.4, 128.3, 128.2, 128.1, 128.0, 125.9, 112.4, 36.2. MS
(relative intensity) m/z: 452 (100), 373 (19), 293 (72), 215 (92), 138
(22), 91 (58). Elem. Anal. (%) Calcd for C23H17Se: C 61.08, H 3.79.
Found: C 61.25, H 3.82.
3-Benzyl-4-(4-chlorophenyl)-2,5-diphenylselenophene
(8e).
1
Yield: 0.180 g (95%). H NMR (CDCl3, 200 MHz): d 7.51–7.45
(m, 2H), 7.40–7.26 (m, 3H), 7.21–7.03 (m, 10H), 6.86–6.70 (m,
4H), 3.82 (s, 2H). 13C NMR (CDCl3, 50 MHz): d 145.4, 144.5,
140.7, 140.5, 137.9, 136.7, 136.2, 135.8, 132.7, 131.7, 129.3, 129.2,
128.5, 128.2, 128.1, 128.0, 127.9, 127.6, 127.0, 125.5, 34.9. MS
(relative intensity) m/z: 484 (100), 291 (36), 191 (20), 145 (72),
91 (27). Elem. Anal. (%) Calcd for C29H21Se: C 71.98, H 4.37.
Found: C 72.21, H 4.43.
General procedure for the palladium-catalyzed coupling re-
action of 6a with arylboronic acids. To a Schlenck tube,
under argon, containing a solution of 3-benzyl-4-bromo-2,5-
diphenylselenophene 6a (0.180 g, 0.40 mmol) in Toluene/Dioxane
(1 : 1, 3.2 mL) was added to Pd(PPh3)4 (0.023 g, 0.02 mmol). The
resulting solution was stirred for 30 min at room temperature.
After this time appropriate arylboronic acid (0.6 mmol) and a
solution of K3PO4 (0.211 g, 1 mmol) in H2O (0.5 mL) were added.
3-Benzyl-4-(3-nitrophenyl)-2,5-diphenylselenophene
(8f).
1
Yield: 0.162 g (90%). H NMR (CDCl3, 200 MHz): d 8.02–7.96
(m, 1H), 7.78–7.74 (m, 1H), 7.55–7.46 (m, 2H), 7.44–7.31 (m,
10H), 6.75–6.70 (m, 2H), 3.83 (s, 2H). 13C NMR (CDCl3,
100 MHz): d 147.8, 146.5, 145.3, 140.2, 140.0, 139.5, 137.6, 136.6,
136.0, 135.4, 129.5, 129.3, 128.7, 128.6, 128.3, 128.1, 128.0, 127.9,
◦
The mixture was stirred at 90 C for 3 h. After this the mixture
was diluted with ethyl acetate (20 mL), and washed with brine
1536 | Org. Biomol. Chem., 2011, 9, 1529–1537
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127.4, 125.8, 125.4, 121.7, 35.1. MS (relative intensity) m/z: 495
(100), 289 (35), 169 (21), 145 (37), 91 (33). HRMS calcd for
C29H21NO2Se: 495.0738. Found: 495.0742.
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Acknowledgements
We are grateful to FAPERGS (PRONEX-10/0005-1), CAPES
(SAUX) and CNPq (CNPq/INCT-catalise) for the financial
support. CNPq is also acknowledged for the fellowships (G. Z.
and D. A. B.).
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