Butyltellurium tribromide: A suitable electrophilic source to cyclization reactions

Article abstract of DOI:10.1055/s-2008-1042926

We present here our results of the electrophilic cyclization reaction of (Z)-chalcogenoenynes using butyltellurium tribromide as an electrophilic source. The cyclization reaction proceeded cleanly under mild reaction conditions and 3-(butyltellanyl)chalcogenophenes were formed in moderate to excellent yields. Subsequent, using these heterocycles as substrate to palladium-catalyzed cross-coupling reactions a new carbon-carbon bond was formed in good yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1042926

914
LETTER
Butyltellurium Tribromide: A Suitable Electrophilic Source to Cyclization
Reactions
E
lectrophilic Cycli
i
zation
e
Reaction
o
g
(
Z
)-Chalcog
o
e
noenynes Alves, Marina Prigol, Cristina W. Nogueira, Gilson Zeni*
Laboratório de Síntese, Reatividade, Avaliação Farmacológica e Toxicológica de Organocalcogênios, CCNE, UFSM,
Santa Maria, Rio Grande do Sul, CEP 97105-900, Brazil
Fax +55(55)32208978; E-mail: gzeni@quimica.ufsm.br
Received 12 December 2007
clization methodology using a tellurium species as elec-
Abstract: We present here our results of the electrophilic cycliza-
tion reaction of (Z)-chalcogenoenynes using butyltellurium tribro-
mide as an electrophilic source. The cyclization reaction proceeded
cleanly under mild reaction conditions and 3-(butyltellanyl)chalco-
trophilic sources. We also report our preliminary results in
the palladium-catalyzed cross-coupling reactions using
these heterocycles as substrate. Since butyltellurium tri-
genophenes were formed in moderate to excellent yields. Subse- bromide (BuTeBr3), a tellurium(IV) species, is more elec-
trophilic and more stable than BuTeBr,6 we tried to use
quent, using these heterocycles as substrate to palladium-catalyzed
cross-coupling reactions a new carbon–carbon bond was formed in
good yields.
BuTeBr3 in the electrophilic cyclization reaction of (Z)-
chalcogenoenynes to obtain 3-(butyltellanyl)chalco-
Key words: tellurium, electrophilic cyclization, chalcogenophenes
genophenes 2 (Scheme 1).
R1
TeBu
R2
1) BuTeBr3, MeCN, r.t.
2) NaBH4, EtOH, r.t.
Heteroannulation processes involving acetylenic com-
pounds bearing a tethered nucleophilic substituent are
among the most versatile and efficient synthetic way to
constructing a wide array of carbocycles and heterocy-
cles.1 In this way, electrophilic cyclization of unsaturated
compounds has proved to be an efficient method for one-
step construction of a substituted heterocyclic unit.2
Important heterocycles such as indoles,2a,b ben-
zo[b]furans,2c,d benzo[b]thiophenes,2e,f benzo[b]seleno-
phenes,2g thiophenes,2h furans,2i and pyrroles2j among
others,2k–r have been accessed using this protocol. This re-
action is believed to proceed through an intramolecular,
stepwise mechanism involving a cationic intermedi-
ate.2b,g,q
RY
R1
Y
R2
Y = Se, Te; R = alkyl; R1, R2 = H, alkyl, aryl
1
2
51–91%
Scheme 1 General scheme for the cyclization reactions
We have found that the reaction of (Z)-selenoenyne 1a
with BuTeBr3 in CH2Cl2 at room temperature yielded 3-
[dibromo(butyl)tellanyl]selenophene 2a in 76% isolated
yield (Scheme 2). The treatment of compound 2a with
NaBH4 in EtOH7 gave the desired product 2b as the prod-
uct in quantitative yield (Scheme 2). Since the product 2b
was obtained in two-step processes, we tried to use a one-
pot reaction to prepare the same product. In this way,
when (Z)-selenoenyne 1a was treated with BuTeBr3 in
CH2Cl2 at room temperature for 24 hours and after that
was added a solution of NaBH4 and EtOH, the product 2b
was obtained in an acceptable yield (Scheme 2).
In the context of heterocyclic compounds, the chalco-
genophene derivatives (selenophene and tellurophene)
play an important role in organic synthesis because of
their excellent electronic properties and environmental
stability. Chalcogenophenes are widely studied agents
with a diverse array of biological effects including potent
antitumor and antiviral activities.3
Br Br
Recently, we reported the electrophilic cyclization reac-
tion of (Z)-selenoenynes with several electrophilic sourc-
es to obtain 3-functionalized selenophenes in good
yields.4 These early studies mainly focused on the prepa-
rations of 3-(butyltellanyl)selenophenes to be used as sub-
TeBu
TeBu
Ph
NaBH4, EtOH, r.t.
Ph
Ph
Ph
Se
2a
Se
2b
76 %
97%
strate
in
the
palladium-catalyzed
reactions.5
BuTeBr3
CH2Cl2
24 h, r.t.
Unfortunately, in that work, we found that the butyltellu-
rium bromide species did not work as electrophilic sourc-
es, as a consequence, 3-(butyltellanyl)selenophene was
not obtained. Herein, we provide an approach in this cy-
TeBu
Ph
Ph
1) BuTeBr3, CH2Cl2, 24 h, r.t.
2) NaBH4, EtOH, r.t.
Ph
n-BuSe
Se
2b
1a
74%
SYNLETT 2008, No. 6, pp 0914–0918
x
x.
x
x.
2
0
0
8
Ph
Advanced online publication: 11.03.2008
DOI: 10.1055/s-2008-1042926; Art ID: S09907ST
© Georg Thieme Verlag Stuttgart · New York
Scheme
phene (2a)
2
Preparation of 3-(butyltellanyl)-2,5-diphenylseleno-

LETTER
Electrophilic Cyclization Reaction of (Z)-Chalcogenoenynes
915
Br Br
Based on the good result obtained on the one-pot proce-
dure described above, we investigated the best experimen-
tal conditions to improve the yield of the product 2b.
Regarding the influence of the solvent in this cyclization
reaction, optimal results were achieved changing CH2Cl2
to MeCN, furnishing the desired product 2b in 91% yield
in a short reaction time (Table 1, entry 2). By using THF,
good yield was also obtained, however, this reaction pro-
ceeded more slowly (Table 1, entry 3). Other solvents
such as MeNO2, DMSO, EtOH, and hexane afforded the
desired product in moderated yields and with longer reac-
tion times (Table 1, entries 1 and 4–7).
R1
TeBu
TeBu
BuTeBr3
R2
NaBH4
EtOH
RSe
R1
R2
R1
R2
Se
Se
1
2
c
RBr
BuTeBr3
Br Br
TeBu
R1
Br Br
TeBu
RSe
R1
Br–
R2
Se
+
R2
R
Br–
a
b
Table 1 Study of the Solvent Effect on Selenoenyne Cyclization
Reactionsa
Scheme 3 Proposed mechanism for the cyclization reactions
Ph
TeBu
Ph
1) BuTeBr3, solvent, r.t.
2) NaBH4, EtOH, r.t., 1 h
very short reaction times (Table 2, entries 1–3). The sele-
noenynes having a tert-butyl or benzyl groups also gave
the product 2b in good yield, however, with higher reac-
tion times (Table 2, entries 4 and 5). However, performing
the reaction with selenoenyne 1f, which has a phenyl
group bonded at the selenium atom, the desired product
was not observed, even under a long reaction time
(Table 2, entry 6).
n-BuSe
Ph
Se
Ph
1a
2b
Entry
Solvent
CH2Cl2
MeCN
THF
Time (h)
Yield of 2b (%)
1
2
3
4
5
6
7
24
1
74
91
89
74
58
72
75
Table 2 Influence of the Group Bonded to a Selenium Atom in the
12
Cyclization Processa
MeNO2
DMSO
EtOH
6
6
Ph
TeBu
Ph
1) BuTeBr3, MeCN, r.t.
2) NaBH4, EtOH, r.t., 1 h
RSe
Ph
36
48
Se
1a–f
2b
Ph
hexane
Entry
(Z)-Selenoenyne 1
1a (R = n-Bu)
1b (R = Me)
1c (R = Et)
Time (h)
Yield of 2b (%)
a Reactions performed in the presence of 1a (0.50 mmol), BuTeBr3
(0.55 mmol), and then NaBH4 (1 mmol) in EtOH (5 mL).
1
2
3
4
5
6
1
1
91
90
90
85
88
–
We believe that the mechanism of this tellurium cycliza-
tion reactions involves the following: (i) coordination of
the carbon–carbon triple bond to the BuTeBr3 to generate
a telluronium intermediate a, (ii) anti attack of the seleni-
um atom on the activated telluronium intermediate to pro-
duce the salt b, and (iii) facile removal of the alkyl group
by the bromine anion present in the reaction mixture to
generate corresponding 3-[dibromo(butyl)tellanyl]sele-
nophene c and one molecule of RBr. The reduction of c
with NaBH4 in EtOH7 gave the corresponding 3-(butyltel-
lanyl)selenophene 2 as the product (Scheme 3).
1
1d (R = t-Bu)
1e (R = Bn)
4
2
1f (R = Ph)
48
a Reactions performed in the presence of (Z)-selenoenyne (0.50
mmol), BuTeBr3 (0.55 mmol) in MeCN (5 mL), and then NaBH4 (1
mmol) in EtOH (5 mL).
Thus, the careful analysis of the optimized reactions re-
vealed that the optimum conditions for this electrophilic
cyclization reaction8 were the combination of 1.0 equiva-
lent of (Z)-selenoenyne, 1.1 equivalents of BuTeBr3, us-
ing MeCN as the solvent at room temperature, and
afterwards treatment with NaBH4 and EtOH. To demon-
strate the efficiency of this reaction, we explored the gen-
erality of our method extending the conditions to other
(Z)-selenoenynes, and these results are summarized in
Table 3.
Since the accomplishment of this reaction probably is de-
pendent on the nature of the group directly linked to the
selenium atom, we decided to explore this influence using
different groups, and the results are shown in Table 2.
Table 2 shows that the efficiency of selenophene synthe-
sis significantly depends on the steric effects of the groups
bonded at selenoenynes. The cyclization reaction occurs
only with selenoenynes having a Se–Csp3 group bonded.
A closer inspection of these results revealed that methyl,
ethyl, and n-butyl groups bonded at the selenium atom re-
sulted in the formation of products in high yields after
Synlett 2008, No. 6, 914–918 © Thieme Stuttgart · New York

916
D. Alves et al.
LETTER
Table 3 Scope and Generality of the Cyclization Reaction Using BuTeBr3 as Electrophilea
Entry
1b
(Z)-Selenoenyne
Time (h)
Product
Yield (%)c
Ph
H
Br Br
TeBu
n-BuSe
1
92
Ph
Ph
Se
Ph
Ph
2a
1a
Ph
H
TeBu
Ph
n-BuSe
2
3
4
5
6
1
91
82
81
79
87
Ph
Se
2b
1a
MeC H
H
4-
6
4
TeBu
n-BuSe
2
4-MeC6H4
C6H4(4-Me)
Se
C6H4(4-Me)
2c
1g
n-Bu
H
TeBu
n-BuSe
0.5
1.5
3
n-Bu
n-Bu
Se
n-Bu
2d
1h
H17C8
H
TeBu
n-BuSe
C8H17
H17C8
Se
C8H17
2e
1i
Ph
H
TeBu
n-BuSe
Ph
n-Bu
Se
n-Bu
2f
1j
HO
H
H
H
TeBu
Ph
HO
7
8
0.25
51
85
n-BuSe
Se
Ph
2g
1k
H
TeBu
n-BuSe
4
Ph
Se
Ph
2h
1l
H
TeBu
n-BuSe
9
1
87
Se
2i
1m
Synlett 2008, No. 6, 914–918 © Thieme Stuttgart · New York

LETTER
Electrophilic Cyclization Reaction of (Z)-Chalcogenoenynes
917
Table 3 Scope and Generality of the Cyclization Reaction Using BuTeBr3 as Electrophilea (continued)
Entry
10
(Z)-Selenoenyne
Time (h)
Product
Yield (%)c
H
H
TeBu
n-BuSe
3
83
67
82
76
75
n-Bu
Se
Se
n-Bu
t-Bu
Ph
2j
1n
H
H
TeBu
n-BuSe
11
12
13
14
2
3
t-Bu
2k
1o
Ph
TeBu
n-BuTe
Ph
Ph
Te
2l
1p
n-Bu
TeBu
n-BuTe
12
10
n-Bu
n-Bu
Te
n-Bu
2m
1q
Ph
TeBu
n-BuTe
Ph
n-Bu
Te
n-Bu
2n
1r
a Reactions performed in the presence of (Z)-selenoenyne (0.50 mmol), BuTeBr3 (0.55 mmol) in MeCN (5 mL), and afterwards NaBH4 (1
mmol) in EtOH (5 mL).
b Reaction without treatment with NaBH4 and EtOH.
c Yields of 2a–n are given for isolated products.
Inspection of Table 3 shows that, in general, all of the re- with BuTeBr3 in MeCN led to corresponding products 2l–
actions proceeded efficiently with good yields. The exper- n in good yields (Table 3, entries 12–14).
iments showed that the reaction with selenoenynes having
The compounds obtained by this protocol appear highly
aryl, aryl-substituted, and alkyl groups gave 3-(butyltella-
promising as intermediates in the preparation of more
nyl)selenophene derivatives in good yields (Table 3, en-
highly substituted selenophenes. Recently, applications of
tries 1–5). To our satisfaction, cyclization of
aryl tellurides utilizing palladium-catalyzed cross-cou-
unsymmetrical selenoenynes also afforded the desired
pling have been described and these compounds act in a
products in satisfactory yields (Table 3, entries 6 and 7),
manner similar to iodine or bromide analogues.5 For in-
although the yields were lower for selenoenynes with a
stance, the resulting 3-(butyltellanyl)selenophenes should
hydroxyl function at the propargyl position. Finally, via
be particularly useful intermediates in many transition-
the protocol described in this study we were able to use the
metal-catalyzed processes, such as Suzuki cross-cou-
terminal (Z)-selenoenynes 1l–o as subtracts which yielded
pling.9 For example, compound 3a has been successfully
the corresponding 3-(butyltellanyl)selenophenes 2h–k in
obtained in a 71% isolated yield by the Suzuki cross-cou-
good yields of isolated products. These products are im-
portant since the 5-position in the selenophene ring is suit-
able to a new transformation (Table 3, entries 8–11).
pling of 2b with phenylethynyl trifluorborate
(Scheme 4).9d In a similar manner, the cross-coupling of
2b with 4-methoxyphenyl trifluorborate gave the corre-
In an attempt to broaden the scope of procedure described sponding selenophene derivative 3b in 68% yield
here, we also investigated the possibility of performing (Scheme 4).9e These results were considered acceptable
the reaction with (Z)-telluroenynes. As illustrated in when compared to iodine analogues.10
Table 3, the electrophilic cyclization reaction of 1p–r
Synlett 2008, No. 6, 914–918 © Thieme Stuttgart · New York

918
D. Alves et al.
LETTER
Larock, R. C. J. Org. Chem. 2005, 70, 1432. (n) Yao, T.;
Ph
Campo, M. A.; Larock, R. C. J. Org. Chem. 2005, 70, 3511.
(o) Zhou, C.; Dubrovsky, A. V.; Larock, R. C. J. Org. Chem.
2006, 71, 1626. (p) Waldo, J. P.; Larock, R. C. Org. Lett.
2005, 7, 5203. (q) Arcadi, A.; Cacchi, S.; Giuseppe, S. D.;
Fabrizi, G.; Marinelli, F. Org. Lett. 2002, 4, 2409. (r) Peng,
A.; Ding, Y. J. Am. Chem. Soc. 2003, 125, 15006. (s) Zeni,
G.; Ludtke, D. S.; Panatieri, R. B.; Braga, A. L. Chem. Rev.
2006, 106, 1032. (t) Zeni, G.; Braga, A. L.; Stefani, H. A.
Acc. Chem. Res. 2003, 36, 731.
Pd(PPh3)4 (15 mol%)
Ag2O, Et3N
MeOH, reflux, 24 h
Ph
BF3K
Ph
Ph
Se
TeBu
Ph
3a
71%
OMe
Ph
Se
2b
Pd(acac)2 (10 mol%)
CuI (20 mol%), Et3N
(3) (a) Shiah, H. S.; Lee, W. S.; Juang, S. H.; Hong, P. C.; Lung,
C. C.; Chang, C. J.; Chou, K. M.; Chang, J. Y. Biochem.
Pharmacol. 2007, 73, 610. (b) Juang, S. H.; Lung, C. C.;
Hsu, P. C.; Hsu, K. S.; Li, Y. C.; Hong, P. C.; Shiah, H. S.;
Kuo, C. C.; Huang, C. W.; Wang, Y. C.; Huang, L.; Chen, T.
S.; Chen, S. F.; Fu, K. C.; Hsu, C. L.; Lin, M. J.; Chang, C.
J.; Ashendel, C. L.; Chan, T. C. K.; Chou, K. M.; Chang, J.
Y. Mol. Cancer Ther. 2007, 6, 193. (c) Shiah, H. S.; Lee,
W. S.; Juang, S. H.; Chang, C. J.; Chang, J. Y. Clin. Cancer
Res. 2005, 11, 9101S.
MeOH, reflux, 4 h
Ph
Ph
Se
MeO
BF3K
3b
68%
Scheme 4 Reactivity of compound 2b in palladium-catalyzed cross
reactions
In summary, we have explored the electrophilic cycliza-
tion reaction of (Z)-chalcogenoenynes using butyltelluri-
um tribromide as an electrophilic source. The cyclization
reactions proceed cleanly under mild reaction conditions
and 3-(butyltellanyl)chalcogenophenes were obtained in
moderate to excellent yields. Subsequently, Suzuki cross-
coupling reactions of compound 2b with alkynyl- or aryl-
trifluorborates proceeded smoothly in satisfactory yields.
Since the yields to the Suzuki cross-coupling using butyl-
tellurium at the 3-position are very similar, compared to
iodine derivatives, we are also studying the behavior of
these compounds using other palladium/copper cross-
coupling reactions. These studies will appear in the litera-
ture in the near future.
(4) Alves, D.; Luchese, C.; Nogueira, C. W.; Zeni, G. J. Org
Chem. 2007, 72, 6726.
(5) (a) Zeni, G.; Ludtke, D. S.; Panatieri, R. B.; Braga, A. L.
Chem. Rev. 2006, 106, 1032. (b) Zeni, G.; Braga, A. L.;
Stefani, H. A. Acc. Chem. Res. 2003, 36, 731; and references
cited therein.
(6) Petragnani, N.; Stefani, H. A. In Tellurium in Organic
Synthesis, 2nd ed.; Academic Press: London, 2007.
(7) Stefani, H. A.; Petragnani, N.; Zukerman-Schpector, J.;
Dornelles, L.; Silva, D. O.; Braga, A. L. J. Organomet.
Chem. 1998, 562, 127.
(8) General Procedure for the BuTeBr3 Cyclizations
To a solution of 0.50 mmol of the appropriate (Z)-
selenoenyne in MeCN (5 mL) was added BuTeBr3 (0.233 g,
0.55 mmol). The reaction mixture was allowed to stir at r.t.
for the time showed in Table 3. After this time, EtOH (5 mL)
and NaBH4 (0.037 g, 1 mmol) were added under vigorous
stirring (gas evolution was observed during this addition).
The reaction mixture was stirred at r.t. for one additional
hour, diluted with EtOAc (20 mL) and washed with H2O (10
mL) and brine (3 × 10 mL). The organic layer was dried over
anhyd Mg2SO4 and concentrated under vacuum to yield the
crude product, which was purified by flash chromatography
on silica gel using hexane as the eluent.
Acknowledgment
We are grateful to FAPERGS, CAPES (SAUX), and CNPq for fi-
nancial support.
References and Notes
Analysis of the 1H NMR and 13C NMR spectra showed that
all the obtained products presented data in full agreement
with their assigned structures.
(1) For representative illustrations, see the following reviews:
(a) Nakamura, I.; Yamamoto, Y. Chem. Rev. 2004, 104,
2127. (b) Zeni, G.; Larock, R. C. Chem. Rev. 2004, 104,
2285. (c) Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. Rev.
2004, 104, 3079. (d) Vizer, S. A.; Yerzhanov, K. B.;
Al Aziz Al Quntar, A.; Dembitsky, V. M. Tetrahedron
2004, 60, 5499.
(2) (a) Barluenga, J.; Trincado, M.; Rubio, E.; Gonzalez, J. M.
Angew. Chem. Int. Ed. 2003, 42, 2406. (b) Yue, D.; Yao, T.;
Larock, R. C. J. Org. Chem. 2006, 71, 62. (c) Yue, D.; Yao,
T.; Larock, R. C. J. Org. Chem. 2005, 70, 10292.
Selected Spectral and Analytical Data for 2b
Yield 0.212g (91%). 1H NMR (200 MHz, CDCl3): d = 7.51–
7.49 (m, 5 H), 7.44–7.28 (m, 6 H), 2.79 (t, J = 7.6 Hz, 2 H),
1.67 (quin, J = 7.6 Hz, 2 H), 1.29 (sext, J = 7.6 Hz, 2 H),
0.84 (t, J = 7.6 Hz, 3 H). 13C NMR (100 MHz, CDCl3): d =
150.92, 150.21, 137.67, 135.75, 135.14, 129.31, 128.93,
128.25, 127.97, 127.76, 126.20, 104.55, 36.64, 24.88, 13.32,
8.88. MS: m/z (rel. intensity) = 468 (37), 411 (11), 284 (72),
202 (100), 77 (6), 57 (5). HRMS: m/z calcd for C20H20SeTe:
469.9792; found: 469.9798.
(d) Arcadi, A.; Cacchi, S.; Fabrizi, G.; Marinelli, F.; Moro,
L. Synlett 1999, 1432. (e) Yue, D.; Larock, R. C. J. Org.
Chem. 2002, 67, 1905. (f) Hessian, K. O.; Flynn, B. L. Org.
Lett. 2003, 5, 4377. (g) Kesharwani, T.; Worlikar, S. A.;
Larock, R. C. J. Org. Chem. 2006, 71, 2307. (h) Flynn, B.
L.; Flynn, G. P.; Hamel, E.; Jung, M. K. Bioorg. Med. Chem.
Lett. 2001, 11, 2341. (i) Sniady, A.; Wheeler, K. A.;
Dembinski, R. Org. Lett. 2005, 7, 1769. (j) Knight, D. W.;
Redfern, A. L.; Gilmore, J. J. Chem. Soc., Perkin Trans. 1
2002, 622. (k) Huang, Q.; Hunter, J. A.; Larock, R. C.
J. Org. Chem. 2002, 67, 3437. (l) Yue, D.; Della Ca, N.;
Larock, R. C. Org. Lett. 2004, 6, 1581. (m) Yao, T.;
(9) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(b) Molander, G. A.; Ellis, N. Acc. Chem. Res. 2007, 40,
275. (c) Stefani, H. A.; Cella, R.; Vieira, A. S. Tetrahedron
2007, 63, 3623. (d) Stefani, H. A.; Cella, R.; Dorr, F. A.;
Pereira, C. M. P.; Zeni, G.; Gomes, M. Tetrahedron Lett.
2005, 46, 563. (e) Cella, R.; Cunha, R. L. O. R.; Reis, A. E.
S.; Pimenta, D. C.; Klitzke, C. F.; Stefani, H. A. J. Org.
Chem. 2006, 71, 244.
(10) Barancelli, D. A.; Alves, D.; Prediger, P.; Stangherlin, E. C.;
Nogueira, C. W.; Zeni, G. Synlett 2008, 119.
Synlett 2008, No. 6, 914–918 © Thieme Stuttgart · New York