Synthesis of 2-alkynyl-tellurophene derivatives via palladium-catalyzed cross-coupling

Article abstract of DOI:10.1055/s-2006-941593

We present herein our results on the palladium-catalyzed cross-coupling of 2-halotellurophene with several terminal alkynes to give the 2-alkynyl-tellurophene derivatives in excellent yields. The reaction proceeded cleanly under mild conditions and was pe

Full text of DOI:10.1055/s-2006-941593

LETTER
3161
Synthesis of 2-Alkynyl-Tellurophene Derivatives via Palladium-Catalyzed
Cross-Coupling
S
R
ynthesis of 2-A
l
o
kynyl-Tellur
d
ophene
D
er
i
r
vatives igo B. Panatieri, Joel S. Reis, Lysandro P. Borges, 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 24 January 2006
Abstract: We present herein our results on the palladium-catalyzed
cross-coupling of 2-halotellurophene with several terminal alkynes
to give the 2-alkynyl-tellurophene derivatives in excellent yields.
The reaction proceeded cleanly under mild conditions and was per-
formed with propargyl alcohols, propargyl amines, propiolate, as
well as alkyl and aryl alkynes, in the presence of PdCl (PPh ) ,
PdCl2(PPh3)2, CuI
R
Te
R
Te
1
X
THF, Et3N, r.t.
R1
2
R1
R = C6H5, C4H9; X = I, Br
R1 = alkyl, aryl, propargyl amines, propargyl alcohols
2
3 2
Et N, THF and CuI.
Scheme 1
3
Key words: vinylic tellurides, palladium, cross-coupling, telluro-
phene, Sonogashira
affords the desired 2-alkynyl tellurophene derivatives 2 in
good yields (Scheme1).
The starting material required for the synthesis, 2-halo-
Organochalcogenide compounds have been synthetic tar-
gets because of their effects on an extraordinary number
of different reactions, including many carbon–carbon
tellurophenes 1, was readily available by using the metal-
6
lation of tellurophene with n-butyllithium followed by
the treatment of 2-(lithium)tellurophene 3 with iodine,
leading the formation of 2-iodotellurophenes 1a,b, iso-
lated in 72% and 85% yields after purification.
1
bond formations, under relatively mild reaction condi-
tions. Furthermore, organochalcogenides have become
attractive synthetic targets because of their chemo-, regio-
2
In addition, 2-bromotellurophene 1c was prepared via
treatment of 2-(lithium)tellurophene 3 with 1,2-dibromo-
and stereoselective reactions and their useful biological
3
activities.
1
(
,1,2,2-tetrachloroethane, isolated in 88% yield
Among organochalcogenides, the tellurophene deriva-
tives play an important role in organic synthesis because
of their excellent electrical properties, processibility, and
environmental stability. However, studies on their chem-
istry are hampered by poor availability of this material.
Scheme 2).7
R
R
Te
n-BuLi, THF
Transition-metal-catalyzed cross-coupling reactions rank
among the most important processes for constructing new
carbon–carbon bonds. After 30 years, palladium-cata-
lyzed coupling of terminal alkynes with the aryl halide,
I2
(BrCCl2)2
R
Te
I
Te Li
R
Te Br
1a R = C4H9 (85%)
1b R = Ph (72%)
3
1c R = C4H9 (88%)
4
commonly referred as Sonogashira reactions, a key stage
in the synthesis of many currently interesting heterocycle-
Scheme 2
5
incorporated compounds, continues to be one of the most
2
powerful and attractive tools for C(sp )–C(sp) bond
Our initial efforts were devoted to the selection of a suit-
able catalyst system for efficient Sonogashira coupling
between 2-halotellurophene and terminal alkynes. Thus,
formation. By contrast, there are no reports on the use of
halogenated tellurophenes as an electrophilic substrate for
C(sp )–C(sp) bond formation using palladium cross-cou-
2
2
-iodo-5-butyl-tellurophene (0.25 mmol) and propargyl
pling reactions.
alcohol (0.75 mmol) were treated in several solvents (2.5
mL) at room temperature with Pd(0) and Pd(II) catalysts,
Herein, we report a new, efficient and mild palladium-cat-
alyzed method to prepare 2-alkynyl tellurophene deriva-
tives. We found that direct coupling of 2-halotellurophene
in the presence and absence of CuI and Et N (0.5 mL).
3
As shown in Table 1, both Pd(0) and Pd(II) catalysts test-
ed did not exhibit catalytic activity when the reaction was
carried out in the presence of pyrrolidine and diethyl-
amine as solvent, even so using CuI as a co-catalyst and
reflux temperature (Table 1, entries 1–5). However, when
DMF, Et N, THF, MeCN, CH Cl , MeOH and hexane
1
with terminal alkynes in the presence of Pd(PPh ) Cl as
3 2 2
catalyst, with CuI as co-catalyst in THF and triethylamine
SYNLETT 2006, No. 18, pp 3161–3163
0
3
.1
1
.2
0
0
6
3
2
2
Advanced online publication: 29.06.2006
DOI: 10.1055/s-2006-941593; Art ID: S00406ST
were used the coupled product was obtained in moderate
to good yields either in the presence of Pd(0) or Pd(II)
©
Georg Thieme Verlag Stuttgart · New York

3
162
R. B. Panatieri et al.
LETTER
Table 1 Optimization of the Reaction Conditionsa
Table 2 2-Alkynyltellurophene 2 Prepared from 2-Iodo-
tellurophene 1a,b and Terminal Alkynes
[
Pd], CuI
solvent
+
PdCl2(PPh3)2, CuI
C4H9
Te
C4H9
Te
I
OH
R
Te
1a,b
I
R
Te
THF, Et3N, r.t.
R1
OH
2
R1
Entry Catalyst (mol%)
Solvent
Yield (%)
n.r.
n.r.
n.r.
n.r.
n.r.
64
Entry
1
R
Alkynes
Yield (%)
1b,d
Pd(PPh ) (20)
Pyrrolidine
Pyrrolidine
Pyrrolidine
3
4
C H
1a
4
9
71
95
2d
OH
Pd(PPh ) (20)
3
4
3
Pd(PPh ) (20)
2
3
4
5
6
1a
3
4
OH
OH
OH
4b
5c
6d
7
Pd(PPh ) Cl (20)
Et NH
3
2
2
2
1a
1a
1a
1a
84
93
95
71
Pd(PPh ) Cl (20)
Et NH
3
2
2
2
Pd(PPh ) Cl (20)
DMF
DMF
DMF
3
2
2
Pd(PPh ) Cl (10)
73
3
2
2
HO
8
Pd(PPh ) (20)
57
3
4
OH
Ph
9
Pd(PPh ) Cl (10)
Et N
63
3
2
2
3
1
1
1
1
0
Pd(PPh ) Cl (10)
THF
71
3
2
2
7
8
1a
1a
OH
97
98
1
Pd(PPh ) Cl (10)
MeCN
CH Cl
54
8
3
2
2
2
Pd(PPh ) Cl (10)
73
3
2
2
2
2
3
Pd(PPh ) Cl (10)
MeOH
Hexane
71
3
2
2
9
1a
96
14
Pd(PPh ) Cl (10)
60
3
2
2
a
Unless otherwise indicated, the reaction was carried out with Et N
10
11
1a
1a
95
80
3
Cl
as base and CuI (10 mol%) as co-catalyst.
b
The reaction was carried out in the absence of Et N.
3
c
The reaction was carried out under reflux.
The reaction was carried out in the absence of CuI.
d
N
1
2
1a
1a
82
O
catalyst (Table 1, entries 6–14). Thus, we chose
PdCl (PPh ) (10 mol%), CuI (10 mol%), THF (2.5 mL),
2
(
1
reaction. In order to demonstrate the efficiency of this re- 15
action, we explored the generality of our method extend-
ing the conditions to other terminal alkynes and the results 16
are summarized in Table 2.
1
1
3
4
81
72
67
94
NEt2
O
2
3 2
-iodo-tellurophene 1a (0.25 mmol), propargyl alcohol 2a
1a
0.75 mmol) and Et N (0.5 mL) at room temperature for
3
OEt
OH
2 hours, as the optimum condition for this coupling
Ph
8
1
b
1b
1b
1b
OH
OH
OH
Concerning the structure of tellurophene, we found that
neither 5-butyl- nor 5-phenyl-2-iodotellurophenes exhib-
ited limitations in this methodology.
1
1
1
7
8
9
94
95
Inspection of Table 2 shows that the reaction worked well
for a variety of propargylic alcohols. Both hindered and
non-hindered propargyl alcohols gave the desired substi-
tuted tellurophene in good yields (Table 2, entries 1–6).
When we performed this reaction with aryl alkynes, no 20
differences were found between electron-withdrawing
and electron-donating substituents (Table 2, entries 8–
1
propargyl morpholynes gave similar yield to tertiary
propargyl amines (Table 2, entries 12 and 13).
HO
1b
1b
1b
1b
92
70
60
69
2
1
0). Our experiments also showed that the reaction with
2
2
Cl
Synlett 2006, No. 18, 3161–3163 © Thieme Stuttgart · New York

LETTER
Synthesis of 2-Alkynyl-Tellurophene Derivatives
3163
Table 2 2-Alkynyltellurophene 2 Prepared from 2-Iodo-
tellurophene 1a,b and Terminal Alkynes (continued)
biological activities of these compounds are under study
1
13
in our laboratory. Analysis of the H NMR and C NMR
spectra showed that all the obtained products presented
data in full agreement with their assigned structures.
PdCl2(PPh3)2, CuI
R
I
Te
a,b
R
Te
2
THF, Et3N, r.t.
R1
R1
1
Acknowledgment
Entry
R
Alkynes
Yield (%)
We are grateful to FAPERGS, CAPES and CNPq for the financial
support. CNPq is also acknowledged for the fellowships (Panatieri
and G.Z.).
2
2
3
4
1b
66
92
N
1b
1b
References and Notes
O
(
1) (a) Zeni, G.; Braga, A. L.; Stefani, H. A. Acc. Chem. Res.
003, 36, 731. (b) Silveira, C. C.; Braga, A. L.; Vieira, A. S.;
O
O
2
2
5
54
Zeni, G. J. Org. Chem. 2003, 68, 662. (c) Zeni, G.;
Panatieri, R. B.; Lissner, E.; Menezes, P. H.; Braga, A. L.;
Stefani, H. A. Org. Lett. 2001, 3, 819.
(
2) (a) Petragnani, N.; Stefani, H. A. Tetrahedron 2005, 61,
Having optimized the reaction conditions for 2-iodotel-
lurophene we turned our attention to 2-bromo-
tellurophene. Thus, we extended our standard catalytic
system, used in the coupling reaction described in
Table 2, to the reaction of 2-bromotellurophene 2 with ter-
minal alkynes. These reactions produced the desired prod-
ucts in lower yields. We screened a representative range
of terminal akynes, the results are shown in Table 3. The
best results were obtained for propargyl alcohols and pro-
pargyl morpholyne (Table 3, entries 1, 2 and 5). Alkynyl
and aryl alkynes gave the coupled products in moderate
yields (Table 3, entries 3 and 4).
1613. (b) Organoselenium Chemistry, In Topics in Current
Chemistry, Vol. 208; Wirth, T., Ed.; Springer-Verlag:
Heidelberg, 2000. (c) Krief, A. In Comprehensive
Organometallic Chemistry II, Vol. 11; Abel, E. V.; Stone, F.
G. A.; Wilkinson, G., Eds.; Pergamon Press: New York,
1995, Chap. 13. (d) Paulmier, C. Selenium Reagents and
Intermediates in Organic Synthesis, In Organic Chemistry
Series 4; Baldwin, J. E., Ed.; Pergamon Press: Oxford,
1986. (e) Petragnani, N. Tellurium in Organic Synthesis;
Academic Press: London, 1994.
(
(
(
3) Nogueira, C. W.; Zeni, G.; Rocha, J. B. T. Chem. Rev. 2004,
104, 6255.
4) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1
975, 16, 4467.
5) (a) Masui, K.; Ikegami, H.; Mori, A. J. Am. Chem. Soc.
004, 126, 5074. (b) Zeni, G.; Nogueira, C. W.; Panatieri, R.
Table 3 2-Alkynyltellurophene 2 Prepared from 2-Bromo-
tellurophene 1c and Terminal Alkynes
2
B.; Silva, D. O.; Menezes, P. H.; Braga, A. L.; Silveira, C.
C.; Stefani, H. A.; Rocha, J. B. T. Tetrahedron Lett. 2001,
42, 7921. (c) Zeni, G.; Lüdtke, D. S.; Nogueira, C. W.;
Panatieri, R. B.; Braga, A. L.; Silveira, C. C.; Stefani, H. A.;
Rocha, J. B. T. Tetrahedron Lett. 2001, 42, 8927.
PdCl2(PPh3)2, CuI
R
Br
R
Te
Te
THF, Et3N, r.t.
R1
R1
1c
2
(
d) Parrish, J. P.; Jung, Y. C.; Floyd, R. J.; Jung, K. W.
Entry
1
R
Alkynes
Yield (%)
50
Tetrahedron Lett. 2002, 43, 7899.
(
6) The tellurophene derivatives were prepared according to:
Barton, T. J.; Roth, R. W. J. Organomet. Chem. 1972, 39,
C66.
7) Inoue, S.; Jigami, T.; Nozoe, H.; Aso, Y.; Ogura, F.; Otsubo,
T. Heterocycles 2000, 52, 159.
C H
4
9
1c
OH
OH
(
2
1c
66
(
8) Typical Procedure for Cross-Coupling Reaction.
A 25-mL, two-necked, round-bottom flask equipped with a
magnetic stir bar and argon was charged sequentially with
Pd(PPh ) Cl (10 mol%), CuI (10 mol%), THF (2.5 mL), 2-
3
4
1c
1c
38
43
3
2
2
iodotellurophene (0.25 mmol), alkyne (0.75 mmol) and Et N
3
(
0.5 mL). The mixture was stirred at r.t. for 12 h. After this
N
5
1c
55
time, the mixture was filtered through a pad of alumina
eluting with 50 mL of EtOAc. The organic phase was
concentrated under vacuum and the residue was purified by
flash chromatography.
O
Selected Spectral Data for 1-(5-Butyltellurophen-2-
In summary, we have demonstrated that treatment of 2-
halotellurophenes with terminal alkynes in THF in the
presence of Pd (PPh ) Cl /CuI (10 mol%) at room tem-
perature results in the corresponding cross-coupled prod-
ucts in good yields. The cross-coupling reaction tolerates
hindered and non-hindered propargyl alcohols, electron-
withdrawing and electron-donating aryl alkynes, propar-
gyl morpholyne, propargyl amine and alkyl alkynes. The
yl)pent-1-yn-3-ol.
1
H NMR (400 MHz, CDCl ): d = 7.54 (d, 1 H, J = 4.08 Hz),
3
2
3 2
2
7
7
1
.17 (d, 1 H, J = 4.06 Hz), 4.5 (t, 1 H, 6.3 Hz), 2.84 (t, 2 H,
.4 Hz), 2.30–2.15 (m, 1 H), 1.79 (quint, 2 H, J = 7.08 Hz),
.60 (quint, 2 H, J = 7.8 Hz), 1.40 (sext, 2 H, J = 7.05), 1.03
1
3
(t, 3 H, J = 7.4 Hz), 0.92 (t, 3 H, J = 7.17 Hz). C NMR (100
MHz, CDCl ): d = 156.63, 142.05, 133.60, 118.87, 95.97,
5.07, 64.47, 36.66, 36.37, 22.03, 13.74, 9.46.
3
8
Synlett 2006, No. 18, 3161–3163 © Thieme Stuttgart · New York