Stereoselective sp2-sp2 bond formation via Negishi cross-coupling of vinylic tellurides and 2-heteroarylzinc chlorides

Article abstract of DOI:10.1016/j.tetlet.2004.04.169

The Negishi cross-coupling reaction of vinylic- and aryltellurides with heteroarylzinc chlorides catalyzed by PdCl₂/CuI is described. This cross-coupling reaction is general and permits the formation of a new sp ²-sp² carbon bond in good yields and high stereoselectivity.

Full text of DOI:10.1016/j.tetlet.2004.04.169

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4823–4826
2
2
Stereoselective sp –sp bond formation via Negishi cross-coupling
of vinylic tellurides and 2-heteroarylzinc chlorides
a,
Gilson Zeni, Diego Alves, Antonio L. Braga, Helio A. Stefani
a
a
b
*
a
and Cristina W. Nogueira
a
Departamento de Qu ꢀı mica, Laborat ꢀo rio de Bioqu ꢀı mica Toxicol ꢀo gica, UFSM, 97105-900 Santa Maria, RS, Brazil
b
Faculdade de Ci ^e ncias Farmac ^e uticas, USP, S ~a o Paulo, SP, 05508-900 Brazil
Received 6 February 2004; revised 29 April 2004; accepted 29 April 2004
Available online
2
Abstract—The Negishi cross-coupling reaction of vinylic- and aryltellurides with heteroarylzinc chlorides catalyzed by PdCl /CuI is
2
2
described. This cross-coupling reaction is general and permits the formation of a new sp –sp carbon bond in good yields and high
stereoselectivity.
ꢀ
2004 Elsevier Ltd. All rights reserved.
Vinylic tellurides are of importance due to their useful
behavior as intermediates in organic synthesis, including
the synthesis of natural products. Of the two isomers,
the Z-vinylic tellurides have been employed more fre-
prompted us to examine the cross-coupling reaction of
Z-, E-vinyl, and aryl tellurides 1a–c with heteroarylzinc
chlorides 2a–c to obtain 2-vinyl- or aryl-heterocycles 3a–
i (Scheme 1).
1
quently as intermediates because of easy availability of
2
these species. Recently a new application of Z-vinylic
tellurides utilizing palladium-catalyzed cross-coupling
Our initial efforts were focused on the reactivity of Z-
vinylic telluride 1a in the cross-coupling reaction with
2-furylzinc chloride 2a, using Negishi conditions. Thus,
treatment of Z-vinylic telluride 1a (1 equiv) with 2-
furylzinc chloride 2a (2 equiv) (prepared in situ by
reaction of furan with n-BuLi in THF followed by
3
9
has been described. In this cross-coupling reaction they
react as aryl or vinyl carbocations in a manner similar to
4
vinyl halides or triflates in the Sonogashira et al., Heck
6
5
7
and Dieck, Suzuki, and Stille and co-workers cross-
coupling reactions with palladium as catalyst.
addition of ZnCl
and using Pd(PPh ) (10 mol %) as catalyst, in presence
2
), in THF/DMF at room temperature
3
4
In the last decade, there have been developments in Pd-
catalyzed coupling systems as a consequence of great
interest in the development of coupling substrates that
are more economic, more easily accessible, and reactive
even under mild conditions. In this way, the Negishi
cross-coupling is a powerful and versatile method for
the construction of new carbon–carbon bond that can
of CuI (1 equiv), affords the corresponding 2-(Z-styryl)-
furan 3a only in low yield (42%) (Scheme 2).
In view of this disappointing result, we decided to
investigate the best experimental conditions for this
cross-coupling reaction. Firstly, we investigated the
influence of the ligands in the palladium complex. As
shown in Table 1, both Pd(0) and Pd(II) with different
ligands, exhibit catalytic activity in this reaction (Table
8
be applied to alkyl, alkenyl, and alkynyl substrates. To
the best of our knowledge, however, no Negishi cross-
coupling reaction using aryl or vinyl tellurides as sub-
2
2
strate in the preparation of sp –sp carbon–carbon bond
has been described so far. Our continuing interest in the
palladium-catalyzed cross-coupling of vinylic tellurides
1
+
R2ZnCl
cat. PdCl
THF
2
, CuI
R1 R2
3a-i
R TeBu
a-c
1
2a-c
1
2
1
1
1
a R = (Z)-PhC=CH
2a - R = 2-furyl
1
2
b R = (E)-PhC=CH
2b - R = 2-thienyl
2
Keywords: Vinylic tellurides; Palladium; Negishi cross-coupling.
Corresponding author. Tel.: +55-55-220-8140; fax: +55-55-220-8978;
e-mail: gzeni@quimica.ufsm.br
R1 = Ph
2c - R = 2-pyridyl
c
*
Scheme 1.
0
040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.169

4824
G. Zeni et al. / Tetrahedron Letters 45 (2004) 4823–4826
Ph
Table 2. Optimization of cross-coupling reaction of vinylic telluride 1a
with 2-furylzinc chloride 2a
3 4
cat. Pd(PPh )
Ph
TeBu
+
ZnCl
O
CuI, THF/DMF
O
1
a
a
2
a
3a 42%
#
1
Condition
PdCl (20%)/CuI (1 equiv)
Et N (2 equiv)
PdCl (20%)/CuI (1 equiv)
Cs CO
PdCl (20%)/CuI (1 equiv)
Yield 3a (%)
2
57
ZnCl , THF
2
b
78 o
3
-
C
2
3
4
5
6
7
2
57
55
56
42
58
75
n-BuLi, THF
78 o
b
2
3
(2 equiv)
-
C
Li
O
O
2
b
K
2
CO
PdCl
PO4 (2 equiv)
3
(2 equiv)
Scheme 2.
2
(20%)/CuI (1 equiv)
b
K
3
PdCl
2
(20%)/CuI (1 equiv)
a
Table 1. Influence of catalyst in the reaction
2
a (1 equiv)
b
#
Catalyst (mol %)
Yield 3a (%)
PdCl (20%)/CuI (1 equiv)
a (2 equiv)
2
2
1
2
3
4
5
6
7
8
9
Pd(PPh
Pd(PPh
3
)
)
4
(20)
Cl (20)
(20)
51
52
45
47
54
52
17
26
35
58
PdCl
2
(20%)/CuI (1 equiv)
3
2
2
2
a (3 equiv)
Pd(OAc)
PdCl
Pd(dba)
2
8
9
PdCl
PdCl
2
(20%)/CuI (20%)
(20%)
22
20
2
(dppe) (20)
(20)
2
2
a
PdCl
PdCl
PdCl
PdCl
PdCl
2
2
2
2
2
(PhCN)
(1)
2
(20)
Yields are given for isolated products.
The reactions were performed in presence of 2a (2 equiv).
b
(5)
(10)
(20)
1
0
a
Ph
All reactions were performed in presence of 2a (2 equiv), 1a (1 equiv),
CuI (1 equiv), using THF/DMF as solvent, at room temperature for
Ph
TeBu
cat. PdCl2, CuI
THF
+
ZnCl
O
O
3a
24 h.
Yields are given for isolated products.
1a
2a
b
75%
Scheme 3.
1; entries 1–6) however, they gave unsatisfactory yields
of the desired product 3a.
2
(3 equiv), PdCl (20 mol %), CuI (1 mmol), in THF
The best yield in the preparation of 2-(Z-styryl)furan 3a
was obtained using PdCl in absence of ligands (Table 1;
2
entry 10) but this result was considered insufficient. We
also observed that the cross-coupling reaction was
(7 mL), at room temperature. Using this reaction con-
dition we are able to prepare the 2-(Z-styryl)furan 3a in
75% (Scheme 3).
greatly affected by increasing the amount of PdCl
% to 20% (Table 1; entries 7–10).
2
from
In order to demonstrate the efficiency of this cross-
coupling reaction, we explored the generality of our
method extending the coupling reaction to other vinyl or
aryl tellurides as well as other heteroarylzinc chlorides
and the results are summarized in Table 3. It is worth
mentioning that the reaction was carried out smoothly
at room temperature with high selectivity, and 3a–i were
obtained in good yields.
1
The influence of other parameters such as the presence
of copper salt, solvent, and base in the reaction was also
investigated. When the reaction of Z-vinylic telluride 1a
10
(
PdCl as catalyst, was carried out in presence of CuI and
1 equiv) with 2-furylzinc chloride 2a (3 equiv) using
2
using THF instead THF/DMF, 3a was obtained in
satisfactory yield (Table 2; entry 7).
1
13
Analysis of the H and C NMR spectra showed that
all the obtained products presented data in full agree-
ment with their assigned structures. The stereochemistry
of the double bond was easily established. As an
On the other hand, the addition of bases such as Et
Cs CO , K CO , and K PO in the reaction did not
3
N,
2
3
2
3
3
4
1
improve the yields (Table 2; entries 1–4).
example, the H spectrum of compound 3a showed a
doublet centered at 6.46 ppm with coupling constant of
12.6 Hz. The other vinylic hydrogen resonates at
6.35 ppm as a doublet, with a coupling constant of
12.6 Hz attributed to the cis-related olefinic hydrogens.
The stereoisomeric purities of the product formed were
identical to that of starting vinylic tellurides, proving the
complete retention of configuration in this coupling.
When the reaction was achieved with catalytic amount
(Table 2; entry 8) or in absence of CuI (Table 2; entry 9),
the desired product 3a was also obtained in lower yield.
We observed that this cross-coupling reaction required
the use of an excess of organozinc reagent (3 equiv).
When 1 or 2 equiv of organozinc reagent were used
unsatisfactory yields of 3a were obtained (Table 2;
entries 5 and 6). Thus, the careful analysis of the opti-
mized reactions revealed that the optimum conditions
for the coupling were found to be the use of Z-vinylic
telluride 1a (1 mmol) and 2-furylzinc chloride 2a
In summary, we have explored the Negishi cross-cou-
pling reaction of vinyl- and aryltellurides with heteroa-
rylzinc chlorides catalyzed by PdCl /CuI and established
2
a new stereoselective route to 2-vinyl- or aryl-hetero-
cycles in good yields. The reaction proceeded cleanly

G. Zeni et al. / Tetrahedron Letters 45 (2004) 4823–4826
4825
Table 3. Cross-coupling products obtained using vinylic tellurides 1a–c and heteroarylzinc chlorides 2a–c
#
Telluride
Heteroaylzinc chloride
Product
Time (h)
32
Yield (%)
75
Ph
Ph
Ph
TeBu
1
ZnCl
O
O
1a
2a
3a
2
1a
28
77
ZnCl
S
S
2
2
a
c
3b
Ph
3
4
5
6
7
8
9
1a
36
34
26
34
30
28
32
72
73
79
73
69
74
71
N
ZnCl
N
3c
Ph
2a
2b
2c
2a
2b
2c
Ph
1b
TeBu
O
3
3
3
d
e
f
1b
1b
Ph
S
N
O
Ph
TeBu
Ph
1c
3g
1c
S
Ph
3
3
h
i
1c
N
Ph
under mild reaction conditions (room temperature) and
was sensitive to nature of catalyst and solvent. We ex-
pect that these findings would be useful to assist in the
choice to introduce a vinyl or aryl group at position 2 of
the heterocycles.
Menezes, P. H.; Braga, A. L.; Stefani, H. A. Org. Lett.
001, 6, 819–821.
. (a) Zeni, G.; Barros, O. S. D.; Moro, A. V.; Braga, A. L.;
Peppe, C. Chem. Commun. 2003, 11, 1258–1259; (b)
Marino, J. P.; Nguyen, H. N. J. Org. Chem. 2002, 67,
2
2
6
291–6296; (c) Zeni, G.; Formiga, H. B.; Comasseto, J. V.
Tetrahedron Lett. 2000, 41, 1311–1313; (d) Tucci, F. C.;
Chieffi, A.; Comasseto, J. V.; Marino, J. P. J. Org. Chem.
1
996, 61, 4975–4989; (e) Barros, S. M.; Dabdoub, M. J.;
Dabdoub, V. B.; Comasseto, J. V. Organometallics 1989,
, 1661–1665.
. Zeni, G.; Braga, A. L.; Stefani, H. A. Acc. Chem. Res.
003, 36, 731–738.
. Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron
Lett. 1975, 16, 4467–4470.
. Dieck, H. A.; Heck, F. R. J. Organomet. Chem. 1975, 93,
Acknowledgements
8
We are grateful to FAPERGS, CAPES, CNPq for
financial support. CNPq is also acknowledged for Ms.
3
4
5
2
(
D.A.) fellowship.
2
6. Suzuki, A. Pure Appl. Chem. 1985, 57, 1749–1758.
59–263.
References and notes
7
. Scott, W. J.; Pe n~ a, M. R.; Sward, K.; Stoessel, S. J.; Stille,
J. K. J. Org. Chem. 1985, 50, 2302–2308.
8. (a) Negishi, E.; Anastasia, L. Chem. Rev. 2003, 103, 1979;
(b) Negishi, E. In Handbook of Organopalladium Chemis-
1
. (a) Marino, J. P.; McClure, M. S.; Holub, D. P.;
Comasseto, J. V.; Tucci, F. C. J. Am. Chem. Soc. 2002,
24, 1664–1668; (b) Zeni, G.; Panatieri, R. B.; Lissner, E.;
1

4826
G. Zeni et al. / Tetrahedron Letters 45 (2004) 4823–4826
try for Organic Synthesis; Wiley and Sons: New York,
002; Vols. 1 and 2; (c) Dabdoub, M. J.; Dabdoub, V. B.;
Marino, J. P. Tetrahedron Lett. 2000, 41, 433–436; (d)
Dabdoub, M. J.; Dabdoub, V. B.; Marino, J. P. Tetrahe-
dron Lett. 2000, 41, 437–440.
400 MHz, d (ppm): 7.44–7.42 (m, 2H); 7.33–7.24 (m,
2
4H); 6.46 (d, J ¼ 12:60 Hz, 1H); 6.35 (d, J ¼ 12:60 Hz,
1H); 6.29 (dd, J ¼ 1:9; 3.20 Hz, 1H); 6.23 (d, J ¼ 3:2 Hz,
1
3
3
1H); NMR C: CDCl , 100 MHz, d (ppm): 152.10,
141.51, 137.39, 128.64, 128.08, 127.96, 127.30, 118.04,
111.15, 109.88. MS m=z (%) 170 (100), 93 (50), 77 (29), 67
(73). IR (KBr, film) m 2927, 2860, 1742, 1479, 1435, 963.
9
. Negishi, E.; King, A. O.; Okukado, N. J. Org. Chem.
977, 42, 1821–1823.
1
1
0. Typical procedure for cross-coupling reaction: A 25 mL,
two-necked, round-bottom flask equipped with a magnetic
stir bar, rubber septum, and argon was charged sequen-
HRMS Calcd for C12H10O: 170.07316. Found: 170.07358.
Typical procedure for the preparation of heteroarylzinc
chloride 2a and 2b: n-Buthyllithium (3 mmol, 1.6 M in
hexane, 1.87 mL) was added to a solution of the appro-
priated heterocycle (3 mmol) in THF (3 mL) at )75 ꢁC and
stirred for 45 min. After this time, a solution of anhydrous
tially with PdCl
THF (1 mL), and the appropriate aryl or vinyl tellurides
a–c (1 mmol). The mixture was stirred at room temper-
ature for 10 min; then heteroarylzinc chloride 2a–c
3.0 mmol) was transferred from other flask and added
2
(0.035 g, 0.2 mmol), CuI (0.19 g, 1 mmol),
1
2
ZnCl (3 mmol, in THF, 3 mL) was added and the mixture
(
was warmed up to room temperature. After 10 min the
compound 2a or 2b was used. Typical procedure for the
preparation of heteroarylzinc chloride 2c: n-Buthyllithium
(3 mmol, 1.6 M in hexane, 1.87 mL) was added to a
solution of 2-bromo pyridine (3 mmol, 0.29 mL) at )75 ꢁC
and stirred for 1 h. After this time the mixture was warmed
up to room temperature and a solution of anhydrous
dropwise. The dark solution was stirred at room temper-
ature for the time indicated in Table 3. After this time, the
mixture was treated with aqueous ammonium chloride
(
30 mL) and CH
2
Cl
2
(3 · 20 mL). The organic phase was
and concentrated under
vacuum. The residue was purified by flash chromatogra-
separated and dried over MgSO
4
phy. Selected spectral and analytical data for: 3a-(Z)-2-
1
2
ZnCl (3 mmol, in THF, 3 mL) was added. After 15 min
this compound was used.
styryl-furan: Yield: 0.127 g (75%). NMR H: CDCl
3
,