Palladium-catalyzed negishi cross-coupling of arylzinc reagents with functionalized vinylic tellurides

Article abstract of DOI:10.1055/s-2006-939065

The Negishi cross-coupling reaction of arylzinc chlorides and bromides with functionalized vinylic tellurides in the presence of a catalytic amount of PdCl₂ in THF at room temperature is described. This cross-coupling reaction is general and pe

Full text of DOI:10.1055/s-2006-939065

LETTER
1035
Palladium-Catalyzed Negishi Cross-Coupling of Arylzinc Reagents with
Functionalized Vinylic Tellurides
P
alladium-Catalyz
i
e
d
N
eg
e
ishi Cross-
g
o
A
rylzinc
R
eagentsAlves, Ricardo F. Schumacher, Ricardo Brandão, 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
ing a vinylic telluride coupling reaction9 to demonstrate
the great applicability of these compounds in organic
synthesis.
Abstract: The Negishi cross-coupling reaction of arylzinc chlo-
rides and bromides with functionalized vinylic tellurides in the
presence of a catalytic amount of PdCl2 in THF at room temperature
is described. This cross-coupling reaction is general and permits the
synthesis of functionalized substituted alkenes in good yields and
high stereoselectivity.
We have reported the reaction of non-functionalized vi-
nylic tellurides with heteroarylzinc chlorides catalyzed by
palladium salts,10 however, to the best of our knowledge,
no Negishi cross-coupling reaction using functionalized
vinylic tellurides as substrate in the preparation of sp2–sp2
carbon–carbon bond has been described so far.11 Hence,
we assume that the use of functionalized vinylic tellurides
would expand the scope of the Negishi cross-coupling
reaction. Thus, our continuing interest in the palladium-
catalyzed cross-coupling of vinylic tellurides12 prompted
us to examine the cross-coupling reaction of functional-
ized vinylic tellurides 1a–f with arylzinc reagents to ob-
tain functionalized alkenes 3a–m (Scheme 1).
Key words: palladium, vinylic tellurides, organozinc, tellurium,
Negishi
Transition-metal-catalyzed cross-coupling reactions be-
tween Csp2-centers have been extensively used for prepar-
ing pharmaceuticals and agrochemical intermediates.1
Conversely in the last decade, there have been develop-
ments of coupling substrates that are more economic,
more easily accessible and reactive even under mild con-
ditions. Whereas Suzuki cross-coupling reactions have
found many applications due to the high functional group
compatibility of boronic acids and esters,2 the Negishi
cross-coupling reaction has found decidedly less appli-
cations due to the water and air instability of most
organozinc species.3 However, the excellent ability of
organozinc species for undergoing transmetallation reac-
tions allows one often to perform Negishi cross-coupling
reactions, a powerful and versatile method for the con-
struction of new carbon–carbon bonds, that can be applied
to alkyl, alkenyl and alkynyl substrates.4
R1
Ar
H
R1
H
PdCl2 (20%), THF
CuI (1 equiv)
Ar–ZnX
+
YR2
BuTe
YR2
1a–f
2a–h
3a–m
50–82%
Ar = aryl, heteroaryl; X = Cl, Br; Y = S, P; R1 = R2= alkyl, aryl, benzyl
Scheme 1
Our initial efforts were devoted to the selection of a suit-
able catalyst system for efficient Negishi cross-coupling
reaction between 1,2-bis(organoylchalcogeno)alkenes 1
with arylzinc chlorides 2 (3 mmol).13 Thus, 1,2-bis(or-
ganoylchalcogeno)alkene 1a (1 mmol) and phenylzinc
chloride 2a (3 mmol) were treated in THF (1 mL) at room
temperature with Pd(0) and Pd(II) catalysts, in the pres-
ence and absence of CuI (Table 1).
In addition, the application of vinylic tellurides utilizing
palladium-catalyzed cross-coupling has been described.
In this case, they behave as aryl or vinyl carbocation
equivalents. They react in a manner similar to vinylic ha-
lides or triflates in the Sonogashira,5 Heck,6 Suzuki,7 and
Stille8 cross-coupling reactions with palladium as a cata-
lyst. In this way, there are some advantages to use vinylic
tellurides instead of the other methods, such as the easy
access by stereoselective reactions to either (Z)- or (E)-
vinylic tellurides, no isomerization of the double bond and
the enhanced stability of these compounds. Besides, the
use of vinylic tellurides in cross-coupling reactions toler-
ates many sensitive functional groups and mild reaction
conditions. We have described the synthesis of poly-
acetylenic acids isolated from Heisteria acuminata by us-
As shown in Table 1, all Pd(0) and Pd(II) with different
ligands tested exhibit a moderate to good catalytic activi-
ty, but the best result was obtained using PdCl2 (20 mol%,
Table 1, entry 7). It is important to note that when the
amount of catalyst is reduced from 20 mol% to 1 mol% a
decrease in the yield was observed (Table 1, entries 7–
10). We also investigated the CuI influence in this cou-
pling. We found that when the reaction was achieved with
a catalytic amount (Table 2, entry 2) or in the absence of
CuI (Table 2, entry 1), the desired product 3a was ob-
tained in an unsatisfactory yield.
SYNLETT 2006, No. 7, pp 1035–1038
0
3.
0
5.
2
0
0
6
Advanced online publication: 24.04.2006
DOI: 10.1055/s-2006-939065; Art ID: S00306ST
© Georg Thieme Verlag Stuttgart · New York

1036
D. Alves et al.
LETTER
Table 1 Influence of Catalyst in the Reactiona
Table 2 Influence of CuI in the Reactiona
Entry
Catalyst (mol%)
Pd(OAc)2 (20)
Pd(PPh3)2Cl2 (20)
Pd(PhCN)2Cl2 (20)
Pd(dppe)2 (20)
Pd(dba)2 (20)
Pd(PPh3)4 (20)
PdCl2 (20)
Yield of 3a (%)
Entry
Condition
Yield of 3a (%)
1
2
65
49
57
67
55
50
82
51
54
60
1
2
3
4
5
6
PhZnCl
17
60
82
15
54
61
PhZnCl/CuI (20%)
PhZnCl/CuI (1 equiv)
PhZnBr
3
4
5
PhZnBr/CuI (20%)
PhZnBr/CuI (1 equiv)
6
a Reactions were performed in the presence of 1a (1 mmol), 2a
(3 mmol), PdCl2 (20 mol%), using THF as solvent, at r.t. for 28 h.
7
8
PdCl2 (1)
9
PdCl2 (5)
spectively). We also observed that electronic effects have
no influence on the coupling reaction. A wide range of
groups attached in the arylzinc chloride such as, electron-
rich, -neutral and -poor were cross-coupled efficiently
under these conditions and produced the functionalized
alkenes in good yields. It is interesting to note that O-, S-,
Se-heteroarylzinc chloride underwent smooth coupling
reaction with 1,2-bis(organoylchalcogeno)alkene 1a
(Table 3, entries 6–8). Differentiation in the reactivity be-
tween chlorine and bromine atoms from arylzinc reagents
can be seen by coupling of arylzinc chloride or bromide
with 1a and the results demonstrated that arylzinc chlo-
rides gave the desired product in higher yields than aryl-
zinc bromides.
10
PdCl2 (10)
a Reactions were performed in the presence of 1a (1 mmol), 2a
(3 mmol), CuI (1 mmol), using THF as solvent at r.t. for 28 h.
Thus, the careful analysis of the optimized reactions
revealed that the optimum condition for this coupling
reaction was found to be the use of 1,2-bis(organoyl-
chalcogeno)alkene 1a (1 mmol), phenylzinc chloride 2a
(3 mmol), PdCl2 (20 mol%), CuI (1 mmol) in THF (1 mL)
at room temperature giving the corresponding vinyl
sulfide 3a in 82% yield (Scheme 2).14
Br
In an attempt to broaden the scope of our methodology,
the possibility of performing the reaction with 1,2-bis(or-
ganoylchalcogeno)alkenes 1b–d and other functionalized
vinylic tellurides such as b-butyltelluro vinylphosphonate
1e and b-butyltelluro vinylphosphine oxide 1f instead of
1a, were also investigated. As illustrated in Table 4, the
cross-coupling reaction of 1b–f and phenylzinc chloride
2a, under the same reaction conditions described in
Table 3, led to the corresponding coupling products 3i–m
in excellent yields (Table 4).
1) BuLi, THF
–78 °C, 45 min
2) ZnCl2, THF
–78 °C → r.t.
H11C5
PdCl2 (20%), THF
CuI (1 equiv)
H
ZnCl
SMe
H11C5
H
BuTe
SMe
2a
3a
82%
1a
In summary, we have explored the Negishi cross-coupling
reaction of aryl- or heteroarylzinc reagents with function-
alized vinylic tellurides in the presence of a catalytic
amount of PdCl2 under mild reaction conditions (r.t.) and
established a new route to the synthesis of functionalized
alkenes in good yields. The pharmacological activities of
these compounds are under study in our laboratory. Anal-
ysis of the 1H NMR and 13C NMR spectra showed that all
the obtained products presented data in full agreement
with their assigned structures.
Scheme 2
In order to demonstrate the efficiency of this reaction, we
explored the generality of our method extending the
conditions to other arylzinc halides and the results are
summarized in Table 3.
Inspection of Table 3 shows that the reaction worked well
for a variety of arylzinc chloride. A closer inspection of
the results revealed that the reaction is not sensitive to the
steric effect of an aromatic ring attached in the arylzinc
chloride.
Acknowledgment
For example, arylzinc chloride bearing a Me substituent at
the o-, m-, p-position gave the similar yield to the no sub-
stituted phenylzinc chloride (Table 3, entries 3 and 1, re-
We are grateful to FAPERGS, CAPES and CNPq for the financial
support. CNPq and CAPES are also acknowledged for the fellow-
ships (D.A. and G.Z.).
Synlett 2006, No. 7, 1035–1038 © Thieme Stuttgart · New York

LETTER
Palladium-Catalyzed Negishi Cross-Coupling of Arylzinc Reagents
1037
Table 4 Cross-Coupling Products Using Functionalized Vinylic
Tellurides 1b–f and Phenylzinc Chloride 2aa
Table 3 Cross-Coupling Products Using Vinylic Telluride 1a and
Arylzinc Reagents 2a–h
ZnCl
H11C5
H11C5
R
PdCl2 (20%), THF
PdCl2 (20%), THF
R–TeBu
+
Ar-ZnX
+
CuI (1 equiv)
r.t., 28 h
CuI (1 equiv)
r.t., 28 h
Ar
SMe
3a–h
BuTe
SMe
1a
2a–h
1b–f
2a
3i–m
Entry ArZnX
Product 3
Yield (%)
Ph
C5H11
Ph
C5H11
MeS
PhS
S
82
66
Ph
MeS
X = Cl
X = Br
1
3k
3j
3i
75%
2a
3a
71%
79%
C5H11
C5H11
C5H11
Ph
Ph
MeS
76
60
(EtO)2OP
(Ph)2OP
2
X = Cl
X = Br
3l
73%
3mb
68%
2b
3b
a Reactions were performed in the presence of 1b–f (1 mmol) and
phenylzinc chloride (2a, 3 mmol).
MeS
3c
72
57
b A mixture of isomers Z:E (75:25) of b-butyltelluro vinylphosphine
oxide was utilized.
3
X = Cl
X = Br
2c
MeS
67
50
References and Notes
4
X = Cl
X = Br
(1) (a) Miyaura, N. Cross-Coupling Reactions. A Practical
Guide; Springer-Verlag: Berlin, 2002. (b) Diederich, F.;
Stang, P. J. Metal-Catalyzed Cross-Coupling Reactions;
Wiley-VCH: Weinheim, 1998.
Cl
Cl
2d
3d
C5H11
(2) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(b) Molander, G. A.; Petrillo, D. E.; Landzberg, N. R.;
Rohanna, J. C.; Biolatto, B. Synlett 2005, 1763.
(c) Molander, G. A.; Figueroa, R. Aldrichimica Acta 2005,
38, 49. (d) Molander, G. A.; Felix, L. A. J. Org. Chem. 2005,
70, 3950. (e) Molander, G. A.; Yun, C. S.; Ribagorda, M.;
Biolatto, B. J. Org. Chem. 2003, 68, 5534. (f) Molander, G.
A.; Biolatto, B. J. Org. Chem. 2003, 68, 4302.
(g) Molander, G. A.; Katona, B. W.; Machrouhi, F. J. Org.
Chem. 2002, 67, 8416. (h) Molander, G. A.; Riveiro, M. R.
Org. Lett. 2002, 4, 107.
74
52
MeS
5
X = Cl
X = Br
CF3
CF3
2ea
3e
C5H11
71
60
MeS
6
X = Cl
X = Br
O
O
2f
3f
(3) (a) Staubitz, A.; Dohle, W.; Knochel, P. Synthesis 2003,
233. (b) Gommermann, N.; Koradin, C.; Knochel, P.
Synthesis 2002, 2143.
(4) (a) Negishi, E.; Anastasia, L. Chem. Rev. 2003, 103, 1979.
(b) Negishi, E. In Handbook of Organopalladium Chemistry
for Organic Synthesis, Vol. 1 and 2; J. Wiley and Sons: New
York, 2002.
C5H11
77
65
MeS
7
X = Cl
X = Br
S
S
2g
3g
C5H11
(5) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett.
1975, 16, 4467.
(6) Dieck, H. A.; Heck, F. R. J. Organomet. Chem. 1975, 93,
259.
78
58
X = Cl
X = Br
MeS
8
Se
Se
2h
3h
(7) Suzuki, A. Pure Appl. Chem. 1985, 57, 1749.
(8) Scott, W. J.; Peña, M. R.; Sward, K.; Stoessel, S. J.; Stille, J.
K. J. Org. Chem. 1985, 50, 2302.
a Prepared by transmetallation from stoichiometric amount of
Grignard reagent and ZnX2 (X = Cl, Br).
(9) Zeni, G.; Panatieri, R. B.; Lissner, E.; Menezes, P. H.; Braga,
A. L.; Stefani, H. A. Org. Lett. 2001, 6, 819.
(10) Zeni, G.; Alves, D.; Braga, A. L.; Stefani, H. A.; Nogueira,
C. W. Tetrahedron Lett. 2004, 45, 4823.
(11) Dabdoub, M. J.; Dabdoub, V. B.; Marino, J. P. Tetrahedron
Lett. 2000, 41, 433.
Synlett 2006, No. 7, 1035–1038 © Thieme Stuttgart · New York

1038
D. Alves et al.
LETTER
and the reaction time was determined monitoring the
reaction by TLC. The reaction mixture was then quenched
with aqueous NH4Cl (30 mL), washed with CH2Cl2 (3 ꢀ 20
mL), dried with MgSO4 and the solvent removed under
vacuum. The products were purified by column
(12) Zeni, G.; Braga, A. L.; Stefani, H. A. Acc. Chem. Res. 2003,
36, 731.
(13) The arylzinc reagents were prepared in situ by the reaction
of aryl halides with n-BuLi in THF followed by addition of
ZnCl2.
(14) 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
sequentially with PdCl2 (0.035 g, 0.2 mmol), CuI (0.19 g,
1 mmol), THF (1 mL) and 1,2-bis(organoylchalcogeno)al-
kene (1a, 0.328 g, 1 mmol). Then, phenylzinc chloride (2a,
3 mmol), previously prepared in another flask was trans-
ferred via cannula at r.t. The black mixture was stirred at r.t.
chromatography. Selected spectral and analytical data for
3a: yield: 0.180 g (82%). 1H NMR: (200 MHz, CDCl3):
d = 7.39–7.24 (m, 5 H), 5.93 (s, 1 H), 2.43 (t, J = 6.76 Hz,
2 H), 2.22 (s, 3 H), 1.33–1.28 (m, 6 H), 0.85 (t, J = 6.32 Hz,
3 H) ppm. 13C NMR: (100 MHz, CDCl3): d = 140.05,
139.35, 128.05, 127.92, 127.01, 123.41, 38.66, 31.30, 28.13,
22.39, 17.85, 13.98 ppm.
Synlett 2006, No. 7, 1035–1038 © Thieme Stuttgart · New York