Mechanism of the carbopalladation of alkynes by aryl-palladium complexes

Article abstract of DOI:10.1016/j.jorganchem.2004.05.032

The carbopalladation between PhPdI(PPh₃)₂ and EtO₂C-CCH gives EtO₂C-C(PdIL₂)CHPh 1, the trans-adduct as the major complex formed by isomerization of the primary cis-adduct EtO₂C-C(PdIL₂)CHPh 2. A multicarbopalladation is also observed. The reaction between trans-PhPdI(PPh₃)₂ and EtO₂C-CCH has been investigated. This carbopalladation step involved in palladium-catalyzed multicomponent reactions with alkynes gives the unusual trans-adduct EtO₂C-C(PdIL₂)CHPh 1 as the major complex formed by isomerization of the primary cis-adduct EtO ₂C-C(PdIL₂)CHPh 2. The carbopalladation was regiospecific. A multicarbopalladation was also observed by successive carbopalladation of EtO₂C-CCH by the vinyl-palladium complexes themselves generated in carbopalladation steps, leading to cationic complexes.

Full text of DOI:10.1016/j.jorganchem.2004.05.032

Journal of Organometallic Chemistry 689 (2004) 4642–4646
www.elsevier.com/locate/jorganchem
Mechanism of the carbopalladation of alkynes by
aryl-palladium complexes
a,
a
b
a,*
Christian Amatore *, Samia Bensalem , Said Ghalem , Anny Jutand
a
´ ´
Departement de Chimie, Ecole Normale Superieure, UMR CNRS-ENS-UPMC 8640, 24 Rue Lhomond, F-75231, Paris Cedex 5, France
b
´ ´ ´ ´
Departement de Chimie, Faculte des Sciences, Universite de Tlemcen, BP 119. M-13000 Tlemcen, Algerie
Received 29 March 2004; accepted 25 May 2004
Available online 3 July 2004
Abstract
The reaction between trans-PhPdI(PPh3)2 and EtO2C–C„CH has been investigated. This carbopalladation step involved in pal-
ladium-catalyzed multicomponent reactions with alkynes gives the unusual trans-adduct EtO2C–C(PdIL2)@CHPh 1 as the major
complex formed by isomerization of the primary cis-adduct EtO2C–C(PdIL2)@CHPh 2. The carbopalladation was regiospecific.
A multicarbopalladation was also observed by successive carbopalladation of EtO2C–C„CH by the vinyl-palladium complexes
themselves generated in carbopalladation steps, leading to cationic complexes.
Ó 2004 Elsevier B.V. All rights reserved.
Keywords: Carbopalladation; Multicarbopalladation; Palladium; Alkynes; Oxidative addition; Vinyl iodide
1. Introduction
In multicomponent reactions (Eq. (1)), one key step is
the reaction of the alkyne with the aryl-palladium(II)
complex formed in the oxidative addition of the aryl ha-
lide to a palladium(0) complex (Eqs. (4) and (5)) [1]. This
step, usually named carbopalladation, is often considered
as being rate-determining in reactions performed with
aryl iodides or activated aryl bromides [1,3].
Alkynes are involved in palladium-catalyzed multi-
component reactions as reported by Cacchi et al. [1]
(Eq. (1)) or in Sonogashira reactions (terminal alkynes)
(Eqs. (2) and (3)) [2].
R
R'
Pd0
-
C_R' + Nu
-
ArX + R_C
+ X
ð1Þ
Carbopalladation
R
R'
Ar
Nu
ð4Þ
ArPdXL2 + R_C C_R'
0
I
Ar
ArX þ RCBCH þ Base Pd =Cu
!
ArCBCR0 þ BaseHþ; Xꢀ
ð2Þ
PdXL2
R
ArPdXL2 + R_C C_H
ð5Þ
Pd0
Ar
ArX þ RCBCH þ Base ! ArCBCR0 þ BaseHþ; Xꢀ
PdXL2
The carbopalladation involving terminal alkynes (Eq.
(5)) might also be a key step in the copper-free Sono-
gashira reactions (Eq. (3)).
The carbopalladation is a syn addition which offers a
cis-adduct in which the aryl group is transferred to the
less hindered position (Eq. (5)) [1]. This reaction was
ð3Þ
*
Corresponding authors. Tel.: +33-1-4432-3872; fax: +33-1-4432-
3325.
E-mail addresses: christian.amatore@ens.fr (C. Amatore), Anny.
Jutand@ens.fr (A. Jutand).
0022-328X/$ - see front matter Ó 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2004.05.032

C. Amatore et al. / Journal of Organometallic Chemistry 689 (2004) 4642–4646
4643
considered to be regio and stereospecific. However,
some palladium-catalyzed multicomponent reactions
are reported to give a mixture of products in which
the Ar group and the nucleophile may be cis and/or
trans [1,4]. This may arise via an isomerization of the
cis-adduct complex first formed in the carbopalladation
step via a zwitterion metal carbene (Eqs. (6a) and (6b))
[4,5]. An alternative mechanism has also been proposed
via g2-vinyl-metal complexes [6].
the carbopalladation gave two main complexes 1 and
2 characterized by two 31P NMR singlets at 20.40
and 22.02 ppm, respectively [7]. Complex 2 (the cis-ad-
duct) is the complex formed after the usual expected
syn addition of Ph–PdI(PPh3)2 on the alkyne (Eq. (7)).
trans-PhPdIL2 + EtO2C_C C_H
EtO2C
EtO2C
Ph
+
Ph
ð7Þ
PdIL2
PdIL2
R
R'
R
R'
1
2
_
trans-adduct
cis-adduct
+
Ar
Ar
PdXL2
PdXL2
cis-adduct
L = PPh3
ð6aÞ
Complexes 1 and 2 have not been reported previously, so
they were identified by comparison with authentic sam-
ples, independently synthesized by an oxidative addition
of a mixture of (E) and (Z) vinylic iodides 3 and 4 (34/
66%) to Pd0(PPh3)4 at room temperature (Eq. (8)).
R
Ar
R'
R
Ar
R'
_
+
PdXL2
PdXL2
trans-adduct
R
R'
R
R'
EtO2C
EtO2C
I
Ph
+
_
Ar
+
Ar
PdXL2
PdXL2
Ph
I
cis-adduct
3
4
ð6bÞ
R
Ar
R'
(E)
(Z)
R
Ar
66%
34%
+
ð8Þ
_
PdXL2
R'
+ Pd0L4
_ 2 L
PdXL2
Ph
EtO2C
PdIL2
EtO2C
PdIL2
trans-adduct
+
Ph
We report herein some investigation on a carbopallada-
tion step which shows that both cis- and trans-adducts
are indeed formed. In addition, a multicarbopalladation
was observed.
L = PPh3
1
2
(20.40 ppm)
64%
(22.02 ppm)
36%
The oxidative addition being stereospecific [8], the vinyl
iodides 3 and 4 should give, respectively, the vinyl-PdIL2
complexes 1 and 2 in the ratio (34/66%) (Eq. (8)). The ox-
idative addition of the mixture of vinyl iodides 3 and 4 to
Pd0(PPh3)4 was monitored by 31P NMR spectroscopy in
CDCl3 under stoichiometric condition (Pd/(3+4)=1). A
singlet at 20.40 ppm was first observed [7] and assigned
to complex 1 because oxidative additions are reported
to be faster with (E) than with (Z) vinyl halides, due to
steric hindrance in the preliminary coordination of the
active Pd0(PPh3)2 to the C@C bond of the vinyl halide
[8]. At longer times, a new singlet appeared at 22.02
ppm and was assigned to complex 2, generated in the
slower oxidative addition of 4. At the end of the oxida-
tive addition, complexes 1 and 2 were detected together
but in the ratio 64/36 instead of the expected ratio 34/
66. This indicates that isomerization of 2 to 1 took place
during the course of the oxidative addition [9].
2. Results and discussion
2.1. Mechanism of the carbopalladation
The reaction of trans-PhPdI(PPh3)2 with EtO2C–
C„CH was monitored by 1H NMR spectroscopy in
CHCl3 and by 31P NMR spectroscopy in CHCl3 or
DMF containing 10% CDCl3. A slow reaction was ob-
served at room temperature between trans-
PhPdI(PPh3)2 (24 mM) and EtO2C–C„CH (48 mM).
The complex trans-PhPdI(PPh3)2, easily identified by
the three sets of protons of the Ph group ligated to
the palladium, was completely consumed after 16 h. In-
terestingly, when only 1 equiv. of EtO2C–C„CH was
involved, EtO2C–C„CH was totally consumed after
7 h, whereas part of the complex trans-PhPdI(PPh3)2
was still detected (40%), suggesting that EtO2C–
C„CH was not only consumed through its reaction
with trans-PhPdI(PPh3)2 but participated simultaneous-
ly in another side-reaction possibly through its reaction
with the complex(es) formed in the carbopalladation
step (vide infra). In the early stage of the reaction,
When the carbopalladation between trans-
PhPdI(PPh3)2 and EtO2C–C„CH was monitored by
1H and 31P NMR spectroscopy in CHCl3, the same
31P NMR singlets at 20.40 and 22.02 ppm were
observed. The two complexes 1 and 2 generated in the

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C. Amatore et al. / Journal of Organometallic Chemistry 689 (2004) 4642–4646
carbopalladation step in Eq. (7) have then been identified.
The complex 2 (cis-adduct) first appeared. It disappeared
gradually with time while complex 1 (trans-adduct) ap-
peared. The ratio of the two complexes then stabilized
to 64/36% in favor of complex 1 which was eventually
formed in higher amount than the expected cis-adduct
2. It was then formed by isomerization of the cis-adduct
2 (initially formed in the carbopalladation step), as
observed independently during the oxidative addition
(Eq. (8)). The isomerization would proceed via one of
the zwitterionic resonance forms (Eq. (9a)) [4,5] or by
resonance with the ester group (Eq. (9b)).
When the amount of PhI was decreased (1 equiv.), i.e.,
when the oxidative addition was made slower, the com-
plexes generated in the carbopalladation were detected
together with trans-PdPdI(PPh3)2. This indicates that
for equivalent amounts of PhI and EtO2C–C„CH,
the time scales of the oxidative addition and carbopalla-
dation may become closer.
2.2. Multicarbopalladation
In the carbopalladation step (Eq. (7)) performed in
the presence of excess EtO2C–C„CH, other minor com-
plexes appeared with time besides complexes 1 and 2.
They were detected by the presence of different sets (at
least six) of quadruplets (CH2) and triplets (CH3) in
EtO2C
_
H
EtO2C
H
(9a)
+
1
Ph
Ph
the H NMR spectrum evidencing different ethyl ester
PdXL2
PdXL2
groups. The NMR spectrum also exhibited broad signals
(at least four) located at low field between 7.8 and 9 ppm,
characteristic of highly conjugated vinylic protons. Some
of these complexes have been characterized by FAB mass
spectrometry. Besides the mass of complexes 1 and 2
(m/z=933 [1+H]+ and [2+H]+), other mass peaks were
observed. They were indicative of successive incorpora-
tions of the EtO2C–C„CH unit into complexes 1 and 2,
with concomitant lost of the iodide ion (m/z=903 [1 (or
2)+EtO2C–C„CH–I]+; m/z=1001 [1 (or 2)+2EtO2C–
C„CH–I]+). The 31P NMR spectrum exhibited at least
three detectable sets of two doublets which were charac-
teristic of magnetically unequivalent PPh3, in contrast
with the singlets observed for complexes 1 and 2 indicative
of two magnetically equivalent PPh3 [7]. This indicates
that in each new complex, the two phosphines sit in a cis
position on the PdII centre. New complexes 5 (or 6) were
then generated by the carbopalladation of EtO2C–
C„CH by the vinyl-palladium complex 1 (or 2) (Eqs.
(10) and (11)). Complexes 5 (or 6) underwent then a sec-
ond carbopalladation with EtO2C–C„CH to give com-
plex 7 (or 8) (Eqs. (10) and (11)). These complexes
released their iodide anion because of the internal com-
plexation of the PdII centre by the carbonyl of the ester
group, making then the two phosphines magnetically
cis-adduct
OEt
H
O
_
+
(9b)
Ph
PdXL2
It is worthwhile to note that the regioselectivity of the
carbopalladation step is the expected thermodynamic
one [1b,1c], i.e., with the PdIL2 moieties located at the
more hindered carbon the C„C bond and the phenyl
group at the less hindered one.
In a previous work, we reported kinetic data on the
oxidative addition of phenyl iodide to Pd0(PPh3)4 (2
mM in DMF) and established that the oxidative addi-
tion was slower in the presence of alkynes (PhC„CH
or EtO2C–C„CH) by complexation of the active
Pd0(PPh3)2 complex by the alkyne which generate the
unreactive complex (g2-PhC„CH)Pd0(PPh3)2 or the
less reactive complex (g2-EtO2C–C„CH)Pd0(PPh3)2
[3]. When PhI (10 equiv.) was added to a solution of
Pd0(PPh3)4 (17 mM) in acetone-d6 containing EtO2C–
C„CH (1 equiv.), trans-PdPdI(PPh3)2 was the main
complex observed at short times. The complexes formed
in the carbopalladation were observed at longer times.
Ph
EtO2C
EtO2C
L
EtO2C
EtO2C
Ph
EtO2C_C C_H
L
EtO2C_C C_H
L
Pd
+
Pd
Pd
(10)
(11)
+
O
C
Ph
O
C
L
L
L
I
-
1
-
OEt
I
OEt
I
5
7
trans-adduct
cis-adduct
cis-adduct
EtO2C
EtO2C
EtO2C
EtO2C
Ph
L
EtO2C_C C_H
L
EtO2C_C C_H
L
Ph
Pd
Pd
+
Ph
Pd
O
L
C
+
L
I
O
C
L
2
-
OEt
-
6
I
OEt
I
8
cis-adduct
cis-adduct
cis-adduct
L = PPh3

C. Amatore et al. / Journal of Organometallic Chemistry 689 (2004) 4642–4646
4645
not equivalent. Such internal complexation of cationic
PdII complexes by the carbonyl of an ester group was re-
cently observed by Liu and coworkers [10] in complexes
formed by multiple insertions of EtO2C–C„CH into
Pd-aryl bonds in cationic [ArPdII(P,N)(MeCN)]+ com-
plexes. Due to the complex mixture of complexes and
overlapping 1H NMR signals, it was difficult to differenti-
ate complexes 5 (or 6) and 7 (or 8).
The carbopalladation was regioselective. Those vinyl-
palladium complexes undergo a first and second carbo-
palladation with EtO2C–C„CH, leading to cationic
vinyl-palladium complexes ligated by two cis phosphines
after release of the iodide ion due to the intramolecular
complexation of the PdII centre by the ester group.
Consequently, cationic complexes were generated by
successive carbopalladation steps to generate cationic
complexes with two phosphines in a cis position. This
multicarbopalladation was observed even under stoichi-
ometric conditions so that PhPdIL2 was not totally con-
verted (40% conversion) while all the alkyne was
consumed. This suggests that the vinyl-PdIL2 complex
1 (or 2) underwent a series of fast carbopalladations
(Eqs. (10) and (11)) before PhPdIL2 was completely con-
verted in the first carbopalladation step.
A related trans–cis isomerization of the first carbopal-
ladation product as well as a second carbopalladation
have also been observed during the hydroarylation of
terminal alkynes catalyzed by Pd(OAc)2, as reported
by Fujiwara and coworkers [11] (Eq. (12)).
4. Experimental
4.1. General
31P NMR spectra were recorded on a Bruker spec-
trometer (101 MHz) and 1H NMR spectra 250 MHz, re-
spectively. Ethyl propiolate was commercial (Acros) and
used after filtration on alumina. PdPdI(PPh3)2 [12],
Pd0(PPh3)4 [13] and the vinylic iodides 3 and 4 [14] were
prepared according to described procedures.
4.2. Characterization of complexes
4.2.1. trans-Ph–PdI(PPh3)2
1H NMR (250 MHz, CDCl3, TMS) d 6.21 (t, J=7 Hz,
2H, m-H of Ph), 6.33 (t, J=7 Hz, 1H, p-H of Ph), 6.60 (d,
J=7 Hz, 2H, o-H of Ph), 7.23 (t, J=12 Hz, J=7 H, m-H
in PPh3), 7.32 (t, J=7 Hz, 6H, p-H in PPh3), 7.50 (dd,
J=7 Hz, 6 Hz, 12H, o-H in PPh3). 31P NMR (101
MHz, CDCl3, H3PO4) d 23.03 (s).
ArH + EtO2C_C C_H
EtO2C
Ar
EtO2C
Pd(OAc)2
TFA
+
EtO2C
Ar
9
10
4.2.2. trans-Adduct EtO2C–C[PdI(PPh3)2]@CHPh 1
1H NMR (250 MHz, CDCl3, TMS) d 0.97 (t, 3H,
J=7 Hz, CH3), 3.51 (q, 2H, J=7 Hz, CH2), 7.5 (m, 18
H, H of PPh3), 7.7 (m, 12 H, H of PPh3), 7.85 (m, 1H,
vinyl H). 31P NMR (101 MHz, CDCl3, H3PO4) d
20.40 (s). FAB mass spectroscopy: m/z=933 [1+H]+,
805 [1ꢀI], 630 [1ꢀEtO2C–C@CHPh].
ð12Þ
In reaction (12), the postulated intermediate complex is
a ‘‘ArPd(OAc)’’ complex which reacts with EtO2C–
C„CH to generate the trans-adduct 11 formed after
isomerization of the primary cis-adduct. Compound 9
was obtained by acidic hydrolysis of 11. A second carbo-
palladation step of EtO2C–C„CH by complex the vi-
nyl-Pd complex 11 generates the cis-adduct 12 whose
acidic hydrolysis gives compound 10.
4.2.3. cis-Adduct EtO2C–C[PdI(PPh3)2]@CHPh 2
1H NMR (250 MHz, CDCl3, TMS) d 1.34 (t, 3H,
J=7 Hz, CH3), 4.27 (q, 2H, J=7 Hz, CH2), 7.5 (m, 18
H, H of PPh3), 7.7 (m, 12 H, H of PPh3), 8.16 (m, 1H,
vinyl H). 31P NMR (101 MHz, CDCl3, H3PO4) d
22.02 (s). FAB mass spectrum: m/z=933 [2+H]+, 805
[2ꢀI], 630 [2ꢀEtO2C–C@CHPh].
EtO2C
Ar
EtO2C
AcO_Pd
AcO_Pd
EtO2C
Ar
12
11
4.2.4. Complexes 5 (or 6), 7 (or 8)
1H NMR (250 MHz, CDCl3, TMS) d 0.7 (t, J=7 Hz),
0.8 (t, J=7 Hz), 1.02 (t, J=7 Hz), 1.29 (t, J=7 Hz), 1.51 (t,
J=7 Hz), 3.0 (q, J=7 Hz); 1.02 (t, J=7 Hz), 3.57 (q, J=7
Hz), 3.8 (q, J=7 Hz), 4.01 (q, J=7 Hz), 4.41 (q, J=7 Hz),
4.43 (q, J=7 Hz). 31P NMR (101 MHz, CDCl3, H3PO4) d
11.75 (d, JPP =19 Hz) with 15.88 (d, JPP =19 Hz); 23.15 (d,
JPP =6 Hz) with 26.57 (d, JPP =6 Hz); 24.72 (d, JPP =8 Hz)
with 27.65 (d, JPP =8 Hz). FAB mass spectra: m/z=903 [5
(or 6)ꢀI]+; m/z=1001 [7 (or 8)ꢀI]+).
3. Conclusion
The carbopalladation step between PhPdI(PPh3)2 and
EtO2C–C„CH has been investigated with the character-
ization of the unusual trans-adduct EtO2C–C(PdIL2)@
CHPh 1 as the major complex formed by isomerization
of the primary cis-adduct EtO2C–C(PdIL2)@CHPh 2.

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C. Amatore et al. / Journal of Organometallic Chemistry 689 (2004) 4642–4646
(b) M. Alami, F. Ferri, G. Linstrumelle, Tetrahedron Lett. 34
(1993) 6403.
Acknowledgement
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Eur. J. Org. Chem. (2004) 366.
This work has been supported by the Centre
National de la Recherche Scientifique (UMR CNRS-
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tetrachloropalladate.
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