On the use of phosphine-free PdCl2(SEt2)2 complex as catalyst precursor for the Heck reaction

Article abstract of DOI:10.1016/S0040-4039(01)01590-8

A simple and efficient experimental protocol has been developed for the catalytic arylation of alkenes by the air and water stable, and phosphine-free compound PdCl₂(SEt₂)₂ associated with tetrabutyl ammonium bromide. Using this catalytic protocol, aryl iodides and bromides, and electron-poor aryl chlorides are coupled with n-butylacrylate and styrene under relatively mild reaction conditions with high catalytic activity. Reaction vessel ultra-trace amounts (ppt) of this Pd precursor promotes the coupling of iodo benzene with n-butylacrylate with turnover numbers (mol product/mol Pd) up to 10⁹.

Full text of DOI:10.1016/S0040-4039(01)01590-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7345–7348
On the use of phosphine-free PdCl2(SEt2)2 complex as catalyst
precursor for the Heck reaction
Adriane S. Gruber, Dirce Pozebon, Adriano L. Monteiro and Ja¨ırton Dupont*
Laboratory of Molecular Catalysis, IQ-UFRGS. Av. Bento Gonc¸alves, 9500 Porto Alegre, 91501-970 RS, Brazil
Received 18 July 2001; revised 23 August 2001; accepted 28 August 2001
Abstract—A simple and efficient experimental protocol has been developed for the catalytic arylation of alkenes by the air and
water stable, and phosphine-free compound PdCl2(SEt2)2 associated with tetrabutyl ammonium bromide. Using this catalytic
protocol, aryl iodides and bromides, and electron-poor aryl chlorides are coupled with n-butylacrylate and styrene under relatively
mild reaction conditions with high catalytic activity. Reaction vessel ultra-trace amounts (ppt) of this Pd precursor promotes the
coupling of iodo benzene with n-butylacrylate with turnover numbers (mol product/mol Pd) up to 109. © 2001 Elsevier Science
Ltd. All rights reserved.
The arylation and vinylation of alkenes (the ‘Heck
reaction’) is one of the most investigated CꢀC coupling
reactions mediated by Pd complexes. The coupling of
aryl iodides and electron-poor aryl bromides with alke-
nes can be catalyzed by almost any Pd(0) or Pd(II)
catalyst precursor under relatively mild reaction condi-
tions and in high turnover numbers (TON). Even lig-
and-less Pd(OAc)2 is an effective catalyst precursor to
promote the coupling of aryl iodides with CꢁC double
bonds.1 However, in the case of less reactive aryl chlo-
rides and electron-rich aryl bromides it is believed that
Pd catalyst precursor should be associated with stabiliz-
ing ligands to effective promote these couplings.2 Thus,
Pd complexes associated with bulky and electron rich
phosphines, imidazol carbenes and palladacycles are
able to catalyze the Heck reaction involving these less
activated aryl bromides and chlorides.1–3 For example,
the cyclopalladated complex [PdCl{C6H3(OPiPr2)2-2,6]
promotes the coupling of electron-rich aryl chlorides
such as 4-chloroanisol with styrene in high yields4 and
the use of Pd2(dba)3 associated with P(tBu)3 that allows
the reaction to be conducted at room temperature.5
Moreover, the reaction conditions, such as the tempera-
ture, solvent, the addition of quaternary ammonium
salt additives,6 or running the reaction in ionic liquids
also have a strong influence on the reactivity of the aryl
halides.7 However, the majority of these catalytic sys-
tems involves usually the use of ‘sensitive’ reagents such
as phosphines and carbenes, or the synthesis of ligands
and their Pd complexes. Therefore, the use of these
methods in organic synthesis is not usually straightfor-
ward. We wish to report here that the air and water
stable and easily prepared compound PdCl2(SEt2)2,
when associated with tetra butyl ammonium bromide,
effectively promotes the Heck reaction involving great
part of the substrates (aryl halides and alkenes) gener-
ally used in organic synthesis. Moreover, we note that
even Pd ultra-trace amounts in the reaction vessel cata-
lyze the coupling of aryl iodides and bromides substi-
tuted with electron-withdrawing groups with alkenes.
The air and water stable PdCl2(SEt2)2 complex was
prepared in almost quantitative yield from the reaction
of lithium tetrachloropalladate with diethylsulfide as
described earlier.8
Scheme 1.
* Corresponding author. Tel.: +55 51 33166321; fax: +55 51 33167304; e-mail: dupont@iq.ufrgs.br
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01590-8

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A. S. Gruber et al. / Tetrahedron Letters 42 (2001) 7345–7348
involving electron-neutral or rich aryl chlorides such as
chlorobenzene or chloro anisol. Notwithstanding the
limitations, this is one of the simplest phosphine-free
palladium catalyst precursor to promote the coupling
of aryl iodides, bromides and electron-poor aryl chlo-
rides with alkenes.
Based on our recent success with sulfur-containing pal-
ladacycles as catalyst precursors in Heck coupling reac-
tions of aryl halides, we employed the same
experimental protocol.9 As in early experiments,
dimethylacetamide (DMA) was chosen as the solvent
and sodium acetate as the base for the reaction of aryl
halides with styrene and n-butylacrylate (Scheme 1) at
120°C using PdCl2(SEt2)2 as catalyst precursors (Table
1).
The use of the salt additive [N(nBu)4Br] is essential to
obtain almost complete arylation of the alkenes. For
example, the reaction of iodobenzene and n-butylacry-
late, under the same reaction conditions described in
Table 1, entry 1, only 44% iodo benzene conversion was
observed in the absence of the ammonium salt.
From the experimental point of view, this method is
extremely simple: an oven-dried resealable Schlenk flask
was evacuated and back-filled with argon and charged
with NaOAc (1.4 mmol), alkene (1.2 mmol), and addi-
tive N(tBu)4Br (0.2 mmol). The flask was evacuated and
back-filled with argon and then the aryl halide (1.0
mmol) and a solution of PdCl2(SEt2)2 in 5 mL of DMA
were added. The reaction mixture was stirred at 120°C
for the desired time (Table 1). The solution was then
taken up in ether (20 mL) and washed with aqueous
NaOH (1 M, 5 mL) and brine (2×5 mL), and then dried
over MgSO4. After filtration, solvent was evaporated to
give the respective product, which was characterized by
Electron-withdrawing groups on the aryl ring increase
the reaction rate. For example, in a competitive experi-
ment mediated by PdCl2(SEt2)2 (2×10−4M) the reaction
of 4-fluoroiodoobenzene, iodobenzene, 4-iodotoluene,
and 4-iodoanisol (0.5 mmol each) with styrene (20
mmol) in DMA (5 mL) at 120°C gave after 30 min the
trans-substituted stilbenes (4-fluorophenyl, phenyl, 4-
methylphenyl, 4-methoxyphenyl) in a proportion of
15:10:8.5:7.7, respectively. This trend is similar to those
observed for the majority of the palladium catalyst
precursors associated or not with phosphine ligands,
suggesting that the aryl halide oxidative addition is the
rate-determining step.1,2 Moreover, these results also
suggest that PdCl2(SEt2)2 acts as reservoir of Pd(0)
catalytic active species.10
1
GC–MS, H and 13C NMR.
As shown in Table 1, PdCl2(SEt)2 generates catalytic
active species for the arylation of styrene and n-butyl
acrylate with aryl iodides, bromides and chlorides acti-
vated with electron withdrawing groups. However,
higher palladium concentrations (0.1 mol%) need to be
used in the case of electron neutral and rich aryl
bromides and electron-poor aryl chlorides in order to
obtain good yields in reasonable reaction times. This
catalytic system fails to promote the Heck reaction
This catalyst system is not sensitive to oxygen and
water, and the reaction can be carried out in air, with
no change in efficiency. For example, the reaction of
4-chloroacetophenone with and styrene, under the same
a
Table 1. Heck reaction between alkenes and aryl halides catalyzed by PdCl2(SEt2)2 (Scheme 1)
Entry
ArX
Alkened
[Pd] (mmol)
T (°C)
Time (h)
Yield (%)b
TONc
1
2
3
4
5
6
7
8
PhI
PhI
PhI
PhI
4-MeC6H4I
4-MeC6H4I
4-MeOC6H4I
4-MeOC6H4I
PhBr
Acrylate
Acrylate
Styrene
Styrene
Acrylate
Styrene
Acrylate
Styrene
Acrylate
Styrene
Acrylate
Styrene
Acrylate
Styrene
Acrylate
Styrene
Acrylate
Styrene
Styrene
Acrylate
2×10−5
2×10−6
2×10−5
2×10−6
2×10−5
2×10−5
2×10−5
2×10−5
1×10-3
120
120
120
120
120
120
120
120
120
150
150
150
120
120
120
120
120
120
120
150
20
50
23
240
20
23
20
23
24
24
24
24
69
27
39
16
48
92
92
22
100
100
71
70
100
98
100
90
45
76
65
38
72
80
98
100
88
95
87
91
50,000
500,000
45,000
350,000
50,000
49,000
50,000
45,000
450
760
650
380
36,000
40,000
49,000
50,000
880
9
10
11
12
13
14
15
16
17
18
19
20
PhBr
1×10−3
1×10−3
1×10−3
2×10−5
2×10−5
2×10−5
2×10−5
1×10−3
1×10−3
1×10−3
1×10−3
4-MeOC6H4Br
4-MeOC6H4Br
4-ClC6H4Br
4-ClC6H4Br
4-MeCOC6H4Br
4-MeCOC6H4Br
4-CNC6H4Cl
4-CNC6H4Cl
4-MeCOC6H4Cl
4-NO2C6H4Cl
950
870
910
a Reaction conditions: DMA (5 mL), NaOAc (1.4 mmol), alkene (1.2 mmol) ArX (1 mmol) and N(nBu)4Br (0.2 mmol).
b GC yield (using undecane as internal standard). Isolated yields after extraction and purification were usually 5–10% lower. trans-Stilbenes were
obtained almost exclusively in the reactions involving styrene.
c TON (mol product/mol of Pd).
d Acrylate=n-butylacrylate.

A. S. Gruber et al. / Tetrahedron Letters 42 (2001) 7345–7348
7347
our results show that even palladium ultra-traces pro-
mote the Heck reaction involving aryl iodides and
bromides substituted with electron withdrawing groups
and therefore, these substrates should be not employed
as benchmarks for testing the catalytic activity of new
Pd catalyst precursors.
Acknowledgements
This work was supported by grants from the CNPq and
FAPERGS (Brazil).
Figure 1. PhI conversion (determined GC using undecane as
internal standard) in the arylation of n-butylacrylate and
styrene promoted by PdCl2(SEt2)2 (2×10−6 mmol) and by the
‘reaction vessel’ Pd catalyst. Reaction conditions: PhI (1.0
mmol) olefin (1.2 mmol); NaOAc (1.4 mmol); DMA (5 mL);
120°C; ꢀ=PdCl2(SEt2)2, n-butylacrylate; ꢁ=washed reac-
tion vessel from reaction ꢀ; ꢂ=PdCl2(SEt2)2, styrene; ꢃ=
washed reaction vessel from reaction ꢂ.
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reaction conditions described in Table 1, entry 19, a
84% arylhalide conversion was observed in the presence
air. Only in cases where catalyst concentrations are
lower than 2×10−5 M should the purified aryl halides
and the olefins be used and the reaction conducted in
an inert atmosphere (N2 or Ar). While investigating the
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(using new resealable Schlenk tube and a new Teflon
coated stirring bar) the ‘washed’ reaction vessel is still
active for the Heck reaction. Thus, after the quantita-
tive arylation of methylacrylate by iodobenzene cata-
lyzed by PdCl2(SEt2)2 ([Pd]/PhI=1/500000) the reaction
vessel and the magnetic stirring bar were washed with
water (3×5 mL) and acetone (3×5 mL) and oven-dried
(1 h). A new loading of reagents: PhI (1 mmol), triethyl-
amine (1.4 mmol) and n-butylacrylate (1.2 mmol) in
DMA (5 mL) were introduced in this ‘washed’ reaction
vessel. After 1 h at 130°C, 20% PhI conversion was
observed. A similar behavior was observed using sty-
rene instead n-butylacrylate (Fig. 1).
3. For a review on the use of palladacycles in homogeneous
catalysis, see: Dupont, J.; Pfeffer, M.; Spencer, J. Eur. J.
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The ‘reaction vessel catalytic activity’ was only sup-
pressed (for Heck-type reactions involving iodo-arenes
or bromo-arenes substituted with electron-withdrawing
groups) when the glass-reaction tube was washed with
aqua regia (3×15 mL), sodium hydroxide (3×15 mL (1
M)), water (3×15 mL) and acetone (3×15 mL) before
being oven-dried (1 h).11 The residual Pd levels have
been measured by ICP-MS analysis of the reaction
vessel and the magnetic stirring bar to be of the order
of 0.05 ppb of Pd (2.3×10−9 mmol of Pd) from an initial
Pd loading of 43 ppb (2×10−6 mmol of Pd) after the
first run and water/acetone washes. These results clearly
show that ultra-trace12 amounts of Pd can promote
these coupling reactions giving an estimated TON of
1×109.13,14
11. Note that Pd on porous glass is an effective heteroge-
neous catalyst for the liquid-phase Heck coupling of
iodobenzene or 4-bromoacetophenone with alkenes: Li,
J.; Mau, A. W.-H.; Strauss, C. R. Chem. Commun. 1997,
1275.
In summary PdCl2(SEt2)2 is an effective catalyst precur-
sor for the Heck reaction involving most aryl halides
(except for electron neutral and rich aryl chlorides)
under relatively mild reaction conditions. Moreover,

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A. S. Gruber et al. / Tetrahedron Letters 42 (2001) 7345–7348
12. The relative component content of a sample is classified
as: major (1–100%), minor (0.01–1%), or trace (less than
0.01%) to ultra-trace (ppb or less). Rubinson, J. F.;
Rubinson, K. A. Contemporary Chemical Analysis, Pren-
tice Hall, Upper Saddle River: NJ, 1998, Chapter 5, pp.
141–143.
norbornene with PhI. (a) Miyazaki, F.; Yamaguchi, K.;
Shibaski, M. Tetrahedron Lett. 1999, 40, 7379; (b) Brunel,
J. M.; Heumann, A.; Buono, G. Angew. Chem., Int. Ed.
2000, 39, 1946.
14. Similar ‘reaction vessel catalytic activities’ were observed
in the Heck reactions promoted by sulfur-containing
palladacycles: Zim, D.; Monteiro, A. L.; Dupont, J.,
unpublished results.
13. TON’s up to 1010 have been reported for the reaction of
PhI with n-butyl acrylate and for the hydro-arylation of