PdCl2(SEt2)2 and Pd(OAc)2: Simple and efficient catalyst precursors for the Suzuki cross-coupling reaction

Article abstract of DOI:10.1016/S0040-4039(00)01472-6

PdCl₂(SEt₂)₂ and Pd(OAc)₂ efficiently promote the cross-coupling of aryl bromides and chlorides with arylboronic acids under mild reaction conditions. These methods tolerate a variety of functional groups and represent, from a synthetic point of view, two of the simplest catalyst precursors that mediate the Suzuki cross-coupling reaction at room temperature. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01472-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 8199–8202
PdCl2(SEt2)2 and Pd(OAc)2: simple and efficient catalyst
precursors for the Suzuki cross-coupling reaction
Danilo Zim, Adriano L. Monteiro and Ja¨ırton Dupont*
Laboratory of Molecular Catalysis, Instituto de Qu´ımica, UFRGS. Av. Bento Gonc¸alves, 9500,
Porto Alegre 91501-970 RS, Brazil
Received 17 August 2000; revised 1 September 2000; accepted 5 September 2000
Abstract
PdCl2(SEt2)2 and Pd(OAc)2 efficiently promote the cross-coupling of aryl bromides and chlorides with
arylboronic acids under mild reaction conditions. These methods tolerate a variety of functional groups
and represent, from a synthetic point of view, two of the simplest catalyst precursors that mediate the
Suzuki cross-coupling reaction at room temperature. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: coupling reactions; palladium catalysts; Suzuki; boronic acids; aryl halides.
The palladium-catalysed Suzuki cross-coupling reaction is one of the most efficient methods
for the construction of carbonꢀcarbon (sp2–sp2) bonds.1 Almost any Pd(II) or Pd(0) derivative,
usually associated with phosphine ligands, promotes this coupling reaction involving aryl iodides
or aryl bromides, substituted with electron-withdrawing groups, in high turnover numbers.2
However, in the case of the less reactive aryl chlorides and electron-rich aryl bromides, the
presence of added ligands is necessary to effectively promote these reactions. In this respect
Pd(II) and/or Pd(0) associated with electron-rich and sterically-demanding phosphines,3 imida-
zole carbenes4 and palladacycles,5 are amongst the most active catalyst precursors that operate
under relatively mild reaction conditions. While investigating the use of sulfur-containing
palladacycles6 as catalyst precursors for Suzuki5e coupling we have observed, in control
experiments, that simple complexes such as Pd(OAc)2 and PdCl2(SEt2)2 also generate catalytic
active species for this coupling reaction. We wish to report that commercially available
palladium acetate and the simple sulfur-containing palladium complex PdCl2(SEt2)2, which is
easy to make, thermally stable and insensitive to air and moisture, can be used in the Suzuki
coupling reaction of various aryl halides at room temperature.
PdCl2(SEt2)2 is easily and quantitatively prepared by simply adding 2.5 molar excess of SEt2
to a solution of sodium tetrachloropalladate at room temperature, using a procedure similar to
that described for the analogous platinum(II) complex.7
* Corresponding author. E-mail: dupont@iq.ufrgs.br
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01472-6

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Based on our recent success with sulfur-containing palladacycles as catalyst precursors in
Suzuki coupling reactions of aryl halides, we employed the same experimental protocol.5e In
initial experiments, DMF was chosen as the solvent and potassium phosphate as the base for the
reaction of 4-bromotoluene with phenylboronic acid (Scheme 1) at 130°C using PdCl2(SEt2)2 or
Pd(OAc)2 as catalyst precursors (entries 1–4, Table 1).
Scheme 1. Suzuki cross-coupling reaction
It is clear from entries 1–4 (Table 1) that the salt additive N(n-Bu)4Br has a beneficial effect
in the case of Pd(OAc)2 and no significant effect when using PdCl2(SEt2)2. The role of this
additive in these systems in not well understood but it is believed that it is involved in the
stabilisation of anionic palladium species such as [BrꢀPdꢀligand]−.8 At the moment we cannot
offer a definitive explanation for the different effect of the salt in each case and investigations
in this direction are currently underway in our laboratory.
Table 1
Suzuki reaction between phenylboronic acid and aryl halides (Scheme 1a)
Entry
ArX
[Pd] (%)
N(n-Bu)4Br %
T/°C
Time/h
Yield/%b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
4-MeC6H4Br
4-MeC6H4Br
4-MeC6H4Br
4-MeC6H4Br
4-MeOC6H4Br
4-MeOC6H4Br
4-MeC6H4Br
2,4-Me2C6H3Br
4-CNC6H4Cl
2,4-Me2C6H3Brd
4-MeOC6H4Br
4-MeOC6H4Br
4-MeC6H4Br
4-MeC6H4Br
1-BrC10H7
PdCl2(SEt)2 (0.02)
Pd(OAc)2 (0.02)
PdCl2(SEt)2 (0.02)
Pd(OAc)2 (0.02)
PdCl2(SEt)2 (0.2)
PdCl2(SEt)2 (0.2)
PdCl2(SEt)2 (0.2)
PdCl2(SEt)2 (0.2)
PdCl2(SEt)2 (0.2)
PdCl2(SEt)2 (0.2)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
Pd(OAc)2 (0.5)
0.2
0.2
130
130
130
130
130
25
1
1
1
41
76
63
51
1
62
96
62
62
96
62
87
2
87
2
87
2
87
2
2
2
87
2
100 (87)c
100 (91)c
100 (92)c
72
25
25
130
130
25
130
25
130
25
130
25
130
130
130
25
130
25
100 (48)c
68
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.2
100 (94)c
94
100 (92)c
100
100
100
1-BrC10H7
4-NO2C6H4Br
4-NO2C6H4Br
3-CF3C6H4Br
4-PhC6H4Br
4-NCC6H4Cl
4-NCC6H4Cl
4-NO2C6H4Cl
4-NO2C6H4Cl
100 (93)c
100 (95)c
100
100
94
85
87
2
100 (92)c
100
130
a Reaction conditions: DMF, K3PO4 (2.0 equivalents).
b GC yield using undecane as internal standard.
c Isolated yield.
d Using 2-tolylboronic acid instead of phenylboronic acid.

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Under this experimental protocol (DMF, K3PO4), PdCl2(SEt2)2 (0.2%) efficiently promotes the
coupling of aryl bromides (containing electron withdrawing or donating groups) and electron
poor aryl chlorides with phenyl boronic acid leading to bis-aryls in high yields (>90%). Note that
this cross-coupling reaction can be performed at room temperature, although longer reaction
times are required compared to those at 130°C (see entries 5–10, Table 1). However, in the case
of electron-rich or electron-neutral aryl chlorides this catalytic system failed under these reaction
conditions.
More interestingly, palladium acetate can be also used in these coupling reactions giving
biaryls in high isolated yields (see entries 11–24). It is noteworthy that aryl iodides and activated
aryl bromides have been coupled with arylboronic acids at room temperature using Pd(OAc)2 in
aqueous media.9 In addition, we found that Pd(OAc)2 in DMF is active in the Suzuki coupling
of neutral and electron-rich arylbromides and even activated aryl chlorides. The reaction can be
performed at room temperature and various functional groups in the aryl halide can be
tolerated.
From an 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 K3PO4 (424 mg, 2.0
mmol), boronic acid (183 mg, 1.5 mmol), and additive N(n-Bu)4Br (64.5 mg, 0.2 mmol). The
flask was evacuated and back-filled with argon and then the aryl halide (1.0 mmol) and a
solution of Pd(OAc)2 (1.12 mg, 0.005 mmol) in 5 mL of dimethylformamide were added. The
reaction mixture was stirred at room temperature until the starting aryl halide had been
completely consumed, as judged by GC analysis. Palladium black was only observed visually in
the reactions performed using more than 0.5% on palladium. 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, the solvent was evaporated to give the respective product, which
1
was characterised by GCMS, H and 13C NMR.
In summary we have shown that under the appropriate reaction conditions, commercially
available palladium acetate effectively promotes the Suzuki cross-coupling reaction of aryl-
boronic acids with various aryl halides (except for electron neutral and rich aryl chlorides). This
is the simplest palladium catalyst system for the generation of biaryls reported to date.
Moreover, these results suggest that only electron neutral and rich aryl chlorides should be used
as benchmarks for testing new palladium catalysts for Suzuki coupling.
Acknowledgements
This work was supported by grants from the PADCT-CNPq and FAPERGS. Help from Dr.
J. Spencer (TRI, England) in the proof reading of the manuscript is greatly appreciated.
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