[{Pd(μ-OH)Cl(IPr)}2]—A Highly Efficient Precatalyst for Suzuki–Miyaura Coupling also Able To Act under Base-Free Conditions

Article abstract of DOI:10.1002/cctc.201600998

[{Pd(μ-OH)Cl(IPr)}₂] [IPr=N,N-bis(2,6-diisopropylphenyl)imidazol-2-ylidene] was found to be a highly efficient precatalyst for Suzuki–Miyaura coupling that is able to act under base-free conditions.

Full text of DOI:10.1002/cctc.201600998

Accepted Article
Title: [{Pd(µ-OH)Cl(IPr)}2] - a highly efficient precatalyst of Suzuki -
Miyaura coupling, able to act also under base-free conditions
Authors: Sylwia Ostrowska, Jan Lorkowski, Maciej Kubicki, and Cezary
Pietraszuk
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To be cited as: ChemCatChem 10.1002/cctc.201600998
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10.1002/cctc.201600998
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COMMUNICATION
[{Pd(µ–OH)Cl(IPr)}2] – a highly efficient precatalyst of Suzuki –
Miyaura coupling, able to act also under base-free conditions
Sylwia Ostrowska, Jan Lorkowski, Maciej Kubicki, Cezary Pietraszuk*
Abstract: [{Pd(µ–OH)Cl(IPr)}2] (IPr = N,N-bis(2,6-diisopropylphenyl)
imidazol-2-ylidene) has been found a highly efficient precatalyst of
Suzuki–Miyaura coupling able to act also under base-free conditions.
base is used in twofold molar excess in relation to the palladium
(SI, Table S1).
To identify the hydroxide-bearing palladium complexes
possibly generated in the course of SM coupling, the reaction of
PEPPSI-IPr (2) with KOH was monitored by 1H NMR
spectroscopy. Treatment of a solution of PEPPSI-IPr with 4
equiv. of KOH resulted in gradual formation of a new complex (a
new singlet at  = 6.35 ppm assigned to olefinic proton of IPr
and a singlet at  = -3.93 ppm). Single crystal obtained from the
reaction mixture was found to be co-crystal of PEPPSI-IPr (2)
and hydroxide dimer [{Pd(µ-OH)Cl(IPr)}2] (1) (Figure S5). The
results indicate that the reaction proceeds according to Scheme
2.
N-Heterocyclic carbenes due to their valuable properties have
become universal ligands in organometallic catalysis.[1] Since
their first application in transition metal catalysis[2]
unprecedented advances have been made in designing of active
NHC-based Pd precatalysts of a variety of coupling processes.[3]
From among these processes, the Suzuki–Miyaura (SM) cross-
coupling is one of the most frequently used in organic
synthesis.[4] Presently, a number of NHC palladium complexes,
including
family
of
[PdCl2(NHC)(pyridine)]
(PEPPSI)
precatalysts,[5] analogues bearing various throw away ligand[6]
and related dimeric complexes [{Pd(µ-Cl)(Cl)(NHC)}2][7] have
been reported to be excellent precatalyst for the Suzuki–Miyaura
coupling.[6b,c, 8]
IPr
H
Cl Pd Cl
N
Cl
Pd
O
PrI
Cl
KOH (4 equiv.)
Pd
- KCl
O
H
IPr
Herein, we report a new NHC palladium hydroxide
complex [{Pd(µ–OH)Cl(IPr)}2] (1) exhibiting high productivity and
activity in Suzuki-Miyaura coupling of chloroarenes with
arylboronic acids and able to act in base-free conditions. The
aim of our study was to design and obtain a catalyst of possibly
the highest activity and efficiency, rather than the one allowing
multiple use. This approach has been earlier suggested in
literature by Gladysz[9a] and recently discussed and supported by
Hubner, de Vries and Farina.[9b]
C6D6, 80 °C, 12 h, H2O
Cl
2
1 yield = 53%
Scheme 2. Reaction of PEPPSI-IPr with KOH
Hydroxide complex 1, being most likely the product of PEPPSI-
IPr activation by hydroxides, was synthesized with an almost
quantitative isolated yield (95%) by treatment of chloride dimer
[{Pd(µ-Cl)Cl(IPr)}2] (3) with an excess of KOH (Scheme 3). Its
structure was confirmed X-ray diffraction (Figure 1).
Beneficial effect of hydroxides on the SM reaction[8a,10,11]
has inspired us to search for precatalysts containing hydroxide
ligand in the coordination sphere. In the preliminary studies we
Scheme 1. SM coupling of chlorobenzene with tolylboronic acid
Scheme 3. Synthesis of [{Pd(µ-OH)Cl(IPr)}2]
The activities of complexes 1, 2 and 3 were compared in a SM
coupling of chlorobenzene with tolylboronic acid (Table 1).
Unlike the other catalysts, complex 1 shows catalytic activity in
base-free conditions (entry 1). The use of low concentrations of
KOH (entries 2, 5 and 8) allows effective course of the reaction
for all catalysts tested. Another slight increase in the reaction
yield was observed when using a high excess of KOH (entries 3,
6, 9). Reactions performed in a base-free conditions or at low
base concentration were nearly completely ceased when air-free
conditions were used (entries 2, 5 and 8).
Sylwia Ostrowska, Jan Lorkowski, Maciej Kubicki, Cezary Pietraszuk
Adam Mickiewicz University in Poznań, Faculty of Chemistry,
Umultowska 89b, 61-614 Poznań, Poland
e-mail: pietrasz@amu.edu.pl
Supporting information for this article is given via a link at the end of the
document.
found that SM coupling of tolylboronic acid with chlorobenzene
(Scheme 1) performed in air, in the presence of [PdCl2(IPr)(3-
chloropyridine)] (2) or the chloride dimer [{Pd(µ-Cl)(Cl)(IPr)}2] (3)
in mild reaction conditions[8b], proceeds efficiently even when the
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9
2-thienyl
phenyl
97
10
11
2,6-dimethylphenyl
phenyl
2,6-dimethylphenyl
(E)-(4-methylstyryl)
88b
93b
Reaction conditions: EtOH, 22 °C, 24 h, air, cat.
1
(0.001 mol%);
[ArCl]:[Ar’B(OH)2]:[KOH] =1.0 : 1.25 : 1.3; a) isolated yield; b) cat. 1 0.01 mol%;
[{Pd(μ-OH)Cl(IPr)}2] (1) has been tested in a number of SM
reactions involving challenging substrates such as 2-
chloropyridine or 2-chloro-1,3-dimethylbenzene and proves
highly active in low concentration and under mild reaction
conditions (Table 2). The studies aimed at optimization of the
catalyst loadings (Table 3) revealed that complex 1 used in
KOH-free conditions allows effective course of the reaction in
concentrations up to 0.1 mol% (entry 2). The maximum values of
TON and TOF obtained in the absence of the base were 710
and 530 h-1, respectively. The addition of twofold molar excess
of KOH relative to palladium enables tenfold reduction in the
catalyst concentration and ensures TON = 7.9 × 103 and TOF =
5.6 × 103 h-1 (entry 5). However, under the conditions typically
used in the SM coupling ([KOH] [ArB(OH)2] = 1 : 1) (entries 6 -
10) catalyst 1 remains active even at concentrations below 1
ppm and can achieve values of TON exceeding 106 and TOF
reaching 5.3 × 106 h-1 (entry 10).
Figure 1. Perspective view of a binuclear complex 1. Ellipsoids are drawn at
the 30% probability level, hydrogen atoms are shown as spheres of arbitrary
radii
Table 1. SM coupling of chlorobenzene with tolylboronic acids in the presence
of complexes 1, 2 and 3. Effect of KOH concentration
Entry
Cat.
1
[KOH] : [Pd]
Yielda [%]
1
2
3
4
5
6
7
8
9
0
72 (5b)
94 (5b)
96 (95b)
0
1
2:1
130:1
0
1
Table 3. SM coupling of chlorobenzene with tolylboronic acids. Optimization of
the catalyst 1 loading
2
90 (3b)
94 (92b)
0
2
2:1
130:1
0
Entry
1 [mol %]
[KOH]:[Pd]
0
Yielda of 6 [%]
2
1
2
3
4
5
6
7
8
9
10
1
88
71b
98
3
0.1
0
85 (5b)
87 (83b)
3
2:1
130:1
1
2:1
3
0.1
2:1
95
Reaction conditions: [Pd] (1 mol%), EtOH, 22 °C,
6
h, air,
79b
99
[ArCl]:[Ar’B(OH)2]:[KOH] = 1 : 1.25 : 1.3; a) isolated yield; b) air-free conditions
0.01
2:1
0.1
1.3 × 103 : 1
1.3 × 104 : 1
1.3 × 105 : 1
1.3 × 106 : 1
1.3 × 107 : 1
Table 2. SM coupling of aryl chlorides with boronic acids in the presence of 1
0.01
95
0.001
92
0.0001 (1 ppm)
91
Entry
Ar
R
Yielda [%]
74b, 53c
0.00001
1
2
3
4
5
6
7
8
phenyl
tolyl
tolyl
tolyl
tolyl
tolyl
tolyl
tolyl
tolyl
99
98
99
78
91
82
86
98
(0.1 ppm)
4-methoxyphenyl
4-acetylphenyl
2-anthracenyl
2-methylphenyl
2-pyridyl
a)
Reaction conditions: EtOH, 24 h, 22 °C, air, [C6H5Cl]:[ArB(OH)2] = 1:1.25;
yield calculated on the basis of GC analysis; b) 40 °C; c) 1 h
Transmetalation followed by reductive elimination is a
probable method of reduction of precatalyst 1 to a catalytically
active palladium(0) complex. Complex 1, thanks to the presence
of hydroxide and chloride ligands in the coordination sphere is
potentially able to undergo transmetalation via two different
pathways, that is via reaction of hydroxide ligand with
arylboronic acid and via reaction of chloride ligand with
trihydroxoboronate derivative [ArB(OH)3]X (Scheme 4).
3-pyridyl
2-thienyl
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systems and preliminary mechanisms explaining the activating
role of oxygen have recently been summarised.[15] The possible
activating role of oxygen in the systems based on N-heterocyclic
carbene complexes has not been studied, although many of
these systems show high activity in aerobic conditions. The
understanding of catalytic activity of 1 in base-free conditions
(this activity is much lower than that in the presence of excess of
the base) needs further studies. Although precatalyst 1, (unlike
complexes 2 and 3) is able to generate the active Pd(0) species
in base-free conditions (Scheme 4), the absence of the base
makes the transmetalation step in catalytic cycle impossible to
take place. We assume that in such conditions the active Pd(0)
complexes undergo two types of oxidative additions, i.e., the
oxidative addition of aryl halide (according to the commonly
accepted mechanism) and oxidative addition of C-B bond of
boronic acid, described by Moreno-Manas.[16] Formation of
unsymmetrical biaryls via reductive elimination requires earlier
formation of suitable dimeric complexes.
In conclusion, NHC palladium hydroxide complex [{Pd(µ–
OH)Cl(IPr)}2] (1), exhibits high catalytic activity in Suzuki–
Miyaura coupling at catalyst loadings down to 0.1 ppm.
Scheme 4. Proposed pathways of generation of active Pd(0) species from
precatalyst 1 via transmetalation
Acknowledgments
Indeed, the reaction of 1 with a fivefold excess of
tolylboronic acid (5) performed in EtOH at 22 °C afforded after 1
h the product 7 in 48% yield as observed by GC, and the
The research was co-financed by the National Centre for
Research and Development (NCBR) under the Project
ORGANOMET No: PBS2/A5/40/2014.
reaction of
1
with potassium tolyltrihydroxyborate (8)[12]
performed in the same conditions gave 7 in 12% yield (Figure
S2). This result confirmed contributions of both pathways in the
reduction of precatalyst 1.
Keywords: Suzuki-Miyaura coupling • palladium catalysis • NHC
complexes • hydroxide complexes • homogeneous catalysis
As the catalytic reactions initiated by 1, 2 and 3 are ac-
companied by the formation of fine black solid, the possibility of
the SM reaction to take place in the systems studied under
heterogeneous catalytic conditions was checked. For this
purpose, for the reaction of chlorobenzene coupling with
tolylboronic acid in the presence of catalysts 1, 2 and 3, the
mercury poisoning experiments[13] were performed. Additional
test was carried out for catalyst 1 in base-free conditions. There
was no reduction in activity of any of the catalysts tested in the
presence of mercury excess (Figure S3). The fine solid formed
in the test reaction (EtOH, 22°C, [ArCl]:[ArB(OH)2]:[Pd]:[KOH] =
1/1.25/1×10-2/2×10-2) was isolated and characterised by
transmission electron microscopy (TEM). The analysis showed
that the solid was made of palladium nanoparticles of 2.3 - 3.1
nm in diameter (Figure S4). Their catalytic activity was tested in
the reaction of chlorobenzene with tolylboronic acid under typical
reaction conditions, both at 22 °C and at the reflux temperature.
Complete catalytic inactivity was observed. These results
strongly suggest that the studied reaction runs under the
homogeneous catalytic conditions.
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[{Pd(µ–OH)Cl(IPr)}2]
Sylwia Ostrowska, Jan
Lorkowski, Maciej Kubicki,
Cezary Pietraszuk*
exhibits high activity in
Suzuki–Miyaura coupling
at catalyst loadings down
to 0.1 ppm and can also
act in base-free conditions
Page No. – Page No.
[{Pd(µ–OH)Cl(IPr)}2] – a
highly efficient
precatalyst of Suzuki –
Miyaura coupling, able to
act also under base-free
conditions.
This article is protected by copyright. All rights reserved.