Application of ortho-palladated homoveratrylamine complex containing mixed phosphorus-nitrogen donors in the Suzuki reaction

Article abstract of DOI:10.1002/aoc.2882

The catalytic activity of [Pd{C₆H₂(CH ₂CH₂NH₂)-(OMe)₂,3,4}Br(PPh ₃)] monomeric ortho-palladated complex of homoveratrylamine and triphenylphosphine was investigated in the Suzuki cross-coupling reaction of various aryl halides with aryl boronic acids. The substituted biaryls were produced in excellent yields using a catalytic amount of this complex in ethanol at 60°C.

Full text of DOI:10.1002/aoc.2882

Full Paper
Received: 4 March 2012
Revised: 18 April 2012
Accepted: 18 April 2012
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.2882
Application of ortho-palladated
homoveratrylamine complex containing
mixed phosphorus–nitrogen donors in
the Suzuki reaction
a,b*
a
a
Abdol R. Hajipour , Hannaneh Rahimi and Fatemeh Rafiee
6 2 2 2 2 2 3
The catalytic activity of [Pd{C H (CH CH NH )-(OMe) ,3,4}Br(PPh )] monomeric ortho-palladated complex of homoveratrylamine
and triphenylphosphine was investigated in the Suzuki cross-coupling reaction of various aryl halides with aryl boronic acids.
ꢀ
The substituted biaryls were produced in excellent yields using a catalytic amount of this complex in ethanol at 60 C. Copyright
©
2012 John Wiley & Sons, Ltd.
Keywords: Suzuki reaction; catalyst; ortho-palladated complex; triphenylphosphine
[
25]
was prepared according to our previous work.
The acetate-
Introduction
bridged ortho-palladated complex was obtained from homovera-
The palladium-catalyzed cross-coupling of nucleophilic organborans
with electrophilic organic halides and triflates, known as the Suzuki
reaction, has emerged as a powerful and versatile tool for the syn-
trylamine by addition of Pd(OAc) in acetonitrile as a binuclear
complex. The halogen-bridged ortho-palladated complex was
2
prepared by the addition of NaBr to a solution of the acetate-
bridged complex in acetone. Addition of triphenylphosphine to
this dimeric ortho-palladated complex [Pd{C H (CH CH NH )–
[
1–5]
thesis of substituted biaryls.
block for a wide range of herbicides, pharmaceuticals, natural
Biaryls are applied as the building
[
6]
[7]
6
2
2
2
2
[
8]
[9]
and bioactive products, microelectrode arrays, conducting
(OMe) ,3,4}(m-Br)]2 in dichloromethane gave the monomeric
2
[
10]
polymers, and liquid crystal materials.
The key benefits of
ortho-palladated complex [Pd{C H (CH CH NH )-(OMe) ,3,4}Br(PPh )].
6
2
2
2
2
2
3
the Suzuki–Miyaura coupling are the mild reaction conditions,
tolerance of a broad range of functionalities, commercial availabil-
ity and easy handling of organoboron reagents, and removal of
Homoveratrylamine as an N-donor ligand is an available and
inexpensive amine. The ortho-palladation reaction of this sub-
strate is simple and leads to an efficient catalyst for coupling
reactions. Homoveratrylamine in combination with triphenylpho-
sphine ligand gave monomeric complex. The monomeric
complex containing mixed phosphorus–nitrogen (P–N) donors
was found to be more active than the corresponding dimeric
one, which contains only a single nitrogen donor especially for
unreactive aryl halides or even aryl chlorides, which are available
and cheap substrates. The monomeric complexes are easier to
reduce to the active Pd(0) species compared with the dimeric
[
11,12]
the nontoxic boron-containing byproducts.
In view of the
importance of biaryls, a number of effective palladium catalytic
systems have been developed for the Suzuki cross-coupling
reaction. Among the new methods the palladacycle catalysts
are the most important classes, used very efficiently in catalysis
[
13–16]
at very low concentration in organic synthesis,
material
[17]
[18]
science, biologically active compounds and macromolecular
[19–21]
chemistry.
The high productivity of the palladacycle cata-
[
35]
lysts is due to the slow generation of low ligated Pd(0) complexes
catalyst.
Herein, the efficiency of monomeric complex is
[
22,23]
from a stable palladium(II) pre-catalyst.
evaluated in the Suzuki cross-coupling reaction (Scheme 1).
Initially, to determine the optimal conditions, Suzuki cross-
coupling reaction was carried out between 4-iodoanisole and
phenylboronic acid using monomeric ortho-palladated complex
in different solvents and bases as shown in Table 1.
In continuation of our recent investigations on the synthesis
and application of palladacycle complexes in cross-coupling reac-
[
24–34]
tions,
CH CH
we now wish to report the extension of the [Pd{C
6 2
H
(
2
2
NH
2
)–(OMe) ,3,4}Br(PPh )] monomeric ortho-palladate
2
3
complex for the cross-coupling reaction of various aryl halides
with aryl boronic acids.
*
Correspondence to: Abdol R. Hajipour, Pharmaceutical Research Laboratory,
Department of Chemistry, Isfahan, University of Technology, Isfahan 84156,
IR Iran. E-mail: haji@cc.iut.ac.ira
Results and Discussion
A suitable chemical production process via palladium catalysis
requires high catalyst productivity and activity. Also the availability
and cost of catalysts and the price of the organic starting materials
are of great importance for industrial processes. Monomeric ortho-
palladated complex [Pd{C H (CH CH NH )–(OMe) ,3,4}Br(PPh )]
a Pharmaceutical Research Laboratory, Department of Chemistry, Isfahan,
University of Technology, Isfahan, 84156, IR Iran
b Department of Pharmacology, University of Wisconsin, Medical School, Madison,
WI 53706-1532, USA
6
2
2
2
2
2
3
Appl. Organometal. Chem. (2012)
Copyright © 2012 John Wiley & Sons, Ltd.

A. R. Hajipour et al.
Scheme 1. The Suzuki cross-coupling reaction by monomeric ortho-palladated complex
Table 1. Optimization of reaction conditions on Suzuki reaction of
Table 2. Optimization of catalyst concentration on the Suzuki reac-
tion of 4-bromobenzonitrile with phenylboronic acid
a
a
4-iodooanisole with phenylboronic acid
b
Entry Solvent
Base Catalyst Temperature Time Conversion
Entry
Catalyst concn (mol%)
Time (h)
Conversion (%)
ꢀ
b
concn
( C)
(h)
(%)
(
mol%)
1
2
3
4
5
6
7
None
0.1
0.2
0.3
0.4
0.5
1
3
0
91
0.8
0.6
1.3
1
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
DMF
EtOH
EtOH
EtOH
EtOH
EtOH
NMP
K
K
K
K
2
2
2
2
CO
CO
CO
CO
3
3
3
3
1
130
60
r.t
1.5
0.7
3.5
1
97
93
89
89
0
100
92
c
c
c
1
1
91
0.5
0.5
0.5
1
60
60
60
130
85
60
75
100
60
60
60
60
60
1
94
—
1
0.5
90
K
K
2
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
0.5
7.5
6
98
44
20
40
70
25
94
66
43
65
10
a
Reaction conditions: 4-bromobenzonitrile (1 mmol), phenylboronic
2
2
2
2
2
acid (1.2 mmol), K
2
CO
3
(2 mmol), monomeric ortho-palladated complex,
Dioxane K
1
ꢀ
EtOH (2 ml), 60 C.
THF
CH CN
K
K
1
12
b
GC yield.
0
1
2
3
4
5
6
3
1
5
Toluene K
1
6
EtOH
EtOH
EtOH
EtOH
EtOH
Cs
Na
2
CO
CO
3
1
0.6
3.5
3
2
3
1
of the procedure was examined using 2-, 3- and 4-bromoacetophe-
none as hindered substituted aryls. Increased hindrance in the
vicinity of the leaving group can cause a decrease in the reaction
conversion (Table 3, entries 10–12). The chemo-selectivity of the
procedure was examined using chlorobromobenzene derivatives
(Table 3, entries 13–16 and 25–27). In these reactions Br acted as
a better leaving group. This catalytic complex was compatible
with a wide range of functional groups such as nitro, cyano,
methoxy, halogen, and carbonyl on aryl halides. As demonstrated
in Table 4 for some of the aryl halides, the monomeric complex (A)
was more active than the dimeric complex (B). In the literature
has been ascribed that difference in the catalytic activity shown
by the monomeric complexes and the dimeric ones resulted
from the triphenylphosphine part. As a result, the monomeric
complexes are easier to be reduced to the active Pd(0) species
compared with the corresponding dimeric ones under the
NaOAc
NaHCO
1
3
1
14
Et
3
N
1
3
a
Reaction conditions: 4-iodooanisole (1 mmol), phenylboronic acid
1.2 mmol), base (2 mmol), monomeric ortho-palladated complex.
(
b
GC yield.
c
base (1 mmol).
As demonstrated in Table 1 (entry 6), K CO as base and ethanol
2
3
as solvent gave the best results. Various catalyst concentrations
were also tested and 0.2 mol% (Table 2, entry 3) gave the best
result. As this catalyst is not sensitive to oxygen, the reactions
were carried out under air atmosphere.
[
35]
same conditions.
We applied the optimized conditions to the Suzuki cross-coupling
reaction of different types of aryl halides with phenylboronic
acids, as shown in Table 3.
Conclusion
As is demonstrated in Table 3, the monomeric ortho-palladated
catalyst can be used for cross-coupling reactions of aryl iodides,
bromides and even less reactive aryl chlorides with aryl boronic
acids in good to excellent yields. We examined the electronic
and steric effects of various aryl halides bearing electron-
donating and electron-withdrawing groups on the resulting
yields and conversion times of the reactions. The substituent
effects in the aryl iodides emerged to be less significant than
in the aryl bromides, and the reactivity of aryl bromides with
electron-withdrawing substituent was higher than that of aryl
bromides with electron-donating substituent. The steric hindrance
We employed monomeric ortho-palladated complex [Pd{C6H2
(CH CH NH )–(OMe) ,3,4}Br(PPh )] as a highly efficient, stable
2
2
2
2
3
catalyst that was non-sensitive to air and moisture was and
easy to prepare for Suzuki reaction of aryl halides with aryl
boronic acids. The Suzuki reaction was carried out under mild
ꢀ
conditions for aryl iodides and aryl bromides at 60 C in ethanol
as green solvent using a catalytic amount of this catalyst. This
catalytic system was also applied for Suzuki cross-coupling of
aryl chlorides that led to C&bond;C bond formation in good to
excellent yields.
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Copyright © 2012 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. (2012)

Application of ortho-palladated homoveratrylamine complex
Table 3. Suzuki cross-coupling reaction using monomeric ortho-palladated complex of homoveratrylamine and triphenylphosphine
b
c
Entry
Ar-X
Boronic agent
Biaryl product
Time (h)
Conversion (%)
Yield (%)
1
2
3
4
5
6
7
8
9
Ph-I
p-MeO-Ph-I
p-O N-Ph-I
N-Ph-I
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
Ph-Ph
p-MeO-Ph-Ph
p-O N-Ph-Ph
m-O N-Ph-Ph
0.2
1.2
1
100
100
100
100
100
100
100
92
90
92
92
89
89
93
86
80
94
90
85
62
93
90
89
88
85
90
80
76
92
95
93
92
91
89
90
2
2
m-O
2
2
1.1
0.25
1.25
1.2
4
Ph-Br
Ph-Ph
p-MeO-Ph-Br
p-MeO-Ph-Ph
p-O
o-O
2
N-Ph-Br
N-Ph-Br
p-O
o-O
2
N-Ph-Ph
N-Ph-Ph
2
2
p-NC-Ph-Br
p-NC-Ph-Ph
0.6
1.5
4
100
100
90
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
p-MeOC-Ph-Br
m-MeOC-Ph-Br
o-MeOC-Ph-Br
p-Cl-Ph-Br
p-MeOC-Ph-Ph
m-MeOC-Ph-Ph
o-MeOC-Ph-Ph
p-Cl-Ph-Ph
5
70
0.08
0.1
0.25
1.25
3
100
100
100
97
m-Cl-Ph-Br
m-Cl-Ph-Ph
o-Cl-Ph-Br
o-Cl-Ph-Ph
p-OHC-Ph-Br
1-Br-Naphthalene
9-Br-Phenanthrene
p-OHC-Ph-Ph
1-Ph-Naphthalene
9-Ph-Phenanthrene
95
2
100
100
100
100
100
100
100
100
100
100
d
d
p-O
2
NPh-Cl
p-O
2
N-Ph-Ph
17
p-OHC-Ph-Cl
p-OHC-Ph-Ph
p-MeO-Ph-Ph
24
Ph-I
p-MeO-PhB(OH)
p-MeO-PhB(OH)
p-MeO-PhB(OH)
p-MeO-PhB(OH)
p-MeO-PhB(OH)
p-MeO-PhB(OH)
p-MeO-PhB(OH)
2
2
2
2
2
2
2
0.3
1.1
1.25
0.17
0.25
0.4
1
p-O
m-O
2
N-Ph-I
N-Ph-I
p-O
2
N-Ph-Ph-p-OMe
2
N-Ph-Ph-p-OMe
2
m-O
p-Cl-Ph-Br
m-Cl-Ph-Br
o-Cl-Ph-Br
p-NC-Ph-Br
p-Cl-Ph-Ph-p-OMe
m-Cl-Ph-Ph-p-OMe
o-Cl-Ph-Ph-p-OMe
p-NC-Ph-Ph
a
Reaction conditions: aryl halide (1 mmol), phenylboronic acid (1.2 mmol), base (2 mmol), monomeric ortho-palladated complex (0.2 mol%), EtOH
ꢀ
(
2 ml), 60 C.
b
TLC and GC yield.
c
Isolated yield.
d
ꢀ
DMF, 120 C.
Experimental
catalyst (0.2 mol%) in ethanol (2 ml) or DMF (for aryl chlorides).
ꢀ
The mixture was heated at 60 C for aryl iodides and bromides
Chemicals
ꢀ
or at 120 C for aryl chlorides using an oil bath and the progress
was monitored by thin-layer chromatography (TLC) (hexane–
EtOAc, 9:1) and gas chromatography (GC). After competition of
the reaction, the mixture was cooled to room temperature and
diluted with n-hexane or ether and water. The organic phase
All melting points were taken on a Gallenkamp melting appara-
tus and are uncorrected. H-NMR spectra were recorded using
1
5
3
00 MHz in CDCl solutions at room temperature (TMS was
used as an internal standard) on a Bruker Avance 500 instru-
ment (Rheinstetten, Germany). FT-IR spectra were recorded on
a spectrophotometer (Jasco-680, Japan). Spectra of solids were
carried out using KBr pellets. Vibrational transition frequencies
was dried over CaCl , filtered and concentrated under reduced
2
pressure using a rotary evaporator. The residue was purified by
silica gel column chromatography. The products were character-
1
13
À1
ized by comparing their melting points, IR, H, C NMR spectra
are reported as wave number (cm ). We used a gas chro-
[
29,36]
with those found in the literature.
matograph (BEIFIN 3420 equipped a Varian CP SIL 5CB column,
3
0 m, 0.32 mm, 0.25 mm) for examination of reaction competition
and yields. Palladium acetate, aryl halides and all chemicals
were purchased from Merck and Aldrich and were used as
received.
Acknowledgements
We gratefully acknowledge the funding support received for
this project from the Isfahan University of Technology (IUT),
IR Iran and Isfahan Science and Technology Town (ISTT), IR
Iran. Further financial support from the Center of Excellence
in Sensor and Green Chemistry Research (IUT) is gratefully
acknowledged.
General Procedure for the Suzuki Cross-Coupling Reaction
To a round-bottomed flask equipped with a magnetic stirring
bar were added aryl halide (1 mmol), phenylboronic acid
(
1.2 mmol), K CO (2 mmol) and monomeric ortho-palladated
2 3
Appl. Organometal. Chem. (2012)
Copyright © 2012 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

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1
2
3
9-Br-Phenanthrene PhB(OH)
2
2
2
2
2
3
A
B
A
B
A
B
A
B
A
B
95
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80
100
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1-Br-Naphthalene
PhB(OH)
PhB(OH)
PhB(OH)
PhB(OH)
2
4
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90
80
[
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p-O
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NPh-Cl
17
24
100
75
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p-OHC-Ph-Cl
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2
C
ꢀ
DMF, 120 C.
[
[
[
2
2
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Appl. Organometal. Chem. (2012)