Phosphine-free Suzuki-Miyaura reactions catalyzed by bishydrazone-Pd-complex

Article abstract of DOI:10.1055/s-2003-38755

Glyoxal bis(methylphenylhydrazone) 1 was prepared and examined as a ligand for the Suzuki-Miyaura cross-coupling reaction of aryl bromides and arylboronic acids. We found phosphine-free catalyst, such as Pd(OAc)₂/hydrazone ligand 1 to be an eff

Full text of DOI:10.1055/s-2003-38755

882
LETTER
Phosphine-Free Suzuki–Miyaura Reactions Catalyzed by Bishydrazone-Pd-
Complex
P
hosphine-Free
a
S
uzuki–M
k
iyaur
a
React
a
ions shi Mino,* Yoshiaki Shirae, Masami Sakamoto, Tsutomu Fujita
Department of Materials Technology, Faculty of Engineering, Chiba University, Inage-ku, Chiba 263-8522, Japan
Fax +81(43)2903401; E-mail: tmino@planet.tc.chiba-u.ac.jp
Received 4 March 2003
Abstract: Glyoxal bis(methylphenylhydrazone) 1 was prepared
and examined as a ligand for the Suzuki–Miyaura cross-coupling
reaction of aryl bromides and arylboronic acids. We found phos-
phine-free catalyst, such as Pd(OAc)2/hydrazone ligand 1 to be an
efficient catalyst for a variety of substrates to produce the coupling
products in good yields at room temperature.
Key words: hydrazone, Suzuki–Miyaura reaction, cross-coupling,
palladium, phosphine-free
The palladium-catalyzed Suzuki–Miyaura cross-coupling
reaction of aryl halides with arylboronic acids and esters
has become a common and convenient synthetic method
in organic chemistry for biaryl compounds.1 The reaction
has been applied to many areas,2 including natural product
synthesis.3 Triarylphosphine/Pd complexes are common-
ly used as catalysts for the reaction.1a In the past few years,
great advances have been made in developing active and
efficient catalysts by modifying traditional ligands and
discovering new ones. Sterically demanding, electron-
rich phosphines, such as tri-t-butylphosphine have shown
high cross-coupling activities for a variety of substrates.4
In the meantime, new types of ligands, such as heterocy-
clic carbenes,5 imine and amine palladacycles,6 oxime
palladacycles,7 diazabutadines,8 and 2-aryl-2-oxazolines9
have also emerged for use in the Suzuki–Miyaura cross-
coupling reaction.
Scheme 1 Suzuki–Miyaura Cross-Coupling Reaction
tive in this reaction (Table 1, entries 1 and 2). In the case
of using 0.1 mol% of Pd(OAc)2 and 0.15 mol% of 1, the
reaction proceeds very well (91%) for 30 min at room
temperature (Table 1, entry 5).
Table 1 Effect of Different Pd-Complexes on the Suzuki–Miyaura
Cross-Coupling Reaction with Phenylboronic Acid
Entry
Catalyst (mol%)
Yield (%)a,b
1
PdCl2 (2), 1 (3)
92
59
99
99
91
99
23
2
PdCl2(MeCN)2 (2), 1 (3)
Pd(OAc)2 (2), 1 (3)
3c
4
The synthesis and properties of palladium complexes with
hydrazone ligands have been previously reported,10 and
we expect hydrazone ligands to have advantages over
phosphine ligands due to their ease of synthesis and air
stability. We report here our initial results for employing
glyoxal bis(methylphenylhydrazone) 1 as a ligand for the
Suzuki–Miyaura cross-coupling reaction (Scheme 1).
Pd(OAc)2 (1), 1 (1.5)
Pd(OAc)2 (0.1), 1 (0.15)
Pd(OAc)2 (0.05), 1 (0.075)
Pd(OAc)2 (0.04), 1 (0.06)
5c
6d
7
a Reaction conditions: 4-bromotoluene (1 mmol), phenylboronic acid
(1.5 mmol), Pd-catalyst, Cs2CO3 (2 mmol), DMF (2 mL), H2O (1 mL),
r.t., 3 h.
Glyoxal bis(methylphenylhydrazone) 1 was easily pre-
pared from glyoxal and 2 equiv of N-methyl-N-phenylhy-
dradine in methanol. Using this hydrazone as ligand, we
observed that the coupling of 4-bromotoluene and phenyl-
boronic acid in the presence of 2 mol% of Pd(OAc)2, 3
mol% of ligand 1, and Cs2CO3 in a DMF–water system
under a normal air atmosphere at room temperature, pro-
ceeded to give 4-methylbiphenyl in 99% yield (Table 1,
entry 3). Other palladium catalysts proved to be less effec-
b Isolated yields.
c This reaction was carried out for 30 min.
d This reaction was carried out for 12 h.
The effect of varying the aryl bromide in the Suzuki–
Miyaura cross-coupling reactions was investigated using
phenylboronic acid as the substrate at room temperature
(Table 2). Using para-substituted aryl bromide, such as 4-
bromobenzaldehyde and 1-bromonaphthalene led to good
yields of the desired products (entries 2–5). Moreover,
ortho-substituted aryl bromide also led to good yields
Synlett 2003, No. 6, Print: 05 05 2003.
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© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

LETTER
Phosphine-Free Suzuki–Miyaura Reactions
883
(entries 6–8). Our attempt to coupling reaction of 1-bro-
mo-2-methylnaphthalene with phenylboronic acid result-
ed in a low yield (entry 9).
The effect of varying the arylboronic acids in the Suzuki–
Miyaura cross-coupling reactions was also investigated
using 4-bromotoluene as the substrate at room tempera-
ture (Table 3). Using para-substituted arylboronic acid
led to moderate to good yields of the desired products (en-
tries 2 and 3); ortho-fluorophenylboronic acid and 1-
naphthaleneboronic acid also led to good yields (entries 4
and 5), but 2-formylphenylboronic acid led to a low yield
(entry 6).
Scheme 2 Preparation of Pd-Complex 2.
To investigate the nature of the catalyst structure, a red
single-crystal of the Pd-complex 2, was obtained from the
reaction of glyoxal bis(methylphenylhydrazone) 1 and
PdCl2(MeCN)2 in acetonitrile (Scheme 2).
Table 2 Suzuki–Miyaura Cross-Coupling Reaction of Aryl
Bromide with Phenylboronic Acid
Entry
Aryl bromide
p-Me-Ph
Yield (%)a,b
1c
2
3
4
5
6
7
8
9
99
89
99
94
92
89
87
88
24
X-ray analysis of 2 showed the hydrazone-derived palla-
dacycle and the palladium atom bound to a couple of ni-
trogen atoms on the ligand. Additionally, the Pd-N bonds
are asymmetric with a difference of 0.262 Å. When 2
mol% of complex 2 was used as catalyst, the reaction of
4-bromotoluene and phenylboronic acid was smoothly
proceeded in 99% yield for 3 h at room temperature.
p-MeO-Ph
p-CHO-Ph
p-t-Bu-Ph
1-naphth
o-MeO-Ph
o-CHO-Ph
o-CN-Ph
2-Me-1-naphth
a Reaction conditions: Aryl bromide (1 mmol), phenylboronic acid
(1.5 mmol), Pd(OAc)2 (2 mol%), Ligand 1 (3 mol%), Cs2CO3
(2 mmol), DMF (2 mL), H2O (1 mL), r.t., 3 h.
b Isolated yield.
c This reaction was carried out for 30 min.
Table 3 Suzuki–Miyaura Cross-Coupling Reaction of 4-Bromo-
toluene with Arylboronic Acid
Figure 1 ORTEP plot of the Pd-complex 2.
Entry
Arylboronic acid
Ph
Yield (%)a,b
1c
2
3
4
5
6
99
98
68
93
86
24
In summary, we demonstrate a general and efficient cata-
lytic system based on Pd(OAc)2/bishydrazone 1 for the
Suzuki–Miyaura cross-coupling reaction of aryl bromides
and arylboronic acids at room temperature.
p-Me-Ph
p-MeO-Ph
o-F-Ph
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Synlett 2003, No. 6, 882–884 ISSN 0936-5214 © Thieme Stuttgart · New York