Homocoupling of arylboronic acids with a catalyst system consisting of a palladium(II) N-heterocyclic carbene complex and p-benzoquinone

Article abstract of DOI:10.1055/s-2007-984531

In the presence of 1-3 mol% SIPr-ligated Pd(OAc)₂ and 0.6 equivalent of p-benzoquinone, various arylboronic acids underwent homocoupling in MeOH at ambient temperature to produce symmetrical biaryls in 38-96% yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-984531

LETTER
1913
Homocoupling of Arylboronic Acids with a Catalyst System Consisting of a
Palladium(II) N-Heterocyclic Carbene Complex and p-Benzoquinone
H
Y
omocoupling of
o
A
rylboronic
s
A
cids hihiko Yamamoto*
Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, O-okayama, Meguro-ku,
Tokyo 152-8552, Japan
Fax +81(3)57343339; E-mail: omyy@apc.titech.ac.jp
Received 12 April 2007
This paper is dedicated to the late Professor Yoshihiko Ito in recognition of his diverse and distinguished contributions to the fields of
organic and organometallic chemistry.
vated temperatures, and/or catalyst loadings of 5–10
Abstract: In the presence of 1–3 mol% SIPr-ligated Pd(OAc) and
2
mol%. Along this line, mild and efficient protocols were
0
.6 equivalent of p-benzoquinone, various arylboronic acids under-
10
realized using aqueous media under air or O2. Alterna-
tive methods were also developed by means of ultrasound
irradiation or other transition-metal catalysts.1
went homocoupling in MeOH at ambient temperature to produce
symmetrical biaryls in 38–96% yields.
1,12
Key words: biaryls, boron, catalysis, coupling, palladium
This author and co-workers have developed Pd(OAc)2-
catalyzed homocoupling that proceeds in methanol at
room temperature under air.13 A serious limitation of our
protocol is low efficiency toward arylboronic acids bear-
ing an electron-withdrawing substituent, resulting in the
low yield of biaryls due to the formation of palladium
black. Although the addition of triphenylphosphine as an
external ligand or use of polyurea-encapsulated catalyst
The synthesis of substituted biaryls has been an important
research objective in organic synthesis, because they
1
constitute significant structural motifs in natural prod-
2
3
4
ucts, functional materials, and catalysts. Transition-
metal-catalyzed cross-coupling between arylboronic
acids and aryl halides, so-called Suzuki–Miyaura cou-
pling, is now one of the most reliable tool to synthesize
II
TM
(
Pd EnCat ) are able to suppress the catalyst deactiva-
5
tion, side products were formed via the aryl group inter-
change between the phosphine and an intermediary
arylpalladium species or oxidation of arylboronic acids,
respectively. Reported in this communication is a new
protocol with wider scope, where N-heterocyclic carbene
unsymmetrical biaryls. The homocoupling of arylboron-
ic acids is an another attractive approach to conveniently
obtain symmetrical biaryls from a single aryl precursor
6
(
Scheme 1). Despite its synthetic potential, this biaryl
formation has been hardly applied to the synthesis of com-
7
(
NHC)-ligated Pd(OAc) is employed as a highly efficient
plex molecules, partly due to its lack of general substrate
2
precatalyst in combination with p-benzoquinone as a
stoichiometric oxidant.
scope as well as mechanistic complexity involving the
oxidative restoration of the Pd(II) catalyst from a Pd(0)
species generated from the reductive elimination of a
8
iPr
iPr
bis(aryl)palladium(II) intermediate.
N
N
N
N
i
i
Pr
O
Pr
O
catalyst, ligand
B(OH)2
Pd
O
Pd
O
O
O
base, oxidant
R
R
R
O
H
H
O
O
H
H
O
Scheme 1
1a (SIPr)Pd(OAc)2(H2O)
1c (SIMes)Pd(OAc)2(H2O)
1d (IMes)Pd(OAc)2(H2O)
1b (IPr)Pd(OAc)2(H2O)
There have been a number of reports on homocoupling of
arylboronic acids, where several additives were found es-
sential to enable efficient catalyst turnover. They include
O
B
O
B
9
O
O
4
5
oxidizing agents to restore Pd(II) species such as metal
salts or organic halides, bases facilitating transmetalation,
and phosphine ligands that stabilize catalysts. In terms of
material economy as well as environmental concern, how-
ever, an alternative method achieving the desired biaryl
formation without such additional reagents is highly ideal.
In addition, most existing methods require polar solvents
with high boiling points such as DMF and DMSO, ele-
Figure 1
To realize homocoupling with general scope, the use of
NHC complexes, (NHC)Pd(OAc) (H O) (1), was pursued
2
2
because this type of complex was proved to be efficient
for aerobic oxidation of alcohols and cross couplings.1
Nevertheless, 1a bearing a commercially available satu-
rated NHC ligand turned out to be less stable under the
aerobic homocoupling conditions. In the presence of 3
mol% 1a, the reaction of p-tolylboronic acid 2a proceeded
with concomitant formation of black particles in methanol
4,15
SYNLETT 2007, No. 12, pp 1913–1916
2
4
.0
7
.2
0
0
7
Advanced online publication: 27.06.2007
DOI: 10.1055/s-2007-984531; Art ID: U03307ST
©
Georg Thieme Verlag Stuttgart · New York

1
914
Y. Yamamoto
LETTER
Table 1 Homocouplings of Arylboronic Acids and Derivativesa
Table 2 Homocoupling of Various Arylboronic Acids with 1aa
Entry
Cat. (mol%)
1a (1)
Substrate
Yield of 3 (%)
3a (88)
Entry 2, R
1a
Yield of 3 (%)
(
mol%)
1
2
3
4
5
6
7
2a
2a
2a
2a
2a
2b
4
1b (1)
3a (quant.)
3a (30)
R
B(OH)2
R
R
1c (1)
1
2
3
4
5
6
7
8
9
2c, OMe
1
3
3
3
1
1
1
1
1
1
3c, 69
1d (1)
3a (35)
2d, NMe2
2e, SMe
2f, SiMe3
2g, t-Bu
3d, 38
Pd(OAc) (1)
3a (22)
3e, 53 (39)b
2
1a (1)
1a (1)
1a (1)
3b (94)
3f, 96 (24)b
3b (77)
3g, 89
3h, 61
3i, 91
3j, 90
3k, 88
3l, 85
8
5
3b (57)
2h, CH=CH2
2i, Cl
a
All reactions were carried out with a substrate (0.5 mmol), a catalyst
0.005 mmol), and pbq (0.6 mmol) in MeOH (10 mL) for 24 h at r.t.
(
under Ar.
2j, CO Et
2
2k, COMe
2l, CHO
under air at room temperature, and after stirring for 24 10
hours, 4,4¢-dimethylbiphenyl was obtained in a lower
yield (69%) than that with Pd(OAc) (94% for 5 h). p-
Cresol was also detected by H NMR. On the basis of
2
B(OH)2
1
these observations, it is supposed that peroxy species
R
R
R
might be detrimental to both the catalyst and the sub-
3m, 84 (76)b
1
1
1
1
2
3
2m, Me
2
1
1
1
8
c
strate. Thus, the catalytic performance of 1a was further
examined using p-benzoquinone (pbq) as a mild and inno-
cent oxidant, because the combination of pbq and the
methanol solvent proved to be efficient for palladium-cat-
2n, OMe
2o, Cl
3n, 91
3o, 95
3p, 74
R
1
6
14
2p, NO2
alyzed alkoxycarbonylation of arylboronates. The same
reaction of 2a was carried out under Ar in the presence of
R
R
R
3
mol% 1a and 0.6 equivalents of pbq to afford 3a in an
improved yield of 89%. The use of other solvents such as
B(OH)2
THF and CHCl resulted in less than 30% yield. A high
3
yield was also obtained, when the loading of 1a was re-
R
R
1
7
3q, 74 (28)b
duced to 1 mol% (Figure 1, Table 1, entry 1). In a simi- 15
2q, Me
3
3
3
lar manner, complex 1b having a unsaturated carbene
1
6
2r, OMe
2s, Cl
3r, 75
ligand gave the homocoupling product quantitatively
entry 2). The significance of the 2,6-diisopropyl-
(
17
3s, 43 (17)b
phenyl group on the ligands SIPr and IPr was clearly
exemplified by the fact that 3a was obtained in less than
B(OH)2
3
5% yield with 1 mol% (SIMes)Pd(OAc) (H O) (1c),
2 2
(
IMes)Pd(OAc) (H O) (1d), or Pd(OAc) otherwise under
Cl
Cl Cl
2
2
2
the same reaction conditions (entries 3–5). Although the 18
2t
3
3t, 0
IPr ligand was superior to its saturated analogue, the latter
was used for the following investigations because of its
ready accessibility. The parent phenylboronic acid (2b)
was uneventfully converted into biphenyl 3b in 94% yield
a
All reactions were carried out with 2 (0.5 mmol), 1a (1–3 mol%),
and pbq (0.3 mmol) in MeOH (10 mL) for 24 h at r.t. under Ar.
b
Yields in parentheses were obtained with 1 mol% 1a.
(
5
entry 6), while the corresponding cyclic boronates 4 and
also underwent homocoupling under the optimal condi-
tions albeit with diminished efficiency (entries 7 and 8).
1
8). This is because of the small coordination space of 1a
due to the sterically demanding SIPr ligand. Increased
The generality of the (SIPr)Pd(II)-catalyzed homocou- catalyst loadings of 3 mol% were required for substrates
pling was investigated as summarized in Table 2. Phenyl- with a strongly coordinating substituent such as NMe
,
2
boronic acids possessing para- or meta-substituent(s) SMe, and trimethylsilyl group (entries 2–4). Similarly, in-
were transformed into the corresponding biaryls in mod- creased catalyst loadings were essential for m-disubstitut-
erate to high isolated yields, while o-chlorophenylboronic ed boronic acids probably due to the steric bulk of these
acid (2t) totally failed to undergo homocoupling (entry substrates (entries 15–17). The most notable aspect is that
Synlett 2007, No. 12, 1913–1916 © Thieme Stuttgart · New York

LETTER
Homocoupling of Arylboronic Acids
1915
the present catalyst system tolerates electron-deficient
substituents such as carbonyl, chloride, and nitro groups
well (entries 7–10, 13, 14, 17). This method also tolerated
a vinyl substituent, and 4,4¢-divinylbiphenyl (3h) was ob-
tained in 61% yield without forming Mizoroki–Heck-type
products (entry 6).
R
3
mol% 1a
R
pbq, MeOH, r.t., 24 h
B(OH)2
1
1
0a 51%
0b 57%
R
9a R = Me
9b R = OMe
c R = Cl
10c 57%
9
Recently, Wang and co-workers reported that p-bro-
mophenylboronate (6) underwent Sonogashira coupling
with trimethylsilylacetylene under microwave irradiation
conditions to give p-alkynylated 7 without loss of the
boronate moiety. Homocoupling of the resulted 7 was
carried out in the presence of 3 mol% 1a to furnish 8 in
B(OH)2
B(OH)2
O
11
12
1
8
Scheme 3
7
4% yield without affecting the silylalkyne moiety
SIPr
PdII
(
Scheme 2). This two-step method provides quite a pow-
HO
MeOH
OH
erful way to 4,4¢-dialkynylbiphenyls, which are useful
building blocks for the assembly of functional organo-
metallic macromolecules.
ArB(OH)2
MeOB(OH)2
MeO
OMe
2
1
9
13
SIPr
SIPr
PdII
O
O
O
Pd0
ref. 18
Br
B
TMS
B
O
Ar
OMe
O
O
6
7
15
ArB(OH)2
MeOB(OH)2
SIPr
SIPr
PdII
3
mol% 1a
Ar-Ar
TMS
TMS
pbq
pbq, MeOH
r.t., 24 h
Ar
Ar
14
8
74%
SIPr Me
O
Scheme 2
Pd0
H
L
PdII OMe
Ar B(OH)2
TS1
O
O
The present protocol was then applied to homocoupling of
styrylboronic acids (Scheme 3). Several p-substituted sty-
rene derivatives having the boronic acid moiety on the ter-
minal vinyl carbon 9a–c was treated with 3 mol% 1a and
TS2
Scheme 4
0
2
1
1
1
.6 equivalent of pbq in MeOH at room temperature for
4 hours under argon. As a result, 1,4-diaryl-1,3-dienes
0a–c were obtained in ca. 50% yields. On the other hand,
-phenylvinylboronic acid (11) and benzofuran derivative
2 gave only trace amounts of the corresponding homo-
with p-benzoquinone as a stoichiometric oxidant. The use
of methanol as solvent proved to be essential, because it
acts as a proton donor to the coordinated quinone in the
catalyst oxidation step, where a putative bis(methoxo)pal-
ladium(II) active catalyst is considered to be restored.
Overall, the homocoupling proceeds efficiently in the ab-
sence of a base additive even at room temperature, and the
desired biaryls were obtained in moderate to high yields.
coupling product under the same reaction conditions.
A plausible catalytic cycle is outlined in Scheme 4. The
catalytically active species is considered to be bis(meth-
oxo)palladium(II) complex 13, which undergoes two-fold
transmetalation with two equivalents of an arylboronic
acid to give rise to bis(aryl)palladium(II) complex 14. As Acknowledgment
previously suggested, the transmetalation steps proceed
efficiently even at ambient temperature, because 13 is
This research was supported by Grant-in-Aid for Young Scientist
A) 17685008 from Ministry of Education, Culture, Sports, Science
(
able to donate its methoxy ligand to the highly oxophilic and Technology, Japan.
2
0
boron center via cyclic transition state TS1. Subsequent
reductive elimination of a biaryl followed by the ligation
of p-benzoquinone might produce h -quinone Pd(0) com-
plex 15. The oxidation of the palladium(0) center with the
2
References and Notes
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quinone ligand is then induced by methanol as a proton
2
1
donor via TS2. As a consequence, bis(methoxo) species
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(
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6
In conclusion, an efficient protocol of homocoupling of
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(
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Pd(OAc) as a precatalyst (1–3 mol%) in combination
2
Synlett 2007, No. 12, 1913–1916 © Thieme Stuttgart · New York

1
916
Y. Yamamoto
LETTER
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(
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To a solution of p-tolylboronic acid 2a (69.8 mg, 0.502
mmol) and p-benzoquinone (33.2 mg, 0.307 mmol) in
MeOH (10 mL) was added 1a (3.25 mg, 0.0051 mmol), and
the flask was evacuated and backfilled with Ar three times at
–78 °C. The reaction mixture was stirred for 24 h at r.t. under
Ar. The solvent was removed in vacuo and the residue was
purified by silica gel column flash chromatography (eluent:
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Other reactions were also carried out in a similar manner. If
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1
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