Ligand promoted palladium-catalyzed homo-coupling of arylboronic acids

Article abstract of DOI:10.1016/S0040-4039(01)00637-2

Palladium-catalysed homo-coupling of arylboronic acids can be promoted by phosphine or phosphite ligands thereby offering a simple and efficient protocol for the synthesis of symmetrical bi-aryl molecules and their higher homologues.

Full text of DOI:10.1016/S0040-4039(01)00637-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4087–4089
Ligand promoted palladium-catalyzed homo-coupling of
arylboronic acids
Man Shing Wong* and Xiao Ling Zhang
Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China
Received 17 January 2001; accepted 12 April 2001
Abstract—Palladium-catalysed homo-coupling of arylboronic acids can be promoted by phosphine or phosphite ligands thereby
offering a simple and efficient protocol for the synthesis of symmetrical bi-aryl molecules and their higher homologues. © 2001
Elsevier Science Ltd. All rights reserved.
The palladium-catalyzed Suzuki cross-coupling of aryl
halides with organoboronic acids or esters has become
one of the most widely investigated and used synthetic
In the course of synthesizing aryl-substituted calixarene
assemblies using a Suzuki cross-coupling protocol, we
have observed that the palladium-catalyzed homo-cou-
pling of arylboronic acids can be enhanced by ligands
at elevated temperatures. We report herein an investiga-
tion of phosphine or phosphite ligand promoted palla-
dium-catalyzed homo-coupling of arylboronic acids
2
2
1,2
methods for C(sp )ꢀC(sp ) bond formation. Bi-aryl
units and their higher homologues constitute important
building blocks in natural products and advanced mate-
rials. Most cross-coupling protocols including phos-
phine ligand promoted and ligandless reaction
conditions utilize a large excess of the organoboronic
reagents in order to drive the reaction with aryl halides
to completion. This is mainly due to undesirable side-
reactions of the arylboronic acids which include homo-
coupling of the arylboronic acid, cross-coupling of
(
Scheme 1).
The investigation was initially carried out with 4-
fluoroboronic acid using ligandless Pd(OAc)2 as the
catalyst in the presence of K CO at 60°C, in DMF for
2
3
2
h under an air atmosphere to afford 4,4%-difluoro-
biphenyl in a moderate yield (Table 1, entry 1). In
contrast, with tri-o-tolylphosphine (P(o-tol) ) as the
the arylboronic acid with3
a
phenyl group of
a triphenylphosphine ligand and decomposition of
the arylboronic acids into phenolic compounds under
the reaction conditions. As arylboronic acids are
easily accessible and stable in air, it is of particular
interest to explore the synthetic utility of the homo-
coupling of arylboronic acids which may provide
a simple and general alternative to the nickel cata-
3
ligand in which Pd(0) species are known to be gener-
7
ated in situ, the homo-coupling reaction proceeded at
a faster rate. The homo-coupling can be further and
efficiently enhanced if the triphenylphosphine (PPh3)
ligand is employed. It is worth mentioning that triethyl
4
lyzed homo-coupling reaction, in the preparation
phosphite (P(OEt) ) was also found to be a useful
3
of symmetrical bi-aryl molecules and their higher homo-
logues. However, there have only been a few studies
in this area so far. Recently, mechanistic aspects
of the palladium-catalyzed homo-coupling of aryl-
ligand in promoting the homo-coupling reaction
(
entries 2–4). However, it is interesting to find that the
catalytic activity of Pd[PPh ] was inferior to that of the
3
4
ligandless Pd(OAc) (entry 5). To evaluate further the
5
2
boronic acids have been proposed. Jackson et al.
scope of the phosphine ligand promoted protocol, sev-
found that the ligandless palladium acetate (Pd(OAc)2)
can catalyze the homo-coupling of arylboronic
acids at ambient temperature, but the reaction proceeds
rather slowly, and affords only moderate isolated
eral reaction parameters based on the PPh ligand were
3
investigated. It was found that proper control of the
6
Pd(II), Ligand
B(OH)2
yields.
K CO , air
R
2
3
R
R
*
Corresponding author. Tel.: 852-2339-7069; fax: 852-2339-7348;
e-mail: mswong@hkbu.edu.hk
Scheme 1.
0
040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00637-2

4
088
M. S. Wong, X. L. Zhang / Tetrahedron Letters 42 (2001) 4087–4089
Table 1. Palladium-catalyzed homo-coupling reaction of arylboronic acids
Entry
Arylboronic acid
Catalyst
Solvent
Temp (°C)
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
9
4-F-Ph-B(OH)2
4-F-Ph-B(OH)2
4-F-Ph-B(OH)2
4-F-Ph-B(OH)2
4-F-Ph-B(OH)2
4-F-Ph-B(OH)2
4-F-Ph-B(OH)2
4-F-Ph-B(OH)2
4-F-Ph-B(OH)2
4-F-Ph-B(OH)2
4-F-Ph-B(OH)2
4-F-Ph-B(OH)2
4-F-Ph-B(OH)2
4-PrS-Ph-B(OH)2
4-PrS-Ph-B(OH)2
4-PrS-Ph-B(OH)2
4-PrS-Ph-B(OH)2
Ph-B(OH)2
Pd(OAc)2
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
Toluene
DMF
DMF
DMF
Toluene
DMF
Toluene
DMF
Toluene
DMF
60
60
60
60
60
25
90
100
120
60
60
60
60
60
90
120
90
90
90
90
90
90
2
2
2
2
2
2
1.7
2
2
2
2
2
2
2
2
2
2
2
2
2
2
4
48
67
79
73
27
21
79
71
55
65
57
Pd(OAc) :2P(o-tol)
2
3
Pd(OAc) :2PPh
2
3
Pd(OAc) :2P(OEt)
2
3
Pd[PPh3]4
Pd(OAc) :2PPh
2
3
3
3
3
Pd(OAc) :2PPh
2
Pd(OAc) :2PPh
2
Pd(OAc) :2PPh
2
10
11
12
13
14
15
16
17
18
19
20
21
22
PdCl :2PPh
2
3
Pd (dba) :2PPh
2
3
3
3
3
3
3
3
3
3
3
3
3
3
b
Pd(OAc) :2PPh
44
2
Pd(OAc) :2PPh
81
72
72
60
81
83
78
85
66
12
2
Pd(OAc) :2PPh
2
Pd(OAc) :2PPh
2
Pd(OAc) :2PPh
2
Pd(OAc) :2PPh
2
Pd(OAc) :2PPh
2
3,5-Me -4-PrO-Ph-B(OH)
Pd(OAc) :2PPh
2
2
2
3,4-MeO -Ph-B(OH)
Pd(OAc) :2PPh
2
2
2
c
3,5-Me -4-DeO-Ph-Ph-B(OH)
Pd(OAc) :2PPh
2
2
2
4-Br-Ph-B(OH)2
Pd(OAc) :2PPh
2
a
b
c
Isolated yield.
Under nitrogen.
De=decyl.
reaction temperature is critical to ensure that the ligand
promoted palladium-catalyzed homo-coupling proceeds
efficiently. The best temperature range was found to be
between 60 and 90°C (entries 3, 6–9). Amongst various
commonly employed palladium compounds, Pd(OAc)2
was found to be the most effective catalyst used in this
improved protocol (entries 3, 5, 10–11). As was the case
with previous findings, oxygen can accelerate the rate of
the homo-coupling reaction (entry 12). In addition to
the electron withdrawing group substituted arylboronic
acids, this improved protocol also works well with
phenylboronic and electron rich arylboronic acids
which, however, appear to require slightly more vigor-
ous reaction conditions (entries 17–20). On the other
hand, the use of the non-polar solvent toluene afforded
a slightly better yield than the polar solvent, DMF. In
addition to the synthesis of bi-aryl molecules, this pro-
tocol can also be applied to the preparation of their
(FRG/00-01/I-40) from the Hong Kong Baptist
University.
References
1
. Suzuki, A. In Metal-catalysed Cross-coupling Reactions;
Diederich, F.; Stang, P. J., Eds. Cross-Coupling Reac-
tions of Organoboron Compounds with Organic
Halides.; Wiley-VCH: Weinheim, 1998; pp. 49–97.
. Suzuki, A. J. Organomet. Chem. 1999, 576, 147–168.
. O’Keefe, D. F.; Dannock, M. C.; Marcuccio, S. M. Tet-
rahedron Lett. 1992, 33, 6679–6682.
2
3
4. Jouaiti, A.; Geoffroy, M.; Bernardinelli, G. Tetrahedron
Lett. 1993, 34, 3413–3416.
5. Moreno-Manas, M.; Perez, M.; Pleixats, R. J. Org.
Chem. 1996, 61, 2346–2351.
6. Smith, K.; Campi, E. M.; Jackson, W. R.; Marcuccio,
S.; Naeslund, C. G. M.; Deacon, G. B. Synlett 1997,
131–132.
8
higher homologues (entry 21). In the case of the bro-
mide-substituted arylboronic acid (entry 22), the low
yield of the homo-product is attributed to the slightly
favorable cross-coupling reaction under the reaction
conditions employed. This has been verified by an
independent competition experiment.
7. Amatore, C.; Jutand, A.; M’Barki, M. Organometallics
1992, 11, 3009–3013.
1
8
. All products were fully characterized by H NMR and
MS. General procedure for the homo-coupling reaction
of arylboronic acids. To a stirred solution of arylboronic
acid (ꢀ0.45 mmol), 5 mol% of Pd(OAc)2 and ligand
In summary, we have developed a general and efficient
phosphine or phosphite ligand promoted palladium-cat-
alyzed homo-coupling of arylboronic acids for the syn-
thesis of symmetrical bi-aryl molecules and their
homologues.
PPh (1:2) in 5 mL of DMF (or toluene), was added 2.5
3
equiv. of K CO . After being heated at 60–90°C for 2 h
2
3
under an air atmosphere, the reaction mixture was
cooled to room temperature, quenched with water and
then extracted with CH Cl2 (3×50 mL). The combined
organic layers were dried over anhydrous MgSO4 and
Acknowledgements
2
This work was supported by Faculty Research Grants
evaporated to dryness. The crude product was purified

M. S. Wong, X. L. Zhang / Tetrahedron Letters 42 (2001) 4087–4089
4089
by silica gel column chromography using petroleum ether
and CH Cl as eluent.
Selected spectroscopic data: product of entry 21: H NMR
J=8.4 Hz, 4H), 7.28 (s, 4H), 3.79 (t, J=6.4 Hz, 4H), 2.34
(s, 12H), 1.83–1.79 (m, 4H), 1.56–1.51 (m, 4H), 1.35–1.24
(m, 24H), 0.88 (t, J=6.8 Hz, 6H). MS (FAB) m/z 674.6
2
2
1
+
(
400 MHz, CDCl ) l 7.67 (d, J=8.4 Hz, 4H), 7.62 (d,
(M ). Mp=102–103°C.
3
.