the need for a cosolvent to ensure swelling of beads to the
-
gel phase. The ionic liquid [bmim][BF
4
] was mixed with
Table 1. Rate Acceleration of the Solid-Phase
four test solvents: dichloromethane, DME, DMF, and
dimethyl acetamide. The mixture with dichloromethane
rapidly turned cloudy, while those with DME and dimethyl
-
Suzuki-Miyaura Reaction by [bmim][BF
4
]
reaction
time
yield (%)
DMF
yield (%)
6
-
1:1 [bmim][BF4 ]/DMF
acetamide gradually separated. Only DMF remained miscible
-
30 min
19
31
38
46
80
48
59
67
74
84
with [bmim][BF
4
] as a homogeneous translucent liquid upon
6
9
0 min
0 min
overnight standing and was hence chosen as the cosolvent.
For our solid-phase reactions, 4-iodophenol was im-
mobilized on the polystyrene-Wang resin according to the
1
20 min
8 h
4
7
trichloroacetimidate procedure of Hanessian and Xie. The
-
resin was then swollen in 1:1 [bmim][BF
by addition of Pd(PPh
4
]/DMF, followed
3
)
4
and catalyst activation by heating
aryl iodide with a set of 10 arylboronic acids bearing a range
of electron-donating and -withdrawing substituents (Table
2). As can be seen, the ionic liquid efficiently promotes the
to 110 °C for 2 h. The resulting orange-red suspension was
heated at 110 °C for a further 2 h after addition of
8
2 3
phenylboronic acid and aqueous Na CO . Upon cooling of
the suspension, workup, and resin cleavage, we were pleased
to obtain ∼70% isolated yield of 4-phenylphenol (Scheme
Table 2. Examples of Ionic Liquid Promoted Solid-phase
Suzuki-Miyaura Cross-coupling
1
, R ) H).
yield (%)a
1:1 conditionsb
yield (%)a
1:9 conditionsb
entry
R
Scheme 1. Ionic Liquid-Accelerated Suzuki-Miyaura
1
2
3
4
5
6
7
8
9
H
74
72
70
61
40
45
42
65
60
73
70
68
64
64
44
40
37
67
63
70
Reactions of Immobilized 4-Iodophenol
4-CHO
3-CHO
4-OPh
3-NHAc
4-OCF3
3,5-diCF3
4-Et
3,4-OCH2O-
4-t-Bu
1
0
a
Isolated yield after silica chromatography, average of three experiments.
b
-
Ratios of 1:1 and 1:9 refer to the proportion (v/v) of [bmim][BF4 ]/DMF.
Suzuki-Miyaura coupling of a variety of arylboronic acids.
With some boronic acids, the conversion was lower due to
their decreased reactivity. Nevertheless, these reactions are
even less efficient without the ionic liquid. For example, the
coupling product of 4-(trifluoromethoxy)phenyl boronic acid
(
entry 6) was obtained in only 26% under control conditions.
The nature of the ionic liquid catalysis is likely to be
Two control experiments served to highlight the impor-
tance of both the ionic liquid and cosolvent. Thus, under
identical reaction conditions with neat DMF in the absence
of any ionic liquid, only 46% of the biaryl product was
isolated. On the other hand, when the solid-phase reaction
was carried out with neat ionic liquid in the absence of any
DMF, no biaryl was detected. Presumably, this is due to poor
penetration of the active catalyst into the unswollen resin
twofold. Besides solvent effects due to the dissolving power
of this polar medium, the formation of N-heterocyclic
carbene complexes by active participation of the ionic liquid
with the transition metal has been suggested and experimen-
tally demonstrated for Pd(0)-catalyzed reactions. In all our
reactions, we have found that the yields are very similar when
the ionic liquid concentration is only 10% of the solvent
volume (Table 2, column 4). Further reduction to 5:95
[
compared to the ionic liquid-free conditions, while 1:99
9,10
beads. A time course of the extent of reaction with 1:1
-
[
bmim][BF
4
]/DMF versus DMF alone (Table 1) confirms
-
bmim][BF
4
]/DMF led to a partial increase in yield
significant rate acceleration in the former case.
The scope of the ionic liquid-accelerated process was
investigated with the parallel reactions of the resin-bound
-
[bmim][BF
4
]/DMF resulted in practically no acceleration
over the control.
(
6) A reviewer points out that this may be due to NaCl present as an
We have attempted recycling of the ionic liquid, which
should contain the catalytically active species, after the solid-
-
impurity in the ionic liquid. Our [bmim][BF4 ] was purchased from Fluka
and used without further purification.
(
7) Hanessian, S.; Xie, F. Tetrahedron Lett. 1998, 39, 733-736.
(8) Recently, ionic liquid-promoted Suzuki reactions were carried out
(9) Xu, L.; Chen, W.; Xiao, J. Organometallics 2000, 19, 1123-1127.
(10) Mathews, C. J.; Smith, P. J.; Welton, T.; White, A. J. P.; Williams,
D. J. Organometallics 2001, 20, 3848-3850.
at ambient temperature with the aid of ultrasound: Rajagopal, R.; Jarikote,
D. V.; Srinivasan, K. V. Chem. Commun. 2002, 616-617.
3072
Org. Lett., Vol. 4, No. 18, 2002