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S. Jadhav et al. / C. R. Chimie 16 (2013) 957–961
Fig. 1. (a) Structure of agarose and (b) photograph of the gel-entrapped base.
aqueous solution makes it useful in numerous applications
[9]. This method of immobilization reduces the amount of
bases required and allows easy separation of the product
from the reaction mixture. Advantages offered by gel-
entrapped bases are that, they are stable in organic
solvents, air stable, and can be separated easily by simple
filtration from the reaction mixture, which simplifies the
product isolation procedure. In addition, the contamina-
tion of inorganic salts in the reaction product is also
avoided.
Recent work in our group has focused on the develop-
ment of gel-entrapped bases as efficient and recyclable
catalysts for organic transformations [10]. The present
work describes the fabrication of an aqueous gel-
entrapped base and its application as an improved tool
in the ligand-free Suzuki–Miyaura cross-coupling reaction.
Initially, 4-bromo benzophenone (1a) and phenyl
boronic acid (2a) were chosen as model reaction partners
to optimize the various reaction conditions, like selection
of solvents, bases and catalyst loading (Scheme 1).
It is known that the nature of the base is an important
factor for determining the efficiency of the Suzuki–
Miyaura cross-coupling reaction [13]. Therefore, the
influence of various bases was investigated for the model
reaction. Several gel-entrapped organic as well as inor-
ganic bases were screened and the superior reaction
efficiency was observed with gel-entrapped NaOH in 95%
ethanol at 80 8C (Table 1, entry 1). There are various reports
emphasizing the important role played by the solvent in
the reaction system, which prompted us to screen various
solvents [14,15]. Screening of solvents indicated that 95%
ethanol was the best one for this system (Table 1, entry 1),
and that its use renders this protocol quite practical and
amenable to large-scale synthesis.
2. Results and discussion
To study the effect of entrapped NaOH and compare the
activity of non-entrapped NaOH, the model reaction was
run under identical condition using solid NaOH, and the
results revealed that the gel-entrapped NaOH showed
higher activity than the non-entrapped one (Table 1, entry
9). This result demonstrates that the gel matrix may
stabilize the active species, enhancing the rate of reaction.
The effect of the concentration of the Pd(dppf)Cl2
complex on the percentage conversion of the model
reaction has been studied and the results are shown in
Table 2. Thus, among the different loadings tested, 1 mol%
proved to be the best one, affording the desired product
with 95% yield using gel-entrapped NaOH in 95% EtOH
(Table 2, entry 3).
The gel-entrapped bases were prepared following the
literature procedure [11]. During the preparation of the
aqua gel, temperature plays a crucial role; preparation of
the gel at low temperatures resulted in a brittle gel, while
high temperatures cause coloration of the gel. The gel-
entrapped bases were light yellow jelly-like substances
that could be cut into cubes (Fig. 1 (b)). The resulting
aqueous gels were then solvent exchanged for ethanol as
reported in the literature [12]. The resulting ethanol-
saturated gels were then used in Suzuki–Miyaura cross-
coupling reactions. The pore in the gel, in which the base is
entrapped, acts as microreactor, which traps the inorganic
salts in the gel, leaving the biaryl products in the reaction
solvent. It also removes residual metal from the reaction
product.
To demonstrate the scope of the gel-entrapped base, the
optimized protocol [4-bromobenzophenone (1 mmol),
phenyboronic acid (1.2 mmol), gel-entrapped NaOH (1 g,
B(OH)2
O
O
Pd(dppf)Cl2
+
Gel-entrapped base,
solvent, heat
Br
3a
1a
2a
Scheme 1. Suzuki–Miyaura cross-coupling reaction using a gel-entrapped base.