150
Transition Met Chem (2012) 37:149–153
But
But
solvent was evaporated under reduced pressure. The crude
product that was purified by column chromatography using
100–200 mesh silica gel and the purified products were
R
N
N
O
R1
N
N
R
Pd
3
But
N
AcO
R2
OH HO
HO
1
But
characterized by comparing their H NMR spectra with
N
R1-R2 = -(CH)4-
4
5
1 R = Me
2 R = Ph
R
R1= H, R2
=
tBu
those found in the literature, namely 4-methylbiphenyl
(Table 4, entries 1, 5, 12, 18 and 22) [18], 4-methoxybi-
phenyl (Table 4, entries 2, 3 and 14) [22], 2-methylbiphenyl
(Table 4, entries 4 and 13) [22], 4-acetylbiphenyl (Table 4,
entries 6 and 15) [25], biphenyl (Table 4, entries 7 and 11)
[18], 4-trifluoromethylbiphenyl (Table 4, entries 8, 9, 10
and 21) [26], 4,40-dimethylbiphenyl (Table 4, entries 16, 19
and 23) [27], 4-methoxyl-40-methyl-1,10-biphenyl (Table 4,
entries 17, 20 and 24) [28].
Me
B
B
Me
N
N
But
But
B
OH HO
But But
6
7
Me
Scheme 1 Structures of selected ligands, complexes and products
2-(N-methylpiperazinyl-N0-methyl)-4,6-di-tert-butyl-phenol
(1) and 2-(N-methylpiperazinyl-N0-phenyl)-4,6-di-tert-butyl-
phenol (2) were prepared as reported [24]. Solvents were
dried with standard methods and freshly distilled prior to
use. NMR spectra were recorded on a Bruker Avance III
400 MHz (1H 400 MHz, 13C 100 MHz) spectrometer. The
NMR studies were carried out using CDCl3 as solvent and
signals are quoted in ppm as d downfield from TMS as
internal standard. Coupling constants are given in Hertz.
NMR multiplicities are abbreviated as follows: s = singlet,
d = doublet, t = triplet, m = multiplet.
Results and discussion
The N,N,O-tridentate ligands 1 or 2 were combined with
Pd(II) in situ and used as catalysts. Our initial attempts at
coupling reactions used palladium acetate and 4-bromo-
toluene and phenylboronic acids as standard substrates. We
also looked at the other factors that influence the reaction,
such as temperature, solvent, base, palladium source,
palladium loading, and Pd:ligand ratio (Scheme 2).
Generally, solvent plays an important role in the palla-
dium-catalyzed Suzuki reaction under both ligand-promoted
[19] and ligand-free [29] conditions. The influence of sol-
vent in the present system was therefore evaluated first
(Table 1), according to the green solvent selection guide
[30]. Methanol was found to be the best solvent in our
screening experiments (Table 1, entries 2 and 7). With tol-
uene and THF, only low to moderate results were obtained
(Table 1, entries 3 and 4).
GLC analysis
GLC experiments were carried out on an Agilent 6890
chromatograph, using an AT.SE-30 column of 50 m
length, 0.32 mm diameter and 0.5 lm film thicknesses.
GLC parameters for Suzuki reactions were as follows:
injector temperature 280 °C; detector temperature 280 °C;
initial temperature 60 °C; initial time 5 min; temperature
ramp 1, 30 °C min-1; final temperature 200 °C; ramp 2,
20 °C min-1; final temperature 250 °C; run time 25 min;
inject 1.0 lL; helium as the GLC carrier gas; pressure of
the system was 3.5 bar.
Herein, tri(p-tolyl)boroxine (Scheme 1, structure 7) and
phenol were observed as side products (determined by GLC-
MS), self-coupling reaction found under air (Table 1, entries
9 and 10). Oxygen is a particular problem with many tran-
sition metal catalyzed reactions, often poisoning the metal
catalyst, as well as causing competing reactions. We suspect
that the Pd(II)/N,N,O-ligand system catalyzes the oxidative
homocoupling of arylboronic acid in air, since the formation
of phenols is usually observed in homocoupling of arylbo-
ronic acids [31]. Hence, subsequent experiments were car-
ried out under an inert nitrogen atmosphere.
General procedure for the Suzuki reactions
The appropriate amounts of ligand and metal precursor were
added to the required solvent (3.0 mL). The mixture was
stirred for 5 min, then the aryl halide (0.5 mmol), phenyl-
boronic acid (0.75 mmol), and base (1.0 mmol) were added,
and the mixture was stirred and reacted under an inert
atmosphere. The course of the reaction was monitored by
GLC-MS analysis, and yields were calculated against the
aryl halides. On completion of the reaction, the solvent was
removed under reduced pressure. The residue was diluted
with H2O (3.0 mL) and Et2O (3.0 mL), followed by the
extraction with Et2O (2 9 3.0 mL). The organic fraction
was dried over anhydrous MgSO4 then filtered and the
The Suzuki cross-coupling strongly dependent on the
palladium source used [32] and the palladium/ligand ratio
[33, 34]. Therefore, the next step was to identify the best
Scheme 2 Suzuki coupling of 4-bromotoluene with phenylboronic
acid in the presence of Pd(II)/L
123