664
JINCHENG MAO et al.
Scheme 1. Coupling between equal amount of arylboronic acid
and dihaloarylenes using different Pd catalysts.
acid. A mixture of dihaloarene (0.4 mmol), arylboronic
acid (0.4 mmol), K2CO3 (0.8 mmol), PdCl2 (7 mol %),
PPh3 (15 mol %), and PEG-400 (2 mL) in a sealed tube
was stirred in air at 70°C for the desired time until com-
plete consumption of starting material as monitored by
TLC.After that the mixture was poured into ethyl acetate,
then washed with water, extracted with ethyl acetate, dried
by anhydrous Na2SO4, then filtered and evaporated under
vacuum, the residue was purified by flash column chro-
matography (petroleum ether or petroleum ether/ethyl
acetate) to afford the corresponding coupling products.
Routine work:
X
ArB(OH)2 (1 equiv.)
Pd cat.
X
X
Ar
Ar
This work:
X
ArB(OH)2 (1 equiv.)
Pd cat.
Ar
X
RESULTS AND DISCUSSION
which stimulates the growth of mammary tumors and
endometriosis via activation of the estrogen receptor [21].
In a pilot experiment, we carried out the reaction of
equal amount of 1,3-diiodoarene and arylboronic acid
as the model reaction to screen the reaction conditions
and the results are depicted in Table 1. It could be seen
that PEG-400 played the key role compared to other
solvents in the process of preferential oxidative addition,
and 75% yield of the desired product can be obtained
(Table 1, entries 1–7). Screening various bases including
organic bases and inorganic bases (Table 1, entries 8–13),
K2CO3 was proved the best (Table 1, entry 9). Despite
this, KOH and Cs2CO3 gave the moderate yields. PPh3
showed higher efficiency as the reaction ligand than all
other employed ligands, such as PCy3, dppe, P(NEt)3 and
P(OPh)3 (Table 1, entries 14–17). We were pleased to find
that PdCl2 showed higher catalytic activity than other
palladium sources (Table 1, entries 18–20). In order to
improve the yield, we screened temperature and reaction
time (Table 1, entries 21–24), 70° and 24 h proved to be
best. In addition, we tried to reduce the amount of catalyst
and ligand but failed (Table 1, entries 25–26). However,
when changing the amount of base to 2 equiv, 97% yield
of the desired product was obtained (Table 1, entry 27).
Normally, a molecule of dihalo reagent coupled with
equal amount of phenylboronic acid gained monosub-
stituted product as shown in Scheme 1. Disubstituted
product can be obtained only with a molecule of dihalo
reagent coupled with two equiv. phenylboronic acid.
How can a molecule of dihalo reagent coupled with
equal amount of phenylboronic acid to gain disubsti-
tuted product? In the mechanism of the Suzuki reac-
tion, Pd(0)-catalyst proceed via repeating the oxidative
addition-transmetalation-reductive elimination catalytic
cycle. If the regenerated Pd(0) catalyst could be ori-
ented to undergo oxidative addition preferentially with
its homogenously generated coupling product, then di-
substituted product can be obtained smoothly. Hu and
co-workers [22] found that the nature of the ligands has
great influence on the oxidative addition rate of a Pd(0)
catalyst. Differently, in the experiment we found that the
solvent can also make the oxidative addition preferen-
tially to process.
EXPERIMENTAL
With the optimized reaction conditions in hand, we next
applied the coupling of 1, 3-diiodoarene and a wide range
of arylboronic acids bearing either electron-donating or
electron-withdrawing groups as summarized in Table 2. To
our delight, excellent yields (79–88%) were achieved in the
coupling of o,m,p-methoxy-substituted arylboronic acid
(Table 2, entries 2–4). Unfortunately, aldehyde-substituted
arylboronic acids gave moderate yields (34–53%) in the
coupling with 1, 3-diiodoarene (Table 2, entries 5–7). We
speculated that electron-withdrawing inductive effects
of aldehyde substituent reduced the electron density of
benzene ring. In addition, methyl, fluoro, chloro, tert-butyl-
All reactions were carried out in air. All halides and
arylboronic acids were readily available. Flash col-
umn chromatography was performed using silica gel
(300–400 mesh). Analytical thin-layer chromatography
was performed using glass plates pre-coated with 200–
400 mesh silica gel impregnated with a fluorescent indi-
cator (254 nm). NMR spectra were measured in CDCl3
on a 400 NMR spectrometer with TMS as an internal
reference. Products were characterized by comparison
of 1HNMR, 13CNMR and TOF-MS data in the literature.
General procedure for Pd-catalyzed coupling be-
tween equal amount of dihaloarene and arylboronic
RUSSIAN JOURNAL OF APPLIED CHEMISTRY Vol. 89 No. 4 2016
Mao, Jincheng
