One-Pot Dual Substitutions by Suzuki–Miyaura Cross-Coupling Reactions
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures and spectral data of all compounds.
strated that this procedure is efficient using as low as
0.01 mol-% of catalyst, and can be performed at room tem-
perature. This method was successfully expanded to two
heterocyclic electrophiles and allowed one-pot dual substi-
tutions of bromobenzyl chloride, 2-chloromethyl-6-bromo-
imidazo[1,2-a]pyridine, and 6-chloro-2-chloromethylimid-
azo[1,2-b]pyridazine, leading to numerous new unsymmetri-
cal methylene-linked biaryl systems.
Acknowledgments
We express grateful acknowledgement to Frederic Montigny (SA-
VIT) for the NMR spectroscopic data.
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Experimental Section
General Method for the Preparation of Compounds 1–18: Into a
dried sealed-tube was introduced, under argon, benzyl chloride
(0.5 mmol), Na2CO3 (1.05 mmol), the corresponding boronic acid
(0.6 mmol), tetrakis(triphenylphosphane)palladium (0.01 mmol),
1,2-dimethoxyethane (2 mL) and water (1 mL). The tube was se-
aled and heated at 100 °C for 4 h. After cooling, the resulting mix-
ture was diluted in water, and the aqueous layer was extracted with
CH2Cl2. The organic layer was dried with MgSO4 and filtered, and
the solvents were evaporated to dryness. The residue was purified
by column chromatography.
General Method for the Preparation of Compounds 19–23: The reac-
tion was carried out as described in the previous method using
0.5 mmol of boronic acid.
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General Method for the Preparation of Compounds 24–38: Into a
dried, sealed tube was introduced, under argon, (ar)alkyl halide
(0.5 mmol), Na2CO3 (1.05 mmol), boronic acid I (0.5 mmol), tetra-
kis(triphenylphosphane)palladium (0.01 mmol), 1,2-dimethoxye-
thane (2 mL) and water (1 mL). The tube was sealed and heated at
100 °C for 4 h. The reaction was followed by TLC. After cooling,
boronic acid II (0.5 mmol) and Na2CO3 (1.05 mmol) were intro-
duced. The tube was sealed, and the mixture was heated at reflux
at 100 °C for 4 h. The reaction was followed by TLC. After cooling,
the resulting mixture was diluted with water, and the aqueous layer
was extracted with CH2Cl2. The organic layer was dried with
MgSO4 and filtered, and the solvents were evaporated to dryness.
The residue was purified by column chromatography.
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Received: June 5, 2008
Published Online: August 26, 2008
Eur. J. Org. Chem. 2008, 4824–4827
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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