NHC-Ligands in the Fluorine-Free Hiyama Reaction
Celite and anhydrous Na2SO4, and then evaporated. The obtained
crude product was purified by recrystallization (MeOH/H2O), or
by flash chromatography on silica gel (ethyl acetate/hexane). Yields
are given in Table 2. Physical, spectroscopic, and analytical data,
as well as literature references of know compounds are given in the
Supporting Information.
essential to obtain the coupling product. Chlorobenzene de-
rivatives bearing electron-withdrawing groups, such as 4-
chlorophenyl methyl ketone and 1-chloro-4-(trifluorome-
thyl)benzene, were arylated with almost quantitative yield
(Table 2, entries 7 and 8). As expected, 3-chloroaniline
showed lower reactivity, but the yield could be increased
from 42 to 63% with the catalytic Pd/salt 5 ratio of 1:5.
Moreover, heterocyclic chlorides (i.e., 2-chloropyridine, 3-
chloro-1-methylquinoline) were satisfactorily coupled with
trimethoxy(phenyl)silane, affording the expected products
with 53 and 66% isolated yield, respectively (Table 2, entries
9 and 11).
Supporting Information (see footnote on the first page of this arti-
cle): Factorial design experiments, general procedure for Hiyama
reaction, characterization data (for compounds 8), 1H and 13C
NMR spectra (for compounds 5 and 8).
Acknowledgments
Financial support from the Spanish Ministerio de Ciencia e Innov-
ación (MICINN) (project numbers CTQ2007-65218, CTQ2011-
24165), from Consolider Ingenio 2010 (CSD2007-00006), from the
Generalitat Valenciana (PROMETEO/2009/0349), and from the
Fondos Europeos para el Desarrollo Regional (FEDER) is ac-
knowledged. I. P. thanks the MICINN for a predoctoral fellowship.
Conclusions
The catalytic system formed in situ from Pd(OAc)2 and
the imidazolium salt 5 (in 1:2, 1:5 and 1:10 ratio), in the
presence of NaOH (50%, w/w aqueous solution) promotes
the Hiyama reaction. Both the amount of palladium and
the salt 5 are crucial for the outcome of the reaction. Thus,
when a Pd/salt 5 ratio higher than 1:5 is used, the amount
of palladium (0.1 mol-% being the level of choice) is the
most important parameter, whereas for lower amounts of
salt 5, both parameters are decisive factors in the yield.
Generally, the use of a 1:5 Pd/salt 5 ratio provided the most
significant improvement in the yields of the coupling prod-
ucts, starting from aryl bromides and aryl chlorides.
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Experimental Section
General Remarks: All commercially available reagents (Acros, Ald-
rich, Fluka) were used without further purification. Melting points
were determined with a Reichert Thermovar hot plate apparatus
and are uncorrected. NMR spectra were recorded with Bruker-Av-
ance 300 and Bruker–Avance 400 spectrometers (300 and 400 MHz
for 1H NMR, and 75 and 100 MHz for 13C NMR, respectively),
using CDCl3 as solvent and TMS as internal standard, except
where otherwise stated; chemical shifts are given in δ (ppm) and
coupling constants (J) in Hertz. Mass spectra (EI) were obtained
at 70 eV with an Agilent 5973 spectrometer, fragment ions in m/z
with relative intensities (%) in parenthesis. Infrared spectra were
recorded with a Perkin–Elmer Spectrum 100 spectrometer as neat
solids. Analytical TLC was performed on Merck aluminum sheets
with silica gel 60 F254. Silica gel 60 (0.04–0.06 mm) was employed
for flash chromatography. Microwave reactions were performed
with a CEM Discover Synthesis Unit (CEM Corp., Matthews, NC)
with a continuous focused microwave power delivery system, in
glass vessels (10 mL) sealed with a septum under magnetic stirring.
General Procedure for the Hiyama Coupling of Aryl Halides with
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(0.001 mmol, 0.2 mg), imidazolium salt 5 (0.002 mmol, 0.6 mg; or
0.005 mmol, 1.5 mg), aryl halide (1 mmol), arylsiloxane
(1.5 mmol), and TBAB if indicated (see Table 1 and Table 2). An
aqueous solution of NaOH (0.1 mL, 50% w/w) was added drop-
wise, the vessel was sealed with a septum, and the mixture was
heated in air at 120 °C by a microwave irradiation of initial power
80 W for 60 min. After allowing the reaction to cool to room tem-
perature, the mixture was extracted with diethyl ether (5ϫ 5 mL),
and the combined organic layers were filtered through a pad of
Eur. J. Org. Chem. 2013, 1479–1484
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