B. P. Bandgar, A. V. Patil / Tetrahedron Letters 46 (2005) 7627–7630
7629
Table 2 (continued)
a,b
Yield (%)
Entry
Arylboronic acid
Acid chloride
Ketone
Time (min)
O
O
1
1
1
5
6
7
Cl
5
20
20
90
—
—
B(OH)2
B(OH)2
OCH
COCl
2
NR
NR
B(OH)2
B(OH)2
B(OH)2
Cl
O
O
O
1
1
2
8
9
0
NR
NR
NR
20
20
20
—
—
—
Cl
Cl
O
B(OH)2
Cl
NR: No reaction.
a
Yields of pure isolated products.
Products were characterized by H NMR, IR, elemental analysis and by comparison with authentic samples.
b
1
acyl chlorides and arylboronic acids under solvent-free
conditions (Scheme 1 and Table 2).
low yields of ketones in polar solvents, drastic condi-
tions and hydrolysis of acid chlorides with hydrated
base were the limitations associated with a more recently
8
The catalytic activity of PdCl was investigated with re-
reported method.
2
spect to loading. After screening different amounts of
the PdCl catalyst, we found that 3.3 mol % of PdCl
worked remarkably well. The results are presented in
Table 1.
Most of the reported Suzuki-coupling reactions for the
synthesis of aryl ketones from arylboronic acids and
acyl chlorides require the use of a ligand and elevated
2
2
6
–9
temperatures.
However, ligandless palladium species
1
2
This study (Table 1) showed that in the absence of cat-
alyst, there was no reaction. The yield of ketone was in-
creased on increasing the amount of catalyst and was
found to be optimal with 3.3 mol % of a catalyst.
give fast coupling reactions and phosphine related side
1
3
reactions can be suppressed. Therefore, the present
methodology is superior in terms of the excellent yields
of ketones under solvent-free, ligand-free and mild con-
ditions in very short reaction times without formation of
a trace amount of any biaryls. It is important to note
that various aryl (Table 2, entries 1–9), heteroaryl (Table
2, entries 10–14) and aliphatic (Table 2, entry 15) boro-
nic acids underwent smooth cross-coupling with a vari-
ety of acyl chlorides under ligandless and solvent-free
conditions at room temperature. It is important to men-
tion that aliphatic (Table 2, entries 16–20), even aryl-
oxylalkyl (Table 2, entry 16) and arylalkyl (Table 2,
entry 17) acyl chlorides did not couple with aryl boronic
acids (Table 2, entries 16–19) even after grinding the
reaction mixture for a longer time (20 min) under the
present reaction conditions. The reaction is not affected
by substituents located either on the boronic acids or on
the acyl chlorides, which opens the way to a general syn-
thesis of ketones. Further work on the synthesis of nat-
ural chalcones using this novel methodology is under
investigation in our laboratory.
The generality of this method is indicated by the re-
sults presented in Table 2. The recently reported
Pd(PPh ) catalyzed synthesis of ketones involved five
3
4
mole equivalents of CsCO , elevated temperatures
3
(
100 °C) and long reaction times (16 h) under anhydrous
6
conditions and a nitrogen atmosphere. Attempts to
couple benzoyl chloride with 2,4,6-trimethylbenzene-
boronic acid using the conditions reported by Wright
et al. for the Suzuki coupling reaction (CsF, DME)
provided the ketone in low yield (19%) whereas the
1
1
6
6
conditions reported by Haddach and McCarthy fur-
nished the corresponding ketone in only a slightly im-
proved yield (50%). In this context, the present
methodology was found to be superior as it provided
an excellent yield of the corresponding ketone (80%)
(
Table 2, entry 5) in a very short time (5 min) under mild
conditions (25 °C). Similarly, cross-coupling of 4-nitro-,
-chloro-, 4-methoxy- and 4-methyl-benzoyl chlorides
4
with benzeneboronic acid using the present method fur-
nished excellent yields of ketones as compared to the low
yields of the corresponding ketones using HaddachÕs
harsher conditions (100 °C). The method reported by
Typical procedure: To a mixture of benzeneboronic acid
(122 mg, 1 mmol), sodium carbonate (212 mg, 2 mol)
and 4-methoxybenzoyl chloride (0.174 ml, 1.5 mmol) in
a mortar, palladium chloride (6 mg, 3.3 mol %) was
added with continuous grinding with a pestle at 25–
30 °C. The reaction was monitored by TLC. After com-
1
0
Bumagin and Korolev can be performed only insofar
as the acid chloride is not susceptible to water. The