957
Table 2. CuFe2O4-catalyzed C-C cross-coupling of terminal
alkynes with aryl halides
Table 3. Reusability of CuFe2O4 nanoparticles and leaching of
Cu and Fe in multicycle alkynylation reactions
CuFe2O4 (10 mol%)
R
Recovered Product yield Cu leakage Fe leakage
Cycle
+ X Ar
R
Ar
CuFe2O4/%
/%a
(in ppm)
(in ppm)
Cs2CO3, N2, 24h
Entry
R
X
Ar
Product Yield/%a
1
2
3
®
97
95
70
68
68
0.35
0.3
0.2
0.06
0.02
0.02
1
2
3
4
5
6
7
8
9
10
11
12
13
14
Ph
Ph
Ph
I
I
I
C6H5
4-COMe-C6H4
4-OMe-C6H4
1
2
3
1
2
4
3
1
2
3
5
6
7
8
70a
48a
51a
58b
35b
42b
48b
20b
25b
25b
65a
55a
51a
58a
aReaction conditions: 1.02 mmol of phenylacetylene, 1.52
mmol of iodobenzene, 10 mol % of CuFe2O4 nanoparticles (for
cycle 1 and the remaining recovered amount of the catalyst
was used for subsequent cycles), 2.0 equiv of Cs2CO3, 5 mL of
1,4-dioxane, 24 h reflux under N2 atmosphere.
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Br C6H5
Br 4-COMe-C6H4
Br 4-CO2Et-C6H4
Br 4-OMe-C6H4
Cl C6H5
Cl 4-COMe-C6H4
Cl 4-OMe-C6H4
More interestingly, substituted aryl halides as well as heteroaryl
iodides (e.g. 2-iodobenzo[d]thiazole and 2-iodopyridine; Entries
13 and 14) also underwent cross-coupling with appreciable
yield.
Then, we turned our attention toward the coupling of alkyl-
alkynes with aryl iodides. Thus, when reactions were carried
out in the presence of 10 mol % of catalyst under optimized
conditions, 55-65% of the cross-coupled products were isolated
(Table 2, Entries 11 and 12).23
Next, we studied the reusability of a heterogeneous
CuFe2O4 catalyst in C-C coupling reactions (Table 3). After
completion of the reaction, the catalyst was recovered by the
application of an external magnet, was washed with ethyl acetate
and then acetone, and was dried in a hot air oven at 120 °C for
2 h. The recovered catalyst was reused under similar conditions
for the next run, and the catalytic behavior of the CuFe2O4
nanoparticles was found to be unaltered (yield, 68%), even up to
three consecutive cycles.
Then, the possibility of Fe and Cu leakage from CuFe2O4
to the medium during the reaction was investigated. After
completion of the reaction, the supernatant was collected and
tested for Fe and Cu by atomic absorption spectroscopy (AAS).
The leaching of Cu and Fe in three consecutive cycles was found
to be ¯0.5 ppm (Table 3), which is well below the permissible
level.24
n-C6H13
n-C6H13
Ph
I
I
I
I
C6H5
4-OMe-C6H4
C7H4NS
C5H4N
Ph
aReaction conditions: 1.02 mmol of phenylacetylene, 1.52
mmol of aryl halide, 10 mol % of CuFe2O4 nanoparticles, 2.0
equiv of Cs2CO3, 5 mL of 1,4-dioxane, 24 h reflux under N2
b
atmosphere. Reaction conditions: 1.02 mmol of phenylacety-
lene, 1.52 mmol of aryl halide, 10 mol % of CuFe2O4 nano-
particles, 2.0 equiv of Cs2CO3, 1.52 mmol KI, 5 mL of 1,4-
dioxane, 24 h reflux under N2 atmosphere.
the role of Fe in catalyst, the reaction was carried out in the
presence of CuO nanoparticles, but poor isolated yield (25%) of
diphenylacetylene was obtained. Thus, it may be concluded that
the synergistic effects of Fe and Cu in CuFe2O4 nanoparticles
cocatalyze the alkynylation reaction and are in line with other
earlier articles.13 The magnetic nature of the copper ferrite
nanoparticles facilitates their easy and quantitative removal from
the reaction medium in the presence of an external magnetic
field for further use.
The reaction conditions were then optimized with different
combinations of solvents and bases. As summarized in Table 1,
the cross-coupling reactions were carried out in different
solvents such as DMF, DMSO, THF, acetonitrile, tert-butanol
(t-BuOH), toluene, and 1,4-dioxane in the presence of com-
monly used bases (t-BuOK, Cs2CO3, K2CO3, Et3N, pyridine,
NaHCO3, and NaOAc). However, 1,4-dioxane and Cs2CO3
served as the best choice for higher yield of the cross-coupled
product. It may be noted that for this cross-coupling the right
choice of solvent/base pair is important. A decrease in the
catalyst loading from 10 to 5 to 1 mol % also afforded the
product in lower yield. Thus, optimum yield of diphenylacety-
lene was obtained when phenylacetylene, iodobenzene, and
10 mol % of copper ferrite nanoparticles were heated in
1,4-dioxane at 110 °C in the presence of Cs2CO3.
In conclusion, for the first time, we have demonstrated a
ligand-free heterogeneous magnetic catalytic system for the C-C
cross-coupling of terminal alkynes with aryl halides. The
synergistic effects of iron and copper in copper ferrite nano-
particles for the alkynylation reaction were exploited. The
catalyst can be recovered quantitatively in presence of external
magnet for further use. The negligible leaching of Cu and Fe
make the catalytic process environment benign. Further inves-
tigations on the catalytic activity of CuFe2O4 nanoparticles in
C-O and C-S cross-coupling reactions are under progress.
DST (Ref. SR/FTP/CS-101/2006), Govt. of India is
gratefully acknowledged for financial support.
After determining the optimized conditions,22 we then
investigated the scope of the magnetic catalyst for the C-C
cross-coupling reactions of differently substituted aryl halides
with phenylacetylene (Table 2).23 We found that only the aryl
iodides gave the cross-coupled product. However, aryl chlorides
and bromides gave the cross-coupled product only when an
equivalent amount of KI was added to the reaction mixture.
This paper is in celebration of the 2010 Nobel Prize
awarded to Professors Richard F. Heck, Akira Suzuki, and
Ei-ichi Negishi.
References and Notes
1
a) Metal-Catalysed Cross-Coupling Reactions, 2nd ed., ed.
by A. de Meijere, F. Diederich, Wiley-VCH, Weinheim,
Chem. Lett. 2011, 40, 956-958
© 2011 The Chemical Society of Japan