Iron catalyzed highly regioselective dimerization of terminal aryl alkynes

Article abstract of DOI:10.1039/c1cc10346f

Iron can catalyze head-to-head dimerization of terminal aryl alkynes to give the corresponding (E) selective conjugated enynes in high yields. A variety of substituted aryl acetylenes underwent smooth dimerization using catalytic FeCl₃ and DMEDA in the presence of KO^tBu.

Full text of DOI:10.1039/c1cc10346f

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COMMUNICATION
Iron catalyzed highly regioselective dimerization of terminal
aryl alkynesw
Ganesh Chandra Midya, Sushovan Paladhi, Kalyan Dhara and Jyotirmayee Dash*
Received 18th January 2011, Accepted 13th April 2011
DOI: 10.1039/c1cc10346f
Iron can catalyze head-to-head dimerization of terminal aryl
alkynes to give the corresponding (E) selective conjugated
enynes in high yields. A variety of substituted aryl acetylenes
underwent smooth dimerization using catalytic FeCl3 and
DMEDA in the presence of KOtBu.
Table 1 Screening of reagents for iron catalyzed dimerization of
phenyl acetylene 1a
Conjugated enynes are the most versatile building blocks in
organic synthesis found in bioactive molecules, drug inter-
mediates, and organic electronic materials.1,2 Dimerization of
terminal alkynes is an atom-economical3 and practical method
to prepare conjugated enynes.4–6 However, a highly selective
synthesis of conjugated enynes by a dimerization is challenging4–6
due to the competitive formation of other three possible (E),
(Z), and gem-enyne6 isomers (Scheme 1).4–6 Although various
transition metal4 and f-element catalysts5 are known to catalyze
the dimerization of terminal alkynes, it is an important goal
to develop clean and economically interesting processes for
selective alkyne dimerization.
Solvent,
temp/1C, time
Ratio,c yield (%)
of 2a (E/Z)
Entry
Cat.a
Baseb
1
2
3
4
5
6
7
8
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
Cs2CO3
K2CO3
K3PO4
KOtBud
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
KOtBu
Toluene, 145, 48 h
Toluene, 145, 72 h
Toluene, 145, 72 h
Toluene, 145, 2 h
Toluene, 145, 2 h
Toluene, 65,15 h
THF, 85, 2 h
CH2Cl2, 85, 2 h
MeCN, 145, 2 h
DMF, 145, 2 h
DMSO, 145, 2 h
Dioxane, 145, 2 h
Neat, 145, 2 h
89 : 11, 48
67 : 33, 50
86 : 14, 35
78 : 22, 65
78 : 22, 73
75 : 25, 50
61 : 29, 67
NR
9
NR
10
11
12
13
75 : 25, 55
74 : 26, 50
72 : 28, 45
71 : 29, 45
Recently iron-based catalytic systems have generated significant
growing interests because iron salts are inexpensive and
readily available.7–10 Iron salts have been used as important
alternatives to established transition metal-catalyzed carbon–
carbon and carbon–hetero bond formation reactions7 including
Sonogashira8 and Suzuki coupling.9 In our efforts directed
towards development of sustainable chemical procedures, we
herein report E-selective head-to-head dimerization of terminal
aryl alkynes catalyzed by a FeCl3-bidentate chelating ligand
system in the presence of KOtBu.
a
b
c
30 mol% of FeCl3 (98%), 3 equiv. of base, E : Z ratios were
determined by 1H NMR analysis of the crude reaction mixture. 2 equiv.
d
of KOtBu.
When phenyl acetylene 1a was treated with FeCl3 (30 mol%)
and DMEDA (L, 30 mol%) in the presence of Cs2CO3 for 48 h
(Table 1, entry 1), the enyne 2a (ratio E/Z = 89 : 11) was
obtained in 48% yield.11 Encouraged by this finding, we
examined the efficiency of this FeCl3 catalyzed ligand system
for dimerization of phenylacetylene 1a as a model system, and
some of the representative results are summarized in Tables 1–3
(and ESIw).
After screening of different bases (entries 1–5), potassium
tert-butoxide (3 equiv.) was found to be the most effective, and
73% yield of the desired product 2a was obtained (E/Z =
78 : 22) using toluene as the solvent at 145 1C for 2 h (entry 5).
The yield and selectivity of product 2a decreased with further
increasing of the reaction time (entry 6). All other tested bases,
such as K2CO3, Cs2CO3 or K3PO4, took longer reaction time
(48 to 72 h) and gave lower yield of enyne 2a (entries 1–3). The
reactions employing different solvents, such as THF (entry 7),
DMF (entry 10), DMSO (entry 11) and dioxane (entry 12),
Scheme 1 Dimerization of terminal alkyne.
Department of Chemical Sciences, Indian Institute of Science
Education and Research Kolkata, Mohanpur, West Bengal 741252,
India. E-mail: jyotidash@iiserkol.ac.in; Fax: +91 3325873020;
Tel: +91 3325873119
w Electronic supplementary information (ESI) available: Detailed
description of experimental procedures, characterization of all com-
pounds. See DOI: 10.1039/c1cc10346f
c
6698 Chem. Commun., 2011, 47, 6698–6700
This journal is The Royal Society of Chemistry 2011

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gave the desired product in low yields, whereas no product was
detected using CH2Cl2 (entry 8) and MeCN (entry 9). The
dimer 2a was obtained in 45% yield under solvent free
conditions (entry 13).
to reagent grade FeCl3 (97%, SRL, entries 1 and 2, Table 2).
On the basis of selectivity, reaction times and yields (Tables 1
and 2 and ESIw), the best result was achieved using 30 mol%
FeCl3, 30 mol% DMEDA, and 3 equiv. of KOtBu in toluene
at 145 1C for 2 h.
We found that a series of aryl acetylenes 1 smoothly
underwent dimerization to produce the head-to-head dimers
2 in good to excellent yield (Table 3). Both strongly electron-
donating and electron-withdrawing groups were compatible
It is intriguing to note that KOtBu alone (entry 4, Table 2)
without the addition of FeCl3 and DMEDA (ESIw) could
promote dimerization leading to 11% of the dimerized product
2a along with 63% of the tert-butoxystyrene 4a (E/Z =
17 : 83).12,13 While in the presence of FeCl3 (30 mol%), the dimer
2a was obtained as the sole product (ESIw), which reveals the
potential role of the iron catalyst in this transformation. In the
absence of base, no reaction took place (entry 3, Table 2).
Recently Buchwald and Bolm reported that FeCl3 catalyzed
reactions may be influenced by trace amounts of copper
impurities.14 However, iron/copper promoted oxidative
homo-coupling reaction of terminal alkynes has been reported
to give the corresponding diynes.15 We have carried out the
dimerization of 1a using copper salts in the presence of L and
KOtBu. Copper salts were found to be ineffective to promote a
dimerization of 1a to give the desired product 2a (entries 10
and 11, Table 2).
Table 3 Iron catalyzed dimerization of aryl acetylenes 1a,b
Entry Substrate 1
Conv.a Ratio of 2 (E/Z)a Yield (%) 2
1
2
499
499
78 : 22
77 : 23c
73
42c
The yield of enyne 2a was significantly decreased using
Fe(acac)3 (entry 6, Table 2) instead of FeCl3 (entry 1). No
product was obtained using FeCl3 on silica gel (entry 5). Our
results show that anhydrous iron salts are more effective
(entries 7 and 8) to catalyze the transformation. We further
found out that the purity of iron source does not play an
important role in this reaction. Anhydrous FeCl2 (beads,
99.99%, Aldrich) could promote the dimerization of 1a to
give the dimer 2a in 63% yield (entry 8, Table 2). Similarly
FeCl3 (99.9%, Aldrich) gave comparable results with respect
3
85
67 : 33
67 : 33
71
67
4
75
5
6
499
499
67 : 33
56 : 44c
55
29c
7
8
499
499
73 : 27
70 : 30
99
97
Table 2 Iron catalyzed dimerization of phenyl acetylene 1a
9
499
493
499
73 : 27
67 : 33
75 : 25
55
73
57
10
11
Ratio of
2 : 4b
Ratio, yield Ratio, yield of
of 2a (E/Z)b 4a (E/Z)b (%)
Entry Cond.a
1
2
3
FeCl3,c L, KOtBu
100 : 0
100 : 0
78 : 22, 73
78 : 22, 71
—
—
12
13
499
75 : 25
78 : 22
59
50
FeCl3,d L, KOtBu
FeCl3,c Ld
No isolated
product
26 : 74 77 : 23, 11 17 : 83, 63
4
5
KOtBu
84
FeCl3 on silica gel,e L, No isolated product
KOtBu
6
7
Fe(acac)3,f L, KOtBu 82 : 18
80 : 20, 45 499 Z, 12
78 : 22, 50 499 Z, 7
FeCl2,6H2O,g L,
85 : 15
14
15
77
84
78 : 22
83 : 17
65
61
KOtBu
FeCl2,h L, KOtBu
100 : 0
100 : 0
5 : 95
67 : 33, 63
55 : 45, 62
—
—
—
—
—
h
8
9
10
11
FeCl2, L, KOtBui
CuCl, L, KOtBu
CuCl2.2H2O, L,
KOtBu
6 : 94
—
16
17
a
495
71 : 29
—
90
a
30 mol% of FeCl3, 30 mol% of L and 3 equiv. of KOtBu were
used. Ratios were determined by 1H NMR analysis of the unpurified
b
—
NR
c
reaction mixture. Purity and source of iron salts: 99.9%, Aldrich,
Determined by 1H NMR analysis of the crude reaction mixture. All
d
e
f
97%, Sisco Research Laboratory (SRL), 5 wt%, Aldrich, 97%,
b
g
h
i
c
the reactions were carried out using 99.9% FeCl3 (Aldrich). In the
Aldrich, 98%, Loba Chemie, 99.99%, Aldrich, Using 40 mol%
of KOtBu for 15 h.
absence of L.
c
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Chem. Commun., 2011, 47, 6698–6700 6699

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with this procedure (Table 3). The yields for the dimerization
ranged from 50 to 99% and the ratio of E and Z head-to-head
dimers varies from 67 : 33 to 83 : 17 in favor of the E isomer.
The dimerization of 4-fluorophenylacetylene 1b in toluene
gave a 67 : 33 mixture of the E and Z dimers in 71% yield
(Table 3, entry 3). The 4-bromophenylacetylene 1c was reacted
under similar conditions (entry 4, Table 3) to give the
corresponding product 2c in 67% yield. When dimerization
of aryl acetylene 1d was carried out in the absence of
ligand (entry 6), the corresponding product 2d was obtained
in 29% yield as nearly 1:1 ratio of E/Z isomers. While in the
presence of ligand L (entry 5) the product 2d was obtained in
improved yield (55%) and selectivity (E/Z = 67:33), which
confirms the key role of ligand in iron catalyzed dimerization.
4-Methyl and 4-methoxy phenylacetylenes (1e,f) furnished the
corresponding dimers 2e,f in near quantitative yield (E/Z =
2.5 : 1, entries 7 and 8).
In summary, we have described a novel iron catalyzed
regioselective dimerization of terminal aryl alkynes to prepare
a variety of conjugated enyne compounds. This catalytic system
represents an alternative to toxic and expensive transition
metals. Further mechanistic investigation is currently underway.
We thank DST and CSIR, India, for funding. GCM and SP
thank CSIR and KD thanks UGC for research fellowship.
Notes and references
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substrates bearing ortho substituents 1m and 1n (entries 15,
16) gave the desired products in good to high yields. Our
results also show that substrates having meta-substituted
phenylacetylenes reacted slower affording the corresponding
products in moderate yields (entries 9–13). For example,
1-ethynyl-3,5-difluorobenzene (1j) was converted to the corre-
sponding dimers in 59% yield with an E/Z ratio of 3 : 1. The
2-ethynyl-6-methoxynaphthalene (1l) furnished the desired
product in 65% yield (entry 14). Under the reaction conditions
employed, aliphatic alkyne 1o did not yield the corresponding
dimer 2o at all (entry 17).
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A plausible reaction mechanism is depicted in Scheme 2.
The catalytic cycle may proceed with the formation of metal
acetylide 5.16 Subsequent head-to-head insertion of alkyne 1
into the acetylide compound 5 would yield the alkenyl inter-
mediate 6. Another molecule of alkyne may react with 6 to
yield the dimer 2 and regenerate the alkynide species 5. While
the reaction proceeds using catalytic KOtBu (40 mol%,
Table 2, entry 8) in the case of 1a to give 2a in 62% yield,
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Scheme 2 Proposed mechanism.
c
6700 Chem. Commun., 2011, 47, 6698–6700
This journal is The Royal Society of Chemistry 2011