Highly regioselective cyclotrimerization of terminal alkynes catalyzed by Fe(II) complexes bearing 2-(benzimidazolyl)-6-(1-(arylimino)ethyl)pyridines

Article abstract of DOI:10.1016/j.catcom.2010.11.013

FeCl₂ ligated with 2-(benzimidazolyl)-6-(1-(arylimino)ethyl) pyridine in the presence of zinc powder and zinc iodide could effectively catalyze cyclotrimerization of intermolecular alkynes to afford benzene derivatives in high regioselectivity. The synthetic usefulness of this catalytic system consisting of Fe(II) complex C1, Zn and ZnI₂ in acetonitrile was tested with various terminal alkynes. In the cases of using aryl substituted alkynes, the 1,2,4-trisubstituted benzenes 2 were found to be the major products.

Full text of DOI:10.1016/j.catcom.2010.11.013

Catalysis Communications 12 (2011) 489–492
Contents lists available at ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Highly regioselective cyclotrimerization of terminal alkynes catalyzed by Fe(II)
complexes bearing 2-(benzimidazolyl)-6-(1-(arylimino)ethyl)pyridines
b,
Yongbing Liu a, Xiaoyu Yan b, Nianfa Yang a, , Chanjuan Xi
⁎
⁎
a
Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry, Xiangtan University, Xiangtan, Hunan 411105, China
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China
b
a r t i c l e i n f o
a b s t r a c t
Article history:
FeCl2 ligated with 2-(benzimidazolyl)-6-(1-(arylimino)ethyl)pyridine in the presence of zinc powder and
zinc iodide could effectively catalyze cyclotrimerization of intermolecular alkynes to afford benzene
derivatives in high regioselectivity. The synthetic usefulness of this catalytic system consisting of Fe(II)
complex C1, Zn and ZnI2 in acetonitrile was tested with various terminal alkynes. In the cases of using aryl
substituted alkynes, the 1,2,4-trisubstituted benzenes 2 were found to be the major products.
© 2010 Elsevier B.V. All rights reserved.
Received 3 September 2010
Received in revised form 15 November 2010
Accepted 15 November 2010
Available online 26 November 2010
Keywords:
Iron(II) complexes
Cyclotrimerization of alkynes
Tridenate nitrogen ligand
Alkynes
1. Introduction
N,N-ligands, and tridentate N,N,N-ligands were proven to be efficient
catalyst precursors for the ethylene oligomerization and polymeriza-
Since the first transition-metal-catalyzed trimerization of al-
kynes to benzene has been demonstrated by Reppe in 1948 [1],
the [2+2+2] cycloaddition of alkynes was extensively studied [2–5].
Although this approach has become one of the most powerful meth-
ods to assemble a benzene ring, it suffers from serious chemo- and
regioselectivity problems which normally lead to a complex mixture
of products, thus severely limiting synthetic utility of this reaction.
Alternative approaches have been proposed to circumvent the lack of
selectivity. Indeed, intramolecular [6,7] or partially intramolecular
reactions of α,ω-diynes with an excess of monoalkynes [8,9] have been
successfully employed to solve the selective problems and have
been elegantly used in the total synthesis of complexly natural and
artificial compounds. On the other hand, several elaborately catalytic
systems involving palladium [10], ruthenium [11], rhodium [12],
cobalt [13–15], iridium [16], and other transition metals [17–19] with
rational ligands have been described to overcome this problem.
Nonetheless, the selectivity of catalytic intermolecular cyclotrimeriza-
tion of alkynes has remained a crucial issue.
tion reaction [27–30]. To our knowledge, iron-catalyzed highly
regioselective cyclotrimerization of intermolecular alkynes has been
rarely explored, although iron-catalyzed cyclotrimerizations of intra-
molecular alkynes have been reported [31,32]. We report herein
FeCl2/2-(benzimidazolyl)-6-(1-(arylimino)ethyl)pyridine complex
catalyzed cyclotrimerization of terminal alkynes with high regios-
electivity (Scheme 1).
2. Results and discussion
The 2-(benzimidazolyl)-6-(1-(arylimino)ethyl)-pyridyliron
dichlorides (C1–C5, Fig. 1) were readily prepared by the reaction of
FeCl2·4H2O with the corresponding 2-(benzimidazolyl)-6-(1-(aryli-
mino)ethyl)-pyridines (L) in ethanol according to the literature [29],
whilst the 2,6-bis(1-(2,6-dimethylphenylamino)ethyl)pyridyliron
chloride (C6, Fig. 1) was prepared by the literature procedure [33].
To examine the catalytic activity of complex C1–C5 on cyclo-
trimerization of intermolecular alkyne, we tested the cyclotrimeriza-
tion of phenylacetylene as a model reaction, which resulted in a
quantitative yield of product 2a with complex C1 in excellent
regioselectivity (Table 1, entry 1). The complexes as precatalyst
both with electron-donating groups (entries 1, and 2) and electron-
withdrawing groups (entries 4, and 5) on the benzene ring of ligands
showed high activities. Complex C3 having bulky group on the
benzene ring showed moderate activity (entry 3) compared with
complexes C1 and C2. When complex C6 was used as a precatalyst
under the same conditions, the reaction proceeded in 80% yield with
lower regioselectivity (entry 6). Since many modifications of the
Iron is an ideal transition metal, given its low price, non-toxicity
and environmentally benign character. Recently, iron complexes are
used as catalysts in synthetic chemistry for carbon–heteroatom [20]
and carbon–carbon bond-forming reactions [21,22]. Low-valent iron
complexes can induce cross-coupling [23], isomerization, and cyclo-
addition [21,24–26]. In addition, iron complexes ligated by bidentate
⁎
Corresponding author.
E-mail address: cjxi@tsinghua.edu.cn (C. Xi).
1566-7367/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2010.11.013

490
Y. Liu et al. / Catalysis Communications 12 (2011) 489–492
Scheme 1. Iron-catalyzed cyclotrimerization of terminal alkynes.
did not proceed without using iron complex (entry 16). Furthermore,
when the FeCl2·4H2O and ligand L1 were blended together as a
precatalyst, the reaction did not proceed (entry 17). Therefore, we
found the following optimized conditions: using complex C1 as a
precatalyst, the model reaction proceeded smoothly in 94% yield with
excellent regioselectivity in acetonitrile at 50 °C for 8 h under nitrogen
atmosphere.
The synthetic usefulness of the catalytic system consisting of Fe(II)
complex C1, Zn and ZnI2 in acetonitrile was tested with various
terminal alkynes (Table 2). In all cases the 1,2,4-trisubstituted
benzenes 2 were found to be the major products. The aryl substituted
terminal alkynes gave the 1,2,4-trisubstituted benzenes 2 in good to
excellent yields (entries 1–10). Aryl group could be borne as both an
electron-donating group (entries 2–4) and electron-withdrawing
group (entries 5–8). When 4-ethynyl-N,N-dimethylaniline 1d was
used as a substrate and the desired product was formed in 53% yield
(entry 4). Cyclotrimerization of 4-ethynylbiphenyl 1i gave 1,2,4-
trisubstituted benzene 2i in 89% yield (entry 9). Cyclotrimerization of
3-ethynylthiophene 1j also gave 1,2,4-trisubstituted benzene 2j in
90% yield (entry 10). When alkyl substituted terminal alkynes were
used, the cyclotrimerization products formed in moderate yields with
lower regioselectivity (entries 11–13). When ethyl propiolate 1n was
used, the product 2n formed in 46% yield with high regioselectivity
(entry 14). Cyclotrimerization of ethynyltrimethylsilane 1o afforded
product in low yield (entry 15). That may attribute to bulky TMS
Fig. 1. Iron complexes.
complexes as precatalyst can be envisaged, we identified the complex
C1 as the precatalyst. Decreasing the temperature from 50 °C to room
temperature, longer reaction time was required to accomplish the
reaction (entry 8). The applicability of solvents was also evaluated
(entries 1 and 9–12). Among several solvents tested, acetonitrile as
solvent afforded asymmetric benzene 2a in almost quantitative yield.
We then examined other zinc salts, for instance, ZnBr2 and ZnCl2
decreased the yield to 57% and 56% yield, respectively (entries 13–14).
It is noteworthy that without addition of any zinc salt, the reaction
proceeded in low yield (entry 15). These results indicated that in the
reaction ZnI2 may be necessary for activation of precatalyst C1
presumably by ligand exchange [34]. On the other hand, the reaction
Table 1
Optimization of the reaction conditions.a
2
Entry
Complex
Solvent
Temp. Time
(°C)
ZnX2
Yield of
Ratio of
2a+3a(%)b
2a/3ac
(h)
1
2
3
4
5
6
7
8
C1
C2
C3
C4
C5
C6
C1
C1
C1
C1
C1
C1
C1
C1
C1
-
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
THF
CH2CI2
Toluene
DMF
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
50
50
50
50
50
50
50
rt
50
50
50
50
50
50
50
50
50
8
8
8
8
8
8
1
24
8
8
8
8
8
8
8
8
8
ZnI2
ZnI2
ZnI2
ZnI2
ZnI2
ZnI2
ZnI2
ZnI2
ZnI2
ZnI2
ZnI2
ZnI2
ZnBr2
ZnCl2
-
94
91
48
93
89
80
55
83
Trace
0
0
9
57
56
16
0
98/2
98/2
98/2
98/2
98/2
79/21
98/2
98/2
-
9
10
11
12d
13
14
15e
16
17
-
-
-
98/2
98/2
-
-
-
ZnI2
ZnI2
FeCI2 4H2O/L1
0
a
Conditions: Phenylacetylene (110 mL, 1 mmol), complex (0.05 mmol), zinc powder (6.5 mg, 0.10 mmol), ZnX2 (0.10 mmol), solvent (2.0 mL).
Isolated yield.
b
c
The isomeric ratio was determined via careful integration of 1H NMR spectra.
1,4-Diphenylbuta-1,3-diene was obtained in 10% yield.
d
e
Mixture of 2a, 3a, 1,4-Diphenylbuta-1,3-diene.

Y. Liu et al. / Catalysis Communications 12 (2011) 489–492
491
Table 2
which can be reduced by Zn powder to give possible intermediates 4
[30,31]. The complex 4 can quickly react with two equivaluents of
alkyne to give metallacyclopentadienes 5 [35]. In some cases of the
reaction, a trace amount of 1,4-diphenylbuta-1,3-diene was detected.
That result confirmed that di(α-aryl)-ferrocyclopentadiene 5 would
be favorable than (α-aryl)-(β-aryl) ones. The intermediate 5 can
further be cyclized to 6 and/or 7 through an insertion or [4+2]-
cycloaddition pathway, respectively. Reductive elimination reaction
of 6 and/or 7 yields benzene derivative 2 and regenerates the low
valent complex 4.
Fe(II) complex C1 catalyzed cyclotrimerization of terminal alkynes.
C1 (5 mol%)
Zn (10 mol%)
ZnI2 (10 mol%)
R
R
R
R
+
CH3CN, 50°C
R
R
1
3
2
R
Yield (%)a
Ratio of 2:3b
98:2
R
Entry
Times (h)
1
2
Ph
1a
1b
8
8
94
91
p-MeC6H4
97:3
3
4
5
6
7
8
9
p-MeOC6H4
1c
1d
1e
1f
8
8
8
8
8
8
8
81
53
92
80
91
94
89
97:3
92:8
98:2
98:2
> 99
> 99
> 99
3. Conclusion
p-Me2NC6H
4
p-CIC6H4
p-FC6H4
We have shown that the cyclotrimerization of aromatic terminal
alkynes can be efficiently catalyzed by iron complexes in acetonitrile
to afford 1,2,4-trisubstituted benzene derivatives in good to excellent
yields. Further investigations of mechanism and applications are still
in progress.
p-AcC6H4
1g
1h
1i
p-MeO2CC6H4
p-PhC6H4
10
1j
8
90
95:5
4. Experimental
S
11
1k
1l
24
24
24
8
54
30
45
46
11
59:41
58:42
62:38
> 99
CI(CH2)3
4.1. Procedure for the preparation of complexes C1–C6
12
13
14c
15
Ph(CH2)2
NC(CH2)3
EtO2C
1m
1n
1o
The complexes C1–C6 were synthesized by the reaction of
FeCl2·4H2O with the corresponding ligands in ethanol. A typical
synthetic procedure for C1 was described as follows: the ligand 2,6-
dimethyl-N-(1-(6-(1-methyl-1 H-benzo[d]imidazol-2-yl)pyridin-2-
yl)ethylidene)aniline (74 mg, 0.21 mmol) and FeCl2·4H2O (79.5 mg,
0.20 mmol) were added to a Schlenk tube, followed by the addition of
freshly distilled ethanol (5 mL) with rapid stirring at room temper-
ature. The solution turned green immediately, and a blue precipitate
formed. The reaction mixture was stirred for 12 h, and then the
precipitate was washed with diethyl ether twice and dried to give the
pure product as a blue powder in 89% yield. IR (KBr; cm−1): 3448 (m),
3066 (m), 2952 (w), 2915 (w), 1560 (vs), 1495 (m), 1472 (s),
1419 (s), 1372 (m), 1323 (s), 1273 (m), 1211 (s), 1100 (m), 1021 (w),
TMS
24
> 99
aIsolated yield.
bThe isometric ratio was determined via careful integration of 1H NMR spectra.
c(E)-Dietyl hex-2-en-4-ynedioate was obtained with 23% isolated yield.
group. When the internal alkynes were treated under this reaction
conditions, the fully substituted benzene was not observed.
Although confirmation of the reaction mechanism must await
further study, we postulate the reaction course as illustrated in
Scheme 2, which based on reported metal-catalyzed reactions [2].
Firstly, the complex C (LFeCl2) may react with ZnI2 to afford LFeI2,
Scheme 2. Possible reaction mechanism.

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Y. Liu et al. / Catalysis Communications 12 (2011) 489–492
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alkynes
Iron(II) complex C1 (24.1 mg, 0.05 mmol), zinc powder (6.5 mg,
0.10 mmol), zinc iodide (32 mg, 0.10 mmol), terminal alkyne
(1 mmol), and acetonitrile (2.0 mL) were added to a pre-dried
screw capped test tube. The mixture was stirred at 50 °C for an
indicated time. The reaction mixture was quenched with hydrochloric
acid (3 M) and extracted with ethyl ether. The combined organic
phase was washed with brine, dried over MgSO4, and concentrated
under reduced pressure. The residue was purified by flash chroma-
tography on silica gel using a mixture of petroleum ether and ethyl
acetate as eluent to afford desired product.
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Acknowledgements
This work was supported by the National Natural Science
Foundation of China (20872076, 20972085 and 21032004), and by
the Specialized Research Fund for the Doctoral Program of Higher
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Appendix A. Supplementary data
Supplementary data to this article can be found online at
doi:10.1016/j.catcom.2010.11.013.
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