Iron-catalyzed cross-coupling reaction of vinyl bromides or chlorides with imidazoles in the absence of ligands and additives

Article abstract of DOI:10.1002/adsc.200900066

Highly effective coupling of imidazoles with (E)-vinyl halides can be achieved by using readily available iron catalysts under ligand-free, copper-free and palladium-free conditions. Coupling of (E)-vinyl bromides led to (Z)-products predominantly, while

Full text of DOI:10.1002/adsc.200900066

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DOI: 10.1002/adsc.200900066
Iron-Catalyzed Cross-Coupling Reaction of Vinyl Bromides
or Chlorides with Imidazoles in the Absence of Ligands and
Additives
Jincheng Mao,a,* Guanlei Xie,a Jiaming Zhan,a Qiongqiong Hua,b and Daqing Shia
a
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials
Science, Suzhou University, Suzhou 215123, Jiangsu, Peopleꢀs Republic of China
Fax : (+86)-512-6588-0089; e-mail: jcmao@suda.edu.cn
Department of Chemistry, Xuzhou Normal University, Xuzhou 221116, Peopleꢀs Republic of China
b
Received: February 1, 2009; Revised: April 10, 2009; Published online: June 2, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900066.
Abstract: Highly effective coupling of imidazoles
with (E)-vinyl halides can be achieved by using
readily available iron catalysts under ligand-free,
copper-free and palladium-free conditions. Coupling
of (E)-vinyl bromides led to (Z)-products predomi-
nantly, while the reactions of (E)-vinyl chlorides af-
forded (E)-isomers as the major products.
(Z)-isomer of the corresponding product. This raises
the question: how can we get the (Z)-products? Fur-
thermore, the availability of ligand-free and readily
available catalytic systems remains of interest when
considering cost and operability.[7]
Iron is an abundant, economical, and environmen-
tally friendly metal that shows increasingly promising
catalytic abilities in many organic transformations, in
particular for C C bond-forming reactions. How-
[8]
À
Keywords: cross-coupling; imidazoles; iron; ligand-
free conditions; vinyl halides
À
G
rarely been reported.[9–12] To the best of our knowl-
edge, there is no example of a vinylation reaction of
imidazoles with vinyl halides using this inexpensive
catalyst through such an economic and effective
N-(1-Alkenyl)imidazoles are versatile intermediates method. Herein, we report the efficient FeCl3-cata-
À
in the preparation of a wide variety of biologically lyzed ligand-free C N couplings between (E)-vinyl
and industrially valuable organic compounds.[1] The halides[13] and imidazoles. In our hands and and in
antifungal and antiparasitic properties of these types contrast to previous reports, couplings of vinyl bro-
of compound are of great interest to medicine and ag- mides afforded (Z)-products predominantly and the
riculture.[2] Thus, a number of methods has been de- couplings of vinyl chlorides resulted in (E)-isomers as
veloped to create these synthetic units in the past de- the major products, which are different from the tra-
cades.[3,4] Among these methods, vinylation reactions ditional reports. Thus, this new method could easily
of imidazoles with vinyl halides were the most effi- meet the demands of different isomers of N-(1-alk-
cient and straightforward, since the traditional meth-
ACHTUNGTRENeNGNU nyl)imidazoles simply by using different types of
ods suffer from harsh reaction conditions or lack of vinyl halides as starting materials.
stereocontrol of the double bond geometry.[4] To our
In order to find the most active ligand-free catalyst
astonishment, there are few reports about this direct system, various iron salts were screened for the N-ary-
coupling reaction until now.[5] Interestingly, we found lation of imidazole with (E)-b-bromostyrene as the
that just 10 mol% of CuI could also effectively cata- model reaction. Optimization data are listed in
lyze the coupling of nitrogen-containing heterocycles Table 1. Initially, a reagent combination of FeCl3,
with vinyl bromides and chlorides under ligand-free K3PO4 and DMF was tested (Table 1, entry 1). To our
and Pd-free conditions.[6] It is noteworthy that the delight, the corresponding product was obtained in
double bond geometry of these vinyl halides was com- 36% yield. The blank experiment indicated that the
pletely retained with our protocol: the coupling reac- presence of iron salt is necessary in our protocol
tions of (E)-vinyl halides led to exclusive (E)-prod- (entry 2). The use of other solvents such as toluene,
ucts, perhaps because the more stable (E)-isomer is NMP (N-methylpyrrolidone), DMSO, or glycol result-
more easily generated compared with the less stable ed in various yields (entries 3–6). Among them,
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Iron-Catalyzed Cross-Coupling Reaction of Vinyl Bromides or Chlorides
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Table 1. Screening of iron catalysts for N-arylation of imida-
zole with (E)-b-bromostyrene.[a]
Vinyl bromides with donor groups (such as methyl or
methoxy groups) at their aromatic rings led to de-
creased yields but higher Z/E ratios (entries 5–9). Ex-
citingly, we even discovered two examples of catalytic
reactions yielding only the (Z)-isomer products in
60% yield and 50% yield, respectively (entries 8 and
9). In these cases, the other isomer was not observed.
For example, a Cl-substituent on the ring of the vinyl
bromide gave better yields of the corresponding prod-
ucts (entries 10–12), while an F-substituent in the
vinyl bromide gave better Z/E ratios of the desired
products (entries 13 and 14). In addition, it is note-
worthy that we were able to get the (Z)-N-(1-alken-
Entry Fe cat.
Base
Solvent T [oC]/ Z/E Yield
t [h]
[%][b]
1
2
3
4
5
6
7
8
9
10
FeCl3
-
K3PO4 DMF
K3PO4 DMF
K3PO4 Toluene 120/24
K3PO4 NMP
K3PO4 DMSO 120/24 80:20 >99
120/24 50:50 36
120/24
–
–
trace
0
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
Fe
120/24 70:30 83
AHCTUNGTREGyNNUN l)imidazoles as the only product (entries 8 and 9 and
13 and 14).
K3PO4 glycol
K2CO3 DMSO 120/24
KOH
120/24
–
–
trace
trace
Using the optimized reaction conditions, we ex-
plored the N-arylation of imidazole with other vinyl
bromides (Z/E=5:7) (Scheme 1). Initial results
showed that the coupling product (Z/E=75:25) was
obtained in 98% yield. In order to explore whether
this protocol was generally selective for (Z)-type
products, pure (Z)-b-bromostyrene was employed as
the substrate: the corresponding (Z)-product (Z/E=
84:16) was acquired with 90% yield. Therefore, the
selectivity rules in this protocol are clearly different
from those of CuI catalytic systems.[5,6] Therefore,
FeCl3 and CuI catalysts may be complementary for
getting desired products in different isomers.
Under similar conditions, coupling reactions of ni-
trogen-containing heterocycles and vinyl chlorides af-
forded lower yields than those of vinyl bromides
(Table 3). However, it was suprising to find that the
(E)-products were obtained predominantly (Table 3,
entry 1). In order to improve our initial result, we per-
DMSO 120/24 70:30 86
Cs2CO3 DMSO 120/24 70:30 73
K3PO4 DMSO 120/24 80:20 80
powder
FeCl2
11
12
13
14
15
16
17[c]
18
19
K3PO4 DMSO 120/24 80:20 90
Fe
Fe2O3
Fe2A(SO4)3 K3PO4 DMSO 120/24 78:22 >99
ACHTUNGTRENNUNG
CHTUNGTRENNUNG
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
K3PO4 DMSO 100/24 67:33 40
K3PO4 DMSO 140/24 60:40 81
K3PO4 DMSO 120/24 60:40 51
K3PO4 DMSO 120/48 70:30 >99
K3PO4 DMSO 100/48 80:20 52
[a]
Iron
catalyst
(0.05 mmol),
(E)-b-bromostyrene
(0.5 mmol), imidazole (0.6 mmol), base (1.0 mmol), sol-
vent (2 mL), 1208C, 24 h, under an argon atmosphere.
Isolated yield (based on vinyl bromide).
[b]
[c]
The catalytic reaction was performed in air.
DMSO proved to be the best solvent with the desired formed the reaction with a longer time (36 h). How-
product being obtained in almost quantitative yield ever, neither yield nor E/Z ratio of the product
(entry 5). It is noteworthy that the stereoselectivity of changed significantly (entry 2 vs. entry 1). In contrast,
the product was 80:20 (Z/E). Subsequently, several when the coupling of (E)-vinyl chloride was per-
bases (K2CO3, KOH, and Cs2CO3) were investigated formed at a higher temperature (1308C), a higher
(entries 7–9), but still K3PO4 gave the highest yield yield was obtained at the expense of the E/Z ratio
(entry 5). Different forms of iron were employed in (entry 3). Other imidazoles derivatives did not afford
the coupling reaction (entries 10–14). It can be seen a better yield than imid
that generally a higher oxidation state of iron is favor-
ACHTUNGTNERaNUNG zole itself using our protocol
able for the catalytic reaction. All of the ironACTHNUGTRNEUNG(III)
salts gave quite similar results (entries 12–14). We
were not able to improve the catalytic conditions by
varying the temperature (entries 15 and 16). Under
the same conditions, the reaction performed in air
gave the desired product with lower stereospecificity
and yield (entry 17). Extension of reaction time did
not lead to enhanced results (entries 18 and 19).
The results that we obtained encouraged us to in-
vestigate the scope of application of this catalytic
system as summarized in Table 2. Couplings of (E)-b-
bromostyrene with different imidazoles gave good
yields and Z/E ratios, although substituents showed a
clear influence on the catalysis (Table 2, entries 1–4). Scheme 1.
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Jincheng Mao et al.
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Table 2. Catalytic N-vinylation of imidazoles with (E)-vinyl bromides by FeCl3.[a]
Entry
1
Vinyl bromide
Product
Z/E
Yield [%][b]
80:20
>99
2
3
90:10
71:29
91
90
4
5
90:10
92:8
63
88
6
85:15
40
7
88:12
>99:1
>99:1
86:14
76
60
50
83
8
9
10
11
60:40
>99
12
13
73:27
72
68
>99:1
14
>99:1
35
[a]
FeCl3 (0.05 mmol), vinyl bromide (0.5 mmol), nitrogen-containing heterocycle (0.6 mmol), K3PO4 (1.0 mmol), DMSO
(2 mL), 1208C, 24 h, under an argon atmosphere.
Isolated yield based on vinyl bromides (average of two runs).
[b]
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Iron-Catalyzed Cross-Coupling Reaction of Vinyl Bromides or Chlorides
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Table 3. Catalytic N-vinylation of imidazoles with (E)-vinyl chlorides by FeCl3.[a]
Entry
1
Het-NH
Product
Z/E
Yield [%][b]
12:88
18:82
32:68
50:50
10:90
17:83
67
53
73
52
56
87
2[c]
3[d]
4
5[e]
6[f]
[a]
All the reactions were processed in DMSO under argon atmosphere at 1208C for 24 h. FeCl3 (0.05 mmol), vinyl chloride
(0.5 mmol), nitrogen-containing heterocycle (0.6 mmol), K3PO4 (1.0 mmol).
Isolated yield based on vinyl chlorides (average of two runs).
For 36 h.
At 1308C.
10 mol% CuI as additive.
20 mol% FeCl3.
[b]
[c]
[d]
[e]
[f]
(entry 4). Using 10% of CuI as the additivie, the de- may serve not only as the substrate but also as the
sired product (Z/E=10/90) was obtained in lower ligand: during the catalytic reaction the double bond
yield (entry 5). It is noteworthy that double-loading from the vinyl halide and both of the nitrogen atoms
of FeCl3 gave a better result (87% yield) (entry 6).
from the heterocycle compounds could participate in
To ensure of the peculiarity and specificity of our the iron coordination. We further speculate that the
catalytic system, we checked that (E)-N-vinylimid- stereogenic configuration of the product may be ascri-
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
Since this is an example of ligand-free coupling, it using readily available iron catalysts under ligand-
is possible that the nitrogen-containing heterocycles free, copper-free and Pd-free conditions. We found
that the coupling of (E)-vinyl bromides led to (Z)-
products predominantly, while the reactions of (E)-
vinyl chlorides afforded (E)-isomers as the major
products. Thus, this could provide a facile means to
satisfy the demand for N-(1-alkenyl)imidazoles in dif-
ferent isomers. It has not escaped our attention that
our catalytic system is low-cost, benign and easily
Scheme 2.
available, which makes this catalytic method very at-
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Jincheng Mao et al.
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General Procedure
FeCl3 (0.1 equiv.), K3PO4 (2.0 equiv.) were added to a screw-
capped test tube. The tube was then evacuated and backfil-
led with argon (3 cycles). DMSO (2 mL), heterocycles
(1.2 equiv.) (if liquid) and vinyl halide (if liquid) (1.0 equiv.)
were added by syringe at room temperature. The tube was
again evacuated and backfilled with argon (3 cycles). The
mixture was heated to 1208C and stirred for 24 h. After
cooling to room temperature, the mixture was diluted with
water, and the combined aqueous phases were extracted
three times with ethyl acetate. The organic layers were com-
bined, dried over Na2SO4, and concentrated to yield the
crude product, which was further purified by silica gel chro-
matography, using petroleum ether and ethyl acetate as elu-
ents to provide the desired product. The identity and purity
or Z/E of the product were confirmed by H, 13C NMR and
HR-mass spectroscopic analysis.
1
[6] J. Mao, Q. Hua, J. Guo, D. Shi, S. Ji, Synlett 2008, 2011.
[7] Recently we reported an example of highly effective
ligand-free iron/copper cocatalyzed alkynylation cou-
pling reactions, see: J. Mao, G. Xie, M. Wu, J. Guo, S.
Ji, Adv. Synth. Catal. 2008, 350, 2477.
[8] For general reviews, see: a) C. Bolm, J. Legros, J. L.
Paih, L. Zani, Chem. Rev. 2004, 104, 6217; b) A. Fꢂrst-
ner, R. Martin, Chem. Lett. 2005, 34, 624.
Acknowledgements
We are grateful to the grants from the National Natural Sci-
ence Foundation of China (No. 20802046) and the Key Labo-
ratory of Organic Synthesis of Jiangsu Province for financial
support. We thank Dr. Marc Creus of University of Basel,
Switzerland for helpful discussions.
[9] M. Taillefer, N. Xia, A. Oualli, Angew. Chem. 2007,
119, 952; Angew. Chem. Int. Ed. 2007, 46, 934.
[10] V. H. Jadhav, D. K. Dumbre, V. B. Phapale, H. B.
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Adv. Synth. Catal. 2009, 351, 1268 – 1272