Iron-catalyzed cross-coupling reactions of terminal alkynes with vinyl iodides

Article abstract of DOI:10.1002/adsc.200900123

A convenient iron-catalyzed cross-coupling reaction of terminal alkynes with vinyl iodides is reported. The reaction was applicable to various acetylenes and vinyl iodides. The present reaction provides an efficient, environmentally friendly protocol to a

Full text of DOI:10.1002/adsc.200900123

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DOI: 10.1002/adsc.200900123
Iron-Catalyzed Cross-Coupling Reactions of Terminal Alkynes
with Vinyl Iodides
Xin Xie,a Xiaobing Xu,a Hongfeng Li,a Xiaolei Xu,a Jingyu Yang,a
and Yanzhong Lia,*
a
Institute of Medicinal Chemistry, Department of Chemistry, East China Normal University, 3663 North Zhongshan Road,
Shanghai 200062, Peopleꢀs Republic of China
Fax : (+86)-021-6223-3969; e-mail: yzli@chem.ecnu.edu.cn
Received: February 21, 2009; Published online: May 28, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900123.
Abstract: A convenient iron-catalyzed cross-cou-
pling reaction of terminal alkynes with vinyl iodides
is reported. The reaction was applicable to various
acetylenes and vinyl iodides. The present reaction
provides an efficient, environmentally friendly pro-
tocol to afford conjugated enyne derivatives in
good to excellent yields under mild conditions.
tween terminal alkynes and vinyl halides via the alk-
ynyl-Grignard produced in situ [Eq. (2)],[5] this is the
AHCTUNGTRENNUNG
first example of an Fe-catalyzed coupling between ter-
minal alkynes and vinyl halides with the assistance of
Grignard reagents. In the past few years, Fe-catalyzed
couplings without the utilization of Grignard reagents
have also drawn considerable attention.[6] For exam-
ple, Bolm et al. reported excellent work on ligand-as-
[7]
[8]
[9]
À
À
À
À
Keywords: C C bond formation; cross-coupling;
sisted Fe-catalyzed C N, C O and C S cross-
À
enynes; iron catalysis; vinyl iodides
coupling reactions and C C cross-coupling between
aryl iodides and terminal alkynes to afford aryl-
AHCTUNGTRENNUNG
alkynes using a sealed tube technique.[10] However, no
example of an Fe-catalyzed cross-coupling of vinyl
halides and terminal alkynes to enynes has been re-
The development of sustainable, environmentally ported to the best of our knowledge [Eq. (3)].
À
benign C C bond forming procedures is one of the
fundamental goals in organic chemistry. The coupling
reaction between sp2 and sp carbon centers is one of
the most utilized cross-coupling reactions for the con-
[1]
À
struction of new C C bonds. It allows the straight-
forward synthesis of conjugated enynes and arylal-
kynes, which are interesting intermediates and build-
ing blocks for the synthesis of a variety of natural
products and pharmaceuticals.[2] Typically, these kinds
of cross-couplings involve the use of both palladium
and copper as catalysts [Eq. (1)].[1] In recent years,
some Pd-free variants were also reported.[3] Although Herein, we would like to present efficient Fe-cata-
significant progress has been made with the regard to lyzed enyne-forming reactions using vinyl iodides and
the Pd/Cu-catalyzed protocols, the search for sustaina- terminal alkynes.
ble, environmentally friendly and less expensive cata-
Initially, we examined the cross-coupling using (E)-
lysts to accomplish such processes is still highly de- 1-(2-iodovinyl)benzene (1a) and phenylacetylene (2a)
sired. In this respect, iron could be the metal of as the prototypical case to optimize the reaction con-
choice for such purposes, because iron compounds are ditions, the results are depicted in Table 1. Several
usually less toxic, low priced and easy to synthesize. kinds of heteroatom-containing compounds such as
There have been a lot of reports concerning the Fe- 1,3-dicarbonyl compounds, amino acids, amines and
catalyzed coupling reactions with the use of Grignard 1,10-phenanthroline were tested as ligands in the
reagents.[4] It is important to note that Nakamura and presence of FeCl3 in toluene with different bases.
co-workers reported the Fe-catalyzed coupling be- Firstly, the reaction was carried out using 15 mol%
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Table 1. Optimization of the reaction conditions for the formation of 3a.
[a]
NMR yields, isolated yields are given in the parentheses. Unless noted, all the reactions
were carried out using 1.0 equiv of 1a and 1.0 equiv of 2a with 3 equiv of base in toluene
at 1108C.
[b]
[c]
[d]
[e]
DMF was used as solvent.
10 mol% of FeCl3 and 10 mol% of L1 were used.
10 mol% of FeCl3 and 20 mol% of L1 were used.
15 mol% of FeCl3 and 15 mol% of L1 were used.
FeCl3 as the catalyst and 30 mol% N,N’-dimethyl- N,N,N’,N’-tetramethylethane-1,2-diamine (TMEDA)
ethane-1,2-diamine as as the ligand at 1108C.[10] It was resulted in the formation of 3a in 56% yield after 48 h
encouraging that the desired (E)-1,4-diphenylbut-1- (Table 1, entry 8). It is interesting to note that tertiary
en-3-yne (3a) was produced in 25% yield after 48 h diamines gave better yields than primary and secon-
(Table 1, entry 1). rac-trans-N,N’-Dimethylcyclohex- dary amines. The best result was achieved when the
ane-1,2-diamine gave a similar result. When dicarbon- reaction was performed in the presence of 1,10-phen-
yl compounds and amino acids were used, no desired
ACHTUNGTRENaNUNG nthroline (L1), affording the target enyne in 82%
product could be detected (Table 1, entries 3–6). Then yield (Table 1, entry 9), along with ca. 2% of 1,4-di-
we turned our attention back to amines. Aniline has phenylbuta-1,3-diyne resulting from the homocou-
no good effect on the coupling reaction, and pling of phenylacetylene. It is noteworthy that the
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Iron-Catalyzed Cross-Coupling Reactions of Terminal Alkynes with Vinyl Iodides
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Table 2. Preparation of enynes from 1-alkynes and vinyl iodides.
[a]
NMR yields, isolated yields are given in the parentheses.
1.5 equiv. of 1d was used, 60% 2b was recovered.
[b]
choice of Cs2CO3 as the base and toluene as the sol- the absence of FeCl3 and ligand led to no detection of
vent was crucial for the enyne-forming reaction. the desired cross-coupling product. Other iron source
When other bases like NaOH, Na2CO3, Et3N and sol- such as FeCl2 or FeACTHNUGTRNEUNG(acac)3 failed to accomplish the
vents such as DMF were employed, no desired enyne coupling reaction or gave very low yields of the
was observed (Table 1, entries 10–13). Decreasing the enynes, respectively (Table 1, entries 14 and 15). It
amount of FeCl3 or ligand resulted in much lower was clear that the optimized reaction conditions was
yields (Table 1, entries 16–18). Controlled reactions in to use 15 mol% FeCl3 as the catalyst and 30 mol%
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temperature and quenched with water and extracted with
ether (3ꢂ20 mL). The extract was washed with brine and
dried over Na2SO4. The solvent was evaporated under
vacuum and the residue was purified by chromatography on
silica gel to afford a light-yellow solid of enyne derivative
1,10-phenanthroline as the ligand, Cs2CO3 as the base
and toluene as the solvent.
Having established an effective iron-catalyzed
system for the coupling reactions, we next explored
the scope of the reaction by treating a variety of vinyl
iodides with different acetylenes under the optimized
reaction conditions. The representative results are
shown in Table 2. The reaction was applicable to vari-
ous acetylenes and vinyl iodides. The coupling of vari-
ous alkenyl iodides with both electron-rich and elec-
tron-deficient acetylenes afforded the products in
good to excellent yields. Acetylenes with an electron-
donating (OMe) aryl group or an electron-withdraw-
ing (Cl) aryl group coupled with (E)-1-(2-iodovinyl)-
benzene (1a) to give rise to the corresponding enynes
in 83% and 98% yields, respectively (Table 2, en-
tries 2 and 3). Alkyl-substituted alkynes led to the de-
sired product in 90% yield (Table 2, entry 4). It is
noteworthy that propargylamine and propargyl ether
are also compatible under the reaction conditions and
furnishing products 3e and 3f in 80% and 60% yields,
1
3h; yield: 156 mg (58%); mp 139–1408C. H NMR (CDCl3,
Me4Si): d=3.72 (s, 3H), 6.13 (d, J=16.0 Hz, 1H,), 6.78 (d,
J=8.0 Hz, 2H), 6.91 (d, J=16.0 Hz, 1H), 7.16–7.30 (m,
6H); 13C NMR (CDCl3, Me4Si): d=55.29, 89.80, 90.26,
105.32, 114.20, 122.14, 127.71, 128.63, 129.05, 132.58, 133.90,
141.27, 160.20; HR-MS: m/z=268.0659, calcd for
C17H13ClO: 268.0655.
Supporting Information
Experimental details and spectroscopic characterization of
all new compounds are given in the Supporting Information
file.
Acknowledgements
À
À
respectively, while the NMePh and OPh groups are
well tolerated (Table 2, entries 5 and 6). When 4-me-
thoxyphenylvinyl iodide (1b) was employed, it cou-
pled with 4-methoxyphenylacetylene (2b), 4-chloro-
phenylacetylene (2c) and N-methyl-N-(prop-2-ynyl)-
benzenamine (2e) to provide the corresponding
enynes 3g, 3h, 3i in high yields (Table 2, entries 7–9).
Alkyl-substituted alkenyl iodide 1c reacted with 2a
and 2b to afford the expected products both in 70%
yields (Table 2, entries 10 and 11). Interestingly, when
a vinyl iodide bearing a propargyl alcohol moiety was
employed, the desired coupling product could also be
obtained in 25% yield.
We are grateful to the National Natural Science Foundation
of China (No. 20572025 and 20872037) for financial support.
We also thank the Lab of Organic Functional Molecules and
the Sino-French Institute of ECNU for support.
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ACHTUNGTRENNUNG
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