First example of transition-metal-free Glaser-type coupling reaction

Article abstract of DOI:10.1080/00397910500187191

In the presence of potassium tert-butoxide and in toluene, 1,1-dibromo-1-alkenes smoothly generated the corresponding Glaser-type coupling-reaction products (1,3-diynes) in moderate to good yields. Copyright Taylor & Francis, Inc.

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First Example of
Transition‐Metal‐Free
Glaser‐Type Coupling Reaction
a
a b
Jincan Yan & Lei Wang
a
Department of Chemistry , Huaibei Coal Teachers
College , Huaibei, Anhui, China
b
State Key Laboratory of Organometallic
Chemistry , Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences , Shanghai, China
Published online: 18 Aug 2006.
To cite this article: Jincan Yan & Lei Wang (2005) First Example of
Transition‐Metal‐Free Glaser‐Type Coupling Reaction, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 35:17,
2333-2338
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Synthetic Communications , 35: 2333–2338, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500187191
First Example of Transition-Metal-Free
Glaser-Type Coupling Reaction
Jincan Yan
Department of Chemistry, Huaibei Coal Teachers College,
Huaibei, Anhui, China
Lei Wang
Department of Chemistry, Huaibei Coal Teachers College,
Huaibei, Anhui, China and State Key Laboratory of Organometallic
Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy
of Sciences, Shanghai, China
Abstract: In the presence of potassium tert-butoxide and in toluene, 1,1-dibromo-1-
alkenes smoothly generated the corresponding Glaser-type coupling-reaction
products (1,3-diynes) in moderate to good yields.
Keywords: 1,1-Dibromo-1-alkenes, Glaser-type reaction, potassium tert-butoxide,
transition-metal free
1
,3-Diynes are very important intermediates and target molecules in biologi-
[1]
cal, polymer, natural-product, and material science. A classical, effective,
and useful method for preparing diacetylenes was discovered by Carl Glaser
in 1869, which involves a cuprous salt (CuCl)–promoted oxidative homo-
coupling reaction of terminal alkynes in the presence of oxygen, ammonia,
[
2]
and ammonium chloride. Subsequently, Cameron observed the effect of
substituting amines for ammonia in the catalyst mixture (CuCl–amine–
[3]
amine HCl-O ).
.
Later, Eglinton and Calbraith found that copper(II)
acetate in pyridine–methanol was an effective reagent for the oxidative
2
Received in Japan February 28, 2005
Address correspondence to Lei Wang, Department of Chemistry, Huaibei Coal
Teachers College, Huaibei, Anhui 235000, China. Fax: 0086 561 3090518; E-mail:
leiwang@hbcnc.edu.cn
2
333

2334
J. Yan and L. Wang
[4]
coupling of acetylenes. In 1960s, Hay noted that acetylenes could be
coupled at room temperature with oxygen or air by using a catalytic amount
0
0
of CuCl–pyridine and CuCl–N,N,N ,N -tetramethylethylenediamine
[
TMEDA) complexes. In the past three decades, a variety of copper salt-
5]
(
amine systems, such as Cu(OAc) –pyridine, CuCl–TMEDA, CuCl2–
[
6]
[7]
2
[
8]
[9]
[10]
CuCl–pyridine,
CuCl–Cu(OAc) –pyridine,
CuCl–TMEDA–pyridine,
[
CuCl(OH)–TMEDA,
and CuI–pyrrolidine
11]
[12]
[13]
CuI–TMEDA,
2
were recommended for this transformation. In addition, the use of
palladium(0) complexes was also invoked and optimized to obtain terminal
[
14]
acetylene homo-coupling products.
Recently, transition-metal-free organic synthetic methodology has
received much attention because of economical and environmental
concerns. Leadbeater and coworkers developed a Suzuki coupling reaction
with PEG–NaOH under microwave irradiation without the need of a
[
15]
transition-metal catalyst.
reaction can be performed under microwave heating and transition-metal-
Later they also observed that the Sonogashira
[
16]
free reaction conditions.
example of a metal-free Heck reaction between styrene and iodobenzene in
Very recently in the literature there has been an
supercritical water and a metal-free biaryl ether synthesis through S Ar-
N
based addition reactions using microwave heating and in DMSO as
[
17]
solvent.
Glaser coupling reaction under transition-metal-free conditions.
However, to the best of our knowledge, there is no report on the
1
Corey and Fuchs,
,1-Dibromo-1-alkenes, which can be easily prepared by the procedure of
[
18]
are important starting materials in organic synthesis.
They can be converted to (Z)-1-aryl(alkenyl)-1-bromo-1-alkenes, 1,1-diaryl
(alkenyl)-1-alkenes, bis-enediynes, and 1-aryl(alkenyl)-1-alkynes via the
palladium-catalyzed Suzuki and Sonogashira cross-coupling reaction.
[19]
On
the other hand, 1,1-dibromo-1-alkenes can also be used as equivalents of
1
the 1,3-diynes.
-bromo-1-alkynes in the palladium-catalyzed Glaser reaction, which afford
[
20]
Here, we report a transition-metal-free Glaser-type
coupling reaction of 1,1-dibromo-1-alkenes in the presence of t-BuOK and
toluene as solvent without any metal catalyst and additive, which affords
the corresponding 1,3-diynes in moderate to good yields (Scheme 1).
In our initial exploration, we observed that the reaction of 1,1-dibromo-2-
(
2-chlorophenyl)-1-ethene in the presence of t-BuOK (4 eq. in toluene, at
208C) went smoothly to generate corresponding 1,3-diynes in good yield
82%) without the addition of any transition metal, ligand, or additive. Of
the bases we tested in the reaction, t-BuONa, KOH, KF, Na CO , KCO ,
1
(
2
3
3
and K PO gave the corresponding products only in 64%, 46%, 34%, 22%,
4
3
Scheme 1.

Transition-Metal-Free Glaser Reaction
2335
2
8%, and 15% yields, respectively. No Glaser-type coupling product was
obtained when the reaction was carried out using triethylamine, diethylamine,
and piperidine as bases. The amount of t-BuOK was also examined. When
the amount of t-BuOK was less than 2 eq., less than 50% yields of Glaser-
type products were formed. The satisfactory results were obtained when the
amount of t-BuOK was in the range of 3 to 5 eq. It is important to note that
the reaction did not result in the formation of product in the absence of t-BuOK.
The proper solvent is very important in this reaction. We conducted
the reaction of 1,1-dibromo-2-(2-chlorophenyl)-1-ethene in the presence of
t-BuOK under different solvents. Among the solvents we investigated,
toluene proved to be the best solvent. Only 35%, 16%, 42%, 21%, and 51%
of the desired products were obtained when the reaction was performed in
DMF, THF, DMSO, acetonitrile, and benzene, respectively.
To survey the generality of this Glaser-type reaction, we investigated the
reactions using a variety of 1,1-dibromo-1-alkenes as the substrates under the
optimized conditions. The results are shown in Table 1. As can be seen from
Table 1, regardless of their electronic characters, 1,1-dibromo-2-aryl-1-
alkenes smoothly produced the desired products in good yields under the
standard reaction conditions (Entries 1–5, Table 1). The results indicated
a
Table 1. Transition-metal-free Glaser-type coupling reaction
Yields
b
(%)
Entry 1,1-Dibromo-1-alkenes
Products
7
8
8
8
1
0
5
2
1
2
3
4
6
5
5
9
2
8
5
6
7
a
Reactions were carried out by mixing 1 mmol of 1,1-dibromo-1-alkene with
mmol of t-BuOK and 5 mL of toluene at 1208C for 4 h.
Isolated yields.
3
b

2336
J. Yan and L. Wang
that the reaction is relatively insensitive to the electronic nature of substituents
and the substitution pattern on the aromatic rings. Fortunately, 2-alkyl-1,1-
dibromo-1-alkenes also generated the corresponding Glaser-type reaction
products in moderate yields (Entries 6 and 7, Table 1).
Until now, the reaction mechanism on the transition-metal-free carbon-
carbon formation reaction (Suzuki, Heck and Sonogashira coupling) is not
[15–17]
yet clear.
This reaction presumably proceeds through the debromination
of 1,1-dibromo-1-alkene in the presence of t-BuOK to form the corresponding
alkynyl bromide intermediate under the reaction conditions. This intermediate
subsequently coupled with terminal alkyne or its derivative to generate homo-
[20]
coupling product in a classic Glaser reaction manner.
is currently underway.
Further investigation
In conclusion, a novel synthetic procedure for the preparation of 1,3-
diynes has been developed, which involves the Glaser-type coupling
reaction of 1,1-dibromo-1-alkenes in the presence of t-BuOK without any
metal catalyst and additive. The advantages of the method are simplicity,
good yields, and environmental friendliness.
EXPERIMENTAL
Melting points were recorded on a WRS-1B melting point apparatus and are
1
uncorrected. All H NMR spectra were recorded on a 60-MHz JEOL MY 60
FT-NMR or a 300-MHz Bruker AZ 300 spectrometer using CDCl as solvent.
3
Chemical shift are given as d value with reference to tetramethylsilane (TMS)
as internal standard. IR spectra were obtained by using a Nicolet NEXUS 470
spectrophotometer. The reagents were received from commercial supply
without purification prior to use. Products were purified by flash-column
chromatography.
General Procedure for the Reaction
Toluene (5 mL) was added to a mixture of 1,1-dibromo-1-alkenes (1.0 mmol)
and t-BuOK (3.0 mmol) in a clean and dry pressure tube. The resulting mixture
was stirred at 1208C for 4 h until completion of the reaction. After cooling, the
mixture was filtered through a pad of silica gel and then the product isolated
via flash chromatography to yield the corresponding Glaser-type coupling
product.
[
21]
1
1
CDCl ) d: 7.52–7.49 (m, 4H), 7.34–7.27 (m, 6H); C NMR (CDCl ) d:
,4-Diphenyl-1,3-butadiyne: mp 87–888C (lit.
888C); H NMR
1
3
(
3
3
2
1
1
32.4, 129.2, 128.4, 121.7, 81.6, 74.0; IR (KBr) n: 2147 (C ;; C) cm
.
(lit.
[21]
1
,4-Bis(4-methylphenyl)-1,3-butadiyne: mp
1
182–1848C
1
838C); H NMR (CDCl ) d: 7.41 (d, J ¼ 8.0 Hz, 4H), 7.12 (d, J ¼ 7.9 Hz,
3

Transition-Metal-Free Glaser Reaction
2337
1
H), 2.35 (s, 6H); C NMR (CDCl ) d: 139.5, 132.4, 129.2, 118.8, 81.6, 73.5,
3
4
2
3
2
1
1.6; IR (KBr) n: 2142 (C ;; C) cm
,4-Bis(2-chlorophenyl)-1,3-butadiyne: mp 138–1408C (lit. 139.5–
.
[22]
1
1
1
7
7
408C); H NMR (CDCl ) d: 7.58–7.55 (m, 2H), 7.43–7.39 (m, 2H), 7.34–
3
13
.20 (m, 4H); C NMR (CDCl ) d: 137.0, 134.4, 130.3, 129.4, 126.6, 121.8,
3
2
1
9.4, 78.4; IR (KBr) n: 2138 (C ;; C) cm
,4-Bis(4-fluorophenyl)-1,3-butadiyne: mp 196–1988C (lit.
.
[23]
1
195–
1
1
4
1
978C); H NMR (CDCl ) d: 7.52–7.48 (m, 4H), 7.07–7.00 (t, J ¼ 8.7 Hz,
3
1
3
H); C NMR (CDCl ) d: 163.1 (d, J ¼ 250.0 Hz), 134.5 (d, J ¼ 8.3 Hz),
3
2
1
17.8, 115.9 (d, J ¼ 22.5 Hz), 80.43, 73.54; IR (KBr) n: 2152 (C ;; C) cm
.
[
24]
1
1
,4-Bis(4-methoxyphenyl)-1,3-butadiyne:
mp 132–1338C;
H
NMR (CDCl ) d: 7.48 (d, J ¼ 8.2 Hz, 4H), 6.92 (d, J ¼ 8.3 Hz, 4H), 3.79
3
1
3
(
s, 6H); C NMR (CDCl ) d: 160.3, 134.2, 114.2, 113.9, 81.2, 72.9, 55.4;
3
2
1
IR (KBr) n: 2142 (C ;; C) cm
.
25] 1
[
7
,9-Hexadecadiyne: Oil;
H NMR (CDCl ) d: 2.24 (t, J ¼ 6.9 Hz,
3
1
3
4
7
H), 1.57–1.26 (m, 16H), 0.89 (t, J ¼ 6.7 Hz, 6H); C NMR (CDCl ) d:
3
2
1
7.4, 65.3, 31.3, 28.5, 28.3, 22.5, 19.2, 14.0; IR (film) n: 2125 (C ;; C) cm
.
[
26] 1
9
,11-Eicosdiyne: Oil;
H NMR (CDCl ) d: 2.23 (t, J ¼ 6.8 Hz, 4H),
3
1
3
1
6
2
1
.57–1.27 (m, 24H), 0.88 (t, J ¼ 6.3 Hz, 6H); C NMR (CDCl ) d: 77.5,
3
5.3, 31.8, 29.1, 29.0, 28.8, 28.4, 22.6, 19.1, 14.0; MS (70 eV) m/z (%):
54 (M -C H , 2), 217 (5), 175 (8), 161 (16), 147 (24), 133 (29), 119 (42),
þ
2
5
2
1
05 (56), 91 (100); IR (film) n: 2129 (C ;; C) cm
.
ACKNOWLEDGMENTS
We gratefully acknowledge financial support by the National Natural Science
Foundation of China (No. 20372024); the Excellent Scientist Foundation of
Anhui Province, China (No. 04046080); the Natural Science Foundation of
the Education Department of Anhui Province, China (No. 2002kj254zd);
the Scientific Research Foundation for the Returned Overseas Chinese
Scholars, State Education Ministry, China (No. 2002247); the Excellent
Young Teachers Program of MOE, China (No. 2024); and the Key Project
of Science and Technology of State Education Ministry, China (No. 0204069).
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