Microwave-assisted copper catalyzed coupling reaction of aryl halides with terminal alkynes

Article abstract of DOI:10.1081/SCC-120004843

Coupling reaction of aryl halides with terminal alkynes using catalyst system of copper (I)-triphenylphosphine proceeds efficiently in the presence of potassium carbonate under microwave irradiation to give the corresponding unsymmetrical acetylenes in go

Full text of DOI:10.1081/SCC-120004843

This article was downloaded by: [University of South Florida]
On: 07 May 2013, At: 09:04
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
MICROWAVE-ASSISTED COPPER CATALYZED COUPLING
REACTION OF ARYL HALIDES WITH TERMINAL ALKYNES
a
a
a
a
a
Jin-Xian Wang , Zhanxiang Liu , Yulai Hu , Bangguo Wei & Liqin Kang
a
Institute of Chemistry, Department of Chemistry, Northwest Normal University, 95 An Ning
Road (E.), Lanzhou, 730070, China
Published online: 16 Aug 2006.
To cite this article: Jin-Xian Wang , Zhanxiang Liu , Yulai Hu , Bangguo Wei & Liqin Kang (2002): MICROWAVE-ASSISTED
COPPER CATALYZED COUPLING REACTION OF ARYL HALIDES WITH TERMINAL ALKYNES, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:13, 1937-1945
To link to this article: http://dx.doi.org/10.1081/SCC-120004843
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-and-conditions
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to
anyone is expressly forbidden.
The publisher does not give any warranty express or implied or make any representation that the contents
will be complete or accurate or up to date. The accuracy of any instructions, formulae, and drug doses should
be independently verified with primary sources. The publisher shall not be liable for any loss, actions, claims,
proceedings, demand, or costs or damages whatsoever or howsoever caused arising directly or indirectly in
connection with or arising out of the use of this material.

SYNTHETIC COMMUNICATIONS, 32(13), 1937–1945 (2002)
MICROWAVE-ASSISTED COPPER
CATALYZED COUPLING REACTION OF
ARYL HALIDES WITH TERMINAL
ALKYNES
Jin-Xian Wang,* Zhanxiang Liu, Yulai Hu,
Bangguo Wei, and Liqin Kang
Institute of Chemistry, Department of Chemistry,
Northwest Normal University, 95 An Ning Road (E.),
Lanzhou 730070, China
ABSTRACT
Coupling reaction of aryl halides with terminal alkynes using
catalyst system of copper (I)-triphenylphosphine proceeds
efficiently in the presence of potassium carbonate under
microwave irradiation to give the corresponding unsymmetri-
cal acetylenes in good yield.
INTRODUCTION
[
1–4]
The palladium-catalyzed
coupling reaction of aryl halides
with terminal alkynes is a useful tool for preparation of unsymmetrical
acetylenes and now widely used for the synthesis of biologically active
*
Corresponding author.
1
937
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

1
938
WANG ET AL.
[5,6]
enyne-compounds.
Because of their importance, a number of methods
have been developed for the synthesis of substituted acetylenes. The most
effectively this reaction proceeds in the presence of catalytic amounts of
palladium complex and cuprous iodide. For example: using Pd(PPh ) Cl -
3
2
2
[7–9]
[10]
[1a]
[11]
CuI,
PdL Cl -CuI/sc CO ,
2
Pd(OAc) -PPh ,
2
Pd(PPh3)4
as
2
2
3
catalysts for the coupling reaction of aryl halides with terminal
alkynes. A few examples of this reaction in aqueous medium have been
[8]
reported.
Generally the reaction proceeds under mild conditions in the pres-
ence of copper iodide, in anhydrous organic solvents involving the inter-
[
12–14]
mediate formation of a copper acetylide.
involve stoichiometric amount of the copper catalyst.
et al.
Most of these reactions
[
15]
Recently, Okuro
have reported the reaction of aryl and vinyl halides with terminal
[16]
alkynes proceeds efficiently in the presence of a catalytic amount of copper
iodide using potassium carbonate as base to give the coupling products in
good yield when an appropriate amount of triphenylphosphin or
[3]
n-Bu NCl are added. On the other hand, there have also been some
4
reports on the allylation of terminal alkynes by copper(I) and phase
transfer catalyzed.
[17,18]
In recent years, microwave-induced rate acceleration technology is
becoming a powerful tool in organic synthesis, because of milder
reaction conditions, reduction of reaction time, enhanced selectivity and
associated ease of manipulation. Some important reviews have been
[
19]
published.
organic reactions. However, few practical applications have been devised
Microwave irradiation has also been applied to several
[
20,21]
for the coupling reaction in the presence of palladium.
There
are no reports on the use CuI-PPh3 as catalyst for the coupling
reaction of aryl halides with terminal alkynes under microwave irradiation
conditions.
RESULTS AND DISCUSSION
We have now found that substituted acetylenes 3a–g can be obtained
from aryl iodides 2 with terminal alkynes 1 using CuI-PPh as catalyst under
3
microwave irradiation conditions. This method is simple, rapid and affords
good yield. The reactions are shown in Scheme 1 and results are summarized
in Table 1. The results in Table 1 show that in the presence of CuI-PPh , a
3
variety terminal alkynes have been converted to the corresponding unsym-
metrical acetylenes in good yield under microwave irradiation conditions.
Under these conditions, 2-iodobenzoic acid is converted exclusively

COUPLING REACTION OF ARYL HALIDES
1939
Scheme 1. Reagents and conditions: i, CuI-PPh
1
3
, K
2
CO
3
, DMF, Ar, MWI, 375 W,
0 min; ii, CuI-PPh , K CO , DMF, MWI, 375 W, 10 min.
3
2
3
Table 1. Fast Copper-Catalyzed Coupling Reaction of Aryl
a
Iodides with Terminal Alkynes Under Microwave Irradiation
Yield
c
(%)
Entry
Product
PhCꢀCPh
1
2
3
4
5
6
7
(3a)
(3b)
(3c)
(3d)
(3e)
(3f )
(3g)
91
84
83
90
92
80
80
p-CH C H CꢀCPh
3
6
4
o-O
p-O
2
NC
NC
6
H
4
CꢀCPh
CꢀCPh
2
H
6 4
p-HO CC H CꢀCPh
2
6
4
p-ClC
HOCH
6
H
4
CꢀCPh
2
CꢀCCH
2
¼CHCH
2
8
(3h)
86
b
65
9
PhCꢀC–CꢀCPh
(3i)
a
The reactions were carried out in the presence of K CO
2
3
3
using CuI-PPh as catalyst in DMF at 375 W for 10 min
b
under argon. Under the same conditions but without the
c
Ar protection, the product is 3i. Isolated yield.
to 3-phenylisocoumarin (3h). In the case of phenylacetylene with iodo-
benzene, However, under the some conditions but without the Ar protec-
tion, the product is 1,4-diphenyl-1,3-butadiyne 3i.
Using the synthesis of 3a as example, we have investigated the effect of
different mole ratios on the reaction of phenylacetylene with iodoarenes

1
940
WANG ET AL.
under microwave irradiation. The results showed that the best mole ratio is
PhC¼CH : PhI : CuI : PPh : K CO ¼ 1.5 : 1.0 : 0.1 : 0.2 : 1.5. The yield of 3a
3
2
3
is 91%. The efficiency of various solvents on the formation of 3a was studied
using microwave irradiation. DMF was found to be an effective solvent for
the reaction. The effect of various solvents in the synthesis of 3a is in the
following order: DMF>DMSO>CH CN>EtOH>benzene. The results
3
are summarized in Table 2. We have also investigated the effect of different
catalysts on the reaction. It was found that the activities of the catalysts are
a,b,c
Table 2. Effect of Various Solvent on the Formation of (3a)
d
Dielectric Constant
(")
Yield of (3a)
(%)
Entry
Solvents
CH CN
DMF
DMSO
Benzene
EtOH
1
2
3
4
5
3
37.5
36.5
46.6
2.3
82
91
86
10
40
24.6
a
The reaction was carried out in the presence of K
2 3
CO using
CuI-PPh
tinuous irradiation under argon. Unless indicated otherwise mol
: K CO
3
as catalyst at a power level of 375 W for 10 min con-
b
ratios PhC¼CH : PhI : CuI : PPh
3
2
3
¼ 1.5 : 1.0 : 0.1 : 0.2 : 1.5.
d
c
The reaction was monitored by TLC on silica gel. Yield of
isolated product.
Table 3. Effect of Catalyst (CuI-PPh
a
3
) and Base on the
Formation of (3a)
b
Entry
Catalyst
Base
Yield of (3a)
1
2
3
4
5
6
7
CuI-PPh
CuI-PPh
CuI-PPh3
CuI-PPh3
CuBr-PPh
3
3
Na CO
2
3
90
55
60
91
82
68
0
NaOH
NaHCO3
K CO
2
2
2
3
3
3
3
3
K
K
CO
CO
CuCl-PPh
PPh3
3
K CO
2
a
The reaction was carried out in DNF at a power level of 375 W
b
for 10 min under argon. Isolated yield.

COUPLING REACTION OF ARYL HALIDES
Table 4. The Effect of Microwave Irradiation Power
1941
a
Irradiation Power (W)
75
40
150
51
300
54
375
78
450
75
750
72
b
Yield (%)
a
2 3 3
The reaction was carried out in the presence of K CO using CuI-PPh
b
as catalyst for 5 min continuous irradiation under argon. Isolated yield.
a
Table 5. The Effect of Microwave Irradiation Time
Irradiation Time (min)
2
5
10
90
15
90
b
Yield (%)
22
78
a
2 3
The reaction was carried out in the presence of K CO
using CuI-PPh3 as catalyst at a power level of 375 W
b
continuous irradiation under argon. Isolated yield.
in the following sequence: CuI/PPh > CuBr/PPh > CuCl/PPh > PPh .
3
3
3
3
The results are summarized in Table 3.
We have also investigated the effects of irradiation power and time on
the reaction. The results are summarized in Tables 4 and 5. It was found that
the highest yield of compound 3a is obtained at a power level of 375 W for
10 min continuous irradiation.
The impact of the microwave irradiation and conventional heat-
3,9,14b,16]
for the formation of compounds 3a–h has been compared
[
ing
and results are summarized in Table 6. The results showed that the synthesis
of 3a–h under microwave irradiation were 48–144 times faster than under
conventional reflux.
Mechanism
[
14b,18]
A possible mechanism
inal acetylenes with iodoarenes is described in Scheme 2. In the first step, the
for the coppe catalyzed coupling of term-
terminal acetylene reacts with CuI-PPh in the presence of base to form the
3
organometallic compound. Then high reactive organometallic compound
enters reaction of cross-coupling with iodoarene to give aryl alkynyl deri-
vative of Cu-PPh . This derivative is unstable and can easily regenerates the
3
CuI and PPh through the reductive elimination of substitution product.
3
The CuI-PPh is thus recycled in the reaction.
3

1
942
WANG ET AL.
Table 6. Comparison of Time and Yields on the Formation of
Compounds 3a–h Using Microwave and Conventional Heating
Conventional Heating
Microwave Heating
Product t/min Yield (%) Power/W t/min Yield (%) t
c
/tmw
3
3
3
3
3
3
3
3
a
b
c
d
e
f
g
h
720
1440
600
720
600
1440
900
480
83
95
84
75
85
92
89
91
375
375
375
375
375
375
375
375
10
10
10
10
10
10
10
10
91
84
83
90
92
80
80
86
72
144
60
72
60
144
90
48
Scheme 2.
EXPERIMENTAL
Microwave irradiation was carried out with a commercial microwave
1
oven GlanzWp 750B at 2450 Hz. H NMR spectra were recorded in CDCl
3
on a BRUKER PT 80A Spectrometer using tetramethylsilane as internal
standard. Chemical shifts were reported as d in ppm. IR spectra were
measured with an Alpha centauri FI-IR spectrometer as KBr discs or film.

COUPLING REACTION OF ARYL HALIDES
1943
Mass spectra were recorded on a QP-1000A GC-MS using the electron
impact mode (70 ev). Melting points were determined with an Electrothermal
micromelting point apparatus and were uncorrected. All solvents were used
without further purification. The remaining chemicals were obtained
from commercial sources. All reactions were conducted under an argon
atmosphere.
General Procedure
In the reaction flask were mixed iodobenene (1.02 g, 5 mmol), alkynes
7.5 mmol), CuI (0.09 g, 0.5 mmol), PPh3 (0.262 g, 1 mmol) and K CO3
1.04 g, 7.5 mmol) in DMF (10 mL), then irradiated at 375 W for 10 min.
(
(
2
After cooling, the product mixture was poured into 30 mL diethyl ether,
then filtered the residue was washed with ether. The combine ether was
washed with the saturated brine (3 Â 10 mL) and dried over magnesium
sulfate. The dried ethereal solution was concentrated. The crude product
was purified by column chromatography on silica gel using petroleum/ethyl
acetate (v/v 1 : 1) as the eluent.
ꢁ
[22]
ꢁ
Diphenylacetylene 3a: M.p. 61–62 C (lit. 62.5 C); MS (m/e, %): 178
M , 96%), 177 (100); IR ꢀ (KBr): 3018, 1598, 1532, 1492, 984, 756, 688;
þ
(
1
H-NMR (CDCl ): 6.98–7.50 (m, 10H, ArH).
3
[23]
ꢁ ꢁ
4
-Methyldiphenylacetylene 3b: M.p. 71–72 C (lit. 70.9–71.8 C); MS
þ
(
1
(
m/e, %): 192 (M , 89), 191 (100), 177 (21); IR ꢀ (KBr): 2857, 2160, 1593,
1
509, 1483, 754, 689; H-NMR (CDCl ): 7.10–7.60 (m, 9H, ArH), 2.34–2.37
s, 3H, CH3).
3
ꢁ
[14b]
ꢁ
43–44 C); MS (m/e,
2
-Nitrodiphenylacetylene 3c: M.p. 43–44 C (lit.
þ
%
): 223 (M , 100), 177 (25); IR ꢀ (KBr): 2188, 1578, 1482, 1523, 1344, 947,
1
59, 687; H-NMR (CDCl ): 7.25–7.66 (m, 8H, ArH), 8.61–8.65 (m, 1H,
7
ArH).
3
ꢁ
[14b]
ꢁ
119–120 C); MS
4
-Nitrodiphenylacetylene 3d: M.p. 119–120 C (lit.
þ
(
7
m/e, %): 223 (M , 100), 177 (92); IR ꢀ (KBr): 2170, 1592, 1511, 1347, 997,
1
64, 688; H-NMR(CDCl ):7.17–7.82(m, 7H, ArH), 8.07–8.18(m, 2H, ArH).
3
ꢁ
[14b]
ꢁ
4
-Carboxyldiphenylacetylene 3e: M.p. 221–222 C (lit.
þ
221–222 C);
MS (m/e, %): 222 (M , 100), 205 (40), 177 (20); IR ꢀ (KBr): 3075, 2600,
1
197, 1604, 1484, 918, 952, 753, 690; H-NMR (CDCl ): 7.03–7.66 (m, 7H,
2
3
ArH), 8.0–8.15 (m, 2H, ArH).
-Chloridiphenylacetylene 3f: M.p. 82–83 C (lit.
ꢁ
[24]
4
81.5–82); MS
þ
þ
(
m/e, %): 214 (M þ 2, 33), 212 (M , 100), 177 (40), 102 (33); IR ꢀ
1
KBr): 2158, 1602, 1484, 1074, 958, 760, 693, 742; H-NMR (CDCl ):
(
3
7.91–7.82 (m, 2H, ArH), 7.17–7.80 (m, 9H, ArH).

1
944
WANG ET AL.
ꢁ
[3]
-Hexene-2-yn-ol 3g: Oil, b.p. 70–72 C/2.7 KPa (lit. 70–72/2.7 KPa);
5
þ
MS (m/e, %): 96 (M , 17), 95 (15), 82 (13), 65 (100); IR ꢀ (KBr): 3300, 2928,
1
854, 2220, 1645, 990, 915; H-NMR (CDCl ): 1.6 (s, 1H, OH), 3.2 (d, 2H,
2
3
¼
CH ), 3.40 (t, 2H, CCH ¼), 4.03 (s, 2H, OCH ), 5.90 (m, 1H, CH¼).
2
2
2
[25]
ꢁ
ꢁ
3
-Phenylisocoumarin 3h: M.p. 88–89 C (lit. 89–91 C); MS (m/e, %):
þ
2
1
8
22 (M , 100), 194 (50), 165 (36), 105 (28); IR ꢀ (KBr): 1750, 1669, 1591,
1
508, 964, 755, 685; H-NMR (CDCl ): 7.05 (s, 1H, HC¼C), 7.16–7.51 (m,
3
H, ArH), 8.20 (d, 1H, ArH).
ꢁ
[26]
ꢁ
1
,4-Diphenyl-1,3-butadiyne 3i: M.p. 87–88 C (lit.
þ
88 C); MS (m/e,
%
): 214 (M ).
ACKNOWLEDGMENTS
This project was supported by the National Natural Science
Foundation of China and the Northwest Normal University Science and
Technology Development Foundation of China.
REFERENCES
1
. (a) Nguefack, J.-F.; Bolitt, V.; Sinou, D. Tetrahedron Lett. 1996, 37,
527; (b) Dieck, H.A.; Heck, R.F. J. Organomet. Chem. 1975, 93, 259;
c) Cassar, L. J. Organomet. Chem. 1975, 93, 253.
5
(
2
3
. Pal, M.; Kundu, N.G. J. Chem. Soc. Perkin Trans. I 1996, 449.
. Yu, J.-M.; Liu, L.; Xu, B.-M.; Liu, Z.-Y.; Shan, S.-X. Acta Chimica
Sinica 1996, 54, 922.
4. Yang, Z.Y.; Barton, D. J. Tetrahedron Lett. 1990, 31, 1039.
5. Nicolaou, K.C.; Dai, W.-M. Angew. Chem. 1991, 103, 1453.
6. Hegedus, L.S. J. Organometal. Chem. 1992, 422, 301.
7. Villemin, D.; Goussu, D. Heterocycles 1998, 29, 1255.
8. Bumagin, N.A.; Sukhomlinova, L.I.; Luzikova, E.V.; Tolstaya, T.P.;
Beletskaya, I.P. Tetrahedron Lett. 1996, 37, 897.
9. Kundu, N.G.; Pal, M.; Nandi, B. J. Chem. Soc. Perkin Trans. I 1998,
561.
10. Carroll, M.A.; Holmes, A.B. Chem. Commun. 1998, 1395.
11. Alami, M.; Ferri, F.; Linstrumelle, G. Tetrahedron Lett. 1993, 34,
6403.
12. Lee, G.C.M.; Tobias, B.; Holmes, J.M.; Harcourt, D.A.; Garst, M.E.
J. Am. Chem. Soc. 1990, 112, 9330.
13. Schmidt-Radde, R.H.; Vollhardt, K.P.C. J. Am. Chem. Soc. 1992, 114,
9713.

COUPLING REACTION OF ARYL HALIDES
1945
1
1
1
4. (a) Okita, T.; Isobe, M. Synlett 1994, 589; (b) Stephens, R.D.; Castro,
C.E. J. Org. Chem. 1963, 28, 3313.
5. Ogawa, T.; Kusume, K.; Tanaka, M.; Hayami, K.; Suzuki, H. Synth.
Commun. 1989, 19, 2199.
6. Okuro, K.; Furuune, M.; Miura, M.; Nomura, M. Tetrahedron Lett.
1992, 33, 5363.
17. Jeffery, T. Tetrahedron Lett. 1989, 30, 2225.
18. Grushin, V.V.; Alper, H. J. Org. Chem. 1992, 57, 2188.
19. For recent reviews, see: (a) Caddick, S. Tetrahedron 1995, 51, 10403;
(b) Strauss, C.R.; Trainor, R.W. Aust. J. Chem. 1995, 48, 1165; (c)
Galema, S.A. Chem. Soc. Rev. 1997, 26, 233; (d) Loupy, A.; Petic, A.;
hamelin, J.; Texier-Boullet, F.; Jacquault, P.; Mathe, D. Synthesis
1998, 1213; (e) Varma, R.S. Green Chem. 1999, 43.
2
2
2
0. Larhed, M.; Haliberg, A. J. Org. Chem. 1996, 61, 9582.
1. Littke, A.F.; Fu, G.C. J. Org. Chem. 1999, 64, 10.
2. Buckingham, J.; Donaghy, S.M. Dictionary of Organic Compounds, 5th
Ed., 07760; Chapman and Hall: New York, 1982.
3. Sioda, R.E.; Cowan, D.O.; Koski, W.S. J. Am. Chem. Soc. 1967,
2
89, 230.
24. Newman, M.A.; Reid, D.S. J. Org. Chem. 1958, 23, 665.
25. Buckley, D.G.; Ritchie, E.; Taylor, W.C. Aut. J. Chem. 1967, 22, 557.
26. Rhee, I.; Ryang, M.; Tsutsumi, S. Tetrahedron Lett. 1969, 52, 4593.
Received in the USA June 23, 2001