A copper- and solvent-free coupling of acid chlorides with terminal alkynes catalyzed by a polystyrene-supported palladium(0) complex under aerobic conditions

Article abstract of DOI:10.1016/j.tetlet.2009.09.029

A polystyrene-supported palladium(0) complex [PS-dpp-Pd(0)] is an efficient catalyst for the copper- and solvent-free acylation of terminal alkynes with different acid chlorides in the presence of triethylamine as base, giving the corresponding ynones in

Full text of DOI:10.1016/j.tetlet.2009.09.029

Tetrahedron Letters 51 (2010) 33–35
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A copper- and solvent-free coupling of acid chlorides with terminal
alkynes catalyzed by a polystyrene-supported palladium(0) complex under
aerobic conditions
*
Mohammad Bakherad , Ali Keivanloo, Bahram Bahramian, Mahbobeh Rajaie
School of Chemistry, Shahrood University of Technology, Shahrood, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A polystyrene-supported palladium(0) complex [PS-dpp-Pd(0)] is an efficient catalyst for the copper- and
solvent-free acylation of terminal alkynes with different acid chlorides in the presence of triethylamine as
base, giving the corresponding ynones in good yields.
Received 24 June 2009
Revised 26 August 2009
Accepted 4 September 2009
Available online 9 September 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Copper-free
Ynones
Supported catalyst
Neat
1. Introduction
minal alkynes with various carboxylic acid chlorides, employing
the heterogeneous palladium complex, [PS-dpp-Pd(0)] 114 as the
a,b-Acetylenic carbonyl derivatives are compounds of consider-
catalyst (Fig. 1) under aerobic conditions.
able interest due to their occurrence in a wide variety of biologi-
cally active molecules and as key synthetic intermediates.1 They
have mainly been used for the preparation of important biologi-
cally active heterocycles.2 Their preparation typically involves the
reaction of alkynyl organometallic reagents of silver,3 copper,4 so-
dium,5 lithium,6 cadmium,7 zinc,8 silicon,9 or tin10 with acid chlo-
rides. The direct coupling of alkynyl palladium reagents with acid
chlorides is an important method for the preparation of alkynyl ke-
tones. However, these methods require anhydrous solvents and in-
ert atmospheres.11
The use of heterogeneous catalysts for coupling reactions leads
to a reduction in waste. As such, highly active polymer-supported
transition metal complexes have attracted significant interest be-
cause they can be easily recovered and reused.12 As part of our
continuing interest in palladium-catalyzed carbon–carbon cross-
coupling reactions,13 we recently reported a mild protocol for the
copper-free Sonogashira coupling of aryl iodides with terminal al-
kynes under aerobic conditions.14
The catalytic activity of complex 1 (0.5 mol %) was studied at
room temperature in a copper-free coupling reaction using p-chlo-
robenzoyl chloride and phenylacetylene (Tables 1 and 2).
We first tested the suitability of various solvents and bases for
the coupling of p-chlorobenzoyl chloride with phenylacetylene
(Table 1). N,N-Dimethylformamide and triethylamine proved to
be good solvents for this coupling reaction (entries 1 and 10).
Among the bases tested, triethylamine was the most efficient (en-
try 1). To our surprise, the highest yield of product was obtained
when the reaction was performed under solvent-free conditions
(Table 2). As shown in Table 2, when the reaction was performed
with Et3N as base, an excellent 98% yield of the product was ob-
tained (entry 2). Increasing the amount of palladium catalyst (en-
try 5) and increasing the reaction time (entry 8) did not increase
the yield of product further. A low palladium concentration re-
sulted in a decreased yield (entry 6).
+
In this work, we describe a copper- and solvent-free method for
the preparation of ynones via palladium-catalyzed reaction of ter-
Ph2P
Cl-
PPh2)2Pd(0)
1
* Corresponding author. Fax: +98 2733335441.
E-mail address: mbakherad@shahroodut.ac.ir (M. Bakherad).
Figure 1.
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.09.029

34
M. Bakherad et al. / Tetrahedron Letters 51 (2010) 33–35
Table 1
Copper-free coupling reaction of p-chlorobenzoyl chloride with phenylacetylene in the presence of different bases and solventsa
O
O
Cl
0.5 mol% PS-dpp-Pd(0)
solvent, base, rt, 15 min
Ph
CH
+
Ph
Cl
Cl
Entry
Solvent
Base
Yieldb (%)
1
2
3
4
5
6
7
8
9
DMF
DMF
DMF
CH3CN
CH3CN
CH3CN
Dioxane
Dioxane
Dioxane
Et3N
Et3N
92
85
83
80
82
77
75
72
78
90
88
86
DIPEAc
Pyridine
Et3N
DIPEA
Pyridine
Et3N
DIPEA
Pyridine
d
10
11
12
—
d
DIPEA
Pyridine
—
d
—
a
b
c
Reaction conditions: p-chlorobenzoyl chloride (1.0 mmol), phenylacetylene (1.0 mmol), base (1.0 mmol), solvent (3 mL), room temperature and aerobic conditions.
GC yield.
Diisopropylethylamine
Solvent employed as base.
d
Table 2
Copper- and solvent-free coupling reaction of p-chlorobenzoyl chloride with phenylacetylene in the presence of different basesa
O
O
Cl
PS-dpp-Pd(0)
neat, base, rt
Ph
CH
+
Ph
Cl
Cl
Entry
Base
[PS-dpp-Pd(0)] (mol %)
Time (min)
Yieldb (%)
1
2
3
4
5
6
7
8
DIPEA
Et3N
Pyridine
Cs2CO3
Et3N
Et3N
Et3N
Et3N
0.5
0.5
0.5
0.5
1.0
0.2
0.5
0.5
15
15
15
15
15
15
30
60
96
98
95
94
98
92
98
98
a
Reaction conditions: p-chlorobenzoyl chloride (1.0 mmol), phenylacetylene (1.0 mmol), base (1.0 mmol), room temperature and aerobic conditions.
GC yield.
b
To examine the scope of this coupling reaction, various benzoyl
2. Typical procedure for the preparation of 1-(4-chlorophenyl)-
3-phenylpropynone (4g), (Table 3, entry 7)
chlorides 2 containing electron-withdrawing or electron-donating
groups were coupled with different terminal alkynes 3 (Table 3).
The results show that this reaction is equally facile with both elec-
tron-donating and electron-withdrawing substituents present on
the aroyl chloride resulting in excellent yields of the corresponding
ynones.
The stability of [PS-dpp-Pd(0)] was studied in recycling reactions
of p-chlorobenzoyl chloride with phenylacetylene. The catalyst was
separated from the reaction mixture by filtration after each experi-
ment, washed with water and acetonitrile and dried carefully before
use in subsequent runs. A yield of compound 4g of 92% was obtained
from the 10th catalyst recycle (Table 4, entry 3).
In conclusion, we have reported [PS-dpp-Pd(0)] as a reusable
catalyst for the heterogeneous copper- and solvent-free synthesis
of ynones at room temperature via coupling of various acid chlo-
rides with terminal alkynes under aerobic conditions. The simple
procedure, short reaction times, high selectivity and excellent iso-
lated yields make this method well-suited for the generation of a
combinatorial library of ynones.
A round-bottomed flask was charged with 4-chlorobenzoyl
chloride (1.0 mmol), phenylacetylene (1.0 mmol), [PS-dpp-Pd(0)]
(0.005 mmol) and Et3N (1.0 mmol). The mixture was stirred at
room temperature for 15 min under aerobic conditions. Upon com-
pletion of the reaction, the mixture was extracted with EtOAc
(2 Â 10 mL).
The organic layer was washed with water to remove the
amine hydrochloride by-product. The organic layer was sepa-
rated, dried over MgSO4, filtered and concentrated under vacuum
to afford the crude product. The residue was purified by column
chromatography using CHCl3–CH3OH (98:2) as eluent to afford
compound 4g. Mp 105–106 °C; IR,
m ;
(KBr): 2200, 1652 cmÀ1
1H NMR d (500 MHz, CDCl3): 7.38–7.50 (m, 5H), 7.62–7.67 (m,
2H), 8.10 (d, 2H, J = 8.70); 13C NMR d (125 MHz, CDCl3): 86.50,
93.44, 120.10, 128.54, 128.83, 130.65, 130.87, 132.90, 135.32,
140.56, 176.80. Anal. Calcd for C15H9ClO: C, 74.85; H, 3.77.
Found: C, 74.68; H, 3.65.

M. Bakherad et al. / Tetrahedron Letters 51 (2010) 33–35
35
Table 3
Copper- and solvent-free coupling reactions of various acyl chlorides with terminal alkynesa
O
O
0.5 mol% PS-dpp-Pd(0)
Cl
R1
R1
HC
R2
R2
+
Et3N, neat, rt, 15 min
2
3
4
Entry
R1
R2
Product
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
n-C4H9
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
4p
90
78
74
87
93
87
98
95
97
83
80
92
94
90
92
94
4-NO2
3-NO2
2-CH3
4-CH3
4-OCH3
4-Cl
2-Cl
H
4-NO2
3-NO2
2-CH3
4-CH3
4-OCH3
4-Cl
2-Cl
a
Reaction conditions: 2 (1.0 mmol), 3 (1.0 mmol), Et3N (1.0 mmol), room temperature and aerobic conditions.
GC yield.
b
Table 4
Copper-and solvent-free coupling reaction of p-chlorobenzoyl chloride with phenylacetylene catalyzed by the recycled catalysta
O
O
Cl
0.5 mol% PS-dpp-Pd(0)
Et3N, neat, rt, 15 min
Ph
CH
+
Ph
Cl
Cl
Entry
Cycle
Yieldb (%)
1
2
3
1
5
10
98
96
92
a
Reaction conditions: p-chlorobenzoyl chloride (1.0 mmol), phenylacetylene (1.0 mmol), triethylamine (1.0 mmol), room temperature and aerobic conditions.
GC yield.
b
4. (a) Normant, J. F. Synthesis 1972, 63; (b) Logue, M. W.; Moore, G. L. J. Org. Chem.
1975, 40, 131; (c) Bourgain, M.; Normant, J. F. Bull. Soc. Chim. Fr. 1973, 2137.
5. Fontaine, M.; Chauvelier, J.; Barchewitz, P. Bull. Soc. Chim. Fr. 1962, 2145.
6. Compagnon, P. L.; Grosjean, B.; Lacour, M. Bull. Soc. Chim. Fr. 1975, 779.
7. Yashina, O. G.; Zarva, T. V.; Vereshchagin, L. I. Zh. Org. Khim. 1967, 3, 219. Chem.
Abstr. 1967, 66, 94664g..
Acknowledgment
The authors are grateful to the Research Council of Shahrood
University of Technology for the financial support of this work.
8. Vereshchagin, L. I.; Yashina, O. G.; Zarva, T. V. Zh. Org. Khim. 1966, 2, 1895.
Chem. Abstr. 1967, 66, 46070p.
9. Walton, D. R. M.; Waugh, F. J. Organomet. Chem. 1972, 37, 45.
10. Logue, M. W.; Teng, K. J. Org. Chem. 1982, 47, 2549.
References and notes
1. (a) Faweett, C. H.; Firu, R. D.; Spencer, D. M. Physiol. Plant Pathol. 1971, 1, 163;
(b) Imai, K. J. Pharm. Soc. 1956, 76, 405; (c) Mead, D.; Asato, A. E.; Denny, M.; Liu,
R. S. H.; Hanzawa, Y.; Taguchi, T.; Yamada, A.; Kobayashi, N.; Hosoda, A.;
Kobayashi, Y. Tetrahedron Lett. 1987, 28, 259; (d) Chowdhury, C.; Kundu, N. G.
Tetrahedron 1999, 55, 7011; (e) Quesnelle, C. A.; Gill, P.; Dodier, M.; St. Laurent,
D.; Serrano-Wu, M.; Marinier, A.; Martel, A.; Mazzucco, C. E.; Stickle, T. M.;
Barrett, J. F.; Vyas, D. M.; Balasubramanian, B. N. Bioorg. Med. Chem. Lett. 2003,
13, 519.
2. (a) Reid, W.; Koenig, E. Justus Leibigs Ann. Chem. 1972, 24, 755; (b) Hojo, M.;
Omita, K.; Hosomi, A. Tetrahedron Lett. 1993, 34, 485; (c) Arcadi, A.; Marenelli,
F.; Rossi, E. Tetrahedron 1999, 55, 13233; (d) Kelin, A. V.; Sromek, A. W.;
Gevorgyan, V. J. Am. Chem. Soc. 2001, 123, 2074; (e) Jeevnandan, A.; Narkunan,
K.; Ling, Y. J. Org. Chem. 2001, 66, 6014; (f) Grotjahn, D. B.; Van, S.; Combs, D.;
Lev, D. A.; Schneider, C.; Rideout, M.; Meyer, C.; Hernandez, G.; Mejorado, L. J.
Org. Chem. 2002, 67, 9200; (g) Karpov, A. S.; Muller, T. J. Org. Lett. 2003, 5, 3451.
3. Davis, R. B.; Scheiber, D. H. J. Am. Chem. Soc. 1956, 78, 1675.
11. (a) Tohda, Y.; Sonogashira, K.; Hagihara, N. Synthesis 1977, 777; (b) Alonso, D.
A.; Najera, C.; Pacheco, M. C. J. Org. Chem. 2004, 69, 1615; (c) Cox, R. J.; Ritson, D.
J.; Dane, T. A.; Berge, J.; Charmant, J. P. H.; Kantacha, A. Chem. Commun. 2005,
1037.
12. (a) McNamara, C. A.; Dixon, M. J.; Bradley, M. Chem. Rev. 2002, 102, 3275; (b)
Clapham, B.; Reger, T. S.; Janda, K. D. Tetrahedron 2001, 57, 4637; (c) de Miguel,
Y. R.; Brule, E.; Margue, R. G. J. Chem. Soc., Perkin Trans. 1 2001, 3085; (d) Nishio,
R.; Sugiura, M.; Kobayashi, S. Chem. Asian. J. 2007, 2, 983; (e) Ye, Z.-W.; Yi, W.-B.
J. Flourine Chem 2008, 129, 1124; (f) Chen, L.; Hong, S.; Zhou, X.; Zhou, Z.; Hou,
H. Catal. Commun. 2008, 9, 2221.
13. (a) Bakherad, M.; Isfahani, H. N.; Keivanloo, A.; Doostmohammadi, N.
Tetrahedron Lett. 2008, 49, 3819; (b) Bakherad, M.; Isfahani, H. N.; Keivanloo,
A.; Sang, G. Tetrahedron Lett. 2008, 49, 6188; (c) Bakherad, M.; Keivanloo, A.;
Bahramian, B.; Kamali, T. A. J. Braz. Chem. Soc. 2009, 20, 907.
14. Bakherad, M.; Keivanloo, A.; Bahramian, B.; Hashemi, M. Tetrahedron Lett. 2009,
50, 1557.