A novel Pd/Ag-catalyzed sonogashira coupling reaction of terminal alkynes with hypervalent iodonium salts

Article abstract of DOI:10.1055/s-2008-1067213

A novel and fast Sonogashira coupling reaction of terminal alkynes with hypervalent iodonium salts was achieved in the presence of catalytic amount of palladium chloride and silver(I) iodide, providing a convenient method for the synthesis of aryl-alkynes in good yields in a short time. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1067213

2
680
SHORT PAPER
A Novel Pd/Ag-Catalyzed Sonogashira Coupling Reaction of Terminal
Alkynes with Hypervalent Iodonium Salts
N
M
ovel Pd/Ag-Catalyze
i
d Sono
n
gashira Reaction Zhu,* Zhongshi Zhou, Rui Chen
College of Biological and Environmental Sciences, Zhejiang Shuren University, Hangzhou 310015, Zhejiang, P. R. of China
Fax +86(571)88297097; E-mail: hzzm60@163.com
Received 13 March 2008; revised 28 April 2008
the corresponding cross-coupling products in good yields
Abstract: A novel and fast Sonogashira coupling reaction of termi-
in a short time.
nal alkynes with hypervalent iodonium salts was achieved in the
presence of catalytic amount of palladium chloride and silver(I) Initially, we mixed one equivalent of phenylacetylene
iodide, providing a convenient method for the synthesis of aryl-
alkynes in good yields in a short time.
(
1a) and diphenyliodonium chloride (2a), two equivalents
of triethylamine, and a catalytic amount (10%) of palladi-
Key words: Sonogashira reaction, terminal alkynes, hypervalent um chloride as catalyst in acetonitrile; we found that the
iodonium salts, Pd/Ag catalyst
coupling reaction occurred slowly and did not reach com-
pletion easily. However, when silver(I) iodide (5%) was
added, the coupling was fast and finished in ten minutes
The formation of a C–C bond by palladium/copper-cata- and a good yield of diphenylacetylene (3a) was obtained.
lyzed coupling of aryl or vinyl halides with terminal These result prompted us to investigate further the reac-
alkynes, known as the Sonogashira reaction, has become tion and a series of experiments were performed to find
1
a powerful tool in organic chemistry. This reaction is fre- the optimum conditions for the coupling of phenylacety-
quently utilized as the key step in natural product lene (1a) and diphenyliodonium chloride (2a). We inves-
2
chemistry and for the synthesis of acetylene compounds, tigated a series of silver salts (e.g., AgI, AgBr, AgCl,
which are potentially useful in optoelectronic applica- Ag SO , and AgNO ) as co-catalyst in the reaction and
2
4
3
3
tions. Typical procedures for the Sonogashira coupling found that silver(I) iodide was the best choice and a 5
utilize catalytic palladium with a copper salt co-catalyst mol% catalytic amount was effective for the coupling. As
and a base. However, the copper salts used as co-catalysts a suitable base, triethylamine was preferred, but diethyl-
can also induce Glaser-type homocoupling of the alkynes amine was also almost equally effective; inorganic bases
4
to the corresponding symmetrical diynes. To avoid this, usually gave lower yields. We also examined several sol-
copper-free Sonogashira reactions using other co-cata- vents for the reaction and found that acetonitrile was the
lysts, such as zinc, tin, boron, aluminum, and silver, have most suitable solvent. Under the optimized conditions, the
1
c,5
been developed in recent years. Pale et al. extensively Sonogashira reaction of alkynes 1 with iodonium salts 2
investigated the Sonogashira coupling reactions of termi- for synthesis of arylalkynes 3 was investigated
nal alkynes with vinyl triflates or aryl iodides in the (Scheme 1), the results are shown in Table 1.
presence of a catalytic amount of tetrakis(triphenylphos-
From Table 1, it is notable that all reactions were complet-
phine)palladium and silver(I) iodide or chloride, and Mori
ed in 40 minutes at room temperature and provided the
developed Pd/Ag-assisted Sonogashira reactions.5 We
c,6
corresponding arylalkynes in good to excellent yields.
When iodonium salts 2c and 2d bearing electron-with-
drawing substituents in the phenyl ring were used, the re-
have recently focused our research on the use of hyperva-
lent iodine compounds in organic synthesis, especially in
the use of hypervalent iodonium salts as alternatives for
actions needed longer times and the yields were somewhat
the replacement of aryl halides or triflates in coupling
lower compared with other iodonium salts (Table 1, en-
tries 3, 4 and 8). When an aliphatic alkyne was used, the
coupling needed a longer reaction time due to the weaker
7
reactions because hypervalent iodonium salts, having the
excellent leaving group ability of a phenyliodanyl group,
can react with a series of nucleophilic reagents under mild
acidity of the acetylenic proton (Table 1, entries 9 and
8
conditions. There are papers on the Sonogashira reaction
of terminal alkynes with hypervalent iodonium salts;9
however, the Pd/Ag-assisted coupling reaction of terminal
alkynes with hypervalent iodonium salts has not been re-
ported. In this paper, we would like to report a novel So-
nogashira protocol in the presence of a catalytic amount of
palladium chloride and silver(I) iodide, which generates
10
1
0).
PdCl2, AgI, Et3N
MeCN
1
+
2 –
R
Ar I Ar X
R
Ar2
1
a R = Ph
2
3
1b R = 4-MeC H4
6
1
1
c R = Bu
d R = (CH2)4Me
Scheme 1
SYNTHESIS 2008, No. 17, pp 2680–2682
x
x.
x
x
.
2
0
0
8
Advanced online publication: 06.08.2008
DOI: 10.1055/s-2008-1067213; Art ID: P04108SS
Georg Thieme Verlag Stuttgart · New York
©

SHORT PAPER
Novel Pd/Ag-Catalyzed Sonogashira Reaction
2681
Table 1 Sonogashira Reaction of Alkynes with Iodonium Salts
1
+
2
–
Entry
Alkyne
Iodonium salt Ar I Ar X
Product
R
Time (min) Isolated yield (%)
Ar2
Ph
+
–
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1b
1b
1b
1c
1d
Ph I Cl
Ph
Ph
Ph
Ph
Ph
3a
3b
3c
3d
3e
3b
3f
15
20
35
40
20
15
20
40
30
40
82
84
74
65
82
88
90
71
82
80
2
2
a
+
–
(4-MeC H ) I BF )
4-MeC H
6
4 2
4
6
4
2
b
+
–
(4-BrC H ) I Br )
4-BrC H
4
6
4 2
6
2
c
+
–
(4-O NC H ) I Br )
4-O NC H
2 6 4
2
6
4 2
2
d
+
–
4-MeOC H I PhBr
4-MeOC H
6
4
6
4
2
e
+
–
Ph I Cl
4-MeC H
Ph
2
6
4
4
4
2
a
+
–
(4-MeC H ) I BF )
4-MeC H
4-MeC H
4
6
4 2
4
6
6
2
b
+
–
(4-O NC H ) I Br )
4-MeC H
4-O NC H
4
3g
3h
3i
2
6
4 2
6
2
6
2
d
+
–
Ph I Cl
Bu
Ph
2
2
a
+
–
10
(4-MeC H ) I BF )
(CH ) Me
4-MeC H
6 4
6
4 2
4
2 4
2
b
In summary, a rapid and convenient method for the forma- 1-Bromo-4-(phenylethynyl)benzene (3c)15
Mp 137–139 °C.
tion of C–C bonds is afforded by the Pd/Ag-assisted
1
Sonogashira coupling reaction of terminal alkynes with
hypervalent iodonium salts. It is simple, fast, and affords
good to excellent yields of arylalkynes.
H NMR (CDCl ): d = 7.22–7.28 (m, 5 H), 7.38–7.46 (m, 4 H).
3
+
MS: m/z (%) = 256 (M , 100).
1
-Nitro-4-(phenylethynyl)benzene (3d)16
Mp 113–115 °C.
Mps were determined on a digital mp apparatus and were not cor-
rected. H NMR spectra were measured on a Bruker AM-400 FT-
NMR spectrometer, and MS were determined on HP5989A mass
1
1
H NMR (CDCl ): d = 7.38–7.40 (m, 3 H), 7.54–7.56 (m, 2 H), 7.68
3
(
d, J = 8.8 Hz, 2 H), 8.24 (d, J = 8.8 Hz, 2 H).
spectrometer. Iodonium salts were prepared according to literature
+
MS: m/z (%) = 223 (M , 100).
procedures.1
1–13
All terminal alkynes are commercially available.
4
-(Phenylethynyl)anisole (3e)16
Arylalkynes 3; General Procedure
Terminal alkyne 1 (0.50 mmol, 1.0 equiv), iodonium salt 2 (0.5
Mp 61–63 °C.
1
H NMR (CDCl ): d = 3.80 (s, 3 H), 6.87 (dd, J = 8.8, 2.0 Hz, 2 H),
3
mmol, 1.0 equiv), Et N (101 mg, 1.0 mmol, 2.0 equiv), PdCl (4.5
3
2
7
.30–7.33 (m, 3 H), 7.45–7.52 (m, 4 H).
mg, 5.0% mmol), and AgCl (6.0 mg, 5.1% mmol) in MeCN (2 mL)
were placed in a glass flask. The mixture was stirred at r.t. for a
short time (Table 1) and then separated by TLC (silica gel, petro-
leum ether); the product, arylalkyne 3, was afforded in good yield
+
MS: m/z (%) = 208 (M , 100).
Di-4-tolylacetylene (3f)17
Mp 138–140.
1
and also characterized by H NMR, MS spectra, and melting point,
which were consistent with the literature data.
1
H NMR (CDCl ): d = 2.36 (s, 6 H), 7.19 (d, J = 7.8 Hz, 4 H), 7.46
3
(
d, J = 7.8 Hz, 4 H).
Diphenylacetylene (3a)14
Mp 59–60 °C.
+
MS: m/z (%) = 206 (M , 100).
1
H NMR (CDCl ): d = 7.32–7.36 (m, 6 H), 7.52–7.55 (m, 4 H).
-(4-Nitrophenylethynyl)toluene (3g)14
Mp 155–157 °C.
3
4
+
MS: m/z (%) = 178 (M , 100).
1
H NMR (CDCl ): d = 2.38 (s, 3 H), 7.24 (d, J = 7.8 Hz, 2 H), 7.46
3
4
-(Phenylethynyl)toluene (3b)14
(
d, J = 7.6 Hz, 2 H), 7.70 (d, J = 7.6 Hz, 2 H), 8.25 (d, J = 8.6 Hz, 2
Mp 70–72 °C.
H).
1
H NMR (CDCl ): d = 2.36 (s, 3 H), 7.15 (d, J = 7.8 Hz, 2 H), 7.32–
+
3
MS: m/z (%) = 237 (M , 100).
7
.34 (m, 3 H), 7.41–7.43 (m, 2 H), 7.51–7.53 (m, 2 H).
+
MS: m/z (%) = 192 (M , 100).
Synthesis 2008, No. 17, 2680–2682 © Thieme Stuttgart · New York

2
682
M. Zhu et al.
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Synthesis 2008, No. 17, 2680–2682 © Thieme Stuttgart · New York