Electrochemical generation of silver acetylides from terminal alkynes with a Ag anode and integration into sequential Pd-catalysed coupling with arylboronic acids

Article abstract of DOI:10.1039/c0cc02633f

An electro-oxidative method for generating silver acetylides from acetylenes with a Ag anode was developed. The reaction could be integrated into a Pd-catalysed electrochemical Sonogashira-type reaction. In the presence of the catalytic amount of Pd(OAc)₂ and 4-BzO-TEMPO, electro-generated silver acetylides reacted immediately with arylboronic acids to afford the corresponding coupling adducts in high yields.

Full text of DOI:10.1039/c0cc02633f

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Electrochemical generation of silver acetylides from terminal alkynes
with a Ag anode and integration into sequential Pd-catalysed coupling
with arylboronic acidsw
Koichi Mitsudo,* Takuya Shiraga, Jun-ichi Mizukawa, Seiji Suga and Hideo Tanaka*
Received 17th July 2010, Accepted 11th October 2010
DOI: 10.1039/c0cc02633f
An electro-oxidative method for generating silver acetylides from
acetylenes with a Ag anode was developed. The reaction could be
integrated into a Pd-catalysed electrochemical Sonogashira-type
reaction. In the presence of the catalytic amount of Pd(OAc)2
and 4-BzO-TEMPO, electro-generated silver acetylides reacted
immediately with arylboronic acids to afford the corresponding
coupling adducts in high yields.
Table 1 Electro-oxidative synthesis of several silver acetylidesa
Entry
1
1
2
Yieldb (%)
88
Silver acetylides are among the oldest organometallics and
several applications to organic syntheses have been reported.1,2
The most common methods for preparing silver acetylides are
(i) the reaction of terminal alkynes with silver salts such as
silver nitrate and silver triflate, and (ii) the reaction of
alkynylsilanes with silver salts.
2
65
70
3c
a
Reaction conditions: 1 (0.2 mmol), DBU (2 equiv.), CH3CN (10 mL),
b
5 mA, 1 F molꢀ1
.
Isolated yield. 1.5 F molꢀ1
.
c
ðiÞ
Table
2 Pd/TEMPO-catalysed electro-oxidative coupling of
phenylacetylene and phenylboronic acid with several basesa
ðiiÞ
We have been interested in the electrochemical
transformation of organometallics and in reactions which
involve thus-generated organometallic species.3 During the
course of our study, we found that terminal alkynes were
transformed easily to silver acetylides under the electro-
oxidative conditions with a Ag anode (Scheme 1). This
electrochemical system for the generation of silver acetylides
could be readily integrated into an electro-oxidative reaction.
The advantage of the reaction is that the synthesis and reaction
of silver acetylide proceeded simultaneously in one reactor. We
report here a facile electrochemical method for the synthesis
of silver acetylides and integration of this method to the
Pd-catalysed electro-oxidative coupling of arylboronic acids
and terminal alkynes.4
Entry
Base
Yieldb (%)
1
2
3
4
5
Et3N
DBU
DABCO
K2CO3
None
51
81
42
24
5
a
Reaction conditions: 1a (0.5 mmol), 3a (0.5 mmol), Pd(OAc)2
(10 mol%), TEMPO (30 mol%), base (2 equiv.), NaClO4 (0.2 M),
CH3CN/H2O (7/1), 50 mA, 4 F molꢀ1
.
Isolated yield.
b
Table
3 Pd/TEMPO-catalysed electro-oxidative coupling of
phenylacetylene and phenylboronic acid with several anodesa
Yieldb (%)
Scheme 1 Strategy for the electro-oxidative synthesis of silver acetylides.
Entry
Anode
Additive
1
2
3
4
5
Ag
Cu
Pt
Pt
Pt
None
None
None
Ag wire
Cu wire
81
56
5
36
2
Division of Chemistry and Biochemistry,
Graduate School of Natural Science and Technology,
Okayama University, 3-1-1 Tsushima-naka, Kita-ku,
Okayama 700-8530, Japan. E-mail: tanaka95@cc.okayama-u.ac.jp;
Fax: +81 86-251-8079; Tel: +81 86-251-8079
w Electronic supplementary information (ESI) available: experimental
details. See DOI: 10.1039/c0cc02633f
a
Reaction conditions: 1a (0.5 mmol), 3a (0.5 mmol), Pd(OAc)2
(10 mol%), TEMPO (30 mol%), DBU (2 equiv.), NaClO4 (0.2 M),
CH3CN/H2O (7/1), 50 mA, 4 F molꢀ1
.
Isolated yield.
b
c
9256 Chem. Commun., 2010, 46, 9256–9258
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We first chose silver phenylacetylide (2a) as a target
compound (Table 1). Electro-oxidation was performed in a
two-compartment cell divided by a glass filter. To the anodic
(entries 3 and 4). The addition of base was indispensable for
the reaction. Without base, the yield of 4aa decreased to 5%
(entry 5).
chamber was added
a
solution of terminal alkyne 1a
To evaluate the utility of the obtained silver acetylide,
several different anodes were used in the reaction (Table 3).
With a Cu anode, the reaction also proceeded to afford internal
alkyne 4aa in 56% yield (entry 2). In contrast, only a trace
amount of 4aa was obtained with a Pt anode, which could not
act as a sacrificial anode (entry 3). These results suggest that
the generation of a metal acetylide, such as silver acetylide or
copper acetylide, might be essential for the reaction. We next
examined the reaction with a Pt anode in the presence of Ag
wire in the reaction mixture. The reaction proceeded, and 4aa
was obtained in 36% yield (entry 4). The lower yield compared
to that of entry 1 might be due to the lower efficiency of the
generation of silver acetylide.
(0.2 mmol) and DBU (1,8-diazabicyclo[5.4.0]undec-7-ene,
2.0 equiv.) in 0.05 M Et4NOTs/CH3CN (10 mL), and to the
cathodic chamber was added a solution of 0.05 M Et4NOTs/
CH3CN (10 mL). Constant-current electrolysis of the solution
afforded silver acetylide 2a in 88% yield (entry 1). Similarly,
silver acetylides 2b and 2c could be obtained in respective yields
of 65% and 70% (entries 2 and 3).
We next investigated the integration of this electrochemical
synthesis of silver acetylides to Pd-catalysed coupling with
arylboronic acids. First, the electro-oxidative coupling of
phenylacetylene (1a) and phenylboronic acid (3a) was carried
out in the presence of several bases (Table 2). In the presence of
Pd(OAc)2 (10 mol%), TEMPO (2,2,6,6-tetramethylpiperidine-
1-oxyl, 30 mol%), and Et3N (2 equiv.), the electrooxidative
coupling reaction proceeded smoothly to afford product 4aa in
51% yield (entry 1). Further screening revealed that the
addition of DBU was highly advantageous for the reaction,
and the yield of 4aa increased drastically up to 81% (entry 2).
The addition of DABCO (1,4-diazabicyclo[2.2.2]octane) or
potassium carbonate did not promote the reaction efficiently
To exploit the utility of this reaction, the scope of the
reaction was investigated (Table 4). During the course of the
optimization of the conditions, we found that the amount of
Pd(OAc)2 could be reduced to 5 mol%, and 4-BzO-TEMPO
was a better mediator than TEMPO. The electro-oxidative
coupling of 1a and 3a afforded 4aa in 93% yield under the
optimized conditions (entry 1). Unexpectedly, the reaction also
proceeded without a mediator to afford 4aa in a similar yield.
Table 4 Pd-catalysed electro-oxidative coupling of terminal alkynes and arylboronic acidsa
Entry
1
1
3
4
Yieldb (%)
93 (91)c
2d
3d
4
91
99 (42)c
91 (84)c
76 (77)c
99
5d
6
7
95c
8
96c
9d
80c
76
10d
a
Reaction conditions: 1 (0.5 mmol), 3 (0.5 mmol), Pd(OAc)2 (5 mol%), 4-BzO-TEMPO (15 mol%), DBU (2 equiv.), NaClO4 (0.2 M), CH3CN/
b
H2O (7/1), 50 mA, 4 F molꢀ1
.
c
Isolated yield. Without mediator. 10 mA of electricity was passed.
d
c
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intermediate, and subsequent reductive elimination would
afford the coupling product and Pd(0) species.5 Pd(II)
complex would be regenerated through the oxidation by
N-oxoammonium cation, which would be generated by the
electro-oxidation of 4-BzO-TEMPO. In the absence of 4-BzO-
TEMPO, silver species would act as a mediator.
In summary, we have developed an electro-oxidative method
for preparing silver acetylides. The in situ integration of the
synthetic procedure of silver acetylides and the Pd-mediatory
electro-oxidative cross-coupling with arylboronic acids were
also successful. The further application of this strategy is being
studied in our laboratory.
Notes and references
1 For a review, see: U. Halbes-Letinois, J.-M. Weibel and P. Pale,
Chem. Soc. Rev., 2007, 36, 759.
Fig. 1 A plausible mechanism for the electro-oxidative coupling of
2 Recent examples, see: (a) S. Kim, B. Kim and J. In, Synthesis, 2009,
1963; (b) B. J. Albert and K. Koide, J. Org. Chem., 2008, 73, 1093;
(c) R. H. Pouwer, J. B. Harper, K. Vyakaranam, J. Michl,
C. M. Williams, C. H. Jessen and P. V. Bernhardt, Eur. J. Org.
Chem., 2007, 241; (d) R. H. Pouwer, C. M. Williams, A. L. Raine
and J. B. Harper, Org. Lett., 2005, 7, 1323; (e) S. P. Shahi and
K. Koide, Angew. Chem., Int. Ed., 2004, 43, 2525; (f) D. Bruyere,
D. Bouyssi and G. Balme, Tetrahedron, 2004, 60, 4007.
3 (a) K. Mitsudo, T. Shiraga, D. Kagen, D. Shi, J. Y. Becker and
H. Tanaka, Tetrahedron, 2009, 65, 8384; (b) K. Mitsudo, T. Ishii and
H. Tanaka, Electrochemistry, 2008, 76, 859; (c) K. Mitsudo,
T. Imura, T. Yamaguchi and H. Tanaka, Tetrahedron Lett., 2008,
49, 7287; (d) K. Mitsudo, T. Shiraga and H. Tanaka, Tetrahedron
Lett., 2008, 49, 6593; (e) K. Mitsudo, T. Kaide, E. Nakamoto,
K. Yoshida and H. Tanaka, J. Am. Chem. Soc., 2007, 129, 2246.
4 Pd or Cu-catalysed coupling of terminal alkynes and arylboronic
acids, see: (a) G. Zou, J. Zhu and J. Tang, Tetrahedron Lett., 2003,
44, 8709; (b) F. Yang and Y. Wu, Eur. J. Org. Chem., 2007, 3476;
(c) C. Pan, F. Luo, W. Wang, Z. Ye and J. Cheng, Tetrahedron Lett.,
2009, 50, 5044; (d) J. Mao, J. Guo and S. J. Ji, J. Mol. Catal. A:
Chem., 2008, 284, 85.
terminal alkynes and arylboronic acids.
For arylboronic acids bearing an electron-donating group, the
addition of mediator was essential. In the reaction of 1a with
3b or 3c, the reactions proceeded smoothly to afford 4ab and
4ac in respective yields of 91% and 99% (entries 2 and 3). In
contrast, in the reaction of electron-deficient arylboronic acids,
the electro-oxidative reaction was not affected by the mediator
(entries 4 and 5). p-Tolylacetylene (1b) exhibited high reactivity
in the reaction, and the corresponding alkynes 4 were
obtained in excellent yields (entries 6–8). In contrast, when
p-nitrophenylacetylene (1d) was used, the yields of 4 were
slightly lower than those of 1a and 1b (entries 9 and 10). We
assumed that this difference is due to the efficiency of the
generation of silver acetylide. Electron-rich alkynes would
interact efficiently with Ag+, and silver acetylide would be
generated faster than electron-deficient alkynes.
5 Another plausible mechanism is that transmetallation with a silver
acetylide would be the first step, and following transmetallation with
arylboronic acid and reductive elimination would afford the
coupling product. The details of the mechanism is currently under
investigation.
A plausible mechanism for the coupling reaction is illustrated
in Fig. 1. First, R1Pd(II)Ln (L = ligand) would be generated
from Pd(II) and arylboronic acid. Following transmetallation
with silver acetylide would give an alkynylpalladium
c
9258 Chem. Commun., 2010, 46, 9256–9258
This journal is The Royal Society of Chemistry 2010