Facile synthesis of substituted alkynes by cyclopalladated ferrocenylimine catalyzed cross-coupling of arylboronic acids/esters with terminal alkynes

Article abstract of DOI:10.1002/ejoc.200700065

A highly efficient and convenient catalytic system for the cross-coupling reaction of arylboronic reagents with terminal alkynes was described by using cyclopalladated ferrocenyhmine (I)/silver oxide as the catalyst at room temperature. This method provides the first examples of a palladacycle-catalyzed cross-coupling reaction of arylboronic acids/esters with terminal alkynes under mild conditions, and also a facile route for the synthesis of substituted alkynes with a low Pd loading of 1 mol-%. The substrates could be extended to electron-poor alkynes, for which the traditional Sonogashira reaction does not proceed. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

Full text of DOI:10.1002/ejoc.200700065

FULL PAPER
DOI: 10.1002/ejoc.200700065
Facile Synthesis of Substituted Alkynes by Cyclopalladated Ferrocenylimine
Catalyzed Cross-Coupling of Arylboronic Acids/Esters with Terminal Alkynes
[a]
[a]
Fan Yang and Yangjie Wu*
Keywords: Palladium / Cross-coupling / Arylboronic acids / Alkynes / Silver
A highly efficient and convenient catalytic system for the
cross-coupling reaction of arylboronic reagents with terminal
alkynes was described by using cyclopalladated ferrocenyli-
mine (I)/silver oxide as the catalyst at room temperature. This
method provides the first examples of a palladacycle-cata-
lyzed cross-coupling reaction of arylboronic acids/esters with
terminal alkynes under mild conditions, and also a facile
route for the synthesis of substituted alkynes with a low Pd
loading of 1 mol-%. The substrates could be extended to
electron-poor alkynes, for which the traditional Sonogashira
reaction does not proceed.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Introduction
In 2001, we found that a novel kind of palladacyclic cata-
lysts: cyclopalladated ferrocenylimines could be used as ef-
ficient catalysts for Heck arylation. Subsequently, we dis-
covered their wide applications in catalytic reactions such
Alkyne moieties are valuable intermediates for the syn-
thesis of numerous natural products and bioactive com-
[
7]
[
1–2]
pounds.
Of the various synthetic approaches available
as Heck reactions both in organic solvent and neat water,
for aryl alkynes, the Sonogashira cross-coupling reaction is
the most commonly used one.[ However, it does not pro-
ceed well for electron-poor alkynes and harsh reaction con-
the dimerization of ArHgCl and Suzuki reactions.[
7–9]
Sil-
3]
ver(I) oxide is known not only to be capable of activating
the C–B bond to form alkyn-1-yl silver with alkynes in situ,
but also to oxidize palladium(0) to palladium(II) species.[
Here we would like to report a general and efficient proto-
col for the synthesis of substituted alkynes by the cyclopal-
ladated ferrocenylimine catalyzed cross-coupling reaction of
arylboronic acids/esters with terminal alkynes in the pres-
[
4]
ditions must be employed (usually temperatures Ͼ70 °C).
10]
So, an easy and convenient approach for the synthesis of
substituted alkynes under mild conditions should be devel-
oped. Up to now, there has been only one report on the
cross-coupling reaction of boronic acids with terminal al-
kynes to afford aryl alkynes.[ This catalytic system was
quite efficient for electron-poor alkynes, but employed a
high loading of the catalyst (5 mol-% of Pd) and did not
work well for the cross-coupling of phenylboronic acid with
phenylacetylene (30% yield). In this case, homocoupling of
5]
ence of Ag O as the additive at room temperature.
2
phenylacetylene occurred to give biphenylbutadiyne (60%) Results and Discussion
as the byproduct.
Palladacycles have emerged as promising catalysts in
C–C and C–heteroatom bond-forming reactions during the
past few years. They are often stable and easy to handle
and can be used as important alternatives to palladium(0)
complexes, but there are no reported examples about the
use of palladacycles as catalysts for the cross-coupling reac-
tion of arylboronic acids with terminal alkynes up to now.
To evaluate the catalytic activity of the cyclopalladated
ferrocenylimine/Ag O system, the reaction conditions were
2
optimized by using phenylboronic acid (1a) with phenyl-
acetylene (2a) as the substrates. The results are summarized
in Table 1 (Figure 1). After various bases such as K PO ,
[
6]
3
4
Cs CO , K CO , KF·2H O, and KOAc were examined,
2
3
2
3
2
KOAc gave the best result (Table 1, Entries 1–5). The oxi-
dative silver salt played a key role in the successful cross-
coupling reactions (Table 1, Entries 5–7). When TBAB was
employed as the additive, it showed no activity for the reac-
[a] Chemistry Department, the Key Laboratory of Chemical Bi-
ology and Organic Chemistry of Henan Province, the Key and tion (Table 1, Entry 6). If the loading of oxidative silver was
Open Laboratory of Applied Chemistry of Henan Universities,
reduced to 10 mol-%, only a yield of 50% was obtained
Zhengzhou University,
Zhengzhou 450052, P. R. China
(Table 1, Entry 7). The cross-coupling reaction proceeded
smoothly under air and gave a yield of 90% (Table 1, En-
try 5). However, the homocoupling product (10%) was ob-
tained as the byproduct. It is notable that when the reaction
Fax: +86-371-67766667
E-mail: wyj@zzu.edu.cn
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
3476
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 3476–3479

Synthesis of Substituted Alkynes by Pd-Catalyzed Cross-Coupling Reactions
FULL PAPER
was performed under a nitrogen atmosphere, an excellent Table 2. Palladacycle-catalyzed cross-coupling of arylboronic rea-
gents with alkynes.[
a]
yield (95%) was obtained and no 1,3-butadiyne was detect-
able (Table 1, Entry 8). However, only a relatively lower
yield (38%) was obtained with the lower catalytic loading
of 0.1 mol-% (Table 1, Entry 9).
Table 1. Palladacycle-catalyzed cross-coupling of phenylboronic
acid with phenylacetylene.[
a]
Entry
Base
PO
CO
CO
KF·2H
KOAc
KOAc
KOAc
KOAc
KOAc
Additive
Yield[b]
1
2
3
4
5
6
7
8
9
K
Cs
3
4
Ag
Ag
Ag
Ag
Ag
2
2
2
2
2
O
O
O
O
O
14
7
Trace
20
90
Trace
50
95
2
3
K
2
3
2
O
[
c]
TBAB
[
[
[
d]
e]
f]
Ag
Ag
Ag
2
2
2
O
O
O
38
[
a] Reaction conditions: PhB(OH)
2
(0.5 mmol), phenylacetylene
0.6 mmol), base (0.75 mmol), additive (0.5 mmol), and palladacy-
Cl (3 mL) for 24 h under air and at room
temperature. [b] Isolated yield. [c] Biphenylbutadiyne (10%) was
obtained as a byproduct. [d] When Ag O (0.05 mmol) was used,
(
cle I (1 mol-%) in CH
2
2
2
biphenylbutadiyne (25%) and biphenyl (25%) were obtained as by-
products. [e] Under a nitrogen atmosphere. [f] Palladacycle
(0.1 mol-%) and under a nitrogen atmosphere.
Figure 1. Palladacycle I.
Under these optimized conditions, the results for investi-
gating the scope of the substrates are summarized in
Table 2. For arylboronic acids or esters, it can be seen that
electron-donating (OCH and CH ), electron-withdrawing
3
3
(
CF ), or heterocyclic aromatic groups had little effect on
3
the cross-coupling reaction and moderate-to-good yields
were obtained. However, for naphthylboronic acids with a
large vicinal steric group (1h), the cross-coupling reaction
did not proceed (Table 2, Entry 10). The cross-coupling of
electron-rich aromatic alkyne 2b proceeded smoothly and
gave a good yield of 88% (Table 2, Entry 1). It is notable
that the electron-poor aromatic alkyne 3-ethynylpyridine
(2c) and ethyl propiolate (2d) also gave moderate yields (71,
75, and 80%, Table 2, Entries 2, 4, and 11, respectively),
whereas the traditional Sonogashira reaction does not work
for electron-poor alkynes. Aliphatic alkynes 2e–g showed a
similar reaction activity, affording moderate-to-good yields
[
(
a] Reaction conditions: arylboronic reagent (0.5 mmol), alkyne
0.6 mmol), KOAc (0.75 mmol), Ag O (0.5 mmol), and palladacy-
cle I (1 mol-%) in CH Cl (3 mL) for 24 h under a nitrogen atmo-
alkyne 2h, the cross-coupling reaction proceeded slowly and sphere at room temperature. [b] Isolated yield. [c] Biaryl (60%) was
a lower yield was obtained (Table 2, Entry 19).
obtained as a byproduct.
2
(Table 2, Entries 12–18). However, for hydroxy containing
2
2
Eur. J. Org. Chem. 2007, 3476–3479
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3477

F. Yang, Y. Wu
FULL PAPER
Scheme 1. Proposed mechanism for the palladium-catalyzed cross-coupling reaction of arylboronic acids with terminal alkynes.
Mechanism
conditions, and also a facile route for the synthesis of sub-
stituted alkynes. The substrate scope can include electron-
poor alkynes, for which the traditional Sonogashira reac-
tion does not proceed. Further studies and applications in
organic synthesis are currently underway in our laboratory.
As shown in Scheme 1, a reaction mechanism for the pal-
ladium-catalyzed cross-coupling reaction of arylboronic ac-
ids with terminal alkynes was proposed on the basis of the
mechanism of previous reports and our results.[
5,10]
The re-
placement reaction of palladium(II) with arylboronic acids
would occur to form palladium(II) intermediate 5. Palladi-
um(II) intermediate 5 could react with alkynylsilver(I) 4 to
Experimental Section
afford palladium(II) intermediate 6. Reductive elimination Typical Procedure for the Cyclopalladated Ferrocenylimine Cata-
lyzed Cross-Coupling Reaction of Arylboronic Reagents with Ter-
minal Alkynes: Under a nitrogen atmosphere, a mixture of the aryl-
boronic reagent (1) (0.5 mmol), alkyne (2) (0.6 mmol), palladacycle
of intermediate 6 could undergo to form desired product 3
and palladium(0). The palladium(0) species can be oxidized
to regenerate palladium(II) by the silver(I) species to close
the catalytic cycle (pathway 1).[
10]
Though mechanistic
2 2 2
I (1 mol-%), Ag O (0.5 mmol), KOAc (0.75 mmol), and CH Cl
(
3 mL) was stirred at room temperature, and the reaction was fol-
pathway 1 provides cross-coupling products, the homo-
coupling of arylboronic acids and alkynes occurred through
pathways 2 and 3. Both pathway 1 and 2 started with oxi-
lowed by TLC or GC. After the reaction was complete, the mixture
was filtered. The solvent was removed under reduced pressure. The
residue was purified by column chromatography (hexane or hexane/
dative addition of alkynylsilver(I) 4 or arylboronic acid 1 ethyl acetate) to afford pure 3.
to palladium(II) intermediate 5. Pathway 3 began with the
Supporting Information (see footnote on the first page of this arti-
replacement reaction of palladium(II) with alkynylsilver(I)
cle): Selected characterization data for compounds 3. The charac-
4. Therefore, the three pathways should be competitive with
[11–23]
terization of these compounds is identical to the literature.
each other. When the reaction activity of the alkyne was
much lower than that of the arylboronic acid, the homo-
coupling product of boronic acid was obtained as the major
product (Table 2, Entry 19).
Acknowledgments
We are grateful to the National Natural Science Foundation of
China (No. 20472074) and the Innovation Fund for Outstanding
Scholar of Henan Province (No. 0621001100) for financial support
of this research.
It should be noted that without the aid of Ag O, a trace
2
amount of desired product 3 was observed (Table 1, En-
try 6). It is suggested that palladium(II) intermediate 6 or 9
could also be formed from the reaction of intermediate 5
or palladium(II) with alkynes 2 in the presence of KOAc,
respectively. However, the rate of this reaction would be
much lower than that of alkynylsilver(I) 4.
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Synthesis of Substituted Alkynes by Pd-Catalyzed Cross-Coupling Reactions
FULL PAPER
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