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Pd/(Cu)/L
X
X=I, Br,Cl,OTf,N
2
BF
4
,etc
Scheme 10.18 Palladium-catalysed Sonogashira coupling reaction.
O
O
R'
R"
Z
R'
Cl
O
Y
R"
X
R'
R"
R'
R"
R'X
CO
R"
X
Z
Y
Scheme 10.19
Selected synthesis and applications of alkynones.
O
X
PdCl
2
(dppf) (1 mol% )
80-120
o
C
CO (1-20 bar)
NEt
3
15 examples
46 -93%
R
R'
R'
R
X=I,Br
Scheme 10.20 First Pd-catalysed carbonylative Sonogashira coupling of organic
halides.
Sonogashira et al. in 1975 (Scheme 10.18).
22
Today, the Sonogashira coup-
ling reaction is one of most powerful processes for C-C bond formation,
especially for the synthesis of substituted alkynes.
23
Carbonylative Sonogashira reactions lead to alkynones, which represent
an interesting structural motif found in numerous biologically active mol-
ecules.
24
Notably, such compounds play a crucial role as key intermediates
in the synthesis of natural products
25
and for the ecient formation of
several heterocycles.
26
Traditionally, alkynones have been synthesized by
transition metal-catalysed cross-coupling reactions of acid chlorides and
terminal alkynes (Scheme 10.19).
27
However, the stability of the respective
acid chlorides is limited and a lack of functional tolerance is another
problem with this methodology. Without doubt, the carbonylative Sonoga-
shira coupling of corresponding terminal alkynes and aryl halides represents
the most straightforward way to construct alkynones.
The first palladium-catalysed carbonylative Sonogashira coupling was re-
ported in 1981 by Kobayashi and Tanaka.
28
Aryl, heterocyclic and vinylic
halides reacted with CO (80 bar) and terminal acetylenes at 120 1C in the
presence of NEt
3
and a catalytic amount of a palladium(II) complex to form
alkynones in 46-93% yield (Scheme 10.20). Remarkably, aryl bromides and
aliphatic alkynes were also included in the range of substrates.
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