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I
COOt Bu
59
(0.005 mol%)
R
+
R
COOtBu
Et
3
N, TBAI
H
2
O, 1 00°C
COOH
OMe
COOt Bu
COOt Bu
Br
COOt Bu
N
F
N
N
Pd
>99%
85%
96%
N
N
Bu
Br
Bu
COOt Bu
59
COOt Bu
N
29%
3%
Scheme 4.35 Heck reaction at low catalyst loading in water.
Pd(OAc)
2
(0.5 mol%)
(1 mol%)
N
2
BF
4
R'
60
R
+
R
R'
EtOH, 36°C, 3 h
HO
COOEt
COOt Bu
COOEt
Ph
NN
Ph
MeO
O
2
N
I
92%
96%
94%
Cl
60
F
3
C
COOEt
Cl
CONH
2
CONH
2
CF
3
U-77863
78%
64%
20%
Scheme 4.36 Heck reaction using arenediazonium salts as pseudohalides.
4.3.2.6 Applications
The Heck reaction is widely used to create C-C bonds in the preparation of
biologically active compounds. A recent example was reported by Duke and
co-workers in 2013.
127
A library of C- and O-prenylated tetrahydroxystilbenes
and O-prenylated cinnamates was prepared and the biological activity of the
compounds towards K562 cancer cells was studied. The key step of the se-
quence was a decarbonylative Heck coupling using an in situ-formed cata-
lytic system consisting of palladium acetate and IPr
HCl (Scheme 4.37).
Compound 61 was identified as a potent growth inhibitor (IC
50
= 0.10 mM).
4.3.3 Sonogashira Coupling and Heck Alkynylation (Copper-
Free Sonogashira Coupling)
The palladium-catalysed cross-coupling reaction between alkynes and aryl
halides was discovered in 1975 by three independent research groups:
Sonogashira,
128
Heck
129
and Cassar.
130
Heck's and Cassar's groups
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