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MeO
MeO
dppfPdCl
2
Zn, Zn(CN)
2
N
O
N
O
BMS-764459
Cl
N
NH
NC
N
NH
NMP, 95 °C
N
OCHF
2
N
OCHF
2
Scheme 3.20 Large-scale cyanation catalyzed by dppfPdCl
2
.
t
-Bu
2
P
Cl
Cullen 1985
Colacot 2004
Pd
Fe
Cl
P
t
-Bu
2
Figure 3.15
Structure of dtbpfPdCl
2
.
NMe
2
Cl
P
Pd
P
Cl
Me
2
N
Guram 2006
Figure 3.16
Structure of [p-Me
2
NC
6
H
4
(t-Bu)
2
P]
2
PdCl
2
.
Cullen and co-workers briefly mentioned the first synthesis of the PdL
2
X
2
complex dtbpfPdCl
2
in 1985.
78
Colacot and co-workers were the first to de-
velop a scalable route to dtbpfPdCl
2
;
79
they also reported its X-ray structure,
in addition to demonstrating its utility as a highly active air-stable pre-
catalyst in Suzuki-Miyaura
80
and a-arylation reactions.
8,81
Since then, this
complex has been used successfully in many challenging cross-coupling
reactions and is deemed to be one of the catalysts of choice for a ''first-pass''
Suzuki-Miyaura reaction
82
and for ''first-pass'' Heck reactions using aryl
bromides.
83
Another prominent L
2
PdX
2
precatalyst, developed by Guram et al.,
84
showed similar activities to dtbpfPdCl
2
in many reactions, but it is devoid
of Fe (Figure 3.16). The trans-dichlorobis[di-tert-butyl(4-dimethylaminophe-
nyl)phosphine]palladium(II) catalyst, [p-Me
2
NC
6
H
4
(t-Bu)
2
P]
2
PdCl
2
, has
since been widely employed as a highly effective precatalyst for a number of
cross-coupling reactions, such as Suzuki-Miyaura coupling of heteroaryl
chlorides
84
and Heck alkynylation (Cu-free Sonogashira) reactions of aryl
chlorides.
50,85
Larsen and co-workers at Amgen reported a practical
synthesis of a p38 MAP (mitogen-activated protein) kinase inhibitor
employing a Pd-catalyzed Suzuki-Miyaura coupling (Scheme 3.21).
86
They
found [p-Me
2
NC
6
H
4
(t-Bu)
2
P]
2
PdCl
2
to be the best performing catalyst.
Carbonylation of aryl halides, in particular of aryl chlorides, is a chal-
lenging C-C bond-forming reaction due to the strong d
p
-p
p
backbonding of
Pd to the CO ligand, when the ligand involved is electron rich. This
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