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t
-Bu
2
P
t
-Bu
2
P
Pd
Ar
Br
O
Ar
enolate
25 °C
-78 °C
Pd
Fe
A
F
e
Ar
Ar'
R
R'
P
t
-Bu
2
t
-Bu
2
P
O
NaO
t
-Bu
rt, 2h
O
Cl
B
+
THF-d8
t
-Bu
2
P
t
-Bu
2
P
Cl
Pd
F
e
Pd(0)
F
e
5mol%
Cl
P
t
-Bu
2
P
t
-Bu
2
31
PNMR
31
PNMR
δ
=54ppm
δ
=63ppm
Scheme 3.24 Mono- versus bidentate reaction pathway involving dtbpf ligand.
OMe
F
O
O
I
HN
HN
OMe
0.1 mol% dtbpfPdC
l
2
F
O
N
O
N
+
F
KOH, H
2
O/acetone
45 °C, 87 %
F
(HO)
2
B
F
3
C
F
3
C
4kgscale
Scheme 3.25 Low-loading Pd-catalyzed Suzuki-Miyaura cross-coupling.
Applications of dtbpfPdCl
2
precatalyst in large-scale reactions are notable.
Gallagher et al. developed a scalable route to uracil derivatives, incorporating
a Pd-catalyzed Suzuki-Miyaura coupling (Scheme 3.25).
91
The catalyst of
choice was dtbpfPdCl
2
, which could be used in a loading as low as 0.1 mol%
to produce 4 kg of the coupled product.
As part of a route to enantiomerically pure 2-arylpyrrolidines,
researchers at GPRD Process Research and Development incorporated a
Suzuki-Miyaura coupling catalyzed by 1 mol% dtbpfPdCl
2
(Scheme 3.26).
92
The cross-coupling was carried out successfully despite the use of the
unstable 2-boronic acid pyrrole coupling partner.
Another noteworthy member of the L
2
PdCl
2
family of catalysts is Xant-
phosPdCl
2
. This precatalyst is also becoming popular as a second-generation
catalyst in industry. A chemoselective Suzuki-Miyaura reaction of bromo-
phenylchloropyrazine was achieved by careful choice of the precatalyst.
93
The use of XantphosPdCl
2
favored oxidative addition on the chloropyrazine
whereas dtbpfPdCl
2
favored reaction with the bromophenyl (Scheme 3.27).
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