Chemistry Reference
In-Depth Information
i
-Pr
i
-Pr
i
-Pr
i
-Pr
Pd
2
(dba)
3
(0.5 mol %)
TNpP (1 mol %)
NaO
t
-Bu
80 °C, 3 h
Br
NH
2
N
i
-Pr
i
-Pr
i
-Pr
i
-Pr
i
-Pr
i
-Pr
97 %
i
-Pr
i
-Pr
Pd(OAc)
2
(1 mol %)
TNpP (1 mol %)
Na
2
CO
3
rt
Me
Me
B(OH)
2
Br
Me
Me
Me
Me
63 %
Me
Me
Figure 2.19 Buchwald-Hartwig and SMC reactions of hindered substrates using
trineopentylphosphine.
reductive elimination induced with the use of dppf allowed for selective
cross-coupling to proceed over other pathways occurring via b-hydride
elimination. Kumada and co-workers established a correlation between in-
creasing P-Pd-P angles (bite angles) with increasing catalyst activity while
studying Kumada-Tamao-Corriu and Negishi reactions of alkyl nucleo-
philes.
74
(dppf)PdCl
2
(bite angle 99.11) significantly outperformed
(dppp)PdCl
2
(bite angle 90.61) and (dppe)PdCl
2
(bite angle 85.81). Driver and
Hartwig also reported the beneficial effects of bidentate (dppf)PdCl
2
in aryl
amination reactions involving primary alkylamines and rationalized that the
high selectivity stemmed from chelation and bite angle effects.
75
The
intermediate four-coordinate (dppf)Pd(Ar)(amido) complexes are devoid of a
vacant coordination site, thus shutting down the b-hydride elimination
pathway.
76
A review by van Leeuwen et al. further covered the significance of
the ligand bite angle.
77
Indeed, it has now been well established that the use
of bidentate ligands in Pd-catalyzed cross-coupling reactions has an accel-
erating effect on reductive elimination.
Building on these original findings, countless studies emerged using dppf
as a supporting ligand. Even today, dppf remains as a useful ligand for Pd-
catalyzed cross-coupling reactions in the fine chemical and pharmaceutical
industries. Johnson Matthey was the first company to commercialize dppf
and also (dppf)PdCl
2
and provide these compounds on an industrial scale.
78
The history of the use of dppf in homogeneous catalysis applications has
been summarized in other work.
79
The aim of this section is to provide a
review of the modern prominent bidentate phosphine ligands in Pd-cata-
lyzed processes. Ferrocene provides an excellent scaffold for ligand synthesis
owing to the relative ease with which it can be functionalized. The methods
of bis-lithiation with 2 equiv. of n-BuLi in the presence of TMEDA (TME-
DA
¼
tetramethylethylenediamine) followed by electrophile capture with
ClPR
2
or, alternatively, treatment of 1,1
0
-bis(dichlorophosphino)ferrocene
with organolithium or Grignard reagents have been used to generate a
substantial library of 1,1
0
-bis(phosphino)ferrocenes (Figure 2.20).
80
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