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In-Depth Information
[Pd(IPr)(allyl)Cl] (84)
(2 mol%)
OH
O
Cl
R''
R
+R''
R
KOtBu, toluene, 80°C
0.5 - 24 h
R'
R'
O
O
O
NN
Pd
Cl
94%
88%
90%
OMe
[Pd(IPr)(allyl)Cl]
84
O
O
N
MeO
81%
86%
Scheme 4.58 Cascade alcohol oxidation/a-arylation using [Pd(IPr)(allyl)Cl].
4.3.6 C-Heteroatom Bond Formation
4.3.6.1 Amination Reactions
The palladium-catalysed amination reaction, also known as Buchwald-
Hartwig cross-coupling, is one of the most ecient methods to create C-N
bonds. Historically, the reaction was pioneered using aminostannanes by
Migita and co-workers in 1983,
164
but the groups of Buchwald
165
and
Hartwig
166
developed more convenient and ecient tin-free protocols about
a decade later, in 1995. Since then, a large number of publications have
appeared regarding this coupling reaction.
167
The mechanism of the re-
action is described in Scheme 4.59. First the palladium source is reduced to
its active Pd(0) form. The next step is the oxidative addition of the aryl halide
to yield a palladium-aryl complex. The coordination of the amine to the
palladium centre can occur through two main pathways, depending on the
nature of the base: (a) if an alkoxide base is used, a Pd-alkoxide complex can
be formed, thus deprotonating the amine, resulting in the formation of the
Pd-N bond; (b) the amine can first coordinate the metal centre to afford a
Pd-NHR
0
R
00
complex, which can be deprotonated by the base to yield the Pd-
NR
0
R
00
complex. Finally, reductive elimination leads to the formation of the
desired C-N bond and the active Pd(0) species is subsequently regenerated.
Since Nolan and co-workers' first report on the use of Pd-NHC systems in
the amination reaction,
168
many other contributions have been presented in
the literature. Some excellent reviews are available that cover most of the
major advances in this field.
9c,d,167
In this section, we focus on the latest
protocols reported since 2010. We pay particular attention to the new cata-
lytic systems that permit the coupling of challenging substrates under mild
conditions (e.g., low catalyst loadings or low temperature).
4.3.6.1.1 Development of New Well-Defined Precatalysts Bearing Bulky
NHC Ligands. Throughout this chapter, the importance of developing
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