Chemistry Reference
In-Depth Information
I
3
-C
3
H
5
)Cl]
2
Si(
n
-Pr)F
2
2.5 mol % [Pd(
η
MeO
H
+
O
KF, DMF, 100 °C
OMe
O
H
83 %
Hiyama 1989
Scheme 1.11 Pd-catalyzed coupling of organosilicon reagents with aryl iodides.
H
N
O
2 mol % PdCl
2
[P(
o
-tolyl)
3
]
2
Br
N
+
NaO
t
-Bu, toluene, 100 °C
O
86 %
Buchwald 1995
Br
H
N
5mol%PdCl
2
[P(
o
-tolyl)
3
]
2
N
+
LiHMDS, toluene, 100 °C
89 %
Hartwig 1995
Scheme 1.12 Pd-catalyzed direct coupling of amines with aryl bromides.
By 1989, it was already possible to achieve C-C bond formation through
cross-coupling reactions using a wide variety of organometallic reagents. The
next breakthrough came with the independent discoveries by Buchwald and
Hartwig that C-N bond formation could also be eciently accomplished
through palladium-catalyzed cross-coupling reactions of free amines with
aryl halides (Buchwald-Hartwig amination) (Scheme 1.12).
46
This method-
ology was also extended to cover C-O and C-S bond formation. Chapter 6,
authored by James Stambuli, provides a specific discussion of the develop-
ment of C-O and C-S bond-forming reactions using cross-coupling
methodologies.
At this stage, it may seem like most of the monumental discoveries had
already been made; however, there is by no means an end to the advance-
ment of cross-coupling reactions. Reports continue to appear in the litera-
ture regarding novel reactivity, enhanced substrate compatibility, new trends
and solutions to previously problematic transformations.
Following the seminal discoveries made before 2000, the first decade of
the new millennium would see the expansion of cross-coupling reactions to
include the use of the previously very challenging aryl chlorides as coupling
partners. This was achieved by the groups of Buchwald,
47
Fu
48
and Koie
49
by means of using bulky, electron-rich monophosphines as ligands.
In addition, enormous progress has been made to be able to employ C(sp
3
)-
based coupling partners, such as alkyl-BR
2
or alkyl halide reagents.
50
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