Chemistry Reference
In-Depth Information
Hartwig 1999
Ph
R
Ph
(
t
-Bu)
2
P
Pd
25 °C
enolate
−78 °C
R
Ar
(DTBPF) Pd
enolate
(DTBPF) Pd(0)
Br
Ph
Fe
O
P(
t
-Bu)
2
1
-bound dtbpf
observed by
31
P NMR
k
Figure 2.12
Stoichiometric enolate arylation with Pd(dtbpf).
the Pd center, leading the authors to speculate that electron-rich, sterically
demanding monophosphines should be suitable for ketone a-arylation
(Figure 2.12).
Indeed, they found that ketone a-arylation, and also the arylation of
malonic esters, employing sterically demanding monophosphines [P(t-Bu)
3
and PCy
3
] as supporting ligands, were highly ecient for coupling of aryl
bromides and aryl chlorides and the Pd/P(t-Bu)
3
system was similarly effective
in room temperature aryl amination reactions of aryl bromides, whereas some
chlorides required higher temperatures (r.t.-70 1C).
49
They also identified
hindered trialkylphosphines to be ecient at promoting Heck-Mizoroki
reactions
50
and the arylation of ethyl cyanoacetate
51
through a series of
fluorescence-based high-throughput screening experiments. This catalyst
system was also used for the N-arylation of indoles and carbamates. In con-
tinuation, Hartwig's group also expanded the use of P(t-Bu)
3
-based catalysts in
a-arylation reactions of ester enolates using either Pd(dba)
2
/P(t-Bu)
3
mixtures
or a single-component pre-ligated Pd(I) dimer, {[P(t-Bu)
3
]PdBr}
2
48,52
(Figure 2.13) (for a detailed discussion on preformed complexes as pre-
catalysts, see Chapter 3).
This dimeric Pd(I) precatalyst, although air sensitive, has also been
demonstrated by Hartwig and co-workers to achieve aryl amination and
Suzuki-Miyaura couplings with aryl chlorides and bromides with ex-
ceptionally high rates.
53,54
In 2000, Beller's group introduced another new type of bulky trialkyl-
phosphine
55
for Suzuki-Miyaura coupling reactions: di-(1-adamantyl)-
n-butylphosphine [Ad
2
P(n-Bu)].
56
The catalyst based on this ligand was
reported to be active for the coupling of chloroarenes with arylboronic acids
with high turnover numbers. Electron-rich, electron-deficient and hetero-
cyclic chloroarenes were all successfully coupled (Figure 2.14).
An entire class of this family of ligands has since been developed and
evaluated by the same group (Figure 2.15, top).
57
The synthesis of these di-
adamantylphosphines involves treating di(1-adamantyl)phosphine with an
alkyl iodide or bromide to give a quaternary phosphonium salt, which is then
liberated by NEt
3
to give the corresponding free ligand (Figure 2.15, bottom).
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