Chemistry Reference
In-Depth Information
Identically with the Pd
2
dba
3
/t-Bu
3
P systems, use of the Pd(I) dimer in
MeCN resulted in exclusive OTf insertion (Scheme 3.33). In THF, oxidative
addition occurred into the C-Cl bond. Interestingly, the reaction rates using
the precatalyst [(t-Bu
3
P)Pd(m-Br)]
2
were much faster than those observed
when using the in situ-formed catalyst. Similarly enhanced reaction rates
were observed in amine arylation (Buchwald-Hartwig) reactions with aryl
chlorides and Suzuki-Miyaura reactions using aryl bromides.
108
The chemoselectivity can be explained by having a closer look at the actual
active catalytic species generated under each set of conditions. It is sug-
gested that in a polar solvent, such as acetonitrile, the active species formed
is the anionic [(t-Bu
3
P)Pd(0)(X)]
,
107
resulting in triflate insertion. In a non-
polar solvent such as THF, the neutral species (t-Bu
3
P)Pd(0) is formed,
favoring insertion into the C-Cl bond. This is consistent with their earlier
studies to support Fu and co-workers' observation
11
that Cy
3
P-based Pd
complexes are suitable for OTf coupling.
The precatalyst [(t-Bu
3
P)Pd(m-Br)]
2
has also been shown to provide regio-
selective
couplings
in
the
case
of
dihalogenated
heterocycles
(Scheme 3.34).
106
The role of the Pd(I) dimer as a precatalyst has been questioned, however.
Schoenebeck and co-workers demonstrated that aryl iodides are in fact able
to react directly with the dimer and undergo oxidative addition.
109
The
second product in this reaction is the corresponding aryl bromide, with the
bromide originating from the precatalyst. This reaction can be made cata-
lytic in Pd by the addition of NBu
4
Br as a bromide source.
[(t-Bu
3
P)Pd(m-Br)]
2
has also been used successfully in cross-coupling re-
actions in industry. Ryberg reported a robust and mild method for the
cyanation of indole (Scheme 3.35).
110
Pd(I) dimer (1.25 mol%) was identified
as the catalyst of choice and provided high yields of the product even on a
5 kg scale.
X
X
1.0 mol % [(
t
-Bu
3
P)Pd(
μ
-Br)]
2
B(OH)
2
Y
Y
+
R
n
X
n
Z
Z
KF, THF:H
2
O, rt
R
n
=1,2
Scheme 3.34 Regioselective
Suzuki-Miyaura
cross-coupling
reaction
using
[(t-Bu
3
P)Pd(m-Br)]
2
.
H
N
H
N
OH
OH
[(
t
-Bu
3
P)Pd(
μ
-Br)]
2
Br
NC
Zn(CN)
2
N
N
Zn, DMF
50
o
C, 1-3h
N
N
O
O
Scheme 3.35 Cyanation reaction using [(t-Bu
3
P)Pd(m-Br)]
2
as catalyst.
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