Chemistry Reference
In-Depth Information
CO
2
K
O
3
-allyl)Cl]
2
(0.5 mol %)
4
(0.5 mol %)
K
2
CO
3
, H
2
O, 50 °C, 4 h
[Pd(
η
I
+ PhB(OH)
2
P
O
O
n = 0: 37%
n = 1: 73%
n = 2: 81%
n = 3: 90%
CO
2
K
n
3
4
Scheme 14.5
couplings of aryl bromides in 10% aqueous methanol (Scheme 14.6).
Complete conversion could be achieved in 1 h using 0.01 mol% palladium at
65 1C.
21
With this system, higher generation numbers gave higher rates
with 4-chloronitrobenzene, but no generation effect was seen with
4-bromotoluene.
22
Poly(ethylene glycol) (PEG) is an interesting water-solubilizing group. The
resulting non-ionic phosphines are often soluble in moderately polar or-
ganic solvents, which facilitates synthesis and purification of the ligands.
They are still hydrophilic enough to partition strongly into water in an
aqueous-biphasic system. In addition, PEG shows temperature-dependent
partitioning between water and organic phases. At low temperature, PEG-
modified phosphines partition into the water layer, whereas the PEG-
modified ligand partitions into the organic phase above its cloud point.
Using a diphenylphosphine-terminated PEG oligomer (n
¼
22) with a cloud
point of 74 1C, little activity is seen below 72 1C.
23
At 74 1C, the catalyst ac-
tivity increases dramatically. This ligand also provides recyclable catalysts
for Suzuki couplings in water.
24
Starting in the mid-1990s, a number of researchers found that sterically
demanding and strongly electron-donating alkylphosphine ligands, such as
tri-tert-butylphosphine, provide much more active and general catalysts for
cross-coupling of aryl halides than triarylphosphines. Building on these
advances, hydrophilic, sterically demanding alkylphosphine ligands have
been prepared to give more active catalysts than TPPTS and related tri-
arylphosphines. The first example of a ligand with these properties was
t-Bu-Amphos, which provided the initial report of a room temperature
Suzuki coupling of aryl halides in an aqueous solvent.
25
Sonogashira and
Heck couplings can also be performed under milder conditions than are
possible with TPPTS-derived catalysts.
26
The Pd/t-Bu-Amphos catalyst can be
used for three reaction cycles using Pd(OAc)
2
as the palladium source, but
up to 10 cycles are possible with a hydrophilic palladacycle precursor.
27
The
t-Bu-Amphos/Pd catalyst has been applied to the Suzuki coupling of
7-bromo- and -iodocyclopenta[d][1,2]oxazines (6, Scheme 14.7).
28
Although t-Bu-Amphos provides highly active catalysts for coupling of aryl
bromides, aryl chlorides were largely unreactive. The cationic ammonium
group decreases the electron-donating ability of t-Bu-Amphos compared
with tri-tert-butylphosphine.
29
The DTBPPS ligand incorporates an anionic
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