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65
(1 mol %)
solvent
K
2
CO
3
, 80 °C, 12 h
Cl
Ph
+ PhB(OH)
2
O
2
N
O
2
N
Pd(OAc)
2
N
(AcO)
2
Pd
N
N
Solvent
water
glycerol
water/glycerol
Yield
12%
36%
82%
N
65
Scheme 14.55
Glycerol in combination with water improves the performance of complex 65
in Suzuki couplings of aryl chlorides (Scheme 14.55).
168
Complex 65 afforded
good yields in water with aryl bromides, but only a 12% yield with 1-chloro-4-
nitrobenzene. A 36% yield was obtained with glycerol as the solvent, but the
yield increased to 82% with 1 : 1 water-glycerol. Good yields (62-86%) were
obtained with unactivated and deactivated aryl chlorides under these
conditions.
14.3.3 Compressed CO
2
Supercritical or liquid carbon dioxide (compressed CO
2
) has attracted sig-
nificant attention as an alternative solvent in a variety of applications, in-
cluding organic synthesis.
169
Carbon dioxide is a widely available and
inexpensive material. With increasing concern about its role in climate
change, there is strong interest in finding uses for captured carbon dioxide.
As a large-scale industrial material, it is relatively safe as it is non-flammable
and fairly environmentally benign upon release. Compressed CO
2
is already
widely used on an industrial scale in processes such as decaffeination of
coffee. Compressed CO
2
has been explored as a replacement for volatile
organic solvents in palladium-catalyzed coupling, although examples remain
limited.
Early work showed that palladium-catalyzed cross-coupling reactions,
including Heck, Suzuki and Stille couplings, could be performed in com-
pressed CO
2
.
170
The systems were generally modestly active and limited to
aryl iodide substrates. Fluorinated ligands often provided the best results
because of the superior solubility of fluorinated hydrocarbons in com-
pressed CO
2
compared with non-fluorinated ligands. The high pressures
required for these reactions (1000-3000 psi) has likely limited the study of
these systems. These types of pressures are not a challenge for industrial-
scale processes, however.
Nucleophilic reagents, such as amines, are a challenge for CO
2
-phase re-
actions, owing to the electrophilicity of carbon dioxide. Amines and carbon
dioxide exist in equilibrium with carbamic acids. Palladium-catalyzed
carbon-nitrogen bond formation was achieved in compressed CO
2
using
N-silylamines as the nitrogen source (Scheme 14.56).
171
The N-silylamines
undergo transmetallation with palladium faster than they react with CO
2
,
resulting in ecient N-arylation. Using Pd(OAc)
2
in combination with
XPhos (2 mol% catalyst), aryl bromides and chlorides could be coupled with
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