Greener Approaches to Cross-Coupling - New Trends in Cross-Coupling: Theory and Applications - page 648

14.2.1 Hydrophilic Metal-Ligand Complexes for Aqueous-
Phase Cross-Coupling
In order to use water to separate homogeneous catalysts from organic
product streams in an aqueous-biphasic solvent system, it is necessary to
design a water-soluble catalyst. In many cases, this is accomplished by using
a hydrophilic supporting ligand for the metal catalyst. 11 A large variety of
hydrophilic ligands have been applied to palladium-catalyzed cross-coupling
reactions. The majority of examples involve modification of known privil-
eged ligand structures by incorporation of a water-solubilizing group. Key
examples and their catalytic applications are highlighted here.
14.2.1.1 Pd-Catalyzed Cross-Coupling with Hydrophilic
Phosphines
The first example of palladium-catalyzed cross-coupling using a water-
soluble ligand was reported by Casalnuovo and Calabrese. 12 They showed
that Pd(TPPMS) 3 [TPPMS ¼ sodium diphenyl(3-sulfonatophenyl)phosphine]
provided an effective catalyst for Suzuki, Heck and Sonogashira coupling of
hydrophilic and hydrophobic aryl iodides and bromides in a water-
acetonitrile solvent system. Building on this seminal report, palladium-
catalyzed cross-coupling using triphenylphosphine derivatives modified
with sulfonate, 13 carboxylate, 14 guanidinium 15 and carbohydrate 16 water-
solubilizing groups have been reported (Scheme 14.2). These ligands provide
effective catalysts for Suzuki, Heck and Sonogashira couplings of aryl iodides
and in some cases aryl bromides at elevated temperatures. Deactivated aryl
bromides and chlorides are largely unreactive with these catalyst systems.
Typically high catalyst loadings and high reaction temperatures are neces-
sary, which make these systems impractical for large-scale application.
Increased ligand steric demand can improve catalyst performance in
cross-coupling reactions. Sulfonation of tri(2,4-dimethylphenyl)phosphine
provides trisodium tri(2,4-dimethyl-5-sulfonatophenyl)phosphine (TXPTS,
Scheme 14.3) as a more hindered analog of TPPTS. 17 The TXPTS ligand
provides more active catalysts than TPPTS for Suzuki, Heck and Sonogashira
couplings. 18 Hydrophilic bidentate ligands have attracted limited attention
in palladium-catalyzed cross-coupling. A sulfonated BINAS/Pd catalyst sys-
tem was the first to catalyze the coupling of an aryl halide with amines in an
aqueous solvent system (Scheme 14.4). 19
Polyionic dendritic triphenylphosphine derivatives have been shown to
provide high-activity palladium catalysts for cross-coupling reactions.
Carboxylate-terminated dendritic phosphine 4 was shown to provide higher
yields in Suzuki coupling of 4-iodotoluene with higher generation number
with water as the only solvent (Scheme 14.5). 20 The hydrophobic dendrimer
core may serve like a micelle, increasing interaction between the hydro-
phobic substrate and the catalyst. Hexacationic quaternary ammonium-
substituted triphenylphosphine 5 provided a highly active catalyst for Suzuki