Greener Approaches to Cross-Coupling - New Trends in Cross-Coupling: Theory and Applications - page 665

E-factor of 11.9 kg waste kg 1 product was achieved by Lipshutz et al. 6a using
micellar catalysis conditions.
14.2.3 Heterogeneous Recyclable Catalysts
Heterogeneous catalysts are preferred for industrial-scale processes owing to
their ease of separation from the product stream and the potential to carry
out reactions in flow. The hydrophilic catalysts described above represent
one approach to making a homogeneous catalyst heterogeneous as part of a
liquid-liquid biphasic solvent system. Aqueous-phase reactions using solid
heterogeneous catalyst systems have also received significant attention. 114
These catalyst systems can be broken down into two classes: nanoparticle
palladium catalysts and molecular palladium species attached to insoluble
support materials.
14.2.3.1 Nanoparticle Catalysts in Aqueous-Phase
Cross-Coupling
Although much effort has been devoted to the design of optimal ligands to
provide high-activity cross-coupling catalysts, the ligand adds to the cost of
the system and increases the amount of waste material produced. Catalysts
that do not rely on dative ligands, such as phosphines or NHCs, are cheaper
and often more robust systems. Ligand-free catalyst systems can offer high
productivity, although most such systems are less reactive than ligand-
supported catalysts towards less reactive aryl electrophiles, such as aryl
chlorides. Leadbeater and Marco demonstrated that Pd(OAc) 2 without other
promoters is an effective catalyst for the Suzuki coupling of aryl bromides on
water with low catalyst loading (0.4 mol%) at 150 1C with microwave heat-
ing. 115 Catalyst loadings as low as ppm levels gave high yields under these
conditions. 116 By using acetone as a water-miscible organic co-solvent, the
reaction temperature required could be lowered to 35 1C. 117
Unsupported palladium nanoparticles can be highly effective catalysts,
but often lose activity as the nanoparticles agglomerate to larger particles
that precipitate from solution. As a result, unsupported nanoparticles often
cannot be used for multiple reaction cycles. To increase the stability of the
nanoparticles, they can be supported on polymeric or inorganic supports
that serve to stabilize the nanoparticles and isolate them to avoid
agglomeration.
A common approach to preparing supported nanoparticles is to use a
polymer with coordinating sites where the palladium ions can coordinate
and that can support the palladium nanoparticles. El-Sayed and co-workers
reported an early example of palladium nanoparticles supported on poly(4-
vinylpyridine) (PVP). 118 The Pd-PVP system effectively catalyzed the Suzuki
coupling of aryl iodides in 40% aqueous ethanol. A highly effective catalyst
system is obtained from palladium nanoparticles supported on polyaniline