Carbon−Carbon Coupling Reactions Catalyzed by Heterogeneous ...

Heterogeneous Pd Catalyzed C−C Coupling Reactions Chemical Reviews, 2007, Vol. 107, No. 1 169
Scheme 61. Pd(NH3)4 2+ /(NH3)Y-Catalyzed Synthesis of
2-Phenylbenzo[b]furans
Table 85. Pd/C-Catalyzed Synthesis of 3-Substituted
Isocoumarins a
a All reactions were carried out using iodide (1.0 equiv), alkyne (2.0
equiv), Et3N (5.0 equiv), and a 1/4/2 ratio of 10% Pd/C (3 mol %),
PPh3, and CuI, in EtOH for 16 h. b Isolated yields.
In this way, 1,2-diphenylethanes 236 and 237 were obtained
from styrene and bromobenzene or o-bromonitrobenzene,
respectively (Scheme 62). 271
Scheme 62. One-Pot Synthesis of 1,2-Diphenylethanes 236
and 237
Pd/C-catalyzed Heck coupling was further combined with
subsequent Suzuki coupling in order to synthesize 4-styrylbiphenyl
240, a substructure of pharmaceutically active
compounds. 271 Because Heck coupling is more selective for
different leaving groups than Suzuki coupling, the Heck
coupling was applied as the first reaction step and Suzuki
coupling as the second (Scheme 63).
Scheme 63. Pd/C-Catalyzed One-Pot Synthesis of
4-Styrylbiphenyl 240
10. Conclusions and Perspectives
Nowadays, Pd-catalyzed homogeneous coupling reactions
belong in the toolbox of each synthetic organic chemist and
have been used in many fields of organic synthesis leading
to products of various interests. However, industrial applications
of these reactions are still challenging because the
catalysts are expensive, cannot be recycled, and are difficult
to remove from the product. The latter fact is a drawback in
particular for pharmaceutical industries.
Although Pd fixed on inorganic and organic supports have
been known for a long time and applied to C-C coupling
reactions in single cases more than 30 years ago, their
versatility has only recently been shown in almost all types
of C-C couplings during the last decades. This methodology
has not been appreciated by many organic chemists so far.
In most cases, their first choice is homogeneous Pd catalysts.
The heterogeneous methodology offers a number of
advantages such as high stability of the catalyst, easy removal
of the catalyst from the reaction mixture by filtration,
reusability of the catalyst for several times with often
minimal loss of activity, and, remarkably, a better performance
than homogeneous Pd catalysts in a considerable
number of cases. On the other hand, catalysis by Pd on solid
supports can require higher reaction temperatures and have
limitations in stereoselective reactions. Pd catalysts supported
by inorganic and organic materials can also offer the
possibility of circumventing ligands such as phosphines or
arsines in certain cases and often do not need water- and
oxygen-free conditions.
The majority of catalysts applied so far are Pd/C catalysts,
which are commercially available in most cases and can
directly be used. Other supported Pd catalysts have to be
prepared by the user. They can provide advantages over Pd/
C, and they can allow tuning of the properties of the catalyst.
Many activities can be expected in this field in future.
The mechanism of most of the coupling reactions catalyzed
by solid-supported Pd is still unclear. Future research in this
field will help the understanding of the sometimes contradictory
results in this field. It has been increasingly accepted
that most heterogeneous Pd catalysts catalyze in a homogeneous
way by leached Pd species, which can re-deposit when
the reaction comes to an end. However, general conclusions
are difficult to attain because in most cases the mechanism
of a certain reaction is affected by the conditions very much.
Although there are also other modern trends in Pd
catalysis, such as polymer-supported Pd, Pd nanoparticles,
or Pd clusters, it can be expected that the application of Pd
supported by inorganic materials will gain increasing importance
and application in future.