Heterocyclic Chemistry at a Glance, Second Edition. John A. Joule and Keith Mills.
© 2013 John Wiley & Sons, Ltd. Published 2013 by John Wiley & Sons, Ltd.
Palladium(0)-catalysed (and related) reactions
The use of palladium catalysis for the construction of new C-C and C-heteroatom bonds to aromatic molecules is
one of the major advances in synthetic organic chemistry in the last 30 years or so. Such processes work equally well
with carbocyclic and heterocyclic systems, are very widely used and are amongst the most important transformations
of modern heterocyclic chemistry. We have gathered a range of examples of typical palladium-catalysed reactions of all
heterocyclic systems together in this chapter as they can be applied generally across the whole range, with the nature
of the heterocycle only being refl ected in secondary effects such as rates and selectivity and, occasionally, stability of
reactants. The chapters discussing particular heterocycles include further examples. Palladium-catalysed processes can
also be employed in the ring synthesis of some heterocyclic systems.
By far the most important reactions involve aromatic halides, where the catalytic species is always Pd(0). A particular
signifi cance of these reactions is that these normally unreactive aromatic-type halogens can be replaced under rela-
tively mild conditions. Another important feature is that they are generally not jeopardised by the presence of, and do
not interfere with, most other functional groups.
These reactions of halides are carried out in the presence of a catalytic amount (usually 1–5%) of a palladium complex,
with a second reactant. The second reactant is most commonly an organometallic nucleophile but other partners, such
as alkenes, carbon monoxide or a range of heteroatom nucleophiles, can also be utilised. Either the halo compound, or
the second reactant, or both, can be heterocyclic.
Typical examples of these transformations are shown in this chapter, illustrating the versatility of the methods; more
examples are given in the chapters devoted to individual heterocyclic systems. The mechanisms and further variations
are discussed in the later sections of this chapter. In a few typical examples, we give the full experimental details but
apart from these we simply indicate ‘Pd(0)’ so as to focus attention on the transformation being achieved.
Catalysts
A number of metals can be used as catalysts in these types of reaction, for example nickel, which is closely related to
palladium, but palladium is by far the most generally useful and understood. In what follows we discuss palladium-
catalysed reactions, apart from a small section on copper.