22 Palladium in Heterocyclic Chemistry
Palladium in its zero oxidation state – Pd(0) – is always the active catalytic species in reactions of halides, but the
metal can be added to the reaction mixture in various ways. It can be added in the zero oxidation state, for example
as tetrakis(triphenylphosphine)palladium(0) [Pd(PPh 3 ) 4 ] or as a mixture of a Pd(0) complex, such as Pd 2 (dba) 3 , with
a phosphine. Alternatively, a Pd(II) compound can be used, either as a mixture of a salt such as palladium acetate
[Pd(OAc) 2 ] with a phosphine or other ligand, or as a pre-formed phosphine complex such as bis(tri-o-tolylphosphine)
palladium dichloride [PdCl 2 (P(o-Tol) 3 ) 2 ]. (Ligands are generally necessary to stabilise Pd(0), but they also may deactivate
it to some degree.) The use of a Pd(II) compound is a common cause of confusion – the true catalyst is still Pd(0), which
is formed in situ in an initiation step: in cross-couplings for example, via conversion into a diarylpalladium by reaction
with RM, followed by reductive elimination.
A number of other agents can bring about reduction of Pd(II) to Pd(0), such as the triethylamine used in Heck reactions,
or triphenylphosphine.
Although there are large numbers of catalyst–ligand combinations in the literature, most reactions are carried out using
one of a small range of well-established standard catalysts. However, there is an important group of newer catalysts that
are particularly useful for less reactive substrates such as chloro-aromatics, and also can improve some other standard
transformations. These newer catalyst combinations generally use highly hindered, electron-rich, phosphines or hetero-
cyclic carbenes as ligands. It may seem curious that highly hindered ligands can increase the reactivity of Pd(0), but the
reason is that they cannot fully ‘saturate’ the metal, as occurs for example with Pd(PPh 3 ) 4 , because there is not enough
space around the metal to accommodate four of these larger ligands. This ‘unsaturated’ Pd(0) is then more reactive than
that in Pd(PPh 3 ) 4 , which is a stable, convenient, easily handled solid, but its reactivity depends on small amounts of
Pd(PPh 3 ) 3 or Pd(PPh 3 ) 2 that form in solution. Electron-rich ligands also increase the reactivity of Pd(0) by increasing
electron density on the metal.
The choice of a catalyst–ligand system for a particular transformation often comes down to experience of related
reactions and/or to trial and error. The particular combination of catalyst, solvent and base can be critical in
some cases.