30 Palladium in Heterocyclic Chemistry
the conditions for electrophilic palladation are not compatible with the other coupling partners, such as boronic acids,
which would react with PdX 2 much faster than would ArH. An exception is the Heck reaction, which can succeed in the
presence of selective oxidants that reconvert Pd(0) into Pd(II) in situ.
A more generally useful method (Direct Arylation), however, uses the Ar^1 - Pd-X, produced by oxidative addition to
Ar^1 X, as the electrophilic reagent to palladate a second component, Ar^2 H.
This can be carried out in a catalytic way under similar conditions to the other major Pd(0) reactions. Again, this is
generally restricted to electron-rich fi ve-membered rings, although pyridine N-oxides do react, very selectively at C-2.
A major advantage is that preparation of an organometallic is not required, although a disadvantage in some cases is
lack of specifi city for particular positions. The mechanism is very similar to cross-coupling, but the transmetallation
step is replaced by the electrophilic metallation step.
Copper-catalysed amination
Copper catalysis, under similar conditions to the palladium reactions, has been found to be particularly useful for amina-
tion of (hetero) aromatic halides, and the complementary method of N-arylation of heterocyclic N-H.
Another very useful N-arylation uses a boronic acid, rather than a halide, as the aryl partner (Chan–Lam reaction). In
this reaction a stoichiometric amount of copper is used – this is not an issue, as copper is vastly cheaper than palladium!