26 Palladium in Heterocyclic Chemistry
Acetylene couplings (Sonogashira reaction)
The Sonogashira reaction, which involves in situ formation of a copper acetylide as the reactive organometallic, is a very
convenient and simple method to link an alkyne to an aromatic ring, but an equivalent standard organometallic cross-
coupling (without copper), using a preformed acetylide, can also be useful on occasion. Iodide is the most common
leaving group in Sonogashira reactions.
Couplings using anions from C-H-acidic compounds
Enolates and related anions, particularly doubly stabilised, generally work well and can introduce multiple functional
groups.
Addition to alkenes: the Heck reaction
The Heck reaction was the fi rst palladium-catalysed reaction to be developed and widely used, and is still very useful
for the introduction of alkenyl groups onto a heterocycle in replacement of a leaving group (normally halogen). It uses
conditions similar to those used for cross-coupling reactions but has the advantage of not requiring an organometallic
reagent. Acrylates have been the most used alkenes; they give rise to (E)-ArCH=CHCO 2 R products. A Heck reaction
using an enol ether as the alkene results, after hydrolysis, in the overall introduction of an acyl group. For a different
type of Heck reaction, see under electrophilic palladation (pages 29–30).
Carbonylation reactions
Reaction of a halide and palladium(0) with carbon monoxide and a nucleophile – water, amine or alcohol – gives an
acid, carboxamide or ester, respectively, (the mechanism is given on page 29).