96 Indoles
Synthesis of indoles from ortho-aminoaryl alkynes (1,2-bond made)
With the advent of palladium-catalysed cross-coupling methodology, indoles can be synthesised starting from arenes in
which a halide is ortho to a nitrogen function – a nitro or amine group or a protected amine. The palladium-catalysed
step involves displacement of the halide with an alkyne with concurrent or later ring closure. When an ortho-nitroaryl
halide is employed for the cross-coupling, ring closure cannot take place until a subsequent reductive step takes the
nitro group down to an amine. Three examples of the several available variants of this theme are shown below.
Synthesis of indoles from ortho-alkylaryl isocyanides (2,3-bond made)
Cyclisation of benzylic anions derived from ortho-alkylaryl isocyanides, formed at low temperature and allowed to
come to room temperature, produces 2-unsubstituted indoles. The synthesis is shown in a simple form in the scheme,
however it is fl exible, for example the initial benzylic anion from ortho-isocyanotoluene can be alkylated with halides
or epoxides, before the ring closure thus providing 3-substituted indoles.
Synthesis of indoles from ortho-acyl anilides (2,3-bond made)
The fl exible Fürstner synthesis depends on the reductive cyclisation of ortho-acylanilides with low valent titanium – the
conditions used for the McMurray coupling of ketones to produce alkenes. Indoles carrying two bulky substituents on
the heterocyclic ring can be assembled in this way.