Fischer indole synthesis

[3][4][5] The reaction of a (substituted) phenylhydrazine with a carbonyl (aldehyde or ketone) initially forms a phenylhydrazone which isomerizes to the respective enamine (or 'ene-hydrazine').

Isotopic labelling studies show that the aryl nitrogen (N1) of the starting phenylhydrazine is incorporated into the resulting indole.

[6][7] Via a palladium-catalyzed reaction, the Fischer indole synthesis can be effected by cross-coupling aryl bromides and hydrazones.

[8] This result supports the previously proposed intermediacy as hydrazone intermediates in the classical Fischer indole synthesis.

These N-arylhydrazones undergo exchange with other ketones, expanding the scope of this method.