Diindolylamine Preparation and Stability Investigations

The synthesis of
diindolylamines via the palladium-catalyzed cross-coupling
of aminoindoles and bromoindoles has been investigated, and efficient
coupling conditions using BrettPhos, Pd­(OAc)2, K2CO3, and tBuOH have been identified. The diindolylamines
were found to be unstable in ambient conditions. Blocking the reactive
3-position of the bromoindole coupling partner with a tert-butyl group results in a diindolylamine with improved air stability.
NMR, CV, and UV–vis studies on an asymmetrically substituted
3-tert-butyl-3′H-diindolylamine indicate that
the instability of the diindolylamine substrates is likely due to
oxidative oligomerization. Literature conditions used for the preparation
of 3-tert-butylindoles afforded only the indole tetramer.
The presence of water during the alkylation reaction was identified
as the cause of the formation of the tetramer. Replacing hygroscopic tBuOH with nonhygroscopic tBuCl as the
alkylating reagent provided access to 7-bromo-3-tert-butyl indole.