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 , K 2 CO 3 , 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 t BuOH with nonhygroscopic t BuCl as the alkylating reagent provided access to 7-bromo-3- tert -butyl indole.