Diindolylamine Preparation and Stability Investigations.

Abstract

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.