Decarboxylative Coupling Reaction of 2-(1H-Indol-3-yl)acetic Acids with Indole, Azaindole, Benzimidazole and Indazole Derivatives

Abstract

3,3′-Diindolylmethanes (DIMs) are an important class of indole alkaloids that exhibit anti-inflammatory and anti-cancer effects. Herein, we report on a new, mild and efficient copper(II)-promoted decarboxylative coupling reaction of 2-(1H-indol-3-yl)acetic acid derivatives (1 a–h) with a variety of (substituted) indoles (2 a–t) yielding (un)symmetrically substituted DIMs (3 a–z, 3 aa–ai). Reaction of 2-(1H-indol-3-yl)acetic acid (1 a) with 7-azaindole led to the 3,3′-connected DIM analog 5 d, while 4-, 5-, and 6-azaindoles and benzimidazole reacted at the N1-nitrogen atom. Reaction of 1 a with 1H-indazoles led to a mixture of 1- and 2-substituted indazole derivatives. The new method allows large-scale synthesis of biologically active DIMs. (Figure presented.).