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‐(1 H ‐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‐(1 H ‐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 N 1‐nitrogen atom. Reaction of 1 a with 1 H ‐indazoles led to a mixture of 1‐ and 2‐substituted indazole derivatives. The new method allows large‐scale synthesis of biologically active DIMs. magnified image