Highly Efficient and Mild Copper‐Catalyzed N‐ and C‐Arylations with Aryl Bromides and Iodides

Abstract

Mild, efficient, copper‐catalyzed N‐arylation procedures for nitrogen heterocycles, amides, carbamates, and C‐arylation procedures for malonic acid derivatives have been developed that afford high yields of arylated products with excellent selectivity. The N‐arylation of imidazole with aryl bromides or iodides was found to be greatly accelerated by inexpensive, air‐stable catalyst systems, combining catalytic copper salts or oxides with a set of structurally simple chelating ligands. The reaction was shown to be compatible with a broad range of aryl halides, encompassing sterically hindered, electron‐poor, and electron‐rich ones, providing the arylated products under particularly mild conditions (50–82 °C). The lower limit in ligand and catalyst loading and the scope of Ullmann‐type condensations catalyzed by complexes bearing those ligands with respect to the nucleophile class have also been investigated. Chelating Schiff base Chxn‐Py‐Al (1 c) generates a remarkably general copper catalyst for N‐arylation of pyrrole, indole, 1,2,4‐triazole, amides, and carbamates; and C‐arylation of diethyl malonate, ethyl cyanoacetate, and malononitrile with aryl iodides under mild conditions (50–82 °C). The new method reported here is the most successful to date with regard to Ullmann‐type arylation of some of these nucleophiles.