Cu-mediated Ullmann-type cross-coupling has experienced significant advances over the last century since the seminal publication by Ullmann in 1901. These advances have significantly expanded the scope of the original classical Ullmann coupling of aryl halides for formation of diaryl compounds to include the formation of carbon−heteroatom and other carbon− carbon bonds. The introduction of bidentate ligands drastically improved the performance of this class of transformations to enable milder reaction conditions that can tolerate a wide range of sensitive functional groups. Recent development of more powerful second-generation bidentate ligands has further allowed the coupling of less reactive aryl chlorides to proceed smoothly and realized low catalyst and ligand loadings for a broad scope of Ullmann-type cross-coupling reactions. As a result of these breakthrough advances in the past decades, Cu-mediated Ullmann-type cross-coupling reactions have been frequently implemented in academic research and have found ubiquitous industrial applications including the preparation of pharmaceutical and agrochemical products. This review provides an overview of selected general Cu-mediated Ullmann-type transformations for the formation of carbon− carbon and carbon−heteroatom (C−N, C−O, C−S, and C−P) bonds and their applications in route design, process development, and scale-up of pharmaceutical and agrochemical processes.

The reinforced molecular recognition of two rigid tetrakisimidazolium macrocycles resulted in highly selective fluorescent recognition of sulfate dianion in water with an unprecedentedly high association constant of 8.6 × 10(9) M(-2). Besides the electrostatic interaction, the single crystal X-ray analysis revealed that sulfate was encapsulated in a pseudohexahedral cavity of a sandwich structure by two orthogonally packed macrocycles via eight hydrogen bonds between the C2 hydrogen atoms of the imidazolium units and the oxygen atoms of sulfate. This sandwich structure was reinforced by the π-π stacking between the phenyl and the triazinonide rings and multiple charge-assisted hydrogen bonds between the peripheral chains and the rigid backbones. Notably, these peripheral-backbone hydrogen bonds rendered the flexible peripheral chains to coil around the sandwich structure to shield sulfate inaccessible to water. This binding process was visible by fluorescence enhancement, which was attributed to a restrained rotation and better conjugation of the macrocycle backbone upon binding to sulfate.

An unprecedented Rh-catalyzed ketone-directed vinylic C-H activation/[4+2] O-annulation of α-aryl enones with internal alkynes followed by a Cu-catalyzed ring contraction in air to provide multiaryl-substituted furan derivatives has been developed. The preliminary mechanism study identifies the active pyrylium salt as the key intermediate.

Cross-coupling: the "chelation-directed control" and "catalytic-system-based control" strategies effectively switch the C2/C3-site selectivity in the heteroarylation of indoles and pyrroles with N-heteroarenes by a palladium-catalyzed twofold C-H activation to form biheteroarenes and are further extended to the synthesis of complex fused tri- and tetracyclic heteroarenes by a tandem fourfold C-H activation.

Herein the Cu-catalyzed direct C-H mono-, di- and triarylations of imidazolium salts with aryl iodides/bromides are accomplished for the first time. The unprecedented alkenylation and alkynylation are also realized using alkenyl and alkynyl iodides, respectively. Moreover, triarylated imidazolium salts with different substituents can be accessed in a modular and one-pot manner. This protocol provides an efficient tool for the assembly of diverse imidazolium-based ionic functional materials. As applicable examples, an electrochromic bisbenzimidazolium salt 7 and a photochromic triarylimidazolium salt 8 are easily obtained.