Ullmann‐Ma Reaction: Development,Scope and Applications in Organic Synthesis†

Copper‐catalyzed cross‐couplings of aryl halides and nucleophiles, traditionally called Ullmann‐type coupling reactions, were initially reported by Ullmann et al. from 1901—1929. A seminal report in 1998 by Ma et al. from Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences revealed an accelerating effect caused by amino acids, which brought Ullmann‐type coupling reactions into a ligand‐accelerating era. From 1999 to the first 10 years of 2000s, the first‐generation ligands were developed by many researchers and promoted Ullmann‐type coupling reactions of aryl iodides and bromides under relatively mild conditions. Amino acid ligands, developed by Ma and coworkers, are one class of the most important first‐generation ligands. In the second 10 years of 2000s, Ma et al. led the discovery of second‐generation ligands for copper‐catalyzed cross‐coupling reactions. Two great breakthroughs have been realized by using second‐generation oxalic diamide and related amide ligands, with aryl chlorides as general coupling partner and with low catalyst loadings. Now copper‐catalyzed cross coupling reactions of aryl halides and nucleophiles with amino acids or oxalic diamides and related amides as ligands are recognized as Ullmann‐Ma reactions and have found extensive applications in organic synthesis.