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.