COPPER-CATALYZED AMINATION OF ARYL AND ALKENYL ELECTROPHILES

摘要

Metal-catalyzed animation of aryl and alkenyl electrophiles has developed into a highly useful synthetic strategy for preparing N-aryl- and N-alkenyl- containing structures. Ullmann first reported Cu-mediated N-arylation reactions of amines in 1903 (Scheme 1) followed closely by Goldberg's report of amide N-arylations (Scheme 2). In these reactions, an aryl halide is condensed with an amine or amide in the presence of base and copper powder or a copper salt at high temperature. The need for stoichiometric amounts of copper and high reaction temperatures combined with the modest yields of product in most cases limits the application of these methods. Despite these limitations, Ullmann and Goldberg condensation reactions represented the state-of-the-art in metal-mediated C-N bond formation for nearly a century. The development of efficient Pd-catalyzed C-N bond-forming reactions that could be carried out under mild conditions with less reactive substrates, such as aryl chlorides, resulted in palladium displac ng copper as the preferred metal for aryl amination reactions in the late 1990s.