Amides copper-catalyzed coupling with aryl

Scheme 1 Selected supporting ligands (L1-L14) for the copper-catalyzed coupling of aryl halides with nitrogen heterocycles and cyclic amides (substrates used a-t)...

Copper-Catalyzed Coupling of Amides with Aryl Halides... 

The use of ligated copper catalysts has dramatically improved the coupling of aryl halides with amides—the Goldberg reaction. . This reaction has been studied intensively because of the utility of the products and the limitations in scope and efficiency of the palladium-catalyzed coupling of aryl halides with amides. Moreover, it is the process that occurs with the broadest scope when conducted with certain ancillary ligands. 

This chapter covers the C(aryl)-N bond formation via copper-catalyzed coupling of nitrogen nucleophiles (N-heterocycles, amines, anilines, amides, ammonia, azides, hydroxylamines, nitrite salts, phosphonic amides) with aryl hahdes. The C(aryl)-N bond formation as a result of the coupling between these nucleophiles and arylboronic acids (the Chan-Lam reaction) will be presented, too. 

In this domino process, benzylamine was reacted with 2-halobenzamides through UUman-type coupling to yield the N-arylated intermediate 144 (Scheme 9.26). Then, a copper-catalyzed aerobic oxidation of 144 afforded the intermediate 145, which underwent an intramolecular nucleophilic addition of the amide to provide 146. Under the used reaction conditions, the intermediate 146 was oxidized to provide the desired products 147 in excellent yield. This protocol was also utilized by Fu et al. [80] by employing easily available a-amino adds instead of benzylamines to synthesize similar analogs. Very recently, the same method was applied for the synthesis of pyrimido[4,5-b]carbazoles by Nagarajan et al. [81]. 

More detailed mechanistic studies have been conducted with isolated ligated copper complexes, along with kinetic studies on reactions catalyzed by complexes of diamine ligands. These studies have shown that copper(I) amidate and imidate complexes are competent to be intermediates in the catalytic coupling of aryl halide with amides and imi-des. These studies also implied that two-coordinate anionic cuprate complexes undergo oxidative addition of the aryl halide more slowly than do related three-coordinate, neutral copper complexes containing a bidentate dative ligand. This conclusion is shown clearly by the formation of coupled product from iodotoluene and the species that equilibrates between the ionic and three-coordinate neutral species (Equation 19.119) and the lack of... 

It should also be noted that copper-catalyzed Ullmann-type coupling of aryl halides with amines yields substituted products [206], and reaction with diphenylamine has been used to form triaryl-amines [207], Triarylamines may also be formed in a variation of the Meyers reaction [47] by displacement by lithium amides of fluoro- or methoxy-substituents activated by an ort/io-ester function [208], The oxidation of a-adducts is discussed in Chapter 11, but it should also be mentioned that aminated products may also be produced by the oxidation of adducts formed by the addition of amide or alkylamide ions at ring carbon atoms carrying hydrogen [209]. 

Scheme 11 Copper(I) oxide/(Ll or L2) or copper iodide/L25-catalyzed coupling of amides with aryl halides...

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