Buchwald—Hartwig arylations primary anilines

Aniline and N-methylaniUne derivatives are the most reliable substrates for the Hartwig-Buchwald coupling, and they experience a high level of functional group tolerance. Similar to the coupling of primary amines, the double arylation of aniline can be a competing side reaction. A slight excess of the amine relative to the aryl component usually diminishes this side reaction. 

In another example, the Buchwald-Hartwig A)-arylation conditions were applied to the cross-coupling reaction of 3,7-dibromo-10-hexyl-10f/-phenothiazine with a variety of primary and secondary anilines and amines, including carbazole, leading to 3,7-diaminophenothiazine derivatives in excellent yields (eq 17). ... 

Metal-catalyzed N-arylation of amines with haloarenes (Buchwald-Hartwig coupling) has been developed since the 1990s and provided more efficient access to carbazoles. Nozaki et al. reported the palladium-catalyzed double N-arylation of primary amines with 2,2 -dihalobiphenyls [8], A variety of dihalobiphenyls 10 and anilines 11 with electron-donating or electron-withdrawing substituent(s) are applicable to give multisubstituted carbazoles 12 in moderate to high yields (Scheme 23.4). 

In papers published back-to-back in 1996, Hartwig and Buchwald reported amination chemistry with palladium complexes of DPPF and BINAP as catalysts [50,86]. These palladium complexes provided animations of aryl bromides and iodides with primary alkyl amines, with cyclic secondary amines, and with anilines. It is ironic that the amination chemistry was first discovered by using a particularly labile phosphine, but was dramatically improved by the use of chelating ligands. 

The tremendous utility of catalytic C-0 and C-N bond formation processes, pioneered by Buchwald and Hartwig, is largely based on the efficiency of palladium-catalyzed systems. However, efficient nickel-catalyzed processes have also been reported for this important class of transformations. The catalytic coupling of aryl chlorides with primary or secondary amines is a particular niche where utility of the nickel-catalyzed process was found. A representative sampling of aniline derivatives prepared by the activity of Ni(cod)2/dppf as the pre-catalyst is depicted below (Figure 3-3). 

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