Aryl Halides with Amines

The reaction of amines with aryl halides requires a catalyst in most cases to initiate the reaction. There are several approaches that result in N-aryl amines. Treatment of cyclohexylamine with p-MeC6H4B(OH)2 and Cu(OAc)2 gave the N-aryl amide in 63% yield. Aryl halides react with amines in the presence of palladium... 

Recently, Taillefer et al. reported an Fe/Cu cooperative catalysis in the assembly of N-aryl heterocycles by C—N bond formation [90]. Similarly, Wakharkar and coworkers described the N-arylation of various amines with aryl halides in the presence of Cu—Fe hydrotalcite [91]. Interestingly, Correa and Bolm developed a novel and promising ligand-assisted iron-catalyzed N-arylation of nitrogen nucleophiles without any Cu co-catalysts (Scheme 6.19) [92]. Differently substituted aryl iodides and bromides react with various amides and N-heterocycles. The new catalyst system consists of a mixture of inexpensive FeCl3 and N,N -dimethylethylenediamine (dmeda). Clearly, this research established a useful starting point for numerous future applications of iron-catalyzed arylation reactions. 

FIGURE 3. Ligands used for the reaction of acyclic secondary amines with aryl halides... 

FIGURE 4. Ligands created for the reaction of acyclic secondary amines with aryl halides following the success of Kumada s ligand in catalyzing that reaction, as shown in equation 5... 

Syntheses of derivatives of indole, carbazole, and other TV-heterocycles using Pd-catalyzed C-N coupling of amines with aryl halides 04MI44. 

The Buchwald-Hartwig reaction has been widely used in organic chemistry for the palladium-catalyzed cross-coupling of amines with aryl halides. In particular, it has been used in conjunction with benzothiophenes for arylamination of the thiophene. The final diarylamine product below demonstrated anti-fungal activity against dermatophytes, yeasts, and the Aspergillus species. ... 

Preparation of aromatic amines by the reaction of aryl halides with aliphatic and aromatic amines has been regarded as a difficult reaction. Recently a facile synthetic method for aromatic amines by amination of aryl halides has been discovered, and rapid progress has occurred in the Pd-catalyzed reaction of amines with aryl halides [1]. One simple example which shows the usefulness of the new method is cited here. The commercially important arylpiperazines 1 have been synthesized by intramoleular N-alkylation of aniline derivatives with N,N-di-(2-chloroethyl)amine (2), which is highly carcinogenic. Now the amines 3 can be prepared efficiently by coupling aryl iodides, bromides or chlorides with N-substituted piperidines. This example provides a big contribution to synthetic chemistry by the new Pd-catalyzed efficient preparative method for arylamines, which are usefial in medicinal and material chemistry. 

Kantam, M. L., Roy, M., Roya, S., Sreedhara, B. and De, R. L. 2008. Polyaniline supported Cul An efficient catalyst for C-N bond formation by N-arylation of iV(//)-heterocycles and benzyl amines with aryl halides and arylboronic acids, and aza-Michael reactions of amines with activated aUcenes. Catal. Commun. 9(13) 2226-2230. 

One of the most versatile and widely employed methods for the construction of aryl C—N bonds is the palladium-catalyzed cross coupling of amines with aryl halides and related electrophiles [4]. These reactions are believed to occur as shown in Scheme 1.1, with the coupling initiated by oxidative addition of the aryl halide to a Pd° complex. The resulting intermediate 1 is converted to a palladium(aryl)(amido) complex 2 through reaction with the amine substrate in the presence of base. Finally,... 

Scheme 13.24 DPPF-supported coupling of primary amines with aryl halides [39],...

Scheme 13.50 Coupling of acyclic aliphatic amines with aryl halides at room temperature [46].

In 2008, Organ et al. reported on the Buchwald-Hartwig coupling of secondary amines with aryl halides catalyzed by (IPr)-Pd-PEPPSI complex 1 [22], providing access to hindered and functionalized aryl amines in good yields. 

Reaction of Alkyl Amines Copper-catalyzed cross-coupling of aliphatic amines with aryl halides has made considerable progress. Several methods have used Ctil with p-amino alcohols L58 [42], amino acids L59, L60 [43], Al,Al-diethyl saUcylaldehyde L61 [44], or p-diketones L62-L65 [45] (Fig. 20.3). Among these, the protocol using p-diketones exhibited the superior results catalyzing the reaction even at room temperature (Scheme 20.19). 

SCHEME 20.24 Cu-catalyzed C—N cross-coupling of secondary alkyl amines with aryl halides. 

In the homogeneous eatalysis domain, veiy recently Jia et al. examined the homogeneous eatalytie ability of one of their newly synthesised complexes [ (DMOX)CdCl 2(/t-Cl)2] (8) (DMOX = 4,5-dihydro-2-(4,5-dihydro-4,4-dime-thyloxazol-2-yl)-4,4-dimethyl-oxazole), for direct C-N crosscoupling of amine with aryl halide. The results point out that Cd(ii) complex 8 shows significant catal5dic activity in C-N crosscoupling of amines with aryl halide (Scheme 17.4). 

The solution to the problem of catalysts for a general reaction of acyclic secondary amines with aryl halides began with the use of Kumada s phosphinoether ligand 1 (Eq. With palladium catalysts bearing Kumada s ligand, high yields were observed for this type of amination reaction. However, the ligand is extremely expensive in its commercially available optically pure form, and the synthesis is multistep. Nevertheless,... 

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