Aryl-nitrogen bond formation

The seminal work by the groups of Hartwig and Buchwald in 1994 on aryl amina-tion chemistry has spurred substantial research on C-N bond formation in general and aryl-nitrogen bond formation in particular [114]. Catalytic aryl amine couplings are usually slow processes, especially when copper catalysis is used, often... 

Reports on the synthesis of five-membered heterocycles by intramolecular nitrogen—nitrogen bond formation (N1—N5) came some years ago from our laboratory [79CC891 81 JCS(Pl) 1891 83JCS(P1)2273]. Thus, 4-alkyl(aryl)amino-l-azabutadienes 2, which are readily available in large scale from alkyl(aryl)imines 1 and aliphatic or aromatic nitriles (70S 142 ... 

The use of hypervalent iodine reagents for heteroatom-heteroatom bond forming reactions is well established in the context of classical oxidation chemistry [1-11]. For example, oxidations of anilines to azobenzenes, thiols to disulfides, and sulfides to sulfoxides with aryl-A3-iodanes were documented decades ago [1-5]. During the last ten years, particular attention has also been given to oxidative transformations of compounds derived from heavier elements, including the interception of reaction intermediates or initially formed products with external nucleophiles. A second important development is the utilization of sulfonyliminoiodanes, ArI = NS02R, for heteroatom-nitrogen bond formation, especially for imidations of sulfur, selenium, phosphorus and arsenic com-... 

Gujadhur, R., Venkataraman, D. and Kintigh, J. T. (2001) Formation of aryl-nitrogen bonds using a soluble copper(I) catalyst. Tetrahedron Lett., 42, 4791 -793. 

In addition to simply mediating the formation of carbon-nitrogen bonds, palladium catalysis can be used to construct these precursors in concert with cyclization. One example of this was demonstrated by Barluenga, where palladium catalysis is employed to form two separate bonds first the carbon-carbon bond via the arylation of the azaallylic anion of imine 19, followed by catalytic carbon-nitrogen bond formation (Scheme 6.38) [50]. 

This chapter covers more specifically the copper-catalyzed C(aryl)-N bond formation via the coupling of aryl halides with nitrogen nucleophiles such as N-heterocycles, amines, anilines, amides, ammonia, azides, hydroxylamines, nitrite salts or phosphonic amides. The C(aryl)-N bond formation as a result of the coupling between these nucleophiles and arylboronic acids (the Chan-Lam reaction) will be also presented. It is worth noting that this chapter mainly focuses on the most significant results and important breakthroughs in this field. 

The carbon-oxygen bond formation follows the same pathway. For both nitrogen-carbon and oxygen-carbon bond formation, a competing reaction is 13-hydride elimination (if a hydride is present at the heteroatom fragment), which lowers the yield and the reduced arene is obtained after reductive elimination. Reductive elimination of the C-N or C-0 fragments should be faster than 13-hydride elimination in order to avoid reduction of the aryl moiety. The side-reaction is shown at the bottom of Figure 13.25. 

Amines are generally prepared by nucleophilic amination, which is a coupling of carbon electrophiles with a nucleophilic amination reagent, NR2, and Ni and Pd catalyzed reaction of aryl halides with arylamines (Hartwig-Buchwald amination) . Thus, the direct C—N bond formation between carbon nucleophiles and electrophilic nitrogen functionality R2N+ constitutes an example of the umpolung methodology. 

The condensation of primary amines with aldehydes and ketones gives products known as imines which contain a C=N double bond. These compounds rapidly decompose or polymerize unless there is at least an aryl group bonded to the nitrogen or to the carbon atom. The latter imines are called Schiff bases, since their synthesis was first reported by Schiff.1 The most common method of obtaining a Schiff base (4) is straightforward, as indicated in the condensation reaction (1) between (1) and (2) with the formation of an intermediate hemiaminal (3). 

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. 

Lithiation of aryltriazenes followed by treatment with an electrophile provides a new approach to benzylamines. The regioselectivity of the reaction can be controlled by means of the substituents on the aryl group. The reaction consists of an intramolecular carbon-carbon bond formation with the aryl ring of a lithiated alkyl group on a 3-nitrogen atom, a 1,2-proton shift, demonstrated by deuterium substitution, and the subsequent release of nitrogen gas.15... 

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