Nitrogen nucleophiles arylation

The addition-elimination mechanism has been used primarily for arylation of oxygen and nitrogen nucleophiles. There are not many successful examples of arylation of carbanions by this mechanism. A major limitation is the fact that aromatic nitro... 

In addition to bromides and iodides, the reaction has been successfully extended to chlorides,163 triflates,164 and nonafluorobutanesulfonates (nonaflates).165 These reaction conditions permit substitution in both electron-poor and electron-rich aryl systems by a variety of nitrogen nucleophiles, including alkyl or aryl amines and heterocycles. These reactions proceed via a catalytic cycle involving Pd(0) and Pd(II) intermediates. 

The conversion of an amide in this way is termed the Hofmann reaction or the Hofmann rearrangement. The mechanism of the reaction involves an intramolecular 1,2-carbon-to-nitrogen nucleophilic shift of the alkyl (or aryl) group... 

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. 

A formally related yet most likely Ullman type of arylation of nitrogen nucleophiles was reported most recently. A bimetallic catalytic system of Fe(acac)3—CuO was shown to be highly active in the simple arylation of a variety of N-heterocycles with aryl iodides and bromides in the presence of CsC03. Although a deeper mechanistic understanding awaits further investigations, the broad scope plus its operational simplicity make this procedure especially amenable to applications on an industrial scale (Scheme 7.6) [10]. 

In the penem series, 2-(heteroatom-substituted)-methyl derivatives have been similarly prepared via the 2-(hydro-xymethyl) key intermediate 71. Some examples of this C-2 functionalization are illustrated in Scheme 39 <1990H(30)799, 1995JME4244>. The reactions involved are O-acylation 72, O-arylation 73 by Mitsunobu coupling, and substitution by nitrogen nucleophiles 74 after OH activation by mesylation. 

Carbanions from hydrocarbons, nitriles, ketones, esters, TV./V-dialkyl acetamides and thioamides, and mono and dianions from (3-dicarbonyl compounds are some of the most common nucleophiles through which a new C-C bond can be formed. This C-C bond formation is also achieved by reaction with aromatic alkoxides. Among the nitrogen nucleophiles known to react are amide ions to form anilines however, the anions from aromatic amines, pyrroles, diazoles and triazoles, react with aromatic substrates to afford C-arylation. 

In addition to the most important 1,2-difunctionalization assisted or catalyzed by palladium(II) complexes, a catalytic 1,1-arylamination process of alkenes, applied to the construction of nitrogen heterocycles from 4-pentenylamides, was realized29,30. The mechanism involves the formation of arylpalladium chloride from alkyl(aryl)stannanes, the addition to the alkene, the isomerization of the adduct to the more stable benzylic palladium complex, and the displacement of palladium by an internal nitrogen nucleophile. In the presence of a substituent, mixtures of diastereomers were generally obtained. 

Nitriles can act as nitrogen nucleophiles in aziridine ring-opening reactions. Two examples are shown in Scheme 25 in which a formal [3-1-2] cycloadduct is the final product. Tosylaziridine 147 was reacted with benzoni-trile and BF3 OEt2 catalysis to produce the r-fused imidazoline 148 <2004TL1137>. The utility of the reaction is limited in the case of cyclic aziridines to benzofused aziridines and either aryl or benzyl nitriles. It was also found that the reaction required stoichiometric BF3. Lesser amounts of Lewis acid reduced the chemical yield drastically. 

Monosubstitution by a nitrogen nucleophile can also be achieved with acetonitrile as the reagent (Scheme 3.19). The mechanism is postulated to proceed through an oxonium intermediate, and the presence of the aryl group may control the regiochemistry [322]. 

The present work situated in this general context, deals with the arylations catalyzed by nickel or palladium complexes, of hard oxygen or nitrogen nucleophiles, using bromo- or chloroarenes (eqn. 1). If necessary, the comparison with the copper systems was also undertaken (ref. 6). 

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