N-alkylation and N-arylation of anilines starting from a mild NMg reagent: Its activation causing the ‘NC’ coupling to extend the unified structure-reactivity relationship

New N-alkylation and N-arylation procedures starting from anilinomagnesium (ArNHMgBr) are reported. For N-alkylation with alkyl bromides, addition of hexamethylphosphoramide to an ArNHMgBr solution in tetrahydrofuran (THF) is effective. After heating at 55°C, N-monoalkylation product was obtained in 60–90% yield, slight dialkylation taking place. The combined use of aryliminodimagnesium [ArN(MgBr)2] with α,ω-dibromoalkanes led to N-arylazacycloalkanes. For N-arylation with iodobenzene, replacement of THF with pyridine and additional use of copper(I) iodide are effective. After heating at 115°C with iodobenzene, mono- and diarylation products were obtained, the former being predominant. The combined use of ArNHMgBr and N,N,N′,N′-tetramethylethylenediamine as the ligand of copper species is effective for elimination of diarylation and other undesired products, and leads to diarylamines in excellent yield. The method is of advantage over the conventional Ullmann and Chapman methods. The polar solvents and copper salt are effective additives for inducing ‘inert combinations’ of ArNHMgBr or ArN(MgBr)2 with alkyl and aryl halides into NC coupling, to extend the unified view proposed for the reactivity of magnesium reagents. The difference in the roles of NMg and NCu species is discussed.

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