Selective N-alkylation of amines using nitriles under hydrogenation conditions: facile synthesis of secondary and tertiary aminesElectronic supplementary information (ESI) available: Experimental procedures and spectroscopic data for all new compounds. See DOI: 10.1039/c1ob06303k

Nitriles were found to be highly effective alkylating reagents for the selective N -alkylation of amines under catalytic hydrogenation conditions. For the aromatic primary amines, the corresponding secondary amines were selectively obtained under Pd/C-catalyzed hydrogenation conditions. Although the use of electron poor aromatic amines or bulky nitriles showed a lower reactivity toward the reductive alkylation, the addition of NH 4 OAc enhanced the reactivity to give secondary aromatic amines in good to excellent yields. Under the same reaction conditions, aromatic nitro compounds instead of the aromatic primary amines could be directly transformed into secondary amines via a domino reaction involving the one-pot hydrogenation of the nitro group and the reductive alkylation of the amines. While aliphatic amines were effectively converted to the corresponding tertiary amines under Pd/C-catalyzed conditions, Rh/C was a highly effective catalyst for the N -monoalkylation of aliphatic primary amines without over-alkylation to the tertiary amines. Furthermore, the combination of the Rh/C-catalyzed N -monoalkylation of the aliphatic primary amines and additional Pd/C-catalyzed alkylation of the resulting secondary aliphatic amines could selectively prepare aliphatic tertiary amines possessing three different alkyl groups. According to the mechanistic studies, it seems reasonable to conclude that nitriles were reduced to aldimines before the nucleophilic attack of the amine during the first step of the reaction. In the presence of nitriles, amines were selectively alkylated under Pd/C- or Rh/C-catalyzed hydrogenation conditions.