Catalytic <i>N</i>‑Alkylation of\n(Hetero)Aromatic Amines and Tandem Annulation Reactions

A general\nand practical approach for <i>N</i>-alkylation\nof heteroaromatic amines with heteroaromatic alcohols is always challenging\nand rarely reported. Here, we designed and synthesized phosphine-free,\nrobust, and efficient N,N-bidentate-Co(II) complexes for a universal <i>N</i>-alkylation of amines strategy. This present catalytic\nmethodology can be applied to a wide range of substrates by varying\nalcohols, including aryl, aliphatic, acyclic, and cyclic groups, with\nheteroaromatic amines such as aminopyridine, 2-aminopyrimidine, and\naminoquinoline to provide diverse monoalkylated organonitrogen compounds\nin good to excellent yields (108 examples). In addition, the utility\nof the developed catalytic protocol was also extended successfully\nfor the dehydrogenative synthesis of biologically important quinoline\nderivatives (11 examples). Particularly, 8-aminoquinoline reacted\ndifferently with tandem <i>N</i>-alkylated-transfer hydrogenative\nbyproduct (<i>N</i>-benzyl-1,2,3,4-tetrahydroquinolin-8-amine)\nwas obtained, revealing the catalytic activity of the complex <b>I</b>. The reaction proceeded under environmentally benign conditions,\nwhich liberates water as the sole byproduct. Notably, a concise synthesis\nof acetylcholinesterase inhibitors (AChEIs) scaffolds as potential\ncognition enhancers illustrated the utility of the present protocol.\nInterestingly, various control and deuterium-labeled experiments were\nperformed, suggesting that the reaction proceeds via the borrowing\nhydrogen pathway.