NHC–amine Ru complex catalyzed selective mono-N-methylation of amines with methanol: understanding the effect of amine ligands

Abstract

The selective mono-N-methylation of amines with methanol remains challenging, particularly for aliphatic amines. Inspired by metal–ligand cooperation, a series of N-heterocyclic carbene (NHC)–amine Ru complexes (Ru1–Ru4) with different amine ligands were developed for this transformation. Among them, complex Ru4 bearing an NHC–aniline ligand with a 7-membered chelate ring displayed the highest activity for the selective mono-N-methylation of amines with methanol. Various substrates, including aromatics, sulfonamides, and aliphatic amines, can be transformed into the desired mono-N-methylation products in excellent yields. Moreover, a series of sensitive groups such as nitro, carbonyl, hydroxyl, trifluoromethyl, and internal vinyl groups were well tolerated. Experimental and theoretical studies revealed that the catalytic mechanism involved an inner-sphere mechanism promoted by an Ru complex with NH₂ as the labile ligand.