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

作者：Cai, Xiuju; Zhou, Xiaoyu; Huang, Ming^*

来源：Organic Chemistry Frontiers, 2023, 11(1): 113-119.

DOI：10.1039/d3qo01097j

• HETEROCYCLIC CARBENE
• HYDROGENATION
• ALKYLATION
• ANILINES
• PEPTIDES
• ALCOHOLS
• STRATEGY
• BEARING
• IR

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.

• 单位
  广东药学院; 中山大学