Effect of the ancillary ligand in N-heterocyclic carbene iridium(III) catalyzed N-alkylation of amines with alcohols

A series of air-stable N-heterocyclic carbene (NHC) Ir(III) complexes (Ir1-6), bearing various combinations of chlorine, pyridine and NHC ligands, were assayed for the N-alkylation of amines with alcohols. It was found that Ir3, with two monodentate 1,3-bis-methyl-imidazolylidene (IMe) ligands, emerged as the most active complex. A large variety of amines and primary alcohols were efficiently converted into mono-N-alkylated amines in 53-96% yields. As a special highlight, for the challenging MeOH, selective N-monomethylation could be achieved using KOH as a base under an air atmosphere. Moreover, this catalytic system was successfully applied to the gram-scale synthesis of some valuable compounds. (C) 2021 Elsevier Ltd. All rights reserved.

Automated summary

The study found that an iridium (III) complex with special ligands exhibited the highest activity in the N-alkylation reaction of amines with alcohols, efficiently converting a large variety of amines and primary alcohols into mono-N-alkylated amines. Selective N-monomethylation of MeOH could be achieved using KOH as a base under an air atmosphere. This catalytic system was also successfully applied to the gram-scale synthesis of some valuable compounds.