Manganese‐Catalyzed Mono‐N‐Methylation of Aliphatic Primary Amines without the Requirement of External High‐Hydrogen Pressure

Abstract

The synthesis of mono‐N‐methylated aliphatic primary amines has traditionally been challenging, requiring noble metal catalysts and high‐pressure H2 for achieveing satisfactory yields and selectivity. Herein, we developed an approach for the selective coupling of methanol and aliphatic primary amines, without high‐pressure hydrogen, using a manganese‐based catalyst. Remarkably, up to 98% yields with broad substrate scope were achieved at low catalyst loadings. Notably, due to the weak base‐catalyzed alcoholysis of formamide intermediates, our novel protocol not only obviates the addition of high‐pressure H2 but also prevents side secondary N‐methylation, supported by control experiments and density functional theory calculations.

Ruthenium Complexes with NNN-Pincer Ligands for N-Methylation of Amines Using Methanol

“… The transition metal-catalyzed N-methylation of amines using MeOH via a BH route offers an efficient method . Various transition metals such as Ir, Ru, , Mn, Fe, and others , have been employed for this purpose (Scheme a). For example, Beller’s group reported a pyridine-based PNP-Mn complex for the N-methylation of anilines with methanol and a wide range of functional groups, including sensitive CC and CO bonds, was tolerated (Scheme b) .…”