Facile Construction of N ‐Methylated Tertiary Amines via Catalyst‐Free Consecutive Reductive Amination/ N ‐Methylation of Carbonyl Compounds With Amines Using DMSO and HCO 2 H/NEt 3

ABSTRACT A catalyst‐free, one‐pot tandem reductive amination/ N ‐methylation of carbonyl compounds with primary amines for the synthesis of N ‐methylated tertiary amines has been developed. Employing a HCO 2 H/NEt 3 (5/2) mixture as the reductant and DMSO as both solvent and methylating agent, this method rapidly produces N ‐methylated tertiary amines from a diverse range of substrates in 76%–96% yields within just 2 h and accommodates a wide variety of functional groups. Furthermore, this protocol is both scalable and directly applicable to the synthesis of pharmaceutically and biologically important compounds. A plausible mechanism for this transformation is outlined based on insights from control experiments and mechanistic investigations.