Tandem synthesis of N-methylated tertiary amines via three-component coupling of carbonyl compounds, amines, and methanol

An Ir-catalyzed tandem synthesis of various N-methylated tertiary amines from three-component coupling of carbonyl compounds, amines, and methanol following reductive amination/N-methylation is reported for the first time. A wide array of substrates with tolerance of different functional groups was demonstrated. The protocol was extended to the synthesis of N-methyl containing pharmaceutically important drug molecules. A probable catalytic cycle was proposed based on various control experiments and different analytical techniques such as NMR, IR and ESI-MS.

Automated summary

This paper reports for the first time an Ir-catalyzed tandem synthesis of various N-methylated tertiary amines through a three-component coupling of carbonyl compounds, amines, and methanol followed by reductive amination/N-methylation. The method demonstrates a wide range of substrate tolerance towards different functional groups and can be applied to the synthesis of pharmaceutically important drug molecules containing N-methyl groups.