Phosphonium-Salt-Catalyzed <i>N</i>-Methylation and <i>N</i>-Formylation of Amines with CO<sub>2</sub>
Changyue Ren, Anke Spannenberg, Thomas Werner
Abstract
The use of CO 2 as a C 1 building block is of great relevance and is a focus of current research. Herein we report the synthesis of air-stable internal phosphonium salts and their application as catalysts in the N -methylation and N -formylation of amines utilizing CO 2 . A series of catalysts were prepared and tested for these valuable transformations. Under the optimized reaction condition, the N -formylation of amines was achieved at 23 °C, 1 bar CO 2 pressure under solvent-free conditions using equimolar amounts of n -hexylsilane as reducing agent. A modification of the reaction conditions led to a selectivity switch, and the N -methylation was realized at 70 °C in acetonitrile using the same catalyst and reductant. In total, 22 amines were converted to the corresponding N -methylated products in up to 99% yield. Moreover, 25 examples of the conversion to the corresponding N- formylated products in up to 96% yield are reported. Both reactions can be performed at large scale. Both the N -methylation and N -formylation reactions were also applied to the late-stage functionalization of the pharmaceutical sertraline. NMR studies and control experiments revealed two different reaction pathways and intermediates for N -methylation and N -formylation.