Efficient Synthesis of 2-Arylpropionitriles Via Selective Monomethylation of Aryl Acetonitriles Using an Easy to Handle Methylation Agent

Abstract

A convenient and safe methylation protocol employing quaternary ammonium salts (PhMe₃NI) as alternative methylating agents for the selective α-methylation of arylacetonitriles is presented. This approach allows for the selective α-methylation of arylacetonitriles, overcoming the limitations of existing techniques, while offering a practical and sustainable solution for late-stage functionalization in medicinal chemistry. The straightforward and safe nature of this methodology makes it particularly well-suited for applications in drug discovery. In our report, we present a diverse set of 18 examples, achieving yields of up to 76 %.