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

Abstract

AbstractA 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 %.