Metal-catalyzed methylthiolation of chloroarenes and diverse aryl electrophiles

In this study, we report the first development of metal catalyzed methylthiolation of chloroarenes and diverse aromatic electrophiles, addressing the persistent challenges of catalyst and intermediate deactivation in the functionalization of less reactive substrates. To overcome these issues, we designed a novel anion-shuttle-type methylthiolation agent, 4-((methylthio)methyl)morpholine, which enables the controlled <i>in situ</i> release of methylthiolate anions, thereby preventing catalyst poisoning and enhancing reactivity. This strategy allows efficient methylthiolation not only of chloroarenes but also of a broad range of aryl electrophiles, including bromoarenes, aryl triflates, aryl tosylates, aryl pivalates, aryl nitriles, and aryl carboxylic acids. The developed system exhibits excellent functional group compatibility, making it applicable to the derivatization of pharmaceuticals and natural products. Furthermore, detailed mechanistic investigations revealed key factors underlying the exceptional efficiency of this methylthiolation agent, providing new insights into C-S bond formation under practical conditions.