Recent Progress in Methylation of (Hetero)Arenes by Cross-Coupling or C-H Activation

Owing to the 'magic methyl effect' on a compound's physical and biological properties, methylation is a strategy frequently used by medicinal chemists in structure-activity relationship studies or in lead optimization. This article highlights the most recent reported methods for the direct methylation of (hetero) arenes, which mainly involve either C-H functionalization or cross-coupling of methylating reagents with (hetero) aryl halides. Methylation of C-H bonds of (hetero)arenes, which is atom economical, has been explored by several research groups in recent years. Given the unmatchable availability of (hetero) aryl halides, we believe that Ni-catalyzed methylation using iodomethane or deuterated iodomethane as the methyl source is one of the most convenient methods.