LAUSR

Abstract Five- and six-membered aromatic rings bearing a methyl group are important molecular fragments in drug discovery. From the medicinal chemistry standpoint, the methyl group might play a pivotal role in improving the biological activities and druggability due to its capability in modulating the molecular conformation as well as the physical and chemical properties (such as lipophilicity and metabolism, etc.). How to effectively install a methyl group in a designated position of an aromatic ring is a long-stand quest and a research hot spot for both medicinal chemists and synthetic organic chemists. In the past few years, significant progresses have been achieved in this field wherein the C–H bond activation and direct methylation become achievable in one step under catalytic conditions. A variety of metal catalysts reported by several research groups are capable of such transformation. The relatively mild reaction conditions and high functional group compatibility make such transformation very attractive for final step synthesis. This paper summarizes such transformation based on their reaction mechanisms, and systematically discusses the reaction conditions and their application of a variety of substrates. It provides both medicinal and synthetic organic chemists the convenience for accessing the most up-to-date methodology, and would foster the potential applications in drug discovery and organic synthesis projects.