Fig. 1: The “magic methyl” effect in medicinal chemistry and undirected methylations of C(sp3)−H bonds.
From: Catalytic undirected methylation of unactivated C(sp3)−H bonds suitable for complex molecules
a Selected examples of drug molecules with an increase in biological activity after installation of methyl groups in the highlighted positions. The methyl groups are highlighted in cyan. b The undirected methylation of activated C(sp3)−H bonds is reported, but the site-selective methylation of unactivated C(sp3)−H bonds is not known. The sites of C−H functionalization is highlighted in green; the installed methyl group is shown in blue. c The drawbacks of Li’s methylation include functionalizations that are unselective and a substrate scope that is limited to alkanes. d The site-selective undirected methylation of unactivated tertiary C(sp3)−H bonds presented in this work is suitable for the late-stage methylation of structurally complex organic molecules. e Proposed mechanism of Ni-catalyzed formation of C(sp3)−methyl bond mediated by photosensitization and ligand-promoted increase in the turnover of the nickel catalyst.
