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Exploring Electrochemical C(sp3)−H Oxidation for the Late-Stage Methylation of Complex Molecules

THE “MAGIC METHYL” EFFECT IN DRUG DISCOVERY

This case study was reported in Exploring Electrochemical C(sp3)–H Oxidation for the Late-Stage Methylation of Complex Molecules | Journal of the American Chemical Society (acs.org) (M. Neurock, J. A. Terrett, S. Lin et al., J. Am. Chem. Soc. 2022, 144, 1187).

The “magic methyl” effect, a dramatic boost in the potency of biologically active compounds from the incorporation of a single methyl group, provides a simple yet powerful strategy employed by medicinal chemists in the drug discovery process. Despite significant advances, methodologies that enable the selective C(sp3)−H methylation of structurally complex medicinal agents remain very limited.

INNOVATIVE STRATEGY FOR A-METHYLATION

In this work, the authors disclose a modular, efficient, and selective strategy for the α-methylation of protected amines (i.e., amides, carbamates, and sulfonamides) by means of electrochemical oxidation.