Catalytic undirected methylation of unactivated C(sp³)-H bonds suitable for complex molecules.

ABSTRACT: In pharmaceutical discovery, the "magic methyl" effect describes a substantial improvement in the pharmacological properties of a drug candidate with the incorporation of methyl groups. Therefore, to expedite the synthesis of methylated drug analogs, late-stage, undirected methylations of C(sp³)-H bonds in complex molecules would be valuable. However, current methods for site-selective methylations are limited to activated C(sp³)-H bonds. Here we describe a site-selective, undirected methylation of unactivated C(sp³)-H bonds, enabled by photochemically activated peroxides and a nickel(II) complex whose turnover is enhanced by an ancillary ligand. The methodology displays compatibility with a wide range of functional groups and a high selectivity for tertiar

SUBMITTER: Tan JF 

PROVIDER: S-EPMC11437150 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature