Manganese-Catalyzed Methylation of C(sp³)–H Bonds α to Heteroatoms

Key words

C–H functionalization - methylation - late-stage diversification - manganese catalysis - C–C bond formation

Significance

White and co-workers report a chemoselective C(sp³)–H methylation of heterocycles by using a three-step protocol. The method was applied to a broad substrate scope, including drug molecules, peptides, and natural products. The ability to introduce a ‘magic methyl’ group in certain pharmacologically relevant compounds has been shown to significantly improve their bioactivity.

Comment

The authors combined a manganese-catalyzed methylene hydroxylation with subsequent iminium/oxonium formation and methylation to achieve the functionalization of various ­heterocyclic cores α to the heteroatom. The ­transformation proceeds at low catalyst loading with remarkable chemoselectivity and moderate to good overall yields.