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Manganese-Catalyzed Methylation of C(sp3)–H Bonds α to Heteroatoms
Late-Stage Oxidative C(sp3)–H Methylation.
15 May 2020 (online)
Key wordsC–H functionalization - methylation - late-stage diversification - manganese catalysis - C–C bond formation
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.
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.