Synfacts 2020; 16(06): 0663
DOI: 10.1055/s-0040-1707804
Metals in Synthesis
© Georg Thieme Verlag Stuttgart · New York

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

Mark Lautens
Joachim Loup
Feng K, Quevedo RE, Kohrt JT, Oderinde MS, Reilly U, White MC. * University of Illinois, Urbana, USA
Late-Stage Oxidative C(sp3)–H Methylation.

Nature 2020;
580: 621-627
Further Information

Publication History

Publication Date:
15 May 2020 (online)



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.