title: C-H methylation of heteroarenes inspired by radical SAM methyl transferase.
abstract: A practical C-H functionalization method for the methylation of heteroarenes is presented. Inspiration from Nature's methylating agent, S-adenosylmethionine (SAM), allowed for the design and development of zinc bis(phenylsulfonylmethanesulfinate), or PSMS. The action of PSMS on a heteroarene generates a (phenylsulfonyl)methylated intermediate that can be easily separated from unreacted starting material. This intermediate can then be desulfonylated to the methylated product or elaborated to a deuteriomethylated product, and can divergently access medicinally important motifs. This mild, operationally simple protocol that can be conducted in open air at room temperature is compatible with sensitive functional groups for the late-stage functionalization of pharmacologically relevant substrates.
authors.affiliation: Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Jinghan
authors.initials: J
authors.lastname: Gui
authors.forename: Qianghui
authors.initials: Q
authors.lastname: Zhou
authors.forename: Chung-Mao
authors.initials: CM
authors.lastname: Pan
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yabe
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Burns
authors.forename: Michael R
authors.initials: MR
authors.lastname: Collins
authors.forename: Martha A
authors.initials: MA
authors.lastname: Ornelas
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ishihara
authors.forename: Phil S
authors.initials: PS
authors.lastname: Baran
mesh_terms: D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D008745:Methylation; D009942:Organometallic Compounds / Q000737:chemistry*; D012436:S-Adenosylmethionine / Q000737:chemistry* / Q000378:metabolism; D013441:Sulfinic Acids / Q000737:chemistry*; D014166:Transferases / Q000378:metabolism; D015032:Zinc / Q000737:chemistry*
chemical_list: D006841:Hydrocarbons, Aromatic; D009942:Organometallic Compounds; D013441:Sulfinic Acids; D012436:S-Adenosylmethionine; D014166:Transferases; D015032:Zinc