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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.

SUBMITTER: Gui J

PROVIDER: S-EPMC3988686 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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C-H methylation of heteroarenes inspired by radical SAM methyl transferase.

Gui Jinghan J Zhou Qianghui Q Pan Chung-Mao CM Yabe Yuki Y Burns Aaron C AC Collins Michael R MR Ornelas Martha A MA Ishihara Yoshihiro Y Baran Phil S PS

Journal of the American Chemical Society 20140321 13

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 de ...[more]

PMID: 24611732

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