C鈥揌 Methylation of Heteroarenes Inspired by Radical SAM Methyl Transferase
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- 作者：Jinghan Gui ; Qianghui Zhou ; Chung-Mao Pan ; Yuki Yabe ; Aaron C. Burns ; Michael R. Collins ; Martha A. Ornelas ; Yoshihiro Ishihara ; Phil S. Baran
- 刊名：Journal of the American Chemical Society
- 出版年：2014
- 出版时间：April 2, 2014
- 年：2014
- 卷：136
- 期：13
- 页码：4853-4856
- 全文大小：459K
- 年卷期：v.136,no.13(April 2, 2014)
- ISSN：1520-5126
文摘
A practical C鈥揌 functionalization method for the methylation of heteroarenes is presented. Inspiration from Nature鈥檚 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.