Bioinspired transfer methylation enabled by a photoactive reagent

Ding Zhang, Weiqiu Liang, Zhihan Zhang (), Lida Tan, Zehao Yuan, Zhennan Hu, Zhibo Liu (), Chao-Jun Li () and Jianbin Li ()
Additional contact information
Ding Zhang: The Chinese University of Hong Kong
Weiqiu Liang: Peking University
Zhihan Zhang: Central China Normal University
Lida Tan: McGill University
Zehao Yuan: The Chinese University of Hong Kong
Zhennan Hu: The Chinese University of Hong Kong
Zhibo Liu: Peking University
Chao-Jun Li: McGill University
Jianbin Li: The Chinese University of Hong Kong

Nature Communications, 2025, vol. 16, issue 1, 1-11

Abstract: Abstract Radical methylation ranks among the most important yet challenging transformations in chemistry and biology, which often involves small and unstable radical intermediates, such as the methyl radical, and results in low reactivity and poor selectivity. Herein, we report a photoactive, biomimetic reagent to address some facets of these challenges by leveraging a bulky and stabilised α-aminomethyl radical, which can offer enhanced control over radical generation and transfer. Our bioinspired transfer methylation protocol enables direct and selective C(sp2)–H methylation across a wide spectrum of heteroarenes, from simple scaffolds to complex drug molecules, including the thus far elusive C4-methylation of free quinolines. Mechanistic studies reveal that the unique α-aminomethyl radical intermediate undergoes an addition-elimination sequence reminiscent of natural methyltransferases and yields balanced reactivity and selectivity.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-61857-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61857-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-61857-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().