Electrochemical reactor dictates site selectivity in N-heteroarene carboxylations

Guo-Quan Sun, Peng Yu, Wen Zhang, Wei Zhang, Yi Wang, Li-Li Liao, Zhen Zhang, Li Li, Zhipeng Lu, Da-Gang Yu () and Song Lin ()
Additional contact information
Guo-Quan Sun: Sichuan University
Peng Yu: Cornell University
Wen Zhang: Cornell University
Wei Zhang: Sichuan University
Yi Wang: Cornell University
Li-Li Liao: Sichuan University
Zhen Zhang: Sichuan University
Li Li: Sichuan University
Zhipeng Lu: Cornell University
Da-Gang Yu: Sichuan University
Song Lin: Cornell University

Nature, 2023, vol. 615, issue 7950, 67-72

Abstract: Abstract Pyridines and related N-heteroarenes are commonly found in pharmaceuticals, agrochemicals and other biologically active compounds1,2. Site-selective C–H functionalization would provide a direct way of making these medicinally active products3–5. For example, nicotinic acid derivatives could be made by C–H carboxylation, but this remains an elusive transformation6–8. Here we describe the development of an electrochemical strategy for the direct carboxylation of pyridines using CO2. The choice of the electrolysis setup gives rise to divergent site selectivity: a divided electrochemical cell leads to C5 carboxylation, whereas an undivided cell promotes C4 carboxylation. The undivided-cell reaction is proposed to operate through a paired-electrolysis mechanism9,10, in which both cathodic and anodic events play critical roles in altering the site selectivity. Specifically, anodically generated iodine preferentially reacts with a key radical anion intermediate in the C4-carboxylation pathway through hydrogen-atom transfer, thus diverting the reaction selectivity by means of the Curtin–Hammett principle11. The scope of the transformation was expanded to a wide range of N-heteroarenes, including bipyridines and terpyridines, pyrimidines, pyrazines and quinolines.

Date: 2023
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41586-022-05667-0 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

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:nature:v:615:y:2023:i:7950:d:10.1038_s41586-022-05667-0

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

DOI: 10.1038/s41586-022-05667-0

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

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