{"id":679988,"date":"2025-07-15T05:15:20","date_gmt":"2025-07-15T02:15:20","guid":{"rendered":"https:\/\/buradabiliyorum.com\/en\/team-discovers-electrochemical-method-for-highly-selective-single-carbon-insertion-in-aromatic-rings\/"},"modified":"2025-07-15T05:15:20","modified_gmt":"2025-07-15T02:15:20","slug":"team-discovers-electrochemical-method-for-highly-selective-single-carbon-insertion-in-aromatic-rings","status":"publish","type":"post","link":"https:\/\/buradabiliyorum.com\/en\/team-discovers-electrochemical-method-for-highly-selective-single-carbon-insertion-in-aromatic-rings\/","title":{"rendered":"Team discovers electrochemical method for highly selective single-carbon insertion in aromatic rings"},"content":{"rendered":"
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\n This illustration visualizes a novel electrochemical transformation in which a single carbon atom\u2014derived from a diazo compound\u2014is selectively inserted into the pyrrole ring via a distonic radical cation intermedia<\/a>te. The origami-like transformation of molecular building blocks symbolizes the precise and programmable synthesis of substituted pyridines. The reaction proceeds under electrochemical conditions without the need for external reagents, showcasing a new strategy for constructing complex aromatic molecules. Credit: Yokohama National University
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A research team has discovered an electrochemical method that allows highly selective para-position single-carbon insertion into polysubstituted pyrroles. Their app<\/a>roach has important applications in synthetic organic chemistry, especially in the field of pharmaceuticals.<\/p>\n

Their work is published in the Journal of the American Chemical Society<\/i> on July 14.<\/p>\n

“We set out to address the longstanding challenge of achieving single-carbon insertion into aromatic rings with precise positional control,” said Mahito Atobe, Professor, Faculty of Engineering, Yokohama National University.<\/p>\n

Transformations that modify aromatic rings are central to pharmaceutical and materials synthesis. However, inserting a single carbon atom into a specific position\u2014especially the para-position\u2014has remained extremely rare. Para position describes the location of substituents, those atoms that replace a hydrogen atom on a molecule. In the single carbon insertion approach, researchers add a single carbon atom into a molecule’s carbon framework. This lengthens a carbon chain or expands a ring by one carbon unit.<\/p>\n

“Our goal was to develop a new, electrochemically driven method that enables this transformation selectively and efficiently, while gaining mechanistic insights into how the electronic structure of the substrate controls the insertion position,” said Atobe.<\/p>\n

This study presents a novel concept for single-carbon insertion chemistry and expands a researcher’s chemical toolbox for synthesizing polysubstituted (hetero)aromatic compounds. Polysubstituted pyrroles are organic compounds that have a pyrrole ring and multiple substituents are joined to it. These compounds play a crucial role in diverse fields, such as natural products, pharmaceuticals, and functional materials. They hold particular interest for pharmaceuticals, where they are fundamental to many approved drugs.<\/p>\n

“We discovered an electrochemical method that enables highly selective para-position single-carbon insertion into polysubstituted pyrroles\u2014an unprecedented transformation,” said Naoki Shida, Associate Professor, Faculty of Engineering, Yokohama National University.<\/p>\n

This reaction is enabled by distonic radical cation intermediates and is governed by the electronic properties of nitrogen-protecting groups.<\/p>\n

“Our findings establish a new strategy for site-selective molecular editing of aromatic rings, expanding the toolkit for synthetic organic chemistry,” said Shida.<\/p>\n

The team demonstrated the electrochemical ring expansion reaction using \u03b1-H diazo esters as a carbynyl anion equivalent. This approach allowed efficient single-carbon insertion into a range of polysubstituted pyrroles, affording structurally diverse pyridine derivatives. They controlled the insertion position through electronic perturbation by the N-protecting group (PG), and achieved unprecedented para-selective insertion by introducing an electron-withdrawing protecting group to the pyrrole derivatives.<\/p>\n

The team used in-situ spectroscopy and theoretical calculations to support the reaction mechanism involving a distonic radical cation intermediate. The spectroscopy and calculations suggest distonic radical cation intermediates are involved, facilitating carbon-atom migration on the aromatic ring and enabling insertion at different positions.<\/p>\n

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Approved drugs like netupitant, esomeprazole, pyridoxine, and opicapone contain benzene and pyridine rings with more than three substituents. These drugs are important medications for wide-ranging health challenges, such as Parkinson’s disease, stomach ulcers, or the control of chemotherapy-induced nausea.<\/p>\n

To synthesize these compounds, researchers have used multiple methods, such as coupling reactions, carbon-hydrogen functionalization, and cyclization reactions. Single-carbon insertion is yet another approach scientists have used to modify polysubstituted (hetero)aromatic compounds. The single-carbon insertion approach significantly alters the structure of the parent skeletons. But up to this point in time, controlling the insertion position had been a significant challenge for researchers. The team’s novel electrochemical method introduces a new concept for single-carbon insertion chemistry.<\/p>\n

Looking ahead, the team’s next step is to expand the scope of this reaction to a broader range of heteroaromatic compounds and complex molecules, including pharmaceutical intermediates.<\/p>\n

“We also aim to integrate this methodology into flow electrolysis systems to improve scalability and efficiency. Ultimately, our goal is to establish a general<\/a> platform for precise molecular editing of aromatic frameworks using electricity as a clean and controllable driving force,” said Atobe.<\/p>\n

The research team includes Tatsuya Morimoto, Su-Gi Chong, and Azusa Kikuchi from Yokohama National University, Japan; Yoshio Nishimoto from Kyoto University, Japan; Taku Suzuki-Osborne from the University of Bath, United Kingdom; Kazuhiro Okamoto from the University of Toyama, Japan; Tomoki Yoneda from International University of Health and Welfare, Japan; and Daisuke Yokogawa from The University of Tokyo, Japan.<\/p>\n

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More information:<\/strong>
\n\t\t\t\t\t\t\t\t\t\t\t\tElectrochemical Single-Carbon Insertion via Distonic Radical Cation Intermediates, Journal of the American Chemical Society<\/i> (2025). DOI: 10.1021\/jacs.5c06798<\/a><\/p>\n<\/p><\/div>\n

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\n\t\t\t\t\t\t\t\t\t\t\t\t\tProvided by
\n\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\t\tYokohama National University
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\n\t\t\t\t\t\t\t\t\t\t\t\tCitation<\/strong>:
\n\t\t\t\t\t\t\t\t\t\t\t\tTeam discovers electrochemical method for highly selective single-carbon insertion in aromatic rings (2025, July 14)
\n\t\t\t\t\t\t\t\t\t\t\t\tretrieved 14 July 2025
\n\t\t\t\t\t\t\t\t\t\t\t\tfrom https:\/\/phys.org\/news<\/a>\/2025-07-team-electrochemical-method-highly-carbon.html\n\t\t\t\t\t\t\t\t\t\t\t <\/p>\n

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