{"id":27106,"date":"2025-07-16T16:07:24","date_gmt":"2025-07-16T10:22:24","guid":{"rendered":"https:\/\/www.revoscience.com\/en\/?p=27106"},"modified":"2025-07-16T16:07:27","modified_gmt":"2025-07-16T10:22:27","slug":"researcher-discovers-electrochemical-method-for-highly-selective-single-carbon-insertion-in-aromatic-rings","status":"publish","type":"post","link":"https:\/\/www.revoscience.com\/en\/researcher-discovers-electrochemical-method-for-highly-selective-single-carbon-insertion-in-aromatic-rings\/","title":{"rendered":"Researcher discovers electrochemical method for highly selective single-carbon insertion in aromatic rings"},"content":{"rendered":"\n
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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 approach has important applications in synthetic organic chemistry, especially in the field of pharmaceuticals.<\/p>\n\n\n\n

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

\u201cWe set out to address the longstanding challenge of achieving single-carbon insertion into aromatic rings with precise positional control,\u201d said Mahito Atobe, Professor, Faculty of Engineering, YOKOHAMA National University. <\/p>\n\n\n\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.<\/p>\n\n\n\n

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.\u00a0<\/p>\n\n\n\n

\u201cOur 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,\u201d said Atobe. <\/p>\n\n\n\n

This study presents a novel concept for single-carbon insertion chemistry and expands a researcher\u2019s chemical toolbox for synthesizing polysubstituted (hetero)aromatic compounds. Polysubstituted pyrroles are\u00a0organic compounds that have a pyrrole ring and multiple substituents joined to it.\u00a0<\/p>\n\n\n\n

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\n\n\n

\u201cWe discovered an electrochemical method that enables highly selective para-position single-carbon insertion into polysubstituted pyrroles\u2014an unprecedented transformation,\u201d said Naoki Shida, Associate Professor, Faculty of Engineering, YOKOHAMA National University. <\/p>\n\n\n\n

This reaction is enabled with distonic radical cation intermediates and is governed by the electronic properties of nitrogen-protecting groups. \u201cOur findings establish a new strategy for site-selective molecular editing of aromatic rings, expanding the toolkit for synthetic organic chemistry,\u201d said Shida.<\/p>\n\n\n\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. <\/p>\n\n\n\n

They controlled the insertion position through electronic perturbation by the\u00a0N<\/em>-protecting group (PG), and achieved unprecedented\u00a0para<\/em>-selective insertion by introducing an electron-withdrawing protecting group to the pyrrole derivatives. <\/p>\n\n\n\n

The team used\u00a0in-situ\u00a0<\/em>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.\u00a0<\/p>\n\n\n\n

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\u2019s disease, stomach ulcers, or the control of chemotherapy-induced nausea. <\/p>\n\n\n\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. <\/p>\n\n\n\n

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\u2019s novel electrochemical method introduces a new concept for single-carbon insertion chemistry.<\/p>\n\n\n\n

Looking ahead, the team\u2019s 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\n\n\n

\u201cWe also aim to integrate this methodology into flow electrolysis systems to improve scalability and efficiency. Ultimately, our goal is to establish a general platform for precise molecular editing of aromatic frameworks using electricity as a clean and controllable driving force,\u201d said Atobe.<\/p>\n\n\n\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 University of Bath, United Kingdom; Kazuhiro Okamoto from 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\n\n\n

<\/p>\n","protected":false},"excerpt":{"rendered":"

A research team has discovered an electrochemical method that allows highly selective para-position single-carbon insertion into polysubstituted pyrroles. <\/p>\n","protected":false},"author":2,"featured_media":27107,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[122],"tags":[],"class_list":["post-27106","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-chemistry"],"featured_image_urls":{"full":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida.webp",1100,1212,false],"thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida-200x200.webp",200,200,true],"medium":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida-613x675.webp",613,675,true],"medium_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida-768x846.webp",750,826,true],"large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida-998x1100.webp",750,827,true],"1536x1536":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida.webp",1100,1212,false],"2048x2048":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida.webp",1100,1212,false],"ultp_layout_landscape_large":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida-1100x800.webp",1100,800,true],"ultp_layout_landscape":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida-870x570.webp",870,570,true],"ultp_layout_portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida-600x900.webp",600,900,true],"ultp_layout_square":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida-600x600.webp",600,600,true],"newspaper-x-single-post":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida-760x490.webp",760,490,true],"newspaper-x-recent-post-big":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida-550x360.webp",550,360,true],"newspaper-x-recent-post-list-image":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida-95x65.webp",95,65,true],"web-stories-poster-portrait":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida-640x853.webp",640,853,true],"web-stories-publisher-logo":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida-96x96.webp",96,96,true],"web-stories-thumbnail":["https:\/\/www.revoscience.com\/en\/wp-content\/uploads\/2025\/07\/cover_shida-150x165.webp",150,165,true]},"author_info":{"info":["RevoScience"]},"category_info":"Chemistry<\/a>","tag_info":"Chemistry","comment_count":"0","_links":{"self":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/27106","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/comments?post=27106"}],"version-history":[{"count":1,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/27106\/revisions"}],"predecessor-version":[{"id":27108,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/posts\/27106\/revisions\/27108"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media\/27107"}],"wp:attachment":[{"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/media?parent=27106"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/categories?post=27106"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.revoscience.com\/en\/wp-json\/wp\/v2\/tags?post=27106"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}