Efficient palladium-catalyzed electrocarboxylation enables late-stage carbon isotope labelling

Efficient palladium-catalyzed electrocarboxylation enables late-stage carbon isotope labelling | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Efficient palladium-catalyzed electrocarboxylation enables late-stage carbon isotope labelling Troels Skrydstrup, Gabriel Batista, Ruth Ebenbauer, Jonas Bergare, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3633932/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Mar, 2024 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Carbon isotope labelling of bioactive molecules is a critical step for accessing the pharmacokinetic and pharmacodynamic properties of new drug entities. Aryl carboxylic acids represent an important class of structural motifs commonly found in many pharmaceutically active molecules and are ideal target structures for the installation of a radioactive tag employing isotopically labelled CO 2 . However, direct isotope incorporation via the reported catalytic reductive carboxylation (CRC) of aryl electrophiles relies on excess CO 2 , which is incompatible with carbon-14 isotope incorporation. Furthermore, the application of some CRC reactions for late-stage carboxylation is limited because of the low tolerance of molecular complexity by the catalytic systems. Herein, we report the development of a practical and affordable electrochemical CRC setup based on palladium catalysis. This approach enables the use of near-stoichiometric 14 CO 2 generated from the primary carbon-14 source Ba 14 CO 3 , facilitating late-stage and single-step carbon-14 labelling of pharmaceuticals and representative precursors. Further studies provide more details in the mechanistic understanding of this process, allowing CRC to be performed in solvents alternative to DMF. The proposed isotope-labelling protocol holds significant promise for immediate impact on drug development programmes. Physical sciences/Chemistry/Catalysis/Electrocatalysis Physical sciences/Chemistry/Catalysis Physical sciences/Chemistry/Organic chemistry/Synthetic chemistry methodology Palladium Electrochemistry Carboxylation Isotopic labelling DFT calculations Full Text Additional Declarations Yes there is potential Competing Interest. Troels Skrydstrup is co-owner of SyTracks A/S, which commercialises COware®. Supplementary Files SISkrydstrup.pdf SI (Skrydstrup) coordinates.txt coordinates.xyz Cite Share Download PDF Status: Published Journal Publication published 22 Mar, 2024 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3633932","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":260022549,"identity":"73f45f9d-bc65-4747-8277-d68461403373","order_by":0,"name":"Troels 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