Ligand-Controlled Regiodivergent and Enantioselective C-H Cyanation of Secondary Amines

Ligand-Controlled Regiodivergent and Enantioselective C-H Cyanation of Secondary Amines | 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 Ligand-Controlled Regiodivergent and Enantioselective C-H Cyanation of Secondary Amines Dan-Qian Xu, Yang-Jie Mao, Huan-Le Li, Qi Pan, Kun Zhou, Zhen-Yuan Xu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6472539/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Jan, 2026 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Aliphatic amines, such as N,N-dialkyl secondary amines, are important chemical entities in biologically active compounds. The regio- and stereoselective C-H functionalisation of acyclic secondary amines are therefore of great interest and importance. Among the possible approaches, the radical-mediated C-H functionalisation of amines via hydrogen atom transfer (HAT) has emerged as powerful strategy to access elaborated amines. However, despite recent advances, the controllable regio-divergent and enantioselective C-H bond transformation of secondary amines at different N-alkyl groups has remained underdeveloped due to the challenging controllable HAT. Herein, we report a Cu-catalysed α'/β-regiodivergent and β-enantioselective cyanation of secondary amine-derived ureas through ligand-controlled adjustable 1,4’/1,5-hydrogen atom transfer. The utilization of a sterically demanding ligand enables the excellent α’-selective C–H cyanation at the N-methyl position, while two novel developed ligands with relatively less steric congestion promote the concise β-chirality construction at the other N-alkyl group. The approach is demonstrated for a broad scope of ureas with wide functional group compatibility including aryl, alkenyl, and alkynyl groups. Mechanistic studies indicate that the copper catalyst coordinating with different sterically hindered ligands could significantly influence the HAT and the radical trapping process Physical sciences/Chemistry/Organic chemistry/Synthetic chemistry methodology Physical sciences/Chemistry/Catalysis/Asymmetric catalysis Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supportinginformation.pdf Ligand-Controlled Regiodivergent and Enantioselective C–H Cyanation of Secondary Amines Cite Share Download PDF Status: Published Journal Publication published 20 Jan, 2026 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-6472539","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":447761864,"identity":"ea1f8de4-19c1-41f0-851c-5c382fb956a7","order_by":0,"name":"Dan-Qian 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