Nitrene-mediated Aminative N–N–N Coupling: Facile Access to Triazene 1-Oxides

Nitrene-mediated Aminative N–N–N Coupling: Facile Access to Triazene 1-Oxides | 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 Research Article Nitrene-mediated Aminative N–N–N Coupling: Facile Access to Triazene 1-Oxides Hao Wang, Shi-Yang Zhu, Hai-Ruo Zhang, Bo-Yang Sun, Zi-Qian Bai, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5667447/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Significant strides have been made in the realm of nucleophile-electrophile coupling reactions over recent decades. However, the development of innovative strategies for nucleophile-nucleophile coupling is still highly sought after. Among these, aminative coupling, especially when involving two nitrogen-connected nucleophiles, is not only rare but also exceedingly challenging. In this work, we present a novel nitrene-mediated aminative N–N–N coupling reaction that employs an anomeric amide as a key reagent to connect amines with nitrosoarenes. This innovative method capitalizes on the in situ generation of an aminonitrene intermediate, which is efficiently captured by nitrosoarenes. The resultant reaction offers a direct, mild, and highly efficient pathway for synthesizing triazene 1-oxides, thereby establishing a new paradigm for aminative coupling between nucleophiles. Our mechanistic studies demonstrate that the \textit{N}-substituents of the amine have a profound impact on the reactivity of the aminonitrene intermediate. Additionally, complementary computational studies suggest that aryl nitroso and aminonitrene coupling is significantly favored due to the substantial reduction in distortion energy, outcompeting alternative nitrene dimerization pathways. Organic Chemistry nitrene aminonitrene aminative coupling triazene 1-oxide Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted 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-5667447","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":391774582,"identity":"f4846b04-1402-4a7c-b951-c50b36079a8f","order_by":0,"name":"Hao Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwklEQVRIiWNgGAWjYBACAwYGxgdgmhlI8hCphdmAZC1sEhCaWC3m7IePVRfU3DHmbwe68G0bg7w5IS2WPWlpt2cce2YmcZiB2XBuG4PhzgZCDjuQY3abh+2wDcNhBjZp3jaGBIMDhLScf2NWzPPvsI38YQb238RpuZFjxszbdtjMAGgLM5FaniVL8/YdNjY8zNgsOeechOEGwg5LPviZ59thw3nnDx/88KbMRp6gLUiAsQFISBCvfhSMglEwCkYBbgAAjxU8IbHe7wQAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-3831-2988","institution":"Nankai University","correspondingAuthor":true,"prefix":"","firstName":"Hao","middleName":"","lastName":"Wang","suffix":""},{"id":391774583,"identity":"87fdf921-c5b2-4364-b60f-81dd20fbe017","order_by":1,"name":"Shi-Yang Zhu","email":"","orcid":"","institution":"Nankai University","correspondingAuthor":false,"prefix":"","firstName":"Shi-Yang","middleName":"","lastName":"Zhu","suffix":""},{"id":391774584,"identity":"d60f0d84-5601-46e7-90c6-d275f32911e0","order_by":2,"name":"Hai-Ruo Zhang","email":"","orcid":"","institution":"Nankai University","correspondingAuthor":false,"prefix":"","firstName":"Hai-Ruo","middleName":"","lastName":"Zhang","suffix":""},{"id":391774585,"identity":"b893ae14-168e-44f0-bfef-574ef46fc927","order_by":3,"name":"Bo-Yang Sun","email":"","orcid":"","institution":"Nankai University","correspondingAuthor":false,"prefix":"","firstName":"Bo-Yang","middleName":"","lastName":"Sun","suffix":""},{"id":391774586,"identity":"23fe8d96-2dce-4af8-89ac-bdb68fcc4740","order_by":4,"name":"Zi-Qian Bai","email":"","orcid":"","institution":"Nankai University","correspondingAuthor":false,"prefix":"","firstName":"Zi-Qian","middleName":"","lastName":"Bai","suffix":""},{"id":391774587,"identity":"e3cd3f1e-eedc-484f-9c15-201d90ff4b2c","order_by":5,"name":"Gang He","email":"","orcid":"","institution":"Nankai University","correspondingAuthor":false,"prefix":"","firstName":"Gang","middleName":"","lastName":"He","suffix":""},{"id":391774588,"identity":"42c809c1-ff2b-4ab7-b6b9-5f059d7d57b1","order_by":6,"name":"Gong Chen","email":"","orcid":"","institution":"Nankai University","correspondingAuthor":false,"prefix":"","firstName":"Gong","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2024-12-18 08:22:35","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-5667447/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5667447/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":71848456,"identity":"8444b264-616c-4b88-af9d-b27412b37045","added_by":"auto","created_at":"2024-12-19 06:58:24","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1254774,"visible":true,"origin":"","legend":"","description":"","filename":"ZhuSY20243Ncoupling.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5667447/v1_covered_603a4aaa-9d92-4f3c-87e9-649ce5791a5c.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eNitrene-mediated Aminative N–N–N Coupling: Facile Access to Triazene 1-Oxides\u003c/strong\u003e\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Nankai University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"nitrene, aminonitrene, aminative coupling, triazene 1-oxide","lastPublishedDoi":"10.21203/rs.3.rs-5667447/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5667447/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eSignificant strides have been made in the realm of nucleophile-electrophile coupling reactions over recent decades. However, the development of innovative strategies for nucleophile-nucleophile coupling is still highly sought after. Among these, aminative coupling, especially when involving two nitrogen-connected nucleophiles, is not only rare but also exceedingly challenging. In this work, we present a novel nitrene-mediated aminative N–N–N coupling reaction that employs an anomeric amide as a key reagent to connect amines with nitrosoarenes. This innovative method capitalizes on the in situ generation of an aminonitrene intermediate, which is efficiently captured by nitrosoarenes. The resultant reaction offers a direct, mild, and highly efficient pathway for synthesizing triazene 1-oxides, thereby establishing a new paradigm for aminative coupling between nucleophiles. Our mechanistic studies demonstrate that the \\textit{N}-substituents of the amine have a profound impact on the reactivity of the aminonitrene intermediate. Additionally, complementary computational studies suggest that aryl nitroso and aminonitrene coupling is significantly favored due to the substantial reduction in distortion energy, outcompeting alternative nitrene dimerization pathways.\u003c/p\u003e","manuscriptTitle":"Nitrene-mediated Aminative N–N–N Coupling: Facile Access to Triazene 1-Oxides","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-19 06:50:16","doi":"10.21203/rs.3.rs-5667447/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fd23e9a9-b8b1-40b9-8cfd-190c1d90f713","owner":[],"postedDate":"December 19th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":41759230,"name":"Organic Chemistry"}],"tags":[],"updatedAt":"2024-12-22T23:47:44+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-19 06:50:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5667447","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5667447","identity":"rs-5667447","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}