Functional-group-convergent synthesis of amides

Functional-group-convergent synthesis of amides | 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 Functional-group-convergent synthesis of amides Muliang Zhang, Yongwen Qi, Tingting Sun, Shi-Kai Tian This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9368274/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 Amide bonds are ubiquitous in biology and synthetic chemistry, forming the backbone of peptides, proteins, pharmaceuticals, polymers, and natural products. Traditional amidation strategies typically rely on the inherent reactivity of carboxylic acids and amines, often requiring activating agents or pre-functionalized derivatives. Here, we report a functional-group-convergent (FGC) strategy for modular amide assembly from readily available starting materials. The method employs visible-light-mediated manganese-catalysed carbonylative amidation, proceeding via a synergistic radical–polar crossover cycle that merges radical and organometallic reactivity. Unactivated alkyl iodides, boronic acids, low-pressure carbon monoxide, and nitrogen-transfer reagents are converted directly into amides under mild conditions, with selective activation of C(sp 3 )–I bonds while preserving C(sp 2 )–I bonds. The approach tolerates diverse functional groups and enables 15 N-labeled amide synthesis using isotopically enriched reagents. Its broad scope and chemoselectivity facilitate late-stage functionalization of complex drugs and natural products, exemplified by the efficient synthesis of Vorinostat and 15 N-labeled (±)-Acoitremon. Physical sciences/Chemistry Physical sciences/Materials science Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryInformation4.9.pdf Supplementary Information 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. 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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-9368274","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":620296425,"identity":"210a625c-b0ca-47a3-b0bc-3fc581907cec","order_by":0,"name":"Muliang Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYHACxgMJQJIfxmsgRg9Yi2QDRDWRWkCEwQFitchPO2Nw4EHNHbvNN9KfP/jBYCO74QDzswf4tDDOzjE4kHDsWfK2GzmGjT0MacYbDrCZG+DTwiwN0sJ2ONnsRg5jMwPD4cQNB3jYJPBpYQNr+Xc42XhG+kOglv+EtfCAtCS2HbYzkEgwBGo5QFiLhHRawYHEvsMJEmfeGM7sMUg2nnmYzQyvFvnZyRsf/vh22J6/Pf3Bhx8VdrJ9x5uf4dUCA4kNYAoUVMzEqAcCeyLVjYJRMApGwUgEAIHmTwqxftDNAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-0415-9444","institution":"University of Science and Technology of China","correspondingAuthor":true,"prefix":"","firstName":"Muliang","middleName":"","lastName":"Zhang","suffix":""},{"id":620296426,"identity":"1071454d-79a4-4cfe-935f-fd8cdf6bff81","order_by":1,"name":"Yongwen Qi","email":"","orcid":"","institution":"University of Science and Technology of China","correspondingAuthor":false,"prefix":"","firstName":"Yongwen","middleName":"","lastName":"Qi","suffix":""},{"id":620296427,"identity":"32094fda-ec2e-4f4f-a55e-6d7b6e140d35","order_by":2,"name":"Tingting Sun","email":"","orcid":"","institution":"University of Science and Technology of China","correspondingAuthor":false,"prefix":"","firstName":"Tingting","middleName":"","lastName":"Sun","suffix":""},{"id":620296428,"identity":"26f3d455-85b7-448f-a833-e750c68091db","order_by":3,"name":"Shi-Kai Tian","email":"","orcid":"https://orcid.org/0000-0002-2938-7013","institution":"University of Science and Technology of China","correspondingAuthor":false,"prefix":"","firstName":"Shi-Kai","middleName":"","lastName":"Tian","suffix":""}],"badges":[],"createdAt":"2026-04-09 11:57:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9368274/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9368274/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106960050,"identity":"f1cb3425-b519-4ea1-9470-34e5720c81f4","added_by":"auto","created_at":"2026-04-15 09:18:16","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1663362,"visible":true,"origin":"","legend":"","description":"","filename":"MS0409.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9368274/v1_covered_f89bbef6-042c-42ec-a5c1-cf81d688aff4.pdf"},{"id":106744459,"identity":"5420755b-9c38-4cbf-9841-03c4820880b3","added_by":"auto","created_at":"2026-04-13 05:05:58","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":17276217,"visible":true,"origin":"","legend":"Supplementary Information","description":"","filename":"SupplementaryInformation4.9.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9368274/v1/89a90445cf6a68db3a3884c9.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Functional-group-convergent synthesis of amides","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"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":"","lastPublishedDoi":"10.21203/rs.3.rs-9368274/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9368274/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAmide bonds are ubiquitous in biology and synthetic chemistry, forming the backbone of peptides, proteins, pharmaceuticals, polymers, and natural products. Traditional amidation strategies typically rely on the inherent reactivity of carboxylic acids and amines, often requiring activating agents or pre-functionalized derivatives. Here, we report a functional-group-convergent (FGC) strategy for modular amide assembly from readily available starting materials. The method employs visible-light-mediated manganese-catalysed carbonylative amidation, proceeding via a synergistic radical–polar crossover cycle that merges radical and organometallic reactivity. Unactivated alkyl iodides, boronic acids, low-pressure carbon monoxide, and nitrogen-transfer reagents are converted directly into amides under mild conditions, with selective activation of C(sp\u003csup\u003e3\u003c/sup\u003e)–I bonds while preserving C(sp\u003csup\u003e2\u003c/sup\u003e)–I bonds. The approach tolerates diverse functional groups and enables \u003csup\u003e15\u003c/sup\u003eN-labeled amide synthesis using isotopically enriched reagents. Its broad scope and chemoselectivity facilitate late-stage functionalization of complex drugs and natural products, exemplified by the efficient synthesis of Vorinostat and\u003csup\u003e 15\u003c/sup\u003eN-labeled (±)-Acoitremon.\u003c/p\u003e","manuscriptTitle":"Functional-group-convergent synthesis of amides","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-13 05:05:52","doi":"10.21203/rs.3.rs-9368274/v1","editorialEvents":[],"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":"c581b67e-e848-4896-ba11-fe83a8557992","owner":[],"postedDate":"April 13th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":66011460,"name":"Physical sciences/Chemistry"},{"id":66011461,"name":"Physical sciences/Materials science"}],"tags":[],"updatedAt":"2026-04-13T05:05:52+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-13 05:05:52","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9368274","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9368274","identity":"rs-9368274","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}