A 100,000-fold Increase in C-H Bond Acidity Gives Palladium a Key Advantage in C(sp3)-H Activation Compared to Nickel

A 100,000-fold Increase in C-H Bond Acidity Gives Palladium a Key Advantage in C(sp3)-H Activation Compared to Nickel | 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 A 100,000-fold Increase in C-H Bond Acidity Gives Palladium a Key Advantage in C(sp3)-H Activation Compared to Nickel Demyan Prokopchuk, Lirong Lin, Tim Schramm, Pavel Kucheryavy, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6482020/v3 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 Sep, 2025 Read the published version in Journal of the American Chemical Society → Version 3 posted You are reading this latest preprint version Show more versions Abstract Carbon-hydrogen bond activation is a pillar of synthetic chemistry. While it is generally accepted that Pd is more facile than Ni in C-H activation catalysis, there are no experimental platforms available to directly compare the magnitude of C-H bond weakening between Ni and Pd prior to bond scission. This work presents the first direct measurements of C( sp 3 )-H bond acidity (p K a ) and bond dissociation free energy (BDFE) for a species containing a ligated alkane-palladium interaction (R 2 CH 2 ---Pd), also known as an agostic interaction. Through standard-state equilibrium measurements and advanced computational modeling, we show that Pd acidifies C( sp 3 )-H bonds a 100,000 times more than Ni (5 p K a units), indicating that acidification is a key factor making Pd a privileged metal in C( sp 3 )-H functionalization reactions.Energy Decomposition Analysis (EDA) calculations show that this is primarily due to a greater electrophilicty of the palladium containing fragment, as forward charge transfer (ΔE CTf ) from the agostic methylene moiety into [Pd] is significantly increased. More broadly, these valuable findings help unravel fundamental performance differences between Earth-abundant and precious metals, potentially guiding future ligand design efforts for catalysis. Physical sciences/Chemistry/Coordination chemistry/Organometallic chemistry/Chemical bonding Physical sciences/Chemistry/Theoretical chemistry/Density functional theory Physical sciences/Chemistry/Inorganic chemistry/Organometallic chemistry/Ligands Physical sciences/Chemistry/Theoretical chemistry/Reaction mechanisms C-H Activation Palladium Agostic Interactions Pincer Ligands Acid-Base Chemistry Density Functional Theory Conformational Analysis Energy Decomposition Analysis Full Text Additional Declarations The authors declare no competing interests. Supplementary Files SI20250728mergedclean.pdf Supporting Information, Experimental and Computational. compSI.zip Computational data. 241029RALLLRPdBr100KB.cif cif file 220310RALLLRPdBr100K2H.cif cif file 240606ralllr424100kaautosqsq.cif cif file 250225RALLLR4515D100K.cif cif file Cite Share Download PDF Status: Published Journal Publication published 08 Sep, 2025 Read the published version in Journal of the American Chemical Society → Version 3 posted You are reading this latest preprint version Show more versions 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-6482020","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":497303076,"identity":"9f58cff9-98c5-478f-99f6-284afe9c8b87","order_by":0,"name":"Demyan 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Theory, Conformational Analysis, Energy Decomposition Analysis","lastPublishedDoi":"10.21203/rs.3.rs-6482020/v3","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6482020/v3","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCarbon-hydrogen bond activation is a pillar of synthetic chemistry. While it is generally accepted that Pd is more facile than Ni in C-H activation catalysis, there are no experimental platforms available to directly compare the magnitude of C-H bond weakening between Ni and Pd prior to bond scission. This work presents the first direct measurements of C(\u003cem\u003esp\u003c/em\u003e\u003csup\u003e3\u003c/sup\u003e)-H bond acidity (p\u003cem\u003eK\u003c/em\u003e\u003csub\u003ea\u003c/sub\u003e) and bond dissociation free energy (BDFE) for a species containing a ligated alkane-palladium interaction (R\u003csub\u003e2\u003c/sub\u003eCH\u003csub\u003e2\u003c/sub\u003e---Pd), also known as an agostic interaction. Through standard-state equilibrium measurements and advanced computational modeling, we show that Pd acidifies C(\u003cem\u003esp\u003c/em\u003e\u003csup\u003e3\u003c/sup\u003e)-H bonds a 100,000 times more than Ni (5 p\u003cem\u003eK\u003c/em\u003e\u003csub\u003ea\u003c/sub\u003e units), indicating that acidification is a key factor making Pd a privileged metal in C(\u003cem\u003esp\u003c/em\u003e\u003csup\u003e3\u003c/sup\u003e)-H functionalization reactions.Energy Decomposition Analysis (EDA) calculations show that this is primarily due to a greater electrophilicty of the palladium containing fragment, as forward charge transfer (ΔE\u003csub\u003eCTf\u003c/sub\u003e) from the agostic methylene moiety into [Pd] is significantly increased. 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