Iron-Catalyzed Cleavage of Allene C=C Double Bond

Iron-Catalyzed Cleavage of Allene C=C Double Bond | 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 Iron-Catalyzed Cleavage of Allene C=C Double Bond Xinxin Wu, Zhaoshan Wang, Qi Zhang, Huiying Liu, Zhigang Ma, Xiancheng Qiu, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5543027/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract While the oxidative cleavage of olefins is well established, the radical-mediated, chemo- and regioselective cleavages of allene C(sp)–C(sp 2 ) and C(sp 3 )–C(sp 2 ) bonds remain unresolved challenges in synthetic chemistry. These challenges primarily stem from the high reactivity of the unique twisted orthogonal π-systems and the regioselectivity issues associated with adjacent C = C double bonds. Herein, we present base metal-catalyzed cleavage of allenic C(sp)–C(sp 2 ) double bonds and C(sp 3 )–C(sp 2 ) single bonds utilizing air as an oxidant. These transformations, initiated by hydrogen atom abstraction (HAA) from the allenic C(sp²)-H bonds, lead to the formation of a diverse range of remotely functionalized ketones, alkylated heteroaryls, alkylated nitriles, and deuterated products, all with remarkable site selectivity. In this strategy, the α-silyl effect plays a key role in activating allenic C(sp 2 )-H bond thus initiating the HAA from allenes and achieving the desired regioselectivity. Physical sciences/Chemistry/Organic chemistry/Synthetic chemistry methodology Physical sciences/Chemistry/Catalysis/Homogeneous catalysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Full Text In organic synthesis, traditional functionalization strategies typically focus on introducing or modifying functional groups without substantially altering the core structure of the molecule. In contrast, deconstructive functionalization offers a compelling alternative by reshaping molecular frameworks, thereby unlocking new chemical space, exposing latent functional groups, and enabling the creation of new functionalities at predefined positions dictated by the structural features of the reactants and the mode of the reaction. The carbon-carbon double bond is a fundamental moiety in organic molecules, and numerous methodologies have been developed to transform alkenes into valuable intermediates and fine chemical products, which are crucial across material science, biochemistry, pharmaceuticals, and the chemical industry 1-3 . Deconstructive functionalization of alkenes, which introduces two functional groups at distinct sites of olefins, has seen significant advancements (Fig. 1a, left). For example, transition-metal-catalyzed C=C bond cleavage reactions, such as olefin metathesis, have been widely applied in the synthesis of natural products and materials 4-6 . Additionally, ozonolysis and related oxidative methods using various organic and inorganic oxidants are well-established for converting a single C=C bond into two carbonyl derivatives 7-15 . Allenes, characterized by their unique twisted orthogonal π-systems, are versatile building blocks in synthetic chemistry. They have been extensively used as precursors in transition metal-catalyzed cross-coupling reactions, radical processes, nucleophilic additions, and other transformations 16-18 . However, the chemo- and regioselective deconstructive fragmentation of one of the two cumulated π-bonds in allenes under mild conditions has not yet been reported (Fig. 1a, right), which significantly limits the exploration and broad application of this unique class of compounds. In this work, we demonstrate an iron-catalyzed selective fragmentation of the allenic C=C double bond, which is accompanied by sp 2 and sp 3 C-H bond cleavages (Fig. 1b). This transformation utilizes air as a mild and environmentally friendly oxidant and employs a cost-effective iron salt catalyst under room temperature conditions. The homolytic cleavage of C-H bonds via hydrogen atom abstraction (HAA) has emerged as a powerful tool for C-H bond functionalization 19-35 . However, while extensive studies have been conducted on the functionalization of sp³ C-H bonds, the functionalization of sp² C-H bonds in allenes via HAA remains rarely explored 36-39 . Due to the inherent nature of the cumulated diene system, reactions involving allenes typically proceed through the cleavage of π-bonds (e.g., radical addition) rather than C-H functionalization 40-42 . Recently, the Liu group and our group independently reported a copper-catalyzed radical relay process for the site-selective functionalization of sp² C-H bonds in allenes (Fig. 1c) 43-46 . In this approach, the HAA process at sp² C-H bonds was achieved by Cu-bound nitrogen-centered radicals (NCRs), leading to the formation of allenic C-radicals, which were subsequently trapped by Cu(II) species to afford allenic products. From the perspective of atom economy and green chemistry, our protocol offers a distinct advantage by employing molecular oxygen from air as the oxidant, instead of relying on synthetically complex N-F reagents for HAA, thereby enhancing operational simplicity (Fig. 1c). Notably, this atom-economical approach integrates both fragmented components rather than discarding one, as is common in conventional olefin oxidation processes. The reaction proceeds via formal isomerization of the cleaved segment into an alkynyl group, which migrates to the γ-position, yielding a wide array of distally alkynylated ketones. This transformation likely involves a remote radical-mediated alkynyl group migration pathway (Fig. 1d), a strategy pioneered by our group and Studer’s group et al . 47-50 To realize a multi-step cascade process for allenic C=C bond cleavage, several significant challenges must be addressed: (1) achieving site-selective HAA from allenic and alkyl C-H bonds under mild conditions; (2) avoiding undesired radical addition to allenes or alkynes; and (3) maintaining reaction conditions that prevent polymerization and overoxidation of allenes while ensuring compatibility and substrate scope. In this strategy, the α-silyl effect plays a pivotal role in achieving the desired regioselectivity and facilitating the initial hydrogen atom abstraction (HAA) from allenes. This is supported by the calculated bond dissociation energies (BDEs) of organosilicon compounds, which demonstrate a significant activation of α-C(sp²)–H bonds compared to their non-silylated counterparts (Fig. 1e). Our recent investigations into the new reactivity of allenes have revealed that substituents in allenes can significantly influence their reaction pathways. Consequently, we subjected phenyl- ( 1a-1 ), tert -butyl- ( 1a-2 ), and silyl-allenes ( 1a-3 ), which contain an allenyl C-H bond, to a screening of reaction parameters (Table 1; for more details, see Supplementary Information). Based on the principles of green chemistry and atom economy, this study successfully utilizes oxygen as both the oxidant and hydrogen atom transfer agent. Initial experimental results demonstrated a lack of reactivity for phenyl and tert -butyl containing allenes 1a-1 and 1a-2 (entries 1 and 2), in contrast to the complete conversion of the structurally similar tert -butyldimethylsilyl (TBS) group-containing allene 1a-3 , which yielded alkynylated product 2a with an excellent yield (entry 3). This finding indicates a dramatic activation of the α-C(sp 2 )–H bond by the silyl group. Density functional theory (DFT) calculations revealed that the primary source of this unexpected reactivity is the weakening of the allenic C(sp 2 )-H bond. Compared to the non-silylated allenes ( 1a-1 and 1a-2 ), the corresponding silylated counterpart ( 1a-3 ) exhibits an unusually weak C(sp 2 )-H bond (79.3 kcal/mol) (Table 1, middle), which is even lower than that of the allylic C(sp 3 )-H bond (88 kcal/mol) and the C(sp 3 )-H bond adjacent to an oxygen atom, such as those in ethanol (95.9 kcal/mol) and tetrahydrofuran (THF) (92.1 kcal/mol). Furthermore, the calculated natural bond orbital (NBO) charges reveal that the sp²-hybridized allenic C1 atom in 1a-3 , bearing a silyl group, exhibits a more negative charge relative to 1a-1 and 1a-2 (Table 1, top). This can be attributed to the electron-donating effect of the silyl group, commonly referred to as the α-silyl effect 51-53 . This suggests that the allenic C1 atom in 1a-3 is more susceptible to undergoing oxidation reactions or HAA processes, which rationalizes its excellent chemo- and regioselectivity. Additionally, more reaction parameters were investigated (Table 1). The use of FeCl 2 , iron meso -tetraphenylporphyrin chloride [Fe(TPP)Cl], or CuOTf as substitutes for Fe(OTf) 2 resulted in lower yields (entries 4-6). When tetrahydrofuran (THF) was used as the solvent instead of ethyl acetate, a comparable yield was still obtained, even though THF has been previously reported to participate in hydrogen atom transfer reactions due to its relatively lower C-H bond dissociation energy. This suggests that the reaction can proceed even in the presence of such activated C-H bonds. Furthermore, it indicates that the C-H bond in allenes is more reactive than that in THF, and that the regioselective cleavage of non-activated sp 3 C-H bonds with higher BDEs is likely to proceed via an intramolecular hydrogen atom transfer (HAT) process, rather than an intermolecular one. Otherwise, THF, with its activated C-H bonds, would have adversely affected the reaction outcome. Additionally, control experiments indicated that the addition of iron salts is essential for the reaction to occur. Moreover, the reaction did not proceed under an inert nitrogen atmosphere, whereas in an oxygen atmosphere, a moderate yield was achieved. This demonstrates that the presence of oxygen in the air plays a crucial role in facilitating the reaction. The optimized reaction conditions for the regioselective cleavage of the C=C bond in allenylsilanes 54,55 , highly valuable building blocks in organic synthesis, were applied to examine the general applicability of our method (Fig. 2). Trisubstituted silylated allenes ( 1a – 1g ) produced regioselective C(sp 3 )-H alkynylated ketones ( 2a – 2g ), with different silyl groups (TBS, TIPS, TES, -Si(Me) 2 Ph) having minimal impact on the yields. Notably, primary, secondary and tertiary C(sp 3 )-H bonds at the γ-position showed excellent compatibility with the protocol. Among these, the -TIPS group provided slightly higher yields, prompting an exploration of aliphatic allenes bearing the -TIPS group. Interestingly, the C(sp 3 )-H bond adjacent to an oxygen atom ( 1h ) also underwent alkynylation with good regioselectivity, though the yield decreased, likely due to the oxidation propensity of the corresponding alkyl radical at the α-position to the oxygen atom. The introduction of a methyl group at the β -position ( 1i ) or elongation of the aliphatic chain ( 1j ) did not affect regioselectivity, providing the desired products ( 2i and 2j ) in high yields. Besides linear C-H bonds, alkynylation also occurred on cyclohexane ring ( 2k ), while the olefin moiety, typically prone to radical reactions, remained intact ( 2l ), demonstrating chemoselectivity between the olefin and allene groups. Substrates bearing elongated aliphatic chains ( 2m , 2n ) at the opposite side of gem -dialkyl-substituted allenes, as well as those containing cyclopropane or cyclobutane groups ( 2o , 2p ), demonstrated compatibility with the reaction conditions. These results highlight the versatility of the methodology in accommodating various sterically hindered and cyclic systems, further broadening the substrate scope of this protocol. However, phenyl allenes substituted with a TIPS group ( 1q ) gave trace product due to alkyl side chain cleavage, whereas phenyldimethylsilyl allene ( 1r ) provided higher yields, also confirming the superior migratory aptitude of the alkynyl group compared to the phenyl group. Both electron-donating and electron-withdrawing substituents afforded the desired alkynylated products in synthetically useful yields ( 2s – 2ab ), and halides, particularly bromides ( 2v , 2ab ), remained unaffected, creating opportunities for further product modification via cross-coupling reactions. Furthermore, naphthyl-substituted allene ( 1ac ) was well-tolerated, yielding the corresponding product ( 2ac ) in excellent yields. To probe the compatibility of disubstituted allene ( 1ad ) with two allenic C(sp 2 )-H bonds, which could compete during the HAA process, the reaction proceeded smoothly to form the aldehyde product ( 2ad ), leaving the low BDE aldehyde sp 2 C-H bond (89 kcal/mol) intact. The scalability and applicability of this method were demonstrated through the successful large-scale preparation of 2c , which proceeded smoothly and yielded results comparable to those of smaller-scale reactions, affirming the practicality of the protocol (Fig. 3, top). Furthermore, the products exhibit versatility in their transformations into other valuable compounds (Fig. 3). For instance, the ketone functionality serves as a useful building block, which can be efficiently reduced to alcohol ( 3 ) using NaBH 4 , yielding excellent results, or converted into an alkene ( 4 ) via a sequential Wittig reaction. Additionally, the TIPS group in alkyne ( 2c ) can be easily removed in the presence of tetrabutylammonium fluoride (TBAF), facilitating a subsequent click reaction with BnN 3 to afford N -heteroarene ( 5 ). Moreover, a Pd-catalyzed cross- coupling reaction between silylated alkyne ( 2c ) and 4-bromoiodobenzene provides an aryl alkyne ( 6 ). The alkynyl group in 2c , being a key synthetic core, can also be stereoselectively transformed into ( E )-alkene ( 7 ), demonstrating the flexibility and synthetic utility of the methodology across multiple chemical transformations. Next, we focused on exploring the reaction mechanism. After stirring TIPS-substituted allene 1c under air and solvent-free conditions for 1.5 hours, the addition of 1 mL acetonitrile yielded a colorless solution (Fig. 4a, top). However, upon the addition of 1.0 equivalent of KI, the mixture turned yellow, suggesting the formation of oxidizing species, such as peroxides, during the reaction. These species oxidized KI to iodine, leading to the observed color change. Crucially, propargylic peroxide ( 8 ) was isolated in excellent yield with complete conversion. The subsequent reaction of 8 , catalyzed by Fe(OTf)₂, produced the desired ketone product ( 2b ) in excellent yield (Fig. 4a, bottom). In contrast, no peroxides were detected for phenyl- or tert -butyl-substituted allene 1a-1 or 1a-2 under the same conditions (Fig. 4b), indicating that the silyl group is essential for this autooxidation process. Since we hypothesized the involvement of allenic or propargylic radicals, we added TEMPO, a well-known radical scavenger, to the reaction with starting material 1c . As expected, no peroxide intermediate ( 8 ) was detected; instead, the TEMPO-trapped product ( 9 ), resulting from the interception of a propargylic radical, was identified through HRMS analysis (Fig. 4c, top), indicating that the reaction probably proceeded through radical mechanism. Moreover, after the autooxidation of 1c , when Fe(OTf) 2 , solvent, and TEMPO were added, only 75% of peroxide ( 8 ) was isolated, with no sign of the migrated product ( 2c ) (Fig. 4c, bottom). In crossover experiments involving 1a and 1m under standard conditions, the absence of cross-coupled products ( 2a’ and 2m’ ) supported the hypothesis that the reaction proceeds via an intramolecular alkynyl group translocation mechanism (Fig. 4d). Based on our mechanistic studies and previous reports, we proposed a plausible pathway for the cleavage of allenic carbon-carbon double bonds, as outlined in Fig. 5. Initially, the allene substrate undergoes an autooxidation process in the presence of molecular oxygen, which involves the cleavage of the allenic C(sp²)-H bond and a resonance isomerization between the allenic radical ( I ) and propargylic radical ( II ). This step results in the formation of a hydroperoxyl radical. The hydroperoxyl radical couples with the propargylic radical to generate a propargylic peroxide ( III ). Next, single-electron reduction of this peroxide by Fe(II) leads to the cleavage of the peroxide bond, producing an alkoxy radical ( IV ). The alkoxy radical then initiates an intramolecular hydrogen atom transfer (HAT) process, forming a remote alkyl radical ( V ) 56-63 . This alkyl radical undergoes intramolecular attack on the adjacent alkynyl group, yielding a five-membered cyclic vinyl radical ( VI ). Finally, the resulting ketyl radical ( VII ), generated from the ring-opening, is oxidized by Fe(III) and deprotonated, resulting in the formation of the alkynyl ketone product, with Fe(II) being regenerated to complete the catalytic cycle. This mechanism highlights the role of both autooxidation and iron-catalyzed radical processes in achieving selective bond cleavage, further supported by the influence of silyl group in promoting key transformations within the catalytic cycle. In summary, this study presents an efficient and regioselective method for the cleavage of allenic C=C bonds via a radical-mediated process. Mechanistic investigations, coupled with experimental validation, underscore the pivotal role of the silyl group in driving the autooxidation process by utilizing air as the oxidant and facilitating single-electron transfer mediated by cost-effective iron salts. This process enables key transformations, including allenic C-H bond cleavage and alkynyl group migration. The method’s scalability, broad substrate scope, and ability to selectively functionalize C(sp³)-H bonds highlight its practical relevance. Additionally, the facile conversion of the reaction products into valuable intermediates—such as alkynes, alkenes, and heterocycles—demonstrates the synthetic versatility and applicability of this approach in organic synthesis. This work not only provides new insights into allene chemistry but also opens up new avenues for further exploration of radical-mediated C-C bond cleavage and C-H functionalization strategies. Declarations Data Availability The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files. Extra data are available from the corresponding author upon request. Supplementary tables and figures, experimental procedures, characterization, and spectra of all materials, are included in the Supplementary Information. Acknowledgment We are grateful for the financial support from the National Natural Science Foundation of China (22001185), the Natural Science Foundation of Jiangsu Province (BK20200852), the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (23KJA150007). We thank Prof. Hao Yu from Fudan University for helpful discussions. Author Information 1 Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren-Ai Road, Suzhou, Jiangsu 215123, China E-mail: [email protected] 2 TandemAI, Building 6, No. 111 Wusongjiang Road, Wuzhong District, Suzhou, Jiangsu 215124, China E-mail: [email protected] Author contributions Z.W., Q.Z., and H.L. performed and analyzed the experiments. Z.M. participated in the early development of the project. X.Q., S.J., and J.Z. prepared part of starting materials. X.W. conceived and designed the project. C.Z. revised the manuscript. All authors prepared this manuscript. Competing Interests The authors declare no competing interests. References Grubbs, R. H. & Chang, S. Recent advances in olefin metathesis and its application in organic synthesis. Tetrahedron 54 , 4413-4450 (1998). McDonald, R. I., Liu, G. & Stahl, S. S. 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Hu, A., Guo, J., Pan, H., Tang, H., Gao, Z. & Zuo, Z. δ-Selective functionalization of alkanols enabled by visible-light-induced ligand-to-metal charge transfer. J. Am. Chem. Soc. 140 , 1612-1616 (2018). Zhu, Y., Huang, K., Pan, J., Qiu, X., Luo, X., Qin, Q., Wei, J., Wen, X., Zhang, L. & Jiao, N. Silver-catalyzed remote Csp 3 -H functionalization of aliphatic alcohols. Nat. Commun. 9 , 2625 (2018). Guan, H., Sun, S., Mao, Y., Chen, L., Lu, R., Huang, J. & Liu, L. Iron(II)-catalyzed site-selective functionalization of unactivated C(sp 3 )−H bonds guided by alkoxyl radicals. Angew. Chem., Int. Ed. 57 , 11413-11417 (2018). Wu, X., Zhang, H., Tang, N., Wu, Z., Wang, D., Ji, M., Xu, Y., Wang, M. & Zhu, C. Metal-free alcohol-directed regioselective heteroarylation of remote unactivated C(sp 3 )-H bonds. Nat. Commun. 9 , 3343 (2018). Table 1 Table 1 is available in the Supplementary Files section. Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryInformation.docx Supplementary Information Table1.docx Cite Share Download PDF Status: Under Review 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-5543027","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":386088956,"identity":"69efa36d-3bf4-45b3-b5ed-149acc9aac34","order_by":0,"name":"Xinxin 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12:34:50","extension":"xml","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":127331,"visible":true,"origin":"","legend":"","description":"","filename":"NCOMMS24787790structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-5543027/v1/8bc9ee2e712ab4e422d6801e.xml"},{"id":97702506,"identity":"1bfde869-c65a-4336-9eeb-e35def530b12","added_by":"auto","created_at":"2025-12-08 12:34:49","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":135544,"visible":true,"origin":"","legend":"\u003cp\u003eOverview and our strategy. a) Cleavage of C=C double bond. b) Regioselective cleavage of allene C(sp\u003csup\u003e2\u003c/sup\u003e)-C(sp) double bond (this work). c) Hydrogen atom abstraction (HAA) from allenic C(sp\u003csup\u003e2\u003c/sup\u003e)-H bond. d) Radical-mediated alkynyl group migration. e) BDE data of allenic C(sp\u003csup\u003e2\u003c/sup\u003e)-H bonds.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5543027/v1/bbae4943bbc3d052eb2d4bdb.jpg"},{"id":97894996,"identity":"8b4a775d-e0b5-4d78-ba43-c1f880f05204","added_by":"auto","created_at":"2025-12-10 15:33:20","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":129511,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSubstrate scope of silyl allenes for the cleavage of C-C double bonds. \u003c/strong\u003eReaction conditions: 1 (0.2 mmol) was stirred under neat condition and under air, followed by addition of Fe(OTf)\u003csub\u003e2\u003c/sub\u003e (10 mol%) and EtOAc (2 mL), then the reaction was stirred for 12 h under N\u003csub\u003e2\u003c/sub\u003e; isolated yields.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5543027/v1/ddecbe930633bcd2d32daf84.jpg"},{"id":97702509,"identity":"26f90e22-cec4-4cf6-a609-66b0d2bbf228","added_by":"auto","created_at":"2025-12-08 12:34:49","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":68801,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScaled-up preparation and product transformations.\u003c/strong\u003e Reaction condition: a) \u003cstrong\u003e2c\u003c/strong\u003e (0.2 mmol), NaBH\u003csub\u003e4\u003c/sub\u003e (1.3 equiv.), MeOH; b) \u003cstrong\u003e2c\u003c/strong\u003e (0.2 mmol), [Ph\u003csub\u003e3\u003c/sub\u003ePMe]Br, NaH, THF, N\u003csub\u003e2\u003c/sub\u003e, 70°C; c) \u003cstrong\u003e2c\u003c/strong\u003e (0.2 mmol), TBAF, THF, RT; then CuSO\u003csub\u003e4\u003c/sub\u003e, sodium ascorbate, BnN\u003csub\u003e3\u003c/sub\u003e, 60°C, 2 h, H\u003csub\u003e2\u003c/sub\u003eO/tBuOH; d) \u003cstrong\u003e2c\u003c/strong\u003e (0.2 mmol, 1.0 equiv.), PdCl\u003csub\u003e2\u003c/sub\u003e(PPh\u003csub\u003e3\u003c/sub\u003e)\u003csub\u003e2\u003c/sub\u003e (0.009 mmol, 4.5 mol%), CuI (0.009 mmol, 4.5 mol%), THF (1.0 mL), Et\u003csub\u003e3\u003c/sub\u003eN (0.2 mL), TBAF (0.40 mL, 1 M in THF) and 4-bromoiodobenzene (0.24 mmol, 1.2 equiv.), 45 \u003csup\u003eo\u003c/sup\u003eC, 4 h. e) \u003cstrong\u003e2c\u003c/strong\u003e (0.2 mmol), DIBAL-H (5 equiv.), Et\u003csub\u003e2\u003c/sub\u003eO (0.1 M), 50 \u003csup\u003eo\u003c/sup\u003eC, 12 h.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5543027/v1/36e5d3cd2e878c64b16e4e49.jpg"},{"id":97894999,"identity":"a99adca6-aa43-439c-bb71-5c9ca08c2dfd","added_by":"auto","created_at":"2025-12-10 15:33:21","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":130484,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMechanistic studies. \u003c/strong\u003ea) Detection of peroxide. b) Investigation on reactivities of phenyl- and \u003csup\u003e\u003cem\u003et\u003c/em\u003e\u003c/sup\u003eBu-allenes.\u0026nbsp; c) TEMPO-trapping experiment. d) Crossover experiments.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5543027/v1/e2295e0cd27e66669a16eccb.jpg"},{"id":97702516,"identity":"060b9298-4fb4-44ac-b154-82a9d30200f5","added_by":"auto","created_at":"2025-12-08 12:34:49","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":64028,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eProposed mechanism.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-5543027/v1/f3f44171c5c8b083697b52b2.jpg"},{"id":98622110,"identity":"0147fdd9-692e-49c6-ac05-1873fc858e61","added_by":"auto","created_at":"2025-12-19 16:45:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1239551,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5543027/v1/df1980a0-4294-41c4-b5cc-36ab03503dc5.pdf"},{"id":97893476,"identity":"e49bfc1b-4068-42eb-b8ee-970883eeeaac","added_by":"auto","created_at":"2025-12-10 15:30:32","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":10595406,"visible":true,"origin":"","legend":"Supplementary Information","description":"","filename":"SupplementaryInformation.docx","url":"https://assets-eu.researchsquare.com/files/rs-5543027/v1/9c0caf36b098a601074d52d0.docx"},{"id":97702507,"identity":"4dece85f-607d-4253-8193-4ae5ef0a3342","added_by":"auto","created_at":"2025-12-08 12:34:49","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":46361,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.docx","url":"https://assets-eu.researchsquare.com/files/rs-5543027/v1/441f9d65aad0722ed55fa893.docx"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Iron-Catalyzed Cleavage of Allene C=C Double Bond","fulltext":[{"header":"Full Text","content":"\u003cp\u003eIn organic synthesis, traditional functionalization strategies typically focus on introducing or modifying functional groups without substantially altering the core structure of the molecule. In contrast, deconstructive functionalization offers a compelling alternative by reshaping molecular frameworks, thereby unlocking new chemical space, exposing latent functional groups, and enabling the creation of new functionalities at predefined positions dictated by the structural features of the reactants and the mode of the reaction.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe carbon-carbon double bond is a fundamental moiety in organic molecules, and numerous methodologies have been developed to transform alkenes into valuable intermediates and fine chemical products, which are crucial across material science, biochemistry, pharmaceuticals, and the chemical industry\u003csup\u003e1-3\u003c/sup\u003e. Deconstructive functionalization of alkenes, which introduces two functional groups at distinct sites of olefins, has seen significant advancements (Fig. 1a, left). For example, transition-metal-catalyzed C=C bond cleavage reactions, such as olefin metathesis, have been widely applied in the synthesis of natural products and materials\u003csup\u003e4-6\u003c/sup\u003e. Additionally, ozonolysis and related oxidative methods using various organic and inorganic oxidants are well-established for converting a single C=C bond into two carbonyl derivatives\u003csup\u003e7-15\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAllenes, characterized by their unique twisted orthogonal \u0026pi;-systems, are versatile building blocks in synthetic chemistry. They have been extensively used as precursors in transition metal-catalyzed cross-coupling reactions, radical processes, nucleophilic additions, and other transformations\u003csup\u003e16-18\u003c/sup\u003e. However, the chemo- and regioselective deconstructive fragmentation of one of the two cumulated \u0026pi;-bonds in allenes under mild conditions has not yet been reported (Fig. 1a, right), which significantly limits the exploration and broad application of this unique class of compounds. In this work, we demonstrate an iron-catalyzed selective fragmentation of the allenic C=C double bond, which is accompanied by sp\u003csup\u003e2\u003c/sup\u003e and sp\u003csup\u003e3\u003c/sup\u003e C-H bond cleavages (Fig. 1b). This transformation utilizes air as a mild and environmentally friendly oxidant and employs a cost-effective iron salt catalyst under room temperature conditions.\u003c/p\u003e\n\u003cp\u003eThe homolytic cleavage of C-H bonds via hydrogen atom abstraction (HAA) has emerged as a powerful tool for C-H bond functionalization\u003csup\u003e19-35\u003c/sup\u003e. However, while extensive studies have been conducted on the functionalization of sp\u0026sup3; C-H bonds, the functionalization of sp\u0026sup2; C-H bonds in allenes via HAA remains rarely explored\u003csup\u003e36-39\u003c/sup\u003e. Due to the inherent nature of the cumulated diene system, reactions involving allenes typically proceed through the cleavage of \u0026pi;-bonds (e.g., radical addition) rather than C-H functionalization\u003csup\u003e40-42\u003c/sup\u003e. Recently, the Liu group and our group independently reported a copper-catalyzed radical relay process for the site-selective functionalization of sp\u0026sup2; C-H bonds in allenes (Fig. 1c)\u003csup\u003e43-46\u003c/sup\u003e. In this approach, the HAA process at sp\u0026sup2; C-H bonds was achieved by Cu-bound nitrogen-centered radicals (NCRs), leading to the formation of allenic C-radicals, which were subsequently trapped by Cu(II) species to afford allenic products. From the perspective of atom economy and green chemistry, our protocol offers a distinct advantage by employing molecular oxygen from air as the oxidant, instead of relying on synthetically complex N-F reagents for HAA, thereby enhancing operational simplicity (Fig. 1c).\u003c/p\u003e\n\u003cp\u003eNotably, this atom-economical approach integrates both fragmented components rather than discarding one, as is common in conventional olefin oxidation processes. The reaction proceeds via formal isomerization of the cleaved segment into an alkynyl group, which migrates to the \u0026gamma;-position, yielding a wide array of distally alkynylated ketones. This transformation likely involves a remote radical-mediated alkynyl group migration pathway (Fig. 1d), a strategy pioneered by our group and Studer\u0026rsquo;s group \u003cem\u003eet al\u003c/em\u003e.\u003csup\u003e47-50\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eTo realize a multi-step cascade process for allenic C=C bond cleavage, several significant challenges must be addressed: (1) achieving site-selective HAA from allenic and alkyl C-H bonds under mild conditions; (2) avoiding undesired radical addition to allenes or alkynes; and (3) maintaining reaction conditions that prevent polymerization and overoxidation of allenes while ensuring compatibility and substrate scope. In this strategy, the \u0026alpha;-silyl effect plays a pivotal role in achieving the desired regioselectivity and facilitating the initial hydrogen atom abstraction (HAA) from allenes. This is supported by the calculated bond dissociation energies (BDEs) of organosilicon compounds, which demonstrate a significant activation of \u0026alpha;-C(sp\u0026sup2;)\u0026ndash;H bonds compared to their non-silylated counterparts (Fig. 1e).\u003c/p\u003e\n\u003cp\u003eOur recent investigations into the new reactivity of allenes have revealed that substituents in allenes can significantly influence their reaction pathways. Consequently, we subjected phenyl- (\u003cstrong\u003e1a-1\u003c/strong\u003e), \u003cem\u003etert\u003c/em\u003e-butyl- (\u003cstrong\u003e1a-2\u003c/strong\u003e), and silyl-allenes (\u003cstrong\u003e1a-3\u003c/strong\u003e), which contain an allenyl C-H bond, to a screening of reaction parameters (Table 1; for more details, see Supplementary Information). Based on the principles of green chemistry and atom economy, this study successfully utilizes oxygen as both the oxidant and hydrogen atom transfer agent. Initial experimental results demonstrated a lack of reactivity for phenyl and \u003cem\u003etert\u003c/em\u003e-butyl containing allenes \u003cstrong\u003e1a-1\u003c/strong\u003e and \u003cstrong\u003e1a-2\u003c/strong\u003e (entries 1 and 2), in contrast to the complete conversion of the structurally similar \u003cem\u003etert\u003c/em\u003e-butyldimethylsilyl (TBS) group-containing allene \u003cstrong\u003e1a-3\u003c/strong\u003e, which yielded alkynylated product \u003cstrong\u003e2a\u003c/strong\u003e with an excellent yield (entry 3). This finding indicates a dramatic activation of the \u0026alpha;-C(sp\u003csup\u003e2\u003c/sup\u003e)\u0026ndash;H bond by the silyl group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDensity functional theory (DFT) calculations revealed that the primary source of this unexpected reactivity is the weakening of the allenic C(sp\u003csup\u003e2\u003c/sup\u003e)-H bond. Compared to the non-silylated allenes (\u003cstrong\u003e1a-1\u003c/strong\u003e and \u003cstrong\u003e1a-2\u003c/strong\u003e), the corresponding silylated counterpart (\u003cstrong\u003e1a-3\u003c/strong\u003e) exhibits an unusually weak C(sp\u003csup\u003e2\u003c/sup\u003e)-H bond (79.3 kcal/mol) (Table 1, middle), which is even lower than that of the allylic C(sp\u003csup\u003e3\u003c/sup\u003e)-H bond (88 kcal/mol) and the C(sp\u003csup\u003e3\u003c/sup\u003e)-H bond adjacent to an oxygen atom, such as those in ethanol (95.9 kcal/mol) and tetrahydrofuran (THF) (92.1 kcal/mol). Furthermore, the calculated natural bond orbital (NBO) charges reveal that the sp\u0026sup2;-hybridized allenic C1 atom in \u003cstrong\u003e1a-3\u003c/strong\u003e, bearing a silyl group, exhibits a more negative charge relative to \u003cstrong\u003e1a-1\u0026nbsp;\u003c/strong\u003eand \u003cstrong\u003e1a-2\u003c/strong\u003e (Table 1, top). This can be attributed to the electron-donating effect of the silyl group, commonly referred to as the \u0026alpha;-silyl effect\u003csup\u003e51-53\u003c/sup\u003e. This suggests that the allenic C1 atom in \u003cstrong\u003e1a-3\u003c/strong\u003e is more susceptible to undergoing oxidation reactions or HAA processes, which rationalizes its excellent chemo- and regioselectivity. Additionally, more reaction parameters were investigated (Table 1). The use of FeCl\u003csub\u003e2\u003c/sub\u003e, iron \u003cem\u003emeso\u003c/em\u003e-tetraphenylporphyrin chloride [Fe(TPP)Cl], or CuOTf as substitutes for Fe(OTf)\u003csub\u003e2\u003c/sub\u003e resulted in lower yields (entries 4-6). When tetrahydrofuran (THF) was used as the solvent instead of ethyl acetate, a comparable yield was still obtained, even though THF has been previously reported to participate in hydrogen atom transfer reactions due to its relatively lower C-H bond dissociation energy. This suggests that the reaction can proceed even in the presence of such activated C-H bonds. Furthermore, it indicates that the C-H bond in allenes is more reactive than that in THF, and that the regioselective cleavage of non-activated sp\u003csup\u003e3\u003c/sup\u003e C-H bonds with higher BDEs is likely to proceed via an intramolecular hydrogen atom transfer (HAT) process, rather than an intermolecular one. Otherwise, THF, with its activated C-H bonds, would have adversely affected the reaction outcome. Additionally, control experiments indicated that the addition of iron salts is essential for the reaction to occur. Moreover, the reaction did not proceed under an inert nitrogen atmosphere, whereas in an oxygen atmosphere, a moderate yield was achieved. This demonstrates that the presence of oxygen in the air plays a crucial role in facilitating the reaction.\u003c/p\u003e\n\u003cp\u003eThe optimized reaction conditions for the regioselective cleavage of the C=C bond in allenylsilanes\u003csup\u003e54,55\u003c/sup\u003e, highly valuable building blocks in organic synthesis, were applied to examine the general applicability of our method (Fig. 2). Trisubstituted silylated allenes (\u003cstrong\u003e1a\u003c/strong\u003e\u0026ndash;\u003cstrong\u003e1g\u003c/strong\u003e) produced regioselective C(sp\u003csup\u003e3\u003c/sup\u003e)-H alkynylated ketones (\u003cstrong\u003e2a\u003c/strong\u003e\u0026ndash;\u003cstrong\u003e2g\u003c/strong\u003e), with different silyl groups (TBS, TIPS, TES, -Si(Me)\u003csub\u003e2\u003c/sub\u003ePh) having minimal impact on the yields. Notably, primary, secondary and tertiary C(sp\u003csup\u003e3\u003c/sup\u003e)-H bonds at the \u0026gamma;-position showed excellent compatibility with the protocol. Among these, the -TIPS group provided slightly higher yields, prompting an exploration of aliphatic allenes bearing the -TIPS group. Interestingly, the C(sp\u003csup\u003e3\u003c/sup\u003e)-H bond adjacent to an oxygen atom (\u003cstrong\u003e1h\u003c/strong\u003e) also underwent alkynylation with good regioselectivity, though the yield decreased, likely due to the oxidation propensity of the corresponding alkyl radical at the \u0026alpha;-position to the oxygen atom. The introduction of a methyl group at the \u003cem\u003e\u0026beta;\u003c/em\u003e-position (\u003cstrong\u003e1i\u003c/strong\u003e) or elongation of the aliphatic chain (\u003cstrong\u003e1j\u003c/strong\u003e) did not affect regioselectivity, providing the desired products (\u003cstrong\u003e2i\u003c/strong\u003e and \u003cstrong\u003e2j\u003c/strong\u003e) in high yields. Besides linear C-H bonds, alkynylation also occurred on cyclohexane ring (\u003cstrong\u003e2k\u003c/strong\u003e), while the olefin moiety, typically prone to radical reactions, remained intact (\u003cstrong\u003e2l\u003c/strong\u003e), demonstrating chemoselectivity between the olefin and allene groups. Substrates bearing elongated aliphatic chains (\u003cstrong\u003e2m\u003c/strong\u003e, \u003cstrong\u003e2n\u003c/strong\u003e) at the opposite side of \u003cem\u003egem\u003c/em\u003e-dialkyl-substituted allenes, as well as those containing cyclopropane or cyclobutane groups (\u003cstrong\u003e2o\u003c/strong\u003e, \u003cstrong\u003e2p\u003c/strong\u003e), demonstrated compatibility with the reaction conditions. These results highlight the versatility of the methodology in accommodating various sterically hindered and cyclic systems, further broadening the substrate scope of this protocol. However, phenyl allenes substituted with a TIPS group (\u003cstrong\u003e1q\u003c/strong\u003e) gave trace product due to alkyl side chain cleavage, whereas phenyldimethylsilyl allene (\u003cstrong\u003e1r\u003c/strong\u003e) provided higher yields, also confirming the superior migratory aptitude of the alkynyl group compared to the phenyl group. Both electron-donating and electron-withdrawing substituents afforded the desired alkynylated products in synthetically useful yields (\u003cstrong\u003e2s\u003c/strong\u003e\u0026ndash;\u003cstrong\u003e2ab\u003c/strong\u003e), and halides, particularly bromides (\u003cstrong\u003e2v\u003c/strong\u003e, \u003cstrong\u003e2ab\u003c/strong\u003e), remained unaffected, creating opportunities for further product modification via cross-coupling reactions.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFurthermore, naphthyl-substituted allene (\u003cstrong\u003e1ac\u003c/strong\u003e) was well-tolerated, yielding the corresponding product (\u003cstrong\u003e2ac\u003c/strong\u003e) in excellent yields. To probe the compatibility of disubstituted allene (\u003cstrong\u003e1ad\u003c/strong\u003e) with two allenic C(sp\u003csup\u003e2\u003c/sup\u003e)-H bonds, which could compete during the HAA process, the reaction proceeded smoothly to form the aldehyde product (\u003cstrong\u003e2ad\u003c/strong\u003e), leaving the low BDE aldehyde sp\u003csup\u003e2\u003c/sup\u003e C-H bond (89 kcal/mol) intact.\u003c/p\u003e\n\u003cp\u003eThe scalability and applicability of this method were demonstrated through the successful large-scale preparation of \u003cstrong\u003e2c\u003c/strong\u003e, which proceeded smoothly and yielded results comparable to those of smaller-scale reactions, affirming the practicality of the protocol (Fig. 3, top). Furthermore, the products exhibit versatility in their transformations into other valuable compounds (Fig. 3). For instance,\u0026nbsp;the ketone functionality serves as a useful building block, which can be efficiently reduced to alcohol (\u003cstrong\u003e3\u003c/strong\u003e) using NaBH\u003csub\u003e4\u003c/sub\u003e, yielding excellent results, or converted into an alkene (\u003cstrong\u003e4\u003c/strong\u003e) via a sequential Wittig reaction. Additionally, the TIPS group in alkyne (\u003cstrong\u003e2c\u003c/strong\u003e) can be easily removed in the presence of tetrabutylammonium fluoride (TBAF), facilitating a subsequent click reaction with BnN\u003csub\u003e3\u003c/sub\u003e to afford \u003cem\u003eN\u003c/em\u003e-heteroarene (\u003cstrong\u003e5\u003c/strong\u003e). Moreover, a Pd-catalyzed cross-\u0026nbsp;coupling reaction between silylated alkyne (\u003cstrong\u003e2c\u003c/strong\u003e) and 4-bromoiodobenzene provides an aryl alkyne (\u003cstrong\u003e6\u003c/strong\u003e). The alkynyl group in \u003cstrong\u003e2c\u003c/strong\u003e, being a key synthetic core, can also be stereoselectively transformed into (\u003cem\u003eE\u003c/em\u003e)-alkene (\u003cstrong\u003e7\u003c/strong\u003e), demonstrating the flexibility and synthetic utility of the methodology across multiple chemical transformations.\u003c/p\u003e\n\u003cp\u003eNext, we focused on exploring the reaction mechanism. After stirring TIPS-substituted allene \u003cstrong\u003e1c\u003c/strong\u003e under air and solvent-free conditions for 1.5 hours, the addition of 1 mL acetonitrile yielded a colorless solution (Fig. 4a, top). However, upon the addition of 1.0 equivalent of KI, the mixture turned yellow, suggesting the formation of oxidizing species, such as peroxides, during the reaction. These species oxidized KI to iodine, leading to the observed color change. Crucially, propargylic peroxide (\u003cstrong\u003e8\u003c/strong\u003e) was isolated in excellent yield with complete conversion. The subsequent reaction of \u003cstrong\u003e8\u003c/strong\u003e, catalyzed by Fe(OTf)₂, produced the desired ketone product (\u003cstrong\u003e2b\u003c/strong\u003e) in excellent yield (Fig. 4a, bottom). In contrast, no peroxides were detected for phenyl- or \u003cem\u003etert\u003c/em\u003e-butyl-substituted allene \u003cstrong\u003e1a-1\u003c/strong\u003e or \u003cstrong\u003e1a-2\u003c/strong\u003e under the same conditions (Fig. 4b), indicating that the silyl group is essential for this autooxidation process. Since we hypothesized the involvement of allenic or propargylic radicals, we added TEMPO, a well-known radical scavenger, to the reaction with starting material \u003cstrong\u003e1c\u003c/strong\u003e. As expected, no peroxide intermediate (\u003cstrong\u003e8\u003c/strong\u003e) was detected; instead, the TEMPO-trapped product (\u003cstrong\u003e9\u003c/strong\u003e), resulting from the interception of a propargylic radical, was identified through HRMS analysis (Fig. 4c, top), indicating that the reaction probably proceeded through radical mechanism. Moreover, after the autooxidation of \u003cstrong\u003e1c\u003c/strong\u003e, when Fe(OTf)\u003csub\u003e2\u003c/sub\u003e, solvent, and TEMPO were added, only 75% of peroxide (\u003cstrong\u003e8\u003c/strong\u003e) was isolated, with no sign of the migrated product (\u003cstrong\u003e2c\u003c/strong\u003e) (Fig. 4c, bottom). In crossover experiments involving \u003cstrong\u003e1a\u003c/strong\u003e and \u003cstrong\u003e1m\u003c/strong\u003e under standard conditions, the absence of cross-coupled products (\u003cstrong\u003e2a\u0026rsquo;\u003c/strong\u003e and \u003cstrong\u003e2m\u0026rsquo;\u003c/strong\u003e) supported the hypothesis that the reaction proceeds via an intramolecular alkynyl group translocation mechanism (Fig. 4d).\u003c/p\u003e\n\u003cp\u003eBased on our mechanistic studies and previous reports, we proposed a plausible pathway for the cleavage of allenic carbon-carbon double bonds, as outlined in Fig. 5. Initially, the allene substrate undergoes an autooxidation process in the presence of molecular oxygen, which involves the cleavage of the allenic C(sp\u0026sup2;)-H bond and a resonance isomerization between the allenic radical (\u003cstrong\u003eI\u003c/strong\u003e) and propargylic radical (\u003cstrong\u003eII\u003c/strong\u003e). This step results in the formation of a hydroperoxyl radical. The hydroperoxyl radical couples with the propargylic radical to generate a propargylic peroxide (\u003cstrong\u003eIII\u003c/strong\u003e). Next, single-electron reduction of this peroxide by Fe(II) leads to the cleavage of the peroxide bond, producing an alkoxy radical (\u003cstrong\u003eIV\u003c/strong\u003e). The alkoxy radical then initiates an intramolecular hydrogen atom transfer (HAT) process, forming a remote alkyl radical (\u003cstrong\u003eV\u003c/strong\u003e)\u003csup\u003e56-63\u003c/sup\u003e. This alkyl radical undergoes intramolecular attack on the adjacent alkynyl group, yielding a five-membered cyclic vinyl radical (\u003cstrong\u003eVI\u003c/strong\u003e). Finally, the resulting ketyl radical (\u003cstrong\u003eVII\u003c/strong\u003e), generated from the ring-opening, is oxidized by Fe(III) and deprotonated, resulting in the formation of the alkynyl ketone product, with Fe(II) being regenerated to complete the catalytic cycle. This mechanism highlights the role of both autooxidation and iron-catalyzed radical processes in achieving selective bond cleavage, further supported by the influence of silyl group in promoting key transformations within the catalytic cycle.\u003c/p\u003e\n\u003cp\u003eIn summary, this study presents an efficient and regioselective method for the cleavage of allenic C=C bonds via a radical-mediated process. Mechanistic investigations, coupled with experimental validation, underscore the pivotal role of the silyl group in driving the autooxidation process by utilizing air as the oxidant and facilitating single-electron transfer mediated by cost-effective iron salts. This process enables key transformations, including allenic C-H bond cleavage and alkynyl group migration. The method\u0026rsquo;s scalability, broad substrate scope, and ability to selectively functionalize C(sp\u0026sup3;)-H bonds highlight its practical relevance. Additionally, the facile conversion of the reaction products into valuable intermediates\u0026mdash;such as alkynes, alkenes, and heterocycles\u0026mdash;demonstrates the synthetic versatility and applicability of this approach in organic synthesis. This work not only provides new insights into allene chemistry but also opens up new avenues for further exploration of radical-mediated C-C bond cleavage and C-H functionalization strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files. Extra data are available from the corresponding author upon request. Supplementary tables and figures, experimental procedures, characterization, and spectra of all materials, are included in the Supplementary Information.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful for the financial support from the National Natural Science Foundation of China (22001185), the Natural Science Foundation of Jiangsu Province (BK20200852), the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (23KJA150007). We thank Prof. Hao Yu from Fudan University for helpful discussions.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003e Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, 199 Ren-Ai Road, Suzhou, Jiangsu 215123, China\u003c/p\u003e\n\u003cp\u003eE-mail: [email protected]\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u0026nbsp;\u003c/sup\u003eTandemAI, Building\u0026nbsp;6,\u0026nbsp;No.\u0026nbsp;111\u0026nbsp;Wusongjiang Road,\u0026nbsp;Wuzhong\u0026nbsp;District,\u0026nbsp;Suzhou, Jiangsu 215124, China\u003c/p\u003e\n\u003cp\u003eE-mail: [email protected]\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eZ.W., Q.Z., and H.L. performed and analyzed the experiments. Z.M. participated in the early development of the project. X.Q., S.J., and J.Z. prepared part of starting materials. X.W. conceived and designed the project. C.Z. revised the manuscript. All authors prepared this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGrubbs, R. H. \u0026amp; Chang, S. Recent advances in olefin metathesis and its application in organic synthesis. \u003cem\u003eTetrahedron\u003c/em\u003e \u003cstrong\u003e54\u003c/strong\u003e, 4413-4450 (1998). \u003c/li\u003e\n\u003cli\u003eMcDonald, R. I., Liu, G. \u0026amp; Stahl, S. S. Palladium(II)-catalyzed alkene functionalization via nucleopalladation: stereochemical pathways and enantioselective catalytic applications. \u003cem\u003eChem. 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Metal-free alcohol-directed regioselective heteroarylation of remote unactivated C(sp\u003csup\u003e3\u003c/sup\u003e)-H bonds. \u003cem\u003eNat. Commun.\u003c/em\u003e \u003cstrong\u003e9\u003c/strong\u003e, 3343 (2018).\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Table 1","content":"\u003cp\u003eTable 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"nature-portfolio","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"","title":"Nature Portfolio","twitterHandle":"","acdcEnabled":false,"dfaEnabled":false,"editorialSystem":"ejp","reportingPortfolio":"","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5543027/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5543027/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eWhile the oxidative cleavage of olefins is well established, the radical-mediated, chemo- and regioselective cleavages of allene C(sp)–C(sp\u003csup\u003e2\u003c/sup\u003e) and C(sp\u003csup\u003e3\u003c/sup\u003e)–C(sp\u003csup\u003e2\u003c/sup\u003e) bonds remain unresolved challenges in synthetic chemistry. These challenges primarily stem from the high reactivity of the unique twisted orthogonal π-systems and the regioselectivity issues associated with adjacent C = C double bonds. Herein, we present base metal-catalyzed cleavage of allenic C(sp)–C(sp\u003csup\u003e2\u003c/sup\u003e) double bonds and C(sp\u003csup\u003e3\u003c/sup\u003e)–C(sp\u003csup\u003e2\u003c/sup\u003e) single bonds utilizing air as an oxidant. These transformations, initiated by hydrogen atom abstraction (HAA) from the allenic C(sp²)-H bonds, lead to the formation of a diverse range of remotely functionalized ketones, alkylated heteroaryls, alkylated nitriles, and deuterated products, all with remarkable site selectivity. In this strategy, the α-silyl effect plays a key role in activating allenic C(sp\u003csup\u003e2\u003c/sup\u003e)-H bond thus initiating the HAA from allenes and achieving the desired regioselectivity.\u003c/p\u003e","manuscriptTitle":"Iron-Catalyzed Cleavage of Allene C=C Double Bond","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-08 12:34:44","doi":"10.21203/rs.3.rs-5543027/v1","editorialEvents":[],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"nature-communications","isNatureJournal":true,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"NCOMMS","sideBox":"Learn more about [Nature Communications](http://www.nature.com/ncomms/)","snPcode":"","submissionUrl":"https://mts-ncomms.nature.com/","title":"Nature Communications","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature Communications","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"fbf8b6ad-ecda-453c-b010-055230eed3ea","owner":[],"postedDate":"December 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":41134236,"name":"Physical sciences/Chemistry/Organic chemistry/Synthetic chemistry methodology"},{"id":41134237,"name":"Physical sciences/Chemistry/Catalysis/Homogeneous catalysis"}],"tags":[],"updatedAt":"2025-12-08T12:34:44+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-08 12:34:44","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5543027","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5543027","identity":"rs-5543027","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}