Copper-catalyzed radical aminocyanation of allenes

Abstract

The aminocyanation of allenes remains an uncharted territory in organic synthesis, despite the significant progress in aminocyanation of other unsaturated hydrocarbons. Current amination strategies for allenes suffer from limitations such as stringent pre-functionalization requirements, costly catalysts and narrow substrate scope. Herein, we report a copper-catalyzed three-component aminocyanation of allenes using N-halobenzenesulfonimides and trimethylsilyl cyanide, achieving simultaneous installation of amine and cyano groups with high regioselectivity. The copper catalyst synergistically facilitates N–X bond homolysis to generate nitrogen-centered radicals and activates cyanide sources, while enabling efficient reaction progression by generating coordination intermediates and radical cations. This work establishes a novel copper-catalyzed strategy for the aminocyanation of allenes, which overcomes key limitations of existing strategies by achieving broad substrate generality without pre-functionalization and offering cost-effective practicality through a copper-catalyzed radical cascade method.

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The difunctionalization of unsaturated hydrocarbons represents a powerful synthetic paradigm for rapidly constructing complex molecules and synthesizing high-value organic compounds.¹ Notably, amine and cyano groups are both privileged structural motifs, ubiquitously embedded in bioactive molecules and functional materials. This renders the development of efficient strategies for the concurrent installation of these functional groups a subject of profound scientific and practical significance.² In recent years, significant advancements have been made in the aminocyanation of unsaturated hydrocarbons via three primary strategies: (1) transition-metal-catalyzed radical coupling/cross-coupling protocols;³ (2) Lewis acid-mediated nucleophilic addition pathways;⁴ and (3) redox-mediated radical addition systems enabled by photo/metal synergistic catalysis or electrocatalysis (Scheme 1a).⁵ These methodologies have successfully achieved aminocyanation across various π-systems including alkenes, alkynes, and 1,3-enynes. Notably, Liu's group accomplished a copper-catalyzed aminocyanation of allenes using N-((3S,5S,7S)-adamantan-1-yl)-N-fluoro-3,5-bis(trifluoromethyl)benzenesulfonamide as the amination agent in 2024.⁶ However, such studies remain limited to isolated examples. This scarcity is likely impeded by three persistent challenges: (1) the cumulative diene structure of allenes introduces three potential reactive sites, complicating regioselectivity control; (2) the heightened reactivity of cumulative double bonds promotes instability in transient radical or metal-complex intermediates during transformation, thereby impeding the formation of the desired products; and (3) the applicability of established aminocyanation systems for allene substrates remains ambiguous. Consequently, the development of a regioselective aminocyanation method specifically tailored for allenes emerges as a critical objective in modern organic synthesis.

Scheme 1 The aminocyanation and amination of unsaturated hydrocarbons.

Allenes, distinguished by their unique 1,2-diene architecture, have emerged as privileged building blocks in organic synthesis due to their exceptional reactivity and structural flexibility, enabling the efficient construction of complex multifunctional molecules through multicomponent tandem reactions.⁷ The amination of allenes is particularly intriguing and has evolved into a vibrant research frontier. Current methodologies and their characteristics can be categorized as follows: (1) transition metal-catalyzed intramolecular amination/cyclization,⁸ while advantageous for atom-economical synthesis of N-heterocycles, suffers from laborious synthesis of substituted allene substrates and challenges in pre-functionalization; (2) Brønsted acid-catalyzed nucleophilic amination,⁹ predominantly limited to intramolecular systems due to diminished nucleophilicity of protonated amines; (3) metal-mediated two-component intermolecular amination,¹⁰ achieving superior regio- and stereo-selectivity via coordination-stabilized intermediates for allylamine derivatives synthesis, yet constrained by expensive catalyst systems and stringent ligand dependency; and (4) hypervalent iodine-mediated oxidative amination,¹¹ which circumvents the need for heavy metal catalysts under mild conditions but faces substrate scope limitations imposed by strong oxidants and limited diversity of applicable amines (Scheme 1b). Recent advances in radical tandem amination of allenes have unveiled two predominant mechanistic paradigms: radical addition-cyclization and radical cross-coupling.¹² Notably, Hu's group achieved a breakthrough in 2024 through visible light/palladium synergistic catalysis, realizing three-component amination of allenes/diazoesters/amines via radical-polar crossover manifolds (Scheme 1c).¹³ Nevertheless, critical challenges persist: electronic and steric effects in pre-functionalized allenes often impede radical attack pathways. Furthermore, polarity mismatches between reaction partners frequently derail nucleophilic addition pathways. In conclusion, there is an urgent need to develop an economical and mild method for the amination of allenes that exhibits wide applicability.

Hence, we herein report a copper-catalyzed, highly regioselective three-component aminocyanation of allenes, employing N-halo-N-(phenylsulfonyl)benzenesulfonamides as aminating agents and cyanide reagents (such as trimethylsilyl cyanide, TMSCN) as the cyanide source. This transformation is initiated through copper-mediated homolytic cleavage of the N–X bond in N-halo-N-(phenylsulfonyl)benzenesulfonamides, generating nitrogen-centered radicals that selectively attack the central carbon of allenes to form allylic radical intermediates. Concurrently, the copper catalyst facilitates the activation of TMSCN to generate a Cu(II)–CN complex. The allylic radical intermediate then undergoes either rapid recombination with the Cu(II)–CN complex or further oxidation to form an allylic cation, which subsequently undergoes nucleophilic combination with the cyanide anion, thereby enabling a highly efficient and controllable cascade process for simultaneous installation of amine and cyano groups (Scheme 1d). Notably, the copper catalyst exhibits dual functionality in this strategy by simultaneously initiating both nitrogen-centered radical formation and the generation of Cu(II)–X species. Crucially, the transient Cu(II)–CN complex promotes the transformation through two mechanistic pathways: (1) rapid coordination with the allylic radical intermediate or (2) oxidation of the allylic radical to a carbocation, enabling subsequent nucleophilic attack by CN⁻. This dual-functional system effectively addresses the persistent challenges in multi-component radical cascades, including poor regiocontrol, competing side reactions, and the instability of reactive intermediates. The strategic advantages of this methodology are manifold: (1) it reports a novel copper-catalyzed radical cascade for aminocyanation of allenes; (2) the cost-effective copper catalyst plays a pivotal role in achieving exceptional site-selectivity; (3) utilization of commercially available and stable reagents as both amine and cyanide sources ensures practical accessibility; and (4) the reaction exhibits broad substrate generality without requiring pre-functionalization, demonstrating good compatibility with diverse substituted allene derivatives.

Our exploration of the aminocyanation of allenes began with (propa-1,2-dien-1-yloxy)-benzene (1a, 0.2 mmol) as the model substrate and commercially available N-fluorobenzenesulfonimide (NFSI, 2a, 1.4 equiv.) and TMSCN (3a, 1.4 equiv.) as the amino and cyanide source, respectively (Table 1). We commenced reaction condition optimization using CuCl (20 mol%) as the catalyst and 1,10-phenanthroline (1,10-Phen, 30 mol%) as the ligand, with dichloromethane (DCM) as the solvent at 70 °C for 12 h. To our delight, the desired aminocyanation product 4a was facilely obtained in 81% yield (entry 1). Its molecular architecture and E/Z configuration were unequivocally confirmed by X-ray crystallography (CCDC 2431861). Under copper/ligand-free conditions, the yield of the target product was trace, demonstrating the critical role of the catalyst (entry 2). To further enhance the yield of product 4a, we first screened a series of copper catalysts. The results indicated that among the tested Cu(I) and Cu(II), CuCl proved to be the most effective one (entries 3–10). Notably, when the CuCl loading was adjusted, either increased to 30 mol% or decreased to 10 mol%, a concomitant reduction in the yield of 4a was observed in both instances (entries 11 and 12). Subsequently, several ligands, including 2,2′-bipyridine, 4,4′-di-tert-butyl-2,2′-bipyridine, 2,2′:6′,2′′-terpyridine, and triphenylphosphine, were explored. However, no enhancement in the yield of 4a was observed (entries 13–16). Notably, phosphine ligands exhibited inferior efficacy compared to nitrogen-based ligands, while tridentate nitrogen ligands showed lower performance relative to their bidentate analogues. During the solvent optimization process, it was observed that solvents such as 1,2-dichloroethane (DCE) and CHCl₃ exhibited inferior performance compared to DCM (entries 17 and 18). Additionally, it was found that lowering the reaction temperature moderately decreased the yield of the target product (entries 19–21). Finally, scale-up experiments using 1a as the model substrate at 1.0 mmol and 10.0 mmol scales afforded product 4a in 59% and 51% yield, respectively, when the reaction time was extended to 48 h and 96 h (entries 22 and 23).

Table 1 Optimization of the reaction conditions^a

Entry	[Cu] (mol%)	[L]	Solvent	Temp. (°C)	Yield^b (%)
a Unless otherwise specified, the reactions were performed in the presence of 1a (0.2 mmol), 2a (1.4 equiv.), 3a (1.4 equiv.), [Cu] (20 mol%), [L] (30 mol%) and solvent (2.0 mL) for 12 h. The E/Z of 4a was >20 : 1. b Isolated yields are given based on 1a. c CuCl (10 mol%). d CuCl (30 mol%). e 1a (1.0 mmol) for 48 h. f 1a (10.0 mmol) for 96 h.
1	CuCl	L1	DCM	70	81
2	—	—	DCM	70	Trace
3	CuBr	L1	DCM	70	72
4	CuI	L1	DCM	70	65
5	Cu2O	L1	DCM	70	76
6	CuCl2	L1	DCM	70	37
7	CuBr2	L1	DCM	70	33
8	CuO	L1	DCM	70	39
9	Cu(OAc)2	L1	DCM	70	43
10	Cu(OTf)2	L1	DCM	70	21
11^c	CuCl	L1	DCM	70	61
12^d	CuCl	L1	DCM	70	46
13	CuCl	L2	DCM	70	74
14	CuCl	L3	DCM	70	76
15	CuCl	L4	DCM	70	64
16	CuCl	L5	DCM	70	32
17	CuCl	L1	DCE	70	8
18	CuCl	L1	CHCl3	70	43
19	CuCl	L1	DCM	30	6
20	CuCl	L1	DCM	50	11
21	CuCl	L1	DCM	60	69
22^e	CuCl	L1	DCM	70	59
23^f	CuCl	L1	DCM	70	51

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With the optimized reaction conditions in hand, we turned our attention to the generality of this aminocyanation (Table 2). Throughout this study, NFSI was hypothesized to act as the radical source to provide ˙N(SO₂Ph)₂ for the subsequent transformations.¹⁴ Based on this hypothesis, initial attempts were made to substitute NFSI with N-chloro-N-(phenylsulfonyl)benzenesulfonamide (2b) and N-bromo-N-(phenylsulfonyl)benzenesulfonamide (2c), whereupon the reaction was also found to proceed. Likewise, using 4-chloro-N-fluoro-N-(phenylsulfonyl)benzenesulfonamide and 4-bromo-N-fluoro-N-(phenylsulfonyl)benzenesulfonamide as the amination agents afforded products 4b and 4c smoothly. Subsequently, guided by previous studies,¹⁵ systematic replacement of the cyanide source was conducted. These investigations revealed that Zn(CN)₂, CuCN, K₄[Fe(CN)₆], and K₃[Co(CN)₆] were also capable of affording product 4a in 19–41% yields.

Table 2 Various amino and cyanide sources^a

a Unless otherwise specified, the reactions were performed in the presence of 1a (0.2 mmol), 2 (1.4 equiv.), 3 (1.4 equiv.), CuCl (20 mol%), 1,10-Phen (30 mol%) and DCM (2.0 mL) at 70 °C for 12 h.

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To further explore the reaction scope, the substrate scope of allenes was systematically investigated (Table 3). When R₁ = ArO, the introduction of diverse substituents on the aromatic ring consistently afforded the desired aminocyanation products 4d–4i with high yields and moderate to good stereoselectivity. Notably, para-substituted electron-donating groups (–Me, –t-Bu, –OMe) exhibited significantly better reaction efficiency compared to para-substituted electron-withdrawing groups (–Cl, –Br, –CF₃). This observed electronic effect may arise from improved stabilization of the allylic radical intermediate through resonance interactions facilitated by electron-rich aryl systems. Additionally, when the phenyl group was replaced with a naphthyl group, the reaction exhibited enhanced stereoselectivity (4j). This enhanced stereoselectivity might be ascribed to the rigid structure of the naphthyl ring, which restricts the configurations of the radical intermediate through steric hindrance effects. Subsequently, the adaptability of the aminocyanation was investigated for allene substrates with R₁ = Ar. The results indicated that while the corresponding products could still be obtained in high yields (4k–4r), a decrease in stereoselectivity was observed. Furthermore, analogous to the R₁ = ArO cases, para-substituted electron-donating groups (–Me, –t-Bu, –OMe) afforded higher yields of aminocyanation products compared to para-substituted electron-withdrawing groups (–Cl, –Br, –CF₃, –CO₂Me).

Table 3 Reaction scope of allenes^a

a Unless otherwise specified, the reactions were performed in the presence of 1 (0.2 mmol), 2a (1.4 equiv.), 3a (1.4 equiv.), CuCl (20 mol%), 1,10-Phen (30 mol%) and DCM (2.0 mL) at 70 °C for 12 h.

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Moreover, when R₁ = ArS or ArNTs, the corresponding aminocyanation products could also be procured in moderate yields (4s–4u), further expanding the substrate versatility of this reaction system. Even trisubstituted allenes with enhanced steric hindrance underwent aminocyanation to deliver products 4v and 4w, demonstrating the reaction's tolerance toward congested substrates. However, it is noteworthy that a representative 1,1-disubstituted allene proved unreactive under the standard conditions, and only a trace amount of the desired product 4x was detected.

To gain some insights into the reaction mechanism, a series of experiments were carried out (Scheme 2). When 2.0 equiv. of radical scavengers such as 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO), 1,1-diphenylethylene or 2,6-di-tert-butyl-4-methylphenol (BHT) were introduced into the standard reaction, the formation of the aminocyanation product 4a was significantly suppressed (Scheme 2a). Notably, both nitrogen-centered radicals (5a, 7a, and 9a) and allyl radicals (6a and 8a) were successfully trapped by these radical inhibitors. These experimental observations strongly suggest that the reaction proceeds through a radical-mediated pathway, as evidenced by the suppression of product formation and the high-resolution mass spectrometry (HRMS) results. Furthermore, to provide more compelling evidence for the hypothesized reaction mechanism, an intermediate trapping experiment was conducted under standard conditions in the absence of the substrate allene 1a (Scheme 2b). At this stage, TMSCN was activated to form the Cu(II)–CN complex, which subsequently coordinated with nitrogen-centered radicals. Compounds 10a and 11a were successfully detected by HRMS. Thereafter, building upon mechanistic predictions and prior studies on related aminocyanations,^3a–3b,16 we conducted a copper complex detection experiment for the template reaction under standard conditions (Scheme 2c). Notably, potential copper complexes (12a and 13a) generated during the reaction process were successfully identified via HRMS (ESI). It was hypothesized that complex 12a originated from a similar intermediate through the loss of Cl and F substituents or Cl and CN groups, while complex 13a resulted from the elimination of the CN group from an analogous copper complex. This critical observation substantiates the hypothesized involvement of copper intermediates in the catalysis, thereby providing additional clarity regarding the potential mechanistic pathway of the overall reaction. Finally, a cationic trapping experiment was performed by introducing 10 equiv. of MeOH under standard conditions, leading to the successful detection of compound 14avia HRMS (Scheme 2d). This result confirms the presence of allyl cations during the reaction process. The detection of these complexes aligns coherently with the previous radical-mediated, and coordination/cationic intermediate processes. This offers a comprehensive framework for understanding the stepwise progression of the reaction.

Scheme 2 Mechanistic investigations.

Based on the aforementioned experimental results and previous literature,^3a,b,17–20 a plausible mechanism for the aminocyanation of allenes is proposed (Scheme 3). Initially, CuCl undergoes oxidation by NFSI to generate the Cu(III)–N species B. This species subsequently undergoes rapid redox isomerization to form the Cu(II) species C and the nitrogen-centered radical D.¹⁷ The radical D then attacks the central carbon of the allene 1a, leading to the formation of the allylic radical E.¹⁸ Subsequently, two parallel pathways are proposed. In the first pathway, the added TMSCN is activated by species C to form the Cu(II)–CN complex F. This intermediate rapidly coordinates with the allylic radical E, forming the key Cu(III) intermediate G.^3a–3b The desired aminocyanation product 4a is then obtained via reductive elimination from intermediate G. Alternatively, in the second pathway, the allylic radical E undergoes further oxidation by the Cu(II)–CN species F to generate the allylic cation H.¹⁹ Subsequent combination of this cationic intermediate with the cyanide anion ultimately yields the desired product 4a as well.²⁰

Scheme 3 Plausible reaction mechanism.

Conclusions

In conclusion, we have developed a novel copper-catalyzed strategy for aminocyanation of allenes through a copper-catalyzed three-component strategy, which simultaneously installs amine and cyano groups with high efficiency via a three-component reaction. In this method, the copper catalyst induces the generation of nitrogen-centered radicals and activates TMSCN, driving the aminocyanation process via dual pathways: radical-coordination complexation and nucleophilic attack of carbocations. Through rational and sophisticated design, this protocol overcomes the limitations of existing approaches, such as laborious substrate pre-functionalization, polarity mismatches between reactants, and instability of intermediates, achieving precise regiocontrol. The broad substrate generality and cost-effectiveness of this reaction provide a novel platform for the difunctionalization of allenes.

Conflicts of interest

There are no conflicts to declare.

Data availability

The data supporting this article have been included as part of the supplementary information (SI). Supplementary information is available. See DOI: https://doi.org/10.1039/d5qo01254f.

CCDC 2431861 contains the supplementary crystallographic data for this paper.²¹

Acknowledgements

We thank the Cooperation Project with Tobacco Research Institute of Hunan Province (No. H2024000422), the Education Foundation of Zhejiang Province (No. Y202456052), the Mechanics Interdisciplinary Fund for Outstanding Young Scholars of Ningbo University (No. ZX2025000404), and the Health Fund of Translational Biomedicine (No. H2024000282) for financial support.

References

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9. For selected papers, see: (a) T. R. Rradhan, A. O. Farah, K. Sagar, H. R. Wise, M. Srimannarayana, P. H.-Y. Cheong and J. K. Park, Acetate Assistance in Regioselective Hydroamination of Allenamides: A Combined Experimental and Density Functional Theory Study, J. Org. Chem., 2024, 89, 5927–5940; (b) A. Quintavalla, D. Carboni, A. Brusa and M. Lombardo, Selective Hydrofunctionalization of N-Allenyl Derivatives with Heteronucleophiles Catalyzed by Brønsted Acids, J. Org. Chem., 2024, 89, 2320–2342; (c) J.-S. Lin, T.-T. Li, G.-Y. Jiao, Q.-S. Gu, J.-T. Cheng, L. Lv and X.-Y. Liu, Chiral Brønsted Acid Catalyzed Dynamic Kinetic Asymmetric Hydroamination of Racemic Allenes and Asymmetric Hydroamination of Dienes, Angew. Chem., Int. Ed., 2019, 58, 7092–7096; (d) I. Dion and A. M. Beauchemin, Asymmetric Brønsted Acid Catalysis Enabling Hydroaminations of Dienes and Allenes, Angew. Chem., Int. Ed., 2011, 50, 8233–8235; (e) N. D. Shapiro, V. Rauniyar, G. L. Hamilton, J. Wu and F. D. Toste, Asymmetric Additions to Dienes Catalysed by a Dithiophosphoric Acid, Nature, 2011, 470, 245–249.
10. For selected papers, see: (a) M. Hourtoule and L. Miesch, Silver-Catalyzed Domino Reaction of CF₃-Substituted N-Allenamides with Primary Amines for the Construction of 2-Amido-5-fluoropyrroles, Org. Lett., 2023, 25, 1727–1731; (b) Z.-R. Yang, B. Zhang, Y.-J. Long and M. Shi, Palladium-catalyzed Hydroamination of Vinylidenecyclopropane-Diester with Pyrroles and Indoles: an Approach to Azaaromatic Vinylcyclopropanes, Chem. Commun., 2022, 58, 9926–9929; (c) J. M. Alonso and M. P. Muñoz, Platinum and Gold Catalysis: à la Carte Hydroamination of Terminal Activated Allenes with Azoles, Org. Lett., 2019, 21, 7639–7644; (d) F. Panahi and B. Breit, Rhodium–Catalyzed Asymmetric Macrocyclization towards Crown Ethers Using Hydroamination of Bis(allenes), Angew. Chem., Int. Ed., 2024, 63, e202317981; (e) L. A. Perego, R. Blieck, A. Groué, F. Monnier, M. Taillefer, I. Ciofini and L. Grimaud, Copper-Catalyzed Hydroamination of Allenes: from Mechanistic Understanding to Methodology Development, ACS Catal., 2017, 7, 4253–4264; (f) I. Bernar, B. Fiser, D. Blanco-Ania, E. Gómez-Bengoa and F. P. J. T. Rutjes, Pd-Catalyzed Hydroamination of Alkoxyallenes with Azole Heterocycles: Examples and Mechanistic Proposal, Org. Lett., 2017, 19, 4211–4214.
11. (a) R. M. Moriarty, T. E. Hopkins, R. K. Vaid, B. K. Vaid and S. G. Levy, Hypervalent Iodine Oxidation of Allenes: Synthesis of 3-Acetoxy-3-alkoxypropynes, 2-Alkoxy-3-tosyloxypropanals and Phenyl-Substituted Propenals and Propenones, Synthesis, 1992, 847–849; (b) N. Purkait, S. Okumura, J. A. Souto and K. Muñiz, Hypervalent Iodine Mediated Oxidative Amination of Allenes, Org. Lett., 2014, 16, 4750–4753.
12. For selected papers, see: (a) E. Azzi, G. Ghigo, L. Sarasino, S. Parisotto, R. Moro, P. Renzi and A. Deagostino, Photoinduced Chloroamination Cyclization Cascade with N-Chlorosuccinimide: From N-(Allenyl)sulfonylamides to 2-(1-Chlorovinyl)pyrrolidines, J. Org. Chem., 2023, 88, 6420–6433; (b) R. M. Ward and J. M. Schomaker, Allene Trifunctionalization via Amidyl Radical Cyclization and TEMPO Trapping, J. Org. Chem., 2021, 86, 8891–8899; (c) H. Xu, T. Han, X. Luo and W.-P. Deng, Construction of 3-Azabicyclo[3.1.0]hexane Backbone by the Reaction of Allenes with Allylamines via, Tandem Michael Addition and Copper-Mediated Oxidative Carbanion Cyclization, Chin. J. Chem., 2021, 39, 666–670; (d) H. Xie, H. Chen, U. Dutta, Y. Lan and B. Breit, Photochemical Asymmetric Palladium-Catalyzed Allylation Reaction: Expeditious Entry to Chiral 1,2-Amino Alcohols and 1,2-Diamines, ACS Catal., 2024, 14, 13352–13361; (e) Y. Guo, C. Empel, C. Pei, H. Fang, S. Jana and R. Koeanigs, Intermolecular Amination of Allenes via 2-Fold Photocatalytic Nitrene Transfer Reactions, Chem Catal., 2022, 2, 2012–2023; (f) O. K. Koleoso, M. Turner, F. Plasser and M. C. Kimber, A Complementary Approach to Conjugated N-acyliminium Formation through Photoredox-Catalyzed Intermolecular Radical Addition to Allenamides and Allencarbamates, Beilstein J. Org. Chem., 2020, 16, 1983–1990.
13. G.-X. Liu, X.-T. Jie, G.-J. Niu, L.-S. Yang, X.-L. Li, J. Luo and W.-H. Hu, Palladium-Catalyzed Three-Component Radical-Polar Crossover Carboamination of 1,3-Dienes or Allenes with Diazo Esters and Amines, Beilstein J. Org. Chem., 2024, 20, 661–671.
14. For selected papers, see: (a) T. Qin, G. Lv, Q. Meng, G. Zhang, T. Xiong and Q. Zhang, Cobalt–Catalyzed Radical Hydroamination of Alkenes with N–Fluorobenzenesulfonimides, Angew. Chem., Int. Ed., 2021, 60, 25949–25957; (b) K. Zhou, L. Yin, Y. Guo, C.-H. Ding and B. Xu, Copper Nitrate Mediated Regioselective Difunctionalization of Alkenes with N-Fluorobenzenesulfonimide: A Direct Approach to β-Aminonitrates, Synthesis, 2023, 744–754; (c) M. T. Muhammad, Y. Jiao, C. Ye, M.-F. Chiou, M. Israr, X. Zhu, Y. Li, Z. Wen, A. Studer and H. Bao, Synthesis of Difluoromethylated Allenes through Trifunctionalization of 1,3-Enynes, Nat. Commun., 2020, 11, 416.
15. For selected reviews, see: (a) Y. Ping, Q. Ding and Y. Peng, Advances in C−CN Bond Formation via C−H Bond Activation, ACS Catal., 2016, 6, 5989–6005; (b) A. M. Siddique, I. N. Pulidindi and Z. Shen, Metal-Catalyzed Cyanation of Aromatic Hydrocarbon with Less Toxic Nitriles as a Cyano Source, Tetrahedron, 2020, 76, 131388; (c) P. Anbarasan, T. Schareina and M. Beller, Recent Developments and Perspectives in Palladium-Catalyzed Cyanation of Aryl Halides: Synthesis of Benzonitriles, Chem. Soc. Rev., 2011, 40, 5049–5067.
16. (a) E.-H. Huang, L.-G. Liu, Y.-W. Yin, H.-X. Dong, J.-J. Zhou, X. Lu, B. Zhou and L. W. Ye, Copper-Catalyzed Enantioselective Desymmetrizing C(sp²)–H Functionalization of Azide-Ynamides via α-Imino Copper Carbenes, Sci. China: Chem., 2024, 67, 2982–2988; (b) D. Hao, Z. Yang, Y. Liu, Y. Li, Y. Liu and P. Liu, Copper-Promoted C1−H Amination of Pyrrolo[1,2-a]quinoxaline with N-Fluorobenzenesulfonimide, J. Mol. Struct., 2022, 1267, 133636.
17. For selected papers, see: (a) H. Xiao, H. Shen, L. Zhu and C. Li, Copper-Catalyzed Radical Aminotrifluoromethylation of Alkenes, J. Am. Chem. Soc., 2019, 141, 11440–11445; (b) M. Mandal, J. A. Buss, S.-J. Chen, C. J. Cramer and S. S. Stahl, Mechanistic Insights into Radical Formation and Functionalization in Copper/N-Fluorobenzenesulfonimide Radical-Relay Reactions, Chem. Sci., 2024, 15, 1364–1373; (c) X. Jia, X. Tian, D. Zhuang, Z. Wan, J. Gu and Z. Li, Copper-Catalyzed Intermolecular Cross-dehydrogenative C−N Coupling at Room Temperature via Remote Activating Group Enabled Radical Relay Strategy, Org. Lett., 2023, 25, 2012–2017; (d) J. Zhang, W. Xie, S. Ye and J. Wu, Synthesis of β-Hydroxysulfones through a Copper(II)-Catalyzed Multicomponent Reaction with the Insertion of Sulfur Dioxide, Org. Chem. Front., 2019, 6, 2254–2259.
18. (a) G. Zhang, T. Xiong, Z. Wang, G. Xu, X. Wang and Q. Zhang, Highly Regioselective Radical Amination of Allenes: Direct Synthesis of Allenamides and Tetrasubstituted Alkenes, Angew. Chem., Int. Ed., 2015, 54, 12649–12653; (b) H. Zhang, Y. Song, J. Zhao, J. Zhang and Q. Zhang, Regioselective Radical Aminofluorination of Styrenes, Angew. Chem., Int. Ed., 2014, 53, 11079–11083.
19. For selected papers, see: (a) N. Lu, Z. Zhang, N. Ma, C. Wu, G. Zhang, Q. Liu and T. Liu, Copper-Catalyzed Difunctionalization of Allenes with Sulfonyl Iodides Leading to (E)-α-Iodomethyl Vinylsulfones, Org. Lett., 2018, 20, 4318–4322; (b) B. Meng and S. Ma, Carbon Carbon Bond Formation via the Electrophilic Addition of Carbocations to Allenes, Org. Lett., 2012, 14, 2674–2677; (c) Z.-Y. Wang, S.-J. Wang, N.-N. Dai, Y. Xiao, Y. Zhou, W.-C. Tian, D. Sun, Q. Li, Y. Wang and W.-T. Wei, Carbon-Carbon Triple Bond Cleavage and Reconstitution to Achieve Aryl Amidation Using Nitrous Acid Esters, Nat. Commun., 2025, 16, 993–1000.
20. Y. Li, X. Zhang and Z. Lian, Copper Catalyzed Cyano-Sulfonylation of Allenes via the Insertion of Sulfur Dioxide toward the Synthesis of (E)-α-Cyanomethyl Vinylsulfones, Org. Chem. Front., 2022, 9, 5141–5146.
21. CCDC 2431861: Experimental Crystal Structure Determination, 2025,  DOI:10.5517/ccdc.csd.cc2mmk4z.

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