An efficient and practical visible-light-driven cascade difluoroalkylation/cyclization of 4-(N-alkyl-N-acrylamido)coumarins has been developed using readily accessible bromodifluoromethylphosphonium bromide ([Ph3PCF2H]+Br-) as a difluoromethyl radical precursor. This protocol enables the rapid construction of a wide range of difluoroalkylated 4,5fused polycyclic coumarin derivatives under mild, additive-and base-free conditions. Moreover, an alternative photoredox-catalyzed intramolecular radical cyclization of 4-(N-alkyl-N-acrylamido)coumarins has been established, providing efficient access to structurally diverse coumarin [4,3-b]pyridinone derivatives. Both transformations proceed smoothly at room temperature, exhibiting broad substrate scope, excellent regioselectivity, and good functional group tolerance. Preliminary mechanistic investigations indicate that the two pathways operate through distinct radical processes involving single electron transfer (SET) and energy transfer (EnT), respectively.
利用易获得的溴代氟甲基溴化磷（[Ph3PCF2H]+Br-）作为二氟甲基自由基前体，开发了一种高效实用的4-（n -烷基- n -丙烯酰胺）香豆素级联二氟烷基化/环化反应。该协议能够在温和，无添加剂和无碱条件下快速构建广泛的二氟烷基化4,5融合多环香豆素衍生物。此外，还建立了另一种光氧化催化的4-（n -烷基- n -丙烯酰胺）香豆素分子内自由基环化反应，为获得结构多样的香豆素[4,3-b]吡啶酮衍生物提供了有效途径。这两种转化都在室温下顺利进行，表现出广泛的底物范围、优异的区域选择性和良好的官能团耐受性。初步的机制研究表明，这两种途径分别通过不同的自由基过程进行，包括单电子转移（SET）和能量转移（EnT）。
{"title":"Visible-Light-Driven Radical Cascade Cyclization of 4-(N-Alkyl-Nacrylamido)coumarins: Access to Difluoroalkylated 4,5-Fused Coumarins and Coumarin[4,3-b]pyridinones","authors":"Jin-Wei Yuan, Shi-Long Zhang, Xin-Ya Wang, Meng Yan, Yong-Mei Xiao, Donghui Wei, Lingbo Qu","doi":"10.1039/d6qo00192k","DOIUrl":"https://doi.org/10.1039/d6qo00192k","url":null,"abstract":"An efficient and practical visible-light-driven cascade difluoroalkylation/cyclization of 4-(<em>N</em>-alkyl-<em>N</em>-acrylamido)coumarins has been developed using readily accessible bromodifluoromethylphosphonium bromide ([Ph<small><sub>3</sub></small>PCF<small><sub>2</sub></small>H]<small><sup>+</sup></small>Br<small><sup>-</sup></small>) as a difluoromethyl radical precursor. This protocol enables the rapid construction of a wide range of difluoroalkylated 4,5fused polycyclic coumarin derivatives under mild, additive-and base-free conditions. Moreover, an alternative photoredox-catalyzed intramolecular radical cyclization of 4-(N-alkyl-N-acrylamido)coumarins has been established, providing efficient access to structurally diverse coumarin [4,3-b]pyridinone derivatives. Both transformations proceed smoothly at room temperature, exhibiting broad substrate scope, excellent regioselectivity, and good functional group tolerance. Preliminary mechanistic investigations indicate that the two pathways operate through distinct radical processes involving single electron transfer (SET) and energy transfer (EnT), respectively.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"90 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A reductive tandem protocol that harnesses CO₂ as a methylene source is reported, enabling direct and modular assembly of biologically relevant 3-aminomethyl chromones from simple o-hydroxyaryl enaminones and amines. The transformation proceeds under mild conditions with simple operation via hydrosilane-mediated four-electron reduction of CO₂, generating reactive imine intermediates in situ for cascade cyclization. This strategy obviates pre-synthesized aminomethylating reagents, exhibits broad substrate tolerance, and provides step-economical access to diverse chromone scaffolds.
{"title":"Carbon dioxide as a methylene donor: modular synthesis of 3-aminomethyl chromones via a reductive tandem reaction †","authors":"Yubing Zhou, Zhongrong Xu, Wei Li, Yimei Zeng, Wenxin Jiang, Jie-Ping Wan, Huanfeng Jiang, Chaorong Qi","doi":"10.1039/d6qo00205f","DOIUrl":"https://doi.org/10.1039/d6qo00205f","url":null,"abstract":"A reductive tandem protocol that harnesses CO₂ as a methylene source is reported, enabling direct and modular assembly of biologically relevant 3-aminomethyl chromones from simple o-hydroxyaryl enaminones and amines. The transformation proceeds under mild conditions with simple operation via hydrosilane-mediated four-electron reduction of CO₂, generating reactive imine intermediates in situ for cascade cyclization. This strategy obviates pre-synthesized aminomethylating reagents, exhibits broad substrate tolerance, and provides step-economical access to diverse chromone scaffolds.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"17 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The termination of the endo-selective cyclization of 2-vinylphenol-derived iodomethylsilyl ether has been limited to hydrogen atom abstraction or transition metal-induced β-hydride elimination, affording non-substituted benzoxasilepines. Herein, we report the efficient access to 5-acylated benzoxasilepines by combining the palladium-catalyzed endo-selective cyclization and NHC-catalyzed radical acylation. This method enables the NHC-catalyzed radical cross-coupling step as an effective termination process for the endo-selective cyclization, yielding a variety of 5-acylated benzoxasilepines with good antifungal activity.
{"title":"Efficient Access to 5-Acylated Benzoxasilepines Enabled by NHC/Pd Cooperative Catalysis","authors":"Lala Wang, Jixing Li, Ziye Cheng, Tingting Li, Huimin Xia, Shi-Chao Ren","doi":"10.1039/d6qo00100a","DOIUrl":"https://doi.org/10.1039/d6qo00100a","url":null,"abstract":"The termination of the endo-selective cyclization of 2-vinylphenol-derived iodomethylsilyl ether has been limited to hydrogen atom abstraction or transition metal-induced β-hydride elimination, affording non-substituted benzoxasilepines. Herein, we report the efficient access to 5-acylated benzoxasilepines by combining the palladium-catalyzed endo-selective cyclization and NHC-catalyzed radical acylation. This method enables the NHC-catalyzed radical cross-coupling step as an effective termination process for the endo-selective cyclization, yielding a variety of 5-acylated benzoxasilepines with good antifungal activity.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"25 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Transfer hydrogenation (TH), as a mild reduction strategy that avoids the use of high-pressure molecular hydrogen, has attracted significant interest for the selective reduction of carbonyl compounds. In this study, density functional theory (DFT) calculations combined with machine learning approaches were employed to systematically investigate the reaction mechanism of Ru(II)-complex-catalyzed base-free transfer hydrogenation under aerobic conditions. By comparing four plausible reaction pathways, the metal-ligand cooperative pathway involving the amide N-H site of the Ru(II) complex (Path D) was identified as the kinetically most favorable route, with the cooperative hydrogen transfer during the dehydrogenation of isopropanol being the rate-determining step. Distortion-interaction analysis, energy decomposition analysis (EDA), and Extended Transition State-Natural Orbitals for Chemical Valence (ETS-NOCV) results reveal that the participation of the auxiliary ligand N-H site in Path D effectively reduces the distortion energy of the transition state and enhances both orbital interactions and dispersion stabilization between the metal center and the substrate, thereby significantly stabilizing the key transition state. Machine learning analysis further indicates that the HOMO-LUMO gap and the metal atomic charge are the primary descriptors governing the reaction free energy barrier, while the reaction free energy of hydride intermediate formation (ΔG(Int2)) exhibits a strong linear correlation with the dehydrogenation barrier ΔG≠, serving as a quantitative predictor of catalytic activity and ligand effects. Overall, this study not only provides an electronic-structure-level understanding of the mechanistic origin and rate-controlling factors of metal-ligand cooperation(MLC) in transfer hydrogenation, but also establishes a transferable structure-reactivity relationship framework for the rational design of efficient transfer hydrogenation catalysts.
{"title":"DFT and Machine Learning Insights into Ru(II) Complex-Catalyzed Transfer Hydrogenation","authors":"Gui-Xiang Zhou, Cheng Hou","doi":"10.1039/d6qo00178e","DOIUrl":"https://doi.org/10.1039/d6qo00178e","url":null,"abstract":"Transfer hydrogenation (TH), as a mild reduction strategy that avoids the use of high-pressure molecular hydrogen, has attracted significant interest for the selective reduction of carbonyl compounds. In this study, density functional theory (DFT) calculations combined with machine learning approaches were employed to systematically investigate the reaction mechanism of Ru(II)-complex-catalyzed base-free transfer hydrogenation under aerobic conditions. By comparing four plausible reaction pathways, the metal-ligand cooperative pathway involving the amide N-H site of the Ru(II) complex (Path D) was identified as the kinetically most favorable route, with the cooperative hydrogen transfer during the dehydrogenation of isopropanol being the rate-determining step. Distortion-interaction analysis, energy decomposition analysis (EDA), and Extended Transition State-Natural Orbitals for Chemical Valence (ETS-NOCV) results reveal that the participation of the auxiliary ligand N-H site in Path D effectively reduces the distortion energy of the transition state and enhances both orbital interactions and dispersion stabilization between the metal center and the substrate, thereby significantly stabilizing the key transition state. Machine learning analysis further indicates that the HOMO-LUMO gap and the metal atomic charge are the primary descriptors governing the reaction free energy barrier, while the reaction free energy of hydride intermediate formation (ΔG(Int2)) exhibits a strong linear correlation with the dehydrogenation barrier ΔG≠, serving as a quantitative predictor of catalytic activity and ligand effects. Overall, this study not only provides an electronic-structure-level understanding of the mechanistic origin and rate-controlling factors of metal-ligand cooperation(MLC) in transfer hydrogenation, but also establishes a transferable structure-reactivity relationship framework for the rational design of efficient transfer hydrogenation catalysts.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"26 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhen-Xu Yang, Bing-Xia Yan, Lei Shi, Lidong Gong, Zhi-Shi Ye
A mild and efficient DMAP/KF co-catalyzed allylic alkylation of gem-diborylalkanes with MBH carbonates has been developed, providing a series of tertiary alkylboronate esters in moderate to excellent yields. Moreover, this strategy is also applicable to the construction of secondary alkylboronic esters using DABCO and LiCl as co-catalysts. The late-stage modification of bioactive molecules, scaled-up reaction and downstream derivatizations documented the practicability of this method. Primary mechanistic studies implicated the alkali metal halide as a co-catalyst is crucial for the observed reactivity.
{"title":"Lewis Base/Alkali Metal Halide Co-catalyzed Allylic Alkylation of gem-Diborylalkanes with MBH Carbonates for the Construction of tert-Alkylboronic Esters","authors":"Zhen-Xu Yang, Bing-Xia Yan, Lei Shi, Lidong Gong, Zhi-Shi Ye","doi":"10.1039/d6qo00181e","DOIUrl":"https://doi.org/10.1039/d6qo00181e","url":null,"abstract":"A mild and efficient DMAP/KF co-catalyzed allylic alkylation of gem-diborylalkanes with MBH carbonates has been developed, providing a series of tertiary alkylboronate esters in moderate to excellent yields. Moreover, this strategy is also applicable to the construction of secondary alkylboronic esters using DABCO and LiCl as co-catalysts. The late-stage modification of bioactive molecules, scaled-up reaction and downstream derivatizations documented the practicability of this method. Primary mechanistic studies implicated the alkali metal halide as a co-catalyst is crucial for the observed reactivity.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"90 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jia-Long Wu, Yuchen Yang, Sheng-Ye Zhang, Xu Liu, Teng Sun, Yanan Zhao, Lijia Wang
Chiral 1,2-amino alcohols are indispensable structural motifs in organic synthesis and pharmaceutical development, with the synthesis of chiral aziridine intermediates being a crucial step. Although experimental data indicate that the enantioselectivity (ee) of chiral aziridines is highly sensitive to ligands, anions, and substituents, the underlying stereocontrol mechanism remains elusive due to the challenges of characterizing transient intermediates. In this work, we utilize density functional theory (DFT) calculations to systematically investigate the factors governing stereoselectivity. Our results reveal that anion-induced non-covalent interactions play a pivotal role in stabilizing the R-configuration transition state (the major product) by lowering the activation barrier. Furthermore, we elucidate how the steric and electronic properties of the ligand scaffold orchestrate the copper center’s chiral pocket. This study provides fundamental mechanistic insights into copper-catalyzed nitrene transfer, establishing a theoretical blueprint for the rational design of advanced asymmetric catalytic systems.
{"title":"Origin of Enantioselectivity in Copper-Catalyzed Aziridination of Enol Silyl Ethers: A Comprehensive DFT Study","authors":"Jia-Long Wu, Yuchen Yang, Sheng-Ye Zhang, Xu Liu, Teng Sun, Yanan Zhao, Lijia Wang","doi":"10.1039/d6qo00231e","DOIUrl":"https://doi.org/10.1039/d6qo00231e","url":null,"abstract":"Chiral 1,2-amino alcohols are indispensable structural motifs in organic synthesis and pharmaceutical development, with the synthesis of chiral aziridine intermediates being a crucial step. Although experimental data indicate that the enantioselectivity (ee) of chiral aziridines is highly sensitive to ligands, anions, and substituents, the underlying stereocontrol mechanism remains elusive due to the challenges of characterizing transient intermediates. In this work, we utilize density functional theory (DFT) calculations to systematically investigate the factors governing stereoselectivity. Our results reveal that anion-induced non-covalent interactions play a pivotal role in stabilizing the R-configuration transition state (the major product) by lowering the activation barrier. Furthermore, we elucidate how the steric and electronic properties of the ligand scaffold orchestrate the copper center’s chiral pocket. This study provides fundamental mechanistic insights into copper-catalyzed nitrene transfer, establishing a theoretical blueprint for the rational design of advanced asymmetric catalytic systems.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"31 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Planar chiral macrocyclic paracyclophanols exhibit configurational lability due to the increased flexibility of their ansa-chains, and isothiourea catalysis has recently provided an effective experimental pathway for the highly enantioselective acylation of this class of compounds with planar chirality. However, systematic studies on the origin of planar chirality of this kind of reaction lag behind. Herein, density functional theory (DFT) was employed to investigate the possible mechanism and origin of planar chirality of the isothiourea (R)-benzotetramisole ((R)-BTM)-catalyzed acylation of paracyclophanols. The favorable pathway includes three steps: SN2-type acyl transfer, acylation coupled with deprotonation of the hydroxyl group, and dissociation of the catalyst. Moreover, distortion–interaction analysis, non-covalent interaction (NCI) analysis, atoms-in-molecules (AIM) analysis, and Fukui function vector calculations were used to further explore the role of the catalyst and key factors governing stereocontrol in the stereoselectivity-determining step.
{"title":"Isothiourea-catalyzed acylation of paracyclophanols for the construction of planar chirality: the mechanism and origin of stereoselectivity","authors":"Haowen Chen, Lan Yu, Donghui Wei","doi":"10.1039/d6qo00184j","DOIUrl":"https://doi.org/10.1039/d6qo00184j","url":null,"abstract":"Planar chiral macrocyclic paracyclophanols exhibit configurational lability due to the increased flexibility of their ansa-chains, and isothiourea catalysis has recently provided an effective experimental pathway for the highly enantioselective acylation of this class of compounds with planar chirality. However, systematic studies on the origin of planar chirality of this kind of reaction lag behind. Herein, density functional theory (DFT) was employed to investigate the possible mechanism and origin of planar chirality of the isothiourea (<em>R</em>)-benzotetramisole (<strong>(<em>R</em>)-BTM</strong>)-catalyzed acylation of paracyclophanols. The favorable pathway includes three steps: S<small><sub>N</sub></small>2-type acyl transfer, acylation coupled with deprotonation of the hydroxyl group, and dissociation of the catalyst. Moreover, distortion–interaction analysis, non-covalent interaction (NCI) analysis, atoms-in-molecules (AIM) analysis, and Fukui function vector calculations were used to further explore the role of the catalyst and key factors governing stereocontrol in the stereoselectivity-determining step.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"19 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Correction for ‘Interactions beyond H-bonding: unveiling the role of unorthodox noncovalent interactions in charged thiourea and its catalytic efficiency’ by Prabhahar Murugan et al., Org. Chem. Front., 2026, https://doi.org/10.1039/d5qo01735a.
{"title":"Correction: Interactions beyond H-bonding: unveiling the role of unorthodox noncovalent interactions in charged thiourea and its catalytic efficiency","authors":"Prabhahar Murugan, Parul Rathour, Dipankar Das, Brijesh Patel, Srinu Tothadi, Bishwajit Ganguly, Saravanan Subramanian","doi":"10.1039/d6qo90023b","DOIUrl":"https://doi.org/10.1039/d6qo90023b","url":null,"abstract":"Correction for ‘Interactions beyond H-bonding: unveiling the role of unorthodox noncovalent interactions in charged thiourea and its catalytic efficiency’ by Prabhahar Murugan <em>et al.</em>, <em>Org. Chem. Front.</em>, 2026, https://doi.org/10.1039/d5qo01735a.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"18 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dominik Bauer, Jonas Kaffenberger, Michael Reggelin, Stefan Immel
Inspired by DFT calculations on the mechanism of the Corey-Winter olefination (CWO), it seemed possible that the desulfuration of isothiocyanates using P(III)-reagents should proceed smoothly to furnish the corresponding isocyanides. A detailed theoretical study on the mechanism of the desulfuration reaction revealed similar intermediates and transition states as compared to the CWO. Here, the only intermediate results from attack of the P reagent on the thiocarbonyl group. This yilde-type structure then undergoes smooth cycloreversion to directly liberate the corresponding isocyanide. The isothiocyanate substrate scope, limitations of the P(III)-reagent, and solvent effects are evaluated computationally and compared to experimental synthetic studies. Experimentally, the functional group tolerance of the isothiocyanate desulfuration proves to be excellent, and a large variety of solvents is tolerated including solvent-free variants. The reaction is pleasing invariant to steric hinderance and proceeds under very mild conditions, rendering this method valuable especially to otherwise difficult to synthesize isocyanides. The kinetics of various desulfuration reactions was followed by NMR spectroscopy, and the scope of this reaction and its applicability to ensuing reactions with and without isolation of the isocyanides is explored.
{"title":"Computational and Synthetic Studies on the Conversion of Isothiocyanates into Isocyanides: Inspirations from the Corey-Winter Olefination","authors":"Dominik Bauer, Jonas Kaffenberger, Michael Reggelin, Stefan Immel","doi":"10.1039/d6qo00120c","DOIUrl":"https://doi.org/10.1039/d6qo00120c","url":null,"abstract":"Inspired by DFT calculations on the mechanism of the Corey-Winter olefination (CWO), it seemed possible that the desulfuration of isothiocyanates using P(III)-reagents should proceed smoothly to furnish the corresponding isocyanides. A detailed theoretical study on the mechanism of the desulfuration reaction revealed similar intermediates and transition states as compared to the CWO. Here, the only intermediate results from attack of the P reagent on the thiocarbonyl group. This yilde-type structure then undergoes smooth cycloreversion to directly liberate the corresponding isocyanide. The isothiocyanate substrate scope, limitations of the P(III)-reagent, and solvent effects are evaluated computationally and compared to experimental synthetic studies. Experimentally, the functional group tolerance of the isothiocyanate desulfuration proves to be excellent, and a large variety of solvents is tolerated including solvent-free variants. The reaction is pleasing invariant to steric hinderance and proceeds under very mild conditions, rendering this method valuable especially to otherwise difficult to synthesize isocyanides. The kinetics of various desulfuration reactions was followed by NMR spectroscopy, and the scope of this reaction and its applicability to ensuing reactions with and without isolation of the isocyanides is explored.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"229 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Suyan Cao, Hailian Li, Jie Zhao, Yuxuan Tang, Liang Xu
In this study, we report an expedient strategy for the construction of a highly bridged model pentacyclic framework resembling the BCDEF ring system of aconitine and racemulosine. Key transformations include a transannular palladium-catalyzed α-vinylation to forge the bicyclo[3.2.1]octane BF ring system, a retro-Mannich/Mannich process to install the requisite C17 amino group with correct stereochemistry, and a silver-catalyzed Conia-ene cyclization to assemble the piperidine E ring. The developed methodology enabled the efficient synthesis of the BEF tricyclic core and, subsequently, the functionalized BCDEF pentacyclic framework. This work establishes a viable synthetic pathway toward the modeled core framework of aconitine-type alkaloids and lays a solid foundation for future total synthesis studies.
{"title":"An expedient modeling construction of the BCDEF pentacyclic ring system analog of aconitine and racemulosine","authors":"Suyan Cao, Hailian Li, Jie Zhao, Yuxuan Tang, Liang Xu","doi":"10.1039/d6qo00212a","DOIUrl":"https://doi.org/10.1039/d6qo00212a","url":null,"abstract":"In this study, we report an expedient strategy for the construction of a highly bridged model pentacyclic framework resembling the BCDEF ring system of aconitine and racemulosine. Key transformations include a transannular palladium-catalyzed α-vinylation to forge the bicyclo[3.2.1]octane BF ring system, a retro-Mannich/Mannich process to install the requisite C17 amino group with correct stereochemistry, and a silver-catalyzed Conia-ene cyclization to assemble the piperidine E ring. The developed methodology enabled the efficient synthesis of the BEF tricyclic core and, subsequently, the functionalized BCDEF pentacyclic framework. This work establishes a viable synthetic pathway toward the modeled core framework of aconitine-type alkaloids and lays a solid foundation for future total synthesis studies.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"18 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147507784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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