Helena Fernández Piedra, Illán Tagarro, Manuel Plaza
This review highlights the use of photochemically excited electron donor–acceptor (EDA) complexes as a sustainable, modern approach to carbon–sulfur bond formation. C–S bonds are essential in various fields, including pharmaceuticals, materials science, and agrochemicals, yet traditional synthetic methods often face challenges such as harsh conditions and high costs. EDA complexes, formed through non-covalent interactions between electron-rich donors and electron-deficient acceptors, undergo visible-light-induced single-electron transfer (SET) to generate reactive radical intermediates. These intermediates enable efficient, selective, and environmentally friendly C–S bond formation under mild conditions. The article explores recent examples of practical applications of these reactions, including their mechanism, providing a comprehensive understanding of these cutting-edge methods and their potential to advance sustainable synthetic chemistry.
{"title":"EDA Complex Photochemistry as a Strategy for C–S Bond Formation","authors":"Helena Fernández Piedra, Illán Tagarro, Manuel Plaza","doi":"10.1039/d5qo00258c","DOIUrl":"https://doi.org/10.1039/d5qo00258c","url":null,"abstract":"This review highlights the use of photochemically excited electron donor–acceptor (EDA) complexes as a sustainable, modern approach to carbon–sulfur bond formation. C–S bonds are essential in various fields, including pharmaceuticals, materials science, and agrochemicals, yet traditional synthetic methods often face challenges such as harsh conditions and high costs. EDA complexes, formed through non-covalent interactions between electron-rich donors and electron-deficient acceptors, undergo visible-light-induced single-electron transfer (SET) to generate reactive radical intermediates. These intermediates enable efficient, selective, and environmentally friendly C–S bond formation under mild conditions. The article explores recent examples of practical applications of these reactions, including their mechanism, providing a comprehensive understanding of these cutting-edge methods and their potential to advance sustainable synthetic chemistry.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"88 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723998","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}
Hejun An, Zhi Cui, Jinchao Liang, Xingxing Ma, Jinglong Chen, Qiuling Song
The difunctionalization of olefins as an effective synthetic strategy has garnered significant attention among organic synthetic chemists, thus enabling complex molecular scaffolds to be assembled in a single step from readily accessible feedstock chemicals. Herein, a nickel-catalyzed reductive difunctionalization of BN-heterocyclic alkenes has been developed. A variety of BN-heterocycles were synthesized utilizing the specific characteristics of selected difunctionalization reactions. Thereby enabling the synthesis of a wider range of BN-heterocycles through further conversions and applications.
{"title":"Fe-Catalyzed B-H and N-H Insertion Reactions of Iodonium Ylides","authors":"Hejun An, Zhi Cui, Jinchao Liang, Xingxing Ma, Jinglong Chen, Qiuling Song","doi":"10.1039/d4qo01916d","DOIUrl":"https://doi.org/10.1039/d4qo01916d","url":null,"abstract":"The difunctionalization of olefins as an effective synthetic strategy has garnered significant attention among organic synthetic chemists, thus enabling complex molecular scaffolds to be assembled in a single step from readily accessible feedstock chemicals. Herein, a nickel-catalyzed reductive difunctionalization of BN-heterocyclic alkenes has been developed. A variety of BN-heterocycles were synthesized utilizing the specific characteristics of selected difunctionalization reactions. Thereby enabling the synthesis of a wider range of BN-heterocycles through further conversions and applications.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"36 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143723999","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}
Yihao Zhang, Peng Zhang, Hang Zhao, Xing Wang, Xia Zhou, Yimou Gong, Lin Wang, Siping Wei, Zhijie Zhang, Qiang Fu
Indoloquinolones and dihydroindoloquinolones are in-demand motifs in medicinal chemistry, yet methods for the controlled synthesis both molecules are scarce. We detail the solvent-controlled switchable photocyclization and dehydrogenative photocyclization of heterocyclic anilides for the rapid and divergent synthesis of indoloquinolinones and dihydroindolo-quinolinones. By using 4CzBnBN and DCM/MeOH as the catalytic system, a photocyclization reaction is achieved with excellent diastereoselectivity and good yields, resulting in the cis-selective synthesis of dihydroindoloquinolinones exclu-sively. Upon changing the solvent to DCE/DMSO, the reaction pathways switch to dehydrogenative photocyclization that provided indoloquinolinones. The success of this reaction hinges on the photophysical properties of the photocatalyst and its combination with specific solvents. Mechanistic studies including Stern-Volmer quenching studies, isotope labeling experiments, Volhard titration methods and DFT calculation have revealed that an energy transfer process is involved in the photocyclization reaction, while both energy transfer and electron transfer processes occur during the dehydrogenative photocyclization reaction. Our research not only provides a novel strategy for the synthesis of medicinally intriguing molecules of indolo-quinolinones and dihydroindoloquinolinones but also offers insights into the modulation of catalytic performance of cya-nocarbazole-based catalysts.
{"title":"Solvent-controlled 4CzBnBN-catalyzed Intramolecular Photocyclization and Dehydrogenative Photocyclization of Indolecarboxamides for the switchable synthesis of indoloquinolones and dihydroindoloquinolones","authors":"Yihao Zhang, Peng Zhang, Hang Zhao, Xing Wang, Xia Zhou, Yimou Gong, Lin Wang, Siping Wei, Zhijie Zhang, Qiang Fu","doi":"10.1039/d5qo00185d","DOIUrl":"https://doi.org/10.1039/d5qo00185d","url":null,"abstract":"Indoloquinolones and dihydroindoloquinolones are in-demand motifs in medicinal chemistry, yet methods for the controlled synthesis both molecules are scarce. We detail the solvent-controlled switchable photocyclization and dehydrogenative photocyclization of heterocyclic anilides for the rapid and divergent synthesis of indoloquinolinones and dihydroindolo-quinolinones. By using 4CzBnBN and DCM/MeOH as the catalytic system, a photocyclization reaction is achieved with excellent diastereoselectivity and good yields, resulting in the cis-selective synthesis of dihydroindoloquinolinones exclu-sively. Upon changing the solvent to DCE/DMSO, the reaction pathways switch to dehydrogenative photocyclization that provided indoloquinolinones. The success of this reaction hinges on the photophysical properties of the photocatalyst and its combination with specific solvents. Mechanistic studies including Stern-Volmer quenching studies, isotope labeling experiments, Volhard titration methods and DFT calculation have revealed that an energy transfer process is involved in the photocyclization reaction, while both energy transfer and electron transfer processes occur during the dehydrogenative photocyclization reaction. Our research not only provides a novel strategy for the synthesis of medicinally intriguing molecules of indolo-quinolinones and dihydroindoloquinolinones but also offers insights into the modulation of catalytic performance of cya-nocarbazole-based catalysts.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"30 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734061","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}
Herein, we reported the first attractive example of visible-light-induced radical cascade cyclization of 2-isocyanobiaryls for the synthesis of phenanthridines via 1,5-hydrogen atom transfer. The reaction circumvents the need for a base, metals, and high temperature, enabling the preparation of phenanthridines with a broad substrate scope and excellent functional group compatibility.
{"title":"Visible-light-induced radical cascade cyclization of 2-isocyanobiaryls via 1,5-hydrogen atom transfer (1,5-HAT)","authors":"Yafei Zhu, Penghua Zhang, Xingqin Tian, Xueqin Wang, Mi Wang, Cuimei Zhang, Jian Chen, Jing Zhang, Guanghui Lv, Yong Wu","doi":"10.1039/d5qo00031a","DOIUrl":"https://doi.org/10.1039/d5qo00031a","url":null,"abstract":"Herein, we reported the first attractive example of visible-light-induced radical cascade cyclization of 2-isocyanobiaryls for the synthesis of phenanthridines <em>via</em> 1,5-hydrogen atom transfer. The reaction circumvents the need for a base, metals, and high temperature, enabling the preparation of phenanthridines with a broad substrate scope and excellent functional group compatibility.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"29 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713216","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}
Yang-Yang Fu, Kun Hu, Song-Yu Hou, Bing-Chao Yan, Xiao-Nian Li, Xing-Zhi Yang, Han-Dong Sun, Pema-Tenzin Puno
Glutinosasins A–D (1–4), four novel 8,14-seco-ent-kaurane diterpenoids featuring an β-carbonyl enol moiety, along with glutinosasin E (5), a new ent-kaurane diterpenoid, were isolated from the aerial part of Isodon glutinosus. Their structures were elucidated through a combinatorial use of spectroscopic methods and single-crystal X-ray diffraction. Quantum chemical calculations further validated the unique structures of 1–4 and supported the presence of enol-enol tautomerism within these molecules. Notably, 4 demonstrated selective inhibitory activity against SW480 tumor cells, with an IC50 value of 2.33 μM, and induced G2/M cell cycle arrest and apoptosis in a dose-dependent manner.
{"title":"8,14-seco-ent-Kaurane Diterpenoids from Isodon glutinosus: Enol-Enol Tautomerism and Antitumor Activity","authors":"Yang-Yang Fu, Kun Hu, Song-Yu Hou, Bing-Chao Yan, Xiao-Nian Li, Xing-Zhi Yang, Han-Dong Sun, Pema-Tenzin Puno","doi":"10.1039/d5qo00356c","DOIUrl":"https://doi.org/10.1039/d5qo00356c","url":null,"abstract":"Glutinosasins A–D (1–4), four novel 8,14-<em>seco</em>-<em>ent</em>-kaurane diterpenoids featuring an <em>β</em>-carbonyl enol moiety, along with glutinosasin E (5), a new <em>ent</em>-kaurane diterpenoid, were isolated from the aerial part of <em>Isodon glutinosus</em>. Their structures were elucidated through a combinatorial use of spectroscopic methods and single-crystal X-ray diffraction. Quantum chemical calculations further validated the unique structures of 1–4 and supported the presence of enol-enol tautomerism within these molecules. Notably, 4 demonstrated selective inhibitory activity against SW480 tumor cells, with an IC<small><sub>50</sub></small> value of 2.33 <em>μ</em>M, and induced G2/M cell cycle arrest and apoptosis in a dose-dependent manner.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"72 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713163","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}
Cyclobutylamines are versatile synthetic frameworks with significant applications in pharmaceuticals and natural products. Herein, we report an iron-catalyzed carboazidation of alkenes, enabling the regioselective synthesis of multi-substituted cyclobutylamines. This method features broad substrate scope, excellent functional group tolerance, and versatile synthetic applications, providing a practical approach to constructing multi-substituted cyclobutylamines with a quaternary-substituted carbon center.
{"title":"Iron-catalyzed Regioselective Carboazidation of Alkenes for the Synthesis of Multi-substituted Cyclobutylamines","authors":"Yufei Li, Yajun Li, Hongli Bao","doi":"10.1039/d5qo00173k","DOIUrl":"https://doi.org/10.1039/d5qo00173k","url":null,"abstract":"Cyclobutylamines are versatile synthetic frameworks with significant applications in pharmaceuticals and natural products. Herein, we report an iron-catalyzed carboazidation of alkenes, enabling the regioselective synthesis of multi-substituted cyclobutylamines. This method features broad substrate scope, excellent functional group tolerance, and versatile synthetic applications, providing a practical approach to constructing multi-substituted cyclobutylamines with a quaternary-substituted carbon center.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"11 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713164","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}
We report a visible-light-mediated three-component reaction via N-centered radical-mediated 1,5-hydrogen atom transfer combined with site-selective remote C(sp3)–H cross-coupling reactions of alkenes with alkyl radicals for the α-C(sp3)–H alkylation of glycine derivatives and peptides. This protocol performs the double functionalization of alkenes and provides a promising alternative route for the modular synthesis of peptide-derived bioactive compounds. Additionally, the potential synthetic value of this transformation is demonstrated in the scale-up reactions and late-stage functionalization of peptides.
{"title":"Photoredox-catalyzed three-component alkylation of glycine derivatives and peptides via a site-selective 1,5-hydrogen atom transfer cascade","authors":"Hongying Fan, Liulin Jiao, Ting Yuan, Jian Chen, Qingyun Gu, Xue Zhang, Jinyu Hou, Zhongzhen Yang, Li Guo, Yong Wu","doi":"10.1039/d5qo00294j","DOIUrl":"https://doi.org/10.1039/d5qo00294j","url":null,"abstract":"We report a visible-light-mediated three-component reaction <em>via</em> N-centered radical-mediated 1,5-hydrogen atom transfer combined with site-selective remote C(sp<small><sup>3</sup></small>)–H cross-coupling reactions of alkenes with alkyl radicals for the α-C(sp<small><sup>3</sup></small>)–H alkylation of glycine derivatives and peptides. This protocol performs the double functionalization of alkenes and provides a promising alternative route for the modular synthesis of peptide-derived bioactive compounds. Additionally, the potential synthetic value of this transformation is demonstrated in the scale-up reactions and late-stage functionalization of peptides.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"215 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143713217","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}
Jinti Moni Kumar, Ivan Huc, Yann Ferrand, Bappaditya Gole
We present an efficient light-driven oligomerization of flat aromatic tetra-amide macrocycles containing photoresponsive 1,8-diazaanthracenes. Oligomers with molecular weights exceeding 10 kDa were straightforwardly obtained, isolated using gel permeation chromatography (GPC), and characterized by NMR and mass spectrometry up to the octamer. We finely tuned the side chain size to exclusively favor the exo- [4+4] photoadduct over the endo, thus controlling the stereoselectivity of the photoreaction to produce a single isomer, which yielded ladder-like architectures. The octamer is a ~10 nm long ladder with a step size of 4.6 Å. The oligomers retained sufficient photoreactivity to undergo further oligomerization, either between themselves or upon adding fresh monomers to generate longer oligomers. These oligomers are fully degradable as thermal reversibility allows for monomer recovery.
{"title":"Unveiling stereoselective ladders via photo-oligomerization of a diazaanthracene macrocycle","authors":"Jinti Moni Kumar, Ivan Huc, Yann Ferrand, Bappaditya Gole","doi":"10.1039/d5qo00159e","DOIUrl":"https://doi.org/10.1039/d5qo00159e","url":null,"abstract":"We present an efficient light-driven oligomerization of flat aromatic tetra-amide macrocycles containing photoresponsive 1,8-diazaanthracenes. Oligomers with molecular weights exceeding 10 kDa were straightforwardly obtained, isolated using gel permeation chromatography (GPC), and characterized by NMR and mass spectrometry up to the octamer. We finely tuned the side chain size to exclusively favor the exo- [4+4] photoadduct over the endo, thus controlling the stereoselectivity of the photoreaction to produce a single isomer, which yielded ladder-like architectures. The octamer is a ~10 nm long ladder with a step size of 4.6 Å. The oligomers retained sufficient photoreactivity to undergo further oligomerization, either between themselves or upon adding fresh monomers to generate longer oligomers. These oligomers are fully degradable as thermal reversibility allows for monomer recovery.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"75 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695855","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}
Highly substituted alkenes are important synthetic intermediates for pharmaceuticals, and the development of such compounds provides a variety of potential alkene monomers for functional polyolefin molecules. At present, a series of syn addition multi-substituted alkenes have been prepared through classical polar addition reactions between alkynes and silylmetal species. However, the anti-selective difunctionalization of alkynes lacks an effective pathway. To the best of our knowledge, there have been no reports of introducing anti C‒Si/C‒Het bonds in one step to construct corresponding difunctional alkenes. Herein, we seek to explore anti-selective 1,2-silylamination of alkynes by combining the addition of silyl radicals to unsaturated C‒C triple bonds and copper chelates assisted functionalization of vinyl radicals. The successful preparation of dozens of anti-silylaminated alkene derivatives, including those involving biologically active patterns, fully validates the generality and universality of this protocol. In addition, multi-dimensional mechanism research experiments and derivatization reactions have fully explored the details and application prospects of this transformation.
{"title":"Copper-Catalyzed anti-Stereoselective 1,2-Silylamination of Alkynes","authors":"Kelu Yan, Xiaoyu Wang, Jiangwei Wen, Qiuyun Li, Jianjing Yang, Xinru Tao, Shenghao Pan, Haosheng Liang, Xiu Wang","doi":"10.1039/d5qo00040h","DOIUrl":"https://doi.org/10.1039/d5qo00040h","url":null,"abstract":"Highly substituted alkenes are important synthetic intermediates for pharmaceuticals, and the development of such compounds provides a variety of potential alkene monomers for functional polyolefin molecules. At present, a series of syn addition multi-substituted alkenes have been prepared through classical polar addition reactions between alkynes and silylmetal species. However, the anti-selective difunctionalization of alkynes lacks an effective pathway. To the best of our knowledge, there have been no reports of introducing anti C‒Si/C‒Het bonds in one step to construct corresponding difunctional alkenes. Herein, we seek to explore anti-selective 1,2-silylamination of alkynes by combining the addition of silyl radicals to unsaturated C‒C triple bonds and copper chelates assisted functionalization of vinyl radicals. The successful preparation of dozens of anti-silylaminated alkene derivatives, including those involving biologically active patterns, fully validates the generality and universality of this protocol. In addition, multi-dimensional mechanism research experiments and derivatization reactions have fully explored the details and application prospects of this transformation.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"28 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695856","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}
Due to the prevalence of trifluoromethylarenes (ArCF3) units in drug-related molecules, direct late-stage functionalization of C(sp3)-F bonds in ArCF3 offers an appealing strategy for rapid derivatization of ArCF3-containing drugs, and holds significant promise in drug discovery and modification. Followed the success of two-component reaction for C(sp3)-F bond functionalization in ArCF3, preliminary studies have also been conducted on non-asymmetric three-component reactions. However, enantioselective three-component reactions in this field have not yet been developed. Herein, we report the first enantioselective three-component aryldifluoromethyl-alkynylation of alkenes through C(sp3)-F bond cleavage via dual photoredox/copper catalysis. This protocol is compatible with a wide array of trifluoromethylarenes bearing diverse substituents, various terminal alkynes and alkenes, enabling straightforward access to structurally diverse ArCF2-containing propargylic compounds in good yields with excellent enantioselectivities under mild conditions. Furthermore, the utility of this protocol was showcased through its application in the late-stage functionalization of a few drugs and bioactive molecular derivatives.
{"title":"Metallaphotoredox-enabled Enantioselective Aryldifluoromethyl-alkynylation of Alkenes via C(sp3)-F Bond Activation","authors":"jialin Huang, Liying Fu, xiaofei Zhao, Xingda Zhao, Zhanyong Tang, Xiaoqiang Ma, Depeng Zhao","doi":"10.1039/d5qo00370a","DOIUrl":"https://doi.org/10.1039/d5qo00370a","url":null,"abstract":"Due to the prevalence of trifluoromethylarenes (ArCF3) units in drug-related molecules, direct late-stage functionalization of C(sp3)-F bonds in ArCF3 offers an appealing strategy for rapid derivatization of ArCF3-containing drugs, and holds significant promise in drug discovery and modification. Followed the success of two-component reaction for C(sp3)-F bond functionalization in ArCF3, preliminary studies have also been conducted on non-asymmetric three-component reactions. However, enantioselective three-component reactions in this field have not yet been developed. Herein, we report the first enantioselective three-component aryldifluoromethyl-alkynylation of alkenes through C(sp3)-F bond cleavage via dual photoredox/copper catalysis. This protocol is compatible with a wide array of trifluoromethylarenes bearing diverse substituents, various terminal alkynes and alkenes, enabling straightforward access to structurally diverse ArCF2-containing propargylic compounds in good yields with excellent enantioselectivities under mild conditions. Furthermore, the utility of this protocol was showcased through its application in the late-stage functionalization of a few drugs and bioactive molecular derivatives.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"57 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695859","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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