1,3-Enynes are valuable structural motifs found in a variety of natural products and pharmaceutical compounds. They also serve as versatile intermediates in synthetic chemistry due to the presence of multiple reactive sites. Among the strategies for constructing 1,3-enynes, hydroalkynylation stands out for its excellent atom and step economy. However, achieving regio- and stereoselective hydroalkynylation of internal alkynes remains a significant synthetic challenge. This review highlights recent advances in the transition metal-catalyzed hydroalkynylation of internal alkynes and outlines emerging strategies and future prospects of this field.
{"title":"Transition metal-catalyzed selective hydroalkynylation of internal alkynes with terminal alkynes","authors":"Jun-Fei Wang, Ping Tian, Yun-Xuan Tan","doi":"10.1039/d5qo01640a","DOIUrl":"https://doi.org/10.1039/d5qo01640a","url":null,"abstract":"1,3-Enynes are valuable structural motifs found in a variety of natural products and pharmaceutical compounds. They also serve as versatile intermediates in synthetic chemistry due to the presence of multiple reactive sites. Among the strategies for constructing 1,3-enynes, hydroalkynylation stands out for its excellent atom and step economy. However, achieving regio- and stereoselective hydroalkynylation of internal alkynes remains a significant synthetic challenge. This review highlights recent advances in the transition metal-catalyzed hydroalkynylation of internal alkynes and outlines emerging strategies and future prospects of this field.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"34 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895745","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}
Disulfide bonds are key structural motifs in bioactive natural products, linker chemistry, and functional materials; however, the selective synthesis of unsymmetrical disulfides remains a significant challenge. In particular, the dithiofunctionalization of C-C unsaturated bonds is underdeveloped, despite its promise for introducing additional molecular complexity. In this work, we report an acid-mediated dithiocyclization strategy for the preparation of heterocycle-appended unsymmetrical disulfides using N-(morpholine-4-dithio)phthalimide. The method applies broadly to nucleophile-tethered alkynes and olefins, affording benzofurans, lactones, cyclic ethers, and pyrrolidines, and it is also amenable to three-component couplings with olefins and TFA. Owing to its wide applicability for 1,2-difunctionalization of C-C unsaturated bonds and the bilateral reactivity of N-(morpholine-4-dithio)phthalimide, this approach provides modular access to heterocycle-appended unsymmetrical disulfides via two consecutive C-SS bond formations. The utility of this method is exemplified by the efficient hybridization of natural product derivatives (e.g., Corsifuran C, Boivinianin A) with bioactive agents (e.g., trimetazidine), highlighting its potential in linker chemistry and drug discovery.
{"title":"Dithiofunctionalization: A Versatile Approach for Constructing Complex Disulfides from Alkenes and Alkynes","authors":"Kazuya Kanemoto, Yuzuki Takami, Eunsang Kwon","doi":"10.1039/d5qo01625h","DOIUrl":"https://doi.org/10.1039/d5qo01625h","url":null,"abstract":"Disulfide bonds are key structural motifs in bioactive natural products, linker chemistry, and functional materials; however, the selective synthesis of unsymmetrical disulfides remains a significant challenge. In particular, the dithiofunctionalization of C-C unsaturated bonds is underdeveloped, despite its promise for introducing additional molecular complexity. In this work, we report an acid-mediated dithiocyclization strategy for the preparation of heterocycle-appended unsymmetrical disulfides using N-(morpholine-4-dithio)phthalimide. The method applies broadly to nucleophile-tethered alkynes and olefins, affording benzofurans, lactones, cyclic ethers, and pyrrolidines, and it is also amenable to three-component couplings with olefins and TFA. Owing to its wide applicability for 1,2-difunctionalization of C-C unsaturated bonds and the bilateral reactivity of N-(morpholine-4-dithio)phthalimide, this approach provides modular access to heterocycle-appended unsymmetrical disulfides via two consecutive C-SS bond formations. The utility of this method is exemplified by the efficient hybridization of natural product derivatives (e.g., Corsifuran C, Boivinianin A) with bioactive agents (e.g., trimetazidine), highlighting its potential in linker chemistry and drug discovery.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"1 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895743","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 visible light-induced C–H alkylation of 1,2,4-triazin-3,5(2H,4H)-diones has been achieved using iodomethyltrimethylphthalate esters as alkylating agents with the advantages as metal or organic-catalyst-free, operational simplicity, mild conditions, a broad substrate scope, and low sensitivity to environmental fluctuations. Notably, the strategy was successfully implemented in a microfluidic reactor with satisfactory yields. Among them, the drug precursor C6isopropylated-1,2,4-triazine-3,5(2H,4H)-dione was obtained in 70% yield via microfluidic synthesis, significantly shortening the synthetic route. This approach provides a green, efficient, and promising platform for synthesising bioactive C6-alkylated 1,2,4-triazin-3,5(2H,4H)-dione derivatives.
{"title":"Visible light-induced C–H alkylation of 1,2,4-triazine-3,5(2H,4H)diones using hypervalent iodine reagents as alkylating source","authors":"Qun-Qun Tian, Wenbo Song, Hong-Yu Zhang, Yuecheng Zhang, Jiquan Zhao","doi":"10.1039/d5qo01585e","DOIUrl":"https://doi.org/10.1039/d5qo01585e","url":null,"abstract":"A visible light-induced C–H alkylation of 1,2,4-triazin-3,5(2H,4H)-diones has been achieved using iodomethyltrimethylphthalate esters as alkylating agents with the advantages as metal or organic-catalyst-free, operational simplicity, mild conditions, a broad substrate scope, and low sensitivity to environmental fluctuations. Notably, the strategy was successfully implemented in a microfluidic reactor with satisfactory yields. Among them, the drug precursor C6isopropylated-1,2,4-triazine-3,5(2H,4H)-dione was obtained in 70% yield via microfluidic synthesis, significantly shortening the synthetic route. This approach provides a green, efficient, and promising platform for synthesising bioactive C6-alkylated 1,2,4-triazin-3,5(2H,4H)-dione derivatives.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"39 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895746","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}
Site-selective connection of peptides is crucial for constructing structurally uniform peptide chimeras bearing multiple functions, for applications such as drug discovery and drug delivery. However, the site-specific connection of two peptides is challenging due to the need to pinpoint two reaction sites among the multiple nucleophilic sites, such as lysine ε-amines. In this work, we developed a peptide–peptide coupling method involving an Ag-catalyzed N-terminus/dehydroalanine (Dha)-selective 1,3-dipolar cycloaddition reaction, yielding peptide chimeras with exclusive endo diastereoselectivity. The use of (S)- and (R)-DTBM-SEGPHOS as chiral ligands enables control over the stereochemistry of the pyrrolidine ring, irrespective of the inherent stereochemistry of the peptides, demonstrating its utility for the late-stage installation of cyclic chiral α,α-disubstituted amino acid residues into peptides. The versatility of this method was further demonstrated through the selective generation of a Dha moiety from various amino acid residues, followed by [3+2] cycloaddition. Notably, generation of the N-terminal imine, exposure of the Dha residue, and [3+2] cycloaddition can be performed in a convergent manner using two distinct peptides and an aldehyde, without isolating each intermediate, enabling their expedient assembly into a chemically robust pyrrolidine ring.
{"title":"Precision Synthesis of Peptide Chimeras through Site-Specific Azomethine Ylide–Dehydroalanine Cycloaddition","authors":"Masaki Iwata, Yuzuki Takami, Sena Miura, Hibiki Ohno, Eunsang Kwon, Naohiko Yoshikai, Kazuya Kanemoto","doi":"10.1039/d5qo01627d","DOIUrl":"https://doi.org/10.1039/d5qo01627d","url":null,"abstract":"Site-selective connection of peptides is crucial for constructing structurally uniform peptide chimeras bearing multiple functions, for applications such as drug discovery and drug delivery. However, the site-specific connection of two peptides is challenging due to the need to pinpoint two reaction sites among the multiple nucleophilic sites, such as lysine ε-amines. In this work, we developed a peptide–peptide coupling method involving an Ag-catalyzed N-terminus/dehydroalanine (Dha)-selective 1,3-dipolar cycloaddition reaction, yielding peptide chimeras with exclusive <em>endo</em> diastereoselectivity. The use of (<em>S</em>)- and (<em>R</em>)-DTBM-SEGPHOS as chiral ligands enables control over the stereochemistry of the pyrrolidine ring, irrespective of the inherent stereochemistry of the peptides, demonstrating its utility for the late-stage installation of cyclic chiral α,α-disubstituted amino acid residues into peptides. The versatility of this method was further demonstrated through the selective generation of a Dha moiety from various amino acid residues, followed by [3+2] cycloaddition. Notably, generation of the N-terminal imine, exposure of the Dha residue, and [3+2] cycloaddition can be performed in a convergent manner using two distinct peptides and an aldehyde, without isolating each intermediate, enabling their expedient assembly into a chemically robust pyrrolidine ring.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"25 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895744","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}
Woohyun Jo, Changsu Ryu, Jung Woon Yang, Seung Hwan Cho
We report a regioselective alkylation of quinolines enabled by activation of 1,1-diborylalkanes with organolithiums. Direct C2-alkylation occurs in THF with tert-butyllithium, whereas C4-alkylation of C2-substituted quinolines proceeds in toluene with phenyllithium. The regioselectivity arises from solvent-dependent lithium aggregation and substrate blocking of the C2-position. This protocol features a broad substrate scope and offers an alternative to multi-step alkylation sequences.
{"title":"Direct Alkylation of Quinolines with Organolithium-Activated 1,1-Diborylalkanes","authors":"Woohyun Jo, Changsu Ryu, Jung Woon Yang, Seung Hwan Cho","doi":"10.1039/d5qo01448d","DOIUrl":"https://doi.org/10.1039/d5qo01448d","url":null,"abstract":"We report a regioselective alkylation of quinolines enabled by activation of 1,1-diborylalkanes with organolithiums. Direct C2-alkylation occurs in THF with tert-butyllithium, whereas C4-alkylation of C2-substituted quinolines proceeds in toluene with phenyllithium. The regioselectivity arises from solvent-dependent lithium aggregation and substrate blocking of the C2-position. This protocol features a broad substrate scope and offers an alternative to multi-step alkylation sequences.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"29 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895505","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}
Marcus Söderström, Esther Oreoluwa Olaniran Håkansson, Luke R Odell
We report the first general strategy for converting trifluoromethylarenes into thioamides and heterocycles through a telescoped two-step, one-pot process. The transformation proceeds via a methyl-dithioester intermediate formed by defluorination and thiolation using the commercially available reagent BF₃·SMe₂, followed by rapid substitution with amines. This operationally simple method enables the synthesis of both primary and secondary thioamides in high yields and is readily extended to heterocycle formation using bifunctional nucleophiles. The approach demonstrates broad substrate scope, including late-stage functionalization of pharmaceuticals (flufenamic acid, cinacalcet, leflunomide, celecoxib) and amino acids/peptides, highlighting its potential in medicinal chemistry. Beyond introducing a new retrosynthetic disconnection, this work unlocks unprecedented CF₃-to-heterocycle transformations, offering a powerful tool for structural diversification and drug design.
{"title":"Late-Stage Defluorinative Functionalization: Synthesis of Thioamides and Heterocycles from Trifluoromethylarenes","authors":"Marcus Söderström, Esther Oreoluwa Olaniran Håkansson, Luke R Odell","doi":"10.1039/d5qo01574j","DOIUrl":"https://doi.org/10.1039/d5qo01574j","url":null,"abstract":"We report the first general strategy for converting trifluoromethylarenes into thioamides and heterocycles through a telescoped two-step, one-pot process. The transformation proceeds via a methyl-dithioester intermediate formed by defluorination and thiolation using the commercially available reagent BF₃·SMe₂, followed by rapid substitution with amines. This operationally simple method enables the synthesis of both primary and secondary thioamides in high yields and is readily extended to heterocycle formation using bifunctional nucleophiles. The approach demonstrates broad substrate scope, including late-stage functionalization of pharmaceuticals (flufenamic acid, cinacalcet, leflunomide, celecoxib) and amino acids/peptides, highlighting its potential in medicinal chemistry. Beyond introducing a new retrosynthetic disconnection, this work unlocks unprecedented CF₃-to-heterocycle transformations, offering a powerful tool for structural diversification and drug design.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"21 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895748","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}
Here we report a nickel/photo co-catalyzed direct radical Si-H arylation of hydrosilanes with aryl halides.Tetrabutylammonium decatungstate (TBADT) serves as a robust hydrogen-atom-transfer (HAT) photocatalyst, working synergistically with a nickel catalyst to mediate the cross-coupling between in situ generated silyl radicals and aryl-nickel intermediates. This protocol features a broad substrate scope, mild photochemical conditions, and excellent functional group tolerance, offering a versatile and sustainable approach for accessing synthetically valuable arylsilanes directly from simple hydrosilanes.
{"title":"TBADT/nickel co-catalyzed arylation of hydrosilanes with aryl halides","authors":"Kaixin Fu, Zilong Yan, Weiping Zheng, Shengchao Yang, Dong Xing, Yong Lu, Zhaolin Fu, Shuanhu Gao","doi":"10.1039/d5qo01479d","DOIUrl":"https://doi.org/10.1039/d5qo01479d","url":null,"abstract":"Here we report a nickel/photo co-catalyzed direct radical Si-H arylation of hydrosilanes with aryl halides.Tetrabutylammonium decatungstate (TBADT) serves as a robust hydrogen-atom-transfer (HAT) photocatalyst, working synergistically with a nickel catalyst to mediate the cross-coupling between in situ generated silyl radicals and aryl-nickel intermediates. This protocol features a broad substrate scope, mild photochemical conditions, and excellent functional group tolerance, offering a versatile and sustainable approach for accessing synthetically valuable arylsilanes directly from simple hydrosilanes.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"25 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145823913","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}
Qi-Xuan Jiang, Kai Xiao, Wei Huang, Feng-Hua Zhang
The multi-component reaction among alkenes, nitriles and carboxylic acids via the radical Ritter-type process is one of the most convenient and efficient methods for obtaining imides. However, these multi-component reactions still have some drawbacks, such as a limited substrate scope. More importantly, new strategies and methods should be developed to achieve selective multi-component reactions. Herein, we described a ligand-controlled copper-catalyzed multi-component reactions to access diverse imides via HAT strategy from the readily available starting material. In this novel methodology, the decomposition of TBPB could be regulated by altering the copper catalyst and ligands, thereby controlling the concentration of the in-situ generated benzoic acid anions, achieving the selective multi-component coupling reactions. The present method exhibits a broad substrate scope for alkenes and 1,3-enynes with good functional group compatibility, high atomic economy and excellent late-stage molecular modifications, demonstrating the significant advantages in practical utility.
{"title":"Ligand-controlled Copper-catalyzed Carboamination Reactions of Styrenes and 1,3-Enynes to Access Diverse Imides","authors":"Qi-Xuan Jiang, Kai Xiao, Wei Huang, Feng-Hua Zhang","doi":"10.1039/d5qo01504a","DOIUrl":"https://doi.org/10.1039/d5qo01504a","url":null,"abstract":"The multi-component reaction among alkenes, nitriles and carboxylic acids via the radical Ritter-type process is one of the most convenient and efficient methods for obtaining imides. However, these multi-component reactions still have some drawbacks, such as a limited substrate scope. More importantly, new strategies and methods should be developed to achieve selective multi-component reactions. Herein, we described a ligand-controlled copper-catalyzed multi-component reactions to access diverse imides via HAT strategy from the readily available starting material. In this novel methodology, the decomposition of TBPB could be regulated by altering the copper catalyst and ligands, thereby controlling the concentration of the in-situ generated benzoic acid anions, achieving the selective multi-component coupling reactions. The present method exhibits a broad substrate scope for alkenes and 1,3-enynes with good functional group compatibility, high atomic economy and excellent late-stage molecular modifications, demonstrating the significant advantages in practical utility.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"46 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145830512","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}
Wuding Sun, Jimin Yang, Kai Di, Luyang Sun, Shuhui Xu, Dong Li, Jinfeng Zhao, Jingping Qu, Yi Luo, Yuhan Zhou
Azulene and its derivatives are important scaffolds with broad applications. The introduction of a trifluoromethyl group is an efficient way to enhance the activity and physicochemical properties of drugs and other functional molecules. However, existing methods for the synthesis of trifluoromethyl azulenes often require harsh conditions or suffer from low yield. Herein, we report a simple, Brønsted acid-catalyzed, intramolecular annulation of 1-phenyl-2-CF3-1,3-enynes for the efficient construction of valuable trifluoromethyl-substituted azulenes. A variety of trifluoromethylated azulenes bearing diverse functional groups, including alkyl, alkoxy, phenyl, and halogen substituents, were synthesized in moderate to good yields under mild conditions. Distinct from other approaches, this method features a metal-free protocol, mild conditions, a one-step procedure, and perfect atom economy. Mechanistic studies involving deuterium-labeling experiments and DFT calculations elucidated the reaction mechanism, which involves triple-bond protonation, ring expansion, and deprotonation.
{"title":"Brønsted acid-catalyzed synthesis of trifluoromethylated azulenes via cyclization of 1-phenyl-2-CF3-1,3-enynes","authors":"Wuding Sun, Jimin Yang, Kai Di, Luyang Sun, Shuhui Xu, Dong Li, Jinfeng Zhao, Jingping Qu, Yi Luo, Yuhan Zhou","doi":"10.1039/d5qo01617g","DOIUrl":"https://doi.org/10.1039/d5qo01617g","url":null,"abstract":"Azulene and its derivatives are important scaffolds with broad applications. The introduction of a trifluoromethyl group is an efficient way to enhance the activity and physicochemical properties of drugs and other functional molecules. However, existing methods for the synthesis of trifluoromethyl azulenes often require harsh conditions or suffer from low yield. Herein, we report a simple, Brønsted acid-catalyzed, intramolecular annulation of 1-phenyl-2-CF<small><sub>3</sub></small>-1,3-enynes for the efficient construction of valuable trifluoromethyl-substituted azulenes. A variety of trifluoromethylated azulenes bearing diverse functional groups, including alkyl, alkoxy, phenyl, and halogen substituents, were synthesized in moderate to good yields under mild conditions. Distinct from other approaches, this method features a metal-free protocol, mild conditions, a one-step procedure, and perfect atom economy. Mechanistic studies involving deuterium-labeling experiments and DFT calculations elucidated the reaction mechanism, which involves triple-bond protonation, ring expansion, and deprotonation.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"91 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145823914","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}
Baoping Ren, Long Sun, Junsheng Zhi, Qun Liu, Yifei Li, Ling Pan
The difluoromethylation of various substrates has experienced significant advancements with the rapid development of photoinduced reactions. However, the difluoromethylation of alkenes are usually limited to addition reactions, the C(sp2)−CF2H construction mostly occur in heteroaromatics. This study presents a novel iridium photocatalyst-cobaloxime co-mediated difluoromethylation of a type of polarized internal alkene, ketene dithioacetal. Mechanistic investigations highlighted the crucial role of the cobaloxime, and subsequent transformations further demonstrated the practical value of the products. This approach offers a promising avenue for utilizing partially fluorinated alkyl sulfinates in radical fluoroalkylation reactions under mild conditions.
{"title":"Photoinduced Iridium-Cobaloxime mediated Alkene C(sp2)-CF2H Cross-coupling：Difluoromethylation of Ketene dithioacetal","authors":"Baoping Ren, Long Sun, Junsheng Zhi, Qun Liu, Yifei Li, Ling Pan","doi":"10.1039/d5qo01628b","DOIUrl":"https://doi.org/10.1039/d5qo01628b","url":null,"abstract":"The difluoromethylation of various substrates has experienced significant advancements with the rapid development of photoinduced reactions. However, the difluoromethylation of alkenes are usually limited to addition reactions, the C(sp<small><sup>2</sup></small>)−CF<small><sub>2</sub></small>H construction mostly occur in heteroaromatics. This study presents a novel iridium photocatalyst-cobaloxime co-mediated difluoromethylation of a type of polarized internal alkene, ketene dithioacetal. Mechanistic investigations highlighted the crucial role of the cobaloxime, and subsequent transformations further demonstrated the practical value of the products. This approach offers a promising avenue for utilizing partially fluorinated alkyl sulfinates in radical fluoroalkylation reactions under mild conditions.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"7 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145823915","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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