Pub Date : 2026-02-05DOI: 10.1021/acs.orglett.6c00194
Yunlong Qin, Yuanyuan Zeng, Weihan Wang, Congcong Zhang, Jianing Zhang, Zerong Guo, Yang Zhao, Qilin Wang
A visible-light-driven skeletal editing strategy that converts readily available isoquinolinium salts into phenylnaphthyl sulfones via a formal CN-to-CC atom-pair swap is presented. The process is triggered by an isoquinolinium–carbonate electron donor–acceptor (EDA) complex that, upon blue-light excitation, undergoes single-electron transfer to initiate a polarity-mismatched (4 + 2) radical annulation with alkynyl sulfones. The reaction proceeds at room temperature without external photocatalysts, tolerates diverse functional groups (including halides), and furnishes the targeted diarylsulfones with high efficiency.
{"title":"Light Illuminates Polarity-Mismatched Cycloaddition to Convert Isoquinoliniums into Phenylnaphthyl Sulfones","authors":"Yunlong Qin, Yuanyuan Zeng, Weihan Wang, Congcong Zhang, Jianing Zhang, Zerong Guo, Yang Zhao, Qilin Wang","doi":"10.1021/acs.orglett.6c00194","DOIUrl":"https://doi.org/10.1021/acs.orglett.6c00194","url":null,"abstract":"A visible-light-driven skeletal editing strategy that converts readily available isoquinolinium salts into phenylnaphthyl sulfones via a formal CN-to-CC atom-pair swap is presented. The process is triggered by an isoquinolinium–carbonate electron donor–acceptor (EDA) complex that, upon blue-light excitation, undergoes single-electron transfer to initiate a polarity-mismatched (4 + 2) radical annulation with alkynyl sulfones. The reaction proceeds at room temperature without external photocatalysts, tolerates diverse functional groups (including halides), and furnishes the targeted diarylsulfones with high efficiency.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"68 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122462","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}
Electrochemical peptide synthesis using triaryl phosphines has been shown to be a promising approach for reducing the amount of waste in peptide synthesis. However, there is room for improvement from the viewpoint of the substrate scope. In this research, we succeeded in improving the reaction efficiency by utilizing a halide mediator. This method is applicable to highly sterically hindered amino acids, such as N-methyl phenylalanine. We also achieved the synthesis of icatibant, consisting of 10 amino acid residues.
{"title":"Halide-Mediated Electrochemical Peptide Synthesis Applicable to Highly Sterically Hindered Amino Acids","authors":"Shingo Shinjo-Nagahara, Goki Hiratsuka, Yohei Okada, Yoshikazu Kitano, Kazuhiro Chiba","doi":"10.1021/acs.orglett.5c05139","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c05139","url":null,"abstract":"Electrochemical peptide synthesis using triaryl phosphines has been shown to be a promising approach for reducing the amount of waste in peptide synthesis. However, there is room for improvement from the viewpoint of the substrate scope. In this research, we succeeded in improving the reaction efficiency by utilizing a halide mediator. This method is applicable to highly sterically hindered amino acids, such as <i>N</i>-methyl phenylalanine. We also achieved the synthesis of icatibant, consisting of 10 amino acid residues.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"8 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115603","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}
Pub Date : 2026-02-05DOI: 10.1021/acs.orglett.5c05278
Anukriti Singhal, Partha Pratim Sen, Sudipta Raha Roy
A visible-light-mediated metallomimetic charge transfer strategy for the amination of the inert C(sp3)–H bond of ethers has been demonstrated. This organocatalytic strategy utilizes a polyaromatic odd alternant hydrocarbon-based photocatalyst exhibiting a Lewis acidic property and, thereby, mimics the transition-metal-like charge transfer process that drives the single-electron transfer process, enabling the C–H bond functionalization under mild and sustainable conditions. The method offers a mechanistically distinct platform for light-driven C–N bond formation, expanding the scope of photoinduced organic transformations.
{"title":"Organocatalytic Visible-Light-Driven Metallomimetic Charge Transfer Process: Application in C(sp3)–N Bond Formation","authors":"Anukriti Singhal, Partha Pratim Sen, Sudipta Raha Roy","doi":"10.1021/acs.orglett.5c05278","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c05278","url":null,"abstract":"A visible-light-mediated metallomimetic charge transfer strategy for the amination of the inert C(sp<sup>3</sup>)–H bond of ethers has been demonstrated. This organocatalytic strategy utilizes a polyaromatic odd alternant hydrocarbon-based photocatalyst exhibiting a Lewis acidic property and, thereby, mimics the transition-metal-like charge transfer process that drives the single-electron transfer process, enabling the C–H bond functionalization under mild and sustainable conditions. The method offers a mechanistically distinct platform for light-driven C–N bond formation, expanding the scope of photoinduced organic transformations.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"276 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115606","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}
Pub Date : 2026-02-05DOI: 10.1021/acs.orglett.5c05336
Natalia Cano-Sampaio, Juan R. Del Valle
Cyclization of serine and threonine-containing N-hydroxy dipeptides under Mitsunobu conditions affords 1,3-oxazinanes via N-acylimine intermediates. Synthesis of the heterocyclic core of the threoglucin family of antibiotics proceeds in high yield to afford the α-quaternary amidoketal dipeptide. The described method provides convenient entry into a new class of constrained peptides featuring Cα-heteroatom substitution.
{"title":"Synthesis of the Threoglucin 1,3-Oxazinane Core via Cyclothreonine Rearrangement","authors":"Natalia Cano-Sampaio, Juan R. Del Valle","doi":"10.1021/acs.orglett.5c05336","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c05336","url":null,"abstract":"Cyclization of serine and threonine-containing <i>N</i>-hydroxy dipeptides under Mitsunobu conditions affords 1,3-oxazinanes via N-acylimine intermediates. Synthesis of the heterocyclic core of the threoglucin family of antibiotics proceeds in high yield to afford the α-quaternary amidoketal dipeptide. The described method provides convenient entry into a new class of constrained peptides featuring Cα-heteroatom substitution.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"91 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115611","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 photocatalyzed decarboxylative hydroalkylation approach has been developed, providing efficient and stereoselective access to synthetically challenging Z-configured allylamine derivatives from carboxylic acids and alkynes. The reaction is mediated by an iron catalyst, offering a green, environmentally benign, and highly atom-economical process. Moreover, this protocol can be extended to the reaction with alkenes to furnish arylamines and aryl ethers. Overall, this strategy establishes a versatile synthetic platform for the functionalization of unsaturated hydrocarbons.
{"title":"Iron-Catalyzed Photoredox Decarboxylative Hydroalkylation with Alkynes and Alkenes","authors":"Zhenzhu Hu, Haoran Yuan, Yuxin Lin, Jing Peng, Xiaoxiao Ma, Rongqiang Li","doi":"10.1021/acs.orglett.5c05310","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c05310","url":null,"abstract":"A photocatalyzed decarboxylative hydroalkylation approach has been developed, providing efficient and stereoselective access to synthetically challenging <i>Z</i>-configured allylamine derivatives from carboxylic acids and alkynes. The reaction is mediated by an iron catalyst, offering a green, environmentally benign, and highly atom-economical process. Moreover, this protocol can be extended to the reaction with alkenes to furnish arylamines and aryl ethers. Overall, this strategy establishes a versatile synthetic platform for the functionalization of unsaturated hydrocarbons.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"83 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122458","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 report a strategy for the methylalkylation of unactivated alkenes via synergistic photoredox/nickel catalysis. This mild transformation employs di-tert-butyl peroxide (DTBP) as a bifunctional reagent, which serves simultaneously as a hydrogen atom transfer (HAT) reagent and a source of methyl radical, thereby facilitating the coupling of malonate-derived radicals with alkenes. By integrating HAT with radical selectivity control, the method enables the formation of two C(sp3)–C(sp3) bonds in a single synthetic operation, offering a streamlined route to valuable three-dimensional scaffolds.
{"title":"Methylalkylation of Unactivated Alkenes by Photoredox/Nickel Catalytic HAT and Radical Selectivity Control","authors":"Hui Zhang, Ying-Jie Wang, Hao-Wen Jiang, Peng-Fei Xu","doi":"10.1021/acs.orglett.5c05168","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c05168","url":null,"abstract":"Herein, we report a strategy for the methylalkylation of unactivated alkenes via synergistic photoredox/nickel catalysis. This mild transformation employs di-<i>tert</i>-butyl peroxide (DTBP) as a bifunctional reagent, which serves simultaneously as a hydrogen atom transfer (HAT) reagent and a source of methyl radical, thereby facilitating the coupling of malonate-derived radicals with alkenes. By integrating HAT with radical selectivity control, the method enables the formation of two C(sp<sup>3</sup>)–C(sp<sup>3</sup>) bonds in a single synthetic operation, offering a streamlined route to valuable three-dimensional scaffolds.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"1 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115604","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}
Pub Date : 2026-02-05DOI: 10.1021/acs.orglett.6c00021
Xuling Chen, Changzhen Zhai, Yan Guo, Lilei Cheng, Tianli Wang, Pengfei Li
The catalytic construction of medium-sized rings, particularly in an enantioselective manner, remains a significant challenge due to inherent entropic penalties and stereocontrol issues, yet it is an area of great interest. Herein, we disclose the development of a general (6 + n) annulation strategy leveraging 2-(4H-benzo[d][1,3]oxazin-4-yl)acrylates as versatile precursors for the efficient assembly of medium-sized rings. Through palladium-catalyzed formal (6 + 5) and (6 + 3) cycloadditions with vinylethylene carbonates (VECs) or trimethylenemethanes (TMMs), we have successfully achieved the regioselective construction of 11- and 9-membered heterocycles, respectively. Of particular note, the enantioselective (6 + 3) annulation, facilitated by rational chiral ligand design, afforded enantioenriched 9-membered heterocycles (up to 75% yield and 93% ee). Featuring readily available starting materials, structural modularity, and mild reaction conditions, this methodology represents a robust platform for accessing synthetically valuable medium-sized ring systems, including their enantioselective variants, thereby addressing a long-standing limitation in organic synthesis.
{"title":"Enantioselective Synthesis of Medium-Sized Rings via a General Palladium-Catalyzed (6 + n) Annulation Platform","authors":"Xuling Chen, Changzhen Zhai, Yan Guo, Lilei Cheng, Tianli Wang, Pengfei Li","doi":"10.1021/acs.orglett.6c00021","DOIUrl":"https://doi.org/10.1021/acs.orglett.6c00021","url":null,"abstract":"The catalytic construction of medium-sized rings, particularly in an enantioselective manner, remains a significant challenge due to inherent entropic penalties and stereocontrol issues, yet it is an area of great interest. Herein, we disclose the development of a general (6 + <i>n</i>) annulation strategy leveraging 2-(4<i>H</i>-benzo[<i>d</i>][1,3]oxazin-4-yl)acrylates as versatile precursors for the efficient assembly of medium-sized rings. Through palladium-catalyzed formal (6 + 5) and (6 + 3) cycloadditions with vinylethylene carbonates (VECs) or trimethylenemethanes (TMMs), we have successfully achieved the regioselective construction of 11- and 9-membered heterocycles, respectively. Of particular note, the enantioselective (6 + 3) annulation, facilitated by rational chiral ligand design, afforded enantioenriched 9-membered heterocycles (up to 75% yield and 93% ee). Featuring readily available starting materials, structural modularity, and mild reaction conditions, this methodology represents a robust platform for accessing synthetically valuable medium-sized ring systems, including their enantioselective variants, thereby addressing a long-standing limitation in organic synthesis.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"177 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146122310","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}
Pub Date : 2026-02-04DOI: 10.1021/acs.orglett.6c00146
Rekha Bai,Wan-Lin Cheng,Chun-Yu Peng,Yu-Hao Chen,Pin-Han Wang,Chin-Fa Lee
A molecular iodine-catalyzed three-component cascade reaction of indoles/pyrroles, anilines, and DABSO has been developed, providing C2-sulfonylated indoles/pyrroles in good to excellent yields. The transformation proceeds via the in situ generation of the arylsulfonyl radical from the reaction of anilines, tBuONO, and DABSO, followed by controlled formation of a carbon-centered radical intermediate. In this radical-mediated cascade reaction, DABSO acts as the sulfone (SO2) source while tBuONO facilitates the generation of reactive species. Moreover, this one-pot transformation proceeds under mild conditions, exhibits a broad substrate scope, and offers an efficient and sustainable strategy for the construction of C2-sulfonated indoles and pyrroles.
{"title":"Regioselective C2-Sulfonylation of Indoles and Pyrroles via SO2 Insertions","authors":"Rekha Bai,Wan-Lin Cheng,Chun-Yu Peng,Yu-Hao Chen,Pin-Han Wang,Chin-Fa Lee","doi":"10.1021/acs.orglett.6c00146","DOIUrl":"https://doi.org/10.1021/acs.orglett.6c00146","url":null,"abstract":"A molecular iodine-catalyzed three-component cascade reaction of indoles/pyrroles, anilines, and DABSO has been developed, providing C2-sulfonylated indoles/pyrroles in good to excellent yields. The transformation proceeds via the in situ generation of the arylsulfonyl radical from the reaction of anilines, tBuONO, and DABSO, followed by controlled formation of a carbon-centered radical intermediate. In this radical-mediated cascade reaction, DABSO acts as the sulfone (SO2) source while tBuONO facilitates the generation of reactive species. Moreover, this one-pot transformation proceeds under mild conditions, exhibits a broad substrate scope, and offers an efficient and sustainable strategy for the construction of C2-sulfonated indoles and pyrroles.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"106 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111171","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}
Catalytic reductive coupling of unsaturated hydrocarbons with carbonyl compounds provides a streamlined alternative to stoichiometric organometallic additions, yet asymmetric variants that directly engage unactivated alkenes remain limited. Here we report a diastereo- and enantioselective nickel-catalyzed intramolecular reductive cyclization of unactivated alkenes and aldehydes. Using a chiral monodentate phosphoramidite ligand and triethylborane as the terminal reductant, the method delivers substituted cyclic alcohols as single diastereomers in up to 98% yield and up to 99% ee, with broad functional-group tolerance including halides, free alcohols, esters, and boronic esters. Applications to bioactive-molecule synthesis are demonstrated, and DFT studies support an enantiodetermining oxidative cyclization pathway.
{"title":"Diastereo- and Enantioselective Nickel-Catalyzed Intramolecular Reductive Cyclization of Unactivated Alkenes and Aldehydes.","authors":"Xiao-Ya Sun, Xiang-Rui Liu, Ye-Wei Huang, Qi-Lin Zhou, Li-Jun Xiao","doi":"10.1021/acs.orglett.6c00185","DOIUrl":"https://doi.org/10.1021/acs.orglett.6c00185","url":null,"abstract":"<p><p>Catalytic reductive coupling of unsaturated hydrocarbons with carbonyl compounds provides a streamlined alternative to stoichiometric organometallic additions, yet asymmetric variants that directly engage unactivated alkenes remain limited. Here we report a diastereo- and enantioselective nickel-catalyzed intramolecular reductive cyclization of unactivated alkenes and aldehydes. Using a chiral monodentate phosphoramidite ligand and triethylborane as the terminal reductant, the method delivers substituted cyclic alcohols as single diastereomers in up to 98% yield and up to 99% ee, with broad functional-group tolerance including halides, free alcohols, esters, and boronic esters. Applications to bioactive-molecule synthesis are demonstrated, and DFT studies support an enantiodetermining oxidative cyclization pathway.</p>","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117216","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}
Pub Date : 2026-02-04DOI: 10.1021/acs.orglett.5c05428
Lu Gan,Xin-Yi Hu,Rong Huang,Li-Fen Ma,Dean Guo,Wei Li
Two heterodimeric sesquiterpenoids, chlorjaponoids A (1) and B (2), were isolated from the whole plants of Chloranthus japonicus. Their structures, characterized by a unique cage-like tetracyclo[8.5.0.02,7.03,13]pentadecane scaffold, were elucidated by comprehensive spectroscopic analysis and confirmed by single-crystal X-ray diffraction. Both compounds demonstrated antihepatic fibrosis activity in vitro.
{"title":"Chlorjaponoids A and B, Two Lindenane–Guaiane Sesquiterpenoid Dimers with a Cage-like Tetracyclo[8.5.0.02,7.03,13]pentadecane Scaffold from Chloranthus japonicus","authors":"Lu Gan,Xin-Yi Hu,Rong Huang,Li-Fen Ma,Dean Guo,Wei Li","doi":"10.1021/acs.orglett.5c05428","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c05428","url":null,"abstract":"Two heterodimeric sesquiterpenoids, chlorjaponoids A (1) and B (2), were isolated from the whole plants of Chloranthus japonicus. Their structures, characterized by a unique cage-like tetracyclo[8.5.0.02,7.03,13]pentadecane scaffold, were elucidated by comprehensive spectroscopic analysis and confirmed by single-crystal X-ray diffraction. Both compounds demonstrated antihepatic fibrosis activity in vitro.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"8 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146111165","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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