Pub Date : 2025-12-08DOI: 10.1021/acs.orglett.5c04559
Zhaoliang Ge,Su-Na Guan,Hao Xu
A highly enantioselective Cu/NHC cooperative catalytic system was developed for the remote ε-alkylation of yne-thiophene esters with enals. The dual catalysis couples a chiral Cu-PyBox complex, which generates a reactive copper-vinylallenylidene intermediate, with an N-heterocyclic carbene (NHC) catalyst that forms a nucleophilic Breslow intermediate via umpolung activation of the enal. The synergistic interaction between the two chiral catalysts enables smooth C-C bond formation at the ε-position, delivering a broad range of 3,3-disubstituted oxindoles in up to 99% ee, >95:5 dr, and 94% yield. Mechanistic studies─including control and nonlinear-effect experiments─reveal that only one NHC molecule participates in the stereodetermining step and that matched chiral configurations of the Cu-PyBox and NHC catalysts are essential for both efficiency and selectivity. This strategy provides a versatile platform for remote asymmetric transformations and the streamlined synthesis of complex oxindole architectures.
{"title":"Copper/N-Heterocyclic Carbene Cooperatively Catalyzed Remote Asymmetric ε-Alkylation of Yne-Thiophene Esters with Enals.","authors":"Zhaoliang Ge,Su-Na Guan,Hao Xu","doi":"10.1021/acs.orglett.5c04559","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04559","url":null,"abstract":"A highly enantioselective Cu/NHC cooperative catalytic system was developed for the remote ε-alkylation of yne-thiophene esters with enals. The dual catalysis couples a chiral Cu-PyBox complex, which generates a reactive copper-vinylallenylidene intermediate, with an N-heterocyclic carbene (NHC) catalyst that forms a nucleophilic Breslow intermediate via umpolung activation of the enal. The synergistic interaction between the two chiral catalysts enables smooth C-C bond formation at the ε-position, delivering a broad range of 3,3-disubstituted oxindoles in up to 99% ee, >95:5 dr, and 94% yield. Mechanistic studies─including control and nonlinear-effect experiments─reveal that only one NHC molecule participates in the stereodetermining step and that matched chiral configurations of the Cu-PyBox and NHC catalysts are essential for both efficiency and selectivity. This strategy provides a versatile platform for remote asymmetric transformations and the streamlined synthesis of complex oxindole architectures.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"209 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696713","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 : 2025-12-08DOI: 10.1021/acs.orglett.5c04587
Satyajit Behera,Neema Patel,Aishwarya Shelke,Suvarn S Kulkarni
Herein, we report the first total synthesis of the trisaccharide repeating unit of Pseudomonas putida TSh18, achieved through a one-pot glycosylation strategy. The synthesis addresses several challenges, including the synthesis of rare sugars d-Fucp4N3 and d-QuipNAc4NAc, installation of consecutive 1,2-cis linkages, and a late-stage amide coupling. Access to d-Fucp4N3 was enabled for the first time by applying a double serial inversion approach. The synthesis was completed in 19 linear steps with an overall yield of 5.5%.
{"title":"One-Pot Assembly of the Rare Sugar Containing Trisaccharide Repeating Unit of Pseudomonas putida TSh-18.","authors":"Satyajit Behera,Neema Patel,Aishwarya Shelke,Suvarn S Kulkarni","doi":"10.1021/acs.orglett.5c04587","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04587","url":null,"abstract":"Herein, we report the first total synthesis of the trisaccharide repeating unit of Pseudomonas putida TSh18, achieved through a one-pot glycosylation strategy. The synthesis addresses several challenges, including the synthesis of rare sugars d-Fucp4N3 and d-QuipNAc4NAc, installation of consecutive 1,2-cis linkages, and a late-stage amide coupling. Access to d-Fucp4N3 was enabled for the first time by applying a double serial inversion approach. The synthesis was completed in 19 linear steps with an overall yield of 5.5%.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"4 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696766","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 : 2025-12-08DOI: 10.1021/acs.orglett.5c04055
Anit Pal,Animesh Das
This work reports ruthenium-catalyzed tandem reductive alkylation of N-heteroarenes to form saturated azacycles. In this reaction, alkyl formates are used as a new class of hydroalkylation reagents with LiI as a promoter. The reaction proceeds via C-O σ-bond cleavage of the formate scaffold, generating a hydride nucleophile and alkyl electrophile. The reaction features a broad substrate scope and produces CO2 as the only byproduct, making the protocol atom efficient and environmentally friendly.
{"title":"Catalytic Reductive Alkylation of Pyridine-Fused N-Heteroarenes Using Alkyl Formates as Transfer Hydroalkylation Reagents.","authors":"Anit Pal,Animesh Das","doi":"10.1021/acs.orglett.5c04055","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04055","url":null,"abstract":"This work reports ruthenium-catalyzed tandem reductive alkylation of N-heteroarenes to form saturated azacycles. In this reaction, alkyl formates are used as a new class of hydroalkylation reagents with LiI as a promoter. The reaction proceeds via C-O σ-bond cleavage of the formate scaffold, generating a hydride nucleophile and alkyl electrophile. The reaction features a broad substrate scope and produces CO2 as the only byproduct, making the protocol atom efficient and environmentally friendly.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"8 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696676","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 : 2025-12-08DOI: 10.1021/acs.orglett.5c04722
Bin Ma,Xinyue Tang,Xin Zhou,Dekun Meng,Anqi Feng,Deyun Qian
Despite the widespread utilization of organoboron compounds across various areas, the efficient construction of stable and enantioenriched boron-centered chiral molecules remains a persistent challenge. Here, we present a nickel-catalyzed system for the asymmetric synthesis of boron-stereogenic heterocycles by the denitrogenative annulation reaction of benzotriazones with alkynes under mild conditions. Newly modified chiral BiIM ligands were the key factor in achieving high reactivity and stereoselectivity (up to 96% yield, 98% ee). This reaction not only enables access to a diverse range of highly functionalized chiral boron-centered compounds but also delivers optically active terminal/internal alkyne and isoquinolone moieties with various potential utility prospects. In addition, we demonstrated postsynthetic functionalization of natural products and drug molecules, along with the photophysical properties and bioimaging capabilities of these tailored boron-stereogenic heterocycles, underscoring their promise as chiral fluorescent probes and versatile platforms in multidisciplinary research.
{"title":"Enantioselective Synthesis of Boron-Stereogenic Heterocycles Enabled by Asymmetric Nickel Catalysis.","authors":"Bin Ma,Xinyue Tang,Xin Zhou,Dekun Meng,Anqi Feng,Deyun Qian","doi":"10.1021/acs.orglett.5c04722","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04722","url":null,"abstract":"Despite the widespread utilization of organoboron compounds across various areas, the efficient construction of stable and enantioenriched boron-centered chiral molecules remains a persistent challenge. Here, we present a nickel-catalyzed system for the asymmetric synthesis of boron-stereogenic heterocycles by the denitrogenative annulation reaction of benzotriazones with alkynes under mild conditions. Newly modified chiral BiIM ligands were the key factor in achieving high reactivity and stereoselectivity (up to 96% yield, 98% ee). This reaction not only enables access to a diverse range of highly functionalized chiral boron-centered compounds but also delivers optically active terminal/internal alkyne and isoquinolone moieties with various potential utility prospects. In addition, we demonstrated postsynthetic functionalization of natural products and drug molecules, along with the photophysical properties and bioimaging capabilities of these tailored boron-stereogenic heterocycles, underscoring their promise as chiral fluorescent probes and versatile platforms in multidisciplinary research.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"38 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696678","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 : 2025-12-08DOI: 10.1021/acs.orglett.5c04555
Hongyin Huang,Yilian Lu,Mengqi Gui,Nianxing Wang,Huaifeng Li
This radical strategy represents the first use of sulfoxonium ylide-derived radicals in 1-naphthol synthesis and overcomes the substrate limitations of classical carbene-based methods. It enables annulation of unactivated terminal alkynes─previously challenging substrates─under mild, metal- and additive-free, visible-light conditions. Mechanistic studies support formation of a highly electrophilic hindered radical cation that undergoes polarity-inverted addition and benzannulation, establishing sulfoxonium ylides as versatile radical precursors for modular 1-naphthol construction.
{"title":"Redox-Neutral Radical Annulation of Challenging Alkynes with Aryl Sulfoxonium Ylides for 1-Naphthol Synthesis.","authors":"Hongyin Huang,Yilian Lu,Mengqi Gui,Nianxing Wang,Huaifeng Li","doi":"10.1021/acs.orglett.5c04555","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04555","url":null,"abstract":"This radical strategy represents the first use of sulfoxonium ylide-derived radicals in 1-naphthol synthesis and overcomes the substrate limitations of classical carbene-based methods. It enables annulation of unactivated terminal alkynes─previously challenging substrates─under mild, metal- and additive-free, visible-light conditions. Mechanistic studies support formation of a highly electrophilic hindered radical cation that undergoes polarity-inverted addition and benzannulation, establishing sulfoxonium ylides as versatile radical precursors for modular 1-naphthol construction.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"209 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696682","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 nickel-catalyzed Satoh-Miura annulation of free benzylamines with alkynes, enabled by a transient directing group (TDG) strategy. The integration of the TDG approach with earth-abundant nickel catalysis provides a straightforward and efficient route for the synthesis of substituted 1-naphthylmethylamines, which exhibits excellent functional group tolerance. Compared with conventional directing group (DG)-directed precious-metal-catalyzed systems for polycyclic aromatic hydrocarbon (PAH) synthesis, this protocol demonstrates advantages in atom- and step-economy, cost effectiveness, and sustainability.
{"title":"Transient Directing Group Enabled Nickel-Catalyzed Satoh-Miura Annulation of Free Benzylamines with Alkynes.","authors":"Chen Ma,Jinlong Liu,Ying Kang,Yuqiang Ren,Xue Meng,Weiwei Li,Shen Li,Xinghao Cai,Shiming Fan,Shouxin Liu","doi":"10.1021/acs.orglett.5c03914","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c03914","url":null,"abstract":"We report a nickel-catalyzed Satoh-Miura annulation of free benzylamines with alkynes, enabled by a transient directing group (TDG) strategy. The integration of the TDG approach with earth-abundant nickel catalysis provides a straightforward and efficient route for the synthesis of substituted 1-naphthylmethylamines, which exhibits excellent functional group tolerance. Compared with conventional directing group (DG)-directed precious-metal-catalyzed systems for polycyclic aromatic hydrocarbon (PAH) synthesis, this protocol demonstrates advantages in atom- and step-economy, cost effectiveness, and sustainability.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"6 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696683","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 : 2025-12-08DOI: 10.1021/acs.orglett.5c04561
Ru-Yi Lu,Shuaijie Jiang,Kejing Zhang,Ming Lu,Pengcheng Wang
Achieving both high density and thermal stability remains challenging in energetic materials. This work presents a targeted co-crystal (DHANP·2HClO4) prepared via molecular self-assembly. It exhibits a density of 2.03 g cm-3 and an onset decomposition temperature of 235 °C, demonstrating an excellent balance between these properties. Compared to conventional perchlorate-based materials, this co-crystal overcomes the typical performance trade-off, offering a promising strategy for designing advanced energetic materials with superior comprehensive performance.
在高能材料中实现高密度和热稳定性仍然具有挑战性。本文通过分子自组装制备了一种靶向共晶（DHANP·2HClO4）。它的密度为2.03 g cm-3，起始分解温度为235℃，证明了这些性能之间的良好平衡。与传统的高氯酸盐基材料相比，这种共晶克服了典型的性能权衡，为设计具有优越综合性能的先进含能材料提供了一种有前途的策略。
{"title":"Breaking the Density-Thermal Stability Trade-Off: Targeted Design and Construction of an Energetic Co-crystal.","authors":"Ru-Yi Lu,Shuaijie Jiang,Kejing Zhang,Ming Lu,Pengcheng Wang","doi":"10.1021/acs.orglett.5c04561","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04561","url":null,"abstract":"Achieving both high density and thermal stability remains challenging in energetic materials. This work presents a targeted co-crystal (DHANP·2HClO4) prepared via molecular self-assembly. It exhibits a density of 2.03 g cm-3 and an onset decomposition temperature of 235 °C, demonstrating an excellent balance between these properties. Compared to conventional perchlorate-based materials, this co-crystal overcomes the typical performance trade-off, offering a promising strategy for designing advanced energetic materials with superior comprehensive performance.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"5 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704582","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 : 2025-12-08DOI: 10.1021/acs.orglett.5c04825
Qinglong Liu,Boyang Mu,Haina Zhao,Wangze Song
A variety of spirocyclobutyl lactams were conveniently prepared by the Brønsted acid-catalyzed α-selective ring-opening of bicyclo[1.1.0]butane (BCB) within 15 min under mild conditions without any photocatalysts, oxidants, metal catalysts, or radical initiators. This reaction involved the rapid ring-opening of BCB to generate carbocation, which further efficiently promoted intramolecular Friedel-Crafts alkylation or intramolecular spirocyclization to access diverse spirocyclobutyl lactams.
{"title":"α-Selective Ring-Opening of Bicyclo[1.1.0]butanes to Access Spirocyclobutyl Lactams.","authors":"Qinglong Liu,Boyang Mu,Haina Zhao,Wangze Song","doi":"10.1021/acs.orglett.5c04825","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04825","url":null,"abstract":"A variety of spirocyclobutyl lactams were conveniently prepared by the Brønsted acid-catalyzed α-selective ring-opening of bicyclo[1.1.0]butane (BCB) within 15 min under mild conditions without any photocatalysts, oxidants, metal catalysts, or radical initiators. This reaction involved the rapid ring-opening of BCB to generate carbocation, which further efficiently promoted intramolecular Friedel-Crafts alkylation or intramolecular spirocyclization to access diverse spirocyclobutyl lactams.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"140 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704585","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 : 2025-12-08DOI: 10.1021/acs.orglett.5c04611
Jing He,Wan Seok Yoon,Jaesook Yun
This work discloses the first enantioselective copper-catalyzed acylation of 1,3-enynes with acyl fluorides. The reaction proceeds via an enantioenriched allenylcopper species that is chemoselectively generated from enynes in the presence of competing acyl fluorides. The resulting products bearing all-carbon quaternary centers are obtained with high enantioselectivity through a copper-oxygen-coordinated transition state. The method provides a practical and scalable strategy for asymmetric C-C bond formation with broad functional group tolerance.
{"title":"Copper-Catalyzed Regio- and Enantioselective Acylation of 1,3-Enynes.","authors":"Jing He,Wan Seok Yoon,Jaesook Yun","doi":"10.1021/acs.orglett.5c04611","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04611","url":null,"abstract":"This work discloses the first enantioselective copper-catalyzed acylation of 1,3-enynes with acyl fluorides. The reaction proceeds via an enantioenriched allenylcopper species that is chemoselectively generated from enynes in the presence of competing acyl fluorides. The resulting products bearing all-carbon quaternary centers are obtained with high enantioselectivity through a copper-oxygen-coordinated transition state. The method provides a practical and scalable strategy for asymmetric C-C bond formation with broad functional group tolerance.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"13 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704580","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 : 2025-12-08DOI: 10.1021/acs.orglett.5c04490
Xuanhao Zhang,Lanting Xu,Bin Wu,Dawei Ma
A method is described for the synthesis of α-aryl and allylic sulfones and sulfonamides through CuBr/oxalamide-catalyzed coupling at 40 °C. This transformation involves coupling with (hetero)aryl or vinyl bromides and 2-substituted sulfonylacetates (or amide analogues), proceeding via spontaneous hydrolysis and decarboxylation. The conditions are compatible with various functional groups and heterocycles, allowing for the diverse syntheses of the target compounds.
{"title":"Assembly of α-Aryl Sulfones and Allyl Sulfones and Their Amide Analogues via Copper-Catalyzed Coupling Reactions.","authors":"Xuanhao Zhang,Lanting Xu,Bin Wu,Dawei Ma","doi":"10.1021/acs.orglett.5c04490","DOIUrl":"https://doi.org/10.1021/acs.orglett.5c04490","url":null,"abstract":"A method is described for the synthesis of α-aryl and allylic sulfones and sulfonamides through CuBr/oxalamide-catalyzed coupling at 40 °C. This transformation involves coupling with (hetero)aryl or vinyl bromides and 2-substituted sulfonylacetates (or amide analogues), proceeding via spontaneous hydrolysis and decarboxylation. The conditions are compatible with various functional groups and heterocycles, allowing for the diverse syntheses of the target compounds.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"3 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696675","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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