{"title":"A chiral ferrocene-based P,Se-ligand for Cu-catalyzed 1,3-dipolar cycloaddition and Pd-catalyzed allylic substitution.","authors":"Ge-Yun You, Yan-Qin Wu, Hao-Song Wei, Hua-Jian Qin, Xing-Jing Huang, Chu-Yao Qiao, Hong-Kai Huang, Cui-Zhen Wang, Bin Feng","doi":"10.1039/d6ob01039c","DOIUrl":"https://doi.org/10.1039/d6ob01039c","url":null,"abstract":"<p><p>A novel chiral ferrocenyl P,Se-ligand has been prepared through an efficient and simple operation. This ligand can be successfully applied in the Cu-catalyzed asymmetric 1,3-dipolar cycloaddition of imino esters with <i>N</i>-phenylmaleimide and Pd-catalyzed allylic substitution of C- and O-nucleophiles, producing a diverse range of products with high yields and enantioselectivities (up to 96% yield and 95% ee).</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Indole dearomative [3,3]-Claisen rearrangement: access to indole alkaloids with C2/C3 quaternary stereocenters.","authors":"Zhi-Hua Ma, Hui Shao, Yu-Ming Zhao","doi":"10.1039/d6ob01177b","DOIUrl":"https://doi.org/10.1039/d6ob01177b","url":null,"abstract":"<p><p>Polycyclic indole alkaloids bearing a C2 and/or C3 quaternary stereocenter feature diverse skeletons and promising biological activities, rendering them important targets in natural product synthesis and medicinal chemistry. A central synthetic challenge in preparing these molecules lies in the efficient construction of the C2 or C3 quaternary stereocenter. The indole dearomative [3,3]-Claisen rearrangement enables the facile assembly of the C2 or C3 quaternary stereocenter of indole, exhibiting excellent stereospecificity, broad functional group tolerance, and versatile product architectures. This transformation has been extensively exploited in the total synthesis of complex indole alkaloids. In this review, we classify indole dearomative [3,3]-Claisen rearrangements into four categories based on substrate types and systematically summarize their synthetic applications in natural product synthesis over the past five decades.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Recent advances in asymmetric electrochemical organocatalysis.","authors":"Huaiyu Hu, Lu Song, Niankai Fu","doi":"10.1039/d6ob01169a","DOIUrl":"https://doi.org/10.1039/d6ob01169a","url":null,"abstract":"<p><p>The strategic integration of asymmetric organocatalysis with electroorganic synthesis has recently emerged as a versatile synthetic platform for the construction of chiral molecular scaffolds in a sustainable fashion. This review summarizes the research progress of asymmetric electrochemical organocatalysis from 2020 to 2026, covering its fundamental principles, mechanistic frameworks, and state-of-the-art advancements. Two core organocatalytic activation modes are systematically elaborated herein: covalent catalysis, represented by enamine catalysis and N-heterocyclic carbene (NHC) catalysis, which generate catalytically active intermediates through covalent bonding; and non-covalent catalysis, which operates hydrogen bonding and ion pairing to activate substrates <i>via</i> weak interactions. The current challenges restricting the development of this field, including reaction compatibility, stereocontrol under electrochemical conditions, and synthetic scalability, are also discussed.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sonochemical <i>N</i>-nitrosation of secondary amines under mild conditions.","authors":"Chitra Nain, Siddhant A Kale, Aayushi Rajput, Seema Dhiman, Mahipal Yadav","doi":"10.1039/d6ob01080f","DOIUrl":"10.1039/d6ob01080f","url":null,"abstract":"<p><p><i>N</i>-Nitrosamines are a structurally important class of compounds that have attracted considerable attention owing to their classification as a regulatory \"cohort of concern\" and their diverse applications in pharmaceutical chemistry and organic synthesis; however, their preparation often relies on harsh reaction conditions and hazardous nitrosating reagents. Herein, we report a rapid and environmentally benign sonochemical protocol for the synthesis of <i>N</i>-nitrosamines using readily available iron(III) nitrate nonahydrate as an inexpensive nitroso source. The transformation proceeds under exceptionally mild conditions without the need for strong acids, oxidants, or specialized nitrosating agents. A broad range of secondary amines, including aliphatic, benzylic, cyclic, heterocyclic, amino acid-derived, and pharmaceutically relevant substrates, undergo efficient nitrosation in good to excellent yields with excellent functional-group tolerance. The methodology also enables the late-stage nitrosation of drug molecules and is readily scalable. Mechanistic studies, including radical-trapping experiments, HRMS, and EPR spectroscopy, provide evidence for the <i>in situ</i> generation of reactive nitrogen oxide species under ultrasonic irradiation. The results support both nitrosonium-ion- and radical-mediated pathways and reveal an acoustic-cavitation-driven nitrate-activation process. This operationally simple and sustainable protocol provides a practical platform for <i>N</i>-nitrosamine synthesis and highlights the potential of sonochemistry in nitrogen-oxide transformations under mild conditions.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":" ","pages":"7753-7760"},"PeriodicalIF":2.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pd-catalyzed, oxidant-promoted, regioselective C(sp<sup>2</sup>)-H/C(sp<sup>3</sup>)-H cross-dehydrogenative coupling for direct <i>ortho</i>-alkoxylation of 1-aryl-1<i>H</i>-indazoles <i>via</i> C-H bond activation.","authors":"Shivani, Janmejaya Sen, Sandeep Chaudhary","doi":"10.1039/d6ob00867d","DOIUrl":"10.1039/d6ob00867d","url":null,"abstract":"<p><p>A highly efficient palladium-catalyzed, PIDA-promoted, regioselective direct C<sub>(sp<sup>2</sup>)</sub>-H <i>ortho</i>-alkoxylation of 1-aryl-1<i>H</i>-indazoles with various primary/secondary aliphatic cyclic/acyclic alcohols has been developed utilizing a cross-dehydrogenative coupling (CDC) strategy. In this study, the developed protocol synthesized various substituted 1-phenyl-1<i>H</i>-indazole derivatives 2a-r/4a-g and substituted C-2'-alkoxylated-1-phenyl-1<i>H</i>-indazoles 5a-e in up to 80% yield. This method accommodates a wide range of alkoxy groups, demonstrates excellent functional group tolerance, and shows broad substrate applicability. A Pd-catalyzed, operationally simplified methodology was employed in the presence of PhI(OAc)<sub>2</sub> as an oxidant and various primary/secondary aliphatic cyclic/acyclic alcohols as solvents at 90 °C for 24 hours, yielding a diverse array of substituted <i>ortho</i>-alkoxyl-1-aryl-1<i>H</i>-indazoles 2a-r/4a-g/5a-e. The mechanistic investigations were performed through several control experiments, which indicated a free-radical-mediated pathway. Furthermore, the protocol demonstrates strong synthetic utility through gram-scale C2'-alkoxylation of 1-aryl-1<i>H</i>-indazoles, including methoxy-to-alcohol conversion, delivering good to excellent yields in a one-pot, scalable process.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":" ","pages":"7784-7794"},"PeriodicalIF":2.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ping Zhang, Chenxi Zhao, Rongjie Hou, Lei Wang, Jie Liu, Yicheng Zhang
{"title":"Metal-free, visible light activation of 4CzIPN for the radical addition of aminoalkyl radicals to allenoates.","authors":"Ping Zhang, Chenxi Zhao, Rongjie Hou, Lei Wang, Jie Liu, Yicheng Zhang","doi":"10.1039/d6ob01042c","DOIUrl":"10.1039/d6ob01042c","url":null,"abstract":"<p><p>Allenoates are versatile synthetic building blocks, yet their photocatalytic transformations remain underexplored and mostly rely on precious metal catalysts. Herein, we report a mild, noble-metal-free photocatalytic system using 4CzIPN as the photocatalyst, enabling efficient visible-light-driven addition of allenoates with Het/Ar-substituted tertiary amines. This protocol features broad substrate scope and high atom economy. Moreover, it clarifies the reaction selectivity mechanism, opening a new avenue for selective allenoate functionalization.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":" ","pages":"7774-7783"},"PeriodicalIF":2.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Alternating iterative exponential growth oligomers as a sequence-defined platform for hydrophilic antibody-drug conjugates.","authors":"Zihuan Fu, Heather D Maynard","doi":"10.1039/d6ob01198e","DOIUrl":"10.1039/d6ob01198e","url":null,"abstract":"<p><p>Antibody-drug conjugates (ADCs) are a powerful therapeutic modality capable of tissue-specific delivery of highly potent cytotoxic warheads. One of the key challenges of ADCs is their hydrophobicity. Conjugation of typically hydrophobic cytotoxins to an antibody alters its physicochemical properties, resulting in decreased stability and poor pharmacokinetics. Herein, we report the synthesis of alternating iterative exponential growth (IEG) oligomers bearing orthogonal functionalities that serve as a versatile platform for installing diverse hydrophilic moieties and cytotoxic payloads. Incorporation of hydrophilic groups can partially offset payload hydrophobicity, yielding ADCs with improved overall hydrophilicity.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":" ","pages":"7795-7802"},"PeriodicalIF":2.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A dark luminol analogue: HRP-catalyzed oxidation of 3-indazolinones to salicylic acid derivatives.","authors":"Noa Naama, Or Kimel, Moshe Portnoy, Doron Shabat","doi":"10.1039/d6ob01194b","DOIUrl":"10.1039/d6ob01194b","url":null,"abstract":"<p><p>Horseradish peroxidase (HRP)-catalyzed oxidation of luminol is a cornerstone chemiluminescent reaction, proceeding through nitrogen extrusion to generate an electronically excited 3-aminophthalate species. Here we report that 3-indazolinones, a structurally related class of heterocycles, undergo an analogous HRP-catalyzed oxidative pathway to yield salicylic acid derivatives, yet do so without any detectable light emission. This \"dark\" reactivity is observed across ten structurally diverse indazolinone substrates, including the amino-substituted analogue most closely resembling luminol itself, and proceeds efficiently under both alkaline and physiological buffer conditions. In contrast to the inefficient, self-limiting oxidation of luminol, indazolinone substrates are consumed nearly quantitatively, although salicylic acid accounts for only a fraction of the theoretical yield, indicating that competing radical-mediated pathways divert much of the reactive flux to unassigned side products. We further demonstrate that this newly uncovered chemistry can be harnessed analytically: a nitro-substituted indazolinone derivative serves as a real-time absorbance-based turn-off probe, while a methyl-acrylate-substituted derivative serves as a fluorescence-based turn-on probe, for monitoring HRP activity. These readouts track substrate consumption more directly than luminol-based chemiluminescent assays. These findings expand the known scope of peroxidase-catalyzed oxidative transformations and establish 3-indazolinones as a versatile new substrate class for both mechanistic enzymology and the design of enzyme-responsive optical probes.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":" ","pages":"7803-7811"},"PeriodicalIF":2.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Electron-transfer-mediated generation and reactions of organopotassium species under flow coexistence conditions.","authors":"Yosuke Ashikari, Manato Takeda, Shuto Wada, Kazuhiro Okamoto, Aiichiro Nagaki","doi":"10.1039/d6ob01268j","DOIUrl":"10.1039/d6ob01268j","url":null,"abstract":"<p><p>Electron-transfer-mediated generation of organometallic intermediates in the presence of electrophiles remains a longstanding challenge because competing reduction pathways often suppress desired bond formation. Herein, we report a flow-enabled coexistence strategy for the generation and reaction of highly reactive organopotassium intermediates. We achieved reductive potassiation of chloromethyl thioethers in the presence of electrophiles, enabling direct generation and trapping of organopotassium intermediates under coexistence conditions. Comparative experiments revealed that the corresponding stepwise protocol afforded significantly lower efficiency, demonstrating the importance of the coexistence conditions. These results establish electron-transfer-mediated coexistence reactions as a practical strategy for the generation and reactions of highly reactive organopotassium intermediates.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":" ","pages":"7690-7693"},"PeriodicalIF":2.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148917620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vignesh Balaraman, Siyam Prasath Kannan, Abimanyu Balakrishnan, Vivekanandhan Nithiyasri, Palathedath Suresh Kumar, Rajesh B R D Yamajala
{"title":"Complementary photochemical and electrochemical oxidation enables sustainable synthesis of benzimidazo[2,1-<i>b</i>]thiazoles from enaminones and 2-mercaptobenzimidazole.","authors":"Vignesh Balaraman, Siyam Prasath Kannan, Abimanyu Balakrishnan, Vivekanandhan Nithiyasri, Palathedath Suresh Kumar, Rajesh B R D Yamajala","doi":"10.1039/d6ob01098a","DOIUrl":"10.1039/d6ob01098a","url":null,"abstract":"<p><p>Two complementary oxidative [3 + 2] cyclization protocols were developed for the synthesis of sulfur-containing benzimidazo[2,1-<i>b</i>]thiazole derivatives from enaminones and 2-mercaptobenzimidazole. The first method exploits visible-light-induced activation through an electron donor-acceptor (EDA) complex, using molecular oxygen as the sole oxidant for C-N and C-S bond formation, whereas the second relies on electrochemical oxidation in an undivided carbon-carbon cell under ambient air, avoiding metal catalysts, additives and stoichiometric chemical oxidants. Both one-step protocols provide high yields, broad substrate scope, excellent functional-group tolerance, short reaction times, scalability, and operational simplicity, offering practical and environmentally benign routes to benzimidazo[2,1-<i>b</i>]thiazole derivatives.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":" ","pages":"7767-7773"},"PeriodicalIF":2.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}