Regina Kohlbecher, Tim Lippert, Hendrik Schröder, Dustin N. Jordan, Christoph Janiak, Thomas J. J. Müller
The strategic combination of Suzuki coupling and Buchwald–Hartwig amination in consecutive (pseudo-)four-component syntheses provides a highly efficient and modular route to meta- and ortho-biaryl-substituted triarylamines (m- and o-bTAA), thereby expanding a substance library that has previously focused on para-bTAA. The broad range of novel bTAA enables comprehensive investigations of their electronic properties and reveals highly tunable emission in solution from blue to yellow, with quantum yields up to 55%, and up to 26% in the solid state. The bTAA also show strong potential as stimulus-responsive luminophores due to their pronounced positive emission solvatochromism, which indicates substantial charge transfer character—particularly in the m-bTAA—as well as aggregation-induced emission in DMSO/water mixtures with with intensity enhancements of up to 75-fold. Quantitative 2D Hammett correlations combined with quantum-chemical calculations systematically rationalize substituent effects not only on the emission properties but also on the low, reversible redox potentials determined by cyclic voltammetry. Cyclic voltammetry further reveals irreversible dimerization processes in certain unsubstituted bTAA. In addition to para-substituents, the biaryl substitution pattern (meta, ortho, or para) also proves to be a finely tunable parameters, opening new opportunities for the rational design of tailored bTAA emitters with predictable structure–property relationships.
{"title":"\u0000Consecutive (Pseudo-)Four-Component Synthesis of Meta- and Ortho-Biaryl Triarylamines with Tunable Emission and Redox Properties","authors":"Regina Kohlbecher, Tim Lippert, Hendrik Schröder, Dustin N. Jordan, Christoph Janiak, Thomas J. J. Müller","doi":"10.1002/ejoc.70312","DOIUrl":"https://doi.org/10.1002/ejoc.70312","url":null,"abstract":"The strategic combination of Suzuki coupling and Buchwald–Hartwig amination in consecutive (<i>pseudo-</i>)four-component syntheses provides a highly efficient and modular route to <i>meta</i>- and <i>ortho</i>-biaryl-substituted triarylamines (<i>m</i>- and <i>o</i>-bTAA), thereby expanding a substance library that has previously focused on <i>para</i>-bTAA. The broad range of novel bTAA enables comprehensive investigations of their electronic properties and reveals highly tunable emission in solution from blue to yellow, with quantum yields up to 55%, and up to 26% in the solid state. The bTAA also show strong potential as stimulus-responsive luminophores due to their pronounced positive emission solvatochromism, which indicates substantial charge transfer character—particularly in the <i>m</i>-bTAA—as well as aggregation-induced emission in DMSO/water mixtures with with intensity enhancements of up to 75-fold. Quantitative 2D Hammett correlations combined with quantum-chemical calculations systematically rationalize substituent effects not only on the emission properties but also on the low, reversible redox potentials determined by cyclic voltammetry. Cyclic voltammetry further reveals irreversible dimerization processes in certain unsubstituted bTAA. In addition to <i>para</i>-substituents, the biaryl substitution pattern (<i>meta</i>, <i>ortho</i>, or <i>para</i>) also proves to be a finely tunable parameters, opening new opportunities for the rational design of tailored bTAA emitters with predictable structure–property relationships.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"27 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115608","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}
Synthesis of a pentasaccharide corresponding to the repeating unit of the cell wall O-polysaccharide of Salmonella riogrande O:40 has been achieved in very good yield. During the process of synthesis, construction of the α-D-galactosamine moiety was achieved by using 2-azido-2-deoxy-D-galactosamine thioglycoside donor in ether-based reaction solvent. Construction of the β-mannosidic linkage in the pentasaccharide was achieved using remotely placed picoloyl group influenced H-bond mediated aglycone delivery. All glycosylation steps were high yielding with satisfactory stereochemistry at the newly formed glycosidic linkages. Azido group was directly converted into acetamido group by the treatment with thioacetic acid and triethylsilane was used as the source of hydrogen in a catalytic transfer hydrogenation condition.
合成了一种与沙门氏菌O-多糖O:40细胞壁重复单元相对应的五糖，产率很高。在合成过程中，采用2-叠氮-2-脱氧-d -半乳糖胺硫苷给体在醚基反应溶剂中构建α- d -半乳糖胺部分。利用远程放置的picoloyl基影响氢键介导的苷元传递，在五糖中构建了β-甘露糖苷键。所有糖基化步骤产率高，新形成的糖苷键具有令人满意的立体化学性质。在催化转移加氢条件下，以三乙基硅烷为氢源，经硫乙酸处理，叠氮基直接转化为乙酰胺基。
{"title":"Synthesis of the Pentasaccharide Repeating Unit Corresponding to the Cell Wall O-Polysaccharide of Salmonella riogrande O:40 (Group R) Strain","authors":"Saikat Dogra, Anup Kumar Misra","doi":"10.1002/ejoc.202501215","DOIUrl":"https://doi.org/10.1002/ejoc.202501215","url":null,"abstract":"Synthesis of a pentasaccharide corresponding to the repeating unit of the cell wall <i>O</i>-polysaccharide of <i>Salmonella riogrande</i> O:40 has been achieved in very good yield. During the process of synthesis, construction of the <i>α</i>-D-galactosamine moiety was achieved by using 2-azido-2-deoxy-D-galactosamine thioglycoside donor in ether-based reaction solvent. Construction of the <i>β</i>-mannosidic linkage in the pentasaccharide was achieved using remotely placed picoloyl group influenced <i>H</i>-bond mediated aglycone delivery. All glycosylation steps were high yielding with satisfactory stereochemistry at the newly formed glycosidic linkages. Azido group was directly converted into acetamido group by the treatment with thioacetic acid and triethylsilane was used as the source of hydrogen in a catalytic transfer hydrogenation condition.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"15 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115612","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}
A practical, continuous flow, biphasic photochemical amination of thioethers, employing N ‐mesyloxycarbamates as nitrene precursors, is reported. Using UVA irradiation at 365 nm and Fe(acac) 3 as a catalyst, the reaction efficiently converts aromatic and aliphatic thioethers into Troc‐protected sulfilimines in high yields. The biphasic ethyl acetate/water system plays a critical role in preventing clogging of the reactor by dissolving the mesylate byproduct.
{"title":"Photochemical Amination of Thioethers Under Biphasic Flow Conditions","authors":"Calvine Lai, Hélène Lebel","doi":"10.1002/ejoc.202501165","DOIUrl":"https://doi.org/10.1002/ejoc.202501165","url":null,"abstract":"A practical, continuous flow, biphasic photochemical amination of thioethers, employing <jats:italic>N</jats:italic> ‐mesyloxycarbamates as nitrene precursors, is reported. Using UVA irradiation at 365 nm and Fe(acac) <jats:sub>3</jats:sub> as a catalyst, the reaction efficiently converts aromatic and aliphatic thioethers into Troc‐protected sulfilimines in high yields. The biphasic ethyl acetate/water system plays a critical role in preventing clogging of the reactor by dissolving the mesylate byproduct.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"8 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097896","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}
This study investigates the synthesis of unsymmetrical ureas involving tetra‐ n ‐butylammonium fluoride (TBAF) catalyzed in situ generation of isocyanate of N ‐alkyl/aryl O ‐phenyl carbamates at room temperature that subsequently reacts with alkyl/aromatic amines to yield unsymmetrical urea with moderate to excellent yields including gram scale synthesis of celiprolol intermediate. The process of employing TBAF an organocatalyst, thus, eliminates the use of hazardous reagents, hence making the process sustainable, cost‐effective, and additive free.
本研究研究了四n - n -丁基氟化铵（TBAF）在室温下原位催化n -烷基/芳基O -苯基氨基甲酸酯异氰酸酯合成不对称尿素的方法，该方法随后与烷基/芳香胺反应生成不对称尿素，产率中等至优异，包括克级合成塞利洛尔中间体。因此，使用TBAF有机催化剂的过程消除了危险试剂的使用，从而使该过程可持续，成本效益高，无添加剂。
{"title":"TBAF‐Catalyzed Conversion of Carbamates Into Unsymmetrical Ureas","authors":"Ajay Singh, Suruchi Ojha, Manish Yadav, Anuj Mishra, Manjinder Singh Gill","doi":"10.1002/ejoc.202500761","DOIUrl":"https://doi.org/10.1002/ejoc.202500761","url":null,"abstract":"This study investigates the synthesis of unsymmetrical ureas involving tetra‐ <jats:italic>n</jats:italic> ‐butylammonium fluoride (TBAF) catalyzed in situ generation of isocyanate of <jats:italic>N</jats:italic> ‐alkyl/aryl <jats:italic>O</jats:italic> ‐phenyl carbamates at room temperature that subsequently reacts with alkyl/aromatic amines to yield unsymmetrical urea with moderate to excellent yields including gram scale synthesis of celiprolol intermediate. The process of employing TBAF an organocatalyst, thus, eliminates the use of hazardous reagents, hence making the process sustainable, cost‐effective, and additive free.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"29 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098119","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}
Two series of novel T-shaped 8-substituted psoralen derivatives bearing (hetero)aryl and arylethynyl substituents were synthesized via Suzuki and Sonogashira coupling starting from 8-methoxypsoralen (8-MOP). Predominantly, electron-donating substituents such as anisyl and phenothiazine were introduced at the 8-position of the psoralen for increasing the electron density in comparison to 8-MOP. Photophysical properties were studied by absorption and emission spectroscopy in solution and in the solid state. Increasing the donor strength of the substituent causes a bathochromic shift of both absorption and emission maxima. The absorption behavior can be correlated with Hammett substituent parameters of remote substituents at the p-aryl moieties that are directly or by ethynyl spacing positioned at the 8-position of psoralen. In most cases, fluorescence in the solid state is more pronounced than in solution. One derivative also displays significant aggregation-induced emission. For two amino-substituted psoralen derivatives, positive emission solvatochromism was observed and associated with a considerable change of dipole moment upon photonic excitation according to Lippert–Mataga analysis. Furthermore, the pKa value of the T-shaped dimethylaminophenyl psoralen derivative was determined from absorption spectra. In addition, emission quenching is caused by protonation on the nitrogen atom. TD-DFT (time-dependent density functional theory) calculations are in good agreement with experimental data and rationalize the electronic structure.
{"title":"T-Shaped 8-Aryl(ethynyl)-Substituted Psoralens With Tunable Charge-Transfer Absorption","authors":"Lena T. Leusch, Thomas J. J. Müller","doi":"10.1002/ejoc.202501175","DOIUrl":"https://doi.org/10.1002/ejoc.202501175","url":null,"abstract":"Two series of novel T-shaped 8-substituted psoralen derivatives bearing (hetero)aryl and arylethynyl substituents were synthesized via Suzuki and Sonogashira coupling starting from 8-methoxypsoralen (8-MOP). Predominantly, electron-donating substituents such as anisyl and phenothiazine were introduced at the 8-position of the psoralen for increasing the electron density in comparison to 8-MOP. Photophysical properties were studied by absorption and emission spectroscopy in solution and in the solid state. Increasing the donor strength of the substituent causes a bathochromic shift of both absorption and emission maxima. The absorption behavior can be correlated with Hammett substituent parameters of remote substituents at the <i>p</i>-aryl moieties that are directly or by ethynyl spacing positioned at the 8-position of psoralen. In most cases, fluorescence in the solid state is more pronounced than in solution. One derivative also displays significant aggregation-induced emission. For two amino-substituted psoralen derivatives, positive emission solvatochromism was observed and associated with a considerable change of dipole moment upon photonic excitation according to Lippert–Mataga analysis. Furthermore, the p<i>K</i><sub>a</sub> value of the T-shaped dimethylaminophenyl psoralen derivative was determined from absorption spectra. In addition, emission quenching is caused by protonation on the nitrogen atom. TD-DFT (time-dependent density functional theory) calculations are in good agreement with experimental data and rationalize the electronic structure.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"260 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146089803","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}
A silver‐ and light‐mediated radical alkoxycarbonylation of quinoxalin‐2(1 H )‐ones has been developed. This direct esterification protocol provides efficient access to quinoxaline‐3‐carboxylates. The operationally simple reaction features good functional group compatibility, and mild conditions. Notably, the successful late‐stage functionalization of complex molecules demonstrates significant synthetic utility for modifying biologically active natural products.
{"title":"Photoinduced Silver(I)‐Mediated Direct Alkoxycarbonylation of Quinoxalin‐2(1 H )‐ones With Alkyloxalyl Chlorides","authors":"Yu‐Tong Zhou, Shi‐Ya He, Wu Liang, Fang Liu, Xin‐Ran Sun, Shao‐Qun Cai, Zhi Yang, Jun‐Fei Zhao, Shi‐Cui Fang, Bin Pan, Fei Du","doi":"10.1002/ejoc.202501140","DOIUrl":"https://doi.org/10.1002/ejoc.202501140","url":null,"abstract":"A silver‐ and light‐mediated radical alkoxycarbonylation of quinoxalin‐2(1 <jats:italic>H</jats:italic> )‐ones has been developed. This direct esterification protocol provides efficient access to quinoxaline‐3‐carboxylates. The operationally simple reaction features good functional group compatibility, and mild conditions. Notably, the successful late‐stage functionalization of complex molecules demonstrates significant synthetic utility for modifying biologically active natural products.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"23 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146070621","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}
We report a telescopic two‐step synthetic strategy for efficiently constructing [1 H ]‐1,2,3‐triazol‐4‐yl modified phenylalanine conjugates. The method combines Sonogashira coupling and a one‐pot domino reaction involving desilylation, azidation, and click chemistry. This protocol enhances the potential for peptide modification and facilitates the synthesis of polyazide derivatives that can be suitable for dendrimeric cores. This reaction yields good results and provides a scalable route, successfully accommodating a wide range of aromatic and heteroaromatic methyl bromides, while achieving excellent chiral integrity and 100% 1,4‐regioselectivity. We also explored the application of a 1,4‐disubstituted [1 H ]‐1,2,3‐triazol‐4‐yl phenylalanine conjugate as a directing group for C(sp 2 )‐H di‐halogenation.
{"title":"Telescopic Synthesis of Triazol‐4‐yl Modified Phenylalanine Conjugates and Peptide Modification Using a Sonogashira Domino Strategy at Room Temperature","authors":"Karuna Thakare, Aman Singh Barahdia, Rahul Jain","doi":"10.1002/ejoc.202501066","DOIUrl":"https://doi.org/10.1002/ejoc.202501066","url":null,"abstract":"We report a telescopic two‐step synthetic strategy for efficiently constructing [1 <jats:italic>H</jats:italic> ]‐1,2,3‐triazol‐4‐yl modified phenylalanine conjugates. The method combines Sonogashira coupling and a one‐pot domino reaction involving desilylation, azidation, and click chemistry. This protocol enhances the potential for peptide modification and facilitates the synthesis of polyazide derivatives that can be suitable for dendrimeric cores. This reaction yields good results and provides a scalable route, successfully accommodating a wide range of aromatic and heteroaromatic methyl bromides, while achieving excellent chiral integrity and 100% 1,4‐regioselectivity. We also explored the application of a 1,4‐disubstituted [1 <jats:italic>H</jats:italic> ]‐1,2,3‐triazol‐4‐yl phenylalanine conjugate as a directing group for C(sp <jats:sup>2</jats:sup> )‐H di‐halogenation.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"117 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146070620","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}
Xifu Liang, Victor Friis, Karolina Agata Szlek, Asger Munk Koue, Jesper Bendix, Lars Skjolding, Sergey Kucheryavskiy, Marco Maschietti, Christian Marcus Pedersen
Michael acceptors derived from biomass resources, such as carbohydrates, have been synthesized and their H 2 S scavenging properties studied. The most promising candidates were compared with the commercial H 2 S scavenger MEA‐triazine by studying the aqueous phase scavenging reactions using in situ Raman spectroscopy and the gas–liquid reactions were evaluated in a flow setup. Based on cost and scavenging efficiency considerations, the industrially most promising candidates were submitted to ecotoxicity studies. We have found three families of Michael acceptors, which are readily available and can be tailor‐made to serve as sulfide scavengers under different conditions.
{"title":"Biomass‐Based H 2 S Scavengers: Michael Acceptors","authors":"Xifu Liang, Victor Friis, Karolina Agata Szlek, Asger Munk Koue, Jesper Bendix, Lars Skjolding, Sergey Kucheryavskiy, Marco Maschietti, Christian Marcus Pedersen","doi":"10.1002/ejoc.202501122","DOIUrl":"https://doi.org/10.1002/ejoc.202501122","url":null,"abstract":"Michael acceptors derived from biomass resources, such as carbohydrates, have been synthesized and their H <jats:sub>2</jats:sub> S scavenging properties studied. The most promising candidates were compared with the commercial H <jats:sub>2</jats:sub> S scavenger MEA‐triazine by studying the aqueous phase scavenging reactions using in situ Raman spectroscopy and the gas–liquid reactions were evaluated in a flow setup. Based on cost and scavenging efficiency considerations, the industrially most promising candidates were submitted to ecotoxicity studies. We have found three families of Michael acceptors, which are readily available and can be tailor‐made to serve as sulfide scavengers under different conditions.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"30 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056030","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}
Lizeth Y. F. Haveman , Albert D. Windhorst , Danielle J. Vugts
The trifluoromethyl (CF3) group is a ubiquitous motif in drug discovery campaigns due to its ability to markedly improve the ADME properties of small molecules while maintaining potency. The isotopologue labeling of CF3‐bearing drugs with fluorine‐18 has gained attention for positron emission tomography (PET) imaging. However, their radiolabeling via conventional 18F‐trifluoromethylation methods relies almost completely on nucleophilic and radical [18F]CF3‐reagents, whereas there remains no general means to incorporate a formal [18F]CF3+ into PET tracer candidates. Herein, we disclose the realization of a novel electrophilic 18F‐labeled trifluoromethylating reagent based on the family of 10‐λ‐3 hypervalent iodines: [18F]Togni reagent I. The method uses nucleophilic ligand substitution at iodine by the [18F]Ruppert–Prakash reagent, providing [18F]Togni reagent I in a radiochemical yield of 4.3 ± 0.8% and a molar activity of 15 ± 9.6 GBq/μmol. Initial studies on the utility of this reagent demonstrate the direct, late‐stage formation of C(sp3)−[18F]CF3 bonds via metallaphotoredox‐mediated conversion of naturally abundant carboxylic acids. Hence, this work illustrates the potential of the novel electrophilic [18F]CF3‐reagent as a complementary approach leading to valuable 18F‐trifluoromethylated architectures in PET tracer development.
{"title":"Synthesis and Application of [18F]Togni Reagent I: An Electrophilic 18F‐Labeled Trifluoromethylating Reagent for Positron Emission Tomography Tracer Synthesis","authors":"Lizeth Y. F. Haveman , Albert D. Windhorst , Danielle J. Vugts","doi":"10.1002/ejoc.202501181","DOIUrl":"10.1002/ejoc.202501181","url":null,"abstract":"<div><div>The trifluoromethyl (CF<sub>3</sub>) group is a ubiquitous motif in drug discovery campaigns due to its ability to markedly improve the ADME properties of small molecules while maintaining potency. The isotopologue labeling of CF<sub>3</sub>‐bearing drugs with fluorine‐18 has gained attention for positron emission tomography (PET) imaging. However, their radiolabeling via conventional <sup>18</sup>F‐trifluoromethylation methods relies almost completely on nucleophilic and radical [<sup>18</sup>F]CF<sub>3</sub>‐reagents, whereas there remains no general means to incorporate a formal [<sup>18</sup>F]CF<sub>3</sub><sup>+</sup> into PET tracer candidates. Herein, we disclose the realization of a novel electrophilic <sup>18</sup>F‐labeled trifluoromethylating reagent based on the family of 10‐λ‐3 hypervalent iodines: [<sup>18</sup>F]Togni reagent I. The method uses nucleophilic ligand substitution at iodine by the [<sup>18</sup>F]Ruppert–Prakash reagent, providing [<sup>18</sup>F]Togni reagent I in a radiochemical yield of 4.3 ± 0.8% and a molar activity of 15 ± 9.6 GBq/μmol. Initial studies on the utility of this reagent demonstrate the direct, late‐stage formation of C(sp<sup>3</sup>)−[<sup>18</sup>F]CF<sub>3</sub> bonds via metallaphotoredox‐mediated conversion of naturally abundant carboxylic acids. Hence, this work illustrates the potential of the novel electrophilic [<sup>18</sup>F]CF<sub>3</sub>‐reagent as a complementary approach leading to valuable <sup>18</sup>F‐trifluoromethylated architectures in PET tracer development.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"29 4","pages":"Article e202501181"},"PeriodicalIF":2.7,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796444","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}
We describe a hexafluoroisopropanol (HFIP)‐promoted epoxide ring‐opening cyclization of readily accessible 2‐[(2‐substituted‐1‐naphthyloxy)methyl]‐3‐aryloxiranes, proceeding via a regioselective 7‐endo cyclization at the peri (C8) position of the naphthalene ring. This transformation provides a new class of naphtho[1,8‐bc]oxepine derivatives with complete regio‐ and diastereoselectivity. The C2 substituent on the naphthalene framework, along with the π‐activating aryl group on the epoxide, plays a pivotal role in enabling the reaction. The method operates under mild conditions, tolerates a broad substrate scope, and is readily amenable to gram‐scale synthesis. Moreover, the versatility of this strategy is underscored by its successful extension to the diastereoselective synthesis of oxepino[4,3,2‐cd]indoles.
{"title":"Synthesis of Naphtho[1,8‐bc]oxepines Through an HFIP‐Promoted Peri‐Selective Arene–Epoxide Cyclization","authors":"Jahnabi Das , Abhijit Gogoi , Sajal Kumar Das","doi":"10.1002/ejoc.202501042","DOIUrl":"10.1002/ejoc.202501042","url":null,"abstract":"<div><div>We describe a hexafluoroisopropanol (HFIP)‐promoted epoxide ring‐opening cyclization of readily accessible 2‐[(2‐substituted‐1‐naphthyloxy)methyl]‐3‐aryloxiranes, proceeding via a regioselective 7‐<em>endo</em> cyclization at the <em>peri</em> (C8) position of the naphthalene ring. This transformation provides a new class of naphtho[1,8‐<em>bc</em>]oxepine derivatives with complete regio‐ and diastereoselectivity. The C2 substituent on the naphthalene framework, along with the <em>π</em>‐activating aryl group on the epoxide, plays a pivotal role in enabling the reaction. The method operates under mild conditions, tolerates a broad substrate scope, and is readily amenable to gram‐scale synthesis. Moreover, the versatility of this strategy is underscored by its successful extension to the diastereoselective synthesis of oxepino[4,3,2‐<em>cd</em>]indoles.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"29 4","pages":"Article e202501042"},"PeriodicalIF":2.7,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145711394","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}
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