Organic Chemistry Frontiers最新文献

{"title":"Rapid Access to Highly Functionalized Thietanes via Electrophilic Thietanylation under Metal-Free Conditions","authors":"NEHA RAJENDRA THAKAR,Pujan Sasmal,Natish .,Ravi Kumar","doi":"10.1039/d6qo01107a","DOIUrl":"https://doi.org/10.1039/d6qo01107a","url":null,"abstract":"Four-membered heterocycles have profound applications in modern drug discovery. While significant attention has been devoted to oxetane and azetidine functionalization, their sulfur counterpart, thietane, remains underdeveloped due to several synthetic challenges. Herein, we disclose the expedient functionalization of thietane trichloroacetimidates (TTAs) under metal-free conditions to form 3,3-disubstituted thietanes. The reaction accommodates diverse nucleophiles bearing nitrogen, carbon, and sulfur and can be easily scaled up to the gram scale. Mechanistic studies revealed the generated carbocation either underwent a ring-opening or was trapped by HFIP to form a stable HFIP adduct.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"7 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019663","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}

{"title":"","authors":"Kaoud Salama,Zeinab Saedi,Martina Kintlova,Tomas Ozdian,Fiorella Meneghetti,Matteo Mori,Marian Hajduch,Petr Dzubak,Jan Pokorny,Alexander Dömling","doi":"10.1039/d6qo01185c","DOIUrl":"https://doi.org/10.1039/d6qo01185c","url":null,"abstract":"Oxa-β-lactams (1,2-oxazetidin-3-ones) constitute the formal oxygen analogues of β-lactams yet remain largely absent from chemical and biological studies because general synthetic access has been lacking, historically limited to specialized cycloaddition and precursor-encoded ring-contraction strategies. We report that incorporation of aminooxyacetic acid into the Ugi multicomponent reaction diverts the canonical reaction manifold and selectively furnishes oxa-β-lactams under mild, room-temperature conditions from simple carbonyl compounds and isocyanides. Automated nanoscale high-throughput experimentation enabled mapping of the accessible reaction space and identification of productive substrate classes, which translated to preparative synthesis of structurally diverse, fully characterized derivatives, including single-crystal X-ray structures. Structural analysis revealed pronounced pyramidalization and reduced coplanarity within the amide substructure, suggesting an electronically perturbed, strain-activated amide motif with potential relevance for covalent ligand design. This possibility was supported by preliminary high-throughput mass spectrometric screening, which identified covalent engagement of a mutant NPM1 W288C target by selected members of the scaffold class. In situ NMR kinetics support a pathway involving oxime formation, isocyanide insertion, and intramolecular O-acyl capture leading to four-membered ring closure, consistent with interception of the Ugi intermediate rather than formation of classical products. Together, this transformation establishes a general entry into oxa-β-lactam chemical space and suggests these underexplored heterocycles may constitute a new class of covalent modifier scaffolds.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"35 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019739","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}

{"title":"Base- and solvent-controlled palladium-catalyzed chemoselective C–H silylation: synthesis of diverse silicon-containing chromones","authors":"Weiwei Lv,Qiaoyun Li,Dong Zhang,Wanying Yang,Youlin Yan,Jing Lu,Wendong Peng,Guolin Cheng","doi":"10.1039/d6qo00974c","DOIUrl":"https://doi.org/10.1039/d6qo00974c","url":null,"abstract":"Herein, we report a palladium-catalyzed three-component reaction between 3-iodochromones, norbornenes (NBEs), and hexamethyldisilane for the diversity-oriented synthesis of silicon-containing chromones. Two switchable chemoselective C–H silylation pathways are achieved by modulating the base and solvent: (a) C–H alkenyl carbosilylation of norbornenes and (b) Catellani-type C–H bis-silylation of 3-iodochromones. When 2,3-dicarbomethoxy-7-oxanorbornadiene (ONBD) is used as both a switch and an ethylene surrogate, both pathways further involve a retro-Diels–Alder reaction to stereospecifically deliver chromone-bearing (Z)-β-substituted vinylsilanes. Control experiments and H/D exchange studies indicate that the carbosilylation products likely originate from the selective desilylative hydrogenation of the bis-silylation products. This protocol provides an efficient and modular platform for the diversity-oriented synthesis of silicon-containing chromones and stereodefined Z-vinylsilanes.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"18 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013649","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}

{"title":"Amine Switch Reverses Radical Generation Order in Regiodivergent Amidosulfenylation of Styrenes","authors":"Vishal Gudaghe,Sumangla Arora,Sujith K P,Kyung-Bin Cho,Anna Lee","doi":"10.1039/d6qo01047d","DOIUrl":"https://doi.org/10.1039/d6qo01047d","url":null,"abstract":"Achieving regioselective radical difunctionalization involving multiple competing radical intermediates remains a longstanding challenge, as reaction outcomes are conventionally rationalized by the intrinsic reactivity of each radical toward the substrate. Here we report a visible-light-mediated amidosulfenylation of styrenes that achieves switchable, regiodivergent synthesis of complementary β-amino sulfides through a simple change in the amine coupling partner. Experimental and computational studies demonstrate that this regioselectivity does not originate from intrinsic radical addition preferences: both aminyl and thiyl radicals add to styrene at the same terminal carbon with negligible barriers. Instead, density functional theory (DFT) calculations reveal that subtle differences in the activation barriers for aminyl- vs. thiyl-radical generation from N-iodosuccinimide (NIS)-based electron donor–acceptor (EDA) complexes determine which radical forms first, and consequently which regioisomer predominates. These findings support the kinetics of radical generation—rather than the radical addition step—as a broadly applicable and computationally predictable strategy for controlling regioselectivity in radical difunctionalization reactions.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"24 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013647","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}

{"title":"Uphill photoisomerization of 1,3-dienes lacking additional conjugated groups","authors":"Laurence N. Rohde, Jr.,Elifnur Yildiz,Augusta Kramer,Nayanika Kalita,Timothy G. Cook,Jochen Autschbach,Steven T. Diver","doi":"10.1039/d6qo01126h","DOIUrl":"https://doi.org/10.1039/d6qo01126h","url":null,"abstract":"In this work, uphill photocatalysis allowed stereoconvergent access to the less stable geometric isomer of 1,2,3-trisubstituted 1,3-dienes. Highly substituted 1,3-dienes are broadly useful for synthetic applications that employ the 1,3-diene as a building block. The overall, two-step process starts with an alkene and an internal alkyne which are joined by ene-yne cross metathesis and is followed by catalytic isomerization with organic and organometallic triplet sensitizers. Previous work with 1,3-dienes was limited to cases where a conjugating group was present, and successful uphill catalysis was due to rotating this conjugating group out of coplanarity with the 1,3-diene. Without additional stabilizing groups, the triplet energy gaps are higher. In this study, both Ir photosensitizers and organic sensitizers such as 2-acetonaphthone were used, where the mechanism of isomerization is unclear due to the possibility of photoredox chemistry. Stern–Volmer plots of individual, stereoisomerically pure E- or Z-isomers showed large differences in their rate of quenching of the triplet energy of the sensitizer, consistent with selective energy transfer. Triplet energy transfer most likely occurs by the Dexter mechanism since cyclovoltammetry studies of the 1,3-diene showed oxidation potentials too high for a redox pathway. Based on DFT calculations, we rationalize the selective energy transfer based on both rotamer populations and the vertical singlet to triplet energy gaps for each single bond rotamer (s-cis and s-trans) corresponding to each of the E and Z stereoisomers of the 1,3-diene. The lowest energy gap was found for the s-trans E-isomer, which also experienced localized spin density on the bond undergoing isomerization. Last, a further study of 1,3-butadiene showed that significant distortion of the diene from coplanarity resulted in a large increase in the vertical triplet energy gap, illustrating that more complex systems where allylic strain may be present, can affect both the single bond conformational equilibria (rotamers) and increase the energy gaps for significantly twisted 1,3-dienes.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"31 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149013648","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}

{"title":"Unlocking the New Reactivity Pattern of Aza-1,6-Enyne: Iodine Catalyzed, Chemo-and Stereoselective Synthesis of Oxazolidinones","authors":"Shivam A Meena,Deepika Thakur,Manvi Sharma,Surya P Tripathi,Antrix Lagwal,Akhilesh K. Verma","doi":"10.1039/d6qo00975a","DOIUrl":"https://doi.org/10.1039/d6qo00975a","url":null,"abstract":"Chemo-and stereoselective cyclization of aza-1,6-enyne is reported, demonstrating an unconventional and metal-free approach to synthesize the oxazolidinone core. The reaction proceeds efficiently in the absence of metal, additive, and solvent, utilizing molecular iodine as a catalyst under neat conditions at room temperature. The reaction selectively engages the carbonyl group (of enone) while leaving the alkene part of enone intact, which provides an alkene handle for further functionalization. This novel cyclization process represents a significant advancement in green chemistry as it eliminates the need of expensive reagents and solvents. The broad substrate scope and simple reaction conditions make this a sustainable, attractive, simple, and practical synthetic strategy. Moreover, the methodology enables the successful incorporation of a deuterated methoxy group when CD3OD is employed. Green-metric analysis revealed the sustainability of the protocol, delivering oxazolidinones with high atom economy (77.59%), complete carbon utilization, favorable reaction mass efficiency (77.6%), and a low E-factor (0.62), highlighting its environmentally benign nature.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"47 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149010351","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}

{"title":"Electrochemical deaminative thiocyanation of aromatic amines","authors":"Yong Liu,Jijin Li,Yuelong He,Lin-Bao Zhang,Weisi Guo","doi":"10.1039/d6qo01128d","DOIUrl":"https://doi.org/10.1039/d6qo01128d","url":null,"abstract":"Deaminative functionalization of aromatic amines through diazotization represents an important strategy for constructing diverse aromatic compounds. Herein, we report an electrochemical protocol for the direct deaminative thiocyanation of aromatic amines via aryl diazonium salts as transient intermediates. TMSNCS serves as a reductant to reduce readily available nitrate, generating NO₂ intermediates. Electrochemical oxidation enables the regeneration of FeIII from FeII. This method features a broad substrate scope, easy scalability and can be applied for late-stage functionalization of bioactive molecules.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"17 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149010377","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}

{"title":"A Cyclopentane-1,2,4-trione Moiety Entrapped in a Porphyrin Scaffold: Head-to-Head Dimerization of meso-Tetraaryl-2,3,21-trioxo-21-carbaporphyrin","authors":"Monika Przewoźnik,Emilia Ganczar,Ewa Pacholska-Dudziak,Bartosz Szyszko,Lechoslaw Latos-Grazynski","doi":"10.1039/d6qo01015f","DOIUrl":"https://doi.org/10.1039/d6qo01015f","url":null,"abstract":"Treatment of meso-tetraaryl-21-carbaporphyrin with either silver(I) trifluoroacetate or [bis(trifluoroacetoxy)iodo]benzene (PIFA) yielded meso-tetraaryl-2,3,21-trioxo-21-carbaporphyrin. The pronounced diatropicity of 2,3,21-trioxo-21-carbaporphyrin is evident from the 1H NMR which shows a significant downfield shift of β-pyrrolic protons and an upfield shift of NH protons, reflecting a strong aromatic ring current effect. Incorporation of cyclopentane-1,2,4-trione in the macrocycle warranted the formation of the unprecedented head-to-head chiral dimer linked by intermolecular N—H···O hydrogen bonds which involved the trione unit and the NH hydrogens located in the porphyrinoid crevice of the partner molecule. The dimer functions as a molecular pivot hinge, allowing enantiomerization via a planar hinge-like motion. This motion occurs about a pivot axis that passes through the centroids of the C₅ and C₅’ trione rings. Dynamic NMR line shape analysis was used to study the enantiomerization process. The data enabled extraction of the rate constants via an Eyring analysis, yielding the activation parameters (ΔH# = +28.9± 2.1 kJ·mol-1, ΔS # > = –48.7 ± 10.9 J·mol-1·K-1, and ΔG#298 = +43.1 ± 5.4 kJ·mol-1). The reaction of the reversible dimerization of 2,3,21-trioxo-21-carbaporphyrin was also studied, and the equilibrium constants (K) were determined as a function of temperature. A van’t Hoff analysis of these data yielded the following thermodynamic parameters: ΔH° = −62.9 ± 1.3 kJ·mol−1, ΔS° = −173 ± 4 J·mol−1 ·K−1, ΔG°₂₉₈ = −4.2 ± 2.5 kJ·mol−1.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"1 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148980735","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}

{"title":"Efficient construction of pyrimido[5,4-c]quinoline-based [5]helicene skeletons via multi-component cascade cyclization enabled by the I 2 -DMSO system","authors":"Yu-Jia Fan,You Zhou,Jia-Hao Zhang,Chun-Yan Wu,Li-Sheng Wang,Jun Ma,Yan-Dong Wu,An-Xin Wu","doi":"10.1039/d6qo00945j","DOIUrl":"https://doi.org/10.1039/d6qo00945j","url":null,"abstract":"We successfully constructed two novel fused heterocyclic frameworks via a tandem cyclization reaction of an in situ generated ketene intermediate with two aromatic amines. This method employs aryl methyl ketones, aromatic amines, and 4hydroxy-1-methylquinolin-2(1H)-one as substrates. The features of this approach include high atom economy and broad substrate scope (40 examples). During the reaction, one C-C bond and two C-N bonds are formed. Notably, the reaction exhibits excellent regioselectivity and specificity in the cyclization. Interestingly, when 2-aminobenzimidazole was used as the amine component, Xray crystallographic analysis unambiguously revealed that the resulting fused product adopts a helical [5]helicene-like architecture, with a terminal dihedral angle (θ) of 37.9° between the least-squares planes of the terminal aromatic rings. This large dihedral angle reflects a highly twisted conformation arising from the steric congestion imposed by the fused heterocyclic core.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"76 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148973585","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}

{"title":"Regioselective Hydroxyesterification of Electron-Rich Alkenes Enabled by Bifunctional mCPBA","authors":"Jaewon Seo,Soogyum Kim,Suji Lee,Jeonghyo Lee","doi":"10.1039/d6qo00700g","DOIUrl":"https://doi.org/10.1039/d6qo00700g","url":null,"abstract":"A regioselective hydroxyesterification of electron-rich alkenes is achieved through the dual role of mCPBA as oxidant and ring-opening nucleophile precursor. Hydroxyesters are obtained with broad scope and high reaction mass efficiency. Mechanistic studies support acid-promoted epoxide activation, where regioselectivity arises from substrate electronics and developing cationic character.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"29 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148973530","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}