Sewon Oh,Houng Kang,Çetin Bayrak,Sobia Jabeen,Rosaura Padilla-Salinas,Brandon J. Orzolek,Guillermo A. Correa Otero,Madeline E. Rotella,Marisa C. Kozlowski
Herein we describe a simple and efficient approach to triazole-based phosphine (ClickPhos) ligands via 1,3-dipolar cycloaddition of alkynylphosphine oxides and azides followed by phosphine oxide reduction. This sequence can be telescoped and performed in parallel to provide libraries of ligands with diverse steric, electronic, and hemilabile coordination character. The formation of both regioisomeric ClickPhos ligands in this thermal protocol is advantageous as a more diverse library of ligands can be obtained. Over 30 unique ClickPhos ligands with different steric and electronic character were synthesized. When used in the Suzuki–Miyaura cross-coupling of multiple identically halogenated heteroarenes (e.g., 3,5-dichloropyridazine), high site selectivity for the more distal halide (e.g., C5) is observed, surpassing the performance of commercial ligands.
{"title":"A new route for the synthesis of triazole phosphine ligands for regioselective Suzuki–Miyaura cross-coupling reactions","authors":"Sewon Oh,Houng Kang,Çetin Bayrak,Sobia Jabeen,Rosaura Padilla-Salinas,Brandon J. Orzolek,Guillermo A. Correa Otero,Madeline E. Rotella,Marisa C. Kozlowski","doi":"10.1039/d6qo01485b","DOIUrl":"https://doi.org/10.1039/d6qo01485b","url":null,"abstract":"Herein we describe a simple and efficient approach to triazole-based phosphine (ClickPhos) ligands via 1,3-dipolar cycloaddition of alkynylphosphine oxides and azides followed by phosphine oxide reduction. This sequence can be telescoped and performed in parallel to provide libraries of ligands with diverse steric, electronic, and hemilabile coordination character. The formation of both regioisomeric ClickPhos ligands in this thermal protocol is advantageous as a more diverse library of ligands can be obtained. Over 30 unique ClickPhos ligands with different steric and electronic character were synthesized. When used in the Suzuki–Miyaura cross-coupling of multiple identically halogenated heteroarenes (e.g., 3,5-dichloropyridazine), high site selectivity for the more distal halide (e.g., C5) is observed, surpassing the performance of commercial ligands.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"90 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149281790","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}
Xiaoyun Ma,Dan-Qing Fu,Hua Zhang,Jian-Ping Tan,Hong Kui Zhang,Yu Feng
Multi-step cascade artificial light-harvesting systems (ALHSs) are ideal biomimetic platforms for simulating natural photosynthesis, but their precise fabrication remains challenging, as most state-of-the-art dendritic ALHSs are confined to one- or two-step energy transfer and suffer from unsatisfactory energy transfer performance. Herein, a tetraphenylethylene-cored polybenzyl ether dendrimer (TPE-D1) was designed and synthesized to fabricate a novel aqueous-phase ALHS with a three-step cascade energy transfer pathway. In this hierarchical system, TPE-D1 acts as the primary light-harvesting antenna, DBT and DCVTJ serve as intermediate energy relays, and MTSIC functions as the final near-infrared energy acceptor. Benefiting from matched spectral overlap and tight intermolecular interactions between successive donor–acceptor pairs, the cascade exhibits high single-step energy transfer efficiencies of 83.7% (TPE-D1 → DBT), 96.9% (TPE-D1-DBT → DCVTJ) and 94.9% (TPE-D1-DBT-DCVTJ → MTSIC), with the second and third relay steps approaching near-unity efficiency. Moreover, the TPE-D1-DBT subassembly was successfully applied to the oxidative hydroxylation of arylboronic acids (OHAA), affording excellent isolated yields, while the full cascade served directional energy migration and near-infrared emission. This work provides a facile strategy for developing high-efficiency multi-cascade biomimetic light-harvesting materials for optoelectronic applications.
{"title":"A Tetraphenylethylene-Cored Polybenzyl Ether Dendrimer for Aqueous Three-Step Cascade Artificial Light-Harvesting and Photocatalytic Oxidative Hydroxylation","authors":"Xiaoyun Ma,Dan-Qing Fu,Hua Zhang,Jian-Ping Tan,Hong Kui Zhang,Yu Feng","doi":"10.1039/d6qo01327a","DOIUrl":"https://doi.org/10.1039/d6qo01327a","url":null,"abstract":"Multi-step cascade artificial light-harvesting systems (ALHSs) are ideal biomimetic platforms for simulating natural photosynthesis, but their precise fabrication remains challenging, as most state-of-the-art dendritic ALHSs are confined to one- or two-step energy transfer and suffer from unsatisfactory energy transfer performance. Herein, a tetraphenylethylene-cored polybenzyl ether dendrimer (TPE-D1) was designed and synthesized to fabricate a novel aqueous-phase ALHS with a three-step cascade energy transfer pathway. In this hierarchical system, TPE-D1 acts as the primary light-harvesting antenna, DBT and DCVTJ serve as intermediate energy relays, and MTSIC functions as the final near-infrared energy acceptor. Benefiting from matched spectral overlap and tight intermolecular interactions between successive donor–acceptor pairs, the cascade exhibits high single-step energy transfer efficiencies of 83.7% (TPE-D1 → DBT), 96.9% (TPE-D1-DBT → DCVTJ) and 94.9% (TPE-D1-DBT-DCVTJ → MTSIC), with the second and third relay steps approaching near-unity efficiency. Moreover, the TPE-D1-DBT subassembly was successfully applied to the oxidative hydroxylation of arylboronic acids (OHAA), affording excellent isolated yields, while the full cascade served directional energy migration and near-infrared emission. This work provides a facile strategy for developing high-efficiency multi-cascade biomimetic light-harvesting materials for optoelectronic applications.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"16 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149281792","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}
The organization of chromophores in condensed states critically influences their photophysical and electronic properties, yet precise control remains challenging. Here, we develop a pyrazole-based steric scaffold for programmable regulation of local chromophore organization through a single installation step. The rigid five-membered pyrazole geometry creates a three-dimensional steric environment, while variation of the 3,5-substituents tunes intermolecular packing and intramolecular interactions. Using perylene diimide (PDI) as a model chromophore, four steric modules with progressively increasing shielding were incorporated into an identical PDI framework. The studies show that these modules systematically regulate PDI organization in aqueous nanoparticles, from extended multilayer π-stacking to predominantly dimeric assemblies, weakly coupled aggregates, and nearly isolated chromophores. The optimized steric environment suppresses intermolecular radical deactivation and enhances the persistence of PDI radical anions. Incorporation of a cationic trimethylammonium group further provides electrostatic protection, facilitating radical generation and achieving high-efficiency photothermal antibacterial activity under 808 nm irradiation. This work establishes geometry-defined steric programming as a modular strategy for precisely controlling chromophore organization and functional properties in condensed states.
{"title":"A Pyrazole-Based Steric Scaffold for Programming Local Chromophore Organization","authors":"Miaomiao Zhen,Xueying Zhang,Ruoxi Liu,Ran Wang,Nan Yao,Wei Wei,Yanqing Xu","doi":"10.1039/d6qo01333c","DOIUrl":"https://doi.org/10.1039/d6qo01333c","url":null,"abstract":"The organization of chromophores in condensed states critically influences their photophysical and electronic properties, yet precise control remains challenging. Here, we develop a pyrazole-based steric scaffold for programmable regulation of local chromophore organization through a single installation step. The rigid five-membered pyrazole geometry creates a three-dimensional steric environment, while variation of the 3,5-substituents tunes intermolecular packing and intramolecular interactions. Using perylene diimide (PDI) as a model chromophore, four steric modules with progressively increasing shielding were incorporated into an identical PDI framework. The studies show that these modules systematically regulate PDI organization in aqueous nanoparticles, from extended multilayer π-stacking to predominantly dimeric assemblies, weakly coupled aggregates, and nearly isolated chromophores. The optimized steric environment suppresses intermolecular radical deactivation and enhances the persistence of PDI radical anions. Incorporation of a cationic trimethylammonium group further provides electrostatic protection, facilitating radical generation and achieving high-efficiency photothermal antibacterial activity under 808 nm irradiation. This work establishes geometry-defined steric programming as a modular strategy for precisely controlling chromophore organization and functional properties in condensed states.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"51 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149251210","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}
Six-membered silacycles are highly valuable and versatile molecular architectures in synthetic, medicinal and materials chemistry, and developing methods to rapidly access these scaffolds remains highly desirable. Although ionic and transition metal-mediated approaches to these compounds are well established, radical reactions offer an attractive alternative. However, broadly applicable protocols remain scarce and highly sought after. Here, taking advantage of the metal-free nature and excellent selectivity of organic photoredox catalysis) we report a light‑mediated cyclization strategy that constructs valuable sila-bicyclo[4.1.0]heptan-2-ones directly from 1,6-sila-enynes and pyridine N-oxide through a radical cascade. The key to the success of this reaction is using 2,6-lutidine N-oxide as the oxygen-centered radical precursor that triggers the β-oxyvinyl radical-mediated cascade reaction under blue-light irradiation. This protocol demonstrates good scalability and broad synthetic utility, as evidenced by wide substrate scope, gram-scale synthesis and diverse downstream derivatizations of the products.
{"title":"Synthesis of six-membered silacycles enabled by organic photoredox catalysis","authors":"Fengjuan Chen,Xiongzu Li,Yuting Yuan,Tao Guo,Shiwei Lü","doi":"10.1039/d6qo01355d","DOIUrl":"https://doi.org/10.1039/d6qo01355d","url":null,"abstract":"Six-membered silacycles are highly valuable and versatile molecular architectures in synthetic, medicinal and materials chemistry, and developing methods to rapidly access these scaffolds remains highly desirable. Although ionic and transition metal-mediated approaches to these compounds are well established, radical reactions offer an attractive alternative. However, broadly applicable protocols remain scarce and highly sought after. Here, taking advantage of the metal-free nature and excellent selectivity of organic photoredox catalysis) we report a light‑mediated cyclization strategy that constructs valuable sila-bicyclo[4.1.0]heptan-2-ones directly from 1,6-sila-enynes and pyridine N-oxide through a radical cascade. The key to the success of this reaction is using 2,6-lutidine N-oxide as the oxygen-centered radical precursor that triggers the β-oxyvinyl radical-mediated cascade reaction under blue-light irradiation. This protocol demonstrates good scalability and broad synthetic utility, as evidenced by wide substrate scope, gram-scale synthesis and diverse downstream derivatizations of the products.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"43 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149251201","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}
Anna S Xenzova,Mikhail O Zubkov,Mikhail Kosobokov,Alexander Dilman
Acridine photocatalysis is one of the most powerful methods for the decarboxylative activation of carboxylic acids, as it enables the generation of free radicals from ubiquitous feedstocks without prefunctionalization. However, the range of alkenes compatible with this type of catalysis is limited to electron-deficient alkenes and dienes. In contrast, donor alkenes and styrenes face problems due to polarity effects and the lack of efficient catalyst turnover pathways. Here, four alkenetype radical traps that enable metal-free alkylation with carboxylic acids are described. In each case, the reaction efficiency is ensured by redox-active benzotriazole-based systems, which reflects its versatility in rational design of photocatalytic processes. As a result, a plethora of decarboxylative processes for the synthesis of ketones and heterocyclic derivatives are presented, and the mechanisms responsible for maintaining the catalytic cycle in these cases are discussed.
{"title":"Design of Benzotriazole-Based Radical Traps for the Alkylation of Alkenes with Carboxylic Acids via Acridine Photocatalysis","authors":"Anna S Xenzova,Mikhail O Zubkov,Mikhail Kosobokov,Alexander Dilman","doi":"10.1039/d6qo01104g","DOIUrl":"https://doi.org/10.1039/d6qo01104g","url":null,"abstract":"Acridine photocatalysis is one of the most powerful methods for the decarboxylative activation of carboxylic acids, as it enables the generation of free radicals from ubiquitous feedstocks without prefunctionalization. However, the range of alkenes compatible with this type of catalysis is limited to electron-deficient alkenes and dienes. In contrast, donor alkenes and styrenes face problems due to polarity effects and the lack of efficient catalyst turnover pathways. Here, four alkenetype radical traps that enable metal-free alkylation with carboxylic acids are described. In each case, the reaction efficiency is ensured by redox-active benzotriazole-based systems, which reflects its versatility in rational design of photocatalytic processes. As a result, a plethora of decarboxylative processes for the synthesis of ketones and heterocyclic derivatives are presented, and the mechanisms responsible for maintaining the catalytic cycle in these cases are discussed.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"7 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149251203","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}
Shi Zang,Zihao Lin,Zhaojun Ding,Jinlian Li,Lutz Ackermann,Jiayu Mo
Nitroarenes serve as fundamental industrial precursors, with nitrobenzene representing the primary source of aniline and its essential downstream applications. While extensive progress has been made in transforming nitro groups into diverse nitrogen-containing functionalities, the strategic dual functionalization of both the N═O bond and the aromatic para-C–H position remains in its infancy. Herein, we disclose an electrochemical strategy that overrides the conventional reactivity patterns of nitroarenes, enabling catalyst-free tandem N═O/para-C–H functionalizations with exceptional chemo- and regioselectivity. This operationally simple method accommodates a broad substrate scope and exhibits good functional group compatibility, providing a step- and atom-economic platform for rapid molecular diversification that significantly expands the synthetic utility of nitroarenes beyond traditional transformations.
{"title":"Catalyst-free electrochemical -C–H functionalization of nitroarenes NO bond activation","authors":"Shi Zang,Zihao Lin,Zhaojun Ding,Jinlian Li,Lutz Ackermann,Jiayu Mo","doi":"10.1039/d6qo01383j","DOIUrl":"https://doi.org/10.1039/d6qo01383j","url":null,"abstract":"Nitroarenes serve as fundamental industrial precursors, with nitrobenzene representing the primary source of aniline and its essential downstream applications. While extensive progress has been made in transforming nitro groups into diverse nitrogen-containing functionalities, the strategic dual functionalization of both the N═O bond and the aromatic para-C–H position remains in its infancy. Herein, we disclose an electrochemical strategy that overrides the conventional reactivity patterns of nitroarenes, enabling catalyst-free tandem N═O/para-C–H functionalizations with exceptional chemo- and regioselectivity. This operationally simple method accommodates a broad substrate scope and exhibits good functional group compatibility, providing a step- and atom-economic platform for rapid molecular diversification that significantly expands the synthetic utility of nitroarenes beyond traditional transformations.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"1 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149251205","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 condition-controlled divergent chlorination-oxidation of tetrahydroquinazolines (THQs) enabled by trichloroisocyanuric acid (TCCA), which serves as both an electrophilic chlorine source and an oxidant. By tuning the reaction conditions, THQs are selectively directed toward either monooxidized dichlorinated tetrahydroquinazolines or fully oxidized dichlorinated quinazolines, providing high yields and broad functional group tolerance. This switchable reactivity enables direct control over the oxidation state and product outcome. Mechanistic investigations, supported by a series of control experiments, provide evidence for the proposed reaction pathway and suggest that chlorination precedes the subsequent oxidation/aromatization step. Notably, the position of the double bond in the monooxidized dichlorinated products was unambiguously established through a combination of thermodynamic considerations and spectroscopic analyses.
{"title":"Condition-Controlled Divergent Oxidation and Chlorination of Tetrahydroquinazolines with Trichloroisocyanuric Acid","authors":"Merve Kalemli,Ziya Dağalan,Fuat Aslan,Sefa Ucar","doi":"10.1039/d6qo01225f","DOIUrl":"https://doi.org/10.1039/d6qo01225f","url":null,"abstract":"We report a condition-controlled divergent chlorination-oxidation of tetrahydroquinazolines (THQs) enabled by trichloroisocyanuric acid (TCCA), which serves as both an electrophilic chlorine source and an oxidant. By tuning the reaction conditions, THQs are selectively directed toward either monooxidized dichlorinated tetrahydroquinazolines or fully oxidized dichlorinated quinazolines, providing high yields and broad functional group tolerance. This switchable reactivity enables direct control over the oxidation state and product outcome. Mechanistic investigations, supported by a series of control experiments, provide evidence for the proposed reaction pathway and suggest that chlorination precedes the subsequent oxidation/aromatization step. Notably, the position of the double bond in the monooxidized dichlorinated products was unambiguously established through a combination of thermodynamic considerations and spectroscopic analyses.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"22 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149251204","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}
Junyuan Yan,Song Wu,Shi Zeng,Xiaomei Li,Zan Xu,Yuhan Lei,Xin Wang,Zhouyu Wang,Xiao-Long He
The atropisomeric C2-arylindole reprsents a typical axially chiral heterobiaryl structure in drug discovery and novel catalyst/ligand design. We herein developed a CPA-catalyzed atroposelective electrophilic amination of C2-arylindoles via the dynamic kinetic resolution process, delivering a wide range of C3-aminated C2-arylindoles in excellent yields (up to 98%) with good enantioselectivities (up to 99:1 er). A plausible transition state involving a multi-functional activation mode was proposed to rationalize the origin of the good enantioselectivity. Synthetic utility was demonstrated by conversion to an axially chiral phosphine ligand with complete enantiopurity retention.
{"title":"Catalytic Atroposelective Amination of 2-Arylindoles via Chiral Phosphoric Acid-enabled Dynamic Kinetic Resolutions","authors":"Junyuan Yan,Song Wu,Shi Zeng,Xiaomei Li,Zan Xu,Yuhan Lei,Xin Wang,Zhouyu Wang,Xiao-Long He","doi":"10.1039/d6qo01197g","DOIUrl":"https://doi.org/10.1039/d6qo01197g","url":null,"abstract":"The atropisomeric C2-arylindole reprsents a typical axially chiral heterobiaryl structure in drug discovery and novel catalyst/ligand design. We herein developed a CPA-catalyzed atroposelective electrophilic amination of C2-arylindoles via the dynamic kinetic resolution process, delivering a wide range of C3-aminated C2-arylindoles in excellent yields (up to 98%) with good enantioselectivities (up to 99:1 er). A plausible transition state involving a multi-functional activation mode was proposed to rationalize the origin of the good enantioselectivity. Synthetic utility was demonstrated by conversion to an axially chiral phosphine ligand with complete enantiopurity retention.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"14 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149251202","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}
Neokotalanol (5), a sulfonium-type α-glucosidase inhibitor derived from the Ayurvedic medicinal plant Salacia, exhibits approximately 2000-fold greater inhibitory activity against maltase–glucoamylase than acarbose, a clinically used α-glucosidase inhibitor. Accordingly, considerable efforts have been devoted over the years to the development of efficient synthetic methods for 5. However, the construction of its thiosugar sulfonium salt framework has conventionally relied on coupling reactions between a thiosugar and polyhydroxy side-chain building blocks, which often result in low yields and require careful control of the stereochemistry. Herein, we report the total synthesis of 5 from D-galactose via a strategy featuring a highly stereoselective intramolecular sulphide cyclisation, which enables direct construction of the thiosugar sulfonium framework without the need for conventional coupling reactions. This key transformation afforded the desired α-isomer of the thiosugar sulfonium salt in 95% isolated yield with high stereoselectivity (α/β = 38:1). This study provides a new synthetic strategy for thiosugar sulfonium salt-type compounds, including 5.
{"title":"Total Synthesis of Neokotalanol: Construction of a Thiosugar Sulfonium Framework via an Efficient and Highly Stereoselective Sulphide Cyclisation","authors":"Katsuki Takashima,Shinya Nakamura,Yuki Kobayashi,Kaho Kurihara,Shinsuke Marumoto,Fumihiro Ishikawa,Weijia Xie,Genzoh Tanabe","doi":"10.1039/d6qo01184e","DOIUrl":"https://doi.org/10.1039/d6qo01184e","url":null,"abstract":"Neokotalanol (5), a sulfonium-type α-glucosidase inhibitor derived from the Ayurvedic medicinal plant Salacia, exhibits approximately 2000-fold greater inhibitory activity against maltase–glucoamylase than acarbose, a clinically used α-glucosidase inhibitor. Accordingly, considerable efforts have been devoted over the years to the development of efficient synthetic methods for 5. However, the construction of its thiosugar sulfonium salt framework has conventionally relied on coupling reactions between a thiosugar and polyhydroxy side-chain building blocks, which often result in low yields and require careful control of the stereochemistry. Herein, we report the total synthesis of 5 from D-galactose via a strategy featuring a highly stereoselective intramolecular sulphide cyclisation, which enables direct construction of the thiosugar sulfonium framework without the need for conventional coupling reactions. This key transformation afforded the desired α-isomer of the thiosugar sulfonium salt in 95% isolated yield with high stereoselectivity (α/β = 38:1). This study provides a new synthetic strategy for thiosugar sulfonium salt-type compounds, including 5.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"34 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149248626","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}
Divergent synthesis is a powerful strategy for constructing diverse molecular scaffolds. However, the sustainable synthesis of both acylated and hydroxyalkylated heterocycles from common precursors in green solvents remains largely unexplored. Here, we first report a photocatalytic divergent strategy for the efficient synthesis of acylated and hydroxyalkylated dibenzo[b,f][1,4]oxazepines using α-keto acids as radical precursors and dimethyl carbonate (DMC) as a green solvent. This transformation proceeds through a photocatalytic radical addition with switchable product selectivity by simply adjusting the reaction conditions, delivering 50 examples in moderate to excellent yields. Mechanistically, photocatalytic decarboxylation affords acyl radicals, and their divergent conversion to either acylated or hydroxyalkylated products is governed by the presence or absence of an oxidant. This strategy offers several significant advantages, including green solvent, room temperature, transition-metal-free, broad substrate applicability, efficient scalability, and the utilization of visible light as an eco-friendly energy source.
{"title":"Photocatalytic Divergent Synthesis to Access Acylated and Hydroxyalkylated Dibenzo[b,f][1,4]oxazepines in Sustainable Solvent","authors":"Fan-Lin Zeng,Tian-Tian Zheng,Bing Yu,Yanli Yin,Teck Peng Loh","doi":"10.1039/d6qo01131d","DOIUrl":"https://doi.org/10.1039/d6qo01131d","url":null,"abstract":"Divergent synthesis is a powerful strategy for constructing diverse molecular scaffolds. However, the sustainable synthesis of both acylated and hydroxyalkylated heterocycles from common precursors in green solvents remains largely unexplored. Here, we first report a photocatalytic divergent strategy for the efficient synthesis of acylated and hydroxyalkylated dibenzo[b,f][1,4]oxazepines using α-keto acids as radical precursors and dimethyl carbonate (DMC) as a green solvent. This transformation proceeds through a photocatalytic radical addition with switchable product selectivity by simply adjusting the reaction conditions, delivering 50 examples in moderate to excellent yields. Mechanistically, photocatalytic decarboxylation affords acyl radicals, and their divergent conversion to either acylated or hydroxyalkylated products is governed by the presence or absence of an oxidant. This strategy offers several significant advantages, including green solvent, room temperature, transition-metal-free, broad substrate applicability, efficient scalability, and the utilization of visible light as an eco-friendly energy source.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"3 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149241465","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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