Pub Date : 2025-10-13Epub Date: 2025-09-29DOI: 10.1039/d5qo01266j
Vitaly V. Shorokhov , Beauty K. Chabuka , Albina A. Nikolaeva , Sergey S. Zhokhov , Ivan A. Andreev , Nina K. Ratmanova , Igor V. Trushkov , Olga A. Ivanova , Igor V. Alabugin
Ylides are versatile reagents known for their dual electrophilic and nucleophilic reactivity, mimicking carbenes in many reactions. In this study, we uncover a previously unreported reactivity pathway for ylides: a methylene insertion into C–C bonds. We show that sulfur ylides can achieve homologation of alkenes and aldehydes before proceeding through the classical Corey–Chaykovsky reaction. This process allows for the dual transfer of CH2 groups to both substrates, yielding benzylcyclopropanes and benzyloxiranes, valuable intermediates in organic synthesis. Remarkably, the same sulfur ylide reagent participates in two distinct carbene-like transformations within this cascade. Mechanistic studies reveal the role of a tightly coordinated stereoelectronic network playing a crucial role in facilitating anionic 1,2-aryl shifts.
{"title":"New mode of sulfur ylides reactivity: stereoelectronic control provides C–C bond insertion before cyclopropanation/epoxidation directly affording homologated three-membered rings","authors":"Vitaly V. Shorokhov , Beauty K. Chabuka , Albina A. Nikolaeva , Sergey S. Zhokhov , Ivan A. Andreev , Nina K. Ratmanova , Igor V. Trushkov , Olga A. Ivanova , Igor V. Alabugin","doi":"10.1039/d5qo01266j","DOIUrl":"10.1039/d5qo01266j","url":null,"abstract":"<div><div>Ylides are versatile reagents known for their dual electrophilic and nucleophilic reactivity, mimicking carbenes in many reactions. In this study, we uncover a previously unreported reactivity pathway for ylides: a methylene insertion into C–C bonds. We show that sulfur ylides can achieve homologation of alkenes and aldehydes before proceeding through the classical Corey–Chaykovsky reaction. This process allows for the dual transfer of CH<sub>2</sub> groups to both substrates, yielding benzylcyclopropanes and benzyloxiranes, valuable intermediates in organic synthesis. Remarkably, the same sulfur ylide reagent participates in two distinct carbene-like transformations within this cascade. Mechanistic studies reveal the role of a tightly coordinated stereoelectronic network playing a crucial role in facilitating anionic 1,2-aryl shifts.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 6852-6863"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145183066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Propargyl sulfonium salts have been reported as novel electron-rich-olefin precursors that undergo an inverse electron-demand Diels–Alder [4 + 2] reaction with tetrazines. This method enables the rapid and modular assembly of structurally diverse propargyl sulfonium salts and tetrazines, offering significant features such as a short reaction time, excellent efficiency, and mild reaction conditions. Notably, this approach has been further extended to propargyl sulfonium–peptide systems for the site-specific labeling of methionine residues in short peptides and the construction of cyclic peptides.
{"title":"An IEDDA reaction of propargyl sulfonium salts and tetrazines: a versatile [4 + 2] modular assembly","authors":"Zheng Wang , Qi Zhu , Jiankang Zhang , Huajian Zhu , Jiaan Shao , Wenteng Chen","doi":"10.1039/d5qo01092f","DOIUrl":"10.1039/d5qo01092f","url":null,"abstract":"<div><div>Propargyl sulfonium salts have been reported as novel electron-rich-olefin precursors that undergo an inverse electron-demand Diels–Alder [4 + 2] reaction with tetrazines. This method enables the rapid and modular assembly of structurally diverse propargyl sulfonium salts and tetrazines, offering significant features such as a short reaction time, excellent efficiency, and mild reaction conditions. Notably, this approach has been further extended to propargyl sulfonium–peptide systems for the site-specific labeling of methionine residues in short peptides and the construction of cyclic peptides.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 7091-7096"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13Epub Date: 2025-09-30DOI: 10.1039/d5qo00797f
Kabali Divya Bharathi , Palani Manikandan , Arasambattu K. Mohanakrishnan
The Diels–Alder (DA) reaction of a series of tetrasubstituted cyclopentadienones (CPDs) with benzo[b]thiophene S,S-dioxide analogues in various solvents at different temperatures led to the formation carbocyclic as well as heterocyclic compounds. The intermediate DA adducts underwent CO extrusion followed by different aromatization patterns depending upon the nature of substituents on dienes as well as dienophiles, and temperature to afford these compounds. At temperatures <150 °C, the adducts mostly furnished annulated benzo[b]thiophenes involving 1,3-H shifts followed by deoxygenation or afforded substituted arenes through SO2 extrusion. However, at an elevated temperature (>200 °C), the intermediate dihydrodibenzothiophene S,S-dioxides underwent an exclusive SO2 elimination pathway followed by an intramolecular cyclization to furnish aryl-/hetero-aryl fused phenanthrene and pyrene derivatives. In contrast, the DA reaction of phenanthrene as well as pyrene fused CPDs required high temperature for CO and SO2 extrusions accompanied by annulation to give the corresponding π-conjugated arenes as well as hetero-arenes. The DA reaction of CPDs could also be performed with 2-indenone as a dienophile to assemble unsymmetrical fluorenones via CO extrusion followed by 1,3-H shift and subsequent oxidation of the resulting fluorenols. Alternatively, the DA reaction of acenaphthene-based CPDs containing electron-withdrawing ester units at 7,9-positions could be carried out with benzo[b]thiophene S,S-dioxides in nitrobenzene at reflux to afford the respective fluorenones involving SO2 extrusion followed by intramolecular anionic cyclization with an ester unit.
{"title":"Diels–Alder reaction of substituted cyclopentadienones with benzothiophene S,S-dioxides: synthesis of dibenzothiophenes, dibenzothiophene S,S-dioxides, acenaphthenes, phenanthrenes, pyrenes, and fluorenones by exploiting thermolysis of Diels–Alder adducts","authors":"Kabali Divya Bharathi , Palani Manikandan , Arasambattu K. Mohanakrishnan","doi":"10.1039/d5qo00797f","DOIUrl":"10.1039/d5qo00797f","url":null,"abstract":"<div><div>The Diels–Alder (DA) reaction of a series of tetrasubstituted cyclopentadienones (CPDs) with benzo[<em>b</em>]thiophene <em>S</em>,<em>S</em>-dioxide analogues in various solvents at different temperatures led to the formation carbocyclic as well as heterocyclic compounds. The intermediate DA adducts underwent CO extrusion followed by different aromatization patterns depending upon the nature of substituents on dienes as well as dienophiles, and temperature to afford these compounds. At temperatures <150 °C, the adducts mostly furnished annulated benzo[<em>b</em>]thiophenes involving 1,3-H shifts followed by deoxygenation or afforded substituted arenes through SO<sub>2</sub> extrusion. However, at an elevated temperature (>200 °C), the intermediate dihydrodibenzothiophene <em>S</em>,<em>S</em>-dioxides underwent an exclusive SO<sub>2</sub> elimination pathway followed by an intramolecular cyclization to furnish aryl-/hetero-aryl fused phenanthrene and pyrene derivatives. In contrast, the DA reaction of phenanthrene as well as pyrene fused CPDs required high temperature for CO and SO<sub>2</sub> extrusions accompanied by annulation to give the corresponding π-conjugated arenes as well as hetero-arenes. The DA reaction of CPDs could also be performed with 2-indenone as a dienophile to assemble unsymmetrical fluorenones <em>via</em> CO extrusion followed by 1,3-H shift and subsequent oxidation of the resulting fluorenols. Alternatively, the DA reaction of acenaphthene-based CPDs containing electron-withdrawing ester units at 7,9-positions could be carried out with benzo[<em>b</em>]thiophene <em>S</em>,<em>S</em>-dioxides in nitrobenzene at reflux to afford the respective fluorenones involving SO<sub>2</sub> extrusion followed by intramolecular anionic cyclization with an ester unit.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 7151-7161"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145189229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13Epub Date: 2025-09-22DOI: 10.1039/d5qo01185j
Keyang Wu , Kirklin L. McWhorter , Ayzia Ford , Liming Tan , Lidia M. Waidmann , Jesus O. Vazquez Hernandez , Madeline M. Garcia , Katherine M. Davis , Gang Li
The efficient construction of carbon–nitrogen bonds is fundamental to the synthesis of pharmaceuticals, agrochemicals, and natural products, particularly for α-amino esters. Transition-metal-catalyzed carbene insertion into N–H bonds offers a powerful approach due to its efficiency and selectivity, but has predominantly been developed using noble metal catalysts. Although, select base metals have been explored, cobalt catalysts remain scarce. Herein, we report an N–H insertion reaction to form α-amino esters catalyzed by a cobaloxime catalyst, using diazo compounds as the carbene precursors. With low catalyst loading, primary, secondary, and (hetero)aromatic amines all react smoothly (up to 97%). While comprehensive mechanistic studies suggest a cobalt alkyl ylide intermediate dominates these reactions, we observe small contributions of a carbene radical. This approach can be applied in the late-stage functionalization of various N-containing bioactive molecules, highlighting its potential synthetic application.
{"title":"Cobaloxime catalyzed carbene insertion into N–H bonds: a streamlined route to α-amino esters with mechanistic insights","authors":"Keyang Wu , Kirklin L. McWhorter , Ayzia Ford , Liming Tan , Lidia M. Waidmann , Jesus O. Vazquez Hernandez , Madeline M. Garcia , Katherine M. Davis , Gang Li","doi":"10.1039/d5qo01185j","DOIUrl":"10.1039/d5qo01185j","url":null,"abstract":"<div><div>The efficient construction of carbon–nitrogen bonds is fundamental to the synthesis of pharmaceuticals, agrochemicals, and natural products, particularly for α-amino esters. Transition-metal-catalyzed carbene insertion into N–H bonds offers a powerful approach due to its efficiency and selectivity, but has predominantly been developed using noble metal catalysts. Although, select base metals have been explored, cobalt catalysts remain scarce. Herein, we report an N–H insertion reaction to form α-amino esters catalyzed by a cobaloxime catalyst, using diazo compounds as the carbene precursors. With low catalyst loading, primary, secondary, and (hetero)aromatic amines all react smoothly (up to 97%). While comprehensive mechanistic studies suggest a cobalt alkyl ylide intermediate dominates these reactions, we observe small contributions of a carbene radical. This approach can be applied in the late-stage functionalization of various N-containing bioactive molecules, highlighting its potential synthetic application.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 6989-7002"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13Epub Date: 2025-09-25DOI: 10.1039/d5qo01085c
Limin Xu , Yuxuan Zhang , Yan Lu , Zhaoguo Zhang
Stereoselective reduction of β-C-glycosidic ketones is an effective method for the synthesis of carbohydrate derivatives. We herein report that β-C-glycosidic ketones, not generally considered as functionalized ketones, are unexpectedly hydrogenated by Ru-diphosphine catalysts with excellent stereoselectivity (up to >99 : 1 dr). Further investigation into the effect of the chiral hydroxyl groups during the reaction has also been conducted. This reaction has been performed on a multi-gram scale, providing a novel approach for the construction of chiral centers in carbohydrate derivatives.
立体选择还原β- c -糖苷酮是合成碳水化合物衍生物的有效方法。我们在此报道，通常不被认为是功能化酮的β- c -糖苷酮，意外地被具有优异立体选择性（高达>；99: 1 dr）的ru -二膦催化剂氢化。对手性羟基在反应中的作用也进行了进一步的研究。该反应在多克尺度上进行，为碳水化合物衍生物的手性中心的构建提供了一种新的方法。
{"title":"Ru-Diphosphine catalyzed asymmetric hydrogenation of unprotected β-C-glycosidic ketones","authors":"Limin Xu , Yuxuan Zhang , Yan Lu , Zhaoguo Zhang","doi":"10.1039/d5qo01085c","DOIUrl":"10.1039/d5qo01085c","url":null,"abstract":"<div><div>Stereoselective reduction of β-<em>C</em>-glycosidic ketones is an effective method for the synthesis of carbohydrate derivatives. We herein report that β-<em>C</em>-glycosidic ketones, not generally considered as functionalized ketones, are unexpectedly hydrogenated by Ru-diphosphine catalysts with excellent stereoselectivity (up to >99 : 1 dr). Further investigation into the effect of the chiral hydroxyl groups during the reaction has also been conducted. This reaction has been performed on a multi-gram scale, providing a novel approach for the construction of chiral centers in carbohydrate derivatives.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 6974-6979"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13Epub Date: 2025-10-07DOI: 10.1039/d5qo01038a
Jian Han , Li-Li Zeng , Yue Zhou , Shi-Han Xu , Liang Shen , Wei Lin , Fen-Er Chen
Vinyl fluoromethyl thioethers are widely employed as pivotal intermediates in organic synthesis and deemed as promising scaffolds in drug candidates. Herein, we report a general and concise strategy for the stereoselective fluoromethylthiolation of enamides, enabling the modular assembly of vinyl di-/trifluoromethyl thioethers from bench-stable fluoromethylthiolating reagents. This mild protocol exhibits broad functional group compatibility, as demonstrated by over 40 examples, including enamides derived from bioactive molecules. Furthermore, the utility of this method is highlighted through the late-stage modification of the approved probenecid drug and a series of synthetic applications. Mechanistic investigations, including control experiments, Stern–Volmer quenching, and light on–off experiments, elucidate the photoredox radical reaction pathway.
{"title":"Photoinduced regio- and stereoselective C(sp2)–H fluoromethylthiolation of enamides","authors":"Jian Han , Li-Li Zeng , Yue Zhou , Shi-Han Xu , Liang Shen , Wei Lin , Fen-Er Chen","doi":"10.1039/d5qo01038a","DOIUrl":"10.1039/d5qo01038a","url":null,"abstract":"<div><div>Vinyl fluoromethyl thioethers are widely employed as pivotal intermediates in organic synthesis and deemed as promising scaffolds in drug candidates. Herein, we report a general and concise strategy for the stereoselective fluoromethylthiolation of enamides, enabling the modular assembly of vinyl di-/trifluoromethyl thioethers from bench-stable fluoromethylthiolating reagents. This mild protocol exhibits broad functional group compatibility, as demonstrated by over 40 examples, including enamides derived from bioactive molecules. Furthermore, the utility of this method is highlighted through the late-stage modification of the approved probenecid drug and a series of synthetic applications. Mechanistic investigations, including control experiments, Stern–Volmer quenching, and light on–off experiments, elucidate the photoredox radical reaction pathway.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 7174-7180"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13Epub Date: 2025-08-28DOI: 10.1039/d5qo01088h
Manik Jana , Gunasekaran Velmurugan , Sumit Sahoo , Peter Comba , Harapriya Rath
The retrosynthetic design and syntheses of three unprecedented core-modified N-confused pentaphyrins (sapphyrins) possessing an E-ethylene bithiophene moiety with tunable Hückel (anti)aromaticity are reported. Solution-state spectroscopic analyses reveal the sustained E-conformation for the ethylene moiety. All three N-confused pentaphyrins exhibited vis-NIR absorption. All possible stereoisomers of the S2N3 hybrid N-confused pentaphyrins have been unravelled via thorough DFT studies. DFT studies support the Hückel π aromaticity of pentaphyrins and but π-antiaromaticity for .
{"title":"Core-modified N-confused pentaphyrin variants with adaptive (anti)aromaticity","authors":"Manik Jana , Gunasekaran Velmurugan , Sumit Sahoo , Peter Comba , Harapriya Rath","doi":"10.1039/d5qo01088h","DOIUrl":"10.1039/d5qo01088h","url":null,"abstract":"<div><div>The retrosynthetic design and syntheses of three unprecedented core-modified N-confused pentaphyrins (sapphyrins) possessing an <em>E</em>-ethylene bithiophene moiety with tunable Hückel (anti)aromaticity are reported. Solution-state spectroscopic analyses reveal the sustained <em>E</em>-conformation for the ethylene moiety. All three N-confused pentaphyrins exhibited vis-NIR absorption. All possible stereoisomers of the S<sub>2</sub>N<sub>3</sub> hybrid N-confused pentaphyrins have been unravelled <em>via</em> thorough DFT studies. DFT studies support the Hückel π aromaticity of pentaphyrins and but π-antiaromaticity for .</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 6885-6893"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144911122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The benzoin condensation of a designed dialdehyde with a terphenyl framework was investigated. When the reaction was carried out in mixed solvents composed of an alcohol and a co-solvent, a precipitate primarily consisting of the cyclic dimer meso- was obtained, indicating a precipitation-driven diastereo- and regioselective self-assembly process. Using this system as a model for precipitation-induced self-assembly based on reversible C–C bond formation, we comprehensively investigated the effects of the alcohol, co-solvent, and alkyl chain length of the substrate on the outcome of the reaction. Notably, the reaction of ethoxy-substituted dialdehyde in MeOH/toluene mixture reached equilibrium efficiently, affording a crystalline precipitate incorporating macrocycle meso- and toluene, from which meso- was isolated in good yield.
{"title":"Precipitation-driven diastereo- and regioselective macrocyclization via benzoin condensation: effects of solvents and alkyl chain lengths","authors":"Kosuke Ono , Junya Fukumoto , Yu Tanoi , Hidetoshi Kawai","doi":"10.1039/d5qo01179e","DOIUrl":"10.1039/d5qo01179e","url":null,"abstract":"<div><div>The benzoin condensation of a designed dialdehyde with a terphenyl framework was investigated. When the reaction was carried out in mixed solvents composed of an alcohol and a co-solvent, a precipitate primarily consisting of the cyclic dimer <em>meso</em>- was obtained, indicating a precipitation-driven diastereo- and regioselective self-assembly process. Using this system as a model for precipitation-induced self-assembly based on reversible C–C bond formation, we comprehensively investigated the effects of the alcohol, co-solvent, and alkyl chain length of the substrate on the outcome of the reaction. Notably, the reaction of ethoxy-substituted dialdehyde in MeOH/toluene mixture reached equilibrium efficiently, affording a crystalline precipitate incorporating macrocycle <em>meso</em>- and toluene, from which <em>meso</em>- was isolated in good yield.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 7162-7167"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13Epub Date: 2025-10-03DOI: 10.1039/d5qo01109d
Xiaoyu Liu , Ya-Ru Wan , Yumeng Yang , Runming Wang , Zili Chen
Chiral phosphine ligands play a pivotal role in gold(i)-catalyzed asymmetric reactions, yet their efficacy is often constrained by limited strategies for chiral induction. While traditional ligands rely primarily on steric effects, the linear geometry of Au(i) centers demands innovative ligand designs capable of synergistic interactions beyond spatial hindrance. This challenge motivates the development of ligands incorporating supplementary weakly coordinating groups to enhance enantiocontrol. We herein report four novel chiral gold(i) complexes based on bis-phosphine monoxide ligands (BPMOs), namely (R)-BINAP(O)-AuCl , (R)-MeO-BiPhep(O)-AuCl , (S)-SegPhos(O)-AuCl and (R,R)-DuPhos(O)-AuCl , derived from commercially available biphosphine ligands via mono-oxidation and Au(i)-complexation. The catalytic utility of these complexes was evaluated in the intramolecular catalytic asymmetric dearomatization (CADA) reaction of β-naphthol derivatives, among which, complex [(R)-BINAP(O)-AuCl] exhibited superior performance, delivering a series of spiro-naphthalenone products in good yields with moderate to high enantiomeric excess. Experimental and computational studies reveal that the PO moiety in facilitates a critical hydrogen-bonding interaction with the substrate, synergizing with Au(i)-alkyne coordination to rigidify the transition state and amplify stereocontrol. This work establishes chiral BPMO–Au(i) complexes as versatile catalysts for asymmetric dearomatization, with demonstrated scalability and applicability toward diverse β-naphthol substrates.
{"title":"A chiral bis-phosphine monoxide–gold(i) complex enables asymmetric dearomative cyclization of β-naphthol derivatives","authors":"Xiaoyu Liu , Ya-Ru Wan , Yumeng Yang , Runming Wang , Zili Chen","doi":"10.1039/d5qo01109d","DOIUrl":"10.1039/d5qo01109d","url":null,"abstract":"<div><div>Chiral phosphine ligands play a pivotal role in gold(<span>i</span>)-catalyzed asymmetric reactions, yet their efficacy is often constrained by limited strategies for chiral induction. While traditional ligands rely primarily on steric effects, the linear geometry of Au(<span>i</span>) centers demands innovative ligand designs capable of synergistic interactions beyond spatial hindrance. This challenge motivates the development of ligands incorporating supplementary weakly coordinating groups to enhance enantiocontrol. We herein report four novel chiral gold(<span>i</span>) complexes based on bis-phosphine monoxide ligands (BPMOs), namely (<em>R</em>)-BINAP(O)-AuCl , (<em>R</em>)-MeO-BiPhep(O)-AuCl , (<em>S</em>)-SegPhos(O)-AuCl and (<em>R</em>,<em>R</em>)-DuPhos(O)-AuCl , derived from commercially available biphosphine ligands <em>via</em> mono-oxidation and Au(<span>i</span>)-complexation. The catalytic utility of these complexes was evaluated in the intramolecular catalytic asymmetric dearomatization (CADA) reaction of β-naphthol derivatives, among which, complex [(<em>R</em>)-BINAP(O)-AuCl] exhibited superior performance, delivering a series of spiro-naphthalenone products in good yields with moderate to high enantiomeric excess. Experimental and computational studies reveal that the PO moiety in facilitates a critical hydrogen-bonding interaction with the substrate, synergizing with Au(<span>i</span>)-alkyne coordination to rigidify the transition state and amplify stereocontrol. This work establishes chiral BPMO–Au(<span>i</span>) complexes as versatile catalysts for asymmetric dearomatization, with demonstrated scalability and applicability toward diverse β-naphthol substrates.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 24","pages":"Pages 7181-7188"},"PeriodicalIF":0.0,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145209715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-13Epub Date: 2025-09-05DOI: 10.1039/d5qo00965k
Konstantin E. Shepelenko , Irina G. Gnatiuk , Andrey A. Aleksandrov , Mikhayl E. Minyaev , Victor M. Chernyshev , Valentine P. Ananikov
The selective C3–H functionalization of 2-substituted heterocyclopentadienes (furan, thiophene and pyrrole) remains challenging owing to the typically higher reactivity of the C5–H and C4–H bonds. In this study, we report a facile method for the selective C3–H acylation of pharmaceutically and agrochemically relevant heterocyclopentadienes bearing N-donor directing groups at the 2-position. This approach utilizes readily available aliphatic, aromatic and heteroaromatic acyl chlorides under catalysis by a Ru/PPh3 system generated in situ from commercially available, bench-stable precursors. The method exhibits broad tolerance toward various N-donor directing groups, including those with unprotected NH moieties potentially susceptible to N-acylation. Preliminary mechanistic studies suggest a reaction pathway involving C–H activation, which is rate-limiting and assisted by the carboxylate anion generated via the partial decomposition of the acyl chloride in a basic medium.
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