Wei Zhao , Sining Wang , Haixing Xu , Kun Zhao , Tao Shu
Herein, we described an efficient gold(I)‐catalyzed redox cycloisomerization/[3+2] dipolar cycloaddition domino reaction of o‐(alkynyl)nitrobenzenes. The domino process involves the in situ generation of α‐oxo gold carbenes via intramolecular redox reactions of alkynes and nitro functional groups, followed by the formation of nitrones and subsequent intramolecular [3+2] dipolar cycloaddition reaction to furnish a diverse array of complex isoxazolidine‐containing polycyclic scaffolds in moderate to good yields, with up to excellent diastereoselectivities.
{"title":"Gold‐Catalyzed Redox Cycloisomerization/[3+2] Dipolar Cycloaddition Domino Reactions: Construction of Isoxazolidine‐Containing Polycyclic Scaffolds","authors":"Wei Zhao , Sining Wang , Haixing Xu , Kun Zhao , Tao Shu","doi":"10.1002/ejoc.202501012","DOIUrl":"10.1002/ejoc.202501012","url":null,"abstract":"<div><div>Herein, we described an efficient gold(I)‐catalyzed redox cycloisomerization/[3+2] dipolar cycloaddition domino reaction of <em>o</em>‐(alkynyl)nitrobenzenes. The domino process involves the in situ generation of α‐oxo gold carbenes via intramolecular redox reactions of alkynes and nitro functional groups, followed by the formation of nitrones and subsequent intramolecular [3+2] dipolar cycloaddition reaction to furnish a diverse array of complex isoxazolidine‐containing polycyclic scaffolds in moderate to good yields, with up to excellent diastereoselectivities.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"29 4","pages":"Article e202501012"},"PeriodicalIF":2.7,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718393","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}
Herein, we report an efficient and scalable synthesis of the core skeleton of elacestrant, a selective estrogen receptor degrader used in breast cancer treatment. The present synthesis features simple synthetic transformations, involving one‐pot conversion of 6‐hydroxy‐1‐tetralone into a cyclic olefin followed by copper‐catalyzed arylation of the cyclic olefin (iodometathesis) with a diaryliodonium salt as a key strategy to achieve the core skeleton on a gram scale. This procedure was extended to the total synthesis of (±)‐elacestrant by employing two different coupling strategies: reductive amination of an aldehyde and nucleophilic substitution of a bromo compound with the core skeleton.
{"title":"Practical Synthesis of Elacestrant, an FDA‐Approved Selective Estrogen Receptor Degrader","authors":"Chandra Shekhar , Pranay Kothuri , Srivari Chandrasekhar , Kiranmai Nayani","doi":"10.1002/ejoc.202501030","DOIUrl":"10.1002/ejoc.202501030","url":null,"abstract":"<div><div>Herein, we report an efficient and scalable synthesis of the core skeleton of elacestrant, a selective estrogen receptor degrader used in breast cancer treatment. The present synthesis features simple synthetic transformations, involving one‐pot conversion of 6‐hydroxy‐1‐tetralone into a cyclic olefin followed by copper‐catalyzed arylation of the cyclic olefin (iodometathesis) with a diaryliodonium salt as a key strategy to achieve the core skeleton on a gram scale. This procedure was extended to the total synthesis of (±)‐elacestrant by employing two different coupling strategies: reductive amination of an aldehyde and nucleophilic substitution of a bromo compound with the core skeleton.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"29 4","pages":"Article e202501030"},"PeriodicalIF":2.7,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704287","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}
The difluoromethyl group is a bioisostere of hydroxy and sulfanyl groups. The photocatalytic reduction of trifluoromethyl groups is one of the most important methods for the synthesis of difluoromethyl compounds. We have developed a photoinduced synthesis of difluoromethyl compounds using a combined method of fluoride‐coupled electron transfer and hydrogen atom transfer. Utilizing benzimidazoline derivatives as photoreductant and hydrogen atom donor, difluoromethylarenes were synthesized through the C–F bond reduction of trifluoromethylarenes. Mechanistic studies indicated that the photoreduction proceeded via an electron‐donor–acceptor complex between trifluoromethylarenes and benzimidazoline derivatives.
{"title":"Fluoride‐Coupled Electron Transfer and Hydrogen‐Atom‐Transfer‐Mediated Synthesis of Difluoromethylarenes","authors":"Tatsuhiro Uchikura , Kaho Ohashi , Fua Akutsu , Takahiko Akiyama","doi":"10.1002/ejoc.202501034","DOIUrl":"10.1002/ejoc.202501034","url":null,"abstract":"<div><div>The difluoromethyl group is a bioisostere of hydroxy and sulfanyl groups. The photocatalytic reduction of trifluoromethyl groups is one of the most important methods for the synthesis of difluoromethyl compounds. We have developed a photoinduced synthesis of difluoromethyl compounds using a combined method of fluoride‐coupled electron transfer and hydrogen atom transfer. Utilizing benzimidazoline derivatives as photoreductant and hydrogen atom donor, difluoromethylarenes were synthesized through the C–F bond reduction of trifluoromethylarenes. Mechanistic studies indicated that the photoreduction proceeded via an electron‐donor–acceptor complex between trifluoromethylarenes and benzimidazoline derivatives.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"29 4","pages":"Article e202501034"},"PeriodicalIF":2.7,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145777791","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 the first rhodium (III)‐catalyzed, (benz)imidazole‐directed site‐ selective [4+2] cyclization of indoles with maleimides, enabling the efficient synthesis of C6‐fused polyheterocyclic indoles. This strategy features with wide substrate scope and excellent functional group tolerance. Mechanistic insights were gained through control experiments, deuterium‐labeling, and competitive studies. Application of this methodology produced novel heterocycles via simple postsynthetic chemical transformations, showcasing the synthetic utility of this approach.
{"title":"Rh(III)‐Catalyzed (Benz)imidazole‐Directed [4+2] Cyclization of Indoles With Maleimides: Facile Access to C6‐Fused Indole Polyheterocyclic Compounds","authors":"Qiang Wang , Maaz Khan , Shuangyuan Chen , Qingqing Wu , Guilong Zhao , Pankaj Jadhav","doi":"10.1002/ejoc.202500924","DOIUrl":"10.1002/ejoc.202500924","url":null,"abstract":"<div><div>We report the first rhodium (III)‐catalyzed, (benz)imidazole‐directed site‐ selective [4+2] cyclization of indoles with maleimides, enabling the efficient synthesis of C6‐fused polyheterocyclic indoles. This strategy features with wide substrate scope and excellent functional group tolerance. Mechanistic insights were gained through control experiments, deuterium‐labeling, and competitive studies. Application of this methodology produced novel heterocycles via simple postsynthetic chemical transformations, showcasing the synthetic utility of this approach.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"29 4","pages":"Article e202500924"},"PeriodicalIF":2.7,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145731881","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 straightforward method for cleaving carbon–carbon bonds under metal‐free, base conditions was reported. Efficient synthesis of desired products with 2,3‐fused diaminoindoles scaffold is achieved by reacting 2,2‐disubstituted indolin‐3‐ones with thioureas, leveraging mild reaction conditions and a short reaction time as advantageous features of the method.
{"title":"Base‐Mediated C–C Bond Cleavage Toward 2‐(2‐ oxo ‐2‐Phenylethyl)‐2‐phenylindolin‐3‐ones","authors":"Faxiu Feng, Wenjun Wang, Xiaoming Liao, Zhuoran Yang, Ping Li, Xiaoxiang Zhang","doi":"10.1002/ejoc.202501196","DOIUrl":"https://doi.org/10.1002/ejoc.202501196","url":null,"abstract":"A straightforward method for cleaving carbon–carbon bonds under metal‐free, base conditions was reported. Efficient synthesis of desired products with 2,3‐fused diaminoindoles scaffold is achieved by reacting 2,2‐disubstituted indolin‐3‐ones with thioureas, leveraging mild reaction conditions and a short reaction time as advantageous features of the method.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043146","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}
Molecular confinement is a viable method to fine‐tune the reactivity of chemical species. Metal–organic cages, which have large void spaces within, are especially attractive entities for encapsulating various guests. Here, a water‐soluble flexible metal–organic cage was used to confine two guest molecules, as either homo‐ or heterodimers with a high uptake efficiency. Photo irradiation of the inclusion complexes results in a smooth photo [2 + 2] dimerization reaction in aqueous solution despite the flexibility of this metal–organic cage. The preorganization of two molecules within the cage was responsible for the smooth photo‐dimerization, both for the homodimer and heterodimer. Kinetic study of the photoreaction revealed a pseudo‐first‐order reaction, implying a preformed dimer of guests within the cage was responsible for the reaction.
{"title":"Confinement‐Induced [2 + 2] Photodimerization of Vinylenes Within a Flexible Metal–Organic Cage","authors":"Jinhua Wang, Tiantian Shao, Ruiling Huang, Ruhai Zuo, Qiaoling Zhang, Chengfeng Xiong, Zhiping Le","doi":"10.1002/ejoc.202500981","DOIUrl":"https://doi.org/10.1002/ejoc.202500981","url":null,"abstract":"Molecular confinement is a viable method to fine‐tune the reactivity of chemical species. Metal–organic cages, which have large void spaces within, are especially attractive entities for encapsulating various guests. Here, a water‐soluble flexible metal–organic cage was used to confine two guest molecules, as either homo‐ or heterodimers with a high uptake efficiency. Photo irradiation of the inclusion complexes results in a smooth photo [2 + 2] dimerization reaction in aqueous solution despite the flexibility of this metal–organic cage. The preorganization of two molecules within the cage was responsible for the smooth photo‐dimerization, both for the homodimer and heterodimer. Kinetic study of the photoreaction revealed a pseudo‐first‐order reaction, implying a preformed dimer of guests within the cage was responsible for the reaction.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"17 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043145","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}
Shishir Singh, Bharat Singh, Suraj Kashyap, Manas K. Ghorai
A simple and atom‐economical protocol to access racemic and nonracemic γ , γ ‐diaryl/heteroaryl‐substituted propylamines in excellent yields (up to 98%) and with moderate enantiomeric excess (up to 62%) starting from azetidines and electron rich arenes/heteroarenes is described. The reaction involves Magic Blue‐initiated and incipient SbCl 5 ‐catalyzed S N 2‐type nucleophilic ring‐opening of activated azetidines with electron rich arenes/heteroarene under mild reaction conditions. The methodology has been efficiently used for the formal synthesis of optically active Tolterodine, an antimuscarinic drug.
{"title":"Magic Blue Initiated S N 2–Type Ring Opening of Azetidines with Electron‐Rich Arenes/Heteroarenes: Formal Synthesis of Nonracemic Tolterodine","authors":"Shishir Singh, Bharat Singh, Suraj Kashyap, Manas K. Ghorai","doi":"10.1002/ejoc.202500836","DOIUrl":"https://doi.org/10.1002/ejoc.202500836","url":null,"abstract":"A simple and atom‐economical protocol to access racemic and nonracemic <jats:italic>γ</jats:italic> , <jats:italic>γ</jats:italic> ‐diaryl/heteroaryl‐substituted propylamines in excellent yields (up to 98%) and with moderate enantiomeric excess (up to 62%) starting from azetidines and electron rich arenes/heteroarenes is described. The reaction involves Magic Blue‐initiated and incipient SbCl <jats:sub>5</jats:sub> ‐catalyzed S <jats:sub>N</jats:sub> 2‐type nucleophilic ring‐opening of activated azetidines with electron rich arenes/heteroarene under mild reaction conditions. The methodology has been efficiently used for the formal synthesis of optically active Tolterodine, an antimuscarinic drug.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"287 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043143","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}
Tatyana V. Gryaznova, Maxim V. Tarasov, Robert R. Fayzullin, Vladimir I. Morozov, Yulia H. Budnikova
The Front Cover shows that ferrocene mediator and electric current can be successfully used under mild, single-stage conditions to obtain practically important bisphosphonates of acridine, xanthene and other molecules. More information on this electrochemical strategy can be found in the Research Article by Yu. H. Budnikova and co-workers (DOI: 10.1002/ejoc.202500983).
{"title":"Front Cover: Electrochemical C(sp2)-H Diphosphorylation With a Redox Mediator: Access to Gem-Bisphosphonates (Eur. J. Org. Chem. 3/2026)","authors":"Tatyana V. Gryaznova, Maxim V. Tarasov, Robert R. Fayzullin, Vladimir I. Morozov, Yulia H. Budnikova","doi":"10.1002/ejoc.70324","DOIUrl":"10.1002/ejoc.70324","url":null,"abstract":"<p><b>The Front Cover</b> shows that ferrocene mediator and electric current can be successfully used under mild, single-stage conditions to obtain practically important bisphosphonates of acridine, xanthene and other molecules. More information on this electrochemical strategy can be found in the Research Article by Yu. H. Budnikova and co-workers (DOI: 10.1002/ejoc.202500983).\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"29 3","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/ejoc.70324","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Guy Pillon, Carlyle Mackenzie, Daniel Zell, Lauren E. Sirois
Photocatalytic reductive radical‐polar crossover is a versatile platform for achieving carbon–carbon bond formations under mild conditions and is complementary to traditional radical reactivity. Herein, we report a study on the reactivity of esters and ketones under this platform to produce cyclic ketone and alcohol products, respectively. The process is amenable to a variety of functionalized systems, and mechanistic experiments suggest intermediacy of both a benzylic radical and anion arising from photocatalytic reduction.
{"title":"Cyclization of Carbonyl Electrophiles via Dual HAT/Photoredox‐Catalyzed Reductive Radical‐Polar Crossover","authors":"Guy Pillon, Carlyle Mackenzie, Daniel Zell, Lauren E. Sirois","doi":"10.1002/ejoc.202500937","DOIUrl":"https://doi.org/10.1002/ejoc.202500937","url":null,"abstract":"Photocatalytic reductive radical‐polar crossover is a versatile platform for achieving carbon–carbon bond formations under mild conditions and is complementary to traditional radical reactivity. Herein, we report a study on the reactivity of esters and ketones under this platform to produce cyclic ketone and alcohol products, respectively. The process is amenable to a variety of functionalized systems, and mechanistic experiments suggest intermediacy of both a benzylic radical and anion arising from photocatalytic reduction.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"396 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146014607","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 metal-free annulative coupling strategy has been developed to synthesize functionalized thiazolidine-4-ones from β-ketothioamides and α-ester sulfoxonium ylides. This cascade process proceeds via concurrent CS and CN bond formation under mild conditions, delivering a wide range of thiazolidine-4-one derivatives in good-to-high yields. The method exhibits excellent functional group tolerance, broad substrate scope, and operational simplicity, with most products isolated via filtration without chromatography. The scalability and synthetic utility were demonstrated through gram-scale synthesis and oxidative late-stage functionalization, highlighting the potential of this strategy for accessing structurally diverse heterocycles.
{"title":"Annulative Coupling of β-Ketothioamides with α-Ester Sulfoxonium Ylides: A Practical Route to Functionalized Thiazolidine-4-Ones","authors":"Trayambek Nath Chaubey, Ajay Kant Gola, Rahul Kumar Saini, Satyendra Kumar Pandey","doi":"10.1002/ejoc.202501166","DOIUrl":"https://doi.org/10.1002/ejoc.202501166","url":null,"abstract":"A metal-free annulative coupling strategy has been developed to synthesize functionalized thiazolidine-4-ones from β-ketothioamides and α-ester sulfoxonium ylides. This cascade process proceeds via concurrent C<span></span>S and C<span></span>N bond formation under mild conditions, delivering a wide range of thiazolidine-4-one derivatives in good-to-high yields. The method exhibits excellent functional group tolerance, broad substrate scope, and operational simplicity, with most products isolated via filtration without chromatography. The scalability and synthetic utility were demonstrated through gram-scale synthesis and oxidative late-stage functionalization, highlighting the potential of this strategy for accessing structurally diverse heterocycles.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"309 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146005791","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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