Breno U. de Abreu, Renata G. Almeida, Ana L. C. Silveira, Leonardo A. Matos, Willian X. C. Oliveira, Maria H. Araujo, Victor F. S. Ramos, Rubem F. S. Menna-Barreto, Chandrakant B. Nichinde, Felipe Fantuzzi, Edmond Gravel, Eric Doris, Eufrânio N. da Silva Júnior, Guilherme A. M. Jardim
{"title":"Synthesis of Naphthoquinones by Pd-Catalyzed Heck–Matsuda Arylation of Lapachol","authors":"Breno U. de Abreu, Renata G. Almeida, Ana L. C. Silveira, Leonardo A. Matos, Willian X. C. Oliveira, Maria H. Araujo, Victor F. S. Ramos, Rubem F. S. Menna-Barreto, Chandrakant B. Nichinde, Felipe Fantuzzi, Edmond Gravel, Eric Doris, Eufrânio N. da Silva Júnior, Guilherme A. M. Jardim","doi":"10.1002/ejoc.70790","DOIUrl":"10.1002/ejoc.70790","url":null,"abstract":"<p>Direct Heck–Matsuda arylation of lapachol provides rapid access to structurally diverse naphthoquinones under homogeneous and heterogeneous palladium catalysis. The methodology features broad substrate scope, gram-scale applicability, and unambiguous structural assignment by single-crystal X-ray diffraction, providing an efficient platform for the diversification of quinones.</p>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"29 38","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejoc.70790","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148836201","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}
Yannik Appiarius, Noah Wolf, Pim Puylaert, Sourabh Kumar, Delia Miguel, Martin Molkenthin, Tim Neudecker, Anne Staubitz
{"title":"Helical Dinaphthothiophenes Reveal the Limits of BN‐Based Optical Tuning","authors":"Yannik Appiarius, Noah Wolf, Pim Puylaert, Sourabh Kumar, Delia Miguel, Martin Molkenthin, Tim Neudecker, Anne Staubitz","doi":"10.1002/ejoc.70848","DOIUrl":"https://doi.org/10.1002/ejoc.70848","url":null,"abstract":"The formal substitution of carbon–carbon (CC) units by boron–nitrogen (BN) units is an established strategy to improve the optical properties of polycyclic aromatic hydrocarbons while retaining their geometries. We report an example of such a substitution in a 7‐thia[5]helicene, which led to almost the same geometry. Although the absorption and fluorescence spectra are alike, BN substitution did not improve the fluorescence quantum yield, which is atypical. Both compounds mostly undergo nonradiative decay pathways, which can be attributed to their helical structure and the heavy‐atom‐effect of the sulfur atom. Compared to the sulfur‐free [5]helicene, racemization occurs very fast at ambient temperature. The molecules demonstrate the limits of BN substitution in improving the optical properties of (thia)helicenes.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"19 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172845","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}
{"title":"Base-Catalyzed Cascade Reaction Between α-Aminomaleimides and Electron-Deficient Olefins: Syntheses of Aza-Bicyclic Maleimides and Tricyclic Spiro-Oxindoles","authors":"Zhi-Bo Liu, Jin-Yu Liu, Xiu-Zhu Meng, Zhong-Quan Xiang, Yu-Hang Fei, Jun-Ran Yang, Yicen Ge, Jinghua Tang","doi":"10.1002/ejoc.70827","DOIUrl":"10.1002/ejoc.70827","url":null,"abstract":"<p>A base-promoted aza-Michael/S<sub><i>N</i></sub>2′ and Michael-Nucleophilic addition sequential reaction enables efficient preparations of aza-bicyclic maleimides and tricyclic spiro-oxindoles in generally good yields (up to 99% yield) with excellent diastereoselectivities (up to 20:1 dr) from α-aminomaleimides and electron-deficient olefins.</p>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"29 38","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860779","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}
Péter Szemesi, Péter Bana, István Greiner, János Éles
{"title":"Continuous-Flow Synthesis of Aripiprazole Through the Safe Utilization of In Situ-Generated THF Hydroperoxide","authors":"Péter Szemesi, Péter Bana, István Greiner, János Éles","doi":"10.1002/ejoc.70801","DOIUrl":"10.1002/ejoc.70801","url":null,"abstract":"<p>A novel continuous-flow synthesis for the antipsychotic aripiprazole has been developed via a two-step, halogen-free route. The first step features the underutilized <i>N</i>-hydroxybutylation reaction employing in situ-generated THF hydroperoxide under reductive conditions. The continuous-flow setup ensures rapid and safe transformation through a telescoped sequence, incorporating on-demand generation and immediate quenching of the remaining hazardous reagent without isolation. This strategy was also applicable to the synthesis of other pharmaceutically relevant intermediates. The first step was integrated with a continuous-flow Mitsunobu reaction employing the Tsunoda reagent to give aripiprazole with high productivity. Overall, the developed process offers an environmentally benign alternative to conventional methods, achieving superior atom economy and reaction mass efficiency while eliminating the need for halogenated alkylating agents typically used in high excess.</p>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"29 38","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893517","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}
{"title":"Recent Advances in Photochemical and Photoelectrochemical Fluoroalkylation: Direct Use of Fluoroalkyl Carboxylic Acids","authors":"Lu Song, Niankai Fu","doi":"10.1002/ejoc.70816","DOIUrl":"10.1002/ejoc.70816","url":null,"abstract":"<p>Extensive research has been dedicated to developing sustainable and practical methodologies for installing fluoroalkyl groups into organic molecules, as such structural modifications can effectively tune the physicochemical and pharmacological properties of drug candidates. Despite significant advances, most established fluoroalkylation protocols still suffer from inherent drawbacks: conventional fluoroalkylating reagents are often expensive, thermally or chemically labile, and difficult to handle. Furthermore, their practical implementation usually requires stoichiometric redox chemicals to facilitate the generation of operative fluoroalkylating intermediates, compromising functional group tolerance and atom economy and ultimately restricting applicability in large-scale synthesis. This review summarizes recent advances in fluoroalkylations using widely available fluoroalkyl carboxylic acids as direct fluoroalkyl radical precursors, highlighting the unique merits, synthetic scope, and future potential of this emerging strategy.</p>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"29 38","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148893521","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}
Biman Bera, Saikat Bera, Shubhankar Kumar Bose, Mrinal K. Bera
{"title":"Visible‐Light‐Driven Regioselective Cross‐Dehydrogenative C–H Thio‐ and Selenocyanation of Indolo[1,2‐a]quinoxalines Under Photocatalyst‐, Oxidant‐ and Metal‐Free Aerobic Conditions","authors":"Biman Bera, Saikat Bera, Shubhankar Kumar Bose, Mrinal K. Bera","doi":"10.1002/ejoc.70888","DOIUrl":"https://doi.org/10.1002/ejoc.70888","url":null,"abstract":"A visible‐light‐promoted cross‐dehydrogenative protocol has been developed for the regioselective thiocyanation and selenocyanation of indolo[1,2‐a]quinoxaline derivatives. This photoinduced transformation proceeds at ambient temperature under metal‐free aerobic conditions without using an external oxidant and any photosensitizer. The key features of this protocol, including high yields, excellent regioselectivity, operational simplicity, broad functional group tolerance, and scalability, make it a synthetically attractive and practical method.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"6 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172967","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}
Himani Sharma, Akanksha Kumari, Suman K. Saha, Nirmal K. Rana
{"title":"Sustainable Catalyst-Free Synthesis of Substituted Pyrazoles Through an Annulation/Oxidation Cascade Under Batch and Continuous-Flow Methods","authors":"Himani Sharma, Akanksha Kumari, Suman K. Saha, Nirmal K. Rana","doi":"10.1002/ejoc.70818","DOIUrl":"10.1002/ejoc.70818","url":null,"abstract":"<p>We describe a catalyst-free synthesis of substituted pyrazoles in good to excellent yields using α,β-unsaturated β-ketoesters and aryl hydrazines under mild reaction conditions. The reaction proceeds through a Michael-initiated ring closure reaction followed by in situ oxidation. A broad range of substrates bearing electron-withdrawing and electron-donating substituents was successfully converted to the corresponding pyrazole derivatives. The method was scalable under batch conditions, demonstrating its practical applicability. In addition, the ester group present in the products could be transformed into the corresponding carboxylic acid and amide derivatives, providing access to structurally diverse pyrazole scaffolds. The protocol was also translated to continuous-flow conditions, offering an efficient and sustainable route to these valuable heterocyclic compounds.</p>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"29 38","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148836200","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}
{"title":"Indole‐ and Benzofuran‐Thioglycoside Synthesis via Palladium‐Catalyzed Migita/Larock Couplings: Synthesis and Photophysical Investigations","authors":"Ailada Charoenpol, Franck Le Bideau, Delphine Naud‐Martin, Florence Mahuteau‐Betzer, Wipa Suginta, Samir Messaoudi","doi":"10.1002/ejoc.70896","DOIUrl":"https://doi.org/10.1002/ejoc.70896","url":null,"abstract":"An efficient catalytic approach for the synthesis of novel indole‐ and benzofuran‐thioglycoside derivatives by using simple cross‐coupling reactions is established. The strategy involves two Pd‐catalyzed cross‐couplings including C─S bond‐forming reaction between glycosyl thiols and <jats:italic>p</jats:italic> ‐iodoalkyne, followed by a Larock reaction. Following this catalytic approach, various indole‐ and benzofuran‐containing thioglycoside derivatives were prepared with moderate to good yields (54%–84%). Among all thioglycoside derivatives synthesized, the fully acetylated <jats:italic>N</jats:italic> ‐Ts indole‐derivative exhibits cytotoxicity against the human colon cancer cell line (HCT116) with an IC <jats:sub>50</jats:sub> at the micromolecular level (6.94 ± 0.94 μM). Furthermore, the photophysical properties of all thioglycoside derivatives are studied.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"31 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172966","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}
Dara T. Curran, Aidan C. Cregan, Niamh E. O’Dwyer, Jimmy Muldoon, Peter A. Byrne
{"title":"Oxidant-Expedited Synthesis of H-Phosphonates","authors":"Dara T. Curran, Aidan C. Cregan, Niamh E. O’Dwyer, Jimmy Muldoon, Peter A. Byrne","doi":"10.1002/ejoc.70693","DOIUrl":"10.1002/ejoc.70693","url":null,"abstract":"<p>A new oxidant-expedited method has been developed that enables synthesis of H-phosphonates from phosphites using extremely mild oxidants (e.g., air or O<sub>2</sub>). H-phosphonates are key building blocks in organophosphorus chemistry due to their multimodal reactivity patterns, which make them versatile reagents in many fields in synthetic chemistry. Using the methodology outlined herein, very high conversions (>85%) were achieved in the formation of a variety of H-phosphonates for reactions using pure O<sub>2</sub> as the oxidant, while reactions in which air was employed as the oxidant also resulted in very high conversions (>92%) except in two very challenging cases involving hydrolytically sensitive products. Unequivocal evidence demonstrating that the transformations are expedited by the presence of oxidants is provided. Along with this, evidence derived from various mechanistic experiments supports the operation of a radical-based mechanism in which water supplies both the hydrogen and the oxygen that become incorporated into the H-phosphonate product in the new P<span></span>H and PO bonds. The methodology reported herein employs acid-free conditions, requires only phosphite, water, and O<sub>2</sub> as reagents, and is thus an exceptionally mild method for accessing a variety of H-phosphonate products.</p>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"29 38","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejoc.70693","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860782","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}
Justus H. Peter, Piet de Jong, Merlin Kleoff, Gesa H. Dreyhsig, Jan-H. Dickoff, Mohsen Adeli, Sebastian Riedel, C. Christoph Tzschucke, Rainer Haag
{"title":"Conversion of Alcohols to Alkyl Chlorides Using the Bichloride Ionic Liquid [NEt3Me][Cl(HCl)n]","authors":"Justus H. Peter, Piet de Jong, Merlin Kleoff, Gesa H. Dreyhsig, Jan-H. Dickoff, Mohsen Adeli, Sebastian Riedel, C. Christoph Tzschucke, Rainer Haag","doi":"10.1002/ejoc.70780","DOIUrl":"10.1002/ejoc.70780","url":null,"abstract":"<p>The solvent-free chlorination of alcohols using the bichloride-based ionic liquid [NEt<sub>3</sub>Me][Cl(HCl)<sub>1.61</sub>] as a hydrogen chloride source is reported. In the presence of a catalytic amount of a carboxylic acid, a variety of alcohols undergo efficient chlorination under mild batch conditions. This method eliminates the need to handle hydrogen chloride gas. Benzyl and secondary alcohols are converted with good to excellent yields, whereas primary aliphatic substrates show moderate reactivity. Notably, short-chain diol substrates primarily yield monochlorinated products, indicating some chemoselectivity under the reaction conditions. Tests for functional group compatibility reveal that ester groups stay intact, while acetals and simple alkyl ethers are cleaved in the strongly acidic environment. The ionic liquid can be recharged with hydrogen chloride and reused in subsequent reactions. Process robustness is demonstrated by gram-scale reactions and straightforward product isolation via distillation or phase separation.</p>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"29 38","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejoc.70780","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148836297","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}