Chandrakant B. Nichinde , Meema Bhati , Amardipsing S. Girase , Baliram R. Patil , Suryakant S. Chaudhari , Rama Krishna Gamidi , Kavita Joshi , Anil K. Kinage
In this investigation, we elucidated, one‐pot two stage efficient synthesis of multifuctionalized spiro[oxindole −3,3′‐pyrrolidine]. The methodology proceeds via organocatalyzed nitro‐Michael addition reaction between indolylidenecyanoesters and nitroalkanes to formed nitro‐Michael adduct which transformed into multifunctionalized 3,3′‐pyrrolidinyl‐spirooxindoles by metal catalyzed reductive cyclization cascade. DFT investigations were conducted to elucidate the mechanism underlying the preferential reduction of the nitro group, with subsequent attack on the nitrile and ester groups remain inert throughout the reaction process. The approach is operationally simple, easily scalable, exhibits compatibility with readily accessible starting material and catalysts, thereby emphasizing cost‐effectiveness.
{"title":"A Sequential Nitro‐Michael Addition and Reductive Cyclization Cascade Reaction for Diastereoselective Synthesis of Multifunctionalized 3,3′‐pyrrolidinyl‐spirooxindoles","authors":"Chandrakant B. Nichinde , Meema Bhati , Amardipsing S. Girase , Baliram R. Patil , Suryakant S. Chaudhari , Rama Krishna Gamidi , Kavita Joshi , Anil K. Kinage","doi":"10.1002/ejoc.202401121","DOIUrl":"10.1002/ejoc.202401121","url":null,"abstract":"<div><div>In this investigation, we elucidated, one‐pot two stage efficient synthesis of multifuctionalized spiro[oxindole −3,3′‐pyrrolidine]. The methodology proceeds via organocatalyzed nitro‐Michael addition reaction between indolylidenecyanoesters and nitroalkanes to formed nitro‐Michael adduct which transformed into multifunctionalized 3,3′‐pyrrolidinyl‐spirooxindoles by metal catalyzed reductive cyclization cascade. DFT investigations were conducted to elucidate the mechanism underlying the preferential reduction of the nitro group, with subsequent attack on the nitrile and ester groups remain inert throughout the reaction process. The approach is operationally simple, easily scalable, exhibits compatibility with readily accessible starting material and catalysts, thereby emphasizing cost‐effectiveness.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 5","pages":"Article e202401121"},"PeriodicalIF":2.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874615","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}
Maria S. Rastorgueva , Dmitrii M. Nikolaev , Mikhail N. Ryazantsev , Alexander Sapegin
A novel method has been successfully developed for the synthesis of medium‐sized heterocycles containing thioamide groups. This approach facilitates the expansion of the imidazoline moiety within the condensed ring system through the action of S‐nucleophiles, enabling access to a broader and more diverse chemical space for natural product analogs and bioactive compounds. A series of [1,4,7]thia‐(oxa−)diazecin‐9‐thiones were efficiently synthesized from diarene‐fused [1.4]heteroazepines using this transformation, achieving yields ranging from 28–58 %.
{"title":"S‐Nucleophilic Imidazoline Ring Expansion: a Novel Approach to the Formation of Medium‐Sized Thiolactames","authors":"Maria S. Rastorgueva , Dmitrii M. Nikolaev , Mikhail N. Ryazantsev , Alexander Sapegin","doi":"10.1002/ejoc.202401191","DOIUrl":"10.1002/ejoc.202401191","url":null,"abstract":"<div><div>A novel method has been successfully developed for the synthesis of medium‐sized heterocycles containing thioamide groups. This approach facilitates the expansion of the imidazoline moiety within the condensed ring system through the action of <em>S</em>‐nucleophiles, enabling access to a broader and more diverse chemical space for natural product analogs and bioactive compounds. A series of [1,4,7]thia‐(oxa−)diazecin‐9‐thiones were efficiently synthesized from diarene‐fused [1.4]heteroazepines using this transformation, achieving yields ranging from 28–58 %.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 5","pages":"Article e202401191"},"PeriodicalIF":2.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142753609","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}
Fahad Alkhathami , Lee Yang Chieng , Yannick Ortin , Marina Rubini , Paul Evans
The novel synthesis of racemic cis‐ and trans‐3‐fluorofebrifugine and halofuginone is described. This straight‐forward seven‐step process relies on an electrophilic fluorination‐allylation sequence that generates a mixture of N‐Cbz protected, diastereomeric 2‐allyl‐3‐fluoropiperidines. On separation, a Wacker oxidation‐methyl functionalisation sequence enabled introduction of the required quinazolinone portion. Finally, removal of the N‐Cbz protecting group lead to isolation of the 3‐fluorofebrifugine dihydrobromide analogues that are of potentially pharmacological use. Analysis of the NMR spectra for each stereoisomer provides information concerning the preferred conformers of the different diastereomers. Evidence indicates that the cis‐diastereomer favours a conformation where the F‐atom occupies an axial orientation. In contrast, for its trans‐stereoisomeric counterpart, the 2‐substituent overrides any F‐atom effect and it preferentially occupies a conformer where both substituents occupy equatorial positions. Finally, interconversion between the cis‐ and trans‐diastereomers was studied. In DMSO‐d6 and as their free‐bases, isomerisation of each diastereomer gave a common 65 : 35 ratio of trans‐ to cis‐3‐fluorofebrifugine. Determination of the reaction rate constants for the isomerisation process at different temperatures enabled calculation of the activation energy barriers, for each process, using an Arrhenius plot. The activation energy barrier for the isomerisation of the trans‐isomer was 94.3±4.9 kJ mol−1, whereas for the cis‐isomer it was 84.5±3.9 kJ mol−1.
{"title":"Synthesis of the cis‐ and trans‐3‐Fluoro Analogues of Febrifugine and Halofuginone","authors":"Fahad Alkhathami , Lee Yang Chieng , Yannick Ortin , Marina Rubini , Paul Evans","doi":"10.1002/ejoc.202400886","DOIUrl":"10.1002/ejoc.202400886","url":null,"abstract":"<div><div>The novel synthesis of racemic <em>cis</em>‐ and <em>trans</em>‐3‐fluorofebrifugine and halofuginone is described. This straight‐forward seven‐step process relies on an electrophilic fluorination‐allylation sequence that generates a mixture of <em>N</em>‐Cbz protected, diastereomeric 2‐allyl‐3‐fluoropiperidines. On separation, a Wacker oxidation‐methyl functionalisation sequence enabled introduction of the required quinazolinone portion. Finally, removal of the <em>N</em>‐Cbz protecting group lead to isolation of the 3‐fluorofebrifugine dihydrobromide analogues that are of potentially pharmacological use. Analysis of the NMR spectra for each stereoisomer provides information concerning the preferred conformers of the different diastereomers. Evidence indicates that the <em>cis</em>‐diastereomer favours a conformation where the F‐atom occupies an axial orientation. In contrast, for its <em>trans</em>‐stereoisomeric counterpart, the 2‐substituent overrides any F‐atom effect and it preferentially occupies a conformer where both substituents occupy equatorial positions. Finally, interconversion between the <em>cis‐</em> and <em>trans‐</em>diastereomers was studied. In DMSO‐d<sub>6</sub> and as their free‐bases, isomerisation of each diastereomer gave a common 65 : 35 ratio of <em>trans</em>‐ to <em>cis‐</em>3‐fluorofebrifugine. Determination of the reaction rate constants for the isomerisation process at different temperatures enabled calculation of the activation energy barriers, for each process, using an Arrhenius plot. The activation energy barrier for the isomerisation of the <em>trans</em>‐isomer was 94.3±4.9 kJ mol<sup>−1</sup>, whereas for the <em>cis</em>‐isomer it was 84.5±3.9 kJ mol<sup>−1</sup>.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 5","pages":"Article e202400886"},"PeriodicalIF":2.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejoc.202400886","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440495","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}
Barbora Zahradníková , Zuzana Mravíková , Viktória Némethová , Petra Polnišerová , Vladimír Frecer , Mária Mečiarová , Radovan Šebesta
Functionalizing and derivatizing pharmaceuticals are essential for preparing new potentially active compounds. This work shows how active esters derived from oseltamivir carboxylate can be useful synthetic tools for accessing various amide derivatives of oseltamivir. Six hydroxylamine active esters were synthesized directly from oseltamivir carboxylate, and their utility in preparing amide derivatives was evaluated. Succinimide ester 5e was the most efficient in terms of its preparation and in synthesizing oseltamivir derivatives.
{"title":"Utilizing N‐Hydroxylamine‐Based Active Esters for the Synthesis of Oseltamivir Amide Derivatives","authors":"Barbora Zahradníková , Zuzana Mravíková , Viktória Némethová , Petra Polnišerová , Vladimír Frecer , Mária Mečiarová , Radovan Šebesta","doi":"10.1002/ejoc.202401139","DOIUrl":"10.1002/ejoc.202401139","url":null,"abstract":"<div><div>Functionalizing and derivatizing pharmaceuticals are essential for preparing new potentially active compounds. This work shows how active esters derived from oseltamivir carboxylate can be useful synthetic tools for accessing various amide derivatives of oseltamivir. Six hydroxylamine active esters were synthesized directly from oseltamivir carboxylate, and their utility in preparing amide derivatives was evaluated. Succinimide ester <strong>5</strong> <strong>e</strong> was the most efficient in terms of its preparation and in synthesizing oseltamivir derivatives.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 5","pages":"Article e202401139"},"PeriodicalIF":2.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874609","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}
Huiwen Meng , Qian Lei , Conger Deng , Linlin Liang , Zijian Wang , Weixin Lei , Honglin Chen
A novel and efficient protocol for the conversion of dimethyl 1, 4‐cyclohexane dicarboxylate (DMCD) into 1, 4‐cyclohexanedimethanol (CHDM) was proposed via catalytic transfer hydrogenation (CTH). In this approach, methanol functioned as both the hydrogen donor and the solvent, and a cost‐effective Cu/ZnO/Al₂O₃/ZrO₂ catalyst was utilized for facilitating the reaction. Under the specified conditions at 235 °C, a conversion of 96.61 % with a selectivity of 60.71 % was achieved. To elucidate the reaction mechanism, comprehensive characterizations were conducted to examine the catalysts with varying ZrO2 contents. The investigation revealed that the reaction begins with the adsorption of DMCD and methanol onto the acidic sites of the catalyst, followed by their activation on the reduced‐state Cu.
{"title":"Catalytic Transfer Hydrogenation of Dimethyl 1, 4‐cyclohexane Dicarboxylate into 1, 4‐cyclohexanedimethanol over Cu/ZnO/Al2O3/ZrO2 Catalysts","authors":"Huiwen Meng , Qian Lei , Conger Deng , Linlin Liang , Zijian Wang , Weixin Lei , Honglin Chen","doi":"10.1002/ejoc.202401184","DOIUrl":"10.1002/ejoc.202401184","url":null,"abstract":"<div><div>A novel and efficient protocol for the conversion of dimethyl 1, 4‐cyclohexane dicarboxylate (DMCD) into 1, 4‐cyclohexanedimethanol (CHDM) was proposed via catalytic transfer hydrogenation (CTH). In this approach, methanol functioned as both the hydrogen donor and the solvent, and a cost‐effective Cu/ZnO/Al₂O₃/ZrO₂ catalyst was utilized for facilitating the reaction. Under the specified conditions at 235 °C, a conversion of 96.61 % with a selectivity of 60.71 % was achieved. To elucidate the reaction mechanism, comprehensive characterizations were conducted to examine the catalysts with varying ZrO<sub>2</sub> contents. The investigation revealed that the reaction begins with the adsorption of DMCD and methanol onto the acidic sites of the catalyst, followed by their activation on the reduced‐state Cu.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 5","pages":"Article e202401184"},"PeriodicalIF":2.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874623","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}
Chiral nitrogen‐, and phosphorus‐based ligands have been extensively investigated in the asymmetric allylic reactions. However, chiral sulfoxides have not been deemed as a class of practical chiral ligands until last decade, despite several distinct advantages over traditional ligand scaffolds, such as the proximity of the chiral information to the metal center and the ability to switch between S and O coordination. This perspective collects the recent development of chiral sulfoxide ligands for asymmetric allylation since the beginning of 2013. In addition, insights into the future development of this type of promising ligand are discussed.
{"title":"Chiral Sulfoxide Ligands in Asymmetric Allylic Substitution","authors":"Xiao Li , Sheng‐Cai Zheng , Xiao‐Ming Zhao","doi":"10.1002/ejoc.202401172","DOIUrl":"10.1002/ejoc.202401172","url":null,"abstract":"<div><div>Chiral nitrogen‐, and phosphorus‐based ligands have been extensively investigated in the asymmetric allylic reactions. However, chiral sulfoxides have not been deemed as a class of practical chiral ligands until last decade, despite several distinct advantages over traditional ligand scaffolds, such as the proximity of the chiral information to the metal center and the ability to switch between <em>S</em> and <em>O</em> coordination. This perspective collects the recent development of chiral sulfoxide ligands for asymmetric allylation since the beginning of 2013. In addition, insights into the future development of this type of promising ligand are discussed.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 5","pages":"Article e202401172"},"PeriodicalIF":2.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874622","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}
István Jablonkai , Marcell M. Bogner , Barnabás Zsignár‐Nagy , József Simon , Gábor London
Polycyclic heteroarenes that contain internal thiophene, furan and pyrrole rings are well‐documented materials due to their presence in fossil fuels and their importance in organic optoelectronic applications. Accordingly, a variety of methods are available for their synthesis. In this report we prepared naphthannulated 4‐membered heteroarene isomers through the PtCl2‐catalyzed 6‐endo cyclization of ethynylbiaryls. Isomers were accessible from two structurally different precursors that contained the ethynyl subunit in different positions. We synthesized two pairs of thiophene‐based ethynylbiaryls where each pair would lead to the same tetracyclic isomer and explored their reactivity in the Pt‐catalyzed transformation. The formation of a detectable amount of inseparable side‐product was observed when the alkyne was introduced onto the benzene ring of the biaryls. This is suggested to be an exo‐methylene group containing derivative that forms via a 5‐exo cyclization pathway. Similarly, naphthannulated benzofuran isomers were prepared following the same strategy and an exo‐methylene‐containing side product was observed when the alkyne unit was on the benzene ring of the biaryl. Finally, novel synthesis methods were described for benzo‐fused carbazoles from ethynylbiaryls containing an alkyne either on the heterocyclic ring or on the phenyl substituent attached to the indole ring. No side‐product formation was detected in this case.
{"title":"Modular Synthesis of Tetracyclic Heteroarenes via Platinum‐Catalyzed Cyclization of Ethynylbiaryl Precursors","authors":"István Jablonkai , Marcell M. Bogner , Barnabás Zsignár‐Nagy , József Simon , Gábor London","doi":"10.1002/ejoc.202401114","DOIUrl":"10.1002/ejoc.202401114","url":null,"abstract":"<div><div>Polycyclic heteroarenes that contain internal thiophene, furan and pyrrole rings are well‐documented materials due to their presence in fossil fuels and their importance in organic optoelectronic applications. Accordingly, a variety of methods are available for their synthesis. In this report we prepared naphthannulated 4‐membered heteroarene isomers through the PtCl<sub>2</sub>‐catalyzed 6‐<em>endo</em> cyclization of ethynylbiaryls. Isomers were accessible from two structurally different precursors that contained the ethynyl subunit in different positions. We synthesized two pairs of thiophene‐based ethynylbiaryls where each pair would lead to the same tetracyclic isomer and explored their reactivity in the Pt‐catalyzed transformation. The formation of a detectable amount of inseparable side‐product was observed when the alkyne was introduced onto the benzene ring of the biaryls. This is suggested to be an <em>exo</em>‐methylene group containing derivative that forms via a 5‐<em>exo</em> cyclization pathway. Similarly, naphthannulated benzofuran isomers were prepared following the same strategy and an <em>exo</em>‐methylene‐containing side product was observed when the alkyne unit was on the benzene ring of the biaryl. Finally, novel synthesis methods were described for benzo‐fused carbazoles from ethynylbiaryls containing an alkyne either on the heterocyclic ring or on the phenyl substituent attached to the indole ring. No side‐product formation was detected in this case.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 5","pages":"Article e202401114"},"PeriodicalIF":2.5,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142874608","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}
1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) is a bicyclic guanidine with booming applications. Bearing both a nucleophilic nitrogen and an electrophilic nitrogen, TBD is a multifunctional and versatile reagent that is able to promote a variety of organic transformations. Although advancements with TBD in the polymer field have been well reviewed and documented, summaries that focus on synthetic methodologies are scarce. This review intends to provide a concise overview of synthetic methods utilizing TBD published over the past two decades. Classified based on the primary function of TBD, diverse transformations are described, and reaction mechanisms are incorporated when necessary. Examples from various fields are covered, including methodology developments, natural product syntheses, medicinal chemistry applications, as well as industrial utilizations.
{"title":"Organic Transformations Utilizing 1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD): A Tale of Two Nitrogens","authors":"Chunling Blue Lan, Karine Auclair","doi":"10.1002/ejoc.202401383","DOIUrl":"https://doi.org/10.1002/ejoc.202401383","url":null,"abstract":"1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD) is a bicyclic guanidine with booming applications. Bearing both a nucleophilic nitrogen and an electrophilic nitrogen, TBD is a multifunctional and versatile reagent that is able to promote a variety of organic transformations. Although advancements with TBD in the polymer field have been well reviewed and documented, summaries that focus on synthetic methodologies are scarce. This review intends to provide a concise overview of synthetic methods utilizing TBD published over the past two decades. Classified based on the primary function of TBD, diverse transformations are described, and reaction mechanisms are incorporated when necessary. Examples from various fields are covered, including methodology developments, natural product syntheses, medicinal chemistry applications, as well as industrial utilizations.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"2017 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083866","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 hydroformylation of α,β‑unsaturated esters represents a highly atom-economical route towards β‑aldehydes with the potential application as precursors for derivatization to pharmaceuticals such as (R)‑Baclofen or Pregabalin. Methyl 4-chlorocinnamate as an α,β‑unsaturated ester has been rarely studied in hydroformylation, particularly with regard to a parameter screening for reaction optimization. In this work, the regioselective hydroformylation of methyl 4‑chlorocinnamate to the desired β‑aldehyde was investigated with a particular focus on the identification of parameters with a significant effect on the regioselectivity and selectivity to the β‑aldehyde amongst all products. The reaction time, solvent, and catalyst loading were initially screened followed by a systematic screening using design of experiments (DoE). The reaction output was analyzed in terms of pressure, temperature and the CO/H2 composition with an unmodified Rh catalyst revealing that while either regioselectivity or overall selectivity (termed selectivity) can attain high values, neither parameter can simultaneously reach optimal levels. As predicted by the model, the experimental results under two different conditions demonstrated excellent regioselectivity (96%) with medium selectivity (57%) and a high selectivity (78 %) with good regioselectivity (93%). Expansion of substrate scope revealed a significant influence of the substituents and thus the electronic effect on the regioselectivity and selectivity.
{"title":"Regioselective Hydroformylation of α,β-Unsaturated Esters: Impact of Reaction Parameters & Reaction Optimization","authors":"Hannah Bork, Harald Gröger","doi":"10.1002/ejoc.202401116","DOIUrl":"https://doi.org/10.1002/ejoc.202401116","url":null,"abstract":"The hydroformylation of α,β‑unsaturated esters represents a highly atom-economical route towards β‑aldehydes with the potential application as precursors for derivatization to pharmaceuticals such as (R)‑Baclofen or Pregabalin. Methyl 4-chlorocinnamate as an α,β‑unsaturated ester has been rarely studied in hydroformylation, particularly with regard to a parameter screening for reaction optimization. In this work, the regioselective hydroformylation of methyl 4‑chlorocinnamate to the desired β‑aldehyde was investigated with a particular focus on the identification of parameters with a significant effect on the regioselectivity and selectivity to the β‑aldehyde amongst all products. The reaction time, solvent, and catalyst loading were initially screened followed by a systematic screening using design of experiments (DoE). The reaction output was analyzed in terms of pressure, temperature and the CO/H2 composition with an unmodified Rh catalyst revealing that while either regioselectivity or overall selectivity (termed selectivity) can attain high values, neither parameter can simultaneously reach optimal levels. As predicted by the model, the experimental results under two different conditions demonstrated excellent regioselectivity (96%) with medium selectivity (57%) and a high selectivity (78 %) with good regioselectivity (93%). Expansion of substrate scope revealed a significant influence of the substituents and thus the electronic effect on the regioselectivity and selectivity.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"77 4 Pt 1 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072910","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 explore a visible light‐enabled radical addition for the construction of N‐sulfonyl and N‐acyliminophosphorane using triarylphosphine and N‐sulfonyl and N‐acylaminopyridinium salts in the absence of transition metal, photocatalyst, oxidant or base. This method employs PAr3 as both the reaction catalyst to promote the generation of amidyl radical via N‐N bond cleavage of N‐sulfonyl and N‐acylaminopyridinium salts, and materials for the preparation of N‐sulfonyl and N‐acyliminophosphorane products. This transformation exhibits abroad substrate scope and good functional group compatibility.
{"title":"Catalyst‐free visible light‐induced N‐N bond cleavage for the synthesis of iminophosphorane using triarylphosphine and N‐sulfonyl and N‐acylaminopyridinium salt","authors":"Xiaotao Qin, Chenglei Yang, Yinjiang Xue, Jinkai Hu, Jinhui Yang, Dianjun Li","doi":"10.1002/ejoc.202401361","DOIUrl":"https://doi.org/10.1002/ejoc.202401361","url":null,"abstract":"Herein, we explore a visible light‐enabled radical addition for the construction of N‐sulfonyl and N‐acyliminophosphorane using triarylphosphine and N‐sulfonyl and N‐acylaminopyridinium salts in the absence of transition metal, photocatalyst, oxidant or base. This method employs PAr3 as both the reaction catalyst to promote the generation of amidyl radical via N‐N bond cleavage of N‐sulfonyl and N‐acylaminopyridinium salts, and materials for the preparation of N‐sulfonyl and N‐acyliminophosphorane products. This transformation exhibits abroad substrate scope and good functional group compatibility.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"168 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072914","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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