Polychloroalkanes are commonly used solvents in organic synthesis, in which dichloromethane and chloroform have been intensively applied in radical-mediated alkene functionalization reactions. However, a general and mild protocol for selective activation of C–H and C–Cl bonds of polychloroalkanes via switchable atom transfer processes is still in demand. Herein, we demonstrate a conceptually distinct strategy for alkyl radicals formation from polychloroalkanes through hydrogen atom transfer or halogen atom transfer event under mild photoredox conditions. By this strategy, stoichiometric hazardous reagents and radical initiators are obviated, instead only simple alkyl amines are used as controllable hydrogen- and halogen-atom transfer reagents. The blueprint for radical reactivity is exploited in defluorinative alkylation of α-trifluoromethyl alkenes, thereby providing an entry to synthetically useful polychloroalkylated gem-difluoroalkenes. Moreover, this protocol features simple catalytic systems and operation, gram scale synthesis, modifications of complex molecules, and diverse product transformations.
{"title":"Controllable atom transfer enables photoredox-catalyzed defluorinative alkylation of trifluoromethyl alkenes with polychloroalkanes","authors":"Mu-Xiang Chen, Xin-Lu Fan, Zi-Yan Wang, Yi-Long Zhu, Xuefei Zhao, Zhenhua Jia, Xu-Hong Hu","doi":"10.1039/d5qo00369e","DOIUrl":"https://doi.org/10.1039/d5qo00369e","url":null,"abstract":"Polychloroalkanes are commonly used solvents in organic synthesis, in which dichloromethane and chloroform have been intensively applied in radical-mediated alkene functionalization reactions. However, a general and mild protocol for selective activation of C–H and C–Cl bonds of polychloroalkanes via switchable atom transfer processes is still in demand. Herein, we demonstrate a conceptually distinct strategy for alkyl radicals formation from polychloroalkanes through hydrogen atom transfer or halogen atom transfer event under mild photoredox conditions. By this strategy, stoichiometric hazardous reagents and radical initiators are obviated, instead only simple alkyl amines are used as controllable hydrogen- and halogen-atom transfer reagents. The blueprint for radical reactivity is exploited in defluorinative alkylation of α-trifluoromethyl alkenes, thereby providing an entry to synthetically useful polychloroalkylated gem-difluoroalkenes. Moreover, this protocol features simple catalytic systems and operation, gram scale synthesis, modifications of complex molecules, and diverse product transformations.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"120 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143832186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Radical Smiles rearrangement as a potent synthetic platform for arene functionalization efficiently facilitates the construction of (hetero)aromatic groups under gentle reaction conditions, and has proven to be a valuable tool for the late-stage functionalization of pharmaceutical molecules of interest. The rapid expansion in this field has resulted in numerous new findings over the past five years, yet no specific review has been focused on the radical Truce-Smiles rearrangement so far. This review offers a comprehensive overview of recent progress in this field and contributes to future research. The synthetic tactics are reviewed by highlighting their product diversity, selectivity and applicability, and the mechanistic rationale where possible. It is expected that this minireview will serve as a source of inspiration for promoting the development of radical Truce−Smiles rearrangement for its potential in drug discovery.
{"title":"Advancements and Perspectives Toward Radical Truce−Smiles−type Rearrangement","authors":"Yuxi Wang, Xinyao Zhang, Kexin Kong, Chao Shu","doi":"10.1039/d5qo00360a","DOIUrl":"https://doi.org/10.1039/d5qo00360a","url":null,"abstract":"Radical Smiles rearrangement as a potent synthetic platform for arene functionalization efficiently facilitates the construction of (hetero)aromatic groups under gentle reaction conditions, and has proven to be a valuable tool for the late-stage functionalization of pharmaceutical molecules of interest. The rapid expansion in this field has resulted in numerous new findings over the past five years, yet no specific review has been focused on the radical Truce-Smiles rearrangement so far. This review offers a comprehensive overview of recent progress in this field and contributes to future research. The synthetic tactics are reviewed by highlighting their product diversity, selectivity and applicability, and the mechanistic rationale where possible. It is expected that this minireview will serve as a source of inspiration for promoting the development of radical Truce−Smiles rearrangement for its potential in drug discovery.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"116 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143832185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aromatic nitriles hold a prominent position in organic synthesis due to the unique importance of the cyanide moiety and also the diverse transformations of such groups to various functionalities. Traditional preparative routes are mainly based on Sandmeyer and Rosenmund–von Braun reactions, using toxic CuCN as a reagent. Organoborons are convenient building blocks for new chemical bond construction, and thus developing transition-metal catalytic systems for the cyanation of arylborons would provide attractive synthetic routes. Herein, we first establish the development of a mild and oxidant-free copper catalytic system for the transnitrilation of arylborons with dimethylmalononitrile (DMMN). The present system features broad scope, high functionality tolerance, scalability and practicality. Moreover, the system can be applied for the late-stage functionalization of various complex molecules. Distinct from the reported transnitrilation systems via polar mechanisms, the current copper system occurred via an unprecedent radical pathway with a Cu0/CuI catalytic cycle. The radical trapping, EPR and XPS experiments all supported the radical reaction mechanism.
{"title":"Copper-catalyzed radical transnitrilation of arylborons with dimethylmalononitrile and mechanistic insights","authors":"Xiaofu Jian, Xibao Zhang, Weilong Xie","doi":"10.1039/d5qo00397k","DOIUrl":"https://doi.org/10.1039/d5qo00397k","url":null,"abstract":"Aromatic nitriles hold a prominent position in organic synthesis due to the unique importance of the cyanide moiety and also the diverse transformations of such groups to various functionalities. Traditional preparative routes are mainly based on Sandmeyer and Rosenmund–von Braun reactions, using toxic CuCN as a reagent. Organoborons are convenient building blocks for new chemical bond construction, and thus developing transition-metal catalytic systems for the cyanation of arylborons would provide attractive synthetic routes. Herein, we first establish the development of a mild and oxidant-free copper catalytic system for the transnitrilation of arylborons with dimethylmalononitrile (DMMN). The present system features broad scope, high functionality tolerance, scalability and practicality. Moreover, the system can be applied for the late-stage functionalization of various complex molecules. Distinct from the reported transnitrilation systems <em>via</em> polar mechanisms, the current copper system occurred <em>via</em> an unprecedent radical pathway with a Cu<small><sup>0</sup></small>/Cu<small><sup>I</sup></small> catalytic cycle. The radical trapping, EPR and XPS experiments all supported the radical reaction mechanism.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"32 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexander Knieb, Thomas Saal, Prabodh Rao, Xanath Ispizua-Rodriguez, G. K. Surya Prakash
A high yielding protocol for the synthesis of valuable monofluoromethyl ketones (MFMK) utilizing fluorobis(phenylsulfonyl)methane (FBSM) is presented. The protocol allows the incorporation of the biologically relevant monofluoromethyl group under mild reaction conditions and in short reaction times. The obtained fluorobis(phenylsulfonyl)methyl ketones can subsequently be selectively reduced to the fluoro(phenylsulfonyl)methyl- and subsequently to monofluoromethyl ketones via zinc-mediated reductive desulfonylation. Furthermore, weak intramolecular van der Waals interactions were observed in fluorobis(phenylsulfonyl)methyl ketones and they were further investigated using nuclear magnetic resonance spectroscopy and single crystal X-ray diffraction analysis. An improved method for the assessment of lipophilic properties of these fluorinated small molecules has been developed and correlated to theoretical log P values.
{"title":"Monofluoromethylation of acyl chlorides and chloroformates employing fluorobis(phenylsulfonyl)methane. Synthesis of monofluoromethyl ketones via selective zinc-mediated reductive desulfonylation","authors":"Alexander Knieb, Thomas Saal, Prabodh Rao, Xanath Ispizua-Rodriguez, G. K. Surya Prakash","doi":"10.1039/d5qo00451a","DOIUrl":"https://doi.org/10.1039/d5qo00451a","url":null,"abstract":"A high yielding protocol for the synthesis of valuable monofluoromethyl ketones (MFMK) utilizing fluorobis(phenylsulfonyl)methane (FBSM) is presented. The protocol allows the incorporation of the biologically relevant monofluoromethyl group under mild reaction conditions and in short reaction times. The obtained fluorobis(phenylsulfonyl)methyl ketones can subsequently be selectively reduced to the fluoro(phenylsulfonyl)methyl- and subsequently to monofluoromethyl ketones <em>via</em> zinc-mediated reductive desulfonylation. Furthermore, weak intramolecular van der Waals interactions were observed in fluorobis(phenylsulfonyl)methyl ketones and they were further investigated using nuclear magnetic resonance spectroscopy and single crystal X-ray diffraction analysis. An improved method for the assessment of lipophilic properties of these fluorinated small molecules has been developed and correlated to theoretical log <em>P</em> values.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"27 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chiral sulfones bearing an quaternary stereocenter are privileged structural units that are found in a variety of biologically active products and drug molecules. Herein, we present a photoinduced asymmetric Truce-Smiles rearrangement to access chiral sulfones bearing an all-carbon quaternary center through radical sulfur dioxide insertion. By using the valine methyl ester as the chiral auxiliary, the desired chiral sulfones are afforded in good yields with good to excellent stereoselectivities. This protocol features mild reaction conditions, broad substrate scope and good stereospecificity.
{"title":"Accessing chiral sulfones with an all-carbon quaternary stereocenter via photoinduced asymmetric Truce-Smiles rearrangement and radical sulfur dioxide insertion","authors":"Chenxin Wang, Wei Xiao, Jie Wu","doi":"10.1039/d5qo00383k","DOIUrl":"https://doi.org/10.1039/d5qo00383k","url":null,"abstract":"Chiral sulfones bearing an quaternary stereocenter are privileged structural units that are found in a variety of biologically active products and drug molecules. Herein, we present a photoinduced asymmetric Truce-Smiles rearrangement to access chiral sulfones bearing an all-carbon quaternary center through radical sulfur dioxide insertion. By using the valine methyl ester as the chiral auxiliary, the desired chiral sulfones are afforded in good yields with good to excellent stereoselectivities. This protocol features mild reaction conditions, broad substrate scope and good stereospecificity.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"37 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143819390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vinyl-fluorides appended to heterocycles are a broadly underdeveloped family of functionality with potential application in bioactive compounds. Herein, we disclose a cross-coupling strategy for the regio- and stereo-controlled synthesis of Z-β- fluorovinyl indoles exclusively in the C-2 position, for which there is currently no reported routes to. Z-fluorovinyl iodonium salts, which are formed from alkynes through a Ag-catalysed process, engage in a palladium-catalysed C-2 C-H functionalisation of indoles (and pyrroles) to achieve a broad scope of β-fluorovinyl heterocycles in good to excellent yields. Mechanistic studies and product derivatisations are provided.
{"title":"Palladium-Catalysed Regio- and Stereo-Controlled C-2 β- Fluorovinylation of Indoles","authors":"Atul K. Chaturvedi, Alastair J. J. Lennox","doi":"10.1039/d5qo00521c","DOIUrl":"https://doi.org/10.1039/d5qo00521c","url":null,"abstract":"Vinyl-fluorides appended to heterocycles are a broadly underdeveloped family of functionality with potential application in bioactive compounds. Herein, we disclose a cross-coupling strategy for the regio- and stereo-controlled synthesis of Z-β- fluorovinyl indoles exclusively in the C-2 position, for which there is currently no reported routes to. Z-fluorovinyl iodonium salts, which are formed from alkynes through a Ag-catalysed process, engage in a palladium-catalysed C-2 C-H functionalisation of indoles (and pyrroles) to achieve a broad scope of β-fluorovinyl heterocycles in good to excellent yields. Mechanistic studies and product derivatisations are provided.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"4 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143822429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
5,5-Dicarbon-substituted hydantoins are the key skeletons of numerous drugs, but a general method for the enantioselective de novo synthesis of such scaffolds is elusive. On the other hand, Urech hydantoin synthesis (UHS) represents an efficient approach for hydantoin preparation, but its enantioselective variant remains unknown. Based on desymmetrization and kinetic resolution strategies, we disclose herein the first example of asymmetric catalytic UHS, providing synthetically challenging thiohydantoins with high stereoselectivities. Readily accessible 2-amino malonic esters and racemic amino esters were employed to react with isothiocyanates in the presence of chiral acids, respectively. The resulting products can be facilely functionalized and serves as pivotal scaffolds in various drugs. Experimental studies and DFT calculations suggest that an unexpected dynamic kinetic resolution in the ester ammonolysis step is responsible for the enantiocontrol.
{"title":"Enantioselective Catalytic Urech Hydantoin Synthesis","authors":"Wen-Ya Zheng, Zi-Qi Wang, Xing-Zi Li, Zhuo-Chen Li, Hua Wu, Abudu Rexit Abulikemu, Yu-Ping He","doi":"10.1039/d5qo00378d","DOIUrl":"https://doi.org/10.1039/d5qo00378d","url":null,"abstract":"5,5-Dicarbon-substituted hydantoins are the key skeletons of numerous drugs, but a general method for the enantioselective de novo synthesis of such scaffolds is elusive. On the other hand, Urech hydantoin synthesis (UHS) represents an efficient approach for hydantoin preparation, but its enantioselective variant remains unknown. Based on desymmetrization and kinetic resolution strategies, we disclose herein the first example of asymmetric catalytic UHS, providing synthetically challenging thiohydantoins with high stereoselectivities. Readily accessible 2-amino malonic esters and racemic amino esters were employed to react with isothiocyanates in the presence of chiral acids, respectively. The resulting products can be facilely functionalized and serves as pivotal scaffolds in various drugs. Experimental studies and DFT calculations suggest that an unexpected dynamic kinetic resolution in the ester ammonolysis step is responsible for the enantiocontrol.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"25 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Photobiocatalysis, which integrates the strengths of visible-light-catalysis and enzymatic catalysis, has established itself as a pivotal tool for asymmetric synthesis. Over the past decade, several naturally occurring enzymes have been repurposed to catalyze diverse unnatural transformations that are notoriously difficult to realize using traditional methods. This Emerging Review focuses on the advancements in photobiocatalysis published from 2022 to December 2024 and also highlights earlier seminal reports related to the first demonstration. We organize this review by the coupling modes of visible-light and enzymes, including net-reduction photoenzymatic catalysis (typically) through the illumination of enzymatic electron donor-acceptor complexes, redox neutral photoenzymatic catalysis via direct-visible-light excitation of enzymes, and synergistic dual photo-/enzymatic catalysis. With each section, the discussion is categorized by the type of enzyme, emphasizing the underlying mechanistic aspects, evolutionary trajectories and representative substrate scopes. We anticipate that this review will inspire further developments and application of photobiocatalysis.
{"title":"Recent Advances in Repurposing Natural Enzymes for New-to-Nature Asymmetric Photobiotransformations","authors":"Fulu Liu, Xichao Peng, Jinhai Yu, Xiaoqiang Huang","doi":"10.1039/d5qo00470e","DOIUrl":"https://doi.org/10.1039/d5qo00470e","url":null,"abstract":"Photobiocatalysis, which integrates the strengths of visible-light-catalysis and enzymatic catalysis, has established itself as a pivotal tool for asymmetric synthesis. Over the past decade, several naturally occurring enzymes have been repurposed to catalyze diverse unnatural transformations that are notoriously difficult to realize using traditional methods. This Emerging Review focuses on the advancements in photobiocatalysis published from 2022 to December 2024 and also highlights earlier seminal reports related to the first demonstration. We organize this review by the coupling modes of visible-light and enzymes, including net-reduction photoenzymatic catalysis (typically) through the illumination of enzymatic electron donor-acceptor complexes, redox neutral photoenzymatic catalysis via direct-visible-light excitation of enzymes, and synergistic dual photo-/enzymatic catalysis. With each section, the discussion is categorized by the type of enzyme, emphasizing the underlying mechanistic aspects, evolutionary trajectories and representative substrate scopes. We anticipate that this review will inspire further developments and application of photobiocatalysis.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"21 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We developed practical reaction conditions and procedure for the direct Suzuki–Miyaura cross-coupling (SMCC) of C(sp2)–B(dan) bonds. Below are important notes to successfully execute the direct SMCC: 1) Dehydrated conditions that exclude as much H2O as possible are required, 2) LiOH is a base of choice, 3) dppf is a ligand of choice when using electron-deficient (hetero)aryl halides [(Het)ArX], 4) P(t-Bu)3 is a ligand of choice when using electron-rich (Het)ArX, 5) COD is a ligand of choice when using (Het)ArX with a protic functional group such as NH2 and OH. Taking heed of these notes enables the direct SMCC of the C(sp2)–B(dan) bond by a wide range of substrates with diverse functional groups, giving the following series of coupling products: Ar–Ar, Ar–HetAr, HetAr–HetAr, alkenyl–Ar, and alkenyl–alkenyl. Sequentially executing distinct types of palladium-catalyzed CCs, such as Buchwald–Hartwig CC + SMCC, Mizoroki–Heck reaction + SMCC, and Sonogashira–Hagihara CC + SMCC, allow to access complex π-conjugated molecules. The B(dan) moiety also exhibits outstanding compatibility with Wittig olefination and Sc(OTf)3-catalyzed acetal-forming reaction, enabling molecular transformations that are otherwise impracticable when using ArB(OH)2. Mechanistic studies suggested the involvement of both path A, wherein a boronate species reacts with an arylpalladium halide, and path B, wherein a boron compound reacts with an arylpalladium hydroxide, at the stage of the transmetalation.
{"title":"Direct Suzuki–Miyaura Cross-Coupling of C(sp2)–B(dan) Bonds Designed in Pursuit of Usability","authors":"Hiroki Andoh, Ryo Nakagawa, Tatsuya Akutagawa, Eiko Katata, Teruhisa Tsuchimoto","doi":"10.1039/d5qo00230c","DOIUrl":"https://doi.org/10.1039/d5qo00230c","url":null,"abstract":"We developed practical reaction conditions and procedure for the direct Suzuki–Miyaura cross-coupling (SMCC) of C(<em>sp</em><small><sup>2</sup></small>)–B(dan) bonds. Below are important notes to successfully execute the direct SMCC: 1) Dehydrated conditions that exclude as much H<small><sub>2</sub></small>O as possible are required, 2) LiOH is a base of choice, 3) dppf is a ligand of choice when using electron-deficient (hetero)aryl halides [(Het)ArX], 4) P(<em>t</em>-Bu)<small><sub>3</sub></small> is a ligand of choice when using electron-rich (Het)ArX, 5) COD is a ligand of choice when using (Het)ArX with a protic functional group such as NH<small><sub>2</sub></small> and OH. Taking heed of these notes enables the direct SMCC of the C(<em>sp</em><small><sup>2</sup></small>)–B(dan) bond by a wide range of substrates with diverse functional groups, giving the following series of coupling products: Ar–Ar, Ar–HetAr, HetAr–HetAr, alkenyl–Ar, and alkenyl–alkenyl. Sequentially executing distinct types of palladium-catalyzed CCs, such as Buchwald–Hartwig CC + SMCC, Mizoroki–Heck reaction + SMCC, and Sonogashira–Hagihara CC + SMCC, allow to access complex π-conjugated molecules. The B(dan) moiety also exhibits outstanding compatibility with Wittig olefination and Sc(OTf)<small><sub>3</sub></small>-catalyzed acetal-forming reaction, enabling molecular transformations that are otherwise impracticable when using ArB(OH)<small><sub>2</sub></small>. Mechanistic studies suggested the involvement of both path A, wherein a boronate species reacts with an arylpalladium halide, and path B, wherein a boron compound reacts with an arylpalladium hydroxide, at the stage of the transmetalation.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"52 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A green and metal-free strategy for the synthesis of diverse structural prolinol derivatives through intramolecular aminoalkoxylation of unfunctionalized olefins in up to 96% isolated yields has been reported. This protocol used easily recyclable NIS as catalysis and accomplished in a mild reaction condition which enabled environmentally friendly alcoholic compounds as reaction solvent and alkoxyl sources. Notably, water is generated as the sole byproduct, emphasizing the green nature of the process. Experimental evidence and DFT calculations support a mechanistic pathway proceeding via aziridinium ion formation rather than through iodonium intermediates; subsequent aziridinium ion ring-opening by alcohol affords the desired products. The NIS catalyst is readily regenerated under an oxygen atmosphere, eliminating the need for transition metals or stoichiometric oxidants. This robust and scalable approach thus represents a valuable advance in the synthesis of prolinol derivatives and highlights the potential of cyclic aziridinium ion intermediates in sustainable nitrogen-heterocycle construction.
{"title":"A Metal-free, Green Strategy for Intramolecular Aminoalkoxylation of Unfunctionalized Olefins via Recyclable NIS Catalysis with Water as the Sole Byproduct","authors":"Hui Sun, Liyuan Zhang, Xin Wu, Bin Cui","doi":"10.1039/d5qo00535c","DOIUrl":"https://doi.org/10.1039/d5qo00535c","url":null,"abstract":"A green and metal-free strategy for the synthesis of diverse structural prolinol derivatives through intramolecular aminoalkoxylation of unfunctionalized olefins in up to 96% isolated yields has been reported. This protocol used easily recyclable NIS as catalysis and accomplished in a mild reaction condition which enabled environmentally friendly alcoholic compounds as reaction solvent and alkoxyl sources. Notably, water is generated as the sole byproduct, emphasizing the green nature of the process. Experimental evidence and DFT calculations support a mechanistic pathway proceeding via aziridinium ion formation rather than through iodonium intermediates; subsequent aziridinium ion ring-opening by alcohol affords the desired products. The NIS catalyst is readily regenerated under an oxygen atmosphere, eliminating the need for transition metals or stoichiometric oxidants. This robust and scalable approach thus represents a valuable advance in the synthesis of prolinol derivatives and highlights the potential of cyclic aziridinium ion intermediates in sustainable nitrogen-heterocycle construction.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"10 1 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143813748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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