Cyclic tetrapeptides (CTPs), which possess unique structures and diverse biological activities, are significant substances in pharmaceutical and therapeutic applications. However, the inherent ring strain in CTPs poses challenges in minimizing racemization and achieving high yields. The antiviral CTP cyclo-(Pro-Leu)₂ and the anticancer CTP cyclo-(Pro-Val)₂ were previously reported with yields of only 5% and 7%, respectively. The diverse array of peptide cyclization conditions significantly impacts the reaction outcomes, making comprehensive optimization a labor-intensive task. Herein, we integrated high-throughput continuous flow technology with machine learning to achieve rapid and comprehensive optimization for the synthesis of challenging CTPs, achieving a 5- to 7-fold improvement in yields for both cyclo-(Pro-Val)2 and cyclo-(Pro-Leu)2 compared to those reported in the literatures. Notably, with the assistance of machine learning, which achieves a root mean square error of 3.6, the optimization workload can be reduced by up to 90%. These advancements could potentially provide a solution for the rapid optimization and synthesis of valuable CTPs.
{"title":"Synthesis of Challenging Cyclic Tetrapeptides by Machine Learning Assisted High-throughput Continuous Flow Technology","authors":"Chaoyi Li, Jiaping Yu, Wanchen Li, Jingyuan Liao, Junrong Huang, Jiaying Liu, Wei Zhao, Yinghe Zhang, Yuxiang Zhu, Hengzhi You","doi":"10.1039/d4qo02225d","DOIUrl":"https://doi.org/10.1039/d4qo02225d","url":null,"abstract":"Cyclic tetrapeptides (CTPs), which possess unique structures and diverse biological activities, are significant substances in pharmaceutical and therapeutic applications. However, the inherent ring strain in CTPs poses challenges in minimizing racemization and achieving high yields. The antiviral CTP cyclo-(Pro-Leu)₂ and the anticancer CTP cyclo-(Pro-Val)₂ were previously reported with yields of only 5% and 7%, respectively. The diverse array of peptide cyclization conditions significantly impacts the reaction outcomes, making comprehensive optimization a labor-intensive task. Herein, we integrated high-throughput continuous flow technology with machine learning to achieve rapid and comprehensive optimization for the synthesis of challenging CTPs, achieving a 5- to 7-fold improvement in yields for both cyclo-(Pro-Val)2 and cyclo-(Pro-Leu)2 compared to those reported in the literatures. Notably, with the assistance of machine learning, which achieves a root mean square error of 3.6, the optimization workload can be reduced by up to 90%. These advancements could potentially provide a solution for the rapid optimization and synthesis of valuable CTPs.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"16 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546820","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}
Cyclopenta-fused polycyclic heteroarenes (CP-PHAs) composed of acenaphthylene and heteroaromatic units have emerged as intriguing photoelectronic materials in view of the electron-accepting feature of the fused CP rings and the tunable electronic properties of the heteroaromatics. To date, Pd-catalyzed aromatic C-H/peri-C-halogen coupling has been used as one of the most general methods to construct such CP-rings. In contrast, Pd-catalyzed direct aromatic C-H/peri-C-H coupling may provide a shortcut to this CP-ring formation, which is applicable to a wide range of polycyclic arenes bearing peri-C-H bonds, but remains unexploited so far. We herein describe a Pd-catalyzed site-specific C-H/peri-C-H annulative coupling between (benzo)thiophenes or indoles with various polycyclic arenes to access a variety of π-extended CP-PHAs. Benzo[b]thiophenes or thiophenes with a 1-naphthalenyl group at the C3 position gave C2-naphthylated CP-PHAs in the Pd(OPiv)2/AgOPiv system, whereas indoles with a 1-naphthalenyl group at the C2 position gave C3-naphthylated CP-PHAs in the Pd(OPiv)2/AgSbF6 system. Notably, deuteration experiments demonstrated that silver salts play a crucial role in the formation of heteroaryl-Ag species via site-specific C-H metalation of heteroaromatics, which subsequently undergo transmetalation with Pd(II) to form heteroaryl-Pd species and activate the peri-C-H bond of the naphthalene group. Furthermore, this method enables the synthesis of structurally diverse CP-PHAs via activation of peri-C-H bonds in large polycyclic aromatic hydrocarbons such as anthracene, phenanthrene, and pyrene.
{"title":"Pd-Catalyzed site-specific heteroaromatic C-H/peri-C-H annulative coupling for synthesis of cyclopenta-fused polycyclic heteroarenes","authors":"Tienan Jin, Masaki Kawata, Sho Aida, Masahiro Terada","doi":"10.1039/d5qo00034c","DOIUrl":"https://doi.org/10.1039/d5qo00034c","url":null,"abstract":"Cyclopenta-fused polycyclic heteroarenes (CP-PHAs) composed of acenaphthylene and heteroaromatic units have emerged as intriguing photoelectronic materials in view of the electron-accepting feature of the fused CP rings and the tunable electronic properties of the heteroaromatics. To date, Pd-catalyzed aromatic C-H/peri-C-halogen coupling has been used as one of the most general methods to construct such CP-rings. In contrast, Pd-catalyzed direct aromatic C-H/peri-C-H coupling may provide a shortcut to this CP-ring formation, which is applicable to a wide range of polycyclic arenes bearing peri-C-H bonds, but remains unexploited so far. We herein describe a Pd-catalyzed site-specific C-H/peri-C-H annulative coupling between (benzo)thiophenes or indoles with various polycyclic arenes to access a variety of π-extended CP-PHAs. Benzo[b]thiophenes or thiophenes with a 1-naphthalenyl group at the C3 position gave C2-naphthylated CP-PHAs in the Pd(OPiv)2/AgOPiv system, whereas indoles with a 1-naphthalenyl group at the C2 position gave C3-naphthylated CP-PHAs in the Pd(OPiv)2/AgSbF6 system. Notably, deuteration experiments demonstrated that silver salts play a crucial role in the formation of heteroaryl-Ag species via site-specific C-H metalation of heteroaromatics, which subsequently undergo transmetalation with Pd(II) to form heteroaryl-Pd species and activate the peri-C-H bond of the naphthalene group. Furthermore, this method enables the synthesis of structurally diverse CP-PHAs via activation of peri-C-H bonds in large polycyclic aromatic hydrocarbons such as anthracene, phenanthrene, and pyrene.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"50 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546818","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 chiral ferrocene-tethered ruthenium diamine catalyst has been developed for asymmetric transfer hydrogenation of ketones, enabling asymmetric reduction of a wide range of ketones including aryl alkyl ketones and cyclic dialkyl ketones with excellent reactivities and enantioselectivities. Efficient dynamic kinetic resolution (DKR) of racemic α-substituted cyclic ketones was established, affording a series of cyclic chiral alcohols with two contiguous stereocenters in high yields and excellent enantio- and diastereoselectivity levels. The chiral ATH Ru catalyst was found to offer practicality, with a TON of up to 4000.
{"title":"A chiral ferrocene-tethered ruthenium diamine catalyst for asymmetric transfer hydrogenation of ketones","authors":"Xinpeng Fu, Hanxiao Yu, Haoyang Gao, Yuhao Dai, He Yang, Wenjun Tang","doi":"10.1039/d5qo00077g","DOIUrl":"https://doi.org/10.1039/d5qo00077g","url":null,"abstract":"A chiral ferrocene-tethered ruthenium diamine catalyst has been developed for asymmetric transfer hydrogenation of ketones, enabling asymmetric reduction of a wide range of ketones including aryl alkyl ketones and cyclic dialkyl ketones with excellent reactivities and enantioselectivities. Efficient dynamic kinetic resolution (DKR) of racemic α-substituted cyclic ketones was established, affording a series of cyclic chiral alcohols with two contiguous stereocenters in high yields and excellent enantio- and diastereoselectivity levels. The chiral ATH Ru catalyst was found to offer practicality, with a TON of up to 4000.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"24 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546665","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}
Here, we report the first dual catalysis involving both anionic and cationic species of an ion-pairing photocatalyst. The key is the development of a photocatalyst composed of pyridinium cations and bromide anions, which upon irradiation facilitate hydrogen atom transfer and single-electron reduction events within their individual catalytic cycles. As a result, this type of ion pair acts as a multifunctional catalyst capable of independently promoting hydrogen transfer and cross-coupling reactions, thereby eliminating the need for any metals or external additives.
{"title":"Dual anion and cation catalysis enabled by an ion-pairing photocatalyst","authors":"Xi-Xian Chen, Xiang Chen, Feng Lan, Teng Zeng, Hao Cui, Xiao Zhang","doi":"10.1039/d5qo00241a","DOIUrl":"https://doi.org/10.1039/d5qo00241a","url":null,"abstract":"Here, we report the first dual catalysis involving both anionic and cationic species of an ion-pairing photocatalyst. The key is the development of a photocatalyst composed of pyridinium cations and bromide anions, which upon irradiation facilitate hydrogen atom transfer and single-electron reduction events within their individual catalytic cycles. As a result, this type of ion pair acts as a multifunctional catalyst capable of independently promoting hydrogen transfer and cross-coupling reactions, thereby eliminating the need for any metals or external additives.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"30 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143546666","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 simple and mild route for the synthesis of substituted thieno[2,3-b]chromen-4-one derivatives with pendant imine is reported via a one-pot three-component reaction from 4-hydroxythiocoumarin, salicylaldehyde/aryl aldehyde and trans-β-nitrostyrene. The reaction proceeds through the Michael addition of 4-hydroxythiocoumarin to trans-β-nitrostyrene followed by a sequence of transformations involving intramolecular cyclization via nucleophilic attack, an unprecedented conversion of oxime-to-amine through a unique disproportionation reaction without requiring any additional reagents, and Schiff’s base formation with salicylaldehyde/aryl aldehyde, yielding the desired product. The process is highly regioselective, enabling the simultaneous formation of one C–C, one C–S, and two C–N bonds in a single step, offering an efficient and mild synthetic route to complex heterocyclic structures.
{"title":"A Regioselective and Sustainable Approach to the Synthesis of Substituted Thieno[2,3-b]chromen-4-ones with Pendant Imine Groups via Base-Promoted Multicomponent Reaction","authors":"Ujjwal Jyoti Goswami, Anjela Xalxo, Abu Khan","doi":"10.1039/d5qo00228a","DOIUrl":"https://doi.org/10.1039/d5qo00228a","url":null,"abstract":"A simple and mild route for the synthesis of substituted thieno[2,3-<em>b</em>]chromen-4-one derivatives with pendant imine is reported <em>via</em> a one-pot three-component reaction from 4-hydroxythiocoumarin, salicylaldehyde/aryl aldehyde and <em>trans</em>-β-nitrostyrene. The reaction proceeds through the Michael addition of 4-hydroxythiocoumarin to <em>trans</em>-β-nitrostyrene followed by a sequence of transformations involving intramolecular cyclization via nucleophilic attack, an unprecedented conversion of oxime-to-amine through a unique disproportionation reaction without requiring any additional reagents, and Schiff’s base formation with salicylaldehyde/aryl aldehyde, yielding the desired product. The process is highly regioselective, enabling the simultaneous formation of one C–C, one C–S, and two C–N bonds in a single step, offering an efficient and mild synthetic route to complex heterocyclic structures.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"35 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538679","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}
Azomethine imines as a class of important dipoles have been widely employed in enantioselective 1,3-dipolar cycloaddition reactions. Copper-catalyzed enantioselective cycloaddition of azomethine imines with alkynes is one of the most efficient tools for furnishing chiral pyrazolines. However, it is difficult to construct fully substituted pyrazolines through such copper-catalyzed reactions because the dipolarophiles are limited to terminal alkynes. Herein, we report a copper-catalyzed enantioselective cycloaddition/amination cascade reaction of azomethine imines, terminal alkynes and O-benzoylhydroxylamines to form chiral amino-substituted bicyclic pyrazolines with high enantioselectivities. This is the first description of direct synthesis of chiral fully substituted pyrazolines from readily available terminal alkynes.
{"title":"Copper-catalyzed enantioselective cycloaddition/amination cascade of azomethine imines, alkynes and O-benzoylhydroxylamines","authors":"Tai-Gang Fan, Bo-Xun Sun, Wei Jiang, Jia Hu, Li-Bo Yang, Yuan Qu, Ya-Min Li","doi":"10.1039/d5qo00061k","DOIUrl":"https://doi.org/10.1039/d5qo00061k","url":null,"abstract":"Azomethine imines as a class of important dipoles have been widely employed in enantioselective 1,3-dipolar cycloaddition reactions. Copper-catalyzed enantioselective cycloaddition of azomethine imines with alkynes is one of the most efficient tools for furnishing chiral pyrazolines. However, it is difficult to construct fully substituted pyrazolines through such copper-catalyzed reactions because the dipolarophiles are limited to terminal alkynes. Herein, we report a copper-catalyzed enantioselective cycloaddition/amination cascade reaction of azomethine imines, terminal alkynes and <em>O</em>-benzoylhydroxylamines to form chiral amino-substituted bicyclic pyrazolines with high enantioselectivities. This is the first description of direct synthesis of chiral fully substituted pyrazolines from readily available terminal alkynes.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"16 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538682","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}
Xue Zhang, Ziqian Xu, Andrey Sukhanov, Xichuan Yang, Ayhan Elmali, Jianzhang Zhao, Bernhard Dick, Ahmet Karatay, violeta voronkova
A compact electron donor-acceptor dyad NI-ICz with 6,12-diphenyl-indolo[3,2-b]carbazole (ICz) as the electron donor and naphthalimide (NI) as the acceptor, was prepared to study the electron transfer (ET) and the thermally-activated delayed fluorescence (TADF) properties. The rigid and bulky electron donor reduces the reorganization energy (λ = 0.96 eV) of the ET, which facilitates the long-lived charge separated (CS) state formation in NI-ICz, by exploiting the Marcus inverted region effect on charge recombination (CR). Transient absorption (TA) spectroscopy reveals the formation of the CS triplet (3CS) states (τ = 8.6 μs in n-hexane, 1.4 μs in toluene, 0.13 μs in acetonitrile). TADF of this dyad is only present in n-hexane but absent in polar solvents, indicating 3CS → 1CS reversed ISC (RISC) is inefficient, which is a solid experimental evidence for the spin-vibronic coupling mechanism of TADF. A small zero-field splitting (ZFS) parameter (ΙDΙ = 900 MHz) of the triplet state of NI-ICz confirming the formation of 3CS state. These results demonstrate the feasibility of achieving long-lived CS state in compact electron donor-acceptor dyads. The findings also highlight the crucial role of the closely-lying 3LE, 1CS and 3CS states in enabling TADF where the 3LE state serves as an essential intermediate state to facilitate RISC in TADF system.
{"title":"Charge separation and intersystem crossing in compact orthogonal and sterically encumbered 6,12-diphenyl indolo[3,2-b]carbazole-naphthalimide electron donor-acceptor dyad","authors":"Xue Zhang, Ziqian Xu, Andrey Sukhanov, Xichuan Yang, Ayhan Elmali, Jianzhang Zhao, Bernhard Dick, Ahmet Karatay, violeta voronkova","doi":"10.1039/d4qo02267j","DOIUrl":"https://doi.org/10.1039/d4qo02267j","url":null,"abstract":"A compact electron donor-acceptor dyad <strong>NI-ICz</strong> with 6,12-diphenyl-indolo[3,2-b]carbazole (ICz) as the electron donor and naphthalimide (NI) as the acceptor, was prepared to study the electron transfer (ET) and the thermally-activated delayed fluorescence (TADF) properties. The rigid and bulky electron donor reduces the reorganization energy (<em>λ</em> = 0.96 eV) of the ET, which facilitates the long-lived charge separated (CS) state formation in <strong>NI-ICz</strong>, by exploiting the Marcus inverted region effect on charge recombination (CR). Transient absorption (TA) spectroscopy reveals the formation of the CS triplet (<small><sup>3</sup></small>CS) states (τ = 8.6 μs in n-hexane, 1.4 μs in toluene, 0.13 μs in acetonitrile). TADF of this dyad is only present in n-hexane but absent in polar solvents, indicating <small><sup>3</sup></small>CS → <small><sup>1</sup></small>CS reversed ISC (RISC) is inefficient, which is a solid experimental evidence for the spin-vibronic coupling mechanism of TADF. A small zero-field splitting (ZFS) parameter (Ι<em>D</em>Ι = 900 MHz) of the triplet state of <strong>NI-ICz</strong> confirming the formation of <small><sup>3</sup></small>CS state. These results demonstrate the feasibility of achieving long-lived CS state in compact electron donor-acceptor dyads. The findings also highlight the crucial role of the closely-lying <small><sup>3</sup></small>LE, <small><sup>1</sup></small>CS and <small><sup>3</sup></small>CS states in enabling TADF where the <small><sup>3</sup></small>LE state serves as an essential intermediate state to facilitate RISC in TADF system.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"29 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538681","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 novel efficient approach for obtaining allylic sulfones was demonstrated via palladium-catalyzed hydrosulfonylation of cyclopropenes. Preliminary mechanistic studies disclosed that π-allyl palladium might be the key intermediate. This process is applicable for a broad range of cyclopropane derivatives, and employs commercially available sodium sulfinates as sulfonyl source. Gram-scale reactions and further derivatizations showed the great synthetic potential of this method for construction of allylic sulfones.
{"title":"Stereoselective synthesis of allylic sulfones via palladium-catalyzed hydrosulfonylation of cyclopropenes","authors":"Suliang Wang, Xuening Li, Jian Song, Xianjie Fang","doi":"10.1039/d5qo00062a","DOIUrl":"https://doi.org/10.1039/d5qo00062a","url":null,"abstract":"A novel efficient approach for obtaining allylic sulfones was demonstrated via palladium-catalyzed hydrosulfonylation of cyclopropenes. Preliminary mechanistic studies disclosed that π-allyl palladium might be the key intermediate. This process is applicable for a broad range of cyclopropane derivatives, and employs commercially available sodium sulfinates as sulfonyl source. Gram-scale reactions and further derivatizations showed the great synthetic potential of this method for construction of allylic sulfones.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"130 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538504","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}
Visible-light-promoted [2+2] cycloaddition/dearomatization of aromatic compounds is an efficient strategy for the synthesis of three-dimensional rigid four-membered ring to realize the modification of organic molecules, which boasts great potential and prospect in developing first class drugs. Herein, cyclobutane-fused indolines were successfully synthesized via photocatalytic intermolecular [2+2] cycloaddition/dearomatization reaction with olefins. This reaction exhibited excellent regio- and stereoselectivity (> 20:1 dr), high atom- and step-economy, and was characterized by mild and green reaction conditions, simple operation, wide range of substrate applicability. The mechanistic control exploration suggested that the [2+2] cycloaddition reaction was initiated by the triplet-triplet energy transfer paradigm.
{"title":"Photocatalytic intermolecular [2+2] cycloaddition/dearomatization of indoles: easy access to cyclobutane-fused indolines","authors":"Zeng Han, Lianhui Wang, Yuanqi Luo, Xiuling Cui","doi":"10.1039/d4qo02302a","DOIUrl":"https://doi.org/10.1039/d4qo02302a","url":null,"abstract":"Visible-light-promoted [2+2] cycloaddition/dearomatization of aromatic compounds is an efficient strategy for the synthesis of three-dimensional rigid four-membered ring to realize the modification of organic molecules, which boasts great potential and prospect in developing first class drugs. Herein, cyclobutane-fused indolines were successfully synthesized via photocatalytic intermolecular [2+2] cycloaddition/dearomatization reaction with olefins. This reaction exhibited excellent regio- and stereoselectivity (> 20:1 dr), high atom- and step-economy, and was characterized by mild and green reaction conditions, simple operation, wide range of substrate applicability. The mechanistic control exploration suggested that the [2+2] cycloaddition reaction was initiated by the triplet-triplet energy transfer paradigm.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"15 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538483","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 variety of pyrazoline-derived N-vinyl nitrones were prepared in moderate to good yields with high diastereoselectivity through base-promoted regioselective [3+2] cycloaddition of N-vinyl chalcone nitrones with hydrazonoyl chlorides under mild reaction conditions. The mechanistic studies revealed that the E-isomer of N-vinyl nitrones facilitated to be converted into pyrazoline-derived N-vinyl nitrones than Z-isomer. The present method features broad substrate scope, good functional group tolerance, high regioselectivity and diastereoselectivity, novel type of N-vinyl nitrones, and N-vinyl nitrones served as dipolarophiles.
{"title":"Synthesis of Pyrazoline-Derived N-Vinyl Nitrones through An Unexpected Selective [3+2] Cycloaddition","authors":"Pei-Wen Qiu, Li-Bing Yan, Li-Fen Ning, Chun-Hua Chen, Hong-Yan Bi, Dong-Liang Mo","doi":"10.1039/d4qo02317j","DOIUrl":"https://doi.org/10.1039/d4qo02317j","url":null,"abstract":"A variety of pyrazoline-derived N-vinyl nitrones were prepared in moderate to good yields with high diastereoselectivity through base-promoted regioselective [3+2] cycloaddition of N-vinyl chalcone nitrones with hydrazonoyl chlorides under mild reaction conditions. The mechanistic studies revealed that the E-isomer of N-vinyl nitrones facilitated to be converted into pyrazoline-derived N-vinyl nitrones than Z-isomer. The present method features broad substrate scope, good functional group tolerance, high regioselectivity and diastereoselectivity, novel type of N-vinyl nitrones, and N-vinyl nitrones served as dipolarophiles.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"9 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538683","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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