The first asymmetric [4+3] cycloaddition of hydroxyphenyl indolinones has been reported to afford a new series of multisubstituted spirooxindole derivatives embedded with an oxadiazepine scaffold with high stereoselectivities. The reaction proceeds via o-QM intermediates produced in situ from hydroxyphenyl indolinones, which could undergo cyclization with azomethine imines under CPA catalysis to deliver a new type of seven-membered spirocyclic oxindole compounds. High yields, exclusive diastereoselectivities, and excellent enantioselectivities as well as wide substrate scope were obtained in this organocatalytic reaction.
{"title":"Asymmetric [4+3] Cycloaddition of Hydroxyphenyl Indolinones to Synthesize Novel Spirooxindoles","authors":"Shuhui Huang, Yongquan Xu, Mohan Li, Lihuan Liao, Weiwu Ren","doi":"10.1039/d5qo00075k","DOIUrl":"https://doi.org/10.1039/d5qo00075k","url":null,"abstract":"The first asymmetric [4+3] cycloaddition of hydroxyphenyl indolinones has been reported to afford a new series of multisubstituted spirooxindole derivatives embedded with an oxadiazepine scaffold with high stereoselectivities. The reaction proceeds via o-QM intermediates produced in situ from hydroxyphenyl indolinones, which could undergo cyclization with azomethine imines under CPA catalysis to deliver a new type of seven-membered spirocyclic oxindole compounds. High yields, exclusive diastereoselectivities, and excellent enantioselectivities as well as wide substrate scope were obtained in this organocatalytic reaction.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"25 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462703","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 are an outstanding class of 1,3-dipolar species that are important synthetic building blocks for di-nitrogenated heterocycles. Despite their significance, the current synthesis of chiral azomethine imines relies on kinetic resolution and remains underdeveloped. Here, we reported a computational study of chiral phosphoric acid (CPA) catalyzed intermolecular [4+2] cycloaddition between methyl diazoacetate and dienes. Our calculations revealed that a diene bearing an electron-donating group facilitates this [4+2] cycloaddition and a narrow chiral pocket of CPA is advantageous for achieving excellent enantioselectivity. The fine-tuned interactions between substrates and the substituents on the sidearms of CPA catalysts are indispensable for excellent enantioselectivity. Through comprehensive mechanistic insights, we have designed a synthetic route for chiral azomethine imines, which holds great potential in organic and medicinal chemistry.
{"title":"Chiral Phosphoric Acid Catalyzed Intermolecular [4+2] Cycloaddition for Chiral Azomethine Imines: Mechanism and Stereochemical Model","authors":"Weichi Chen, Zhongqing Qu, Shuanglin Qu, Abing Duan","doi":"10.1039/d5qo00203f","DOIUrl":"https://doi.org/10.1039/d5qo00203f","url":null,"abstract":"Azomethine imines are an outstanding class of 1,3-dipolar species that are important synthetic building blocks for di-nitrogenated heterocycles. Despite their significance, the current synthesis of chiral azomethine imines relies on kinetic resolution and remains underdeveloped. Here, we reported a computational study of chiral phosphoric acid (CPA) catalyzed intermolecular [4+2] cycloaddition between methyl diazoacetate and dienes. Our calculations revealed that a diene bearing an electron-donating group facilitates this [4+2] cycloaddition and a narrow chiral pocket of CPA is advantageous for achieving excellent enantioselectivity. The fine-tuned interactions between substrates and the substituents on the sidearms of CPA catalysts are indispensable for excellent enantioselectivity. Through comprehensive mechanistic insights, we have designed a synthetic route for chiral azomethine imines, which holds great potential in organic and medicinal chemistry.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"81 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462704","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}
Shan-Shan Liu, Jiang-Nan Zheng, Zhi-Wen Zhao, Yi Zhang, Ping He, Yong-Jie Wu, Jiang-Tao Feng, Long Wang, Zhi-Lin Ren
An efficient synthesis of pyrrole derivatives is achieved via ordered isocyanide insertion reaction, driven by ring strain and mediated by intramolecular non-covalent bonds. This method harnesses the strategic design of precursors to control reactivity, ensuring selectivity and high yields. The strategy is noteworthy for its innovative utilization of α, β-unsaturated ketone, which concurrently serves as both a directing group and an integral reaction substrate. Additionally, we have demonstrated the sequential de-tert-butylation of the same substrate under alkaline or acidic conditions. The plausible mechanism has been further corroborated through DFT theoretical calculations, providing a solid foundation for our proposed route.
{"title":"Synthesis of Pyrrole Derivatives via Ordered Isocyanide Insertion Reaction Driven by Ring Strain Mediated by Non-covalent Bond Interactions","authors":"Shan-Shan Liu, Jiang-Nan Zheng, Zhi-Wen Zhao, Yi Zhang, Ping He, Yong-Jie Wu, Jiang-Tao Feng, Long Wang, Zhi-Lin Ren","doi":"10.1039/d4qo02144d","DOIUrl":"https://doi.org/10.1039/d4qo02144d","url":null,"abstract":"An efficient synthesis of pyrrole derivatives is achieved via ordered isocyanide insertion reaction, driven by ring strain and mediated by intramolecular non-covalent bonds. This method harnesses the strategic design of precursors to control reactivity, ensuring selectivity and high yields. The strategy is noteworthy for its innovative utilization of α, β-unsaturated ketone, which concurrently serves as both a directing group and an integral reaction substrate. Additionally, we have demonstrated the sequential de-tert-butylation of the same substrate under alkaline or acidic conditions. The plausible mechanism has been further corroborated through DFT theoretical calculations, providing a solid foundation for our proposed route.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"19 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143462709","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}
Herein we disclose a catalytic asymmetric desymmetrization of cyclopentene-1,3-diones via formal diaza-ene reaction/tautomerization with donor-acceptor hydrazones. H8-TRIP catalyst was found to be effective for this reaction. The chiral cyclopentane 1,3-diones embedded with hydrazone motif were obtained in good to high yields with excellent diastereo- and good to high enantioselectivities. The scope of the reaction was broad and few applications including a pyrazole formation reaction have been demonstrated.
{"title":"Organocatalytic Asymmetric Desymmetrization of Cyclopentene-1,3-diones via Formal Diaza-ene Reaction with Donor–Acceptor Hydrazones","authors":"Subhankar Biswas, Subhas Chandra Pan","doi":"10.1039/d5qo00081e","DOIUrl":"https://doi.org/10.1039/d5qo00081e","url":null,"abstract":"Herein we disclose a catalytic asymmetric desymmetrization of cyclopentene-1,3-diones via formal diaza-ene reaction/tautomerization with donor-acceptor hydrazones. H8-TRIP catalyst was found to be effective for this reaction. The chiral cyclopentane 1,3-diones embedded with hydrazone motif were obtained in good to high yields with excellent diastereo- and good to high enantioselectivities. The scope of the reaction was broad and few applications including a pyrazole formation reaction have been demonstrated.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"65 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443950","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}
Herein, we uncover a hitherto hidden role of H-TEDA(BF4)2 – a cheap, stable, recoverable by-product of radical C(sp3)–H fluorinations using Selectfluor®. This forms a photoactive, mixed heteroaggregate with Selectfluor® which underlies the reactivity of visible light photochemical fluorination reactions of unactivated C(sp3)–H bonds. Where previous reports claim to be ‘photocatalytic’, reactions work without photocatalyst when H-TEDA(BF4)2 is dosed in at the start. Our results demonstrate that ‘photocatalysts’ are only necessary to generate a sufficient amount of nascent H-TEDA(BF4)2, whose heteroaggregate with Selectfluor® takes over as the main photoactive species. Mechanistic studies suggest the formation of a heterocomplex between H-TEDA(BF4)2 and Selectfluor® under photoirradiation, which generates TEDA•2+. A salient feature of our method is its flexibility to use the C(sp3)–H precursor substrate as the limiting reactant, simplifying isolations of products from unreacted precursors.
{"title":"A Protodefluorinated Selectfluor® Heteroaggregate Photoinduces Direct C(sp3)−H Fluorinations Without Photocatalyst","authors":"Shahboz Yakubov, Joshua Philip Barham","doi":"10.1039/d5qo00149h","DOIUrl":"https://doi.org/10.1039/d5qo00149h","url":null,"abstract":"Herein, we uncover a hitherto hidden role of H-TEDA(BF4)2 – a cheap, stable, recoverable by-product of radical C(sp3)–H fluorinations using Selectfluor®. This forms a photoactive, mixed heteroaggregate with Selectfluor® which underlies the reactivity of visible light photochemical fluorination reactions of unactivated C(sp3)–H bonds. Where previous reports claim to be ‘photocatalytic’, reactions work without photocatalyst when H-TEDA(BF4)2 is dosed in at the start. Our results demonstrate that ‘photocatalysts’ are only necessary to generate a sufficient amount of nascent H-TEDA(BF4)2, whose heteroaggregate with Selectfluor® takes over as the main photoactive species. Mechanistic studies suggest the formation of a heterocomplex between H-TEDA(BF4)2 and Selectfluor® under photoirradiation, which generates TEDA•2+. A salient feature of our method is its flexibility to use the C(sp3)–H precursor substrate as the limiting reactant, simplifying isolations of products from unreacted precursors.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"25 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443951","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}
Herein, we demonstrate a robust palladium/norbornene-catalyzed deoxygenative ortho-benzylation of aryl iodides with non-derivatized benzyl alcohol, enabling assembly of various diarylmethanes with high efficiency. Assisted by carbodiimides, alcohol was transiently converted into corresponding isoureas, which further polarize C-O bond, and facilitated the reaction with key ANP intermediate through nitrogen atom coordination. The salient features of this methodology include operational simplicity, high chemoselectivity, and broad substrate scope. Preliminary mechanistic investigation determined the higher reactivity of isourea over benzyl (pseudo)halide.
{"title":"Deoxygenative ortho-Benzylation of Aryl Iodides with Benzyl Alcohol via Palladium/Norbornene Cooperative Catalysis","authors":"Shaowen Ling, Shuaichen Zheng, Baolong Xu, Hui Liu, Xinjin Li, Feng-Gang Sun","doi":"10.1039/d5qo00094g","DOIUrl":"https://doi.org/10.1039/d5qo00094g","url":null,"abstract":"Herein, we demonstrate a robust palladium/norbornene-catalyzed deoxygenative ortho-benzylation of aryl iodides with non-derivatized benzyl alcohol, enabling assembly of various diarylmethanes with high efficiency. Assisted by carbodiimides, alcohol was transiently converted into corresponding isoureas, which further polarize C-O bond, and facilitated the reaction with key ANP intermediate through nitrogen atom coordination. The salient features of this methodology include operational simplicity, high chemoselectivity, and broad substrate scope. Preliminary mechanistic investigation determined the higher reactivity of isourea over benzyl (pseudo)halide.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"1 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443986","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}
Xinyue Hao, Bin Wang, Zhuangfei Tian, Zhouchang Yao, Tianzhang Qiao, Ling Huang, Haigen Fu
Heterobiaryl and heterobiaryl N-oxide atropisomers are important scaffolds in various chiral ligands, organocatalysts, and bioactive molecules. Here, we report a highly efficient biocatalytic route for the asymmetric synthesis of axially chiral heterobiaryl amines and heterobiaryl N-oxide amines via dynamic kinetic resolution (DKR). This novel DKR process features a racemization strategy promoted by forming a labile transition state via non-covalent interaction and coupled with a stereoselective reduction catalyzed by engineered imine-reductases (IREDs). Directed evolution of an IRED from Streptomyces sp. GF3546 provided two variants: S-IRED-Ss-M14 is superior for synthesizing diverse heterobiaryl amines, especially ones containing multiple heteroatoms; S-IRED-Ss-M16 is efficient for constructing heterobiaryl N-oxide amines. Both engineered IRED variants showed broad substrate scope with a high level of yield and enantioselectivity (up to 98% yield and >99:1 enantiomeric ratio). This evolvable IREDs-catalyzed DKR represents a promising solution for the atroposelective preparation of challenging axially chiral heterocyclic atropisomers.
{"title":"Biocatalytic atroposelective synthesis of heterobiaryls and heterobiaryl N-oxides via dynamic kinetic resolution","authors":"Xinyue Hao, Bin Wang, Zhuangfei Tian, Zhouchang Yao, Tianzhang Qiao, Ling Huang, Haigen Fu","doi":"10.1039/d5qo00011d","DOIUrl":"https://doi.org/10.1039/d5qo00011d","url":null,"abstract":"Heterobiaryl and heterobiaryl N-oxide atropisomers are important scaffolds in various chiral ligands, organocatalysts, and bioactive molecules. Here, we report a highly efficient biocatalytic route for the asymmetric synthesis of axially chiral heterobiaryl amines and heterobiaryl N-oxide amines via dynamic kinetic resolution (DKR). This novel DKR process features a racemization strategy promoted by forming a labile transition state via non-covalent interaction and coupled with a stereoselective reduction catalyzed by engineered imine-reductases (IREDs). Directed evolution of an IRED from Streptomyces sp. GF3546 provided two variants: S-IRED-Ss-M14 is superior for synthesizing diverse heterobiaryl amines, especially ones containing multiple heteroatoms; S-IRED-Ss-M16 is efficient for constructing heterobiaryl N-oxide amines. Both engineered IRED variants showed broad substrate scope with a high level of yield and enantioselectivity (up to 98% yield and >99:1 enantiomeric ratio). This evolvable IREDs-catalyzed DKR represents a promising solution for the atroposelective preparation of challenging axially chiral heterocyclic atropisomers.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"1 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443954","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}
In contrast to the π-electrophilic transition metal-catalyzed cycloisomerization of enynes, systematic studies on the reaction of enynes by activation of carbonyl groups conjugated to alkynes are lacking. Herein, we report the metal-free cycloisomerization of 7-en-2-yn-1-ones to gem-difluorinated and gem-chlorofluorinated bicyclo[3.1.0]hexanes using electrophilic halogenating agents.
{"title":"Cycloisomerization of 7-En-2-yn-1-ones to Bicyclo[3.1.0]hexanes Using Electrophilic Fluorination or Chlorination Agents","authors":"Yuki Yasuda, Daisuke Sato, Akira Tsubouchi, Akio Saito","doi":"10.1039/d4qo02373k","DOIUrl":"https://doi.org/10.1039/d4qo02373k","url":null,"abstract":"In contrast to the π-electrophilic transition metal-catalyzed cycloisomerization of enynes, systematic studies on the reaction of enynes by activation of carbonyl groups conjugated to alkynes are lacking. Herein, we report the metal-free cycloisomerization of 7-en-2-yn-1-ones to gem-difluorinated and gem-chlorofluorinated bicyclo[3.1.0]hexanes using electrophilic halogenating agents.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"76 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443948","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}
Susana García-Abellán, Asier Urriolabeitia, Victor Polo, Manuel Iglesias
The [2+2+2] cycloaddition of alkynes and nitriles is an efficient and atom-economic method for the synthesis of pyridines. However, most of the examples so far reported entail the use of diynes, which circumvents selectivity issues but limits the scope of the reaction—with examples of discrete alkynes being scarce. Moreover, the most widely used catalysts are Co(I) complexes featuring Cp or Cp* ligands, which are either too unstable to store or require harsh conditions to promote the cycloaddition reaction. This work describes a mild method for the preparation of a wide range of pyridines employing a Co(I) active species generated in situ from a well-defined, air-stable Co(III) complex—namely, [CoCp*(CH3CN)(P-N)][BF4]2—upon treatment with NaBEt3H. This complex, which contains a hemilabile P-N ligand, has been found to be substantially more active than complexes featuring monodentate or bidentate phosphanes. This behavior has been ascribed to the inadequate stabilization of the resulting Co(I) species for the former, or overstabilization of the Co(III) complex in the case of the latter. A comprehensive DFT study has been conducted to elucidate the experimentally observed chemo- and regioselectivity by examining the competitive pathways following the oxidative coupling of CoCp*(bisalkyne) complex, taking under account the participation of triplet states and intersystem crossing points.
{"title":"In situ generated cobalt(I) catalyst for the efficient synthesis of novel pyridines: Revisiting the mechanism of [2+2+2] cycloadditions","authors":"Susana García-Abellán, Asier Urriolabeitia, Victor Polo, Manuel Iglesias","doi":"10.1039/d5qo00222b","DOIUrl":"https://doi.org/10.1039/d5qo00222b","url":null,"abstract":"The [2+2+2] cycloaddition of alkynes and nitriles is an efficient and atom-economic method for the synthesis of pyridines. However, most of the examples so far reported entail the use of diynes, which circumvents selectivity issues but limits the scope of the reaction—with examples of discrete alkynes being scarce. Moreover, the most widely used catalysts are Co(I) complexes featuring Cp or Cp* ligands, which are either too unstable to store or require harsh conditions to promote the cycloaddition reaction. This work describes a mild method for the preparation of a wide range of pyridines employing a Co(I) active species generated in situ from a well-defined, air-stable Co(III) complex—namely, [CoCp*(CH3CN)(P-N)][BF4]2—upon treatment with NaBEt3H. This complex, which contains a hemilabile P-N ligand, has been found to be substantially more active than complexes featuring monodentate or bidentate phosphanes. This behavior has been ascribed to the inadequate stabilization of the resulting Co(I) species for the former, or overstabilization of the Co(III) complex in the case of the latter. A comprehensive DFT study has been conducted to elucidate the experimentally observed chemo- and regioselectivity by examining the competitive pathways following the oxidative coupling of CoCp*(bisalkyne) complex, taking under account the participation of triplet states and intersystem crossing points.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"48 1 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443949","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}
Ya-Zhen Zeng, Wang Zhang, Man-Yi Han, Peng Wang, Hanmin Huang
α-Carbonyl carbocations, serving as the umpolung forms of the synthetically fundamental α-carbonyl carbanions, are highly reactive species. The controlled generation and subsequent strategic employment of these reactive intermediates remain challenging. Herein, we report a photoredox-catalyzed approach for generating α-carbonyl carbocations from the corresponding α-carbonyl radicals through a single electron transfer (SET) oxidation process. These α-carbonyl radicals are readily accessible through radical addition to various α,β-unsaturated carbonyl compounds, including α,β-unsaturated esters, acid, amides and ketones. Furthermore, the Ritter reaction can be initiated by addition of acetonitrile to α-carbonyl carbocations, enabling the general synthesis of α-tertiary amino acid derivatives. This method features strong acid free, terminal oxidant free, mild conditions, visible light, without pre-functionalization, broad substrate scope, good group tolerance, etc. Moreover, further extention to the late-stage modifacation of natural products through this photoredox-catalyzed generation and utilization of α-carbonyl carbocations is also demonstrated.
{"title":"Photoredox-Catalyzed Generation of α-Carbonyl Carbocations: General Access to α-Tertiary Amino Acid Derivatives","authors":"Ya-Zhen Zeng, Wang Zhang, Man-Yi Han, Peng Wang, Hanmin Huang","doi":"10.1039/d4qo02306d","DOIUrl":"https://doi.org/10.1039/d4qo02306d","url":null,"abstract":"α-Carbonyl carbocations, serving as the umpolung forms of the synthetically fundamental α-carbonyl carbanions, are highly reactive species. The controlled generation and subsequent strategic employment of these reactive intermediates remain challenging. Herein, we report a photoredox-catalyzed approach for generating α-carbonyl carbocations from the corresponding α-carbonyl radicals through a single electron transfer (SET) oxidation process. These α-carbonyl radicals are readily accessible through radical addition to various α,β-unsaturated carbonyl compounds, including α,β-unsaturated esters, acid, amides and ketones. Furthermore, the Ritter reaction can be initiated by addition of acetonitrile to α-carbonyl carbocations, enabling the general synthesis of α-tertiary amino acid derivatives. This method features strong acid free, terminal oxidant free, mild conditions, visible light, without pre-functionalization, broad substrate scope, good group tolerance, etc. Moreover, further extention to the late-stage modifacation of natural products through this photoredox-catalyzed generation and utilization of α-carbonyl carbocations is also demonstrated.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"64 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435255","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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