Juliane S. Falcão, Marcos V. O. Da Silva, Edivaldo S. Dos Santos Rodrigues, Osvaldo A. Santos-Filho, Paulo Costa, Guilherme S Caleffi
A mild and highly efficient one-pot asymmetric transfer hydrogenation (ATH) of challenging, electron-rich 3arylidenechroman-4-ones is reported. The protocol utilizes a Ru(II)-catalyst under neutral conditions (HCO₂Na) to reduce both the C=C and C=O bonds, affording valuable cis-3-benzylchroman-4-ols with excellent diastereo-and enantioselectivities (up to 99:1 er). The key to this success was the strategic use of intramolecular hydrogen bonding; we discovered that a C2'phenol forms an unprecedented eight-membered pseudo-ring that acts as a powerful directing group for the ketone reduction. This new mechanistic principle was rigorously supported by DFT calculations of reactivity descriptors and transition state energies. The protocol's synthetic utility was showcased in the enantioselective total syntheses of five homoisoflavonoids, enabling the first stereochemical assignment of Portulacanones A and B and the synthesis of (+)-Brazilane, which clarifies its absolute configuration in the literature.
{"title":"Asymmetric Transfer Hydrogenation of Polyoxygenated 3-Arylidenechroman-4-ones: A Powerful Tool for the Total Synthesis of Natural Homoisoflavonoids","authors":"Juliane S. Falcão, Marcos V. O. Da Silva, Edivaldo S. Dos Santos Rodrigues, Osvaldo A. Santos-Filho, Paulo Costa, Guilherme S Caleffi","doi":"10.1039/d5qo01629k","DOIUrl":"https://doi.org/10.1039/d5qo01629k","url":null,"abstract":"A mild and highly efficient one-pot asymmetric transfer hydrogenation (ATH) of challenging, electron-rich 3arylidenechroman-4-ones is reported. The protocol utilizes a Ru(II)-catalyst under neutral conditions (HCO₂Na) to reduce both the C=C and C=O bonds, affording valuable cis-3-benzylchroman-4-ols with excellent diastereo-and enantioselectivities (up to 99:1 er). The key to this success was the strategic use of intramolecular hydrogen bonding; we discovered that a C2'phenol forms an unprecedented eight-membered pseudo-ring that acts as a powerful directing group for the ketone reduction. This new mechanistic principle was rigorously supported by DFT calculations of reactivity descriptors and transition state energies. The protocol's synthetic utility was showcased in the enantioselective total syntheses of five homoisoflavonoids, enabling the first stereochemical assignment of Portulacanones A and B and the synthesis of (+)-Brazilane, which clarifies its absolute configuration in the literature.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"123 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145813188","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}
Raquel Pérez Guevara, Diego Folgueira Iravedra, Lorena Alonso-Marañon, Montserrat Martínez, José Pérez Sestelo
A tandem indium(III)-catalyzed cyclization and intermolecular hydrofunctionalization of 1,6-enynes for the stereoselective synthesis of functionalized carbo- and heterocycles is reported. The synthetic transformation involves a regio- and stereoselective 5-exo-dig 1,6-enyne cyclization followed by intermolecular nucleophilic addition of alcohols (including water), carboxylic acids, arenes and trimethylsilyl azide. Remarkably, the reaction proceeds under mild reaction conditions with low catalyst loading (5 mol%) using unexpensive commercial indium(III) halides in good yields with broad chemoselectivity and high regio- and stereoselectivity,
{"title":"Tandem indium(III)-catalyzed cyclization and intermolecular hydrofunctionalization of 1,6-enynes","authors":"Raquel Pérez Guevara, Diego Folgueira Iravedra, Lorena Alonso-Marañon, Montserrat Martínez, José Pérez Sestelo","doi":"10.1039/d5qo01388g","DOIUrl":"https://doi.org/10.1039/d5qo01388g","url":null,"abstract":"A tandem indium(III)-catalyzed cyclization and intermolecular hydrofunctionalization of 1,6-enynes for the stereoselective synthesis of functionalized carbo- and heterocycles is reported. The synthetic transformation involves a regio- and stereoselective 5-exo-dig 1,6-enyne cyclization followed by intermolecular nucleophilic addition of alcohols (including water), carboxylic acids, arenes and trimethylsilyl azide. Remarkably, the reaction proceeds under mild reaction conditions with low catalyst loading (5 mol%) using unexpensive commercial indium(III) halides in good yields with broad chemoselectivity and high regio- and stereoselectivity,","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"28 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145813190","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}
Liyuan Meng, Ran Fang, Simeng Qi, Yuanjun Song, Lizi Yang
The copper-catalyzed boronation of conjugated trienes offers a promising route to organoboron compounds but is often limited by selectivity challenges. While previous studies have demonstrated its potential, a detailed mechanistic understanding of regioselectivity and stereoselectivity has been lacking. In this study, we present a comprehensive density functional theory (DFT) investigation that clarifies the reaction mechanism and the key factors influencing selectivity. Our calculations reveal a unified catalytic cycle involving η²-coordination of the copper-boryl catalyst, migratory insertion, 1,3-copper migration, and methanol-assisted protonation. The 3,4-insertion step is found to be kinetically favored, with final product selectivity determined in the later stages of the reaction. Regioselectivity is governed by electronic effects during protonation, while stereoselectivity is driven by non-covalent interactions during 1,3-copper migration. Subtle modifications, such as adding an aryl group adjacent to the boron, can reverse stereoselectivity by altering these interactions. Ligand choice also plays a critical role: bulkier N-heterocyclic carbene (NHC) ligands stabilize transition states, enhancing selectivity, while triphenylphosphine (PPh₃) ligands lead to multiple competing pathways. Additionally, the pre-existing boron group actively regulates regioselectivity by stabilizing intermediate states, favoring 1,4-regioselectivity. These insights provide a framework for designing catalytic systems that enable selective functionalization of polyunsaturated substrates.
{"title":"Theoretical Insights into the Cu-Catalyzed Boronation of Conjugated Trienes: Mechanism and Selectivity Control","authors":"Liyuan Meng, Ran Fang, Simeng Qi, Yuanjun Song, Lizi Yang","doi":"10.1039/d5qo01600b","DOIUrl":"https://doi.org/10.1039/d5qo01600b","url":null,"abstract":"The copper-catalyzed boronation of conjugated trienes offers a promising route to organoboron compounds but is often limited by selectivity challenges. While previous studies have demonstrated its potential, a detailed mechanistic understanding of regioselectivity and stereoselectivity has been lacking. In this study, we present a comprehensive density functional theory (DFT) investigation that clarifies the reaction mechanism and the key factors influencing selectivity. Our calculations reveal a unified catalytic cycle involving η²-coordination of the copper-boryl catalyst, migratory insertion, 1,3-copper migration, and methanol-assisted protonation. The 3,4-insertion step is found to be kinetically favored, with final product selectivity determined in the later stages of the reaction. Regioselectivity is governed by electronic effects during protonation, while stereoselectivity is driven by non-covalent interactions during 1,3-copper migration. Subtle modifications, such as adding an aryl group adjacent to the boron, can reverse stereoselectivity by altering these interactions. Ligand choice also plays a critical role: bulkier N-heterocyclic carbene (NHC) ligands stabilize transition states, enhancing selectivity, while triphenylphosphine (PPh₃) ligands lead to multiple competing pathways. Additionally, the pre-existing boron group actively regulates regioselectivity by stabilizing intermediate states, favoring 1,4-regioselectivity. These insights provide a framework for designing catalytic systems that enable selective functionalization of polyunsaturated substrates.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"45 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145813189","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}
Functionalization of the C(sp2)–H bond is a challenging yet highly useful synthetic task due to its relative inertness and commonality among functional groups. Arene thianthrenation is an emerging C(sp2)–H bond activation strategy featuring high chemo- and regioselectivity in the modification of structurally diverse substrates. The resultant aryl thianthrenium (Ar–TT⁺) salts exhibit divergent single- and two-electron reactivity modes, which have enabled new C(sp2)–bond formation to the main group elements through mechanistically distinct routes. This review complements the existing literature on the two-electron behavior of Ar–TT⁺ salts by highlighting the enhanced control of radical reactivity achieved in the site-selective thianthrenation of arenes and subsequent C(sp2)–S bond homolysis to generate aryl radicals. Discussion of the structural and electronic properties of Ar–TT⁺ salts promoting single-electron reactivity under mild conditions, functional group tolerance, enhanced platform cross-compatibility, and increased potential for sustainability through catalysis is a thematic focus throughout. Identification of these prior methodological advancements culminates in a prospectus on the opportunities for future reaction development.
{"title":"Radical Reactivity of Aryl Thianthrenium Salts","authors":"Ryan A Pohorenec, Shiqing Xu","doi":"10.1039/d5qo01417d","DOIUrl":"https://doi.org/10.1039/d5qo01417d","url":null,"abstract":"Functionalization of the C(sp2)–H bond is a challenging yet highly useful synthetic task due to its relative inertness and commonality among functional groups. Arene thianthrenation is an emerging C(sp2)–H bond activation strategy featuring high chemo- and regioselectivity in the modification of structurally diverse substrates. The resultant aryl thianthrenium (Ar–TT⁺) salts exhibit divergent single- and two-electron reactivity modes, which have enabled new C(sp2)–bond formation to the main group elements through mechanistically distinct routes. This review complements the existing literature on the two-electron behavior of Ar–TT⁺ salts by highlighting the enhanced control of radical reactivity achieved in the site-selective thianthrenation of arenes and subsequent C(sp2)–S bond homolysis to generate aryl radicals. Discussion of the structural and electronic properties of Ar–TT⁺ salts promoting single-electron reactivity under mild conditions, functional group tolerance, enhanced platform cross-compatibility, and increased potential for sustainability through catalysis is a thematic focus throughout. Identification of these prior methodological advancements culminates in a prospectus on the opportunities for future reaction development.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"31 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796443","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 straightforward protocol for accessing imidazo[2,1-b][1,3,4]thiadiazoles via I2-catalyzed tandem Michael addition-oxidative cyclization has been developed. Three-component approach to access imidazo[2,1-b][1,3,4]thiadiazoles from hydrazone, chalcone, and KSCN has been demonstrated. Both I2 and DMSO are essential and the reaction progressed through a radical pathway. The strategy is also extendable towards the synthesis of imidazo[1,2-a]pyridine and benzo[d]imidazo[2,1-b]thiazole derivatives. Wide functional group tolerances, the use of simple and unfunctionalized building blocks and inexpensive catalyst, large-scalability, and easy execution are the notable features of this approach.
{"title":"I2/DMSO-Enabled Cascade Michael Addition/Oxidative Cyclization: Access to Imidazo[2,1-b][1,3,4]thiadiazoles","authors":"Sourav Das, Suvam Paul, Tathagata Choudhuri, Ramendra Pratap, Avik Kumar Bagdi","doi":"10.1039/d5qo01432h","DOIUrl":"https://doi.org/10.1039/d5qo01432h","url":null,"abstract":"A straightforward protocol for accessing imidazo[2,1-b][1,3,4]thiadiazoles via I2-catalyzed tandem Michael addition-oxidative cyclization has been developed. Three-component approach to access imidazo[2,1-b][1,3,4]thiadiazoles from hydrazone, chalcone, and KSCN has been demonstrated. Both I2 and DMSO are essential and the reaction progressed through a radical pathway. The strategy is also extendable towards the synthesis of imidazo[1,2-a]pyridine and benzo[d]imidazo[2,1-b]thiazole derivatives. Wide functional group tolerances, the use of simple and unfunctionalized building blocks and inexpensive catalyst, large-scalability, and easy execution are the notable features of this approach.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"37 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801453","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}
Jianquan Hong, Feng Zheng, Xiaoyu Wang, Pengyang Cao, Dejing Yin, Wenqi Li, Xiaoxu Liu, Qiang Wang, Jie Wang and Changge Zheng
A simple and practical synthetic method for the construction of N-trifluoromethylthio-1H-isochromen-1-imines from o-alkynyl aryl primary amides using N-trifluoromethylthiolation/iminolactonization was developed. This unique strategy possesses a broad substrate scope, excellent compatibility, and operational simplicity, providing convenient access to target compounds in moderate to excellent yields.
以炔基芳基伯胺和n-三氟甲基硫代为原料，建立了一种简单实用的合成n-三氟甲基硫代- h -异色胺的方法。这种独特的n -三氟甲基硫酰化和亚内酯化策略具有广泛的底物范围，良好的相容性和操作简单性，为中等至优异收率的目标化合物提供了方便的途径。
{"title":"Synthesis of N-trifluoromethylthio-1H-isochromen-1-imines via N-trifluoromethylthiolation/iminolactonization of o-alkynyl aryl amides with N-trifluoromethylthiosaccharin","authors":"Jianquan Hong, Feng Zheng, Xiaoyu Wang, Pengyang Cao, Dejing Yin, Wenqi Li, Xiaoxu Liu, Qiang Wang, Jie Wang and Changge Zheng","doi":"10.1039/D5QO01223F","DOIUrl":"10.1039/D5QO01223F","url":null,"abstract":"<p >A simple and practical synthetic method for the construction of <em>N</em>-trifluoromethylthio-1<em>H</em>-isochromen-1-imines from <em>o</em>-alkynyl aryl primary amides using <em>N</em>-trifluoromethylthiolation/iminolactonization was developed. This unique strategy possesses a broad substrate scope, excellent compatibility, and operational simplicity, providing convenient access to target compounds in moderate to excellent yields.</p>","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":" 3","pages":" 1029-1034"},"PeriodicalIF":4.7,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785958","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}
Xiaoli Su, Wei Wei, Zhaojun Ding, Jiazan Li, Jinlian Li, Jiayu Mo
Electrosynthesis, which facilitates redox events in metal-catalyst free conditions, has garnered significant interest. Herein, we explore this promising methodology by introducing an application of paired electrolysis for the cross-coupling of nitroarenes with alkyl bromides. This approach enables the synthesis of aromatic tertiary amines from readily available and cost-effective starting materials under mild redox conditions. By leveraging the advantages of electrosynthesis, we achieve efficient transformations with good functional group compatibility, thereby contributing to the sustainable modification of valuable bioactive molecules.
{"title":"Electrochemically driven reductive coupling of nitroarenes with alkyl bromides","authors":"Xiaoli Su, Wei Wei, Zhaojun Ding, Jiazan Li, Jinlian Li, Jiayu Mo","doi":"10.1039/d5qo01269d","DOIUrl":"https://doi.org/10.1039/d5qo01269d","url":null,"abstract":"Electrosynthesis, which facilitates redox events in metal-catalyst free conditions, has garnered significant interest. Herein, we explore this promising methodology by introducing an application of paired electrolysis for the cross-coupling of nitroarenes with alkyl bromides. This approach enables the synthesis of aromatic tertiary amines from readily available and cost-effective starting materials under mild redox conditions. By leveraging the advantages of electrosynthesis, we achieve efficient transformations with good functional group compatibility, thereby contributing to the sustainable modification of valuable bioactive molecules.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"18 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785959","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}
Asymmetric dearomatization reactions (CADA) have become fundamental chemical transformations in organic synthesis to rapidly assemble structurally diverse chiral carbocycles and heterocycles found in a plethora of bioactive molecules. Aromatic nitro compounds, which are readily available starting materials in both industrial and academic society, have been proved to be reactive towards various reaction partners, facilitating a range of asymmetric dearomatization reactions. Moreover, the nitro group in the products serves as a handle for further synthetic transformation, paving the way to valuable N-containing molecules. In this review, we systematically summarize recent advances in nitro(hetero)arenes-enabled CADA, with a detailed discussion of diverse types of reactions, involving asymmetric cycloaddition, asymmetric Michael addition, and asymmetric interrupted Barton-Zard reaction. The reaction mechanisms, substrate scope, and practical applications of these transformations are comprehensively analyzed. Finally, we offer insights into the current limitations of this field, which are expected to inspire further exploratory research.
{"title":"Recent Advances in Asymmetric Dearomatization of Nitro(hetero)arenes","authors":"Huamin Wang, Hongding xie, Su-Min Guo, Rui Duan, Ying-Wu Lin, Junliang Zhang","doi":"10.1039/d5qo01566a","DOIUrl":"https://doi.org/10.1039/d5qo01566a","url":null,"abstract":"Asymmetric dearomatization reactions (CADA) have become fundamental chemical transformations in organic synthesis to rapidly assemble structurally diverse chiral carbocycles and heterocycles found in a plethora of bioactive molecules. Aromatic nitro compounds, which are readily available starting materials in both industrial and academic society, have been proved to be reactive towards various reaction partners, facilitating a range of asymmetric dearomatization reactions. Moreover, the nitro group in the products serves as a handle for further synthetic transformation, paving the way to valuable N-containing molecules. In this review, we systematically summarize recent advances in nitro(hetero)arenes-enabled CADA, with a detailed discussion of diverse types of reactions, involving asymmetric cycloaddition, asymmetric Michael addition, and asymmetric interrupted Barton-Zard reaction. The reaction mechanisms, substrate scope, and practical applications of these transformations are comprehensively analyzed. Finally, we offer insights into the current limitations of this field, which are expected to inspire further exploratory research.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"9 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785957","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}
Chenglin Wu, Jiawen Gu, Shijie Ni, Zhe Sheng, Liu Wang, Wei Xie, Yixin Xu and Xiaoming Xin
Benzohydroxamic acid represents an inexpensive and readily available reagent. Herein, a novel, metal- and base-free amination of maleimide with benzohydroxamic acid has been established. This method features environmental friendliness, mild conditions, and operational simplicity, affording a series of aminomaleimides in good yields with broad functional group compatibility. Previous studies on C–N bond construction have primarily relied on the coupling of C–X (X = hydrogen, halogen, boron, sulfonate, carboxyl, etc.) with N–H. In contrast, the present work represents a rare example of C–N bond formation via C–H/N–Y (Y ≠ H) coupling.
{"title":"Metal-, oxidant- and base-free direct C–H amination of maleimides enabled by versatile benzohydroxamic acids","authors":"Chenglin Wu, Jiawen Gu, Shijie Ni, Zhe Sheng, Liu Wang, Wei Xie, Yixin Xu and Xiaoming Xin","doi":"10.1039/D5QO01525A","DOIUrl":"10.1039/D5QO01525A","url":null,"abstract":"<p >Benzohydroxamic acid represents an inexpensive and readily available reagent. Herein, a novel, metal- and base-free amination of maleimide with benzohydroxamic acid has been established. This method features environmental friendliness, mild conditions, and operational simplicity, affording a series of aminomaleimides in good yields with broad functional group compatibility. Previous studies on C–N bond construction have primarily relied on the coupling of C–X (X = hydrogen, halogen, boron, sulfonate, carboxyl, <em>etc</em>.) with N–H. In contrast, the present work represents a rare example of C–N bond formation <em>via</em> C–H/N–Y (Y ≠ H) coupling.</p>","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":" 3","pages":" 997-1002"},"PeriodicalIF":4.7,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785961","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}
The direct functionalization of C(sp3)–H bonds in amines has emerged as a powerful and atom-economical strategy for constructing structurally diverse nitrogen-containing molecules without requiring prefunctionalized substrates. Over the past decade, visible-light photoredox catalysis has evolved into a versatile platform for such transformations, offering high functional-group tolerance, mild reaction conditions, and distinct modes of ionic and radical activation. This review provides a comprehensive, mechanism-oriented summary of recent developments in photoredox-catalyzed C(sp3)–H functionalization of amines. We focus on three principal mechanistic pathways: (i) Iminium-ion pathways, involving the reaction of electrophilic iminium intermediates with nucleophiles; (ii) Enamine pathways, wherein iminium intermediates undergo tautomerization to nucleophilic enamine species that react with electrophilic partners;; (iii) Radical pathways, featuring coupling or addition processes mediated by radical species; (iv) Carbanion pathways, where nucleophilic carbanions engage electrophilic partners. These strategies collectively enable a diverse range of C–C and C–X bond-forming reactions—including alkylation, arylation, alkenylation, acylation, phosphonylation, alkynylation, cyanation, carboxylation, amination, boronation, and oxidation. Particular emphasis is placed on advances in asymmetric catalysis, cooperative metal–photoredox systems, and radical–radical cross-coupling. We also critically examine persistent challenges—such as achieving regio- and stereocontrol, expanding substrate scope, and enhancing sustainability—and outline future opportunities for innovation. By integrating mechanistic insight with synthetic scope, this review establishes a framework for the rational design of next-generation catalytic systems, underscoring the transformative potential of photoredox catalysis in late-stage functionalization, medicinal chemistry, and green synthesis.
{"title":"Photoredox-Enabled C(sp³)–H Functionalization of Amines through Iminium Ions, Radicals, and Carbanions","authors":"Chen Xue-Ying, Yan Zhang, Gao Chao, Guo-Qiang Xu","doi":"10.1039/d5qo01507c","DOIUrl":"https://doi.org/10.1039/d5qo01507c","url":null,"abstract":"The direct functionalization of C(sp3)–H bonds in amines has emerged as a powerful and atom-economical strategy for constructing structurally diverse nitrogen-containing molecules without requiring prefunctionalized substrates. Over the past decade, visible-light photoredox catalysis has evolved into a versatile platform for such transformations, offering high functional-group tolerance, mild reaction conditions, and distinct modes of ionic and radical activation. This review provides a comprehensive, mechanism-oriented summary of recent developments in photoredox-catalyzed C(sp3)–H functionalization of amines. We focus on three principal mechanistic pathways: (i) Iminium-ion pathways, involving the reaction of electrophilic iminium intermediates with nucleophiles; (ii) Enamine pathways, wherein iminium intermediates undergo tautomerization to nucleophilic enamine species that react with electrophilic partners;; (iii) Radical pathways, featuring coupling or addition processes mediated by radical species; (iv) Carbanion pathways, where nucleophilic carbanions engage electrophilic partners. These strategies collectively enable a diverse range of C–C and C–X bond-forming reactions—including alkylation, arylation, alkenylation, acylation, phosphonylation, alkynylation, cyanation, carboxylation, amination, boronation, and oxidation. Particular emphasis is placed on advances in asymmetric catalysis, cooperative metal–photoredox systems, and radical–radical cross-coupling. We also critically examine persistent challenges—such as achieving regio- and stereocontrol, expanding substrate scope, and enhancing sustainability—and outline future opportunities for innovation. By integrating mechanistic insight with synthetic scope, this review establishes a framework for the rational design of next-generation catalytic systems, underscoring the transformative potential of photoredox catalysis in late-stage functionalization, medicinal chemistry, and green synthesis.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"29 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145785960","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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