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}
Mechanophoric hydrogels undergo visible color changes or alterations in optical properties in response to mechanical stimuli. Achieving mechanophoric features in hydrogel materials involves careful control of the polymer microstructure, as well as the incorporation of mechanoresponsive molecular entities known as mechanophores. Upon mechanical activation, mechanophores undergo reversible or irreversible molecular rearrangements, leading to a visual response. This review serves as a practical reference for selecting and designing mechanophores, and classifies their mode of action. By consolidating key information on molecular and materials design criteria, it focuses specifically on mechanophoric responses within hydrogel networks and provides insight into pioneering contributions, as well as some of the most recent advances and literature examples. The multidisciplinary nature of this rapidly growing research field requires expertise in organic synthesis, physical polymer chemistry and photophysics, making this review a valuable resource for researchers interested in the fundamental developments or applications of mechanophoric hydrogel materials.
{"title":"Mechanophoric hydrogels: when mechanical stress produces useful responses","authors":"Franciela Arenhart Soares, Pol Besenius","doi":"10.1039/d4qo02060j","DOIUrl":"https://doi.org/10.1039/d4qo02060j","url":null,"abstract":"Mechanophoric hydrogels undergo visible color changes or alterations in optical properties in response to mechanical stimuli. Achieving mechanophoric features in hydrogel materials involves careful control of the polymer microstructure, as well as the incorporation of mechanoresponsive molecular entities known as mechanophores. Upon mechanical activation, mechanophores undergo reversible or irreversible molecular rearrangements, leading to a visual response. This review serves as a practical reference for selecting and designing mechanophores, and classifies their mode of action. By consolidating key information on molecular and materials design criteria, it focuses specifically on mechanophoric responses within hydrogel networks and provides insight into pioneering contributions, as well as some of the most recent advances and literature examples. The multidisciplinary nature of this rapidly growing research field requires expertise in organic synthesis, physical polymer chemistry and photophysics, making this review a valuable resource for researchers interested in the fundamental developments or applications of mechanophoric hydrogel materials.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"6 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435253","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 this report, we describe a nickel-free, zinc-induced reductive coupling between (hetero)aryl diazonium salts and electrophilic chalcogen species under mild reaction conditions. This nonbasic protocol offers excellent chemoselectivity and substrate tolerance, yielding a broad spectrum of unsymmetrical diaryl and aryl–alkyl chalcogenides with good to excellent yields. Moreover, scale-up reactions, late-stage modifications of bioactive molecules and versatile product derivations have been conducted to showcase the practicality of this system. Preliminary mechanistic studies suggest the involvement of a single-electron transfer (SET) process from zinc to diazonium salts or the formation of zinc thiolate via oxidative addition of S–S bonds, revealing the versatile roles of zinc in this Sandmeyer-type sulfuration, which has been rarely studied.
{"title":"Zn-promoted Sandmeyer-type reductive chalcogenation of (hetero)aryl diazonium salts","authors":"Qiujin Fan, Yanchuang Zhao, Junhong Wang, Ying Bai, Shengbin Zhou, Xinxin Shao","doi":"10.1039/d5qo00103j","DOIUrl":"https://doi.org/10.1039/d5qo00103j","url":null,"abstract":"In this report, we describe a nickel-free, zinc-induced reductive coupling between (hetero)aryl diazonium salts and electrophilic chalcogen species under mild reaction conditions. This nonbasic protocol offers excellent chemoselectivity and substrate tolerance, yielding a broad spectrum of unsymmetrical diaryl and aryl–alkyl chalcogenides with good to excellent yields. Moreover, scale-up reactions, late-stage modifications of bioactive molecules and versatile product derivations have been conducted to showcase the practicality of this system. Preliminary mechanistic studies suggest the involvement of a single-electron transfer (SET) process from zinc to diazonium salts or the formation of zinc thiolate <em>via</em> oxidative addition of S–S bonds, revealing the versatile roles of zinc in this Sandmeyer-type sulfuration, which has been rarely studied.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"13 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435254","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}
Honglin Qiu, Jiadong Zhou, Yi Feng, Linlin Liu, Zengqi Xie
This article presents the successful synthesis of a novel series of core-extended quasi-planar nonastarazine (NSA) derivatives, featuring diverse arm configurations, through one-pot sequential reactions. Analysis of their single-crystal structures reveals that the three arms are nearly coplanar, ensuring good conjugation for this series of molecules. The UV-vis absorption and photoluminescence spectra of these NSA derivatives indicate that their photophysical properties are primarily dominated by the extended arms, a finding supported by theoretical calculations of frontier orbital energy levels. The designable topological molecule structures and excellent fluorescence properties of these core-extended NSAs endow them high potentials for applications in molecular electronics.
{"title":"Core-Extended Nonastarazines Featuring Diverse Arm Configurations via One-Pot Sequential Reactions","authors":"Honglin Qiu, Jiadong Zhou, Yi Feng, Linlin Liu, Zengqi Xie","doi":"10.1039/d4qo02403f","DOIUrl":"https://doi.org/10.1039/d4qo02403f","url":null,"abstract":"This article presents the successful synthesis of a novel series of core-extended quasi-planar nonastarazine (NSA) derivatives, featuring diverse arm configurations, through one-pot sequential reactions. Analysis of their single-crystal structures reveals that the three arms are nearly coplanar, ensuring good conjugation for this series of molecules. The UV-vis absorption and photoluminescence spectra of these NSA derivatives indicate that their photophysical properties are primarily dominated by the extended arms, a finding supported by theoretical calculations of frontier orbital energy levels. The designable topological molecule structures and excellent fluorescence properties of these core-extended NSAs endow them high potentials for applications in molecular electronics.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"31 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435256","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-Li Hu, Ding Dong, Jian-Jun Zhao, Kun Hu, Ling-Mei Kong, Yun-Xia Hu, Xing-Ren Li, Song-Yu Li, Yin Nian, Gang Xu
Ascynols A–C (1–3), three polycyclic polyprenylated acylphloroglucinol (PPAP) derivatives sharing an unusual cyclopentane core, were isolated from the aerial parts of Hypericum ascyron L. Compounds 1 and 3 were elucidated to possess two novel 6/6/5/5 and 5/5 architectures, respectively. Additionally, twenty-four analogues (4–27) were also obtained, among which fourteen are new compounds. These compounds represent 11 different structural types and can be categorized into 6 groups based on their biosynthetic origin. Their structures were determined from spectroscopic analysis, quantum chemical calculation, and X-ray diffraction data. All the isolates are decorated with a methyl group at C-5 instead of a prenyl or geranyl group as in most other PPAPs. Biologically, sixteen compounds were identified as potent inhibitors of low-voltage-gated calcium channels (LVGCCs; Cav3.1–3.3), with IC50 values ranging from 1.89 to 16.55 μmol L−1. Moreover, compound 23 exhibited strong and dose-dependent antinociception in an acetic acid-induced mouse model of visceral pain and its effect is comparable to that of Z944, a representative LVGCC inhibitor under clinical trial.
{"title":"5-Methylated polyprenylated acylphloroglucinol derivatives as low-voltage-gated Ca2+ channel inhibitors","authors":"Ya-Li Hu, Ding Dong, Jian-Jun Zhao, Kun Hu, Ling-Mei Kong, Yun-Xia Hu, Xing-Ren Li, Song-Yu Li, Yin Nian, Gang Xu","doi":"10.1039/d4qo02233e","DOIUrl":"https://doi.org/10.1039/d4qo02233e","url":null,"abstract":"Ascynols A–C (<strong>1–3</strong>), three polycyclic polyprenylated acylphloroglucinol (PPAP) derivatives sharing an unusual cyclopentane core, were isolated from the aerial parts of <em>Hypericum ascyron</em> L. Compounds <strong>1</strong> and <strong>3</strong> were elucidated to possess two novel 6/6/5/5 and 5/5 architectures, respectively. Additionally, twenty-four analogues (<strong>4–27</strong>) were also obtained, among which fourteen are new compounds. These compounds represent 11 different structural types and can be categorized into 6 groups based on their biosynthetic origin. Their structures were determined from spectroscopic analysis, quantum chemical calculation, and X-ray diffraction data. All the isolates are decorated with a methyl group at C-5 instead of a prenyl or geranyl group as in most other PPAPs. Biologically, sixteen compounds were identified as potent inhibitors of low-voltage-gated calcium channels (LVGCCs; Ca<small><sub>v</sub></small>3.1–3.3), with IC<small><sub>50</sub></small> values ranging from 1.89 to 16.55 μmol L<small><sup>−1</sup></small>. Moreover, compound <strong>23</strong> exhibited strong and dose-dependent antinociception in an acetic acid-induced mouse model of visceral pain and its effect is comparable to that of Z944, a representative LVGCC inhibitor under clinical trial.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"64 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427069","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}
Julio C. Flores-Reyes, Yoarhy A. Amador-Sánchez, Alejandro Valderrama-Celestino, Bertha Daniela Barrios-Campos, Ricardo A. Peralta, Michael Huxley, Ilich A. Ibarra, Alejandro Islas-Jácome, Diego Solis-Ibarra, Eduardo González-Zamora
The dual-state emission (DSE) phenomenon has become crucial for developing dual-state emission luminogens (DSEgens) that exhibit efficient luminescence in both solution and solid states, addressing the limitations of conventional, phase-restricted fluorophores. Compounds exhibiting excited-state intramolecular proton transfer (ESIPT) mechanisms are especially valuable for enhancing emission stability across these states, offering significant potential in optoelectronics, bioimaging, and sensing applications. In this study, we report the synthesis of six new pyrazolyl-pyrrolo[3,4-b]pyridin-5-ones through an Ugi-Zhu-3CR coupled to an aza-Diels-Alder/N-acylation/decarboxylation/dehydration cascade sequence. An x-ray ORTEP confirms unequivocally the structure of one of the synthesized compounds. These ones demonstrate intriguing photophysical properties such as large Stokes shifts (>11,900 cm⁻¹) in solution and robust solid-state emission via Excited-State Intramolecular Proton Transfer (ESIPT) mechanism. Complementary DFT and TD-DFT calculations confirm weak but allowed transitions involving both pyrazole and pyrrolo[3,4-b]pyridin-5-one moieties, in agreement with experimental observations. This work represents the first application of an isocyanide-based multicomponent reaction for DSEgen synthesis, paving the way for innovative advances in the design of organic luminescent materials.
{"title":"Dual-State Emission of Pyrazolyl-Pyrrolo[3,4-b]pyridin-5-ones via Excited-State Intramolecular Proton Transfer (ESIPT): Multicomponent Synthesis and Optical Characterization","authors":"Julio C. Flores-Reyes, Yoarhy A. Amador-Sánchez, Alejandro Valderrama-Celestino, Bertha Daniela Barrios-Campos, Ricardo A. Peralta, Michael Huxley, Ilich A. Ibarra, Alejandro Islas-Jácome, Diego Solis-Ibarra, Eduardo González-Zamora","doi":"10.1039/d4qo02256d","DOIUrl":"https://doi.org/10.1039/d4qo02256d","url":null,"abstract":"The dual-state emission (DSE) phenomenon has become crucial for developing dual-state emission luminogens (DSEgens) that exhibit efficient luminescence in both solution and solid states, addressing the limitations of conventional, phase-restricted fluorophores. Compounds exhibiting excited-state intramolecular proton transfer (ESIPT) mechanisms are especially valuable for enhancing emission stability across these states, offering significant potential in optoelectronics, bioimaging, and sensing applications. In this study, we report the synthesis of six new pyrazolyl-pyrrolo[3,4-b]pyridin-5-ones through an Ugi-Zhu-3CR coupled to an aza-Diels-Alder/N-acylation/decarboxylation/dehydration cascade sequence. An x-ray ORTEP confirms unequivocally the structure of one of the synthesized compounds. These ones demonstrate intriguing photophysical properties such as large Stokes shifts (>11,900 cm⁻¹) in solution and robust solid-state emission via Excited-State Intramolecular Proton Transfer (ESIPT) mechanism. Complementary DFT and TD-DFT calculations confirm weak but allowed transitions involving both pyrazole and pyrrolo[3,4-b]pyridin-5-one moieties, in agreement with experimental observations. This work represents the first application of an isocyanide-based multicomponent reaction for DSEgen synthesis, paving the way for innovative advances in the design of organic luminescent materials.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"80 1 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435257","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}
Heteroaromatic installation and peripheral modifications are the most common reactions in the pharmaceutical industry. However, the synthesis of biologically important aminonitrile-functionalized heteroaromatics remains unexplored. Although nucleophilic aminonitrile introduction and Strecker reaction under enantioselective catalytic conditions enable facile access to chiral aminonitriles, these approaches largely disfavor substrates with highly steric substituents on the imine carbon atom, thus affording limited products. Herein, we report an efficient and versatile method that combines the traditional methods to generate α-aryl-α-heteroaryl-aminonitriles. This methodology exhibits a broad scope and can form bonds even when using low-reactive Friedel–Crafts nucleophiles through a mild and practical protocol. It should be highlighted that the catalyst loading could be reduced to parts per billion, giving rise to phenomenal turn-over-number (TON) and turn-over-frequency (TOF) values. Interestingly, different stereochemistries between the pyrrole and indole adducts were obtained with the same (R)-derived chiral phosphoric acid catalysis. Computational studies have indicated that this unpredicted stereoreversal is due to the coordination system between iminonitriles and catalysts, helping us understand the origin of the stereochemical outcome of the traditional Friedel–Crafts reaction.
{"title":"Enantioselective modular synthesis of α-aryl-α-heteroaryl aminonitriles with parts per million organocatalyst loading: mechanistic investigation for stereochemical origins","authors":"Yusuke Oyamada, Kaito Ishikawa, Tsunayoshi Takehara, Takeyuki Suzuki, Shuichi Nakamura","doi":"10.1039/d4qo02362e","DOIUrl":"https://doi.org/10.1039/d4qo02362e","url":null,"abstract":"Heteroaromatic installation and peripheral modifications are the most common reactions in the pharmaceutical industry. However, the synthesis of biologically important aminonitrile-functionalized heteroaromatics remains unexplored. Although nucleophilic aminonitrile introduction and Strecker reaction under enantioselective catalytic conditions enable facile access to chiral aminonitriles, these approaches largely disfavor substrates with highly steric substituents on the imine carbon atom, thus affording limited products. Herein, we report an efficient and versatile method that combines the traditional methods to generate α-aryl-α-heteroaryl-aminonitriles. This methodology exhibits a broad scope and can form bonds even when using low-reactive Friedel–Crafts nucleophiles through a mild and practical protocol. It should be highlighted that the catalyst loading could be reduced to parts per billion, giving rise to phenomenal turn-over-number (TON) and turn-over-frequency (TOF) values. Interestingly, different stereochemistries between the pyrrole and indole adducts were obtained with the same (<em>R</em>)-derived chiral phosphoric acid catalysis. Computational studies have indicated that this unpredicted stereoreversal is due to the coordination system between iminonitriles and catalysts, helping us understand the origin of the stereochemical outcome of the traditional Friedel–Crafts reaction.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"3 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427068","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}
Diazo compounds are a class of readily available and versatile reagents in modern organic synthesis that have been used as valuable synthetic building blocks for a diverse range of important organic transformations due to their convenient preparation and high reactivity. In this review, the advancements in the synthesis of nitrogen-containing heterocycles via Rh(III)-catalyzed chelation-assisted tandem C-H activation/carbene insertion/annulation with diazo compounds as carbene precursors have been summarized. A variety of structurally diverse nitrogen heterocyclic scaffolds, such as indoles, isoindolones, carbazoles, isoquinolines, isoquinolones, 2H-indazoles, indazolones, cinnolines, 2,3-benzodiazepines, azepines, diazepinones can be easily prepared from different diazo compounds in a highly efficient and environmentally benign manner.
{"title":"Recent advances in the synthesis of nitrogen heterocycles via Rh(III)-catalyzed chelation-assisted C-H activation/annulation with diazo compounds","authors":"Jidan Liu, Ruilian Liang, Qinglian Yan, Liyao Zheng, Zhao-Qing Liu, Shouzhi Pu","doi":"10.1039/d5qo00111k","DOIUrl":"https://doi.org/10.1039/d5qo00111k","url":null,"abstract":"Diazo compounds are a class of readily available and versatile reagents in modern organic synthesis that have been used as valuable synthetic building blocks for a diverse range of important organic transformations due to their convenient preparation and high reactivity. In this review, the advancements in the synthesis of nitrogen-containing heterocycles via Rh(III)-catalyzed chelation-assisted tandem C-H activation/carbene insertion/annulation with diazo compounds as carbene precursors have been summarized. A variety of structurally diverse nitrogen heterocyclic scaffolds, such as indoles, isoindolones, carbazoles, isoquinolines, isoquinolones, 2H-indazoles, indazolones, cinnolines, 2,3-benzodiazepines, azepines, diazepinones can be easily prepared from different diazo compounds in a highly efficient and environmentally benign manner.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"9 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427067","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：