Unproductive consumption of catalysts is a common hurdle in developing efficient catalytic reactions. In the realm of N-heterocyclic carbene (NHC) organic catalysis, attention has mainly been focused on the involvement of air (oxygen) and water in the deactivation (unproductive consumption) of the catalysts. Here, we disclose that the carbene catalyst can react with sulfonates via a redox process that converts NHCs into the corresponding urea molecules. This process involves rather complicated steps that ultimately transfer the oxygen atom from the sulfonate to the carbene. NHCs with different structures exhibit varying degrees of tendency in the oxidation process. Since many substrates and reagents involved in NHC catalysis possess oxidizing abilities, our study suggests that investigating potential redox processes of NHC catalysts is crucial for developing future generations of effective NHC catalysts and reactions. Our study also offers new mechanistic insights into the possible reactivities of NHCs and their adducts with other molecules.
{"title":"Redox reaction between N-heterocyclic carbenes and sulfonates: insights into unproductive catalytic paths","authors":"Jia Song, Wei Wang, Guanjie Wang, Wen-Xin Lv","doi":"10.1039/d4qo02196g","DOIUrl":"https://doi.org/10.1039/d4qo02196g","url":null,"abstract":"Unproductive consumption of catalysts is a common hurdle in developing efficient catalytic reactions. In the realm of N-heterocyclic carbene (NHC) organic catalysis, attention has mainly been focused on the involvement of air (oxygen) and water in the deactivation (unproductive consumption) of the catalysts. Here, we disclose that the carbene catalyst can react with sulfonates <em>via</em> a redox process that converts NHCs into the corresponding urea molecules. This process involves rather complicated steps that ultimately transfer the oxygen atom from the sulfonate to the carbene. NHCs with different structures exhibit varying degrees of tendency in the oxidation process. Since many substrates and reagents involved in NHC catalysis possess oxidizing abilities, our study suggests that investigating potential redox processes of NHC catalysts is crucial for developing future generations of effective NHC catalysts and reactions. Our study also offers new mechanistic insights into the possible reactivities of NHCs and their adducts with other molecules.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"77 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987270","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}
Mengzhe Pan, Feng-Wei Guo, Xinjie Sun, Jie Zhang, Wei Lu, Lubin Xu, Fangzhi Hu, Shuai-Shuai Li
The hydride transfer-enabled divergent application of 5-amino-isoxazoles for the controllable construction of diverse tetrahydroquinolines and tetrahydroquinazolines was disclosed unprecedentedly by the process of ring-cleavage/Beckmann rearrangement, dearomative-spirocyclization, or N,N′-dialkylation of the amino group with the employment of different Lewis acids.
{"title":"Divergent application of 5-amino-isoxazoles for the construction of nitrogen heterocycles via the hydride transfer strategy","authors":"Mengzhe Pan, Feng-Wei Guo, Xinjie Sun, Jie Zhang, Wei Lu, Lubin Xu, Fangzhi Hu, Shuai-Shuai Li","doi":"10.1039/d4qo02059f","DOIUrl":"https://doi.org/10.1039/d4qo02059f","url":null,"abstract":"The hydride transfer-enabled divergent application of 5-amino-isoxazoles for the controllable construction of diverse tetrahydroquinolines and tetrahydroquinazolines was disclosed unprecedentedly by the process of ring-cleavage/Beckmann rearrangement, dearomative-spirocyclization, or <em>N</em>,<em>N</em>′-dialkylation of the amino group with the employment of different Lewis acids.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"27 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987685","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}
Despite significant advances in C(sp3)–H bond functionalization, the development of methods that are site-selective and capable of diverse bond formation remains a challenge. In addition, the preparation of olefins from aliphatics through cleavage of vicinal C(sp3)–H bonds remains difficult due to a lack of stereoselectivity and over-oxidation. To address these challenges, we have developed a transition metal catalyst- and external oxidant-free electrochemical C(sp3)–H oxygenation platform that enables highly stereoselective synthesis of aryl alkenes and diverse benzylic functionalizations to form various C–C and C–heteroatom bonds. This method involves site-selective benzylic C(sp3)–H trifluoroacetoxylation followed by elimination or substitution with diverse carbon- or heteroatom-based nucleophiles to form functionalized products. The utility of this protocol is further demonstrated by the desaturation of methyl dehydroabietate at the decagram scale and transformations of the resulting alkene. This study provides a platform for the diversity-oriented functionalization of both simple alkyl arenes and complex molecules.
{"title":"Diverse C(sp3)–H functionalizations through electrochemical benzylic oxygenation","authors":"Yan He, Tian-Sheng Chen, Xuesen Fan, Hai-Chao Xu","doi":"10.1039/d4qo02022g","DOIUrl":"https://doi.org/10.1039/d4qo02022g","url":null,"abstract":"Despite significant advances in C(sp<small><sup>3</sup></small>)–H bond functionalization, the development of methods that are site-selective and capable of diverse bond formation remains a challenge. In addition, the preparation of olefins from aliphatics through cleavage of vicinal C(sp<small><sup>3</sup></small>)–H bonds remains difficult due to a lack of stereoselectivity and over-oxidation. To address these challenges, we have developed a transition metal catalyst- and external oxidant-free electrochemical C(sp<small><sup>3</sup></small>)–H oxygenation platform that enables highly stereoselective synthesis of aryl alkenes and diverse benzylic functionalizations to form various C–C and C–heteroatom bonds. This method involves site-selective benzylic C(sp<small><sup>3</sup></small>)–H trifluoroacetoxylation followed by elimination or substitution with diverse carbon- or heteroatom-based nucleophiles to form functionalized products. The utility of this protocol is further demonstrated by the desaturation of methyl dehydroabietate at the decagram scale and transformations of the resulting alkene. This study provides a platform for the diversity-oriented functionalization of both simple alkyl arenes and complex molecules.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"23 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142986061","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}
Yaoluo Hu, Ya Hong, Yuting Zheng, Yi Huang, Jixiang Chen, Xingxing Wu
Phenanthrenequinones (PQs) are extensively studied in synthetic chemistry and materials science, exhibiting noteworthy biological activities essential for drug discovery. The development of efficient synthetic methods for PQ preparation has thus garnered significant attention, particularly through metal-catalyzed transformations. In this study, we present an N-heterocyclic carbene organocatalytic approach that enables the rapid construction of a diverse range of PQs and their derivatives without the need for stoichiometric oxidants or metal mediators. Mechanistically, the initial carbene-catalyzed formation of a benzoin adduct between the aldehyde and ester is critical in initiating a subsequent annulation reaction involving an aryl radical species. Our method represents the first example on the direct construction of PQ frameworks from simple starting materials by means of small-molecule catalysts. Furthermore, the catalytically obtained PQ products exhibit notable antimicrobial activity against common plant pathogens, offering promising potential for agrochemical development.
{"title":"Synthesis of Antimicrobial Active 9,10-Phenanthrenequinones by Carbene Organocatalytic Tandem Reactions","authors":"Yaoluo Hu, Ya Hong, Yuting Zheng, Yi Huang, Jixiang Chen, Xingxing Wu","doi":"10.1039/d4qo02193b","DOIUrl":"https://doi.org/10.1039/d4qo02193b","url":null,"abstract":"Phenanthrenequinones (PQs) are extensively studied in synthetic chemistry and materials science, exhibiting noteworthy biological activities essential for drug discovery. The development of efficient synthetic methods for PQ preparation has thus garnered significant attention, particularly through metal-catalyzed transformations. In this study, we present an N-heterocyclic carbene organocatalytic approach that enables the rapid construction of a diverse range of PQs and their derivatives without the need for stoichiometric oxidants or metal mediators. Mechanistically, the initial carbene-catalyzed formation of a benzoin adduct between the aldehyde and ester is critical in initiating a subsequent annulation reaction involving an aryl radical species. Our method represents the first example on the direct construction of PQ frameworks from simple starting materials by means of small-molecule catalysts. Furthermore, the catalytically obtained PQ products exhibit notable antimicrobial activity against common plant pathogens, offering promising potential for agrochemical development.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"1 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981322","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}
Jiaqiong Sun, Guangfan Zheng, Ge Zhang, Yan Li, Qian Zhang
This review offers a comprehensive overview of recent advancements in the asymmetric construction of C–N bonds involving radical intermediates. Enantioselective radical amination strategies have proven to be highly effective for synthesizing chiral amines and nitrogen-containing heterocycles. Significant progress has been made in the enantioselective installation of N–containing groups into halogenated alkanes, alkanes, olefins, and dienes with asymmetric formation of C–N bonds as the key step via diversified pathways including reductive elimination, radical-polar crossover, amino group substitution, and radical-radical cross-coupling, etc. This review highlights these recent developments and the mechanistic insights that drive these transformations.
本综述全面概述了涉及自由基中间体的 C-N 键不对称构建的最新进展。事实证明，对映选择性自由基胺化策略在合成手性胺和含氮杂环方面非常有效。通过还原消除、自由基-极性交叉、氨基取代和自由基-自由基交叉偶联等多种途径，以不对称形成 C-N 键为关键步骤，将含 N 基团对映选择性地安装到卤代烷、烷烃、烯烃和二烯中的研究取得了重大进展。本综述重点介绍了这些最新进展以及驱动这些转化的机理见解。
{"title":"Recent advances in enantioselective construction of C–N bonds involving radical intermediate","authors":"Jiaqiong Sun, Guangfan Zheng, Ge Zhang, Yan Li, Qian Zhang","doi":"10.1039/d4qo02268h","DOIUrl":"https://doi.org/10.1039/d4qo02268h","url":null,"abstract":"This review offers a comprehensive overview of recent advancements in the asymmetric construction of C–N bonds involving radical intermediates. Enantioselective radical amination strategies have proven to be highly effective for synthesizing chiral amines and nitrogen-containing heterocycles. Significant progress has been made in the enantioselective installation of N–containing groups into halogenated alkanes, alkanes, olefins, and dienes with asymmetric formation of C–N bonds as the key step via diversified pathways including reductive elimination, radical-polar crossover, amino group substitution, and radical-radical cross-coupling, etc. This review highlights these recent developments and the mechanistic insights that drive these transformations.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"43 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142975560","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}
Morita-Baylis-Hillman adducts has become an efficient synthon for the construction of C-C or C-heteroatom bonds, and has been widely used in the asymmetric synthesis of various new optically pure compounds. The use of Morita-Baylis-Hillman acetates in asymmetric catalytic reactions has exploded since the pioneering work of Kim and co-workers. In this review, the remarkable progress of Morita-Baylis-Hillman adducts in the asymmetric construction of chiral compounds from 2012 are summarized and discussed based on the different reaction types.
{"title":"Recent Advances in Catalytic Asymmetric Reactions of Morita–Baylis–Hillman adducts","authors":"Xu-Hong Duan, Hui-Ru Du, Yong-Xing Song","doi":"10.1039/d4qo02212b","DOIUrl":"https://doi.org/10.1039/d4qo02212b","url":null,"abstract":"Morita-Baylis-Hillman adducts has become an efficient synthon for the construction of C-C or C-heteroatom bonds, and has been widely used in the asymmetric synthesis of various new optically pure compounds. The use of Morita-Baylis-Hillman acetates in asymmetric catalytic reactions has exploded since the pioneering work of Kim and co-workers. In this review, the remarkable progress of Morita-Baylis-Hillman adducts in the asymmetric construction of chiral compounds from 2012 are summarized and discussed based on the different reaction types.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"28 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142975557","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}
Utilizing a regioselective hydrogen atom transfer (RHAT) strategy, this study demonstrates a triple RHAT process accompanied by C–O bond homolysis to generate unusual less-conjugated or contra-thermodynamic olefins, a transformation rarely documented in the literature. The key to this conversion is the uncommon RHAT from the secondary ether C–H bond, rather than the weaker tertiary acetal C–H bond. This protocol offers a diverse class of synthetically versatile, less-conjugated, or contra-thermodynamic olefins.
{"title":"Constructing less-conjugated olefins via unusual regioselective hydrogen atom transfer from acetals","authors":"Zhaoshan Wang, Huiying Liu, Tian-Tian Liu, Qixiang Wang, Youhao Wei, Xiaoguang Bao, Xinxin Wu","doi":"10.1039/d4qo02099e","DOIUrl":"https://doi.org/10.1039/d4qo02099e","url":null,"abstract":"Utilizing a regioselective hydrogen atom transfer (RHAT) strategy, this study demonstrates a triple RHAT process accompanied by C–O bond homolysis to generate unusual less-conjugated or contra-thermodynamic olefins, a transformation rarely documented in the literature. The key to this conversion is the uncommon RHAT from the secondary ether C–H bond, rather than the weaker tertiary acetal C–H bond. This protocol offers a diverse class of synthetically versatile, less-conjugated, or contra-thermodynamic olefins.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"17 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142975559","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}
Klaus Meerholz, Lukas Böher, Philipp Weitkamp, Thorsten Limböck, Nora Gildemeister, Daniele Fazzi, Manuela Schiek, Ruth Bruker, Roland Schaefer, Dirk Hertel, Klas Lindfors
In amorphous organic semiconductors, charge transport typically takes place via slow hopping processes, but it is known that molecular aggregation can lead to enhanced exciton and charge transport through coupling of the transition dipole moments. In this work, we investigate the optical, morphological, and electronic properties of thin films of a merocyanine dye, which aggregates easily due to its dipolar character. Firstly, in spin-coated thin films the degree of aggregation of can be tuned by thermal annealing, leading to strong spectral shift alongside with strong Davydov splitting of > 800 meV. At the same time, the mobility increases by approximately three orders of magnitude. We combine variable angle spectroscopic ellipsometry and polarization-resolved absorption spectroscopy with density functional theory to demonstrate that the aggregated molecules are oriented in an upright, standing configuration (“tip-on”) relative to the substrate surface. This arrangement involves a co-facial orientation of the molecular pi-systems, which is advantageous for lateral charge transport. Secondly, by utilizing highly oriented pyrolytic graphite as an ordered substrate and low-rate vacuum deposition, we are able to template the growth of the merocyanine layer and to substantially improve the in-plane morphological order. By combining atomic force microscopy and photoluminescence microspectroscopy we observe large oriented domains of 100s of µm2 in size, emitting linearly polarized light, whereby maintaining the edge-on molecular arrangement. This promises a further significant enhancement of lateral charge carrier mobility.
{"title":"Influencing Optical and Charge Transport Properties by Controlling the Molecular Interactions of Merocyanine Thin Films","authors":"Klaus Meerholz, Lukas Böher, Philipp Weitkamp, Thorsten Limböck, Nora Gildemeister, Daniele Fazzi, Manuela Schiek, Ruth Bruker, Roland Schaefer, Dirk Hertel, Klas Lindfors","doi":"10.1039/d4qo02088j","DOIUrl":"https://doi.org/10.1039/d4qo02088j","url":null,"abstract":"In amorphous organic semiconductors, charge transport typically takes place via slow hopping processes, but it is known that molecular aggregation can lead to enhanced exciton and charge transport through coupling of the transition dipole moments. In this work, we investigate the optical, morphological, and electronic properties of thin films of a merocyanine dye, which aggregates easily due to its dipolar character. Firstly, in spin-coated thin films the degree of aggregation of can be tuned by thermal annealing, leading to strong spectral shift alongside with strong Davydov splitting of > 800 meV. At the same time, the mobility increases by approximately three orders of magnitude. We combine variable angle spectroscopic ellipsometry and polarization-resolved absorption spectroscopy with density functional theory to demonstrate that the aggregated molecules are oriented in an upright, standing configuration (“tip-on”) relative to the substrate surface. This arrangement involves a co-facial orientation of the molecular pi-systems, which is advantageous for lateral charge transport. Secondly, by utilizing highly oriented pyrolytic graphite as an ordered substrate and low-rate vacuum deposition, we are able to template the growth of the merocyanine layer and to substantially improve the in-plane morphological order. By combining atomic force microscopy and photoluminescence microspectroscopy we observe large oriented domains of 100s of µm2 in size, emitting linearly polarized light, whereby maintaining the edge-on molecular arrangement. This promises a further significant enhancement of lateral charge carrier mobility.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"48 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142975556","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}
Jia-Huan Cui, Mei Tan, Jun Zhang, Yan He, Xingguang Li, Pei-Nian Liu
A simple protocol for the synthesis of trisubstituted furans via visible-light-driven regioselective cascade cyclization of vinyl sulfoxonium ylides with azides has been achieved. The reaction proceeds through the formation of a novel α-enone-α’-amide sulfoxonium ylide, which undergoes cyclization upon blue light irradiation to yield trisubstituted furan scaffold. This method offers advantages including the absence of transition metals and photocatalysts, as well as the desired trisubstituted furans were prepared in good to excellent yields.
{"title":"Highly Selective Visible-Light-Induced Cascade Cyclization of Vinyl Sulfoxonium Ylides with Azides: A Novel Synthetic Approach to Trisubstituted Furans","authors":"Jia-Huan Cui, Mei Tan, Jun Zhang, Yan He, Xingguang Li, Pei-Nian Liu","doi":"10.1039/d4qo02195a","DOIUrl":"https://doi.org/10.1039/d4qo02195a","url":null,"abstract":"A simple protocol for the synthesis of trisubstituted furans via visible-light-driven regioselective cascade cyclization of vinyl sulfoxonium ylides with azides has been achieved. The reaction proceeds through the formation of a novel α-enone-α’-amide sulfoxonium ylide, which undergoes cyclization upon blue light irradiation to yield trisubstituted furan scaffold. This method offers advantages including the absence of transition metals and photocatalysts, as well as the desired trisubstituted furans were prepared in good to excellent yields.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"52 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142975558","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}
Evgeny M. Buev, Vladimir Moshkin, Vyacheslav Sosnovskikh
Aminomethylation of alkenes is a convenient methodology for the synthesis of aliphatic amines. This direction encompasses various methods, mainly allowing functionalization of the C=C bond of the molecule with the aminomethyl fragment at one atom and hydrogen or heteroatom at the other. This paper describes a three-step approach to the aminomethylation of electron-deficient alkenes, facilitating their α,β-difunctionalization and an introduction of two aminomethyl fragments into both positions of the alkene. The initial [3+2]-cycloaddition reaction of nonstabilized azomethine ylide at the C=C double bond of enones and subsequent treatment with alkyl halides lead to the formation of a key intermediate of the process – quaternary ammonium salt of 3-acylpyrrolidine. Heating of such salt in a polar solvent in the presence of a nucleophile results in a tandem Hofmann elimination/Michael addition to give 2-heteromethyl-4-aminobutan-1-ones with high diastereoselectivity and good to high overall yields. The proposed method benefits from inexpensive and available reagents, does not require noble metal catalysis and provides opportunities to apply a wide range of nucleophiles and alkyl halogenides, resulting in broad customization of the introduced heteromethyl moieties.
{"title":"Three-step alkylaminomethylative α,β-difunctionalization of enones","authors":"Evgeny M. Buev, Vladimir Moshkin, Vyacheslav Sosnovskikh","doi":"10.1039/d4qo02259a","DOIUrl":"https://doi.org/10.1039/d4qo02259a","url":null,"abstract":"Aminomethylation of alkenes is a convenient methodology for the synthesis of aliphatic amines. This direction encompasses various methods, mainly allowing functionalization of the C=C bond of the molecule with the aminomethyl fragment at one atom and hydrogen or heteroatom at the other. This paper describes a three-step approach to the aminomethylation of electron-deficient alkenes, facilitating their α,β-difunctionalization and an introduction of two aminomethyl fragments into both positions of the alkene. The initial [3+2]-cycloaddition reaction of nonstabilized azomethine ylide at the C=C double bond of enones and subsequent treatment with alkyl halides lead to the formation of a key intermediate of the process – quaternary ammonium salt of 3-acylpyrrolidine. Heating of such salt in a polar solvent in the presence of a nucleophile results in a tandem Hofmann elimination/Michael addition to give 2-heteromethyl-4-aminobutan-1-ones with high diastereoselectivity and good to high overall yields. The proposed method benefits from inexpensive and available reagents, does not require noble metal catalysis and provides opportunities to apply a wide range of nucleophiles and alkyl halogenides, resulting in broad customization of the introduced heteromethyl moieties.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"74 6 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142975562","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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