Robert Junior Kolman, Petra Švaco, Maja Majerić Elenkov, Irena Dokli
The versatile reactivity of propargylic epoxides and alcohols, due to the presence of a triple bond, is used in the synthesis of various organic compounds and building blocks. However, there are not many known methods for the preparation of optically pure propargylic epoxides and alcohols, and the existing ones often require specific reagents. Halohydrin dehalogenases (HHDHs) can be used to obtain enantiomerically pure compounds from racemic epoxides. These important biocatalysts facilitate epoxide ring-opening reactions with unnatural nucleophiles such as azides. Here we report the first biocatalytic transformation of propargylic epoxides using HHDHs. Six propargylic epoxides with different substituents were synthesized. Kinetic resolution reactions catalyzed by HHDHs in the presence of azide were performed. Two enzymes with opposite stereoselectivities, HheC and HheA2-N178A were used and yielded azido alcohols (98 - >99% ee, E-value >200) and epoxides (up to 88% ee). Best performing p-tolyl propargylic epoxide derivative was used in a sequence of two enzymatic reactions to obtain both enantiomers of the secondary alcohol and (R)-primary alcohol in > 99% ee, respectively, through complete conversion of the starting epoxide. The obtained azido alcohols were used in further transformations. Click reactions with terminal acetylenes gave triazolyl propargylic alcohols (>99% ee, up to 98% yield). In the case of primary azido alcohol, the click reaction was followed by intramolecular cyclization to form the dihydrofuranyl triazole motif that is found in biologically active compounds.
{"title":"Synthesis and HHDH-Catalyzed Kinetic Resolution of Propargylic Epoxides","authors":"Robert Junior Kolman, Petra Švaco, Maja Majerić Elenkov, Irena Dokli","doi":"10.1002/adsc.202400734","DOIUrl":"https://doi.org/10.1002/adsc.202400734","url":null,"abstract":"The versatile reactivity of propargylic epoxides and alcohols, due to the presence of a triple bond, is used in the synthesis of various organic compounds and building blocks. However, there are not many known methods for the preparation of optically pure propargylic epoxides and alcohols, and the existing ones often require specific reagents. Halohydrin dehalogenases (HHDHs) can be used to obtain enantiomerically pure compounds from racemic epoxides. These important biocatalysts facilitate epoxide ring-opening reactions with unnatural nucleophiles such as azides. Here we report the first biocatalytic transformation of propargylic epoxides using HHDHs. Six propargylic epoxides with different substituents were synthesized. Kinetic resolution reactions catalyzed by HHDHs in the presence of azide were performed. Two enzymes with opposite stereoselectivities, HheC and HheA2-N178A were used and yielded azido alcohols (98 - >99% ee, E-value >200) and epoxides (up to 88% ee). Best performing p-tolyl propargylic epoxide derivative was used in a sequence of two enzymatic reactions to obtain both enantiomers of the secondary alcohol and (R)-primary alcohol in > 99% ee, respectively, through complete conversion of the starting epoxide. The obtained azido alcohols were used in further transformations. Click reactions with terminal acetylenes gave triazolyl propargylic alcohols (>99% ee, up to 98% yield). In the case of primary azido alcohol, the click reaction was followed by intramolecular cyclization to form the dihydrofuranyl triazole motif that is found in biologically active compounds.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142023065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexander Shuvaev, Matvey Feoktistov, Fedor Teslenko, Leonid Fershtat
Synthetic electrochemistry may establish direct routes to a preparation of a plethora of organic substances, which are hardly accessible by conventional experimental techniques. Herein, we present an electrochemically-driven method for an assembly of a broad range of rare heterocyclic mesoionic entities – 1,2,3-triazole 1-imines. These nitrogen heterocycles were prepared through a transition-metal- and exogenous oxidant-free strategy using a C/Ni electrode pair. Over 30 examples of thus synthesized 1,2,3-triazole 1-imines illustrate selectivity and practical utility of this approach. Key solvent-controlled reactivity patterns for the formation of the triazole imine scaffold were revealed indicating a modulation ability of the developed approach. These experimental findings were additionally justified based on cyclic voltammetry (CV) data and density functional theory (DFT) calculations. Moreover, according to differential scanning calorimetry (DSC) data, some of the prepared 1,2,3-triazole 1-imines correspond to the thermally stable species with an onset decomposition temperature up to 190 oC.
{"title":"Electrochemical Approach Toward Mesoionic 1,2,3-Triazole 1-Imines","authors":"Alexander Shuvaev, Matvey Feoktistov, Fedor Teslenko, Leonid Fershtat","doi":"10.1002/adsc.202400761","DOIUrl":"https://doi.org/10.1002/adsc.202400761","url":null,"abstract":"Synthetic electrochemistry may establish direct routes to a preparation of a plethora of organic substances, which are hardly accessible by conventional experimental techniques. Herein, we present an electrochemically-driven method for an assembly of a broad range of rare heterocyclic mesoionic entities – 1,2,3-triazole 1-imines. These nitrogen heterocycles were prepared through a transition-metal- and exogenous oxidant-free strategy using a C/Ni electrode pair. Over 30 examples of thus synthesized 1,2,3-triazole 1-imines illustrate selectivity and practical utility of this approach. Key solvent-controlled reactivity patterns for the formation of the triazole imine scaffold were revealed indicating a modulation ability of the developed approach. These experimental findings were additionally justified based on cyclic voltammetry (CV) data and density functional theory (DFT) calculations. Moreover, according to differential scanning calorimetry (DSC) data, some of the prepared 1,2,3-triazole 1-imines correspond to the thermally stable species with an onset decomposition temperature up to 190 oC.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Metal hydride catalyzed hydrogen atom transfer (MHAT) reaction of 1,6-enyne and electron-poor alkene progresses through a radical cascade, involving ene-yne cyclization and exocyclic C-C bond formation superseding the direct reductive olefin cross-coupling; which is realized in the current study. The generality of this reaction manifold is demonstrated with a range of functionalized 1,6-enyne and dienes and involving structurally distinct electron-poor olefins and alkynes as partners. Current work unveils a merger of MHAT-based olefin-hydro functionalization with radical ene-one cyclization.
{"title":"Radical Carbocyclization Intercepted Reductive C-C Bond Formation Between 1,n-Enynes or Dienes and Electron-Poor Olefins/Alkynes","authors":"Subhadeep Hazra, Manveer Patel, Jaideep Saha","doi":"10.1002/adsc.202400503","DOIUrl":"https://doi.org/10.1002/adsc.202400503","url":null,"abstract":"Metal hydride catalyzed hydrogen atom transfer (MHAT) reaction of 1,6-enyne and electron-poor alkene progresses through a radical cascade, involving ene-yne cyclization and exocyclic C-C bond formation superseding the direct reductive olefin cross-coupling; which is realized in the current study. The generality of this reaction manifold is demonstrated with a range of functionalized 1,6-enyne and dienes and involving structurally distinct electron-poor olefins and alkynes as partners. Current work unveils a merger of MHAT-based olefin-hydro functionalization with radical ene-one cyclization.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fengkai Sun, Man Miao, Wenxue Li, Xiao-Bing Lan, Jiang-Qiang Yu, Jian Zhang, Zhenyu An
A direct electrochemical redox reaction involving radical cross-coupling cyclization for the synthesis of pyrrolo[1,2-a]quinoxaline derivatives from 1-(2-aminophenyl)pyrroles and CH3CN has been developed, which includes the functionalization of C(sp3)-H bonds as well as the construction of C-C and C-N bonds. Notably, the control and deuterium-labelling experiments suggest that CH3CN in this reaction acts as both a carbon source via C-C cleavage and solvent. The reaction features metal- and oxidant-free conditions, and various substituted pyrrolo[1,2-a]quinoxaline derivatives were obtained.
{"title":"Direct C–C Bond Cleavage of CH3CN as a Single-Carbon Synthon：Synthesis of Pyrrolo[1,2-a]quinoxalines via Electrochemical Oxidation","authors":"Fengkai Sun, Man Miao, Wenxue Li, Xiao-Bing Lan, Jiang-Qiang Yu, Jian Zhang, Zhenyu An","doi":"10.1002/adsc.202400886","DOIUrl":"https://doi.org/10.1002/adsc.202400886","url":null,"abstract":"A direct electrochemical redox reaction involving radical cross-coupling cyclization for the synthesis of pyrrolo[1,2-a]quinoxaline derivatives from 1-(2-aminophenyl)pyrroles and CH3CN has been developed, which includes the functionalization of C(sp3)-H bonds as well as the construction of C-C and C-N bonds. Notably, the control and deuterium-labelling experiments suggest that CH3CN in this reaction acts as both a carbon source via C-C cleavage and solvent. The reaction features metal- and oxidant-free conditions, and various substituted pyrrolo[1,2-a]quinoxaline derivatives were obtained.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142007734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The transition metal catalyzed cyclization of alkene-tethered carbamoyl chloride has now emerged as a vital tool to construct oxindoles bearing all carbon quaternary centers. However, most of these reactions proceed via carbometalation-initiated 5-exo-trig cyclization followed by nucleophilic trapping of the resulting σ alkyl-metal species to achieve diverse functionalized oxindoles. The 6-endo-trig type cyclization of alkene-tethered carbamoyl chloride has been rarely reported. Herein, a zinc-mediated carbamoyl amination of alkylidenecyclopropane-tethered carbamoyl chlorides with anilines for the synthesis of functionalized 2-quinolones was developed. A range of different substituted 2-quinolones were prepared in 65-89% yields from alkylidenecyclopropane-tethered carbamoyl chlorides and aniline derivatives using Zn/TMSCl system.
{"title":"Zinc-Mediated Carbamoyl Amination of Alkylidenecyclopropane-Tethered Carbamoyl Chlorides: Synthesis of Functionalized 2-Quinolones","authors":"Jing-Tong Deng, Ming Lang, jin-bao peng","doi":"10.1002/adsc.202400849","DOIUrl":"https://doi.org/10.1002/adsc.202400849","url":null,"abstract":"The transition metal catalyzed cyclization of alkene-tethered carbamoyl chloride has now emerged as a vital tool to construct oxindoles bearing all carbon quaternary centers. However, most of these reactions proceed via carbometalation-initiated 5-exo-trig cyclization followed by nucleophilic trapping of the resulting σ alkyl-metal species to achieve diverse functionalized oxindoles. The 6-endo-trig type cyclization of alkene-tethered carbamoyl chloride has been rarely reported. Herein, a zinc-mediated carbamoyl amination of alkylidenecyclopropane-tethered carbamoyl chlorides with anilines for the synthesis of functionalized 2-quinolones was developed. A range of different substituted 2-quinolones were prepared in 65-89% yields from alkylidenecyclopropane-tethered carbamoyl chlorides and aniline derivatives using Zn/TMSCl system.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142013977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The replacement of benzene rings with saturated bioisosteric counterparts is a key priority in drug discovery programs, and disubstituted bicyclo[2.1.1]hexanes have been recognized as flexible molecular scaffolds that could act as <i>ortho</i>‐substituted benzene bioisosteres. In this study, we outline the synthesis of a wide range of 2‐substituted bicyclo[2.1.1]hexan‐1‐ols, which have the potential to emulate <i>ortho</i>‐phenolic derivatives, via SmI<sub>2</sub>‐mediated reductive cyclization reactions. The synthetic utility of this methodology was exemplified by the preparation of several saturated analogs of pharmaceutically relevant compounds.
{"title":"Synthesis of 2‐Substituted Bicyclo[2.1.1]hexan‐1‐ols via SmI2‐Mediated Reductive Cyclization Reactions","authors":"Chih-Wei Hsu, Chun-Fu Wu, Yung-Chi Lee, Woo-Jin Yoo","doi":"10.1002/adsc.202400891","DOIUrl":"https://doi.org/10.1002/adsc.202400891","url":null,"abstract":"The replacement of benzene rings with saturated bioisosteric counterparts is a key priority in drug discovery programs, and disubstituted bicyclo[2.1.1]hexanes have been recognized as flexible molecular scaffolds that could act as <i>ortho</i>‐substituted benzene bioisosteres. In this study, we outline the synthesis of a wide range of 2‐substituted bicyclo[2.1.1]hexan‐1‐ols, which have the potential to emulate <i>ortho</i>‐phenolic derivatives, via SmI<sub>2</sub>‐mediated reductive cyclization reactions. The synthetic utility of this methodology was exemplified by the preparation of several saturated analogs of pharmaceutically relevant compounds.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Formates are abundantly available and inexpensive commodity chemical, widely used in laboratory and industrial organic synthesis. Formates are promising hydrogen carrier and green C1 source, and have also been a subject of research as SET re‐ductants in recent years. Compared to the toxic and flammable gas carbon monoxide, which also serves as a C1 source, for‐mates are easier to handle, store, and transport, and are more environmentally friendly. Therefore, in recent studies of radical reactions, formate is not only as an ideal source of green carbonyl, which is of great significance to synthesize carboxyl compounds with various structures, but also as a SET reductant for editing organic molecules either in scientific research or industrial production. The activation and conversion of formate, as a source of C1 or a SET reductant, is a very challenging and hot research field in organic synthesis.
甲酸盐是一种来源丰富、价格低廉的商品化学品，广泛用于实验室和工业有机合成。甲酸盐是一种很有前途的氢载体和绿色 C1 源，近年来也成为 SET 还原剂的研究课题。与同样作为 C1 源的有毒易燃气体一氧化碳相比，甲酸酯更易于处理、储存和运输，而且更加环保。因此，在近年来的自由基反应研究中，甲酸酯不仅是一种理想的绿色羰基源，对合成各种结构的羧基化合物具有重要意义，而且在科学研究或工业生产中也是一种编辑有机分子的 SET 还原剂。作为 C1 源或 SET 还原剂，甲酸酯的活化和转化是有机合成领域极具挑战性的热门研究领域。
{"title":"Formate Salts: The Rediscovery of Their Radical Reaction under Light Irradiation Opens New Avenues in Organic Synthesis","authors":"Qing Shen, kun cao, Xiaoqing Wen, Jiahong Li","doi":"10.1002/adsc.202400682","DOIUrl":"https://doi.org/10.1002/adsc.202400682","url":null,"abstract":"Formates are abundantly available and inexpensive commodity chemical, widely used in laboratory and industrial organic synthesis. Formates are promising hydrogen carrier and green C1 source, and have also been a subject of research as SET re‐ductants in recent years. Compared to the toxic and flammable gas carbon monoxide, which also serves as a C1 source, for‐mates are easier to handle, store, and transport, and are more environmentally friendly. Therefore, in recent studies of radical reactions, formate is not only as an ideal source of green carbonyl, which is of great significance to synthesize carboxyl compounds with various structures, but also as a SET reductant for editing organic molecules either in scientific research or industrial production. The activation and conversion of formate, as a source of C1 or a SET reductant, is a very challenging and hot research field in organic synthesis.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhou Sun, Jia-Xuan Liu, Lin Shi, Ming Yang, Yuan Wang, Ya-Ping Han, Xiaojun Yao, Yong-Min Liang
Optically active molecule architectures stand as an important class of organic compounds and occupy a key role in academic and industrial communities. Particularly, the molecules bearing quaternary carbon are of vital importance because of its favorable conformation and valuable three‐dimensional molecules, which frequently play a key role in a broad spectrum of functional materials, pharmaceutical relevant natural molecules, and agrochemicals. Over the past few decades, a large amount of synthetic strategies for the enantioselective construction of compounds with chiral quaternary carbon centers have been the focus of a number of research initiatives. In this review, the state‐of‐the‐art toward the synthesis of enantioenriched molecules bearing quaternary stereocenters are summarized, which could be segmented into four categories: 1) Construction of optically active quaternary carbon centers by addition to prochiral sp2 carbon; 2) Construction of optically active all‐carbon quaternary stereocenters via substitution at non‐chiral tetra‐substituted carbon; 3) Construction of optically active all‐carbon quaternary stereocenters via kinetic resolution; 4) Construction of optically active all‐carbon quaternary stereocenters via desymmetrization reactions.
{"title":"New Synthetic Approaches for the Construction of Enantioenriched Molecules Bearing Quaternary Stereocenters","authors":"Zhou Sun, Jia-Xuan Liu, Lin Shi, Ming Yang, Yuan Wang, Ya-Ping Han, Xiaojun Yao, Yong-Min Liang","doi":"10.1002/adsc.202400732","DOIUrl":"https://doi.org/10.1002/adsc.202400732","url":null,"abstract":"Optically active molecule architectures stand as an important class of organic compounds and occupy a key role in academic and industrial communities. Particularly, the molecules bearing quaternary carbon are of vital importance because of its favorable conformation and valuable three‐dimensional molecules, which frequently play a key role in a broad spectrum of functional materials, pharmaceutical relevant natural molecules, and agrochemicals. Over the past few decades, a large amount of synthetic strategies for the enantioselective construction of compounds with chiral quaternary carbon centers have been the focus of a number of research initiatives. In this review, the state‐of‐the‐art toward the synthesis of enantioenriched molecules bearing quaternary stereocenters are summarized, which could be segmented into four categories: 1) Construction of optically active quaternary carbon centers by addition to prochiral sp2 carbon; 2) Construction of optically active all‐carbon quaternary stereocenters via substitution at non‐chiral tetra‐substituted carbon; 3) Construction of optically active all‐carbon quaternary stereocenters via kinetic resolution; 4) Construction of optically active all‐carbon quaternary stereocenters via desymmetrization reactions.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rhodium-catalyzed oxidative coupling of acetanilides and alkynes via C-H activation is the most powerful synthetic tool for producing the indole motif from commercially available precursors. However, this reaction usually requires large catalyst loadings (5 mol% of rhodium). In this study, a 1,2-diphenylcyclopentadienyl ligand-based catalyst was developed that works well at 1 mol% loading of rhodium. DFT calculations of the C-H activation step provided insight into its high catalytic activity. The catalyst efficiency was also demonstrated in the synthesis of naturally occurring isocoumarins, such as polygonolide, tubakialactone B and penicimarine F. The developed catalytic protocols tolerate a wide range of functional groups, for example, halide, nitro, hydroxy, and alkoxy.
{"title":"Rhodium Catalysts Based on Phenyl Substituted Cp Ligands for Indole Synthesis via Oxidative Coupling of Acetanilides and Alkynes","authors":"Vladimir Kharitonov, Dmitry Muratov, Alexey Rodionov, Yulia Nelyubina, Mher Navasardyan, Mikhail Nechaev, Dmitry Loginov","doi":"10.1002/adsc.202400716","DOIUrl":"https://doi.org/10.1002/adsc.202400716","url":null,"abstract":"Rhodium-catalyzed oxidative coupling of acetanilides and alkynes via C-H activation is the most powerful synthetic tool for producing the indole motif from commercially available precursors. However, this reaction usually requires large catalyst loadings (5 mol% of rhodium). In this study, a 1,2-diphenylcyclopentadienyl ligand-based catalyst was developed that works well at 1 mol% loading of rhodium. DFT calculations of the C-H activation step provided insight into its high catalytic activity. The catalyst efficiency was also demonstrated in the synthesis of naturally occurring isocoumarins, such as polygonolide, tubakialactone B and penicimarine F. The developed catalytic protocols tolerate a wide range of functional groups, for example, halide, nitro, hydroxy, and alkoxy.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daliah Farajat, Jean-Louis Do, Pat Forgione, Tomislav Friščić, Louis A. Cuccia, Chao-Jun Li
Quinolines are a ubiquitous heterocyclic aromatic scaffold, which can be found in many natural and synthetic products. They are highly valued for their pharmacological and electrochemical properties, encouraging the discovery of new routes for quinoline synthesis and diversification. Polyaryl-substituted quinolines have recently surged as useful substrates for a wide variety of applications, yet their synthetic routes remain difficult and inefficient. Herein, we report a rapid and novel mechanochemical Friedländer synthesis of polyaryl-substituted quinolines under basic conditions using ball milling. Optimized reaction conditions result in moderate to excellent yields ranging from 69% to >95% and demonstrates broad functional group tolerance at 1 hour reaction times. We further demonstrate a new route for the synthesis of photocatalyst DPQN2,4-di-OMe and photo-ligand PPQN2,4-di-OMe as well as OLED donor-acceptor pCzPPQ, electron transport material oligoquinoline TQB and organic semiconductor DPA. A gram-scale reaction was also achieved using Resonant Acoustic Mixing (RAM), providing an isolated yield of 87% after a simple recrystallization in ethanol.
{"title":"Shaking Up the Friedländer Reaction: Rapid, Scalable Mechanochemical Synthesis of Polyaryl-substituted Quinolines","authors":"Daliah Farajat, Jean-Louis Do, Pat Forgione, Tomislav Friščić, Louis A. Cuccia, Chao-Jun Li","doi":"10.1002/adsc.202400862","DOIUrl":"https://doi.org/10.1002/adsc.202400862","url":null,"abstract":"Quinolines are a ubiquitous heterocyclic aromatic scaffold, which can be found in many natural and synthetic products. They are highly valued for their pharmacological and electrochemical properties, encouraging the discovery of new routes for quinoline synthesis and diversification. Polyaryl-substituted quinolines have recently surged as useful substrates for a wide variety of applications, yet their synthetic routes remain difficult and inefficient. Herein, we report a rapid and novel mechanochemical Friedländer synthesis of polyaryl-substituted quinolines under basic conditions using ball milling. Optimized reaction conditions result in moderate to excellent yields ranging from 69% to >95% and demonstrates broad functional group tolerance at 1 hour reaction times. We further demonstrate a new route for the synthesis of photocatalyst DPQN2,4-di-OMe and photo-ligand PPQN2,4-di-OMe as well as OLED donor-acceptor pCzPPQ, electron transport material oligoquinoline TQB and organic semiconductor DPA. A gram-scale reaction was also achieved using Resonant Acoustic Mixing (RAM), providing an isolated yield of 87% after a simple recrystallization in ethanol.","PeriodicalId":118,"journal":{"name":"Advanced Synthesis & Catalysis","volume":null,"pages":null},"PeriodicalIF":5.4,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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