Article
Chemistry, Organic
Jie Huo, Xiao Geng, Wanmei Li, Pengfei Zhang, Lei Wang
Summary: Switchable multicomponent reactions have been developed to construct compound libraries with diverse and complex skeletons by altering the reaction conditions. This study presents a regioselectivity-switchable formal [1 + 2 + 2] cycloaddition reaction using difluoroalkyl compounds, enaminones, and RNHNH2, with 1-methylindazol-3-amine as a traceless mediator. The reaction switches the inherent regioselectivity from 1,3,4-trisubstituted pyrazoles to 1,4,5-trisubstituted pyrazoles. Notable features include mild conditions, simple operation, and broad scopes.
Article
Biochemistry & Molecular Biology
Grzegorz Mloston, Katarzyna Urbaniak, Marcin Palusiak, Zbigniew J. Witczak, Ernst-Ulrich Wuerthwein
Summary: The in situ-generated N-aryl nitrile imines derived from trifluoroacetonitrile can smoothly undergo (3+2)-cycloadditions onto the enone fragment of the levoglucosenone molecule, yielding the corresponding, five-membered cycloadducts. In contrast to the 'classic' C(Ph),N(Ph) nitrile imine, reactions with fluorinated C(CF3),N(Ar) analogues lead to stable pyrazolines in a chemo- and stereoselective manner. The reaction pathway is determined by kinetic control.
Article
Chemistry, Organic
Zhongxue Fang, Qihao Jin, Xinyu Wang, Yongquan Ning
Summary: A transition-metal-free [2 + 1 + 3] cycloaddition reaction of trifluoroacetaldehyde N-sulfonylhydrazone and hexahydro-1,3,5-triazine was described, providing a general synthesis of diverse trifluoromethylated 2,3,4,5-tetrahydro-1,2,4-triazines in good yields (81-97%) with a broad substrate scope, including aryl, benzyl, and alkyl hexahydro-1,3,5-triazine.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Yin Zhou, Cheng-Feng Gao, Hai Ma, Jing Nie, Jun-An Ma, Fa-Guang Zhang
Summary: This article presents a quadruple functionalization approach for the construction of fully substituted N-1-aryl 3-di/trifluoro-methyl-4/5-cyanopyrazole pharmacophores. The one-pot strategy offers access to a diverse library of compounds, some of which have potent inhibitory activity against cyclooxygenase 2 (COX-2).
CHEMISTRY-AN ASIAN JOURNAL
(2022)
Article
Chemistry, Organic
Hyun Ji Jeon, Su Min Park, Yu Lim Lee, Sang-gi Lee
Summary: The palladium-catalyzed divergent asymmetric synthesis of chiral spiro-furanindoline derivatives is described. The zwitterionic alkoxy pi-allyl Pd(II) intermediate, generated catalytically from vinyl ethylene carbonate (VEC), could undergo ligand-controlled enantio-and diastereoselective dipolar [3 + 2] spiroannulation with indole-based azadienes to afford the optically active spiro-furanindolines embedding an all-carbon quaternary stereocenter in high yields (up to 99%) with good to excellent stereoselectivities (up to 99% ee and up to >94:6 dr).
Article
Chemistry, Organic
Ruijie Shi, Limei Gao, Weiji Chen, Yangqing Shi, Zhixing Cao, Yongsheng Zheng, Jikai Liu
Summary: An unprecedented [2+2+2] cycloaddition reaction between 1,3,5-triazinanes and diethyl acetylene dicarboxylate has been disclosed, providing an efficient and mild approach to synthesize a variety of functionalized tetrahydropyrimidines in moderate to excellent yields (up to 99% yield) without the need for a catalyst. Preliminary mechanistic investigations have been conducted to elucidate the reaction process.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Kai-Wen Hu, Xiao You, Xiaoan Wen, Haoliang Yuan, Qing-Long Xu, Zengwei Lai
Summary: An efficient and environmentally friendly method for synthesizing thiazolidine-2-imine and oxazolidine-2-one derivatives has been developed. The method utilizes [3 + 2] annulation reactions to achieve good to excellent yields of the desired products. The strategy can be performed on a gram scale and is tolerant of a wide range of functional groups.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Mei-Mei Li, Hui Huang, Wanrong Tian, Yiru Pu, Chaozheng Zhang, Jirui Yang, Qing Ren, Feiyan Tao, Yun Deng, Jun Lu
Summary: A highly efficient potassium carbonate-mediated [3 + 2] cycloaddition reaction has been developed for the synthesis of multi-substituted pyrazoles using hydrazonoyl chlorides and cinnamic aldehydes. This protocol offers a broad substrate coverage, good functional group tolerance, wide scalability, operational simplicity, and convenient construction of pyrazole scaffolds.
Article
Chemistry, Organic
Greta Utecht-Jarzynska, Karolina Nagla, Grzegorz Mloston, Heinz Heimgartner, Marcin Palusiak, Marcin Jasinski
Summary: In this study, N-aryl nitrile imines derived from trifluoroacetonitrile were efficiently reacted with polycyclic 1,4-quinones to yield fused pyrazole derivatives as the exclusive products. The method provided a straightforward access to trifluoromethylated polycyclic pyrazoles, which were previously little known.
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Martin Linden, Silja Hofmann, Antonia Herman, Nicole Ehler, Robin M. M. Baer, Siegfried R. R. Waldvogel
Summary: This study presents the first electrochemical approach for the direct synthesis of pyrazolines and pyrazoles from easily accessible hydrazones and dipolarophiles. The method allows for large-scale production and even conversion of highly sensitive alkenes. The use of a biphasic system with sodium iodide as a supporting electrolyte and mediator is cost-effective. Mechanistic insight is provided by the isolation of key intermediates, and the synthesis of a commercial herbicide safener further highlights the significance of this reaction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Gaosheng Yang, Dongcheng Zheng, Rui Zhang, Wenlong Chen, Pengfei Yang, Zhuo Chai
Summary: Under the influence of simple Lewis acid catalysts, 2-(1-aroylcyclopropyl)malonates exhibited distinctive reactivities in annulation reactions with aryl/alkyl aldehydes, paraformaldehyde, and 1,3,5-triazinanes. Three structurally diverse cyclic products that are typically difficult to obtain were produced with moderate to good yields and excellent diastereoselectivities. Possible reaction pathways leading to these products were proposed based on control experiments.
Article
Chemistry, Organic
Dongcheng Zheng, Rui Zhang, Wenlong Chen, Pengfei Yang, Zhuo Chai, Gaosheng Yang
Summary: Under the influence of simple Lewis acid catalysts, 2-(1-aroylcyclopropyl)malonates display unique reactivity in annulation reactions with aryl/alkyl aldehydes, paraformaldehyde, and 1,3,5-triazinanes. Three structurally diverse cyclic products, which are difficult to obtain otherwise, are generated in moderate to good yields with excellent diastereoselectivities. Possible reaction pathways leading to these products are proposed based on control experiment results.
Article
Chemistry, Organic
Liang Tu, Limei Gao, Xiaomeng Wang, Ruijie Shi, Rupei Ma, Junfei Li, Xiaoshuang Lan, Yongsheng Zheng, Jikai Liu
Summary: An efficient [3 + 2] cycloaddition reaction of in situ generated nitrile imines with enamides has been developed, leading to a wide range of functionalized pyrazoline derivatives in moderate to good yields (up to 96%) under very mild conditions. The protocol demonstrates broad substrate scope, good functional group tolerance, and operational simplicity, with the products easily transformable into useful pyrazoles via a one-pot process.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Xue-Song Zhou, Zhihan Zhang, Wen-Yuan Qu, Xiao-Peng Liu, Wen-Jing Xiao, Min Jiang, Jia-Rong Chen
Summary: We report a cooperative catalytic system comprising a chiral nickel Lewis acid catalyst and an organic photocatalyst fueled by visible-light irradiation that allows for the hitherto elusive asymmetric [3 + 2] photocycloaddition of β-keto esters with vinyl azides under redox-neutral conditions. This protocol enables highly enantioselective construction of polycyclic densely substituted 3,4-dihydro-2H-pyrrole heterocycles featuring two contiguous tetrasubstituted carbon stereocenters, including a useful chiral N,O-ketal motif that is not easily accessible with other catalytic methods. Mechanistic studies revealed that the overall reactivity relies on the seamless integration of dual roles of nickel catalysts by the catalytic formation of the substrate/Ni complex, assisting both photoredox event and enantioselective radical addition.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Xue-Song Zhou, Zhihan Zhang, Wen-Yuan Qu, Xiao-Peng Liu, Wen-Jing Xiao, Min Jiang, Jia-Rong Chen
Summary: We report a cooperative catalytic system that enables the elusive asymmetric [3 + 2] photocycloaddition of beta-keto esters with vinyl azides under redox-neutral conditions, using a chiral nickel Lewis acid catalyst and an organic photocatalyst fueled by visible-light irradiation. This protocol allows for the highly enantioselective construction of polycyclic densely substituted 3,4-dihydro-2H-pyrrole heterocycles featuring two contiguous tetrasubstituted carbon stereocenters.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Andrew C. Jones, William I. Nicholson, Jamie A. Leitch, Duncan L. Browne
Summary: The nickel-catalyzed cross-electrophile coupling of aryl halides and alkyl halides enabled by ball-milling is efficient and green, achieving reductive C-C bond formation under a mechanochemical manifold. The mechanical action provided by ball milling allows for the use of a variety of zinc sources to turnover the nickel catalytic cycle, resulting in the synthesis of 28 cross-electrophile coupled products.
Article
Chemistry, Organic
Harry R. Smallman, Jamie A. Leitch, Tom McBride, Steven Ley, Duncan L. Browne
Summary: Continuous flow systems have unique advantages in the generation and manipulation of sensitive reactive intermediates like ketenes, and various methods have been developed in the past decade for generating ketenes in continuous flow using chemical, thermal, and photochemical activation modes. This article discusses these advancements and the downstream reactivity of ketenes in continuous flow technology.
Review
Chemistry, Multidisciplinary
Matthew T. J. Williams, Louis C. Morrill, Duncan L. Browne
Summary: Ball mills input energy by pulverising contents of the jar to samples, while enantioselective organocatalytic reactions proceed through perceived transition states. This review focuses on the combination of organocatalytic reactions with mechanochemical ball milling conditions, with particular emphasis on stereoselectivity control.
Article
Chemistry, Organic
Mishra Deepak Hareram, Albara A. M. A. El Gehani, James Harnedy, Alex C. Seastram, Andrew C. Jones, Matthew Burns, Thomas Wirth, Duncan L. Browne, Louis C. Morrill
Summary: A new electrochemical method for the generation of alkoxy radicals from alcohols using proton-coupled electron transfer (PCET) approach has been reported. The method allows the functionalization of cycloalkanols and access to a broad range of synthetically useful distally functionalized ketones. The products can be orthogonally derivatized through chemoselective transformations. The electrochemical process has been successfully performed on a gram scale in continuous single-pass flow.
Article
Chemistry, Multidisciplinary
Robert R. A. Bolt, Sarah E. Raby-Buck, Katharine Ingram, Jamie A. Leitch, Duncan L. Browne
Summary: This article describes the use of temperature-controlled mechanochemistry for the mechanochemical nickel-catalyzed Suzuki-Miyaura coupling. The method eliminates the need for bulk solvents and is not affected by air/moisture, and has been successfully scaled up using twin-screw extrusion.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Harry R. Smallman, Guilherme A. Brancaglion, Julio C. Pastre, Duncan L. Browne
Summary: A flow chemistry process for the generation and use of acylketene precursors through extrusion of nitrogen gas is reported. The development of a suitable continuous protocol is dependent on the balance of reaction concentration and pressure in the flow reactor. The process allows access to captured acylketene scaffolds using volatile amine nucleophiles and has been demonstrated on a gram scale. Thermal gravimetric analysis is used to determine the temperature set point of the reactor coils for different acyl ketene precursors. The simultaneous generation and reaction of two reactive intermediates derived from nitrogen extrusion are demonstrated.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Physical
Andrew C. Jones, Matthew T. J. Williams, Louis C. Morrill, Duncan L. Browne
Summary: The cross-electrophile coupling of twisted amides or heteroaryl halides with alkyl halides using ball milling is described in this study. The nickel-catalyzed process is operationally simple and does not require inert atmosphere or dry solvents.
Editorial Material
Chemistry, Physical
Alexander Angerhofer, Matej Balaz, Viktor Balema, Ana M. Belenguer, Richard G. Blair, Elena Boldyreva, Carsten Bolm, Lars Borchardt, Adam B. Braunschweig, Duncan L. Browne, Stephen Craig, Lamis El Wenni, Franziska Emmerling, Michael Ferguson, Cecilia Fiore, Tomislav Friscic, Kimichika Fukushima, Felipe Garcia, Lori Gonnet, Sven Gratz, Rafael A. R. Hernandez, Hajime Ito, Stuart L. James, Deniz Karabiyikli, Jeung Gon Kim, Koji Kubota, Frederic Lamaty, Giulio Lampronti, Jamie Leitch, Stipe Lukin, James Mack, Lucia Maini, Sharmarke Mohamed, Audrey Moores, Karthik Nagapudi, Francesco Puccetti, Mi Tian, Qian Yu
FARADAY DISCUSSIONS
(2023)
Article
Chemistry, Applied
Ian Priestley, Claudio Battilocchio, Andrei V. Iosub, Fabien Barreteau, Gavin W. Bluck, Kenneth B. Ling, Katharine Ingram, Maria Ciaccia, Jamie A. Leitch, Duncan L. Browne
Summary: Chemical reactions in a ball mill and without a bulk reaction solvent have different safety profiles compared to stirred solution reactions. We present and describe steps for researchers to consider the hazards and measures to minimize risks to themselves and their colleagues.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2023)
Article
Chemistry, Applied
Matthew T. J. Williams, Louis C. Morrill, Duncan L. Browne
Summary: A mechanochemical nickel-catalyzed intramolecular difunctionalization reaction of alkene tethered aryl halides with alkyl halides is developed for the synthesis of 3,3-disubstituted heterocycles, namely oxindoles, with shorter reaction times compared to solution-phase methods. The process is solvent minimized by employing liquid-assisted grinding (LAG) quantities of DMA and avoids the need for chemical activation of the terminal reductant (manganese) through mechanical grinding. The reaction can be scaled up to yield gram quantities of product and modest enantioinduction is possible with a chiral PyrOx ligand.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Correction
Chemistry, Applied
Ian Priestley, Claudio Battilocchio, Andrei Iosub, Fabien Barreteau, Gavin W. Bluck, Kenneth B. Ling, Katharine Ingram, Maria Ciaccia, Jamie A. Leitch, Duncan L. Browne
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2023)
Article
Multidisciplinary Sciences
Calum Patel, Emy Andre-Joyaux, Jamie A. Leitch, Xabier Martinez de Irujo-Labalde, Francesco Ibba, Job Struijs, Mathias A. Ellwanger, Robert Paton, Duncan L. Browne, Gabriele Pupo, Simon Aldridge, Michael A. Hayward, Veronique Gouverneur
Summary: This article introduces a method of reacting acid-grade fluorspar with dipotassium hydrogen phosphate under mechanochemical conditions, resulting in a solid product suitable for forming sulfur-fluorine and carbon-fluorine bonds.
Article
Chemistry, Multidisciplinary
Lorenzo Pontini, Jamie A. Leitch, Duncan L. Browne
Summary: This study presents a solvent-free method for synthesizing cyclopropanes via a ball-milling-enabled Simmons-Smith reaction. By utilizing mechanochemical techniques to activate zinc(0), this protocol, which is simple to operate under air, enables the synthesis of various cyclopropane structures and gram-scale production.
Article
Chemistry, Multidisciplinary
Camila Souza Santos, Renan Rodini Mattioli, Julia Soares Baptista, Vitor Menezes H. da Silva, Duncan L. Browne, Julio Cezar Pastre
Summary: In this study, we have successfully synthesized 4-acetylaminophthalimides and other nitrogenated aromatic compounds using two chitin-derived furans, namely 3-acetamido-5-ethylfuran (3A5EF) and 3-acetamido-5-(1-hydroxyethyl)furan (3A5HF). The transformation involves the formation of a 7-oxa-norbornene backbone through a Diels-Alder adduct, followed by a dehydration/aromatisation process in an acidic/acetylating medium. The yields of nitrogenated aromatic compounds ranged from 16% to 80%. This work represents an important step in expanding the synthetic toolbox of chitin-derived furans for the production of nitrogenated aromatic compounds.
Review
Chemistry, Multidisciplinary
Robert R. A. Bolt, Jamie A. Leitch, Andrew C. Jones, William Nicholson, Duncan L. Browne
Summary: This tutorial review discusses the translation from batch-mode ball-milling to flow-mode reactive extrusion using twin-screw extrusion. Mechanochemistry has been established as a powerful approach in sustainable organic synthesis, mainly due to the opportunities offered in solvent-free or highly solvent-minimized reaction systems. However, limitations in scale-up still exist.
CHEMICAL SOCIETY REVIEWS
(2022)
