Article
Chemistry, Organic
Xinkan Yang, Gavin Chit Tsui
Summary: Organic molecules with the trifluoromethyl group are important in pharmaceuticals, agrochemicals, and materials. New trifluoromethylation methods need to address efficiency, selectivity, and the source of CF3. Fluoroform has emerged as an attractive source of CF3 and can be used to efficiently and selectively synthesize trifluoromethylated compounds.
Article
Chemistry, Organic
Qile Wang, Thomas R. Hoye
Summary: The study presents a novel Cu(I)-catalyzed reaction for introducing different substituents onto benzyne molecules, showing potential for various applications.
Article
Chemistry, Multidisciplinary
Debasish Mandal, Suman Maji, Tanay Pal, Soumya Kumar Sinha, Debabrata Maiti
Summary: This review provides a comprehensive overview of the transition metal-mediated construction of C(sp(3), sp(2), and sp)-CF3 bonds in aliphatic and aromatic hydrocarbons. It discusses various trifluoromethylating agents and their mechanisms. This review is of great significance for further development in trifluoromethylation reactions and agrochemical drugs.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Xian-Zhou Zheng, Kai Chen, Jun-An Xiao, Jun Li, Sha-Sha Wang, Qing-Lan Zhao, Hao-Yue Xiang, Xiao-Qing Chen, Hua Yang
Summary: In a newly developed palladium-catalysed enantioselective nucleophilic substitution reaction, an unusual temperature-enantioselectivity relationship was observed where higher enantioselectivity was achieved at an abnormally high temperature (140 degrees C) in less than 5 minutes. Experimental and computational studies suggest that temperature-dependent changes in the rate-determining steps may be responsible for the abnormal effect of temperature on stereocontrol in this process.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Multidisciplinary
Xiaoyu Zhan, Hongyu Liu, Rui Liu, Yanmin Huang, Yungui Peng
Summary: Here, a green and sustainable electrochemical strategy is reported for the a-alkylation of tertiary amines using halogenated alkanes under undivided electrolytic conditions. The reaction proceeds through an organozinc reagent produced at the cathode and an iminium ion produced at the anode, resulting in the formation of a-alkylated amines. The reaction shows wide-ranging functional-group and substrate compatibilities, and utilizes the challenging technique of convergent pair electrolysis.
Article
Chemistry, Organic
Zheng Fang, Biqiong Hong, Wei Wu, Zhiqiang Weng
Summary: We report a metal-free amination reaction using 1-(3,3,3-trifluoro-2-oxopropyl)pyridin-1-ium bromide and alpha,beta-unsaturated carbonyl compounds with NH4OAc or amines. The reaction yields a series of 3-trifluoromethyl aniline derivatives as major products. The reaction proceeds through a cascade process involving 1,4-Michael addition and intramolecular addition to form a dienone intermediate.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Zi-Qi Zhang, Yi-Hao Xu, Jing-Cheng Dai, Yan Li, Jie Sheng, Xi-Sheng Wang
Summary: A facile and efficient approach for the synthesis of CF3-containing dioxodibenzothiazepines has been developed via copper-catalyzed trifluoromethylation/cyclization of alkynes utilizing a radical relay strategy. This method demonstrates low catalyst loading, high regiocontrol, and broad scope under mild conditions, proving its versatility and potential for further derivatization.
Article
Chemistry, Organic
Mahdieh Esi Firuz, Saideh Rajai-Daryasarei, Frank Rominger, Abbas Biglari, Saeed Balalaie
Summary: A simple and highly efficient strategy has been developed for direct C-H trifluoromethylation at C-3 of imidazopyridines and C-8 of quinoxalines using the readily available Langlois reagent through the KMnO4/AcOH system. This protocol exhibited a wide range of substrate compatibility and provided moderate-to-excellent yields of both products. It represents the first report of regioselective functionalization of quinoxalines at the C-8 position and mechanistic studies demonstrated a radical pathway.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Casey B. Ritts, Thomas R. Hoye
Summary: This study presents a sulfurane-mediated method for the formation of dimeric dibenzofuran helicenes under thermal conditions. Experimental and DFT studies support a ligand coupling mechanism involving tetracarbo-ligated S(IV) intermediates, resulting in the generation of polycyclic aromatic compounds with the de novo generation of five new rings in a single operation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Wei Wu, Shunli Wen, Xinyu Zhang, Qi Lin, Zhiqiang Weng
Summary: A highly efficient and regioselective synthesis of highly substituted 2-trifluoromethyl pyrrole derivatives is reported via a silver-catalyzed cyclization of vinyl azides with ethyl 4,4,4-trifluoro-3-oxobutanoate. Various types of alpha-(heteo)aryl, alkyl, alpha-aryl, and alpha,beta-disubstituted vinyl azides can participate in this transformation. The proposed reaction mechanism involves the addition of in situ generated 2H-azirine to the diketone species, followed by intramolecular addition, N-C-1 cleavage, and elimination.
Article
Chemistry, Multidisciplinary
Maximilian Scheruebl, Constantin G. Daniliuc, Armido Studer
Summary: The article introduces the application of arynes as radical acceptors, showing how the stable radical TEMPO can react with different ortho-substituted benzynes to generate aryl radicals for subsequent cyclizations, eventually being trapped by TEMPO. This method provides a novel approach for the convenient synthesis of various dihydrobenzofurans, oxindoles, and sultones.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Stanna K. Dorn, Annika E. Tharp, M. Kevin Brown
Summary: The study introduces an efficient, modular, and enantioselective approach towards accessing novel variants of double-allylation reagents via Cu/Pd-catalyzed alkenylation of alkenylboron derivatives. It demonstrates a novel use of allylBdan reagent directly in a stereocontrolled allylation without initial deprotection. These allylation products are utilized in a second intermolecular allylation to access complex diol motifs, signaling the importance and utility of this method in accessing complex structural motifs in a rapid manner.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Chunxiang Pan, Chunhui Yang, Kangkui Li, Keyang Zhang, Yuanbin Zhu, Shiyuan Wu, Yongyun Zhou, Baomin Fan
Summary: An efficient, catalyst/photocatalyst-free, and cost-effective methodology has been developed for the synthesis of beta,gamma-unsaturated nitriles from alpha,beta-unsaturated carboxylic acids. The reaction proceeded in an environmentally benign atmosphere of blue light-emitting diode irradiation with K2CO3 and water at room temperature, showing high yields (up to 83%) with a wide range of substrates.
Article
Chemistry, Multidisciplinary
Xinrui Dong, Wenhua Jiang, Dexiang Hua, Xiaohui Wang, Liang Xu, Xiaoxing Wu
Summary: The addition of trifluoromethyl sulfonyl radicals to alkynes is a valuable method for constructing highly functionalized sulfonyl compounds. This process shows broad functional group compatibility and potential in drug discovery and chemical biology.
Article
Chemistry, Organic
Jing Liu, Yisa Xiao, Jian Hao, Qilong Shen
Summary: A copper-catalyzed trifluoromethylation of (hetero)-arylboronic acid pinacol esters with YlideFluor was described, allowing the preparation of trifluoromethylated (hetero)arenes. The reaction conditions are mild and compatible with a broad range of functional groups. The application of this method for trifluoromethylation of drug and OLED molecules was demonstrated.
Article
Chemistry, Physical
Yanhui Wang, Xiaotian Qi, Qiao Ma, Peng Liu, Gavin Chit Tsui
Summary: The diastereoselective synthesis of densely functionalized tetrasubstituted (E)-monofluoroalkenes via Pd(0)-catalyzed base-free Suzuki-Miyaura crosscouplings offers a significant method for producing pharmaceutically relevant compounds. Computational studies support the reaction design, revealing an intriguing mechanism of C-F bond activation leading to complete control of stereoselectivity. This method does not require extraneous base assistance, making it a powerful tool for stereocontrolled synthesis of monofluoroalkenes.
Article
Chemistry, Organic
Yuwei Zong, Qiao Ma, Gavin Chit Tsui
Summary: In this study, a nucleophilic vinylic substitution reaction was developed to efficiently synthesize trisubstituted alkenes with stereocontrol under simple conditions. Additionally, dimerization of monofluoroalkenes to form (E,E)-divinyl ethers was observed, triggered by adventitious water in the reaction mixture.
Article
Chemistry, Organic
Yanhui Wang, Qiao Ma, Gavin Chit Tsui
Summary: A highly diastereoselective Pd(0)-catalyzed synthesis of difluorinated 1,3-dienes has been described, utilizing a stereoselective twofold Pd-catalyzed Miyaura borylation/Suzuki-Miyaura cross-coupling of the C-F bond. The modular synthesis of symmetrical and unsymmetrical difluorinated 1,3-dienes is achievable through different reaction pathways.
Article
Chemistry, Organic
Min Li, Yanhui Wang, Gavin Chit Tsui
Summary: A new Pd-catalyzed reaction was described for the stereoselective synthesis of valuable monofluorinated dienes. By using a catalytic system involving Pd(0) and dppe as the ligand, the reaction successfully achieved Stille-type cross-coupling between gem-difluoroalkenes and vinyl- and allyltin reagents.
Article
Chemistry, Organic
Xinkan Yang, Gavin Chit Tsui
Summary: Organic molecules with the trifluoromethyl group are important in pharmaceuticals, agrochemicals, and materials. New trifluoromethylation methods need to address efficiency, selectivity, and the source of CF3. Fluoroform has emerged as an attractive source of CF3 and can be used to efficiently and selectively synthesize trifluoromethylated compounds.
Article
Chemistry, Organic
Yanhui Wang, Yihan Tang, Yuwei Zong, Gavin Chit Tsui
Summary: We describe a method for the selective C-F bond functionalization of tetrasubstituted gem-difluoroalkenes and trisubstituted monofluoroalkenes using Grignard reagents without the transition metal catalyst.
Article
Chemistry, Organic
Yuwei Zong, Yihan Tang, Gavin Chit Tsui
Summary: In this paper, we describe a highly selective Rh(I)-catalyzed defluorinative coupling of boronic acids with (E)-beta-monofluoroacrylates, which yields trisubstituted (Z)-alkene products with excellent diastereoselectivity and an inversion of double bond geometry. Experimental and computational studies demonstrate that Rh(I)-facilitated beta-F elimination is preferred over competing beta-H elimination and protodemetalation.
Article
Chemistry, Organic
Kun She, Feng Liang, Shichao Tian, Hengshan Wang, Gavin Chit Tsui, Quande Wang
Summary: An N-hetercyclic carbene-catalyzed three-component acyldifluoromethylation reaction has been developed, providing a practical route for the synthesis of pharmaceutically relevant compounds without the need for transition metals or photocatalysts. Late-stage acyldifluoromethylation of drug analogues was also successfully demonstrated in this study. The reaction utilizes NaSO2CF2H as the source of the CF2H radical with an oxidant for radical relay.
Article
Chemistry, Inorganic & Nuclear
Ziwei Luo, Dominique Cahard, Gavin Chit Tsui
Summary: This article summarizes the latest research reports on the application of fluoroform in organic synthesis since 2017, including direct trifluoromethylation facilitated by organic and inorganic bases, preparation of trifluoromethylation reagents based on transition metals and borazine, and radio-labeled fluoroform.
JOURNAL OF FLUORINE CHEMISTRY
(2023)
Letter
Chemistry, Organic
Hao Tan, Yuwei Zong, Yihan Tang, Gavin Chit Tsui
Summary: In this paper, a highly diastereoselective rhodium(I)-catalyzed C-F bond functionalization of gem-difluoroalkenes with arylboronic acids is described. Unlike previously developed methods using Pd(II) and Pd(0) catalysts, the Rh(I)/BINAP catalytic system enables the C-F bond arylation of both trisubstituted beta,beta-difluorostyrene and tetrasubstituted beta,beta-difluoroacrylate, resulting in the synthesis of valuable monofluoroalkenes with a >99:1 diastereomeric ratio.
Article
Chemistry, Organic
Lu Lin, Peng Wang, Tao Dong, Gavin Chit Tsui, Saihu Liao
Summary: Here, we present a transition-metal-free and visible-light-mediated radical 1-fluorosulfonyl-2-heteroarylation of alkenes, which enables the synthesis of a variety of SO2F-containing quinoxalin-2(1H)-ones, a critical structural motif widely found in biologically active molecules. Furthermore, we demonstrate the application of this method in the modification of other heterocycles and drug molecules, as well as ligation chemistry via SuFEx click reactions.
Article
Chemistry, Organic
Gavin Chit Tsui, Yuwei Zong, Ziwei Luo
Summary: We report a novel palladium(0)-catalyzed defluorosilylation method for highly stereoselective synthesis of tetrasubstituted vinylsilanes containing monofluoroalkene motif. This is the first example of C-heteroatom bond formation from C-F bond using Pd catalytic manifold.
Article
Chemistry, Organic
Jinlian Wang, Ziwei Luo, Yili Wu, Yihan Tang, Xinkan Yang, Gavin Chit Tsui
Summary: We present a simple method for the allylic difluoromethylation of unactivated alkenes. Unlike previous methods that required prefunctionalized allylic substrates, this reaction uses readily available alkenes under mild conditions. Visible light irradiation with PIDA and the use of copper catalyst effectively diverts the reaction towards allylic difluoromethylation rather than hydrodifluoromethylation.
Article
Chemistry, Organic
Ziwei Luo, Gavin Chit Tsui
Summary: We described a novel domino radical cyclization/bis(pentafluoroethylation) of 1,6-dienes for the synthesis of pyrrolidine and cyclopentane derivatives containing two C2F5 groups. This reaction efficiently constructs three carbon-carbon bonds in one step. The reagent [CuCF2CF3] is easily prepared from inexpensive pentafluoroethane and the reaction conveniently runs at room temperature in open air.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Multidisciplinary
Ren-Xiao Liang, Jian-Fei Chen, Ying-Ying Huang, Ya-Ping Yu, Han-Yue Zhang, Yu-Feng Song, Gavin Chit Tsui, Yi-Xia Jia
Summary: Highly enantioselective palladium-catalyzed dearomative reductive Heck reaction and domino Heck-Suzuki reaction of 2-CF3-indoles have been developed. A variety of indolines bearing different stereocenters can be obtained using different reaction systems.
CHEMICAL COMMUNICATIONS
(2022)
