Article
Chemistry, Multidisciplinary
Guangwu Sun, Herui Liu, Xiu Wang, Wenbo Zhang, Wenjun Miao, Qinyu Luo, Bing Gao, Jinbo Hu
Summary: In this manuscript, a novel palladium-catalyzed coupling reaction between gem-difluoroalkenes and aryl boronic acids is reported, which yields bioactive indane-type ketones with an all-carbon alpha-quaternary center. The mechanism involves a water-induced defluorination and cross-coupling cascade pathway, supported by characterization and stoichiometric reactions of the key intermediates RCF2PdII. The use of vinyl difluoromethylene motif as an in situ carbonyl precursor is unprecedented in transition-metal-catalyzed coupling reactions, and it is expected to spark broad interest in ketone synthesis, fluoroalkene functionalization, and design of new synthetic protocols based on the unique reactivity of difluoroalkyl palladium(II) species.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Heng Lu, Ruo-Xuan Xiao, Chang-Yun Shi, Zi-Lan Song, Hou-Wen Lin, Ao Zhang
Summary: A convenient and efficient synthesis of aryldifluoromethyl aryl ethers (ArCF2OAr') was achieved via Nickel-catalyzed aryloxydifluoromethylation with arylboronic acids. This method offers easily accessible starting materials, good tolerance of functionalities, and mild reaction conditions. The synthesized compounds were successfully applied in the total synthesis of a difluoromethylated PD-1/PD-L1 immune checkpoint inhibitor with improved metabolic stability and enhanced antitumor efficacy.
COMMUNICATIONS CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Felipe Verdugo, Ricardo Rodino, Martin Calvelo, Jose Luis Mascarenas, Fernando Lopez
Summary: The reactivity of carbonyl-tethered alkylidenecyclopropanes (ACPs) can be directed towards tandem cycloisomerization/cross-coupling processes by using Pd-0 catalysts with phosphorus-based monodentate ligands. This allows for the synthesis of a wide variety of highly functionalized cyclic alcohols and amines through the formation of key pi-allyl oxapalladacyclic intermediates which are trapped with external nucleophilic partners.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Jin-He Na, Xiang Liu, Jia-Wen Jing, Jing Wang, Xue-Qiang Chu, Mengtao Ma, Hao Xu, Xiaocong Zhou, Zhi-Liang Shen
Summary: A step-economical and efficient one-pot reaction was developed for the direct cross-coupling of aryl fluorosulfate with aryl bromide. This reaction, conducted at room temperature in THF solvent, does not require the use of preprepared/commercial organometallic reagents. By utilizing nickel catalyst, magnesium turnings, and lithium chloride, the desired biaryls were obtained in moderate to good yields with reasonable functional group compatibility.
Article
Chemistry, Multidisciplinary
Kotaro Kikushima, Kohei Yamada, Narumi Umekawa, Natsumi Yoshio, Yasuyuki Kita, Toshifumi Dohi
Summary: Catalyst-free access to aryldifluoromethyl ketones has been achieved through decarboxylative arylation of alpha,alpha-difluoro-beta-ketoacid salts using diaryliodonium(iii) salts. The products were successfully transformed into the corresponding esters, amides, and difluoromethyl compounds. This strategy provides access to fluorine-containing drugs, thus contributing to drug design.
Article
Chemistry, Applied
Sara Payamifar, Foad Kazemi, Babak Kaboudin
Summary: This study introduced a convenient nickel-catalyzed protocol for the Suzuki-Miyaura coupling reaction using a simple mixture of Ni(II) and unfunctionalized beta-cyclodextrin in water. The environmentally friendly and cost-efficient method allows the synthesis of biaryls from arylboronic acids and various aryl halides. The catalyst can be recycled for multiple runs with only a small decrease in catalytic activity.
APPLIED ORGANOMETALLIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Dejiang Zhang, Zhi Xu, Ting Tang, Liyuan Le, Cairong Wang, Nobuaki Kambe, Renhua Qiu
Summary: In this study, a general method for the synthesis of unsymmetric diarylmethanes from (hetero)aryl methylhalides and Sb-aryl stibines is described. The protocol has a broad substrate scope and good functional group tolerance. Gram-scale synthesis of drug molecules and their derivatives was efficiently achieved using this method.
Article
Chemistry, Multidisciplinary
Chang Xu, Ming-Kuan Wang, Shu Zhang, Xingang Zhang
Summary: In this study, a nickel-catalyzed method for the alkyl-arylation of 3,3,3-trifluoropropene with tertiary alkyl iodides and arylzinc reagents is reported. This method overcomes previous challenges and is of significant importance for the transformation of 3,3,3-trifluoropropene into medicinal compounds.
COMMUNICATIONS CHEMISTRY
(2022)
Article
Chemistry, Organic
Chen Zhang, Na-Na Ma, Zi-Lun Yu, Chuanji Shen, Xiaocong Zhou, Xue-Qiang Chu, Weidong Rao, Zhi-Liang Shen
Summary: The efficient palladium-catalyzed direct reductive cross-coupling reaction proceeds smoothly at room temperature with moderate to good yields, showing reasonable functional group tolerance. The one-pot reaction using readily available aryl bromide as a coupling partner is simple to handle, avoiding the use of pre-prepared organometallic reagents.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Multidisciplinary
Badr Jismy, Gerald Guillaumet, Mohamed Akssira, Abdellatif Tikad, Mohamed Abarbri
Summary: A convenient and efficient synthetic route to C3-arylated 7-trifluoromethylpyrazolo[1,5-a]pyrimidin-5-one derivatives has been developed via Suzuki-Miyaura cross-coupling reaction. The method enables the synthesis of a variety of arylated compounds with potential anti-inflammatory properties and neurodegenerative disorder targeting abilities.
Article
Chemistry, Organic
Xiaoshen Ma, Charles S. Yeung
Summary: Our study focused on achieving C(sp(2))-C(sp(3)) coupling reactions using 2,2-difluorobicyclo[1.1.1]pentane (BCP-F-2) building blocks. Through comparison of reactivities between BCP and BCP-F-2 analogues, we found that the Barluenga coupling reaction showed promising results, expanding the potential applications of BCP-F-2 in organic chemistry and medicinal chemistry.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Trong Nguyen Huu Phan, Jihong Lee, Hyunik Shin, Jeong-Hun Sohn
Summary: The Pd-catalyzed/Cu-mediated oxidative dehydrosulfurative carbon-oxygen cross-coupling reaction offers a facile access to biologically and pharmacologically valuable 2-aryloxypyrimidine derivatives due to the ready availability of diverse DHPMs and aryl alcohols.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
Xinyu Guan, Haoran Zhu, Tom G. Driver
Summary: A simple copper-catalyzed reaction involving nitroarenes and aryl boronic acids to form diarylamines has been described, with phenyl silane as the stoichiometric terminal reductant. The cross-coupling reaction requires low concentrations of CuX and diphosphine, tolerates a wide range of functional groups, and proceeds via a nitrosoarene intermediate catalyzed by copper.
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
Shan Jiang, Zi-Tong Zhang, David James Young, Lu-Lu Chai, Qi Wu, Hong-Xi Li
Summary: A photoinduced nickel-catalyzed cross-coupling reaction of arylsulfinates with (hetero)aryl halides has been achieved using visible light. The reaction showed a broad substrate scope and good functional group tolerance, providing diarylsulfones in moderate to excellent yields. The mechanism involves oxidative addition, single-electron oxidation, reductive elimination, and electron transfer.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Multidisciplinary
Shuo Chen, Zijian Wang, Shasha Geng, Hongdan Zhu, Zhengli Liu, Yun He, Qian Peng, Zhang Feng
Summary: This study developed an iron-catalyzed cross-electrophile coupling method using an iron/B(2)pin(2) catalytic system to couple inert C-O bonds with alkyl bromides. The reaction showed good efficiency in generating alkylated products from aryl and heteroaryl carbamates under mild conditions. The protocol exhibited good functional group compatibility and allowed late-stage functionalization of biorelevant compounds, making it suitable for applications in medicinal chemistry.
Review
Chemistry, Multidisciplinary
Minqi Zhou, Zhang Feng, Xingang Zhang
Summary: The site-selective modification of amino acids, peptides, and proteins has been an important topic in organic synthesis, medicinal chemistry, and chemical biology. The introduction of fluorine functionalities into these compounds has been a useful approach to alter their properties. Direct fluorination/fluoroalkylation of proteins has gained attention due to the unique properties of fluorine, and recent advances in the synthesis of fluorinated amino acids and peptides have been summarized in this article. Two strategies, based on fluorinated building blocks and direct fluorination/fluoroalkylation, have been discussed, providing powerful tools for selective access to fluorinated amino acids, peptides, and proteins.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Shuai Chen, Xueying Guo, Haoran Hou, Shasha Geng, Zhengli Liu, Yun He, Xiao-Song Xue, Zhang Feng
Summary: The development of aryl alkyl sulfides as dichotomous electrophiles for site-selective silylation via C-S bond cleavage has been achieved. Iron-catalyzed selective cleavage of C(aryl)-S bonds can occur in the presence of beta-diketimine ligands, and the cleavage of C(alkyl)-S bonds can be achieved by t-BuONa without the use of transition metals, resulting in the corresponding silylated products in moderate to excellent yields. Mechanistic studies suggest that Fe-Si species may undergo metathesis reactions during the cleavage of C(aryl)-S bonds, while silyl radicals are involved during the cleavage of C(alkyl)-S bonds.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Xin Zeng, Yao Li, Qiao-Qiao Min, Xiao-Song Xue, Xingang Zhang
Summary: The use of metal catalysts in controlling the reactivity of carbenes is widely used in organic synthesis, but the transfer of difluorocarbenes remains a challenge. In this study, isolable copper(I) difluorocarbene complexes were developed and used as catalysts for difluorocarbene transfer reactions. This strategy allows for the modular synthesis of organofluorine compounds and provides access to a variety of difluoromethylene-containing products. Mechanistic studies reveal a nucleophilic addition mechanism involving electrophilic copper(I) difluorocarbenes.
Article
Chemistry, Physical
Na Rao, Yun-Ze Li, Yun-Cheng Luo, Yanxia Zhang, Xingang Zhang
Summary: The nickel-catalyzed multicomponent dicarbofunctionalization of alkenes is a convenient method for synthesizing complex organofluorine compounds, but the catalytic carbofluoroalkylation of electron-deficient alkenes is still underdeveloped. In this study, a nickel-catalyzed three-component aryldifluoroalkylation reaction was reported, which involves the reaction of industry-relevant acrylonitrile and acrylate with arylboronic acids and difluoroalkyl halides. The reaction can be extended to a four-component nickel-catalyzed carbonylation reaction. This modular catalytic synthesis offers synthetic convenience, high functional group tolerance, and the ability to construct complex difluoroalkylated compounds efficiently. The utility of this synthesis has also been demonstrated by transforming the resulting products into fluorinated compounds of medicinal interest.
Article
Chemistry, Multidisciplinary
Yun-Cheng Luo, Ming-Kuan Wang, Ling-Chao Yu, Xingang Zhang
Summary: Here, we report a nickel-catalyzed selective C(sp(2))-F bond alkylation of HFO-1234yf with alkylzinc reagents, resulting in 2-trifluoromethylalkenes that can serve as versatile synthons for diversified transformations. Mechanistic studies reveal that the addition of lithium salt is crucial for promoting the oxidative addition of Ni-0(L-n) to the C-F bond, and less electron-rich N-based ligands exhibit comparable or higher oxidative addition rates compared to electron-rich phosphine ligands.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Xue-Ying Zhang, Shi-Ping Sun, Yue-Qian Sang, Xiao-Song Xue, Qiao-Qiao Min, Xingang Zhang
Summary: A palladium-catalyzed reductive difluorocarbene transfer reaction that utilizes chlorodifluoromethane as a precursor has been developed, allowing difluorocarbene to couple with two electrophiles. This new mode of difluorocarbene transfer reaction produces difluoromethylated (hetero)arenes from aryl halides/triflates and proton sources, with high functional group tolerance and synthetic convenience. Mechanistic studies reveal an unexpected Pd-0/II catalytic cycle involved in the reductive difluorocarbene transfer.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Xing Gao, Xiaoxiao Ren, Wei Deng, Xingang Zhang
Summary: This study reports a copper-catalyzed hydrodifluoroallylation of cyclopropenes and alkenyl boronates with 3,3-difluoroallyl sulfonium salts. The reaction shows high efficiency and stereoselectivity, allowing the synthesis of various gem-difluoroallyl cyclopropanes and borylalkanes under mild reaction conditions. The use of chiral phosphine ligand improves the enantioselectivity of the reaction. This method offers synthetic convenience, high functional group tolerance, and synthetic versatility of the resulting products.
CHINESE JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Organic
Wenping Ding, Minqi Zhou, Huayu Li, Miao Li, Yanping Qiu, Yu Yin, Lifeng Pan, Wenchao Yang, Yanan Du, Xingang Zhang, Zhijun Tang, Wen Liu
Summary: Modification of organic molecules with fluorine functionalities is a critical approach for developing new pharmaceuticals. In this study, a multienzyme strategy for biocatalytic fluoroalkylation was reported, which involved the use of SAM-dependent methyltransferases and fluorinated SAM cofactors. The strategy demonstrated successful late-stage site-selective fluoroalkylation of the complex molecule vancomycin, with conversions up to 99%.
Article
Chemistry, Physical
Ming-Kuan Wang, Yun-Cheng Luo, Hai-Yang Zhao, Yanxia Zhang, Dawei Zhang, Xingang Zhang
Summary: A cobalt-catalyzed trans-selective arylfluoroalkylation of cyclopentenes has been developed for the efficient synthesis of polysubstituted cyclopentanes. The reaction exhibits broad substrate scope, high functional group tolerance, and synthetic convenience.
Article
Chemistry, Physical
Ling-Chao Yu, Yun-Cheng Luo, Wei Feng, Shu Zhang, Xingang Zhang
Summary: A new organic catholyte material, sodium 2-(4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl-4-yl)-2,2-difluoroacetate (DFTEMPO), is created by introducing a fluorine functionality into 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO), showing higher cell voltage, rate capability, and cycle stability in aqueous redox flow batteries (ARFBs).
JOURNAL OF MATERIALS CHEMISTRY A
(2023)
Article
Chemistry, Multidisciplinary
Hao-Wen Li, Yun-Cheng Luo, Ling-Chao Yu, Xingang Zhang
Summary: A palladium-catalyzed gem-difluoroallylation of propargyl sulfonates with gem-difluoroallylboron has been developed, providing a synthetic route to 3,3-difluoro-skipped 1,5-enynes with high efficiency and regioselectivity. The resulting products can serve as versatile synthons for diversified transformations and have potential applications in medicinal chemistry.
CHEMICAL COMMUNICATIONS
(2023)
Review
Chemistry, Physical
Shasha Geng, Chaoqun Shi, Bohao Guo, Haoran Hou, Zhengli Liu, Zhang Feng
Summary: Transition-metal-catalyzed reductive cross-coupling reactions using diboron reagents as reductants have gained prominence due to their simplicity and good compatibility, offering advantages over conventional cross-coupling reactions.
Article
Chemistry, Organic
Jia Jia, Shuai Chen, Ting Mao, Jinlan Li, Weipiao Li, An-Jun Wang, Dezhi Yang, Zhengli Liu, Chun-Yang He, Zhang Feng
Summary: Herein, we describe a t-BuONa-promoted method for the site-selective silylation of 2H-indazoles. Control over the silylation site is achieved through substituents. Using SEM as a protecting group, the N-SEM 2H-indazoles can be easily deprotected and converted to silylated 1H-indazoles. This protocol shows broad substrate scope and excellent functional group tolerance, with preliminary experimental studies suggesting the involvement of silyl radicals in the reaction.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Xiaoxiao Ren, Xing Gao, Qiao-Qiao Min, Shu Zhang, Xingang Zhang
Summary: This research reports a novel method for constructing the alkylCF(2)-alkyl bond using alkylzirconocene as a catalyst to promote the reaction between unactivated difluoroalkyl iodides and bromides and alkyl- and silyl-alkenes under visible light irradiation without a catalyst. The resulting difluoroalkylated compounds can serve as versatile synthons in organic synthesis, and the reaction can also be applied to other fluorinated compounds.
