Review
Chemistry, Physical
Kuai Wang, Wangqing Kong
Summary: Organofluorine compounds have received significant attention in various industries due to their unique chemical and physical properties. However, the synthesis of these compounds still faces challenges, including difficulties in handling fluorinating reagents and controlling chemoselectivity. In recent decades, the development of Nickel-catalyzed defluorinative cross-couplings has provided powerful strategies for the construction of fluorinated organic compounds. This review summarizes important advances in this field, focusing on aryl fluorides, gem-difluorovinyl, and trifluoromethyl compounds.
Article
Chemistry, Multidisciplinary
Yisa Xiao, Weichen Huang, Qilong Shen
Summary: A method for the stereoselective construction of Z-monofluoroalkenes by nickel-catalyzed defluorinative coupling of gem-difluoroalkenes in mild conditions was described. The combination of lithium organoborate and ZnBr2 generated in situ lithium aryl zincates, which facilitated the transmetalation step of the nickel-catalyzed cross-coupling reaction.
CHINESE CHEMICAL LETTERS
(2022)
Article
Chemistry, Organic
Zichen Pan, Xiuqi Wang, Shuaishuai Zhao, Hongping Deng, Mengtao Ma, Fei Xue
Summary: We have successfully developed a convergent paired electrolysis strategy for defluorinative thiolation using thiols and gem-difluoroalkenes as precursors. This protocol shows excellent tolerance towards a wide range of functional groups, demonstrated by successful late-stage defluorothiolation of complex molecules. Additionally, this strategy enables gram-scale synthesis by efficiently utilizing both anodic oxidation and cathodic reduction processes.
Article
Chemistry, Organic
Lin Zhu, Jie Huang, Fanling Meng, Ziyun Tan, Xiao Meng, Yang Xiao, Lanlan Zhang, Wenyi Li, Chao Wang
Summary: A NiH-catalyzed migratory and non-migratory gem-difluoroallylation reaction of alkenyl amines with trifluoromethyl alkenes has been developed. This reaction offers high selectivity and diversity for the synthesis of fluoro-containing amines, which is beneficial for drug discovery.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Multidisciplinary Sciences
Bingnan Du, Chun-Ming Chan, Pui-Yiu Lee, Leong-Hung Cheung, Xin Xu, Zhenyang Lin, Wing-Yiu Yu
Summary: The authors developed diverse 2,2-difluorovinyl benzoates as versatile building blocks for modular synthesis of gem-difluoroenol ethers and gem-difluoroalkenes using nickel-catalyzed cross coupling. The method allows for late-stage functionalization of multifunctionalized bioactive molecules due to the diversity of the building blocks and excellent functional group tolerance.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Bin Zhao, Zichen Pan, Jiayu Pan, Hongping Deng, Xiaoli Bu, Mengtao Ma, Fei Xue
Summary: We report a regiodivergent defluorinative carboxylation of gem-difluorocyclopropanes achieved by subtly modulating the electrochemical conditions. This method allows for the selective synthesis of branched and linear monofluoroalkene carboxylic acids in moderate to high yields and with exclusive regioselectivities. The protocol is green, using atmospheric CO2 as the C1 source and not requiring transition metals, and can be scaled up and applied to late-stage functionalization of complex compounds.
Article
Chemistry, Multidisciplinary
Ziqi Zhu, Lin Lin, Jieshuai Xiao, Zhuangzhi Shi
Summary: The stereo- and enantioselective cross-electrophile coupling involving C-F bond activation was successfully achieved using a chiral nickel complex and B(2)pin(2) as a stoichiometric reductant. The reaction allows the construction of a C(sp(2))-C(sp(3)) bond under mild conditions, resulting in a variety of monofluoroalkenes bearing stereogenic allylic centers. Initial mechanistic studies suggest a radical chain pathway may be involved in the C-F bond activation process.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Xingxiu Yan, Shengchun Wang, Zhao Liu, Yujie Luo, Pengjie Wang, Wenyan Shi, Xiaotian Qi, Zhiliang Huang, Aiwen Lei
Summary: A precise electro-reduction strategy for the synthesis of gem-difluoroalkenes is reported. Direct or indirect electrolysis is used for precise reduction, and a catalyst- and metal-free condition is developed. Furthermore, a novel electro-Ni-catalytic system is established for the electrochemical synthesis of gem-difluoroalkenes.
SCIENCE CHINA-CHEMISTRY
(2022)
Article
Chemistry, Physical
Jichao Xiao, John Montgomery
Summary: A simple procedure for the nickel-catalyzed defluorinative alkylation of unactivated aliphatic aldehydes is reported. The protocol exhibits broad substrate scope, mild conditions, and a simple catalytic setup.
Article
Chemistry, Organic
Haiyan Dong, Zhiyang Lin, Chuan Wang
Summary: In this study, cycloalkyl silyl peroxides (CSP) were successfully utilized as electrophilic coupling partners in cross-electrophile coupling reactions for the first time. Diverse CSP compounds were efficiently cross-coupled with a range of alpha-trifluoromethyl alkenes under nickel catalysis with zinc as a reducing agent, leading to the synthesis of gem-difluoroalkenes with a pendent ketone moiety and excellent functionality tolerance.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Zhiyang Lin, Yun Lan, Chuan Wang
Summary: A reductive allylic defluorinative reaction of trifluoromethyl alkenes with terminal epoxides was reported, which involves iodide-mediated regioselective ring opening and a nickel-catalyzed radical-type cross-coupling to provide diverse tertiary gemdifluorobishomoallylic alcohols in moderate to high yields. Notably, this reaction is conducted under mild conditions without requiring any external ligand or proton donor.
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, Multidisciplinary
Chang Zhang, Zhiyang Lin, Yufei Zhu, Chuan Wang
Summary: A novel chromium-catalyzed reaction was reported for the efficient synthesis of gem-difluorohomoallylic alcohols, with high chemoselectivity towards formyl moiety conversion in the presence of other functionalities. Simple derivatizations of the hydroxyl group of the coupling products demonstrate the utility of this method.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Zhenghong Zhou, Jimin Yang, Bo Yang, Yang Han, Lijuan Zhu, Xiao-Song Xue, Feng Zhu
Summary: This study presents a pioneering example of nickel-catalysed enantioconvergent Stille cross-coupling reactions. The reactions result in the formation of C-C bonds in good to high yields with excellent stereoselectivity, providing a practical and cost-effective method for synthesis. The innovative use of synergistic photoredox/nickel catalysis enables a novel single-electron transmetalation process, opening up new research possibilities in the field of Stille reactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Wei Tang, Pei Fan
Summary: A nickel-catalyzed regioselective cross-electrophilic ring opening reaction of sulfonyl-protected aziridines with trifluoromethyl-substituted alkenes has been reported, providing a new and efficient entry to prepare gem-difluorobishomoallylic sulfonamides. Moreover, the scaffold of 6-fluoro-1,2,3,4-tetrahydropyridine can be constructed starting from the ring opening products via NaH-mediated intramolecular defluorinative nucleophilic vinylic substitution.
Article
Chemistry, Multidisciplinary
Sheng Xu, Herong Chen, Zhijun Zhou, Wangqing Kong
Summary: Catalytic alkene difunctionalization using decatungstate photo-HAT and nickel catalysis allows for the direct activation of aliphatic C-H bonds, enabling the installation of highly functionalized C(sp(3))-hybrid centers. This strategy demonstrates practicality in selective late-stage functionalization of natural products and concise synthesis of pharmaceutically relevant molecules.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Yate Chen, Zhengtian Ding, Yiming Wang, Wenfeng Liu, Wangqing Kong
Summary: This study describes an unprecedented nickel-catalyzed domino reductive cyclization of alkynes and o-bromoaryl aldehydes, providing straightforward access to biologically significant indanones and spiroindanone pyrrolidine derivatives in good yields with excellent regio- and diastereoselectivity. Preliminary mechanistic studies suggest that indanones are formed through cyclization of o-bromoaryl aldehydes and alkynes to form indenol intermediates, followed by hydrogen autotransfer.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Zhengtian Ding, Yiming Wang, Wenfeng Liu, Yate Chen, Wangqing Kong
Summary: The study presents an unprecedented nickel-catalyzed one-pot synthesis of enantioenriched spiroindanones from readily available 1,6-enynes and o-formylarylboronic acids. The reaction proceeds smoothly under redox-neutral conditions, demonstrating excellent regio-, enantio-, and diastereoselectivity with a broad substrate scope.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Xiao-Wang Chen, Jun-Ping Yue, Kuai Wang, Yong-Yuan Gui, Ya-Nan Niu, Jie Liu, Chuan-Kun Ran, Wangqing Kong, Wen-Jun Zhou, Da-Gang Yu
Summary: The asymmetric reductive carbo-carboxylation of alkenes via nickel catalysis provides an efficient method for the synthesis of carboxylic acids with mild reaction conditions, wide substrate scope, and good selectivity. This approach opens up a new avenue for the total synthesis of chiral natural products using CO2.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Qi Pan, Yuanyuan Ping, Yifan Wang, Ya Guo, Wangqing Kong
Summary: This study presents a catalyst-controlled dicarbofunctionalization of alkenes for the synthesis of five- and six-membered benzo-fused lactams bearing all-carbon quaternary centers. Different regioselectivity patterns can be achieved by using chiral bidentate ligands, resulting in high yields and excellent enantioselectivities. The synthetic value of this regiodivergent protocol is demonstrated by the preparation of biologically relevant molecules and structural scaffolds.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Hengxu Li, Jiachang Chen, Jueqi Dong, Wangqing Kong
Summary: A Ni-catalyzed reductive arylcyanation of alkene using an environmentally benign and nontoxic organo cyanating reagent has been developed. This method allows for the rapid synthesis of cyanosubstituted oxindoles and isoquinoline-1,3-diones with high functional group tolerance, and also features an enantioselective version for the construction of enantiomerically enriched 3-cyanomethyl oxindoles. Additionally, this approach has been successfully applied to the synthesis of natural alkaloids (+)-esermethole and (+)-physostigmine.
Article
Chemistry, Multidisciplinary
Yuanyuan Ping, Xiao Li, Qi Pan, Wangqing Kong
Summary: Ligand-directed divergent synthesis is a strategy that can transform common starting materials into distinct molecular scaffolds. This strategy enables the rapid construction of structurally rich collection of small molecules for biological evaluation and reveals novel modes of catalytic transformation, representing one of the most sought-after challenges in synthetic chemistry.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Yuanyuan Ping, Qi Pan, Ya Guo, Yongli Liu, Xiao Li, Minyan Wang, Wangqing Kong
Summary: Switchable selectivity in skeletal rearrangement can be achieved by controlling the migratory aptitude of different groups. Modifying the ligands on the metal catalyst and changing the oxidation states of the metal allow control over the migratory ability. This method enables site-selective activation and reorganization of C-C bonds and has been used for the synthesis of fluorine-containing scaffolds with medicinal relevance.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Kuai Wang, Jiachang Chen, Wenfeng Liu, Wangqing Kong
Summary: The introduction of fluorine-containing groups into organic molecules can significantly affect their physical and chemical properties and has been widely used in drug discovery and development. In this study, a nickel-catalyzed asymmetric cyclization reaction was described, which enables the efficient synthesis of synthetically attractive 4-fluorovinyl-substituted 2-pyrrolidones. This protocol shows high chemo-, regio-, and enantioselectivities and can be utilized in the synthesis of the antiepileptic drug Seletracetam.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Zhengtian Ding, Wangqing Kong
Summary: Carbonyl-containing oxindoles are ubiquitous core structures in many biologically active natural products and pharmaceutical molecules. Nickel-catalyzed reductive aryl-acylation and reductive aryl-esterification reactions provide 3,3-disubstituted oxindoles with ketone and ester functionality at the 3-position, respectively.
Review
Chemistry, Multidisciplinary
Qi Pan, Yuanyuan Ping, Wangqing Kong
Summary: The use of nickel catalysts in reductive cyclization/cross-coupling reactions allows the construction of valuable chiral heterocycles with quaternary stereocenters. This method offers advantages in building C(sp3)-C bonds, but limitations including low chemoselectivity and availability of organometallic nucleophiles restrict its application. This Account presents recent research on tuning the selectivity and cyclization mode of reductive cyclization/cross-couplings using nickel catalysts. It demonstrates the synthetic potential of this approach and the control of migratory aptitude through ligand modification and nickel oxidation state.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Sheng Xu, Yuanyuan Ping, Wei Li, Haoyun Guo, Yinyan Su, Ziyang Li, Minyan Wang, Wangqing Kong
Summary: In this study, we achieved enantioselective C(sp3)-H functionalization of undirected oxacycles using photo-HAT/nickel dual catalysis, allowing for the direct construction of high-value and enantiomerically enriched oxacycles from simple and abundant hydrocarbon feedstocks. The synthetic utility of this strategy was further demonstrated through late stage functionalization of natural products and the synthesis of pharmaceutically relevant molecules. Experimental and density functional theory calculation studies provided detailed insights into the mechanism and origin of enantioselectivity for the asymmetric C(sp3)-H functionalization.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Wenfeng Liu, Yang Ke, Chuhan Liu, Wangqing Kong
Summary: Here, we describe a method for the direct and selective acylation and alkynylation of C(sp(3))-H bonds of saturated hydrocarbons using synergistic decatungstate photo-HAT and nickel catalysis. This method exhibits excellent site selectivity and efficiently constructs a wide variety of high-value compounds from abundant hydrocarbon feedstocks.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Herong Chen, Zhijun Zhou, Wangqing Kong
Summary: The new nickel-catalyzed direct coupling reaction can directly convert alkenes and methanol into valuable allylic alcohols with good yield and selectivity, and has a wide range of applicable substrates. This method has also been successfully applied to the synthesis of [5,6]-bicyclic hemiacetals.