Article
Chemistry, Organic
Zhi Chen, Wenkai Zhu, Chaodong Wang, Ning Xu, Qianxi Jin, Xule Huang, Shengjie Song, Jianjun Li
Summary: Difluorinated compounds play an important role in organic synthesis and medicinal chemistry due to fluoride's ability to modify molecule properties. This paper presents an efficient method for difluorination of inert C(sp(3))-H bonds using an N-directed 1,5-hydrogen-atom transfer (1,5-HAT) strategy. The approach allows for late-stage difluorination of complex molecules and can tolerate various functional groups. The proposed mechanism involves the formation of an amine radical cation and a radical chain propagation process, providing a new avenue for nitrogen-centered radical generation in the 1,5-HAT reaction.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Organic
Danna Chen, Xuege Yang, Dongyin Wang, Yanni Li, Lou Shi, Deqiang Liang
Summary: We describe an electrophotocatalytic cascade reaction of alkenes with fluoromethanesulfinate salts, which enables tri- or difluoromethylation and cyclization. This reaction proceeds under mild electrode potentials without the need for external oxidants and is applicable to a broad range of alkenes, producing a diverse array of fluoromethylated heterocycles. The use of the inexpensive photocatalyst eosin Y allows for good functional-group tolerance and accommodates unactivated olefins, which are typically not compatible with previous oxidative cyclizations of alkenes unless a strong chemical oxidant is present. Preliminary mechanistic studies suggest the involvement of both electrolysis and the reductive quenching photocatalytic cycle of eosin Y.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Yuanqiang Guo, Ruiguo Wang, Hongjian Song, Yuxiu Liu, Qingmin Wang
Summary: The protocol described in this study utilizes electrochemical cathode reduction to generate trifluoromethyl radicals using an inexpensive and readily available trifluoromethylation reagent (IMDN-SO2CF3). The reaction can be efficiently conducted without the need for additional redox reagents, allowing for electrochemical trifluoromethylation/cyclization for the synthesis of isoquinoline-1,3-diones and oxindoles. This strategy demonstrates good functional group tolerance and a broad substrate scope.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Organic
Xi Hu, Minglin Tao, Kaixing Gong, Qin Feng, Xiao Hu, Yanni Li, Shaoguang Sun, Deqiang Liang
Summary: An electrochemical or photoelectrochemical regioselective polyfluoroalkylation/cyclization cascade of 3-aza-1,5-dienes with sodium fluoroalkanesulfinates is reported. This protocol provides 3-polyfluoroalkylated 4-pyrrolin-2-ones in a one-step reaction from readily available N-vinylacrylamides, demonstrating broad substrate scope, good functional group tolerance, and scalability without the need for mild conditions, oxidants, transition metals, or electrolytes.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Xin He, Zhicheng Chen, Xianghui Zhu, Hao Liu, Yanjie Chen, Zhizhong Sun, Wenyi Chu
Summary: A metal and oxidant free photoredox catalyzed trifluoromethylation protocol of 2H-indazoles was developed using Eosin Y as the photocatalyst and recoverable ionic liquids as the solvents. Trifluoromethylated products were obtained in moderate to good yields under mild conditions. The reaction proceeded via a free-radical mechanism with broad substrate range, excellent regioselectivity, and good functional group tolerance. Furthermore, the protocol demonstrated its utility in the synthesis of a highly selective ligand for estrogen receptor beta (ER beta) and the drug granisetron. This protocol provides a mild and environmentally friendly solution for trifluoromethylation reaction.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Organic
Guillaume Levitre, Albert Granados, Maria Jesuprimes Cabrera-Afonso, Gary A. Molander
Summary: In this study, a metallaphotoredox method using a dual catalysis system of boronic acids was developed for the preparation of fluoroalkylarenes. The mild conditions of this method allow for a broad range of functional group tolerance, including substrates containing aldehydes, free phenols, and N-Boc-protected amines.
Article
Chemistry, Applied
Yang Li, Wei-Fang Zuo, Jian-Hua Chen, Wei Li, Jinfeng Zheng, Bo Han, Xiang Li, Wei Huang
Summary: In this study, we present a [3+2] cycloaddition reaction using rationally designed trisubstituted cyclic alpha-chloroamides as potent synthons for synthesizing valuable spirocyclic gamma-lactam architectures. The protocol exhibits high yields, substrate compatibility, and scalability. Moreover, this study demonstrates the utilization of enaminone C-N bond cleavage to engineer biologically relevant spirocyclic gamma-lactam skeletons, which is a rare example in the field.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Jing Qi, Jinhui Xu, Hwee Ting Ang, Bingbing Wang, Nipun Kumar Gupta, Srinivas Reddy Dubbaka, Patrick O'Neill, Xianwen Mao, Yanwei Lum, Jie Wu
Summary: In this study, a novel electrophotochemical approach is presented for the selective trifluoromethylation of (hetero)-arenes using trifluoroacetic acid (TFA) as the CF3 source. The method offers sustainable and environmentally-friendly synthesis of CF3-, CF2H-, and perfluoroalkyl-containing (hetero)-arenes with improved chemoselectivity by light irradiation.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Yuan Shi, Kai Wang, Yuxin Ding, Yuanyuan Xie
Summary: A simple metal-free protocol for C-H trifluoromethylation of hydrazones via electrolysis was developed. This environmentally friendly transformation exhibited high efficiency, good tolerance, and the ability to scale-up functionalization, yielding the desired products in moderate to good yields. Additionally, different trifluoromethyl reagents were used to achieve high yields for substrates containing either electron-donating or electron-withdrawing groups. The radical mechanism was confirmed through control experiments.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Organic
A. Young Ji, Annaram Thirupathi, Joon Young Hwang, Yuri Kim, Gyuri Han, Kwang-Hyun Ahn, Kyungtae Kang, Eun Joo Kang
Summary: The Fe-III(phen)(3) catalysis of the benzylic C(sp(3))-H azidation of indoles has been studied. The Fe(III) complex can selectively oxidize indoles to form arene radical cations, which are transformed into benzylic C(sp(3)) radical intermediates. This strategy exhibits a difference in reactivity between N-heteroarenes and benzene, which is difficult to achieve via direct hydrogen abstraction approaches. Various biorelevant azide precursors were constructed, highlighting the utility of this mild first-row transition-metal catalyst system.
Article
Chemistry, Organic
A. Young Ji, Annaram Thirupathi, Joon Young Hwang, Yuri Kim, Gyuri Han, Kwang-Hyun Ahn, Kyungtae Kang, Eun Joo Kang
Summary: The FeIII(phen)3 catalysis of benzylic C(sp3)-H azidation of indoles was studied. The Fe(III) complex can selectively oxidize indoles to form arene radical cations, which further transform into benzylic C(sp3) radical intermediates. This strategy exhibits a difference in reactivity between N-heteroarenes and benzene, which is difficult to achieve via direct hydrogen abstraction approaches. Various biorelevant azide precursors were synthesized, demonstrating the utility of this mild first-row transition-metal catalyst system.
Article
Chemistry, Organic
Yuichi Ikemoto, Sho Chiba, Zhenyao Li, Qiang Chen, Hiroki Mori, Yasushi Nishihara
Summary: Copper-catalyzed carboazidation of alkenes with trimethylsilyl azide and cyclic ethers has been achieved, allowing cyclic ethers to be used as alkylating reagents under oxidative conditions. Styrene derivatives and 1,1-diaryl alkenes can be used as starting materials to obtain carboazidation products. The reaction proceeds via a radical pathway, as shown by radical trapping and clock experiments.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Leilei Wang, Leiyang Lv, Zhiping Li
Summary: In this study, the concomitant functionalization of two distinct alpha-C-H bonds of carbonyls integrated with unactivated olefins and tert-butyl hydroperoxide was achieved in one pot using Bronsted acid catalysis and radical relay coupling. The method yielded a variety of structurally valuable unsymmetrical peroxy 1,9-diketones in moderate to good yields under metal-free conditions.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Review
Chemistry, Multidisciplinary
Pan Xiao, Xavier Pannecoucke, Jean-Philippe Bouillon, Samuel Couve-Bonnaire
Summary: Decarboxylation strategy is a powerful tool for the synthesis of fluorine-containing organic compounds, and can be achieved through the reaction of non-fluorinated carboxylic acids with fluorinating reagents, as well as the exploration and use of fluorine-containing carboxylic acids in decarboxylative transformations.
CHEMICAL SOCIETY REVIEWS
(2021)
Article
Chemistry, Organic
Pan Zhou, Shanya Lu, Xiaoqiang Wu, Wei Zhong, Tao Xu
Summary: A cross-coupling reaction between aldehydes and alpha-trifluoromethyl alkyl bromides was successfully developed using a dual nickel/photoredox catalysis system. This reaction afforded alpha-trifluoromethyl ketones under mild conditions (visible light, ambient temperature, no strong base) with a wide range of substrates bearing various functional groups. The selectivity of the trifluoromethyl group on one side of the ketones can be modulated by different reagents, allowing for tunable access to these ketones.
Article
Chemistry, Physical
Zhe Wang, Jiang-Tao Cheng, Zhichao Shi, Na Wang, Feng Zhan, Sheng-Peng Jiang, Jin-Shun Lin, Yuyang Jiang, Xin-Yuan Liu
Summary: This study reported a first catalytic enantioselective intermolecular radical aminotrifluoromethylation of alkene with hydrazine and Togni's reagent by Cu(I)/CPA cooperative catalysis, accessing enantioenriched diarylmethylamines. The highly asymmetric induction of C-N bond formation was achieved by using a CPA catalystviahydrogen-bonding and ion pair interaction, leading to high enantioselectivity and excellent chemoselectivity.
Article
Chemistry, Applied
Zhichao Shi, Tingting Fan, Xun Zhang, Feng Zhan, Zhe Wang, Lei Zhao, Jin-Shun Lin, Yuyang Jiang
Summary: A Y(OTf)(3)-catalyzed reaction has been developed for the efficient synthesis of imidazolidines, which show promising anti-tumor activity against various human cancer cell lines. Mechanistic investigations suggest these imidazolidines are formed through an S(N)1-like pathway.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Multidisciplinary
Feng Zhan, Zhe Wang, Guan-Zheng Wu, Zhichao Shi, Xun Zhang, Qinglu Zuo, Jin-Shun Lin, Yuyang Jiang
Summary: A TfOH-catalyzed [3+2] cycloaddition of donor-acceptor oxiranes with isothiocyanates was developed, allowing for the synthesis of highly substituted 1,3-oxathiolane-2-imines with high yields, Z-selectivity, and excellent functional group tolerance. The reaction protocol can be easily scaled up to gram level and the cycloadduct can be transformed into 1,3-oxathiolane-2-one through acid hydrolysis with moderate yield.
Article
Chemistry, Multidisciplinary
Wang Xia, Zi-An Zhou, Jie Lv, Shao-Hua Xiang, Yong-Bin Wang, Bin Tan
Summary: A new organocatalytic approach was developed for the synthesis of N-naphthyl phenothiazine and phenoxazine scaffolds through azo-group enabled C-H amination of arenes. This reaction showcased operational simplicity, substrate generality, and excellent functional group compatibility, with the catalyst efficiency preserved after 5 catalytic cycles.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Na Wang, Li-Wen Fan, Jin Zhang, Qiang-Shuai Gu, Jin-Shun Lin, Guo-Qiang Chen, Xin-Yuan Liu, Peiyuan Yu
Summary: This study investigates the highly enantioselective intramolecular hydroamination reaction and uncovers its uncommon reaction mechanism. The reactivity of this reaction is primarily determined by the substituents on the internal carbon of the alkene, as well as the substituents on the terminal alkene carbons. The lower acidity of chiral phosphoric acids compared to chiral NTPAs results in a slower reaction.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Review
Chemistry, Multidisciplinary
Jun Kee Cheng, Shao-Hua Xiang, Bin Tan
Summary: This paper describes the strategies to address the challenges in efficient synthetic access and skeletal variety within the organocatalytic context. The approaches include modulating nucleophilicity, designing electron-withdrawing activating groups, and using electrophilic arene precursors for arylation. These strategies have led to the synthesis of structurally diverse axially chiral compounds.
ACCOUNTS OF CHEMICAL RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Shi-Jiang He, Shuai Zhu, Sheng-Qi Qiu, Wei-Yi Ding, Jun Kee Cheng, Shao-Hua Xiang, Bin Tan
Summary: This study discovered a novel type of axially chiral anthrone-derived skeleton by introducing axial chirality on symmetric anthrone skeletons through stereoselective condensation. The enantioenriched anthrones could be further transformed into dibenzo-fused seven-membered N-heterocycles with well-defined stereogenic center via Beckmann rearrangement.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Pengquan Chen, Mei-Jun Lv, Jun Kee Cheng, Shao-Hua Xiang, Xiang-Zhong Ren, Junmin Zhang, Bin Tan
Summary: Azonaphthalenes have been confirmed as effective arylation reagents for various asymmetric transformations. In this study, a highly efficient approach to form triaryl-substituted all-carbon quaternary stereocenters through chiral phosphoric acid-catalyzed enantioselective arylation of 3-aryl-2-oxindoles with azonaphthalenes is revealed. This chemistry is scalable and demonstrates excellent functional group tolerance, providing a series of 3,3-disubstituted 2-oxindole derivatives in good yields with excellent enantiocontrol.
Article
Chemistry, Multidisciplinary
Peng-Ying Jiang, San Wu, Guan-Jun Wang, Shao-Hua Xiang, Bin Tan
Summary: QUINAPs have been widely used in enantioselective transformations, but their limited substrate range and high cost hinder their broader application. In this study, we report the first atroposelective oxidation of an N atom using a chiral ketone catalyst, allowing the kinetic resolution of QUINAPOs with excellent enantioselectivity. The enantioenriched products can be easily converted into the desired QUINAP targets without loss of stereochemical integrity. Mechanistic investigations reveal the involvement of a dioxirane as the active catalytic species.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Ming Wu, Yi-Wei Chen, Qian Lu, Yong-Bin Wang, Jun Kee Cheng, Peiyuan Yu, Bin Tan
Summary: A highly efficient method for the synthesis of atropisomers through functionalization of the Si-C bond between dinaphthosiloles and silanol nucleophiles was presented. The versatile nature of the Si-C bond allows for the facile derivatization of chiral products into other functional atropisomers.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Si-Li Lin, Ye-Hui Chen, Huan-Huan Liu, Shao-Hua Xiang, Bin Tan
Summary: In this study, chiral cyclobutene units were synthesized using bicyclo[1.1.0]butanes for the first time, offering an efficient and asymmetric route with good regio- and enantiocontrol. Control experiments verified the formation of a key carbocation intermediate at the benzylic position.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Ye-Hui Chen, Meng Duan, Si-Li Lin, Yu-Wei Liu, Jun Kee Cheng, Shao-Hua Xiang, Peiyuan Yu, Kendall N. Houk, Bin Tan
Summary: This article introduces an effective strategy for umpolung functionalization of imines through aromatization. The attachment of strongly electron-withdrawing groups to imines enhances their reactivity, enabling direct amination of (hetero)arenes. Additionally, the use of chiral catalysts allows for the synthesis of (hetero)aryl C-N atropisomers or enantioenriched aliphatic amines.
Article
Chemistry, Multidisciplinary
Peng-Ying Jiang, San Wu, Guan-Jun Wang, Shao-Hua Xiang, Bin Tan
Summary: QUINAPs are a crucial class of chiral compounds that have remarkable features in stereoinduction. However, their restricted substrate range and expensive price limit their broader utilization. In this study, the first atroposelective oxidation of an N atom using a chiral ketone catalyst was described, allowing the kinetic resolution of QUINAPOs with excellent enantioselectivity. Mechanistic investigations revealed the role of a dioxirane as the active catalytic species. The developed protocol has practicality and can be applied in enantioselective transformations.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Ming Wu, Yi-Wei Chen, Qian Lu, Yong-Bin Wang, Jun Kee Cheng, Peiyuan Yu, Bin Tan
Summary: Chiral organosilanes are important chemical entities in the development of functional organic materials, asymmetric catalysis, and medicinal chemistry. An efficient method for atroposelective synthesis of biaryl siloxane atropisomers via organocatalytic Si-C bond functionalization of dinaphthosiloles with silanol nucleophiles is presented. The reaction proceeds through an asymmetric protonation and simultaneous Si-C bond cleavage/silanolysis sequence in the presence of a newly developed chiral Bronsted acid catalyst. The versatile nature of the Si-C bond expands the applicability of this method.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Heng-Hui Li, Shaoyu Li, Jun Kee Cheng, Shao-Hua Xiang, Bin Tan
Summary: An efficient photocatalytic system for obtaining functionalized N-heterobiaryls under mild conditions is described, suitable for gram-scale synthesis. The method demonstrates practicality and accessibility using commercially available starting materials.
CHEMICAL COMMUNICATIONS
(2022)
