Article
Chemistry, Organic
Lin Xie, Ruizhe Cao, Yingxue Huang, Qian Zhang, Zeguo Fang, Dong Li
Summary: An efficient cascade bicyclization strategy for the construction of gamma-lactam containing 3,3-disubstituted oxindole derivatives under silver catalysis is described. The method enables the sequential assembly of both unactivated and activated double bonds in N-phenyl-4-pentenamide and N-methyl-N-phenylacrylamide in one pot through a cascade intramolecular cyclization/radical addition/cyclization process. Two N-heterocycles with one C-N bond and two C-C bonds were formed simultaneously.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Article
Chemistry, Organic
Tinghui Zhang, Ziwei Zhong, Zi Zeng, Zitong Zhu, Fei Wang, Yuxin Zhang, Xiaohua Liu, Maoping Pu, Xiaoming Feng
Summary: The asymmetric synthesis of enantioenriched C3-arylated oxindoles has been achieved via the Friedel-Crafts alkylation of 3-bromo-3-substituted oxindoles with arenes and heteroarenes, using a chiral N,N'-dioxide/transition metal complex as the catalyst.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Shuai Zhang, Nan Jiang, Jun-Zhao Xiao, Guo-Qiang Lin, Liang Yin
Summary: A copper(I)-catalyzed asymmetric hydrophosphination of 3,3-disubstituted cyclopropenes is reported, providing a range of highly selective phosphine derivatives. The method shows broad substrate scope and the high stereoselectivity is attributed to the stability of the Cu(I)-(R,R)-QUINOXP* complex and its asymmetric induction. Finally, the method is used for the synthesis of new chiral phosphine-olefin compounds, one of which serves as a wonderful ligand in Rh-catalyzed asymmetric conjugate addition.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Shuai Zhang, Nan Jiang, Jun-Zhao Xiao, Guo-Qiang Lin, Liang Yin
Summary: Herein, a copper(I)-catalyzed asymmetric hydrophosphination method for 3,3-disubstituted cyclopropenes is reported. The method provides phosphine derivatives with high diastereo- and enantioselectivities. It has a broad substrate scope and the high stereoselectivity is attributed to the stability and asymmetric induction of the Cu(I)-(R,R)-QUINOXP* complex. The method is also used for the synthesis of new chiral phosphine-olefin compounds, which serve as ligands in Rh-catalyzed asymmetric conjugate addition reactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Jabir Khan, Naveen Yadav, Aparna Tyagi, Chinmoy Kumar Hazra
Summary: In this study, a mild and metal-free approach for synthesizing valuable and sterically demanding unsymmetrical 3,3-disubstituted 2-oxindoles via reductive cyclization of alpha-ketoamides is reported. This protocol, initiated by a silyl cation and catalyzed by a Bronsted acid, offers excellent regioselectivity and good functional group tolerance. It provides an easy access to the scaffolds of azonazine and its derivatives with an excellent syn-diastereoselectivity bearing all carbon quaternary stereocenters.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Jing Sun, Chen Yan, Qiu Sun, Ying Han, Chao-Guo Yan
Summary: In chloroform, the p-TsOH promoted annulation reaction of 3-(indol-3-yl)maleimides and (indol-2-yl)diphenylmethanols resulted in functionalized pyrrolo[3 ',4 ':6,7]cyclohepta[1,2-b:4,5-b ']diindoles with satisfactory yields, demonstrating a formal [4+3] cycloaddition and an unprecedented rearrangement of the maleimide motif. Alternatively, the reaction of 3-(indol-3-yl)maleimides and 3-hydroxy-3-(indol-3-yl)-indolin-2-ones in acetonitrile produced functionalized spiro[indoline-3,9 '-pyrrolo[3 ',4 ':4,5]cyclopenta[1,2-b]indole] in good yields and with high diastereoselectivity. On the other hand, the p-TsOH promoted reaction of 3-(indol-3-yl)maleimides and 2-hydroxy-2-(indol-3-yl)-indene-1,3-diones yielded functionalized spiro[indene-2,9 '-pyrrolo[3 ',4 ':4,5]cyclopenta[1,2-b]indoles] as major products and spiro[indene-2,9 '-pyrrolo[3 ',4 ':6,7]cyclohepta[1,2-b:4,5-b ']diindoles] as minor products.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Qianwen Jiang, Dekun Zhang, Mengyao Tang, Hua Liu, Xiaoyu Yang
Summary: A novel kinetic resolution method has been developed for the synthesis of 3,3-disubstituted indolines with C3-quaternary stereocenters. The method utilizes triazane formation reaction and dehydrogenation reaction to achieve high enantioselectivity. This method has significant synthetic value.
SCIENCE CHINA-CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Xuan Huang, Hongling Wang, Qingxiang Cao, Yong Li, Junmin Zhang
Summary: A simple and direct method to synthesize 3,3-disubstituted oxindoles was disclosed using readily available formaldehyde and isatins (and their imines) as substrates under microwave heating with a mild base. Formaldehyde acts as both a reductant (via a Cannizzaro process with isatin) and an electrophile in the reaction.
Article
Chemistry, Organic
Vidyasagar Maurya, Mahesh S. Kutwal, Chandrakumar Appayee
Summary: A novel catalytic asymmetric reaction for the synthesis of disubstituted 4-oxocyclohexanecarbaldehyde using acetone and cinnamaldehyde has been developed. By changing the enantiomer of one of the chiral catalysts, both enantiomers of the same diastereomeric products can be obtained in good yield and diastereoselectivity. The practicality of this methodology is demonstrated through gram-scale synthesis.
Review
Chemistry, Applied
Sushovan Paladhi, Jin Hyun Park, Barnali Jana, Han Yong Bae, Choong Eui Song
Summary: This review summarizes recent advances in the construction of all-carbon quaternary or hetero-carbon quaternary stereocenters via metal-catalyzed and organocatalyzed asymmetric conjugate addition to β,β-disubstituted nitroalkenes, focusing on the scope, applications, and mechanisms of these reactions.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Binghao Liu, Xiao-Yong Duan, Jiahan Li, Yatong Wu, Yanting Li, Jing Qi
Summary: A new enantio- and diastereoselective reaction has been developed for the synthesis of various spirocyclic bisoxindole alkaloids. This reaction exhibits a broad substrate scope and excellent enantioselectivity, and allows for the creation of two contiguous sterically congested all-carbon quaternary stereocenters.
Article
Chemistry, Organic
Sivaparwathi Golla, Naveenkumar Anugu, Swathi Jalagam, Hari Prasad Kokatla
Summary: A transition-metal and hydride-free reductive aldol reaction has been developed using rongalite for the synthesis of biologically active 3,3'-disubstituted oxindoles from isatin derivatives. This method offers high yields of 3-hydroxy-3-hydroxymethyloxindoles and 3-amino-3-hydroxymethyloxindoles, making it suitable for gram scale synthesis with cost-effective rongalite.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Organic
Yang Wang, Mo Yang, Yuan-Yuan Sun, Zheng-Guang Wu, Hong Dai, Shuhua Li
Summary: In this study, the first intramolecular C-N bond formation of phenylpropanamide derivatives via organocatalytic oxidative reactions was reported, yielding 3,3-disubstituted oxindole derivatives with up to 99% yield. The high efficiency of this reaction is demonstrated by the ability to perform the reaction on a gram scale under transition metal-free mild conditions. Additionally, DFT calculation of the catalytic oxidative transformation pathway was also studied.
Article
Chemistry, Multidisciplinary
Xiao-Jing Zhao, Zi-Hao Li, Tong-Mei Ding, Jin-Miao Tian, Yong-Qiang Tu, Ai-Fang Wang, Yu-Yang Xie
Summary: The challenging direct asymmetric catalytic aerobic oxidative cross-coupling of 2-naphthylamine and 2-naphthol using a novel Cu-I/SPDO system has been successfully developed for the first time, achieving high enantioselectivities and good yields. The DFT calculations suggest that specific interactions and stacking between the coupling partners play vital roles in the enantiocontrol of this reaction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Hiyori Takebe, Seijiro Matsubara
Summary: 2,6-Disubstituted cuneane has the potential to serve as a novel chiral scaffold and a p-disubstituted benzene bioisostere. It is a constitutional isomer of a 1,4-disubstituted cubane obtained through a metal-catalyzed skeletal rearrangement. Unlike the highly symmetrical 1,4-disubstituted cubane, the isomerized 2,6-disubstituted cuneane is a chiral molecule with C-2 symmetry. Examination of various chiral catalysts revealed that the Pd-pincer catalyst provides good asymmetric induction.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Jiuling Li, Dong Xing, Wenhao Hu
Summary: An efficient synthesis method for alpha-halo-alpha-arylseleno ketones has been developed through gem-difunctionalization of alpha-diazoarylketones with diaryldiselenides and N-halosuccinimides. A series of products were obtained in excellent yields and chemoselectivities under mild conditions. The transformation is proposed to occur via the generation of a key intermediate arylselenenyl halide from diaryldiselenides/N-halosuccinimides, followed by addition with alpha-diazoarylketones to form the desired gem-difunctionalization products.
MOLECULAR DIVERSITY
(2021)
Article
Chemistry, Organic
Farrukh Sajjad, Alavala Gopi Krishna Reddy, Dong Xing, Suzhen Dong, Wenhao Hu
Summary: An unprecedented synthetic route towards a variety of 3-anilino-1H-indoles has been achieved through a domino ruthenium-catalyzed annulation and subsequent iron-promoted fragmentation and rearrangement. The strategy is applicable to deliver diversely substituted indole esters, with compound 4i exhibiting the best inhibitory activity with an IC50 value of 0.05 mu M, paving the way for the discovery of promising lead compounds in the future.
Article
Chemistry, Multidisciplinary
Guizhi Dong, Ming Bao, Xiongda Xie, Shikun Jia, Wenhao Hu, Xinfang Xu
Summary: The study presents an unprecedented catalytic asymmetric allylation of isatins and isatin-derived ketimines via a gold and chiral organocatalyst cooperative catalysis strategy, leading to the expeditious synthesis of chiral 2,5-disubstituted alkylideneoxazolines with vicinal stereogenic centers. The mechanism involves an alkylgold intermediate, and the X-ray crystal structure of the allylgold species reveals its unique stability and reactivity. Additionally, an asymmetric formal hetero-ene reaction of the gold intermediate is enabled with the assistance of a quinine-derived squaramide catalyst, extending the synthetic applications of gold complexes and the versatility of gold catalysis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Medicinal
G. Lakshma Reddy, Rupam Sarma, Shuhao Liu, Weifeng Huang, Jinping Lei, Jiasheng Fu, Wenhao Hu
Summary: This study describes the design and synthesis of novel benzo[4,5]imidazo[1,2-a]pyrazin-1-amine derivatives, which showed promising A(2A) adenosine receptor antagonist activity, with compound 27 demonstrating good activity and potential application in T-cell activation. Molecular docking studies were conducted to explain the observed binding affinity of compound 27.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Ming Bao, Jinzhou Chen, Chao Pei, Sujie Zhang, Jinping Lei, Wenhao Hu, Xinfang Xu
Summary: An unprecedented gold-catalyzed ketene C=O/C=C bifunctionalization method has been developed, initiated by gold-catalyzed Wolff rearrangement of diazoketone to form the ketene intermediate, followed by nucleophilic addition and terminated with two divergent cyclization processes. Depending on the nucleophiles used, different cyclization pathways are observed, leading to the formation of different products, providing a novel reaction pattern for the ketene dual functionalization.
SCIENCE CHINA-CHEMISTRY
(2021)
Article
Chemistry, Physical
Kemiao Hong, Shanliang Dong, Xinxin Xu, Zhijing Zhang, Taoda Shi, Haoxuan Yuan, Xinfang Xu, Wenhao Hu
Summary: An enantioselective intermolecular Mannich-type interception of phenolic oxonium ylides with imines has been developed using cooperative catalysis with achiral dirhodium complex and chiral phosphoric acid. The synthesis of enantioenriched 2,2-disubstituted dihydrobenzofurans with good to high yield and high to excellent enantioselectivity under mild conditions was achieved. Preliminary antitumor activity study showed high anticancer potency of the reduction product 7 against human lung adenocarcinoma cells (A549 cells, IC50 = 9.13 mu M).
Article
Chemistry, Multidisciplinary
Zhenghui Kang, Wenju Chang, Xue Tian, Xiang Fu, Wenxuan Zhao, Xinfang Xu, Yong Liang, Wenhao Hu
Summary: The study presents a novel asymmetric allylation reaction through ternary cooperative catalysis, enabling the expedient access to chiral alpha,alpha-disubstituted ketones with high enantioselectivity. Experimental and computational studies have elucidated the mechanism and origin of enantioselectivity in this three-component reaction.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Organic
Xiangrong Liu, Xue Tian, Jiawu Huang, Yu Qian, Xinfang Xu, Zhenghui Kang, Wenhao Hu
Summary: An enantioselective three-component reaction of alpha-propargylic-3-indolymethanol with diazoindolinone and alcohol has been achieved under the cocatalysis of Rh(II) and chiral phosphoric acid (CPA). The reaction proceeds through regio- and enantiospecific addition of an in situ formed oxonium ylide to the alpha-propargylic indole iminium ion, providing an efficient access to chiral propargylic indole derivatives with high yields and enantioselectivities.
Article
Chemistry, Physical
Yong-Liang Su, Geng-Xin Liu, Luca De Angelis, Ru He, Ammar Al-Sayyed, Kirk S. Schanze, Wen-Hao Hu, Huang Qiu, Michael P. Doyle
Summary: This study demonstrates the efficient generation of functionalized derivatives through photocatalyzed multicomponent reactions using nitrogen aromatic heterocycles, alkenes, and diazo compounds. The reaction shows high functional group tolerance and exacting regioselectivities. Mechanistic studies, including photophysical measurements, provide insights into this radical cascade reaction.
Article
Chemistry, Organic
Xiang Fu, Jie Tang, Ruyu Hua, Xiaoqian Li, Zhenghui Kang, Huang Qiu, Wenhao Hu
Summary: This study reports two DNA-compatible reactions with alkenes and diazo compounds, providing hydroalkylation and cyclopropanation products in moderate to excellent yields. These transformations not only offer new access to C(sp3)-C(sp3) bond formation in DELs with excellent functional group tolerance, but also represent practical ligation methods to introduce functionalized molecules into DNA.
Article
Chemistry, Organic
Su Zhou, Qianqian Liu, Ming Bao, Jie Huang, Junjian Wang, Wenhao Hu, Xinfang Xu
Summary: A new synthesis method for 2-indolyl indolone N-oxides via gold(i)-catalyzed cascade reaction of o-nitroalkynes with indoles has been developed, leading to highly efficient conversion into 2-indolylbenzoxazinone with strong blue fluorescence. The synthesized compounds were also evaluated for their antitumor activity in small cell lung cancer, with compounds 3d and 4s showing high anticancer potency against SCLC cells.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Organic
Kai Zhou, Ming Bao, Hongkai Sha, Guizhi Dong, Kemiao Hong, Xinfang Xu, Wenhao Hu
Summary: A Rh-catalyzed diastereoselective three-component reaction has been developed for the efficient synthesis of vicinal diamine derivatives with two tertiary stereocenters in high yields (75%->95%) and high to excellent diastereoselectivities. The generated product can be easily converted to free diamines via hydrolysis of the imine motif under mild conditions.
ORGANIC CHEMISTRY FRONTIERS
(2021)
Article
Chemistry, Organic
Farrukh Sajjad, Yanmei Chen, Xue Tian, Suzhen Dong, Alavala Gopi Krishna Reddy, Wenhao Hu, Dong Xing
Summary: An efficient strategy for the construction of 1,4-oxazines from simple alpha-amino ketones and diazo pyruvates catalyzed by RuCl3 was reported, showing promising anticancer activities towards HCT116. This transformation involves a tandem N-H insertion/cyclization sequence via an enol formation under mild reaction conditions with broad functional group tolerance.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Qiyao Zheng, Hui Dong, Jianshan Mo, Yi Zhang, Jie Huang, Shumin Ouyang, Shuo Shi, Kai Zhu, Xinming Qu, Wenhao Hu, Peiqing Liu, Yuanxiang Wang, Xiaolei Zhang
Summary: Constitutive activation of STAT3 is common in NSCLC and plays a crucial role in cancer progression and acquired resistance to targeted therapies. W2014-S, a novel STAT3 inhibitor, demonstrated significant anti-tumor activities by disrupting STAT3 signaling and sensitizing resistant NSCLC cells to EGFR-TKIs in vitro and in vivo. Combining W2014-S with gefitinib could be a promising strategy to overcome EGFR-TKIs acquired resistance in NSCLC patients.
Article
Chemistry, Organic
Jiuling Li, Bin Li, Juan Chen, Xinyu Jia, Min Wang, Chengjun Hao, Xinhua Zheng, Hongmei Dai, Wenhao Hu
Summary: A series of gem-chlorosulfurization products bearing difluoromethyl substituents were synthesized directly from p-toluenesulfonyl difluorodiazoethane (TsCF2CHN2), disulfides, and PhICl2 in high to excellent yields without the need for any catalysts or additives. The products showed high functional group compatibility and could be efficiently converted to sulfur-containing and aryl substituted difluoromethyl derivatives through a feasible multi-component operation.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2021)