Application of 3-Methyl-2-vinylindoles in Catalytic Asymmetric Povarov Reaction: Diastereo- and Enantioselective Synthesis of Indole-Derived Tetrahydroquinolines

Dai, Wei; Jiang, Xiaoli; Tao, Ji-Yu; Shi, Feng

doi:10.1021/acs.joc.5b02476

Cited by 96 publications

(30 citation statements)

References 55 publications

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“…Afterwards, Shi and co‐workers [240] applied a similar methodology to the enantioselective synthesis of 2,3,4‐trisubstituted indole‐based tetrahydroquinolines 232 using 3‐methyl‐2‐styrylindoles 231 as dienophiles in the one‐pot three‐component Povarov reaction with anilines 204 and aldehydes 39 (Scheme 85). The reaction proceeded most efficiently in toluene in the presence of chiral phosphoric acid ( R )‐ VIIIc bearing bulky 9‐anthracenyl fragments at 3,3′‐positions to give heterocycles 232 with three contiguous stereogenic centers in generally high yield and moderate to excellent stereoselectivity ( dr >19:1, 68–96% ee ).…”

Section: Inverse Electron Demand Asymmetric Aza‐diels‐alder Reactionsmentioning

confidence: 99%

Catalytic Asymmetric Aza‐Diels‐Alder Reaction: Pivotal Milestones and Recent Applications to Synthesis of Nitrogen‐Containing Heterocycles

2021

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In this review, the pivotal achievements and recent advances in catalytic asymmetric aza‐DAR reported up to 2020 are retrospectively considered and their potency for enantioselective synthesis of useful chiral piperidine, quinoline, pyridazine, oxazine and oxadiazine derivatives and fused compounds of higher molecular complexity bearing these pharmacology‐relevant heterocyclic scaffolds is demonstrated. The reported data are systematized according both to key electron transfer modes (normal or invers electron demand reactions) and to main types of attainable heterocyclic products. Of significant attention are an analysis of activation strategies (complexation, enamine or enolate formation, H‐bonding, etc.) applicable to reactions with particular types of dienes and dienophiles and identification of plausible reaction pathways (either concerted or stepwise) over stereoselective cyclization processes. The review contains 310 references and 122 synthetic schemes.

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Section: Inverse Electron Demand Asymmetric Aza‐diels‐alder Reactionsmentioning

confidence: 99%

Catalytic Asymmetric Aza‐Diels‐Alder Reaction: Pivotal Milestones and Recent Applications to Synthesis of Nitrogen‐Containing Heterocycles

2021

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“…13a, 16 So, we further examined the applicability of 3-alkyl-2-vinylindoles 1 in catalytic asymmetric three-component Povarov reactions with anilines 10 and aldehydes 11 (Scheme 6), which smoothly took part in the desired Povarov reaction under the catalysis of CPA-3 to give chiral indole-derived tetrahydroquinolines 12 in high yields and excellent stereoselectivities (up to 99% yield, all >95:5 dr, up to 96% ee). 17 The reaction pathway was suggested to involve a stepwise process of a vinylogous Mannich reaction and the intramolecular Friedel-Crafts reaction, which were activated by CPA via forming hydrogen bonds.…”

Section: Syn Lettmentioning

confidence: 99%

Design and Application of 3-Alkyl-2-vinylindoles in Brønsted Acid Catalyzed Reactions

Mei

Shi

2016

Synlett

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Our group has designed and developed 3-alkyl-2-vinylindoles as a new type of vinylindoles, which have displayed versatile reactivity in Brønsted acid catalyzed reactions. For instance, this class of vinylindoles can act as 2C building blocks in [n+2] cyclizations, as 2,3-disubstituted indoles in dearomatizations, and as NCC building blocks in [3+2] cyclodimerizations. This article summarizes the main contributions of our group in this research field. 1 Introduction 2 As 2C building blocks in [n+2] cyclizations 3 As 2,3-disubstituted indoles in dearomatization 4 As NCC building blocks in [3+2] cyclodimerizations 5 Summary and outlook Key words vinylindole, cyclization, dearomatization, chiral phosphoric acid, organocatalysis Guangjian Mei (left) was born in Henan Province, P. R. of China, in 1988. He received his bachelor's degree in chemistry at Zhengzhou University in 2011. From 2011 to 2016, he pursued his Ph.D. degree in organic synthesis methodology and total synthesis of natural products at Peking University under the guidance of Prof. Zhen Yang and Prof. Chuang-Chuang Li. In 2016, he joined Professor Feng Shi's group at Jiangsu Normal University as a chemist. His current research interests focus on organic synthesis methodology and synthesis of pharmaceutical target molecules. Feng Shi (right) received her Master's degree at Jiangsu Normal University (P. R. of China) in 2004 and then worked at this university as a lecturer. She became an Associate Professor in 2010 at Jiangsu Normal University and got her Ph.D. degree in 2013 at Soochow University (P. R. of China) under the supervision of Prof. Shu-Jiang Tu and Prof. Liu-Zhu Gong. During this period, she spent half a year to work as a visiting scholar in the group of Prof. Teck-Peng Loh at Nanyang Technological University (Singapore). She started her independent career from 2013 and was appointed as a full professor at the Jiangsu Normal University in 2014. Her research interests focus on the organocatalytic asymmetric reactions for the enantioselective construction of heterocyclic frameworks. Since starting the independent work, she has designed a series of chiral Brønsted acid catalyzed cascade reactions, cyclizations and multicomponent reactions to construct a variety of chiral heterocyclic scaffolds containing an indole or spirooxindole moiety. She has published more than 40 papers as a corresponding author in peer-reviewed international journals during the last three years. She is a recipient of the 'Thieme Chemistry Journal Award' (2015) and the 'Outstanding Youth Funds of Jiangsu Province' (2016).

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“…Moreover, the indole nucleus is commonly found in several natural products and displays an indispensable role in therapeutic chemistry (Tzvetkov et al, 2014;Gurer-Orhan et al, 2016;Kumar et al, 2016;Johansson et al, 2013;Blunt et al, 2011;Gul & Hamann, 2005;Sugiyama et al, 2009;Bao et al, 2007;Shaaban et al, 2002;Shaaban & Abdel-Aziz, 2007;Ali Khan et al, 2018;Ndagijimana et al, 2013). Although indole derivatives have been the target of synthetic exploration for many years, more anticancer compounds incorporating the indole scaffold with improved anticancer properties are desired for the systematic study of structure-activity relationships (Hassam et al, 2012;Dai et al, 2016;Singh et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, crystal structures, antiproliferative activities and reverse docking studies of eight novel Schiff bases derived from benzil

et al. 2020

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Eight novel Schiff bases derived from benzil dihydrazone (BDH) or benzil monohydrazone (BMH) and four fused-ring carbonyl compounds (3-formylindole, FI; 3-acetylindole, AI; 3-formyl-1-methylindole, MFI; 1-formylnaphthalene, FN) were synthesized and characterized by elemental analysis, ESI–QTOF–MS, 1H and 13C NMR spectroscopy, as well as single-crystal X-ray diffraction. They are (1Z,2Z)-1,2-bis{(E)-[(1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethane (BDHFI), C32H24N6, (1Z,2Z)-1,2-bis{(E)-[1-(1H-indol-3-yl)ethylidene]hydrazinylidene}-1,2-diphenylethane (BDHAI), C34H28N6, (1Z,2Z)-1,2-bis{(E)-[(1-methyl-1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethane (BMHMFI) acetonitrile hemisolvate, C34H28N6·0.5CH3CN, (1Z,2Z)-1,2-bis{(E)-[(naphthalen-1-yl)methylidene]hydrazinylidene}-1,2-diphenylethane (BDHFN), C36H26N4, (Z)-2-{(E)-[(1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethanone (BMHFI), C23H17N3O, (Z)-2-{(E)-[1-(1H-indol-3-yl)ethylidene]hydrazinylidene}-1,2-diphenylethanone (BMHAI), C24H19N3O, (Z)-2-{(E)-[(1-methyl-1H-indol-3-yl)methylidene]hydrazinylidene}-1,2-diphenylethanone (BMHMFI), C24H19N3O, and (Z)-2-{(E)-[(naphthalen-1-yl)methylidene]hydrazinylidene}-1,2-diphenylethanone (BMHFN) C25H18N2O. Moreover, the in vitro cytotoxicity of the eight title compounds was evaluated against two tumour cell lines (A549 human lung cancer and 4T1 mouse breast cancer) and two normal cell lines (MRC-5 normal lung cells and NIH 3T3 fibroblasts) by MTT assay. The results indicate that four (BDHMFI, BDHFN, BMHMFI and BMHFN) are inactive and the other four (BDHFI, BDHAI, BMHFI and BMHAI) show severe toxicities against human A549 and mouse 4T1 cells, similar to the standard cisplatin. All the compounds exhibited weaker cytotoxicity against normal cells than cancer cells. The Swiss Target Prediction web server was applied for the prediction of protein targets. After analyzing the differences in frequency hits between these active and inactive Schiff bases, 18 probable targets were selected for reverse docking with the Surflex-dock function in SYBYL-X 2.0 software. Three target proteins, i.e. human ether-á-go-go-related (hERG) potassium channel, the inhibitor of apoptosis protein 3 and serine/threonine-protein kinase PIM1, were chosen as the targets. Finally, the ligand-based structure–activity relationships were analyzed based on the putative protein target (hERG) docking results, which will be used to design and synthesize novel hERG ion channel inhibitors.

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Application of 3-Methyl-2-vinylindoles in Catalytic Asymmetric Povarov Reaction: Diastereo- and Enantioselective Synthesis of Indole-Derived Tetrahydroquinolines

Cited by 96 publications

References 55 publications

Catalytic Asymmetric Aza‐Diels‐Alder Reaction: Pivotal Milestones and Recent Applications to Synthesis of Nitrogen‐Containing Heterocycles

Catalytic Asymmetric Aza‐Diels‐Alder Reaction: Pivotal Milestones and Recent Applications to Synthesis of Nitrogen‐Containing Heterocycles

Design and Application of 3-Alkyl-2-vinylindoles in Brønsted Acid Catalyzed Reactions

Synthesis, crystal structures, antiproliferative activities and reverse docking studies of eight novel Schiff bases derived from benzil

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