Organocatalytic Atroposelective Synthesis of Indole Derivatives Bearing Axial Chirality: Strategies and Applications

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(18), P. 2562 - 2580

Published: Sept. 2, 2022

Catalytic atroposelective syntheses of axially chiral compounds have stimulated extensive interest in multiple communities, such as synthetic chemistry, biochemistry, and materials science, because the intriguing characteristics atropisomerism. In particular, atropisomeric indole derivatives, which contain a kind five-membered heterocyclic framework, are widely distributed number natural alkaloids, biologically relevant compounds, ligands, organocatalysts. Hence, catalytic synthesis derivatives bearing axial chirality is considerable importance has become an emerging focus research. However, there substantial challenges associated with including remote ortho-substituents around axis, lower barrier for rotation, weaker configurational stability than that six-membered biaryls. Therefore, development effective strategies toward urgent task.In order to tackle these accomplish task, our group devised unique strategy designing indole-derived platform molecules developing organocatalytic enantioselective transformations synthesize derivatives; asymmetric organocatalysis tremendous advantages was research area recognized by Nobel Prize Chemistry 2021. This Account summarizes endeavors chirality. brief, we developed series molecules, indolylmethanols, (hetero)aryl indoles, oxindole-based styrenes, N-aminoindoles, indole-based homophthalic anhydrides, introducing different functional groups onto ring achieve new reactivity modulate reactive site ring. As result, possess versatile capable undergoing variety preparing structurally diversified chirality.We used plenty chirality, alkene-indoles, N-pyrrolylindoles, isochromenone-indoles. addition, gave thorough detailed understanding designed reaction investigating pathway activation mode. More importantly, studied biological activity some products performed catalyst design on basis moieties, helpful disclosing more applications chirality.In future, will indubitably remain frontier topic catalysis chemistry despite challenging issues, instance, novel unconventional into powerful catalysts or discovery potent drug candidates. We hope efforts summarized this encourage chemists worldwide devise innovative solving issues field, thus promoting its higher level.

Language: Английский

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Atropisomers beyond the C–C axial chirality: Advances in catalytic asymmetric synthesis

Chem, Journal Year: 2022, Volume and Issue: 8(7), P. 1855 - 1893

Published: May 6, 2022

Language: Английский

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Organocatalytic Atroposelective Synthesis of N−N Axially Chiral Indoles and Pyrroles by De Novo Ring Formation

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(17)

Published: Jan. 26, 2022

Abstract The first highly atroposelective construction of N−N axially chiral indole scaffolds was established via a new strategy de novo ring formation. This makes use the organocatalytic asymmetric Paal–Knorr reaction well‐designed N ‐aminoindoles with 1,4‐diketones, thus affording ‐pyrrolylindoles in high yields and excellent atroposelectivities (up to 98 % yield, 96 ee). In addition, this is applicable for synthesis bispyrroles 97 More importantly, such heterocycles can be converted into organocatalysts applications catalysis, some molecules display potent anticancer activity. work not only provides but also offers members atropisomer family promising synthetic medicinal chemistry.

Language: Английский

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Transition Metal-Catalyzed Biaryl Atropisomer Synthesis via a Torsional Strain Promoted Ring-Opening Reaction

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(12), P. 1620 - 1633

Published: June 1, 2022

ConspectusArising from the restricted rotation of a single bond caused by steric or electronic effects, atropisomerism is one few fundamental categories for molecules to manifest their three-dimensional characters into which axially chiral biaryl compounds fall. Despite widespread occurrence skeletons in natural products, bioactive molecules, and ligands/organocatalysts, catalytic asymmetric methods synthesis these structures still lag behind demand. Major challenges preparation biaryls include accessing highly sterically hindered variants while controlling stereoselectivity. A couple useful strategies have emerged direct last two decades.Recently, we engaged atropisomers via transition metal catalysis, including ring-openings dibenzo cyclic compounds. During studies, serendipitously discovered that substituents adjacent axis cause be distorted minimize repulsion. The display higher reactivity ring-opening reactions than non-distorted molecules. In other words, torsional strain can promote reaction. On basis this concept, successfully realized reaction diaryliodoniums, silanes, 9H-fluoren-9-ols, delivered several differently substituted ortho tetra-substituted high enantioselectivity. not only activates substrates toward under mild conditions but also changes chemoselectivity bond-breaking events. palladium-catalyzed carboxylation S-aryl dibenzothiophenium, inversed selectivity exocyclic C–S cleavage reaction.In Account, summarize our studies on copper-, rhodium-, as collection straightforward with enantiopurity above-mentioned strain-promoted coupling strategy. part, energies are discussed aid density functional theory (DFT) calculations.

Language: Английский

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Rhodium-Catalyzed Asymmetric C–H Functionalization Reactions

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(16), P. 10079 - 10134

Published: Aug. 1, 2023

This review summarizes the advancements in rhodium-catalyzed asymmetric C–H functionalization reactions during last two decades. Parallel to rapidly developed palladium catalysis, rhodium catalysis has attracted extensive attention because of its unique reactivity and selectivity reactions. In recent years, Rh-catalyzed have been significantly many respects, including catalyst design, reaction development, mechanistic investigation, application synthesis complex functional molecules. presents an explicit outline catalysts ligands, mechanism, scope coupling reagents, applications.

Language: Английский

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Catalytic Asymmetric Synthesis of Axially Chiral 3,3'‐Bisindoles by Direct Coupling of Indole Rings

Chinese Journal of Chemistry, Journal Year: 2022, Volume and Issue: 40(18), P. 2151 - 2160

Published: May 31, 2022

Comprehensive Summary A new strategy for the enantioselective synthesis of axially chiral 3,3'‐bisindoles was devised by direct coupling two indole rings. This makes use C3‐umpolung reactivity 2‐indolylmethanols, which enables catalytic asymmetric addition reaction 2‐indolylmethanols with rationally designed 2‐substituted indoles, thus constructing 3,3'‐bisindole scaffolds in overall excellent yields (up to 98%) high enantioselectivities 96 : 4 er). approach not only has overcome challenges five‐five‐membered heterobiaryls, but also represents a application catalysis. More importantly, this class can undergo variety post‐functionalizations give 3,3'‐bisindole‐based organocatalysts, have found their preliminary applications

Language: Английский

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Organocatalytic Enantioselective Synthesis of Axially ChiralN,N′‐Bisindoles

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(15)

Published: Feb. 7, 2023

This study establishes the first organocatalytic enantioselective synthesis of axially chiral N,N'-bisindoles via phosphoric acid-catalyzed formal (3+2) cycloadditions indole-based enaminones as novel platform molecules with 2,3-diketoesters, where de novo indole-ring formation is involved. Using this new strategy, various were synthesized in good yields and excellent enantioselectivities (up to 87 % yield 96 ee). More importantly, class exhibited some degree cytotoxicity toward cancer cells was derived into phosphine ligands high catalytic activity. provides a strategy for using asymmetric organocatalysis realize applications such scaffolds medicinal chemistry catalysis.

Language: Английский

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Atropisomers with Axial and Point Chirality: Synthesis and Applications

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(18), P. 2545 - 2561

Published: Sept. 9, 2022

ConspectusEnantiopure atropisomers have become increasingly important in asymmetric synthesis and catalysis, pharmaceutical science, material science since the discovery of inherent features axial chirality originating from rotational restriction. Despite advances made this field to date, it remains highly desirable construct structurally diverse with potentially useful functions. We propose superposition match point as a strategy access complex building blocks for organic because merging atropisomeric backbones one or more extra chiral elements can topologically broaden three-dimensional environments create scaffolds multiple tunable parameters. Over past decade, we successfully implemented strategic design develop series enantiopure utilized synergistic functions these molecules enhance transfer various catalytic transformations.In Account, present several novel superposed developed our laboratory. In studies, was used synthesize both biaryl non-biaryl commercially available sources. Consequently, were demonstrate importance synergetic specific enantioselective reactions. For example, aromatic amide-derived atropisomers, simplified Xing-Phos arrays, broadly employed Ag-catalyzed [3 + 2] cycloaddition by reactions aldiminoesters activated alkenes imines, well being solvating agents discrimination optically active mandelic acid derivatives. Considering powerful potential also explored transition-metal-catalyzed construction backbone (Ar–alkene, Ar–N axis) bearing ligands functional molecules.The studies presented herein are expected stimulate further research efforts on development matching chirality. addition electron stereohindrance effects, synergy between axial/point groups is proven be special function that cannot ignored promoting reactivity chirality-transfer efficiency synthesis. types capable versatile coordination metal catalysts catalysis highlight power synthetically atropisomers.

Language: Английский

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Single‐Step Synthesis of Atropisomers with Vicinal C−C and C−N Diaxes by Cobalt‐Catalyzed Atroposelective C−H Annulation

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(39)

Published: Aug. 2, 2022

The atroposelective synthesis of atropisomers with vicinal diaxes remains rare and challenging, due to the steric influence between two axes their unique topology. Herein, we disclose a single-step construction C-C C-N chiral by cyclopentadiene (Cp)-free cobalt-catalyzed intramolecular C-H annulation, providing desired diaxial structures decent stereocontrols both (up >99 % ee 70 : 1 dr). optically pure products bearing fluorophores show circular polarized luminescence (CPL) properties, being candidate materials for potential CPL applications. Atropisomerization experiments density function theory (DFT) calculations are conducted study rotational barriers rotation pathways diaxes.

Language: Английский

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Design and catalytic atroposelective synthesis of axially chiral isochromenone-indoles

Science China Chemistry, Journal Year: 2022, Volume and Issue: 65(10), P. 1929 - 1937

Published: Sept. 13, 2022

Language: Английский

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