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

Accounts of Chemical Research, Год журнала: 2022, Номер 55(18), С. 2562 - 2580

Опубликована: Сен. 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.

Язык: Английский

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

Chem, Год журнала: 2022, Номер 8(7), С. 1855 - 1893

Опубликована: Май 6, 2022

Язык: Английский

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Organocatalytic Enantioselective Synthesis of Axially Chiral Molecules: Development of Strategies and Skeletons

Accounts of Chemical Research, Год журнала: 2022, Номер 55(20), С. 2920 - 2937

Опубликована: Сен. 30, 2022

The growing importance of axially chiral architectures in different scientific domains has unveiled shortcomings terms efficient synthetic access and skeletal variety. This account describes our strategies answering these challenges within the organocatalytic context where emergence bifunctional catalysts such as phosphoric acids (CPAs) proven invaluable controlling sense axial chirality. wide occurrence bi(hetero)aryl skeletons privileged structures constitutes a strong motivation to devise more effective arylation methods. Our design revolves around modulating intrinsic nucleophilicity aromatic amines alcohols. first approach involves an electron-withdrawing activating group which could associate with catalyst for reactivity enhancement selectivity control. resonance arenes offers unique mechanistic possibility select between sites. C2-Azo- nitroso-substituted naphthalenes undergo atroposelective ortho C- or N-arylation (hetero)aromatic nucleophiles. For monocyclic benzenes, programmable charge localization leads regioselective activation by catalytic control alone aided substrate design. instance, selective addition nitroso nitrogen enables successive annulation initiated amine yield N-arylbenzimidazoles. In biomimetic manner, finely tuned direct para-selective nucleophilic azobenzenes. second strategy employs electrophilic arene precursors occurs via rearomatization central-to-axial chirality transfer. enabled (imino)quinones indoles phenylindole atropisomers. By adapting this chemistry additional oxidation event liberate carbonyl functionalities, aryl-o-naphthoquinone aryl-p-quinone atropisomers were attained. Along development new strategies, deriving been another consistent theme research program. functionalization alkynes provides broad entry atropisomeric alkenes. monofunctionalization through interception vinylidene-quinone-methide (VQM) intermediate 2-naphthols yielded EBINOL scaffolds. designing internal directing group, dihalogenation was realized using abundant alkali halides despite their weak nucleophilicities poor solubilities. N-alkylation alkenes pursued prepare multifunctionalized alkene that be converted into 2-arylpyrroles synthesis B-aryl-1,2-azaborines containing C-B axis accomplished CPA effects desymmetrization defines configuration distal bond. Inspired scaffold allenes, we leveraged developed achieve para-addition dearomatization judiciously designed azobenzenes, led structurally novel cyclohexadienylidene-based hydrazones. To complement structures, cyclohexadienyl oxime ethers also attained CPA-catalyzed condensation hydroxylamines spiro[4.5]trienones.

Язык: Английский

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Stereoselective construction of atropisomers featuring a C–N chiral axis

Green Synthesis and Catalysis, Год журнала: 2022, Номер 3(2), С. 117 - 136

Опубликована: Янв. 4, 2022

Atropisomeric C–N compounds belong to an important class of axially chiral compounds. However, whereas the asymmetric synthesis biaryl atropisomers have been well established, general and efficient strategies access single enantiomers are still rare. Until recently, innovative methods developed, providing new opportunities for highly stereoselective this vital atropisomers. Herein, we comprehensively summarize development in emerging field give some insights into future advance. Emphasis is placed on synthetic strategies.

Язык: Английский

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Asymmetric Synthesis of Axially Chiral C−N Atropisomers

Chemistry - A European Journal, Год журнала: 2022, Номер 28(28)

Опубликована: Фев. 22, 2022

Molecules with restricted rotation around a single bond or atropisomers are found in wide number of natural products and bioactive molecules as well chiral ligands for asymmetric catalysis smart materials. Although most these compounds biaryls heterobiaryls displaying C-C stereogenic axis, there is growing interest less common more challenging axially C-N atropisomers. This review offers an overview the various methodologies available their synthesis. A brief introduction initially given to contextualize skeletons, including historical background examples containing axes. The preparation different families based then presented from anilides five- six-membered ring heterocycles. Special emphasis has been modern catalytic strategies over past decade synthesis scaffolds. Applications methods biologically active will be highlighted along text.

Язык: 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, Год журнала: 2022, Номер 61(17)

Опубликована: Янв. 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.

Язык: Английский

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

Accounts of Chemical Research, Год журнала: 2022, Номер 55(12), С. 1620 - 1633

Опубликована: Июнь 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.

Язык: Английский

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

Chinese Journal of Chemistry, Год журнала: 2022, Номер 40(18), С. 2151 - 2160

Опубликована: Май 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

Язык: Английский

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Construction of axial chirality via asymmetric radical trapping by cobalt under visible light

Nature Catalysis, Год журнала: 2022, Номер 5(9), С. 788 - 797

Опубликована: Сен. 15, 2022

Язык: Английский

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Organocatalytic Enantioselective Synthesis of Axially ChiralN,N′‐Bisindoles

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(15)

Опубликована: Фев. 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.

Язык: Английский

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