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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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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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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Atroposelective Synthesis of 1,1′‐Bipyrroles Bearing a Chiral N−N Axis: Chiral Phosphoric Acid Catalysis with Lewis Acid Induced Enantiodivergence

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(16)

Опубликована: Фев. 17, 2022

Abstract We present herein a highly efficient atroposelective synthesis of axially chiral 1,1′‐bipyrroles bearing an N−N linkage from simple hydrazine and 1,4‐diones. Further product derivatizations led to bifunctional compounds with high potential in asymmetric catalysis. For this chrial phosphoric acid (CPA)‐catalyzed double Paal–Knorr reaction, intriguing Fe(OTf) 3 ‐induced enantiodivergence was also observed.

Язык: Английский

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Catalytic Asymmetric Construction of Axially and Centrally Chiral Heterobiaryls by Minisci Reaction

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(13), С. 6040 - 6049

Опубликована: Март 24, 2022

Axially chiral biaryls and heterobiaryls constitute the most represented subclass of atropisomers with prevalence in natural products, bioactive compounds, privileged ligand/catalysts, optically pure materials. Despite many ionic protocols for their construction, radical-based variants represent another highly desirable intriguing strategy but are far less developed. Moreover, efficient synthesis axially heterobiaryl molecules, especially ones having multiple heteroatoms other types elements, through radical routes remains extremely limited. We herein disclose first catalytic asymmetric, metal-free construction centrally by Minisci reaction 5-arylpyrimidines α-amino acid-derived redox-active esters. This is enabled use 4CzIPN as an organic photoredox catalyst conjunction a phosphoric acid catalyst. The achieved variety interesting featuring union α-branched amine generally excellent regio-, diastereo-, enantioselectivity (up to 82% yield; >19:1 dr; >99% ee). finding also builds up new platform development desymmetrization methods via radical-involved atroposelective functionalization at heteroarene prochiral heterobiaryls.

Язык: Английский

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Enantioselective Synthesis of N−N Bisindole Atropisomers

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(44)

Опубликована: Сен. 15, 2022

N-N Atropisomers are a common motif in natural products and represent significant dimension for exploration modern pharmaceutical medicinal chemistry. However, the catalytic atroposelective synthesis of such molecules remains challenging, hampering meaningful development. In particular, an enantioselective bisindole atropisomers is unprecedented. Herein, first via palladium-catalyzed de novo construction one indole skeleton presented. A wide variety axially chiral bisindoles were generated good yields with excellent enantioselectivities cascade condensation/N-arylation reaction. Structurally diverse indole-pyrrole, indole-carbazole, non-biaryl-indole possessing axis accessed using this protocol. Moreover, investigations density functional theory (DFT) calculations provided insight into reaction mechanism enantiocontrol.

Язык: Английский

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Design and catalytic atroposelective synthesis of axially chiral isochromenone-indoles

Science China Chemistry, Год журнала: 2022, Номер 65(10), С. 1929 - 1937

Опубликована: Сен. 13, 2022

Язык: Английский

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Catalytic Asymmetric Synthesis of Atropisomers Bearing Multiple Chiral Elements: An Emerging Field

Angewandte Chemie International Edition, Год журнала: 2023, Номер 63(3)

Опубликована: Ноя. 2, 2023

With the rapid development of asymmetric catalysis, demand for enantioselective synthesis complex and diverse molecules with different chiral elements is increasing. Owing to unique features atropisomerism, catalytic atropisomers has attracted a considerable interest from chemical science community. In particular, introducing additional elements, such as carbon centered chirality, heteroatomic planar helical into provides an opportunity incorporate new properties axially compounds, thus expanding potential applications atropisomers. Thus, it important perform transformations synthesize bearing multiple elements. spite challenges in transformations, recent years, chemists have devised powerful strategies under organocatalysis or metal synthesizing wide range enantioenriched Therefore, become emerging field. This review summarizes progress this field indicates challenges, thereby promoting horizon.

Язык: Английский

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Enantioselective Synthesis of N−N Biaryl Atropisomers through Iridium(I)‐Catalyzed C−H Alkylation with Acrylates

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(37)

Опубликована: Май 4, 2023

Abstract Enantioselective synthesis of N−N biaryl atropisomers is an emerging area but remains underexplored. The development efficient in great demand. Herein, the construction through iridium‐catalyzed asymmetric C−H alkylation reported for first time. In presence readily available Ir precursor and Xyl‐BINAP, a variety axially chiral molecules based on indole‐pyrrole skeleton were obtained good yields (up to 98 %) with excellent enantioselectivity 99 % ee). addition, bispyrrole could also be synthesized enantioselectivity. This method features perfect atom economy, wide substrate scope, multifunctionalized products allowing diverse transformations.

Язык: Английский

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