Organocatalytic Asymmetric Synthesis of Indole-Based Chiral Heterocycles: Strategies, Reactions, and Outreach

Accounts of Chemical Research, Journal Year: 2019, Volume and Issue: 53(2), P. 425 - 446

Published: Dec. 10, 2019

Indole-based chiral heterocycles constitute a class of important heterocyclic compounds that are found in numerous pharmaceuticals, functional materials, and catalysts or ligands. Catalytic asymmetric synthesis, for which the 2001 Nobel Prize Chemistry was awarded, has been demonstrated to be most efficient method accessing compounds. Therefore, catalytic synthesis indole-based attracted great interest from scientific community. However, strategies toward this goal rather limited, challenges remain field, such as metal contamination products, limited number platform molecules with versatile reactivity, reactions offer high step economy, atom excellent enantiocontrol. novel urgently needed. To achieve goal, our group developed series unique strategies, designing developing their corresponding organocatalytic access heterocycles. In Account, we describe efforts address remaining research field. Namely, have designed vinylindoles, indolylmethanols, arylindoles indole derivatives construction scaffolds structural diversity complexity. Based on reactivities these molecules, accomplished cycloaddition, cyclization, addition dearomatization economy Using wide range heterocycles, including five-membered seven-membered axially tetrasubstituted synthesized efficiency enantioselectivity. addition, investigated properties some bioactivities activities, showed potent anticancer activities promising catalysis. These results help elucidate potential applications drug development catalysts. The undoubtedly become will continue hot topic field catalysis synthesis. Our efforts, summarized not only open window future innovative but also inspire chemists worldwide confront prompt further advances.

Language: Английский

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A Strategy for Synthesizing Axially Chiral Naphthyl‐Indoles: Catalytic Asymmetric Addition Reactions of Racemic Substrates

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 58(42), P. 15104 - 15110

Published: Aug. 23, 2019

Abstract A new strategy for enantioselective synthesis of axially chiral naphthyl‐indoles has been established through catalytic asymmetric addition reactions racemic with bulky electrophiles. Under phosphoric acid catalysis, azodicarboxylates and o ‐hydroxybenzyl alcohols served as but reactive electrophiles that were attacked by C2‐unsubstituted naphthyl‐indoles, which underwent a dynamic kinetic resolution to afford two series in good yields (up 98 %) high enantioselectivities 98:2 er).

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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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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Progress in organocatalytic asymmetric (4+3) cycloadditions for the enantioselective construction of seven-membered rings

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(4), P. 966 - 992

Published: Feb. 15, 2023

Language: Английский

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Quinone methides and indole imine methides as intermediates in enantioselective catalysis

Nature Synthesis, Journal Year: 2022, Volume and Issue: 1(6), P. 426 - 438

Published: June 6, 2022

Language: Английский

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Asymmetric (4+n) Cycloadditions of Indolyldimethanols for the Synthesis of Enantioenriched Indole‐Fused Rings

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(37)

Published: June 24, 2023

Catalytic asymmetric construction of chiral indole-fused rings has become an important issue in the chemical community because significance such scaffolds. In this work, we have accomplished first catalytic (4+2) and (4+3) cycloadditions 2,3-indolyldimethanols by using indoles 2-naphthols as suitable reaction partners under catalysis phosphoric acids, constructing enantioenriched six-membered seven-membered high yields with excellent enantioselectivities. addition, approach is used to realize enantioselective challenging tetrahydroindolocarbazole scaffolds, which are found show promising anticancer activity. More importantly, theoretical calculations pathways activation mode offer in-depth understanding class indolylmethanols. This work not only settles challenges realizing indolyldimethanols but also provides a powerful strategy for rings.

Language: Английский

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Catalytic asymmetric (3 + 3) cycloaddition between different 2-indolylmethanols

Science China Chemistry, Journal Year: 2024, Volume and Issue: 67(8), P. 2629 - 2636

Published: June 26, 2024

Language: Английский

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Axially Chiral Aryl‐Alkene‐Indole Framework: A Nascent Member of the Atropisomeric Family and Its Catalytic Asymmetric Construction

Chinese Journal of Chemistry, Journal Year: 2020, Volume and Issue: 38(6), P. 543 - 552

Published: March 21, 2020

Summary of main observation and conclusion A new class axially chiral aryl‐alkene‐indole frameworks have been designed, the first catalytic asymmetric construction such scaffolds has established by strategy organocatalytic ( Z / E )‐selective enantioselective (4+3) cyclization 3‐alkynyl‐2‐indolylmethanols with 2‐naphthols or phenols (all >95 : 5 , up to 98% yield, 97% ee). This reaction also represents alkene‐heteroaryl scaffolds, which will add a member atropisomeric family. approach not only confronted great challenges in constructing but provided powerful for frameworks.

Language: Английский

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Organocatalytic Enantioselective Synthesis of Chiral Allenes: Remote Asymmetric 1,8‐Addition of Indole Imine Methides

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(39), P. 17049 - 17054

Published: June 18, 2020

An organocatalytic enantioconvergent synthesis of chiral tetrasubstituted allenes is disclosed. With suitable phosphoric acid catalysts, a range racemic indole-substituted propargylic alcohols reacted with nucleophiles to provide efficient access series enantioenriched high enantioselectivities. Control experiments suggested mechanism involving remotely controlled asymmetric 1,8-addition the in situ generated indole imine methide via bifunctional transition state.

Language: Английский

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