Enantioselective Synthesis of Heteroatom‐Linked Non‐Biaryl Atropisomers

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(30)

Published: May 15, 2024

Atropisomers hold significant fascination, not only for their prevalence in natural compounds but also biological importance and wide-ranging applications as chiral materials, ligands, organocatalysts. While biaryl heterobiaryl atropisomers are commonly studied, the enantioselective synthesis of less abundant heteroatom-linked non-biaryl presents a formidable challenge modern organic synthesis. Unlike classical atropisomers, these molecules allow rotation around two bonds, resulting low barriers to enantiomerization through concerted bond rotations. In recent years discovery new configurationally stable rare scaffolds such aryl amines, ethers sulfones well innovative methodologies control configuration have been disclosed literature constitute topic this minireview.

Language: Английский

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Development of Configurationally Labile Biaryl Reagents for Atropisomer Synthesis

European Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 27(28)

Published: May 16, 2024

Abstract Axially chiral biaryl scaffolds are important in pharmaceuticals, natural products, and asymmetric synthesis. Atroposelective ring‐opening of configurationally labile reagents via dynamic kinetic transformation provides a valuable approach to access axially atropisomers. This review summarizes seminal contributions recent advancements on this topic based the use different types reagents.

Language: Английский

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Enantioselective Synthesis of Planar/Multiple Chiral [n]Cyclophanes through Asymmetric Allylation

Chinese Journal of Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 7, 2025

Comprehensive Summary Planar‐chiral cyclophanes with carbon‐centered chirality are important targets in natural products and pharmaceuticals. However, synthesizing such planar chiral two stereogenic elements via a one‐step asymmetric reaction remains formidable challenge. Herein, we present an efficient kinetic resolution method for planar‐chiral [ n ]cyclophanes chirality. This is achieved through the enantioselective allylation of racemic aldehyde catalyzed by Bi(OAc) 3 phosphoric acid. The delivers multiple high yields excellent enantioselectivities, showcasing remarkable efficiency ( s factor up to 292). broad substrate scope, scalability, potential derivatization highlight value this methodology. DFT calculations have also been performed provide insights into origin experimentally observed diastereo‐ enantioselectivity reaction.

Language: Английский

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Cocatalyst-Dependent Divergent Amination of Alkylgold Intermediates with Azodicarboxylates

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 5211 - 5218

Published: March 12, 2025

The asymmetric electrophilic amination using azodicarboxylates as the N-source for construction of C–N bond has attracted much attention over past decades. However, use in situ formed nucleophilic intermediates, rather than bench-stable reagents, remains elusive and challenging. Herein, we disclose an enantioselective reaction generated alkylgold species with under a gold complex chiral quinine-derived squaramide (QN-SQA) synergetic catalysis, leading to alkylideneoxazolines nitrogen-containing tertiary carbon stereocenter good high yields enantioselectivities. Moreover, starting from same oxazoles incorporating aminomethyl group on 5-position could be obtained by Brønsted acid relay catalysis via alkylideneoxazoline species. This method offers complementary approach through interception With this strategic protocol, further synthetic applications can envisioned catalytic C–C C–X bonds.

Language: Английский

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Catalytic Enantioselective Friedel–Crafts Reactions of Arenes Enabled by Iranium/Irenium-Ion-Triggered Electrophilic Functionalization

Synlett, Journal Year: 2025, Volume and Issue: unknown

Published: April 14, 2025

Abstract The catalytic asymmetric Friedel–Crafts reactions of (hetero)arenes represent a cornerstone in synthetic chemistry due to their ability efficiently incorporate aromatic rings into complex molecular architectures. This account presents comprehensive overview recent advancements the enantioselective (hetero)arenes, with particular focus on that facilitate introduction multiple C–C bonds via iranium/irenium-ion-triggered electrophilic processes. We examine detail strategies and methodologies employed achieve stereoselective incorporation unsaturated bonds, highlighting construction diverse structural scaffolds. Additionally, this showcases broad range applications powerful transformation organic synthesis. 1 Introduction 2 Catalytic Enantioselective Reactions Thiiranium/Thiirenium Ions 2.1 Arylthiiranium/Arylthiirenium-Ion-Triggered 2.2 Trifluoromethylthiiranium/Trifluoromethylthiirenium-Ion-Triggered 3 Haliranium 3.1 Chloriranium-Ion-Triggered 3.2 Bromiranium-Ion-Triggered 3.3 Iodiranium-Ion-Triggered Asymmetric Oxidative Arylation Alkenes 4 Conclusion Outlook

Language: Английский

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Rhodium(III)-Catalyzed Redox-Neutral [4 + 2] Annulation of 3,5-Diaryloxadiazoles with Alkynes: A Dual C–H Activation Strategy for Constructing C–N Atropisomers

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

A rhodium(III)-catalyzed dual-ring formation via cascade C-H activation/[4 + 2] annulation of 3,5-diaryoxadiazoles with alkynes was developed. This strategy has been demonstrated a variety 3,5-diaryloxadiazoles and alkynes, it successfully scaled up to gram-scale synthesis, highlighting its potential significance in the direct construction C-N atropisomers. Furthermore, cleavage N-O bond is essential for bicyclic structure absence an external oxidant. Mechanistic studies revealed that at 3-phenyl group oxadiazole likely rate-determining step this reaction.

Language: Английский

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Catalytic enantioselective synthesis of inherently chiral calix[4]arenes via organocatalyzed aromatic amination enabled desymmetrization

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 26, 2025

Inherently chiral calix[4]arenes represent a distinct class of frameworks whose chirality arises from the dissymmetry entire molecule. Although these scaffolds have been widely applied in various research fields, their catalytic enantioselective synthesis remains largely underexplored. Herein, we report inherently using an organocatalyzed desymmetrization method. By phosphoric acid catalysis, asymmetric electrophilic amination reactions phenol-containing prochiral led to range with high yields and enantioselectivities. Significantly, practicability this method is underscored by its successful implementation as little 0.05 mol% catalyst, without compromising reaction efficiency enantioselectivity. Moreover, aminophenol moiety products could be easily modified produce unique diverse N,O-heterocycles, well simple meta-amino-substituted calix[4]arene, which shown promising potential development new catalysts.

Language: Английский

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Catalytic Enantioselective Synthesis of Axially Chiral Diaryl Ethers Via Asymmetric Povarov Reaction Enabled Desymmetrization

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

Axially chiral diaryl ethers represent a distinct class of atropisomers, characterized by unique dual C─O axes system, which have been found in variety natural products, pharmaceuticals, and ligands. However, the catalytic enantioselective synthesis these atropoisomers poses significant challenges, due to difficulty controlling both axes, their more flexible conformations. Herein, an efficient protocol for axially is presented using organocatalyzed asymmetric Povarov reaction-enabled desymmetrization, followed aromatizations. This method yields wide range novel quinoline-based ether good high enantioselectivities. Notably, various aromatization protocols are developed, resulting diverse set polysubstituted quinoline-containing atropisomers. Thermal racemization studies suggested excellent configurational stabilities atropisomers (with barriers up 38.1 kcal mol

Language: Английский

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Evolution in the asymmetric synthesis of biaryl ethers and related atropisomers

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(54), P. 6837 - 6846

Published: Jan. 1, 2024

Axially chiral biaryl ethers and related compounds hold valuable potential in natural products, medicinal chemistry, catalysis; however, their asymmetric syntheses have always been overlooked compared to other biaryl/hetero-biaryl atropisomers. Unlike the later class molecules bearing a single axis, former category possesses unique type of atropisomerism two axes. Due great importance diverse research domains, catalytic atropselective ether synthesis has recently witnessed an upsurge. This highlight article provides elaborated view on developments synthetic methods that explored achieve dual axial chirality scaffolds.

Language: Английский

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Enantioselective Synthesis of Heteroatom‐Linked Non‐Biaryl Atropisomers

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(30)

Published: May 15, 2024

Abstract Atropisomers hold significant fascination, not only for their prevalence in natural compounds but also biological importance and wide‐ranging applications as chiral materials, ligands, organocatalysts. While biaryl heterobiaryl atropisomers are commonly studied, the enantioselective synthesis of less abundant heteroatom‐linked non‐biaryl presents a formidable challenge modern organic synthesis. Unlike classical atropisomers, these molecules allow rotation around two bonds, resulting low barriers to enantiomerization through concerted bond rotations. In recent years discovery new configurationally stable rare scaffolds such aryl amines, ethers sulfones well innovative methodologies control configuration have been disclosed literature constitute topic this minireview.

Language: Английский

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