Rhodium(III)-Catalyzed Atroposelective Indolization to Access Planar-Chiral Macrocycles

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(42), С. 29214 - 29223

Опубликована: Окт. 9, 2024

Macrocycles incorporating conformationally defined indoles are widely found in bioactive natural products. However, the catalytic enantioselective synthesis of planar-chiral via indolization involving macrocyclization remains elusive. Herein, we present first rhodium(III)-catalyzed atroposelective macrocyclization, which involves C-H activation aniline, and a subsequent oxidation [3 + 2] annulation reaction with an intramolecular alkyne. This protocol achieves construction indoles, planar chirality control single step. Importantly, this strategy produces macrocyclic atropisomers bearing full-carbon ansa chains, represent challenging targets organic synthesis. Thermodynamic experiments revealed that rotational barrier chain-linked atropisomer was lower than oxa-ansa chain. The mechanism elucidated by computational studies, alkyne insertion steps collectively determined enantioselectivity.

Язык: Английский

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Pd/NHC sequentially catalyzed atroposelective synthesis of planar-chiral macrocycles

Chemical Science, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Planar-chiral macrocycles play a pivotal role in host-guest chemistry and drug discovery. However, compared with the synthesis of other types chiral compounds, asymmetric construction planar-chiral still remains forbidding challenge. Herein, we report sequential palladium N-heterocyclic carbene catalysis to build macrocycles. This protocol features broad scope good functional group tolerance, allows rapid assembling excellent enantioselectivities.

Язык: Английский

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

Chinese Journal of Chemistry, Год журнала: 2025, Номер 43(11), С. 1263 - 1270

Опубликована: Март 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.

Язык: Английский

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Asymmetric construction of axial and planar chirality with N-heterocyclic carbene (NHC) organocatalysis

Science China Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Окт. 30, 2024

Язык: Английский

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Recent Advances on Catalytic Atroposelective Synthesis of Planar‐Chiral Macrocycles

Angewandte Chemie International Edition, Год журнала: 2024, Номер unknown

Опубликована: Авг. 6, 2024

Planar-chiral skeletons widely exist in natural products, bioactive compounds, and other functional molecules. Although significant progress has been made the field of asymmetric synthesis centrally or axially chiral molecules over past years, enantioselective constructing planar chirality is still a big obstacle numerous efforts have this field. Previous works mainly focused on assembly planar-chiral [2,2]-paracyclophanes metallocenes. This Minireview describes recent advancements catalytic macrocycles, including ansa chain construction, plane formation transformation strategies. It anticipated that will sever as source inspiration for developing new unconventional procedures access to skeletons.

Язык: Английский

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An Approach for Highly Enantioselective Synthesis of meta-Disubstituted [n]Paracyclophanes

The Journal of Organic Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Сен. 27, 2024

Atroposelective synthesis of

Язык: Английский

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Catalytic Enantioselective Macrocyclization for the Synthesis of Planar‐Chiral Cyclophanes: Recent Updates

European Journal of Organic Chemistry, Год журнала: 2024, Номер 27(47)

Опубликована: Авг. 28, 2024

Abstract The planar chirality of macrocycles is a fascinating research topic. Locking the configurational flip between benzene ring and macrocycle leads to chirality, which can significantly enhance biological activity cyclophanes. Planar‐chiral cyclophanes are widely used in pharmaceuticals, chiral catalysts, functional materials. However, accessing planar‐chiral via asymmetric catalysis has remained challenging. Among various strategies, macrocyclization provides powerful tool for This method allows control when constructing greatly improves efficiency. There three types reactions: transition metal‐catalyzed, organocatalyzed, biocatalyzed. In addition, confinement strategy breaks through conservative synthetic approaches. review summarizes these achievements, aiming highlight catalytic synthesis inspire interested researchers.

Язык: Английский

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Conformationally Defined Planar-Chiral [n]Paracyclophanes Stabilized by Chiral Ansa Chains

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

Although chiral substituents have been incorporated into ansa chains to stabilize the conformations of cyclophanes and modulate the biological activities pharmaceuticals, asymmetric syntheses these atropisomers relies on substrate-induced diastereoselective macrocyclization. Consequently, enantio-, atrop-, macrocyclizations are yet be reported. Herein, we describe a N-heterocyclic carbene (NHC) phosphoric acid (CPA) dual-catalytic process for desymmetrization 1,3-diols, achieve macrocyclization stereoselective control over two elements. It was deduced that hydrogen bonding CPA with 1,3-diols enhanced diastereoselectivity process. As result, various planar-chiral bearing were synthesized. Thermodynamic experiments revealed presence an all-carbon quaternary carbon center chain significantly increased rotational barriers cyclophanes. Moreover, density functional theory calculations suggested substituent shrinks by compressing bond angle, thereby rendering conformational rotation reaction more challenging.

Язык: Английский

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Enantio-, atrop-, and diastereoselective macrolactonization to access type III cyclophanes

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Апрель 3, 2025

Язык: Английский

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N-Heterocyclic carbene-catalyzed enantioselective (dynamic) kinetic resolution for the assembly of inherently chiral macrocycles

Chemical Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

We have successfully achieved the highly enantioselective synthesis of inherently chiral macrocycles through NHC-catalyzed asymmetric esterification heterocalixaromatics.

Язык: Английский

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