Organocatalytic Enantioselective Synthesis of Axially ChiralN,N′‐Bisindoles

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(15)

Published: Feb. 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.

Language: 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, Journal Year: 2023, Volume and Issue: 62(37)

Published: May 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.

Language: Английский

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Cobalt-catalyzed atroposelective C−H activation/annulation to access N−N axially chiral frameworks

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Aug. 29, 2023

The N-N atropisomer, as an important and intriguing chiral system, was widely present in natural products, pharmaceutical lead compounds, advanced material skeletons. anisotropic structural characteristics caused by its special axial rotation have always been one of the challenges that chemists strive to overcome. Herein, we report efficient method for enantioselective synthesis axially frameworks via a cobalt-catalyzed atroposelective C-H activation/annulation process. reaction proceeds under mild conditions using Co(OAc)2·4H2O catalyst with salicyl-oxazoline (Salox) ligand O2 oxidant, affording variety products high yields enantioselectivities. This protocol provides approach facile construction atropisomers further expands range derivatives. Additionally, electrocatalysis, desired were also successfully achieved good excellent efficiencies

Language: Английский

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Enantioselective Strategies for The Synthesis of N−N Atropisomers

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(31)

Published: April 25, 2023

Axially chiral compounds have been always considered a laboratory curiosity with rare prospects of being applied in asymmetric synthesis. Things changed very quickly the last twenty years when it was understood important role and enormous impact that these medicinal, biological material chemistry. The synthesis atropisomers became rapidly expanding field recent reports on development N-N strongly prove how this research is hot topic open to new challenges frontiers This review focuses advances enantioselective highlighting strategies breakthroughs obtain novel stimulating atropisomeric framework.

Language: Английский

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Chiral Acid-Catalyzed Atroposelective Indolization Enables Access to 1,1′-Indole-Pyrroles and Bisindoles Bearing a Chiral N–N Axis

Organic Letters, Journal Year: 2023, Volume and Issue: 25(9), P. 1553 - 1557

Published: March 1, 2023

We present herein a highly atroposelective indolization for the efficient synthesis of 1,1'-biheteroaryls bearing chiral N-N axis. Under cooperative catalysis phosphoric acid and InBr3, reactions between 2,3-diketoesters 1,3-dione-derived enamines resulted in enantioselective construction 1,1'-pyrrole-indoles with up to 92% yield, 94% enantiomeric excess (ee), or bisindoles ee. Derivatizations these compounds diverse functionalized linked axially biheteroaryls have also been demonstrated.

Language: Английский

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Catalytic N-Acylation for Access to N–N Atropisomeric N-Aminoindoles: Choice of Acylation Reagents and Mechanistic Insights

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(9), P. 6926 - 6935

Published: April 18, 2024

The synthesis of N–N axial compounds containing aromatic acyl amides using common acylation reagents remains challenging. We describe a highly atropenantioselective N-aminoindoles axes. A chiral cyclic isothiourea is used as the sole organic catalyst in transformation N-acylation reaction. Aroyl chlorides have been to construct atropisomeric through N-acylation. N-aminoindole products, which bear stereogenic axes, were synthesized with high yields and enantioselectivities. Some enantiopure products exhibited promising antibacterial activities against plant pathogens.

Language: Английский

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Pd-catalyzed asymmetric Larock reaction for the atroposelective synthesis of N─N chiral indoles

Science Advances, Journal Year: 2024, Volume and Issue: 10(19)

Published: May 10, 2024

Atropisomeric indoles defined by a N─N axis are an important class of heterocycles in synthetic and medicinal chemistry material sciences. However, they remain heavily underexplored due to limited methods challenging stereocontrol over the short bonds. Here, we report highly atroposelective access axially chiral via asymmetric Larock reaction. This protocol leveraged powerful role phosphoramidite ligand attenuate common dissociation original reaction, forming with excellent functional group tolerance high enantioselectivity palladium-catalyzed intermolecular annulation between readily available o -iodoaniline alkynes. The multifunctionality prepared allowed diverse post-coupling transformations, affording broad array functionalized indoles. Experimental computational studies have been conducted explore reaction mechanism, elucidating enantio-determining rate-limiting steps.

Language: Английский

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Organocatalytic atroposelective synthesis of axially chiral N,N′-pyrrolylindoles via de novo indole formation

Chemical Science, Journal Year: 2023, Volume and Issue: 14(43), P. 12091 - 12097

Published: Jan. 1, 2023

The first organocatalytic atroposelective synthesis of axially chiral N,N'-pyrrolylindoles based on o-alkynylanilines was successfully established via de novo indole formation catalyzed by phosphoric acid (CPA). This new synthetic strategy introduced CPA-catalyzed asymmetric 5-endo-dig cyclization well-designed containing a pyrrolyl unit, resulting in wide range high yields with exclusive regioselectivity and excellent enantioselectivity (up to 99% yield, >20 : 1 rr, 95 5 er). Considering the potential biological significance N-N atropisomers, preliminary activity studies were performed revealed that these structurally important had low IC50 value promising impressive cytotoxicity against several kinds cancer cell lines. DFT reveal N-nucleophilic mediated CPA is rate- stereo-determining step, which ligand-substrate dispersion interactions facilitate axial chirality target products.

Language: Английский

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Catalytic Asymmetric Synthesis of N—N Atropisomers

Chinese Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 43(6), P. 1977 - 1977

Published: Jan. 1, 2023

The N-N bond is widely found in natural products and bioactive compounds.The atropisomerism of bond, however, has been dismissed for a long time due to the stereotype that axis unstable.The electronic barrier stemming from repulsive interaction between lone pairs on two nitrogen atoms leads rotationally hindered axis, resulting stable atropisomers.Since first report 2021, catalytic asymmetric synthesis atropisomers developed rapidly into an emerging area.These reactions include N-H functionalization, desymmetrization atroposelective de novo construction (hetero-)aromatic rings.The axially chiral compounds are valuable molecules, terms their potential application ligand/catalysts design biological activity evaluation.Herein, state-of-the-art summarized.

Language: Английский

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Atroposelective Synthesis of N–N Axially Chiral Bipyrroles via Rhodium-Catalyzed C–H Insertion Reaction

Organic Letters, Journal Year: 2023, Volume and Issue: 25(26), P. 4808 - 4812

Published: June 27, 2023

An atroposelective synthesis of bipyrroles with an axially chiral N-N bond has been established via a rhodium-catalyzed C-H insertion reaction to provide the desired atropisomers in good yields (up 97% yield) excellent enantioselectivities 99% ee).

Language: Английский

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