Organocatalytic diastereo- and atroposelective construction of N–N axially chiral pyrroles and indoles

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 15, 2024

Abstract The construction of N–N axially chiral motifs is an important research topic, owing to their wide occurrence in natural products, pharmaceuticals and ligands. One efficient method the atroposelective dihydropyrimidin-4-one formation. We present herein a direct catalytic synthesis atropisomers with simultaneous creation contiguous axial central chirality by oxidative NHC ( N -heterocyclic carbenes) catalyzed (3 + 3) cycloaddition. Using our method, we are able synthesize structurally diverse pyrroles indoles vicinal or bearing 2,3-dihydropyrimidin-4-one moiety moderate good yields excellent enantioselectivities. Further synthetic transformations obtained derivative products demonstrated. reaction mechanism origin enantioselectivity understood through DFT calculations.

Language: Английский

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Atroposelective Synthesis of Triaryl α‐Pyranones with 1,2‐Diaxes by N‐Heterocyclic Carbene Organocatalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(52)

Published: Oct. 31, 2022

Atropisomers bearing multiple stereogenic axes are of increasing importance to the field material science, pharmaceuticals, and catalysis. However, atroposelective construction multi-axis atropisomers remains rare challenging, due intrinsical difficulties in stereo-control axes. Herein, we demonstrate a single-step new class 1,2-diaxially chiral triaryl α-pyranones by an N-heterocyclic carbene organocatalytic asymmetric [3+3] annulation well-designed alkynyl acylazolium precursors enolizable sterically hindered 2-aryl ketones. The protocol features broad substrate scope (>50 examples), excellent (most cases >20 : 1 dr, up 99.5 0.5 er), potentially useful synthetic applications. success this reaction relies on rational design structurally matched partners careful selection catalytic system. DFT calculations have also been performed discover rationalize origin high stereoselectivity reaction.

Language: Английский

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Enantioselective Access to Triaryl-2-pyrones with Monoaxial or Contiguous C–C Diaxes via Oxidative NHC Catalysis

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(4), P. 2565 - 2575

Published: Feb. 6, 2023

We present herein an unprecedented stereoselective synthesis of triaryl-2-pyrones with monoaxial or contiguous diaxes from readily available starting materials. This N-heterocyclic carbene catalysis method adopts atroposelective annulation 2-aryketones ynals under oxidative conditions. The includes the construction one two axes in a single operation, achieves step economy, and affords axially chiral moderate to good yields, high excellent enantioselectivities. DFT calculations relative energies stereoisomers rotational barriers were performed.

Language: Английский

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N-Heterocyclic Carbene-Catalyzed Atroposelective Synthesis of N–N Axially Chiral 3-Amino Quinazolinones

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(13), P. 8752 - 8759

Published: June 16, 2023

Although the atroposelective synthesis of biaryls and related compounds bearing axially chiral C–C bonds is well-known, C–N bond-containing relatively less explored, construction N–N has received only scant attention. Demonstrated herein N-heterocyclic carbene (NHC)-catalyzed selective amidation reaction, leading to 3-amino quinazolinones. The NHC-catalyzed reaction quinazolinones containing a free N–H moiety with α,β-unsaturated aldehydes under oxidative conditions furnished atropisomeric quinazolinone derivatives mild broad scope. Preliminary studies on experimental density functional theory-based rotational barrier determination are also presented.

Language: Английский

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Enantioselective Synthesis of Axially Chiral Diaryl Ethers via NHC Catalyzed Desymmetrization and Following Resolution

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(4)

Published: Nov. 29, 2023

Axially chiral diaryl ethers are present in numerous natural products and bioactive molecules. However, only few catalytic enantioselective approaches have been established to access ether atropisomers. Herein, we report the N-heterocyclic carbene-catalyzed synthesis of axially via desymmetrization prochiral 2-aryloxyisophthalaldehydes with aliphatic alcohols, phenol derivatives, heteroaromatic amines. This reaction features mild conditions, good functional group tolerance, broad substrate scope excellent enantioselectivity. The utility this methodology is illustrated by late-stage functionalization, gram-scale synthesis, diverse enantioretentive transformations. Control experiments DFT calculations support association NHC-catalyzed following kinetic resolution enhance

Language: Английский

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Alkynyl Acylazolium: A Versatile 1,3‐Bielectrophilic 3C‐Synthon in NHC‐Organocatalysis

The Chemical Record, Journal Year: 2023, Volume and Issue: 23(7)

Published: March 21, 2023

Abstract N ‐Heterocyclic carbene (NHC) organocatalysis has emerged as a powerful tool in the field of modern organic synthesis especially asymmetric construction various cyclic skeletons. As an emerging NHC‐bound 1,3‐bielectrophilic intermediate, alkynyl acylazolium drawn substantial attention recent years, and been used versatile 3C‐synthon synthesizing valuable molecules since its discovery. In this review, focused on different pathways for formation acylazoliums from precursors like alkynoic esters, acids ynals, advances transformations applications pioneered or developed over last decade under NHC‐catalysis were summarized comprehensively. At same time, outlook further investigation exploration novel reaction modes future was also discussed.

Language: Английский

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An Assembly of Pyrano[3,2‐b]indol‐2‐ones via NHC‐Catalyzed [3 + 3] Annulation of Indolin‐3‐ones with Ynals^†

Chinese Journal of Chemistry, Journal Year: 2024, Volume and Issue: 42(13), P. 1487 - 1492

Published: March 10, 2024

Comprehensive Summary We report herein an unprecedented N ‐heterocyclic carbene‐catalyzed formal [3 + 3] annulation of ynals with ‐Ts indolin‐3‐ones under the oxidation condition affording functionalized pyrano[3,2‐ b ]indol‐2‐ones. The alkynyl acylazoliums via combination a carbene in presence oxidate proved to be important intermediates for success this transformation. This method features broad substrate scope and mild conditions, including axially chiral skeletons suitable substitutions.

Language: Английский

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Catalytic Asymmetric Synthesis of Unnatural Axially Chiral Biaryl δ‐Amino Acid Derivatives via a Chiral Phenanthroline‐Potassium Catalyst‐Enabled Dynamic Kinetic Resolution

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(36)

Published: June 15, 2024

Axially chiral biaryl δ-amino acids possess significantly different conformational properties and environment from centrally amino acids, therefore, have drawn considerable attention in the fields of synthetic medicinal chemistry. Herein, a novel phenanthroline-potassium catalyst has been developed by constructing well-organized axially ligand composed one 1,10-phenanthroline unit two 1,1'-bi-2-naphthol (BINOL) units. In presence this catalyst, good to excellent yields enantioselectivities (up 99 % yield, 98 : 2 er) achieved ring-opening alcoholytic dynamic kinetic resolution variety lactams, thereby providing an efficient protocol for catalytic asymmetric synthesis unnatural acid derivatives.

Language: Английский

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Divergent Synthesis of Axially Chiral 2-Pyranones and Fused 2-Pyridones via N-Heterocyclic Carbene-Catalyzed Atroposelective [3 + 3] Annulation

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

An N-heterocyclic carbene-catalyzed atroposelective [3 + 3] annulation of alkynyl acylazoliums with benzothiazole derivatives has been developed for the divergent synthesis axially chiral triaryl 2-pyranones and fused 2-pyridones. The regioselectivity this protocol depends on structure benzothiazoles three different nucleophilic centers. obtained frameworks represent a new class arylheterocycle atropisomers, which may be potentially useful in medicinal chemistry.

Language: Английский

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Chemodivergent Parallel Kinetic Resolution of Paracyclophanes: Enantiomer Fishing with Different Substrates

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(46)

Published: July 25, 2024

Abstract An unprecedented chemodivergent strategy for parallel kinetic resolution (PKR) is disclosed through which two planar chiral products bearing different structures were simultaneously afforded with opposite stereoselectivities. Two achiral esters are activated by one single N‐heterocyclic carbene (NHC) catalyst to react the enantiomers of racemic imine substrate in a fashion. distinct and stereoselectivities respectively from same reaction system good excellent yields, enantio‐ diastereoselectivities. Control experiments studies carried out probe dynamic properties during progress. The pyridine lactam show interesting applications both asymmetric synthesis pesticide development.

Language: Английский

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