Enantioselective Synthesis of N‐N Atropisomers by Palladium‐Catalyzed C−H Functionalization of Pyrroles

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(21)

Published: March 21, 2023

The catalytic asymmetric construction of N-N atropisomeric biaryls remains a formidable challenge. Studies them lag far behind studies the more classical carbon-carbon biaryl atropisomers, hampering meaningful development. Herein, first palladium-catalyzed enantioselective C-H activation pyrroles for synthesis atropisomers is presented. Structurally diverse indole-pyrrole possessing chiral axis were produced with good yields and high enantioselectivities by alkenylation, alkynylation, allylation, or arylation reactions. Furthermore, kinetic resolution trisubstituted heterobiaryls sterically demanding substituents was also achieved. Importantly, this versatile functionalization strategy enables iterative exquisite selectivity, expediting formation valuable, complex, atropisomers.

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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Construction of Axially Chiral Arylpyrroles via Atroposelective Diyne Cyclization

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(23)

Published: March 30, 2023

Axially chiral biaryls widely exist in natural products and pharmaceuticals are used as ligands catalysts asymmetric synthesis. Compared to the well-established axially 6-membered biaryl skeletons, examples of 5-membered have been quite scarce, mono-substituted 3-arylpyrrole atropisomers not reported. Here, we disclose a copper-catalyzed atroposelective diyne cyclization for construction range arylpyrrole good excellent yields with generally enantioselectivities via oxidation X-H insertion vinyl cations. Importantly, this protocol only represents first synthesis atropisomers, but also constitutes example atropisomer Theoretical calculations further support mechanism cation-involved elucidate origin enantioselectivity.

Language: Английский

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Recent advances in the construction of axially chiral arylpyrroles

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(9), P. 2480 - 2491

Published: Aug. 9, 2023

Language: Английский

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Diastereo- and atroposelective synthesis of N-arylpyrroles enabled by light-induced phosphoric acid catalysis

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

Published: Aug. 9, 2023

The C-N axially chiral N-arylpyrrole motifs are privileged scaffolds in numerous biologically active molecules and natural products, as well ligands/catalysts. Asymmetric synthesis of N-arylpyrroles, however, is still challenging, the simultaneous creation contiguous axial central chirality remains unknown. Herein, a diastereo- atroposelective N-arylpyrroles enabled by light-induced phosphoric acid catalysis has been developed. key transformation one-pot, three-component oxo-diarylation reaction, which simultaneously creates quaternary stereogenic center. A broad range unactivated alkynes were readily employed reaction partner this transformation, products obtained good yields, with excellent enantioselectivities very diastereoselectivities. Notably, skeletons represent interesting structural that could be used ligands catalysts asymmetric catalysis.

Language: Английский

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Recent advances in organocatalytic atroposelective reactions

Beilstein Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 21, P. 55 - 121

Published: Jan. 9, 2025

Axial chirality is present in a variety of naturally occurring compounds, and becoming increasingly relevant also medicine. Many axially chiral compounds are important as catalysts asymmetric catalysis or have chiroptical properties. This review overviews recent progress the synthesis via organocatalysis. Atroposelective organocatalytic reactions discussed according to dominant catalyst activation mode. For covalent organocatalysis, typical enamine iminium modes presented, followed by N -heterocyclic carbene-catalyzed reactions. The bulk devoted non-covalent activation, where Brønsted acids feature most prolific catalytic structure. last part article discusses hydrogen-bond-donating other motifs such phase-transfer catalysts.

Language: Английский

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Atroposelective Synthesis of Heterobiaryls through Ring Formation

Chemistry - A European Journal, Journal Year: 2023, Volume and Issue: 29(27)

Published: March 6, 2023

Atropisomeric heterobiaryls play a vital role in natural products, chiral ligands, organocatalysts, and other research fields, which have aroused great interest from chemists recent years. Until now, growing number of optically active based on indole, quinoline, isoquinoline, pyridine, pyrrole, azole, benzofuran skeletons been successfully synthesized through metal or organic catalytic cross-coupling, functionalization prochiral racemic heterobiaryls, ring formation. Among different strategies for the atroposelective synthesis strategy formation has become tool toward this goal. In review, we summarize enantioselective axially approaches, such as cycloaddition, cyclization, chirality conversion. Meanwhile, reaction mechanism corresponding applications are also discussed.

Language: Английский

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Molecular Editing of Pyrroles via a Skeletal Recasting Strategy

ACS Central Science, Journal Year: 2023, Volume and Issue: 9(9), P. 1758 - 1767

Published: Aug. 15, 2023

Heterocyclic scaffolds are commonly found in numerous biologically active molecules, therapeutic agents, and agrochemicals. To probe chemical space around heterocycles, many powerful molecular editing strategies have been devised. Versatile C-H functionalization allow for peripheral modifications of heterocyclic motifs, often being specific taking place at multiple sites. The past few years seen the quick emergence exciting "single-atom skeletal editing" strategies, through one-atom deletion or addition, enabling ring contraction/expansion structural diversification, as well scaffold hopping. construction heterocycles via deconstruction simple is unknown. Herein, we disclose a new method which name recasting strategy. Specifically, by tapping on 1,3-dipolar property azoalkenes, recast pyrroles to fully substituted pyrroles, phosphoric acid-promoted one-pot reaction consisting dearomative rearomative reconstruction steps. allows easy access synthetically challenging tetra-substituted otherwise difficult synthesize. Furthermore, construct N-N axial chirality our pyrrole products, accomplish facile synthesis anticancer drug, Sutent. potential application this other has also demonstrated.

Language: Английский

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Catalytic asymmetric dearomatization of phenols via divergent intermolecular (3 + 2) and alkylation reactions

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

Published: Aug. 25, 2023

Abstract The catalytic asymmetric dearomatization (CADA) reaction has proved to be a powerful protocol for rapid assembly of valuable three-dimensional cyclic compounds from readily available planar aromatics. In contrast the well-studied indoles and naphthols, phenols have been considered challenging substrates intermolecular CADA reactions due combination strong aromaticity potential regioselectivity issue over multiple nucleophilic sites (O, C2 as well C4). Reported herein are chiral phosphoric acid-catalyzed divergent common with azoalkenes, which deliver tetrahydroindolone cyclohexadienone products bearing an all-carbon quaternary stereogenic center in good yields excellent ee values. Notably, simply adjusting temperature leads chemo-divergent (3 + 2) alkylation reactions. Moreover, stereo-divergent synthesis four possible stereoisomers kind achieved via changing sequence catalyst enantiomers.

Language: Английский

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Copper-catalysed asymmetric annulation of yne-allylic esters with amines to access axially chiral arylpyrroles

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

Published: Aug. 10, 2024

The construction of atropisomers with 1,2-diaxes, while maintaining high enantiocontrol, presents a significant challenge due to the dynamic nature steric hindrance at ortho-aryl substituents. Although various catalytic asymmetric methods have been developed for accessing axially chiral arylpyrroles, synthesis arylpyrroles 1,2-diaxes in manner has remained rare. Herein, authors report diverse and C-C C-N axes through copper-catalysed asymmetirc [4 + 1] annulation yne-allylic esters arylamines via remote stereocontrol strategy. This approach provides facile access broad range heterobiaryl (67 examples) excellent enantioselectivities, each bearing one or two C-C/C-N axes, demonstrating its versatility efficiency. utility this methodology is further highlighted by transformation product into phosphine ligand, thioureas use catalysis.

Language: Английский

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