Enantioselective Synthesis of Atropisomers via Vinylidene ortho-Quinone Methides (VQMs)

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(19), P. 2780 - 2795

Published: Sept. 19, 2022

ConspectusAtropisomers, arising from conformational restriction, are inherently chiral due to the intersecting dissymmetric planes. Since there numerous applications of enantiopure atropisomers in catalyst design, drug discovery, and material science, asymmetric preparation these highly prized molecules has become a flourishing field synthetic chemistry. A number catalysts, procedures, novel concepts have been developed for manufacture atropisomeric molecules. However, intrinsic properties different types featuring biaryl, hetero-biaryl, or non-biaryl architectures, only very few methods pass rigorous inspection considered generally applicable. The development broadly applicable strategy various is challenge. In this Account, we summarize our recent studies on enantioselective synthesis using vinylidene ortho-quinone methides (VQMs) as pluripotent intermediates.The most appealing features VQMs disturbed aromaticity axial chirality allene fragment. At outset, organic neglected their principal liabilities: ephemeral nature, extraordinary reactivity, multireaction sites. domestication transient intermediate was demonstrated by situ catalytic generation VQMs, reactivity selectivity were fully explored judiciously modifying precursors tuning systems. variety axially heterocycles achieved through five-, six-, seven- nine-membered ring formation VQM intermediates with kinds branched nucleophilic functional groups. C–N axis could be constructed via N-annulation desymmetrization preformed scaffolds. We take advantage high electrophilicity toward series sulfur carbon based nucleophiles leading vinyl arenes. Furthermore, helical compounds realized cycloaddition consecutive annulation intermediates. These achievements that work nuclear parent collective distinct complex optically active atropisomers. Recently, isolation structural characterization elusive which questioned putative decades. successful provided direct evidence existence an unprecedented opportunity directly investigate reactivity. good thermal stability reserved isolated great potential reagents expanded border

Language: Английский

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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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Catalytic Asymmetric Synthesis of Axially Chiral Diaryl Ethers through Enantioselective Desymmetrization

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(14)

Published: Feb. 10, 2023

Axially chiral diaryl ethers are a type of unique atropisomers bearing two potential axes, which have applications in variety research fields. However, the catalytic enantioselective synthesis these ether is largely underexplored when compared to asymmetric biaryl or other types atropisomers. Herein, we report highly efficient through an organocatalyzed desymmetrization protocol. The phosphoric acid-catalyzed electrophilic aromatic aminations symmetrical 1,3-benzenediamine substrates afforded series excellent yields and enantioselectivities. facile construction heterocycles by utilizations 1,2-benzenediamine moiety products provided access structurally diverse novel azaarene-containing

Language: Английский

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Catalytic Asymmetric Diastereodivergent Synthesis of 2-Alkenylindoles Bearing both Axial and Central Chirality

Precision Chemistry, Journal Year: 2024, Volume and Issue: 2(5), P. 208 - 220

Published: April 23, 2024

The catalytic asymmetric diastereodivergent synthesis of axially chiral 2-alkenylindoles was established via phosphoric acid-catalyzed addition reactions C3-unsubstituted with

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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Design and Catalytic Asymmetric Synthesis of Furan‐Indole Compounds Bearing both Axial and Central Chirality

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(8)

Published: Dec. 29, 2023

Abstract In the chemistry community, catalytic asymmetric synthesis of furan‐based compounds bearing both axial and central chirality has proven to be a significant but challenging issue owing importance difficulty in constructing such frameworks. this work, we have realized first five‐five‐membered via organocatalytic (2+4) annulation achiral furan‐indoles with 2,3‐indolyldimethanols uncommon regioselectivity. By strategy, furan‐indole were synthesized high yields excellent regio‐, diastereo‐, enantioselectivities. Moreover, theoretical calculations conducted provide an in‐depth understanding reaction pathway, activation mode, origin selectivity.

Language: Английский

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Atroposelective Access to 1,3‐Oxazepine‐Containing Bridged Biaryls via Carbene‐Catalyzed Desymmetrization of Imines

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(1)

Published: Sept. 10, 2022

Abstract We disclose herein an atroposelective synthesis of novel bridged biaryls containing medium‐sized rings via N‐heterocyclic carbene organocatalysis. The reaction starts with addition the catalyst to aminophenol‐derived aldimine substrate. Subsequent oxidation and intramolecular desymmetrization lead formation 1,3‐oxazepine‐containing in good yields excellent enantioselectivities. These biaryl products can be readily transformed into chiral phosphite ligands. Preliminary density function theory calculations suggest that origin enantioselectivity arises from more favorable frontier molecular orbital interactions transition state leading major product.

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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Asymmetric rhodium-catalyzed click cycloaddition to access C–N axially chiralN-triazolyl indoles

Chemical Science, Journal Year: 2023, Volume and Issue: 14(19), P. 5182 - 5187

Published: Jan. 1, 2023

The copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is regarded as a prime example of "click chemistry", but the asymmetric click internal alkynes still remains challenging. A new Rh-catalyzed N-alkynylindoles with azides was developed, providing atroposelective access to C-N axially chiral triazolyl indoles, type heterobiaryl, excellent yields and enantioselectivity. This approach efficient, mild, robust atom-economic, features very broad substrate scope easily available Tol-BINAP ligands.

Language: Английский

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Silver-Catalyzed Direct Nucleophilic Cyclization: Enantioselective De Novo Synthesis of C–C Axially Chiral 2-Arylindoles

Organic Letters, Journal Year: 2023, Volume and Issue: 25(3), P. 522 - 527

Published: Jan. 18, 2023

Atropisomeric indoles widely exist in natural products, pharmaceuticals, functional materials, and catalysts for their featured biological activities, photoelectric properties, catalytic while facile de novo construction of this motif remains underexplored. Herein, we report a chiral silver phosphate-catalyzed direct 5-endo-dig nucleophilic cyclization 2-alkynylanilins under mild conditions, affording various C-C axially 2-arylindoles high to excellent yields enantioselectivities. Control experiments implied the cooperative catalysis AgOAc phosphoric acid, wherein former accelerated desired transformation latter improved enantioselectivity. In addition, as first example silver-catalyzed enantioselective synthesis indole skeletons, synthetic applications products' thermal stability have been investigated.

Language: Английский

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