Synthesis of Atropisomers by Transition-Metal-Catalyzed Asymmetric C–H Functionalization Reactions

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(35), С. 14025 - 14040

Опубликована: Авг. 25, 2021

Transition-metal-catalyzed enantioselective C-H functionalization has become a powerful strategy for the formation of C-C or C-X bonds, enabling highly asymmetric synthesis wide range enantioenriched compounds. Atropisomers are widely found in natural products and pharmaceutically relevant molecules, have also applications as privileged frameworks chiral ligands catalysts. Thus, research into routes atropisomers garnered great interest recent years. In this regard, transition-metal-catalyzed emerged an atom-economic efficient toward their synthesis. Perspective, approaches by reactions summarized. The main focus here is on catalysis via Pd, Rh, Ir complexes, which been most frequently utilized catalysts among reported reactions. Finally, we discuss limitations available protocols give outlook possible future avenues research.

Язык: Английский

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Organocatalytic Atroposelective Synthesis of Indole Derivatives Bearing Axial Chirality: Strategies and Applications

Accounts of Chemical Research, Год журнала: 2022, Номер 55(18), С. 2562 - 2580

Опубликована: Сен. 2, 2022

Catalytic atroposelective syntheses of axially chiral compounds have stimulated extensive interest in multiple communities, such as synthetic chemistry, biochemistry, and materials science, because the intriguing characteristics atropisomerism. In particular, atropisomeric indole derivatives, which contain a kind five-membered heterocyclic framework, are widely distributed number natural alkaloids, biologically relevant compounds, ligands, organocatalysts. Hence, catalytic synthesis derivatives bearing axial chirality is considerable importance has become an emerging focus research. However, there substantial challenges associated with including remote ortho-substituents around axis, lower barrier for rotation, weaker configurational stability than that six-membered biaryls. Therefore, development effective strategies toward urgent task.In order to tackle these accomplish task, our group devised unique strategy designing indole-derived platform molecules developing organocatalytic enantioselective transformations synthesize derivatives; asymmetric organocatalysis tremendous advantages was research area recognized by Nobel Prize Chemistry 2021. This Account summarizes endeavors chirality. brief, we developed series molecules, indolylmethanols, (hetero)aryl indoles, oxindole-based styrenes, N-aminoindoles, indole-based homophthalic anhydrides, introducing different functional groups onto ring achieve new reactivity modulate reactive site ring. As result, possess versatile capable undergoing variety preparing structurally diversified chirality.We used plenty chirality, alkene-indoles, N-pyrrolylindoles, isochromenone-indoles. addition, gave thorough detailed understanding designed reaction investigating pathway activation mode. More importantly, studied biological activity some products performed catalyst design on basis moieties, helpful disclosing more applications chirality.In future, will indubitably remain frontier topic catalysis chemistry despite challenging issues, instance, novel unconventional into powerful catalysts or discovery potent drug candidates. We hope efforts summarized this encourage chemists worldwide devise innovative solving issues field, thus promoting its higher level.

Язык: Английский

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Atropisomers beyond the C–C axial chirality: Advances in catalytic asymmetric synthesis

Chem, Год журнала: 2022, Номер 8(7), С. 1855 - 1893

Опубликована: Май 6, 2022

Язык: Английский

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Organocatalytic Enantioselective Synthesis of Axially Chiral Molecules: Development of Strategies and Skeletons

Accounts of Chemical Research, Год журнала: 2022, Номер 55(20), С. 2920 - 2937

Опубликована: Сен. 30, 2022

The growing importance of axially chiral architectures in different scientific domains has unveiled shortcomings terms efficient synthetic access and skeletal variety. This account describes our strategies answering these challenges within the organocatalytic context where emergence bifunctional catalysts such as phosphoric acids (CPAs) proven invaluable controlling sense axial chirality. wide occurrence bi(hetero)aryl skeletons privileged structures constitutes a strong motivation to devise more effective arylation methods. Our design revolves around modulating intrinsic nucleophilicity aromatic amines alcohols. first approach involves an electron-withdrawing activating group which could associate with catalyst for reactivity enhancement selectivity control. resonance arenes offers unique mechanistic possibility select between sites. C2-Azo- nitroso-substituted naphthalenes undergo atroposelective ortho C- or N-arylation (hetero)aromatic nucleophiles. For monocyclic benzenes, programmable charge localization leads regioselective activation by catalytic control alone aided substrate design. instance, selective addition nitroso nitrogen enables successive annulation initiated amine yield N-arylbenzimidazoles. In biomimetic manner, finely tuned direct para-selective nucleophilic azobenzenes. second strategy employs electrophilic arene precursors occurs via rearomatization central-to-axial chirality transfer. enabled (imino)quinones indoles phenylindole atropisomers. By adapting this chemistry additional oxidation event liberate carbonyl functionalities, aryl-o-naphthoquinone aryl-p-quinone atropisomers were attained. Along development new strategies, deriving been another consistent theme research program. functionalization alkynes provides broad entry atropisomeric alkenes. monofunctionalization through interception vinylidene-quinone-methide (VQM) intermediate 2-naphthols yielded EBINOL scaffolds. designing internal directing group, dihalogenation was realized using abundant alkali halides despite their weak nucleophilicities poor solubilities. N-alkylation alkenes pursued prepare multifunctionalized alkene that be converted into 2-arylpyrroles synthesis B-aryl-1,2-azaborines containing C-B axis accomplished CPA effects desymmetrization defines configuration distal bond. Inspired scaffold allenes, we leveraged developed achieve para-addition dearomatization judiciously designed azobenzenes, led structurally novel cyclohexadienylidene-based hydrazones. To complement structures, cyclohexadienyl oxime ethers also attained CPA-catalyzed condensation hydroxylamines spiro[4.5]trienones.

Язык: Английский

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Carbene‐Catalyzed Asymmetric Construction of Atropisomers

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(50), С. 26026 - 26037

Опубликована: Июль 16, 2021

Atropisomeric molecules have found proven applications and shown promising potential in chemistry medicine. The design of N-heterocyclic carbene (NHC) catalyzed reactions to construct atropisomerically enriched has emerged as an important research topic recent years. These include kinetic resolutions, asymmetric desymmetrizations, central-to-axial chirality conversions, cycloadditions. This Minireview evaluates summarizes the progress NHC-based organic catalysis for access atropisomers, briefly states our personal perspectives on future advancement this topic. NHC provided rich unique reaction modes that led success synthesis central-chiral molecules. It is expected similar could also be achieved developing prepare atropisomeric molecules, including those not easily accessible by other methods.

Язык: Английский

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Geminal-atom catalysis for cross-coupling

Nature, Год журнала: 2023, Номер 622(7984), С. 754 - 760

Опубликована: Сен. 20, 2023

Язык: Английский

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Stereoselective construction of atropisomers featuring a C–N chiral axis

Green Synthesis and Catalysis, Год журнала: 2022, Номер 3(2), С. 117 - 136

Опубликована: Янв. 4, 2022

Atropisomeric C–N compounds belong to an important class of axially chiral compounds. However, whereas the asymmetric synthesis biaryl atropisomers have been well established, general and efficient strategies access single enantiomers are still rare. Until recently, innovative methods developed, providing new opportunities for highly stereoselective this vital atropisomers. Herein, we comprehensively summarize development in emerging field give some insights into future advance. Emphasis is placed on synthetic strategies.

Язык: Английский

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Asymmetric Synthesis of Axially Chiral C−N Atropisomers

Chemistry - A European Journal, Год журнала: 2022, Номер 28(28)

Опубликована: Фев. 22, 2022

Molecules with restricted rotation around a single bond or atropisomers are found in wide number of natural products and bioactive molecules as well chiral ligands for asymmetric catalysis smart materials. Although most these compounds biaryls heterobiaryls displaying C-C stereogenic axis, there is growing interest less common more challenging axially C-N atropisomers. This review offers an overview the various methodologies available their synthesis. A brief introduction initially given to contextualize skeletons, including historical background examples containing axes. The preparation different families based then presented from anilides five- six-membered ring heterocycles. Special emphasis has been modern catalytic strategies over past decade synthesis scaffolds. Applications methods biologically active will be highlighted along text.

Язык: Английский

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Organocatalytic Atroposelective Synthesis of N−N Axially Chiral Indoles and Pyrroles by De Novo Ring Formation

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(17)

Опубликована: Янв. 26, 2022

Abstract The first highly atroposelective construction of N−N axially chiral indole scaffolds was established via a new strategy de novo ring formation. This makes use the organocatalytic asymmetric Paal–Knorr reaction well‐designed N ‐aminoindoles with 1,4‐diketones, thus affording ‐pyrrolylindoles in high yields and excellent atroposelectivities (up to 98 % yield, 96 ee). In addition, this is applicable for synthesis bispyrroles 97 More importantly, such heterocycles can be converted into organocatalysts applications catalysis, some molecules display potent anticancer activity. work not only provides but also offers members atropisomer family promising synthetic medicinal chemistry.

Язык: Английский

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

Accounts of Chemical Research, Год журнала: 2022, Номер 55(19), С. 2780 - 2795

Опубликована: Сен. 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

Язык: Английский

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