Recent Advances in Catalytic Asymmetric Construction of Atropisomers

Chemical Reviews, Год журнала: 2021, Номер 121(8), С. 4805 - 4902

Опубликована: Март 27, 2021

Atropisomerism is a stereochemical behavior portrayed by three-dimensional molecules that bear rotationally restricted σ bond. Akin to the well-represented point-chiral molecules, atropisomerically chiral compounds are finding increasing utilities in many disciplines where molecular asymmetry influential. This provides steady demand on atroposelective synthesis, numerous synthetic pursuits have been rewarded with conceptually novel and streamlined methods while expanding structural diversity of atropisomers. review summarizes key achievements stereoselective preparation biaryl, heterobiaryl, nonbiaryl atropisomers documented between 2015 2020. Emphasis placed strategies for each class, examples cited illustrate potential applications accessed atropochiral targets.

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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Access to axially chiral styrenes via a photoinduced asymmetric radical reaction involving a sulfur dioxide insertion

Chem Catalysis, Год журнала: 2022, Номер 2(1), С. 164 - 177

Опубликована: Янв. 1, 2022

Язык: Английский

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Carbene-catalyzed atroposelective synthesis of axially chiral styrenes

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Янв. 10, 2022

Abstract Axially chiral styrenes bearing a axis between sterically non-congested acyclic alkene and an aryl ring are difficult to prepare due low rotational barrier of the axis. Disclosed here is N -heterocyclic carbene (NHC) catalytic asymmetric solution this problem. Our reaction involves ynals, sulfinic acids, phenols as substrates with NHC catalyst. Key steps involve selective 1,4-addition anion acetylenic acylazolium intermediate sequential E -selective protonation set up affords axially product > 99:1 e.r ., 20:1 / Z selectivity, excellent yields. The sulfone carboxylic ester moieties in our styrene products common bioactive molecules catalysis.

Язык: Английский

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Axially chiral alkenes: Atroposelective synthesis and applications

Tetrahedron Chem, Год журнала: 2022, Номер 1, С. 100009 - 100009

Опубликована: Март 1, 2022

Axial chirality is historically epitomized by biaryl compounds containing rotationally impeded aryl-aryl linkage. As the field of atroposelective catalysis advances, synthesis and application less common scaffolds such as alkenes have now come to fore. The manifestation axial in aryl was hypothesized 1928 first resolution achieved nearly a decade later. However, catalytic asymmetric construction axially chiral open-chain appeared only 2017 which ushered renewed focus on these structures. In principle, possess an alkene group tethered at one end stereogenic axis, greatly reduces overall rigidity. To date, atropisomers with C (vinyl)-C (aryl) (vinyl)-heteroatom bond been reported. Considering rapid growth synthetic utility alkenes, this review intends provide historical overview discusses new developments. It hope that timely discussion would motivate continued nascent field.

Язык: Английский

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Quinone methides and indole imine methides as intermediates in enantioselective catalysis

Nature Synthesis, Год журнала: 2022, Номер 1(6), С. 426 - 438

Опубликована: Июнь 6, 2022

Язык: Английский

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Recent developments on 1,2-difunctionalization and hydrofunctionalization of unactivated alkenes and alkynes involving C–S bond formation

Organic Chemistry Frontiers, Год журнала: 2023, Номер 10(5), С. 1322 - 1345

Опубликована: Янв. 1, 2023

Functionalization of alkenes/alkynes is a highly effective route to achieve molecular complexity. This review summarizes recent progresses on the 1,2-difunctionalization/hydrofunctionalization unactivated with C−S bond formation.

Язык: Английский

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

ACS Catalysis, Год журнала: 2023, Номер 13(4), С. 2565 - 2575

Опубликована: Фев. 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.

Язык: Английский

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Catalytic atroposelective synthesis

Nature Catalysis, Год журнала: 2024, Номер 7(5), С. 483 - 498

Опубликована: Апрель 30, 2024

Язык: Английский

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