Recent Advances in Catalytic Asymmetric Construction of Atropisomers

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(8), P. 4805 - 4902

Published: March 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.

Language: Английский

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

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(35), P. 14025 - 14040

Published: Aug. 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.

Language: Английский

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Rh(III)-Catalyzed Asymmetric Synthesis of Axially Chiral Biindolyls by Merging C–H Activation and Nucleophilic Cyclization

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(24), P. 9527 - 9532

Published: June 4, 2019

Enantiomeric access to pentatomic biaryls is challenging due their relatively low rotational barrier. Reported herein the mild and highly enantioselective synthesis of 2,3′-biindolyls via underexplored integration C–H activation alkyne cyclization using a unified chiral Rh(III) catalyst. The reaction proceeded initial followed by cyclization. A rhodacyclic intermediate has been isolated from stoichiometric activation, which offers direct mechanistic insight.

Language: Английский

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Stereoselective synthesis and applications of spirocyclic oxindoles

Organic Chemistry Frontiers, Journal Year: 2021, Volume and Issue: 8(5), P. 1026 - 1084

Published: Jan. 1, 2021

This review summaries recent synthetic developments towards spirocyclic oxindoles and applications as valuable medicinal targets.

Language: Английский

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

Chem, Journal Year: 2022, Volume and Issue: 8(7), P. 1855 - 1893

Published: May 6, 2022

Language: Английский

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A Bulky Chiral N-Heterocyclic Carbene Palladium Catalyst Enables Highly Enantioselective Suzuki–Miyaura Cross-Coupling Reactions for the Synthesis of Biaryl Atropisomers

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(37), P. 14938 - 14945

Published: Aug. 28, 2019

Axially chiral biaryl scaffolds are essential structural units in chemistry. The asymmetric Pd-catalyzed Suzuki–Miyaura cross-coupling reaction has been widely recognized as one of the most practical methods for constructing atropisomers biaryls. However, longstanding challenges remain this field. For example, substrate scope is often narrow and specialized, functional groups heterocycles can lead to reduced reactivity selectivity, bulky ortho-substituents usually needed, reported generally inapplicable tetra-ortho-substituted We have developed an unprecedented highly enantioselective N-heterocyclic carbene (NHC)-Pd catalyzed synthesis atropisomeric These reactions enable efficient coupling aryl halides (Br, Cl) or triflates with various types boron compounds (B(OH)2, Bpin, Bneo, BF3K), tolerate a remarkably broad (>41 examples), employ low loading catalyst (0.2–2 mol %), proceed under mild conditions. protocol provided general access biaryls heterobiaryls excellent enantioselectivities (up 99% ee) no need using ortho-substituted substrates was effective tetra-ortho-substituent Moreover, method successfully applied diastereo- ternaphthalenes. Critical success development application extremely C2-symmetric NHC, (R,R,R,R)-DTB-SIPE, ligand palladium. To best our knowledge, first (>90% example NHC-metal-catalyzed C(sp2)–C(sp2) reaction.

Language: Английский

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Chiral Cyclopentadienyl Ligands: Design, Syntheses, and Applications in Asymmetric Catalysis

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 60(24), P. 13198 - 13224

Published: July 16, 2020

The creation of new chiral ligands capable providing high stereocontrol in metal-catalyzed reactions is crucial modern organic synthesis. production bioactive molecules as single enantiomers increasingly required, and asymmetric catalysis with metal complexes constitutes one the most efficient synthetic strategies to access optically active compounds. Herein we offer a historical overview on development derivatives ubiquitous cyclopentadienyl ligand (CpX ), detail their successful application broad range transformations. Those include functionalization challenging C-H bonds beyond, giving an extensive catalogue valuable molecules. A critical comparison existing families, design, synthesis, complexation different metals also provided. In addition, future research directions are discussed further enhance performance CpX enantioselective catalysis.

Language: Английский

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Transition Metal Catalyzed Enantioselective C(sp²)–H Bond Functionalization

ACS Catalysis, Journal Year: 2020, Volume and Issue: 10(23), P. 13748 - 13793

Published: Nov. 12, 2020

Direct catalytic transformation of C–H bonds to new functionalities has provided a powerful strategy synthesize complex molecular scaffolds in straightforward way. Unstinting efforts the synthetic community have helped overcome long-standing major challenge regioselectivity by introducing directing group concept. However, full potential cannot be realized unless activated are stereochemically controlled. The enantioselective bond functionalization could provide an imperative tool for sustainable way synthesizing chiral scaffolds. Despite intrinsic challenges achieving stereocontrol, developed different tools order achieve stereoselective functionalization. In this review, we discuss remarkable recent advances emerging area C(sp2)–H highlight and opportunities, emphasizing techniques so far.

Language: Английский

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Diverse Approaches for Enantioselective C−H Functionalization Reactions Using Group 9 Cp^xM^III Catalysts

Chemistry - A European Journal, Journal Year: 2020, Volume and Issue: 26(33), P. 7346 - 7357

Published: Jan. 29, 2020

Transition-metal-catalyzed C-H functionalization reactions with Cp*MIII catalysts (M=Co, Rh, Ir) have found a wide variety of applications in organic synthesis. Albeit the intrinsic difficulties achieving catalytic stereocontrol using these due to their lack additional coordination sites for external chiral ligands and conformational flexibility Cp ligand, enantioselective Group 9 metal triad Cp-type been intensively studied since 2012. In this minireview, progress according type catalyst used are summarized discussed. The development Cpx complexes thereof, artificial metalloenzymes, carboxylate-assisted activations, alkylations assisted by carboxylic acids or sulfonates, transient directing groups

Language: Английский

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Rhodium-Catalyzed Atroposelective C–H Arylation: Efficient Synthesis of Axially Chiral Heterobiaryls

Journal of the American Chemical Society, Journal Year: 2019, Volume and Issue: 141(24), P. 9504 - 9510

Published: June 2, 2019

Rhodium(I)-catalyzed atroposelective C–H arylation of heterobiaryls was presented. In the presence a Rh catalyst derived from [Rh(C2H4)2Cl]2 and TADDOL-derived monodentate phosphonite, with 2-pyridine, 2-isoquinoline their analogs as directing groups, series axially chiral were obtained in excellent yields enantioselectivities (up to 99% yield, 97% ee) via direct functionalization reaction. The products this method provide platform for synthesis biaryl ligands catalysts. As demonstration, N-oxide synthesized product one step could act an efficient asymmetric allylation benzaldehyde allyltrichlorosilane, leading homoallyl alcohol enantiocontrol.

Language: Английский

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