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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Organocatalytic Asymmetric Synthesis of Indole-Based Chiral Heterocycles: Strategies, Reactions, and Outreach

Accounts of Chemical Research, Journal Year: 2019, Volume and Issue: 53(2), P. 425 - 446

Published: Dec. 10, 2019

Indole-based chiral heterocycles constitute a class of important heterocyclic compounds that are found in numerous pharmaceuticals, functional materials, and catalysts or ligands. Catalytic asymmetric synthesis, for which the 2001 Nobel Prize Chemistry was awarded, has been demonstrated to be most efficient method accessing compounds. Therefore, catalytic synthesis indole-based attracted great interest from scientific community. However, strategies toward this goal rather limited, challenges remain field, such as metal contamination products, limited number platform molecules with versatile reactivity, reactions offer high step economy, atom excellent enantiocontrol. novel urgently needed. To achieve goal, our group developed series unique strategies, designing developing their corresponding organocatalytic access heterocycles. In Account, we describe efforts address remaining research field. Namely, have designed vinylindoles, indolylmethanols, arylindoles indole derivatives construction scaffolds structural diversity complexity. Based on reactivities these molecules, accomplished cycloaddition, cyclization, addition dearomatization economy Using wide range heterocycles, including five-membered seven-membered axially tetrasubstituted synthesized efficiency enantioselectivity. addition, investigated properties some bioactivities activities, showed potent anticancer activities promising catalysis. These results help elucidate potential applications drug development catalysts. The undoubtedly become will continue hot topic field catalysis synthesis. Our efforts, summarized not only open window future innovative but also inspire chemists worldwide confront prompt further advances.

Language: Английский

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Recent advances in the synthesis of axially chiral biarylsviatransition metal-catalysed asymmetric C–H functionalization

Chemical Communications, Journal Year: 2019, Volume and Issue: 55(59), P. 8514 - 8523

Published: Jan. 1, 2019

Recent advances in the synthesis of axially chiral biarylsviatransition metal-catalysed asymmetric C–H functionalization are reported.

Language: Английский

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Asymmetric organocatalysis: an enabling technology for medicinal chemistry

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(3), P. 1522 - 1586

Published: Jan. 1, 2021

This review provides a comprehensive overview of the recent applications organocatalytic strategies in pharmaceutical synthesis, with focus on preparation antiviral, anticancer, neuroprotective, cardiovascular, antibacterial and antiparasitic agents.

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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Copper(I)-Catalyzed Asymmetric Reactions Involving Radicals

Accounts of Chemical Research, Journal Year: 2019, Volume and Issue: 53(1), P. 170 - 181

Published: Oct. 28, 2019

ConspectusAsymmetric functionalization of alkyl radicals represents a robust yet underdeveloped method for efficient construction and decoration carbon skeletons in chiral organic molecules. In this field, we have been inspired by the excellent redox, radical trapping, Lewis acidic properties copper to develop several catalytic modes asymmetric reactions involving radicals. At beginning, discovered tandem hydrotrifluoromethylation unactivated alkenes enantioselective alkoxylation remote C(sp3)–H bonds copper/chiral phosphate relay catalysis. This success has stimulated us an three-component 1,2-dicarbofunctionalization 1,1-diarylalkenes using similar strategy via intermediates. Meanwhile, also secondary amine cooperative catalyst intramolecular cyclopropanation α-aldehyde methylene groups as C1 sources. The trapping intermediates CuII species during reaction was essential chemoselectivity toward cyclopropanation.Encouraged enantiocontrol with effective species, then sought single-electron-transfer Subsequently, successfully achieved series highly 1,2-aminofluoroalkylation, -aminoarylation, -diamination, -aminosilylation, -oxytrifluoromethylation alkenes. key high enantioinduction believed be CuII/chiral complexes. Besides, achiral pyridine ligand found indispensable achieving enantioselectivity, presumably stabilization CuIII 1,2-alkoxytrifluoromethylation reaction. discovery reminded tuning redox chemoreactivity centers ancillary ligand. As result, subsequently identified cinchona alkaloid-derived sulfonamides novel neutral-anionic hybrid ligands simultaneous chemo- enantiocontrol. We thus accomplished 1,2-iminoxytrifluoromethylation under catalysis copper/cinchona sulfonamide ligand, affording trifluoromethylated isoxazolines enantiomeric excess. Our copper-catalyzed provide expedient access diverse range valuable molecules broad application potential areas synthesis, medicine, agrochemical, material sciences.

Language: Английский

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Transition Metal‐Catalyzed Enantioselective C−H Functionalization via Chiral Transient Directing Group Strategies

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(45), P. 19773 - 19786

Published: July 20, 2020

Abstract Transition metal‐catalyzed enantioselective functionalization of C−H bond, the most abundant functionality in organic molecules, has emerged as an expedient synthetic approach to streamline synthesis complex chiral molecules. Despite significant progress, traditional directing group‐enabled strategies require additional steps for installation and removal groups from target molecule. The recently developed asymmetric using transient ( c TDGs) offers a promising alternative that can circumvent this obstacle therefore simplify process. In Minireview, we briefly discuss advent recent advances emerging concept, with emphasis on discussing creation various stereogenic centers developments TDGs. Applications natural product ligand derivatizations are also discussed. We hope Minireview will highlight great potential strategy help inspire further endeavors.

Language: Английский

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

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(18), P. 2562 - 2580

Published: Sept. 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.

Language: Английский

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Design and Catalytic Asymmetric Construction of Axially Chiral 3,3′‐Bisindole Skeletons

Angewandte Chemie International Edition, Journal Year: 2018, Volume and Issue: 58(10), P. 3014 - 3020

Published: Nov. 21, 2018

Abstract The first catalytic asymmetric construction of 3,3′‐bisindole skeletons bearing both axial and central chirality has been established by organocatalytic addition reactions 2‐substituted 3,3′‐bisindoles with 3‐indolylmethanols (up to 98 % yield, all >95:5 d.r., >99 ee ). This reaction also represents the highly enantioselective axially chiral skeletons, utilizes strategy introducing a bulky group ortho ‐position prochiral 3,3′‐bisindoles. not only provides good example for simultaneously controlling in one operation, but serves as new backbones from substrates.

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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