Late-stage C–H functionalization offers new opportunities in drug discovery

Nature Reviews Chemistry, Год журнала: 2021, Номер 5(8), С. 522 - 545

Опубликована: Июль 13, 2021

Язык: Английский

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C–H activation

Nature Reviews Methods Primers, Год журнала: 2021, Номер 1(1)

Опубликована: Июнь 17, 2021

Язык: Английский

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Toolbox for Distal C–H Bond Functionalizations in Organic Molecules

Chemical Reviews, Год журнала: 2021, Номер 122(6), С. 5682 - 5841

Опубликована: Окт. 18, 2021

Transition-metal-catalyzed C–H activation has developed a contemporary approach to the omnipresent area of retrosynthetic disconnection. Scientific researchers have been tempted take help this methodology plan their synthetic discourses. This paradigm shift helped in development industrial units as well, making synthesis natural products and pharmaceutical drugs step-economical. In vast zone bond activation, functionalization proximal bonds gained utmost popularity. Unlike bonds, distal is more strenuous requires distinctly specialized techniques. review, we compiled various methods adopted functionalize mechanistic insights within each these procedures, scope methodology. With give complete overview expeditious progress made field organic chemistry while also highlighting its pitfalls, thus leaving open for further modifications.

Язык: Английский

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Arene diversification through distal C(sp ² )−H functionalization

Science, Год журнала: 2021, Номер 372(6543)

Опубликована: Май 13, 2021

Transition metal-catalyzed aryl C-H activation is a powerful synthetic tool as it offers step and atom-economical routes to site-selective functionalization. Compared with proximal ortho-C-H activation, distal (meta- and/or para-) remains more challenging due the inaccessibility of these sites in formation energetically favorable organometallic pretransition states. Directing catalyst toward bonds requires judicious template engineering design, well prudent choice ligands. This review aims summarize recent elegant discoveries exploiting directing group assistance, transient mediators or traceless directors, noncovalent interactions, ligand selection control activation.

Язык: Английский

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A Perspective on Late-Stage Aromatic C–H Bond Functionalization

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(6), С. 2399 - 2414

Опубликована: Янв. 27, 2022

Late-stage functionalization of C-H bonds (C-H LSF) can provide a straightforward approach to the efficient synthesis functionalized complex molecules. However, LSF is challenging because bond must be in presence various other functional groups. In this Perspective, we evaluate aromatic on basis four criteria─reactivity, chemoselectivity, site-selectivity, and substrate scope─and our own views current challenges as well promising strategies areas growth going forward.

Язык: Английский

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Transition-Metal-Catalyzed C–H Bond Activation for the Formation of C–C Bonds in Complex Molecules

Chemical Reviews, Год журнала: 2023, Номер 123(12), С. 7692 - 7760

Опубликована: Май 10, 2023

Site-predictable and chemoselective C–H bond functionalization reactions offer synthetically powerful strategies for the step-economic diversification of both feedstock fine chemicals. Many transition-metal-catalyzed methods have emerged selective activation bonds. However, challenges regio- chemoselectivity with application to highly complex molecules bearing significant functional group density diversity. As molecular complexity increases within structures risks catalyst intolerance limited applicability grow number groups potentially Lewis basic heteroatoms. Given abundance bonds already diversified such as pharmaceuticals, natural products, materials, design selection reaction conditions tolerant catalysts has proved critical successful direct functionalization. such, innovations formation carbon–carbon been discovered developed overcome these limitations. This review highlights progress made metal-catalyzed C–C forming including alkylation, methylation, arylation, olefination targets.

Язык: Английский

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

ACS Catalysis, Год журнала: 2020, Номер 10(23), С. 13748 - 13793

Опубликована: Ноя. 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.

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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New horizons for catalysis disclosed by supramolecular chemistry

Chemical Society Reviews, Год журнала: 2021, Номер 50(13), С. 7681 - 7724

Опубликована: Янв. 1, 2021

Recent advancements in supramolecular catalysis are reviewed, which show the potential of related tools when applied to organic synthesis. Such recognized as innovative instruments that can pave way alternative synthetic strategies.

Язык: Английский

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Diboron(4)‐Catalyzed Remote [3+2] Cycloaddition of Cyclopropanes via Dearomative/Rearomative Radical Transmission through Pyridine

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(52)

Опубликована: Ноя. 8, 2022

Abstract Ring structures such as pyridine, cyclopentane or their combinations are important motifs in bioactive molecules. In contrast to previous cycloaddition reactions that necessitated a directly bonded initiating functional group, this work demonstrated novel through‐(hetero)arene radical transmission concept for selective activation of remote bond. An efficient, metal‐free and atom‐economical [3+2] between 4‐pyridinyl cyclopropanes alkenes alkynes has been developed modular synthesis pyridine‐substituted cyclopentanes, cyclopentenes bicyclo[2.1.1]hexanes difficult access using known methods. This complexity‐building reaction was catalyzed by very simple inexpensive diboron(4) compound took place via dearomative/rearomative processes. The substrate scope broad more than 100 new compounds were prepared generally high yields. Mechanistic experiments density function theory (DFT) investigation supported relay catalytic cycle involving alkylidene dihydropyridine intermediates boronyl transfer.

Язык: Английский

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