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

Science, Journal Year: 2021, Volume and Issue: 372(6543)

Published: May 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.

Language: Английский

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

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(12), P. 7692 - 7760

Published: May 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.

Language: Английский

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

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(20), P. 2920 - 2937

Published: Sept. 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.

Language: Английский

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Recent development in transition metal-catalysed C–H olefination

Chemical Science, Journal Year: 2021, Volume and Issue: 12(8), P. 2735 - 2759

Published: Jan. 1, 2021

Transition metal-catalysed functionalizations of inert C-H bonds to construct C-C represent an ideal route in the synthesis valuable organic molecules. Fine tuning directing groups, catalysts and ligands has played a crucial role selective bond (sp2 or sp3) activation. Recent developments these areas have assured high level regioselectivity olefination reactions. In this review, we summarized recent progress oxidative sp2 sp3 with special emphasis on distal, atroposelective, non-directed directed olefination. The scope, limitation, mechanism various transition reactions been described briefly.

Language: Английский

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Transition-metal catalyzed C–H activation as a means of synthesizing complex natural products

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(21), P. 7461 - 7503

Published: Jan. 1, 2023

Over the past few decades, advent of C–H activation has led to a rethink among chemists about synthetic strategies employed for multi-step transformations.

Language: Английский

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Emergence of Pyrimidine-Based meta-Directing Group: Journey from Weak to Strong Coordination in Diversifying meta-C–H Functionalization

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(3), P. 354 - 372

Published: Jan. 12, 2022

C-H activation has emerged as a powerful transformative synthetic tool to construct complex molecular frameworks, which are ubiquitous in natural products, medicines, dyes, polymers, and many more. However, reactivity selectivity, arising from the inertness of bonds their overabundance organic molecules, two major fundamental challenges developing various carbon-carbon (C-C) carbon-heteroatom (C-X) bond formation reactions via technique. Functional groups with coordinating capacity transition metal catalysts, profoundly known directing (DGs), have shown great promise exerting selective activation, often called site-selective or regioselective transformation target molecule. Advent group (DG)-assisted strategies not only resolved selectivity issues but also offers unique solution rapid synthesis molecules convenient predictable manner. Our laboratory, this regard, is fascinated by prospect DG-assisted distal functionalization arenes, remotely located existing group. Notably, opposition proximal ortho-C-H proceeded an energetically favorable five- seven-membered metallacycle, remained formidable challenge it required large macrocyclic metallacycle. Therefore, designing suitable template that would maintain distance geometric relationship between appended auxiliary order ensure prolific delivery catalyst closest proximity targeted was key success. In Yu devised elegant "U-shaped" for first time execute meta-C-H recruiting cyano-based initial effort diversify scope using led us realize "cyano-based DGs" intrinsically limited weak ability, competitive binding mode (end-on vs side-on), incompatibility acidic basic reaction conditions. search robust auxiliary, we were intrigued possibility strongly ability pyrimidine quinoline-based DGs.In Account, describe our journey weakly DG pyrimidine-based achieve diverse electronically sterically unbiased arenes. While some functionalizations achieved finding conditions, others mechanistic understanding. development realm constrained short linkers, attached arene interest through 2-4 atoms. later studies, demonstrated can be attained even though 10-atoms away arene. More importantly, transient successfully utilized deliver olefination arenes situ imine formation, provided step-economic route activation.We hope Account will stimulate further design provide guiding platform future functionalization.

Language: Английский

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Weak bonding strategies for achieving regio- and site-selective transformations

Chem, Journal Year: 2022, Volume and Issue: 8(2), P. 414 - 438

Published: Jan. 25, 2022

Language: Английский

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Empirical Guidelines for the Development of Remote Directing Templates through Quantitative and Experimental Analyses

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(6), P. 2793 - 2803

Published: Feb. 2, 2022

The ability to differentiate and selectively activate remote C-H bonds represents a perennial challenge in the field of activation. Since its first report 2012, now-established "directing template" (DT) approach remains demonstrably effective for functionalization bonds. As selectivity is hypothesized be principally determined by optimal positioning reactive catalyst target bond, DT's spatial factors are particularly important toward achieving high selectivity, though systematic study on requisite remain unelucidated. Through an in-depth analysis 119 structurally unique published DTs, this summarizes key that central at defined aryl positions, which experimentally corroborated through development new aliphatic meta para-selective DTs electronically unbiased arenes. These empirical rules, summarize distance geometric factors, expected useful tools future site-selective arene activation as well other reactions rely covalent/noncovalent DT-mediated regioselection.

Language: Английский

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Distal meta-alkenylation of formal amines enabled by catalytic use of hydrogen-bonding anionic ligands

Chem, Journal Year: 2023, Volume and Issue: 9(4), P. 989 - 1003

Published: Jan. 24, 2023

Language: Английский

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Pd-catalyzed regioselective activation of C(sp²)–H and C(sp³)–H bonds

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Differentiating between two highly similar C-H bonds in a given molecule remains fundamental challenge synthetic organic chemistry. Directing group assisted strategies for the functionalisation of proximal has been known last few decades. However, distal bond is strenuous and requires distinctly specialised techniques. In this review, we summarise advancement Pd-catalysed C(sp

Language: Английский

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