Toolbox for Distal C–H Bond Functionalizations in Organic Molecules

Chemical Reviews, Journal Year: 2021, Volume and Issue: 122(6), P. 5682 - 5841

Published: Oct. 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.

Language: Английский

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Achieving Site-Selectivity for C–H Activation Processes Based on Distance and Geometry: A Carpenter’s Approach

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(24), P. 10571 - 10591

Published: May 21, 2020

The ability to differentiate between highly similar C–H bonds in a given molecule remains fundamental challenge organic chemistry. In particular, the lack of sufficient steric and electronic differences located distal functional groups has prevented development site-selective catalysts with broad scope. An emerging approach circumvent this obstacle is utilize distance target bond coordinating group, along geometry cyclic transition state directed activation, as core molecular recognition parameters multiple bonds. Perspective, we discuss advent recent advances concept. We cover wide range transition-metal-catalyzed, template-directed remote activation reactions alcohols, carboxylic acids, sulfonates, phosphonates, amines. Additionally, review eminent examples which take advantage non-covalent interactions achieve regiocontrol. Continued advancement distance- geometry-based differentiation for regioselective functionalization may lead ultimate realization editing: freedom modify molecules at any site, order.

Language: Английский

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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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Strategic evolution in transition metal-catalyzed directed C–H bond activation and future directions

Coordination Chemistry Reviews, Journal Year: 2020, Volume and Issue: 431, P. 213683 - 213683

Published: Dec. 9, 2020

Language: Английский

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Traditional and sustainable approaches for the construction of C–C bonds by harnessing C–H arylation

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Feb. 28, 2022

Abstract Biaryl scaffolds are found in natural products and drug molecules exhibit a wide range of biological activities. In past decade, the transition metal-catalyzed C–H arylation reaction came out as an effective tool for construction biaryl motifs. However, traditional reactions have limitations like harsh conditions, narrow substrate scope, use additives etc. therefore encouraged synthetic chemists to look alternate greener approaches. This review aims draw general overview on bond formation C–C bonds with aid different methodologies, majorly highlighting sustainable

Language: Английский

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Molecular editing of aza-arene C–H bonds by distance, geometry and chirality

Nature, Journal Year: 2022, Volume and Issue: 610(7930), P. 87 - 93

Published: Aug. 9, 2022

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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Chiral Transient Directing Groups in Transition-Metal-Catalyzed Enantioselective C–H Bond Functionalization

ACS Catalysis, Journal Year: 2020, Volume and Issue: 10(21), P. 12898 - 12919

Published: Oct. 21, 2020

Transition-metal-catalyzed C–H bond functionalization has known a rapid evolution in the last years, offering modern strategies for reaching high molecular complexity step- and atom-economical way. Despite indisputable advances, selectivity issues still remain, given ubiquity of bonds on molecules; thus, several approaches have been developed to tackle this challenge. Among them, use transient directing group emerged as an effective tool, circumventing need extra synthetic steps install then cleave molecule. More recently, strategy successfully applied even more challenging transition-metal-catalyzed enantioselective functionalization. This review will highlight discuss main advances made chiral C(sp2)–H C(sp3)–H by transition-metal catalysis.

Language: Английский

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Palladium-Catalyzed meta-C–H Allylation of Arenes: A Unique Combination of a Pyrimidine-Based Template and Hexafluoroisopropanol

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(28), P. 12453 - 12466

Published: June 4, 2020

Controlling remote selectivity and delivering novel functionalities at distal positions in arenes are an important endeavor contemporary organic synthesis. In this vein, template engineering mechanistic understanding of new functionalization strategies essential for enhancing the scope such methods. Herein, meta-C–H allylation has been achieved with aid a palladium catalyst, pyrimidine-based auxiliary, allyl phosphate. 1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) was found as critical solvent transformation. The role HFIP throughout catalytic cycle systematically studied. A broad substrate phenethyl ether, phenol, benzylsulfonyl ester, phenethylsulfonyl phenylacetic acid, hydrocinnamic 2-phenylbenzoic acid derivatives demonstrated. Interestingly, conformationally flexible have also selectively allylated meta-position using combination 1H NMR, 31P ESI-MS, kinetic experiments, density functional theory (DFT) computations suggested that reaction proceeds through ligand-assisted activation, addition forming Pd-π-allyl complex which is then followed by turnover determining C–C bond formation step leading to meta-allylated product.

Language: Английский

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Decoding Directing Groups and Their Pivotal Role in C−H Activation

Chemistry - A European Journal, Journal Year: 2021, Volume and Issue: 27(49), P. 12453 - 12508

Published: May 26, 2021

Synthetic organic chemistry has witnessed a plethora of functionalization and defunctionalization strategies. In this regard, C-H been at the forefront due to multifarious applications in development simple complex molecular architectures holds brilliant prospect drug discovery. Despite explored tremendously by chemists, strategy still enjoys employment novel metal catalysts as well metal-free ligands. Moreover, switch photo- electrochemistry widened our understanding alternative pathways via which reaction can proceed these strategies have garnered prominence when applied activation. chemists foraging for new directing groups templates selective activation bonds from myriad carbon-hydrogen aromatic aliphatic systems. As matter fact, varying groups, scientists found answer challenge distal bond remained an obstacle very long time. These frequently harnessed selectively activating natural products, drugs, macromolecules decorated with multiple bonds. This itself was before commencement field site other than targeted could modify hamper biological activity pharmacophore. Total synthesis pharmacophore often faces difficulty superfluous steps towards functionalization. solved late-stage simply harnessing green conditions seen light past few decades rising concern about environmental issues. Therefore, or usage non-toxic metals recently showcased number elegant works. Also, research across world are developing rational group free non-directed protocols that just guided review encapsulates works pertinent discusses science devoted it fundamental level. gives readers broad how work, execution various catalysts, groups. not only helps budding scientist his/her but also matured mind searching out A detailed picture its progress time portrayed lucid scientific language motive inculcate educate minds beautiful overview most relevant significant era. The unique trait is description classification their utility over wide substrate scope. allows experimental chemist understand applicability domain employ any substrate.

Language: Английский

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